The significance of serum urea and renal function in patients with heart failure.

PubMed

Gotsman, Israel; Zwas, Donna; Planer, David; Admon, Dan; Lotan, Chaim; Keren, Andre

2010-07-01

Renal function and urea are frequently abnormal in patients with heart failure (HF) and are predictive of increased mortality. The relative importance of each parameter is less clear. We prospectively compared the predictive value of renal function and serum urea on clinical outcome in patients with HF. Patients hospitalized with definite clinical diagnosis of HF (n = 355) were followed for short-term (1 yr) and long-term (mean, 6.5 yr) survival and HF rehospitalization. Increasing tertiles of discharge estimated glomerular filtration rate (eGFR) were an independent predictor of increased long-term survival (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.47-0.91; p = 0.01) but not short-term survival. Admission and discharge serum urea and blood urea nitrogen (BUN)/creatinine ratio were predictors of reduced short- and long-term survival on multivariate Cox regression analysis. Increasing tertiles of discharge urea were a predictor of reduced 1-year survival (HR, 2.13; 95% CI, 1.21-3.73; p = 0.009) and long-term survival (HR, 1.93; 95% CI, 1.37-2.71; p < 0.0001). Multivariate analysis including discharge eGFR and serum urea demonstrated that only serum urea remained a significant predictor of long-term survival; however, eGFR and BUN/creatinine ratio were both independently predictive of survival. Urea was more discriminative than eGFR in predicting long-term survival by area under the receiver operating characteristic curve (0.803 vs. 0.787; p = 0.01). Increasing tertiles of discharge serum urea and BUN/creatinine were independent predictors of HF rehospitalization and combined death and HF rehospitalization. This study suggests that serum urea is a more powerful predictor of survival than eGFR in patients with HF. This may be due to urea's relation to key biological parameters including renal, hemodynamic, and neurohormonal parameters pertaining to the overall clinical status of the patient with chronic HF.

Clinical and Biochemical Characteristics of Brain-Dead Donors as Predictors of Early- and Long-Term Renal Function After Transplant.

PubMed

Kwiatkowska, Ewa; Domański, Leszek; Bober, Joanna; Safranow, Krzysztof; Pawlik, Andrzej; Ciechanowski, Kazimierz; Wiśniewska, Magda; Kędzierska, Karolina

2017-08-01

Organs from brain-dead donors are the main source of allografts for transplant. Comparisons between living-donor and brain-dead donor kidneys show that the latter are more likely to demonstrate delayed graft function and lower long-term survival. This study aimed to assess the effects of various clinical and biochemical factors of donors on early- and long-term renal function after transplant. We analyzed data from kidney recipients treated between 2006 and 2008 who received organs from brain-dead donors. Data from 54 donors and 89 recipients were analyzed. No relation was observed between donor sodium concentration and the presence of delayed graft function. Donor height was positively correlated with creatinine clearance in recipients in the 1 to 3 months after renal transplant. Donor diastolic blood pressure was negatively correlated with estimated glomerular filtration rate throughout the observation period. Donor age was negatively correlated with the allograft recipient's estimated glomerular filtration rate throughout 4 years of observation. Donor estimated glomerular filtration rate was positively correlated with that of the recipient throughout 3 years of observation. The results of this study indicate that various factors associated with allograft donors may influence graft function.

Dehydration upon admission is a risk factor for incomplete recovery of renal function in children with haemolytic uremic syndrome.

PubMed

Ojeda, José M; Kohout, Isolda; Cuestas, Eduardo

2013-01-01

Haemolytic uremic syndrome (HUS) is the most common cause of acute renal failure and the second leading cause of chronic renal failure in children. The factors that affect incomplete renal function recovery prior to hospital admission are poorly understood. To analyse the risk factors that determine incomplete recovery of renal function prior to hospitalisation in children with HUS. A retrospective case-control study. age, sex, duration of diarrhoea, bloody stools, vomiting, fever, dehydration, previous use of antibiotics, and incomplete recovery of renal function (proteinuria, hypertension, reduced creatinine clearance, and chronic renal failure during follow-up). Patients of both sexes under 15 years of age were included. Of 36 patients, 23 were males (65.3%; 95%CI: 45.8 to 80.9), with an average age of 2.5 ± 1.4 years. Twenty-one patients required dialysis (58%; 95% CI: 40.8 to 75.8), and 13 (36.1%; 95% CI: 19.0 to 53.1) did not recover renal function. In the bivariate model, the only significant risk factor was dehydration (defined as weight loss >5%) [(OR: 5.3; 95% CI: 1.4 to 12.3; P=.0220]. In the multivariate analysis (Cox multiple regression), only dehydration was marginally significant (HR: 95.823; 95% CI: 93.175 to 109.948; P=.085). Our data suggest that dehydration prior to admission may be a factor that increases the risk of incomplete recovery of renal function during long-term follow-up in children who develop HUS D+. Consequently, in patients with diarrhoea who are at risk of HUS, dehydration should be strongly avoided during outpatient care to preserve long-term renal function. These results must be confirmed by larger prospective studies.

Relation of Worsened Renal Function during Hospitalization for Heart Failure to Long-Term Outcomes and Rehospitalization

PubMed Central

Lanfear, David E.; Peterson, Edward L.; Campbell, Janis; Phatak, Hemant; Wu, David; Wells, Karen; Spertus, John A.; Williams, L. Keoki

2010-01-01

Worsened renal function (WRF) during heart failure (HF) hospitalization is associated with in-hospital mortality, but there are limited data regarding its relationship to long-term outcomes after discharge. The influence of WRF resolution is also unknown. This retrospective study analyzed patients who received care from a large health system and had a primary hospital discharge diagnosis of HF between 1/2000 and 6/2008. Renal function was estimated from creatinine levels during hospitalization. The first available value was considered baseline. WRF was defined a creatinine increase of ≥0.3mg/dl on any subsequent hospital day compared to baseline. Persistent WRF was defined as having WRF at discharge. Proportional hazards regression, adjusting for baseline renal function and potential confounding factors, was used to assess time to re-hospitalization or death. Among 2465 patients who survived to discharge, 887 (36%) developed WRF. Median follow up was 2.1 years. In adjusted models, WRF was associated with higher rates of post-discharge death or re-hospitalization (HR 1.12, 95%CI 1.02 – 1.22). Among those with WRF, 528 (60%) had persistent WRF while 359 (40%) recovered. Persistent WRF was significantly associated with higher post-discharge event rates (HR 1.14, 95%CI 1.02 – 1.27), whereas transient WRF showed only a non-significant trend towards risk (HR 1.09 95%CI 0.96-1.24). In conclusion, among patients surviving hospitalization for HF, WRF was associated with increased long-term mortality and re-hospitalization, particularly if renal function did not recover by the time of discharge. PMID:21146690

Characteristics of long-term live-donor pediatric renal transplant survivors: a single-center experience.

PubMed

El-Husseini, Amr A; Foda, Mohamed A; Osman, Yasser M; Sobh, Mohamed A

2006-05-01

To study the characteristics and the predictors of survival observed in our pediatric live-donor renal transplant recipients with an allograft that functioned for more than 10 yr. One hundred fifteen children underwent renal transplantation between 1976 and 1995. Of these, 30 had functioning allografts for more than 10 yr (range, 11-18). The patients included 18 males and 12 females, with a mean age at transplantation of 13 yr (range, 5-18). Characteristics of the patients, data on graft survival, and determinants of outcome were obtained by reviewing all medical charts. At most recent follow-up (January 2005), the mean daily dose of azathioprine was 1.2 mg/kg (range, 1-2) and that of prednisone was 0.16 mg/kg (range, 0.1-0.2). Mean creatinine clearance was 72 mL/min per 1.73 m(2) (range, 45-112). Acute rejection occurred in 14 (47%) patients. Seven patients had one episode, five had two episodes, and two had three episodes of acute rejection. Three patients (10%) developed malignancy. A substantial proportion of patients (44%) were short, with a height standard deviation score (SDS) less than -1.88, which is below the third percentile for age and gender. One quarter of the patients, more commonly the females, were obese. Other complications included osteoporosis in 16 (53%) patients, avascular bone necrosis in four (13%), post-transplantation diabetes mellitus in three (10%), and hypertension in 18 (60%). Twelve (40%) patients were married and 27% had children post-transplantation. The independent determinants of long-term graft survival were acute rejection and post-transplant hypertension. Despite good renal function, long-term pediatric renal transplant survivors are at risk of significant morbidity. The determinants of long-term graft survival are acute rejection and post-transplant hypertension.

Clinicopathological findings, treatment response and predictors of long-term outcome in a cohort of lupus nephritis patients managed according to the Euro-lupus regime: a retrospective analysis in Sri Lanka.

PubMed

Herath, Nalaka; Ratnatunga, Neelakanthi; Weerakoon, Kosala; Wazil, Abdul; Nanayakkara, Nishantha

2017-02-02

Despite the improvement in survival of patients with lupus nephritis (LN) globally, there is sparse data from Sri Lanka (SL). The current study aims to describe the clinicopathological findings, treatment response and predictors of long-term outcome of patients with WHO class III-IV LN in SL, managed according to the Euro-lupus regime. Of 72 patients, 64 were females. In half of them, LN was diagnosed within the 1st year of the illness. The most common presenting feature was sub-nephrotic proteinuria. Sixteen and twenty patients had nephrotic syndrome and abnormal renal function respectively at the time of diagnosis. Fifty-four patients (75%) responded to the Euro-lupus regimen [CR, 20 (28%); PR, 34(47%)]. Later at 6 months, 65 patients (90%) achieved remission [CR, 31(43%); PR, 34 (47%)]. Seven patients experienced treatment failure. During the total duration of follow up, 54 patients remained in complete or partial remission, 26 developed renal relapses, and 19 suffered severe infective episodes. Renal relapses were more common in people who achieved partial remission than complete remission. The long term renal outcome was not associated with age, sex, severity of proteinuria, class of LN or initial renal function. Patients who achieved remission at 6 months had a good long-term outcome. The demographic and clinical features of WHO class III and IV LN in Sri Lankan patients were similar to that reported in the global literature. 75% of patients responded to the Euro-lupus regimen. Therefore, this regime is a suitable initial regimen for LN patients in SL. Good long-term renal outcome can be predicted by early response to therapy. Further studies are necessary to explore better treatment options for patients who fail to achieve remission during initial therapy.

Acute renal failure requiring renal replacement therapy in the intensive care unit: impact on prognostic assessment for shared decision making.

PubMed

Johnson, Robert F; Gustin, Jillian

2011-07-01

A 69-year-old female was receiving renal replacement therapy (RRT) for acute renal failure (ARF) in an intensive care unit (ICU). Consultation was requested from the palliative medicine service to facilitate a shared decision-making process regarding goals of care. Clinician responsibility in shared decision making includes the formulation and expression of a prognostic assessment providing the necessary perspective for a spokesperson to match patient values with treatment options. For this patient, ARF requiring RRT in the ICU was used as a focal point for preparing a prognostic assessment. A prognostic assessment should include the outcomes of most importance to a discussion of goals of care: mortality risk and survivor functional status, in this case including renal recovery. A systematic review of the literature was conducted to document published data regarding these outcomes for adult patients receiving RRT for ARF in the ICU. Forty-one studies met the inclusion criteria. The combined mean values for short-term mortality, long-term mortality, renal-function recovery of short-term survivors, and renal-function recovery of long-term survivors were 51.7%, 68.6%, 82.0%, and 88.4%, respectively. This case example illustrates a process for formulating and expressing a prognostic assessment for an ICU patient requiring RRT for ARF. Data from the literature review provide baseline information that requires adjustment to reflect specific patient circumstances. The nature of the acute primary process, comorbidities, and severity of illness are key modifiers. Finally, the prognostic assessment is expressed during a family meeting using recommended principles of communication.

Influence of minor deterioration of renal function after PCI on outcome in patients with ST-elevation myocardial infarction.

PubMed

Kanic, Vojko; Suran, David; Vollrath, Maja; Tapajner, Alojz; Kompara, Gregor

2017-10-01

Our aim was to assess the possible impact of a deterioration of renal function (DRF) not fulfilling the criteria for acute kidney injury after percutaneous coronary intervention (PCI) on outcome in patients with ST-elevation myocardial infarction (STEMI) on 30-day and long-term outcomes. Data is lacking on the influence of DRF after PCI on outcome in patients with STEMI. The present study is an analysis of 2572 STEMI patients who underwent PCI. The group with DRF (1022 patients) and the group without DRF (1550 patients) were compared. Thirty-day and long-term all-cause mortality were observed. Data was analyzed using descriptive statistics. Similar mortality was observed in both groups at day 30 (4.2% patients with DRF died vs 3.2% without DRF; ns) but more patients had died in the DRF group (18.9% patients with DRF vs 14.0% without DRF; P = 0.001) by the end of the observation period. After adjustments, DRF did not independently predict long-term mortality. Age more than 70 years, bleeding, hyperlipidemia, renal dysfunction on admission, anemia on admission, diabetes, PCI of LAD, the use of more than 200 mL contrast, but not DRF after PCI, were identified as independent prognostic factors for increased long-term mortality. Renal dysfunction, bleeding, contrast >200 mL, hyperlipidemia, age >70 years, anemia, and PCI LAD predicted DRF. DRF identified patients at increased risk of higher long-term mortality but was not independently associated with mortality. © 2017, Wiley Periodicals, Inc.

Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease.

PubMed

Germain, Dominique P; Waldek, Stephen; Banikazemi, Maryam; Bushinsky, David A; Charrow, Joel; Desnick, Robert J; Lee, Philip; Loew, Thomas; Vedder, Anouk C; Abichandani, Rekha; Wilcox, William R; Guffon, Nathalie

2007-05-01

Fabry disease, an inherited deficiency of the lysosomal enzyme alpha-galactosidase A, causes progressive intralysosomal accumulation of globotriaosylceramide (GL-3) and premature death from renal, cardiac, and cerebrovascular manifestations. To determine the long-term safety and efficacy of recombinant human alpha-galactosidase A, an open-label, phase III extension study was conducted, involving 58 patients who had classic Fabry disease and completed a 20-wk, double-blind, randomized, placebo-controlled, phase III study of agalsidase beta and were transitioned to an extension trial to receive biweekly 1 mg/kg agalsidase beta for up to an additional 54 mo. GL-3 accumulation was evaluated in the capillary endothelia of the skin, kidney, and heart. Renal function was assessed. By month 54, all patients with optional kidney biopsies (n = 8) maintained complete GL-3 clearance in renal capillary endothelial cells and multiple cell types. Continued, complete clearance of skin (31 of 36) and heart (six of eight) capillary endothelium was demonstrated. Mean plasma GL-3 levels remained decreased in the normal range. Median serum creatinine and estimated GFR remained stable (normal) in patients with renal data at month 54 (n = 41). Six patients had renal disease progression; most (four of six) were older than 40 yr and had significant proteinuria at baseline and evidence of sclerotic glomeruli pretreatment. Adverse events were generally mild and unrelated to treatment. The most common treatment-related adverse events were infusion-associated reactions, which decreased over time. Long-term agalsidase beta therapy stabilizes renal function in patients without renal involvement at baseline, maintains reduction of plasma GL-3, and sustains GL-3 clearance in capillary endothelial cells and multiple renal cell types.

Longitudinal changes in kidney parenchymal volume associated with renal artery stenting.

PubMed

Modrall, J Gregory; Timaran, Carlos H; Rosero, Eric B; Chung, Jayer; Plummer, Mitchell; Valentine, R James; Trimmer, Clayton

2012-03-01

This study assessed the longitudinal changes in renal volume after renal artery stenting (RAS) to determine if renal mass is preserved by stenting. The study cohort consisted of 38 patients with longitudinal imaging available for renal volume quantification before and after RAS. Renal volume was estimated as (kidney length) × (width) × (depth/2) based on preoperative renal imaging. For each patient, the clinical response of blood pressure (BP) and renal function to RAS was categorized according to modified American Heart Association guidelines. Changes in renal volume were assessed using paired nonparametric analyses. The cohort was a median age of 69 years (interquartile range [IQR], 60-74 years). A favorable BP response was observed in 11 of 38 patients (28.9%). At a median interval between imaging studies of 21 months (IQR, 13-32 months), ipsilateral renal volume was significantly increased from baseline (146.8 vs 133.8 cm(3);P = .02). This represents a 6.9% relative increase in ipsilateral kidney volume from baseline. A significant negative correlation between preoperative renal volume and the relative change in renal volume postoperatively (r = -0.42; P = .0055) suggests that smaller kidneys experienced the greatest gains in renal volume after stenting. It is noteworthy that the 25 patients with no change in BP or renal function-clinical failures using traditional definitions-experienced a 12% relative increase in ipsilateral renal volume after RAS. Multivariate analysis determined that stable or improved renal volume after stenting was an independent predictor of stable or improved long-term renal function (odds ratio, 0.008; 95% confidence interval, 0.000-0.206; P = .004). These data lend credence to the belief that RAS preserves renal mass in some patients. This benefit of RAS even extends to those patients who would be considered treatment failures by traditional definitions. Patients with stable or increased renal volume after RAS had more stable renal function during long-term follow-up, whereas patients with renal volume loss after stenting were prone to deterioration of renal function. Published by Mosby, Inc.

Renal Function of Rats in Response to 37 Days of Head-Down Tilt

NASA Technical Reports Server (NTRS)

Wang, Tommy J.; Wade, Charles E.; Dalton, Bonnie P. (Technical Monitor)

2001-01-01

Spaceflight induces changes in human renal function, suggesting similar changes may occur in rats. Since rats continue to be the prime mammalian model for study in space, the effects of chronic microgravity on rat renal function should be clarified. Acute studies in rats using the ground-based microgravity simulation model, head-down tilt (HDT), have shown increases in glomerular filtration rate (GFR), electrolyte excretion, and a diuresis. However, long term effects of HDT have not been studied extensively. This study was performed to elucidate rat renal function following long-term simulated microgravity. Chronic exposure to HDT will cause an increase in GFR and electrolyte excretion in rats, similar to acute exposures, and lead to a decrease in the fractional excretion of filtered electrolytes. Experimental animals (HDT, n=10) were tail-suspended for 37 days and renal function compared to ambulatory controls (AMB, n=10). On day 37 of HDT, GFR, osmolal clearance, and electrolyte excretion were decreased, while plasma osmolality and free water clearance were increased. Urine output remained similar between groups. The fractional excretion of the filtered electrolytes was unchanged except for a decrease in the percentage of filtered calcium excreted. Chronic exposure to HDT results in decreased GFR and electrolyte excretion, but the fractional excretion of filtered electrolytes remained primarily unaffected.

Relation of worsened renal function during hospitalization for heart failure to long-term outcomes and rehospitalization.

PubMed

Lanfear, David E; Peterson, Edward L; Campbell, Janis; Phatak, Hemant; Wu, David; Wells, Karen; Spertus, John A; Williams, L Keoki

2011-01-01

Worsened renal function (WRF) during heart failure (HF) hospitalization is associated with in-hospital mortality, but there are limited data regarding its relation to long-term outcomes after discharge. The influence of WRF resolution is also unknown. This retrospective study analyzed patients who received care from a large health system and had a primary hospital discharge diagnosis of HF from January 2000 to June 2008. Renal function was estimated from creatinine levels during hospitalization. The first available value was considered baseline. WRF was defined a creatinine increase ≥ 0.3 mg/dl on any subsequent hospital day compared to baseline. Persistent WRF was defined as having WRF at discharge. Proportional hazards regression, adjusting for baseline renal function and potential confounding factors, was used to assess time to rehospitalization or death. Of 2,465 patients who survived to discharge, 887 (36%) developed WRF. Median follow-up was 2.1 years. In adjusted models, WRF was associated with higher rates of postdischarge death or rehospitalization (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.02 to 1.22). Of those with WRF, 528 (60%) had persistent WRF, whereas 359 (40%) recovered. Persistent WRF was significantly associated with higher postdischarge event rates (HR 1.14, 95% CI 1.02 to 1.27), whereas transient WRF showed only a nonsignificant trend toward risk (HR 1.09, 95% CI 0.96 to 1.24). In conclusion, in patients surviving hospitalization for HF, WRF was associated with increased long-term mortality and rehospitalization, particularly if renal function did not recover by the time of discharge. Copyright © 2011 Elsevier Inc. All rights reserved.

Long-term health and work outcomes of renal transplantation and patterns of work status during the end-stage renal disease trajectory.

PubMed

van der Mei, Sijrike F; Kuiper, Daphne; Groothoff, Johan W; van den Heuvel, Wim J A; van Son, Willem J; Brouwer, Sandra

2011-09-01

The aim of this study was to examine the health- and work outcomes of renal transplant recipients long-term after transplantation as well as the pattern of work status, work ability and disability benefits during the end-stage renal disease (ESRD) trajectory that precedes transplantation. 34 transplant recipients completed interviews 3, 13 months and >6 years posttransplantation. Health status (SF-36), work ability (WAI), and fatigue (CIS) were assessed by questionnaires, clinical data were derived from medical charts, and data on functional limitations were extracted from the social security system database. The work status trajectory preceding transplantation was examined retrospectively. Of the 34 third wave transplant recipients, 29% were severely fatigued. Compared with the general working population, recipients experienced worse general health and less vitality. Non-working recipients had worse renal function and general health, and more limitations in physical functioning compared to working recipients. The WAI score indicated moderate work ability for 60% of the employed recipients. Although 67% were employed (45% parttime), 30% of those working still received some disability benefits. Social insurance physicians found variable levels of functional limitations. The mean work status trajectory showed more sickness absence and less work ability during dialysis, but after transplantation, both work status and work ability generally improved. Transplant recipients have a compromised health status which leads to functional limitations and disability. Although work status improved after transplantation, a substantial number of the transplant recipients received disability benefits. The negative health consequences of anti-rejection medications may play an important role in long-term work ability. These results indicate that a 'new' kidney has advantages over dialysis with respect to work, but does not necessarily leads to 'normal' work outcomes.

Lowering of blood pressure by chronic suppression of central sympathetic outflow: insight from prolonged baroreflex activation

PubMed Central

Iliescu, Radu

2012-01-01

Device-based therapy for resistant hypertension by electrical activation of the carotid baroreflex is currently undergoing active clinical investigation, and initial findings from clinical trials have been published. The purpose of this mini-review is to summarize the experimental studies that have provided a conceptual understanding of the mechanisms that account for the long-term lowering of arterial pressure with baroreflex activation. The well established mechanisms mediating the role of the baroreflex in short-term regulation of arterial pressure by rapid changes in peripheral resistance and cardiac function are often extended to long-term pressure control, and the more sluggish actions of the baroreflex on renal excretory function are often not taken into consideration. However, because clinical, experimental, and theoretical evidence indicates that the kidneys play a dominant role in long-term control of arterial pressure, this review focuses on the mechanisms that link baroreflex-mediated reductions in central sympathetic outflow with increases in renal excretory function that lead to sustained reductions in arterial pressure. PMID:22797307

Impact of Stone Removal on Renal Function: A Review

PubMed Central

Wood, Kyle; Keys, Tristan; Mufarrij, Patrick; Assimos, Dean G

2011-01-01

Stone removal can improve renal function by eradicating obstruction and, in certain cases, an underlying infection. Stone-removing procedures, however, may negatively impact functional integrity. Many things may impact the latter, including the procedures used, the methods of assessing function, the time when these assessments are made, the occurrence of complications, the baseline condition of the kidney, and patient-related factors. In the majority of cases, little significant functional impairment occurs. However, there are gaps in our knowledge of this subject, including the cumulative effects of multiple procedures violating the renal parenchyma and long-term functional outcomes. PMID:21935339

[Is there an age limit for cadaveric kidney donors currently?].

PubMed

Cofán Pujol, F; Oppenheimer Salinas, F; Talbot-Wright, R; Carretero González, P

1996-12-01

The insufficient number of kidney transplants has gradually raised the age limit to the cadaver kidney donor. The use of grafts harvested from older donors has been debated due to the existing structural and functional changes that might influence renal function and long-term graft survival. The foregoing aspects are discussed herein. The anatomical, histological and functional changes in the kidney associated with ageing are analyzed. The clinical experience with renal grafts from older donors before and after cyclosporine became available are reviewed. The ethical issues on whether grafts from very old donors should be used and who should receive these grafts are discussed. The use of grafts from donors over 60 years old had no significant short and medium term differences in comparison with younger donors in terms of graft survival, although a higher incidence of acute tubular necrosis and poor renal function have been observed. There are no conclusive studies on the long-term effects on graft survival when kidneys from donors aged over 65 are utilized. In our experience, the results achieved with grafts from donors over 70 has been unsatisfactory. The guidelines utilized in the selection of grafts derived from older donors are presented. Grafts from donors aged 60 to 70 may be utilized in renal transplantation following precise selection criteria. Graft survival has been satisfactory, although a higher incidence of acute tubular necrosis and higher creatinine levels have been observed. We do not advocate the use of grafts from donors over 70, except in very exceptional cases. Long-term multicenter studies on grafts from very old donors and trials using alternative immunosuppressor modalities that might permit optimal use of these grafts are warranted.

Better microvascular function on long-term treatment with lisinopril than with nifedipine in renal transplant recipients.

PubMed

Asberg, A; Midtvedt, K; Vassbotn, T; Hartmann, A

2001-07-01

The prevalence of hypertension in renal transplant recipients is high but the pathophysiology is poorly defined. Impaired endothelial function may be a factor of major importance. The present study addresses the effects of long-term treatment with either lisinopril or slow-release nifedipine on microvascular function and plasma endothelin in renal transplant recipients on cyclosporin A (CsA). Seventy-five hypertensive renal transplant recipients were double-blind randomized to receive slow-release nifedipine (NIF, n=40) or lisinopril (LIS, n=35). Ten normotensive, age-matched recipients served as controls. All patients received CsA-based immunosuppressive therapy including prednisolone and azathioprine. Microvascular function was assessed in the forearm skin vasculature, using laser Doppler flowmetry in combination with post-occlusive reactive hyperaemia and endothelial-dependent function during local acetylcholine (ACh) stimulation. The analysis of microvascular function (AUC(rh)) showed that nifedipine-treated patients had significantly lower responses compared with lisinopril-treated patients (20+/-17 and 43+/-20 AU x min respectively, P=0.0016). Endothelial function was borderline significantly lower in the NIF group compared with the LIS group (640+/-345 and 817+/-404 AU x min respectively, P=0.056). The responses in the LIS group were comparable with those in non-hypertensive controls (AUC(rh) was 37+/-16 and AUC(ACh) was 994+/-566 AU x min). Plasma endothelin-1 concentrations were significantly higher in the NIF group compared with the LIS group (0.44+/-0.19 vs. 0.34+/-0.10 fmol/ml respectively, P=0.048), and were 0.29+/-0.09 fmol/ml in the control patients. AUC(ACh) was associated with plasma endothelin-1 (P=0.0053), while AUC(rh) was not (P=0.080). The study indicates that long-term treatment with lisinopril, when compared with nifedipine, yields a more beneficial effect on microvascular function in hypertensive renal transplant recipients on CsA. The beneficial microvascular effect may be mediated in part by an endothelin-1-associated effect on the endothelium.

[Volume Homeostasis and Renal Function in Rats Exposed to Simulated and Actual Microgravity

NASA Technical Reports Server (NTRS)

Tucker, Bryan J.

1993-01-01

This project has investigated mechanisms that influence alterations in compartmental fluid and electrolyte balance in microgravity and evaluates countermeasures to control renal fluid and electrolyte losses. Determining the alterations due to space flight in fluid compartments and renal function is an important component in understanding long term adaptation to spaceflight and the contribution to post-flight orthostatic intolerance. Four definition phase studies and two studies examining neuro-humoral and vascular mechanisms have been completed.

Native kidney function following liver transplantation using calcineurin inhibitors: single-center analysis with 20 years of follow-up.

PubMed

LaMattina, John C; Mezrich, Joshua D; Fernandez, Luis A; D'Alessandro, Anthony M; Djamali, Arjang; Musat, Alexandru I; Pirsch, John D; Foley, David P

2013-01-01

The incidence of chronic kidney disease (CKD) in liver transplant recipients has been estimated to be from 18% to 28% at 10 yr after transplantation. As outcomes from liver transplantation continue to improve, long-term native kidney function in these recipients becomes more critical to patient survival. We analyzed 1151 adult, deceased-donor, single-organ primary liver transplantations performed at our center between 7/17/84 and 12/31/07. Analysis of renal function was performed on 972 patients with liver allograft survival >1 yr. Kaplan-Meier analysis revealed that 3%, 7%, and 18% of liver transplant recipients with allograft survival >1 yr developed end-stage renal disease (ESRD) at five, 10, and 20 yr, respectively. Significant independent risk factors for ESRD included dialysis during the transplant hospitalization, the stage of CKD at one yr, hypercholesterolemia, non-Caucasian race, and hepatitis C as the primary indication for liver transplantation. The initial immunosuppression of essentially all recipients was a calcineurin inhibitor-based regimen. Close, long-term follow-up of liver transplant recipients permits optimal management of liver allograft and native renal function and can lead to excellent long-term outcomes despite a calcineurin inhibitor-based immunosuppressive regimen. © 2013 John Wiley & Sons A/S.

Capsulotomy for treatment of compartment syndrome in patients with post extracorporeal shock wave lithotripsy renal hematomas: safe and effective, but also advisable?

PubMed

Al Ghazal, Andreas; Schnoeller, Thomas J; Baechle, Christian; Steinestel, Julie; Jentzmik, Florian; Steffens, Sandra; Hirning, Christian; Schrader, Mark; Schrader, Andres J

2014-07-08

To examine whether surgical decompression of hematomas by capsulotomy can help to improve long-term renal function following extracorporeal shock wave lithotripsy (SWL). This study retrospectively identified 7 patients who underwent capsulotomy for post SWL renal hematomas between 2008 and 2012. The control group comprised 8 conservatively treated patients. The median follow-up time was 22 months. The two groups were comparable in age, gender, body mass index, risk factors for developing hematomas (renal failure, urinary flow impairment, indwelling ureteral stent and diabetes mellitus) and the selected SWL modalities. Hematoma size was also similar. However, significantly more patients in the surgical group had purely intracapsular hematomas (85.7% vs. 37.5%) without a potentially pressure-relieving capsular rupture. There were no significant differences in the post-interventional drop in hemoglobin, rise in retention parameters or drop in glomerular filtration rate (GFR). No capsulotomy-related complications were observed, but surgery required a significantly longer hospital stay than conservative management (median, 9 days vs. 5 days). The two groups also showed comparable recovery of renal function at long-term follow-up (median change in GFR from baseline, 97.1% and 97.8%, respectively). Since renal function did not differ between the two treatment groups, the conservative management remains the standard treatment for post-SWL renal hematoma.

Long-term results with renal autotransplantation for ureteral replacement.

PubMed

Bodie, B; Novick, A C; Rose, M; Straffon, R A

1986-12-01

From 1970 to 1984 renal autotransplantation was performed on 23 patients to replace all or a major portion of the ureter. The conditions necessitating ureteral replacement were postoperative ureteral injury in 16 cases, recurrent renal colic in 4, urinary undiversion in 2 and an atonic ureter in 1. Six patients presented with a solitary kidney and 1 underwent staged bilateral autotransplantation. After autotransplantation urinary continuity was restored by ureteroneocystostomy in 11 patients, pyelovesicostomy in 7, ureteroureterostomy in 2, pyeloureterostomy in 2 and ureterosigmoidostomy in 1. Postoperatively, there was no mortality and all but 1 of the autotransplanted kidneys functioned immediately. Two kidneys required removal postoperatively owing to bleeding. Currently, 20 patients are alive with functioning renal autotransplants at intervals of 1.5 to 14 years. The current serum creatinine level in these patients ranges from 1.1 to 2.2 mg. per dl., which in each case is improved or stable compared to the preoperative determination. Only 1 patient has experienced chronic bacteriuria. We conclude that renal autotransplantation provides excellent long-term treatment for patients who require ureteral replacement.

Renal recovery and long-term survival following acute kidney injury after coronary artery surgery: a nationwide study.

PubMed

Helgadottir, S; Sigurdsson, M I; Palsson, R; Helgason, D; Sigurdsson, G H; Gudbjartsson, T

2016-10-01

Acute kidney injury (AKI) is a relatively common complication following CABG and is associated with adverse outcomes. Nonetheless, we hypothesized that the majority of patients make a good long-term recovery of their renal function. We studied the incidence and risk factors of AKI together with renal recovery and long-term survival in patients who developed AKI following CABG. This nationwide study examined AKI among 1754 consecutive patients undergoing CABG in 2001-2013. AKI was defined according to the KDIGO criteria. Postoperatively 184 (11%) patients developed AKI; 121 (7%), 27 (2%), and 36 (2%) at stages 1, 2, and 3, respectively. AKI was an independent risk factor for chronic kidney disease (CKD) and AKI patients had worse post-operative outcomes. Lower pre-operative glomerular filtration rate, higher EuroSCORE and BMI, diabetes, reoperation, and units of red blood cells transfused were independent risk factors of AKI. At post-operative day 10, renal recovery rates, defined as serum creatinine ratio <1.25 of baseline, were 96 (95% CI 91-99%), 78 (95% CI 53-90%), and 94% (95% CI 77-98%) for AKI stages 1, 2, and 3, respectively. Long-term survival was predicted by AKI with 10-year survival of patients without AKI being 76% and those with AKI stages 1, 2, and 3 being 63%, 56%, and 49%, respectively (P < 0.001). Depending on the severity of the initial AKI, 78-97% of patients made good recovery of their kidney function. However, AKI was significantly linked to progression to CKD and long-term survival remained markedly affected by the severity of the initial kidney injury. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Effects of adding Rheum officinale to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on renal function in patients with chronic renal failure: A meta-analysis of randomized controlled trials
.

PubMed

Yang, Yue; Ma, Ye-Ping; Zhang, Zheng; Dai, Pei-Lin; Li, Ping; Li, Wen-Ge

2018-06-01

Rheum officinale is a traditional medicinal herb used widely in China to treat chronic renal failure, but the proof of evidence-based medicine is poor. This meta-analysis aims to assess the benefits of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) supplemented with Rheum officinale for delaying the progression of chronic renal failure. The MEDLINE, EMBASE, Cochrane Library, SinoMed, Chinese National Knowledge Infrastructure, Wanfang, and VIP databases were searched to identify studies published before September 2016 that investigated the effects of ACEI/ARB plus the Chinese patented medicine Rheum (CPM-Rheum) compared to ACEI/ARB alone in lowering serum creatinine (SCr) and blood urea nitrogen (BUN) levels in chronic renal failure patients. Review Manager 5.3 was used to perform the meta-analysis. Fixed- and random-effects models were used to analyze the data. The meta-analysis included nine clinical trials. Comparisons of patients before and after treatment with ACEI/ARB plus CPM-Rheum or ACEI/ARB alone revealed that ACEI/ARB plus CPM-Rheum resulted in significantly greater reductions in SCr (short-term: weighted mean difference (WMD): 17.26, 95% confidence interval (CI): 7.28 - 27.24; long-term: WMD: 63.71, 95% CI: 51.01 - 76.41) and BUN (short-term: WMD: 1.70, 95% CI: 1.27 - 2.12; long-term: WMD: 3.98, 95% CI: 3.14 - 4.82) than ACEI/ARB alone. In patients with chronic renal failure, the addition of CPM-Rheum to ACEI/ARB significantly lowered both SCr and BUN, particularly after long-term administration. Thus, the combination of ACEI/ARB and CPM-Rheum may improve the treatment of patients with impaired renal function.
.

Long-Term Renal Function Recovery following Radical Nephrectomy for Kidney Cancer: Results from a Multicenter Confirmatory Study.

PubMed

Zabor, Emily C; Furberg, Helena; Lee, Byron; Campbell, Steven; Lane, Brian R; Thompson, R Houston; Antonio, Elvis Caraballo; Noyes, Sabrina L; Zaid, Harras; Jaimes, Edgar A; Russo, Paul

2018-04-01

We sought to confirm the findings from a previous single institution study of 572 patients from Memorial Sloan Kettering Cancer Center in which we found that 49% of patients recovered to the preoperative estimated glomerular filtration rate within 2 years following radical nephrectomy for renal cell carcinoma. A multicenter retrospective study was performed in 1,928 patients using data contributed from 3 independent centers. The outcome of interest was postoperative recovery to the preoperative estimated glomerular filtration rate. Data were analyzed using cumulative incidence and competing risks regression with death from any cause treated as a competing event. This study demonstrated that 45% of patients had recovered to the preoperative estimated glomerular filtration rate by 2 years following radical nephrectomy. Furthermore, this study confirmed that recovery of renal function differed according to preoperative renal function such that patients with a lower preoperative estimated glomerular filtration rate had an increased chance of recovery. This study also suggested that larger tumor size and female gender were significantly associated with an increased chance of renal function recovery. In this multicenter retrospective study we confirmed that in the long term a large proportion of patients recover to preoperative renal function following radical nephrectomy for kidney tumors. Recovery is more likely among those with a lower preoperative estimated glomerular filtration rate. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Change in Renal Function among HIV-Infected Koreans Receiving Tenofovir Disoproxil Fumarate-Backbone Antiretroviral Therapy: A 3-Year Follow-Up Study.

PubMed

Lee, Kyoung Hwa; Lee, Ji Un; Ku, Nam Su; Jeong, Su Jin; Han, Sang Hoon; Choi, Jun Yong; Song, Young Goo; Kim, June Myung

2017-07-01

Tenofovir disoproxil fumarate (TDF) is commonly prescribed as a fixed-dose, co-formulated antiretroviral drug for HIV-1 infection. The major concern of long-term TDF use is renal dysfunction. However, little is known about the long-term patterns of changes in renal function in HIV-infected Koreans receiving TDF. We prospectively followed 50 HIV-infected Koreans, performing laboratory tests every 3 months during the first year and every 6 months for the next 2 years. Urine N-acetyl-β-D-glucosaminidase (NAG) and plasma cystatin-C were measured using samples collected in the first year. Data on renal function were retrospectively collected on HIV-infected patients receiving first-line TDF (n=40) and in antiretroviral therapy (ART)-naïve patients (n=24) for 3 years. Renal function was evaluated as estimated glomerular filtration rate (eGFR) from serum creatinine [Modification of Diet in Renal Disease (MDRD)] and cystatin-C. The eGFR (cystatin-C) showed significant changes from 0 to 48 wks (p=0.002), with the lowest levels at 24 wks (84.3±18.8 mL/min vs. 90.3±22.5 mL/min, p=0.021 by post hoc test). Urine NAG levels did not differ at 0, 12, 24, and 48 wks, although eGFR (MDRD) significantly decreased from 0 (98.7±18.9 mL/min/1.73 m²) to 144 wks (89.0±14.7 mL/min/1.73 m²) (p=0.010). The first-line TDF group had significantly lower eGFR (MDRD) than the ART-naïve group at 144 wks (89.7 mL/min/1.73 m² vs. 98.4 mL/min/1.73 m², p=0.036). Thirteen (26%) participants experienced a decrease in renal impairment of 10 mL/min/1.73 m² in eGFR (MDRD) at 144 wks. These data suggest that clinically meaningful renal injury can develop in HIV-infected Koreans receiving long-term TDF. © Copyright: Yonsei University College of Medicine 2017

Long-term treatment of severe hypertension with minoxidil.

PubMed Central

Nawar, T.; Nolin, L.; Plante, G. E.; Caron, C.; Montambault, P.

1977-01-01

Minoxidil, a new potent hypotensive agent, was used as the primary antihypertensive agent in 11 patients--10 men and 1 woman aged 35 to 54 years with severe hypertension that was refractory to treatment with maximal (or maximally tolerated) doses of conventional antihypertensive agents. Six patients had severely impaired renal function and three of them were undergoing long-term hemodialysis. The patients were given 2.5 to 40 mg/d of minoxidil for periods of 2 to 29 months. All except one who was almost anuric received propranolol and diuretics. Blood pressure was controlled satisfactorily in all patients. In two patients the hypertension became partially resistant after 1 year of treatment. The main side effects were sodium retention, tachycardia and hirsutism. Renal function remained stable or improved and hemodialysis was discontinued in two patients. Minoxidil is a remarkably potent hypotensive with relatively few side effects and seems particularly advantageous in patients with chronic renal failure. PMID:603847

Predicting long-term renal damage in children with vesicoureteral reflux under conservative initial management: 205 cases in a tertiary referral center.

PubMed

Alvarez, Natalia; Alvira, Reyes Delgado; Ruiz, Yurema Gonzalez; Atuan, Rafael Fernandez; Hinojosa, Alexander Siles; Heras, Miguel Angel Rihuete; Roldan, Marisa Justa; Romero, Jesus Gracia

2018-01-01

Vesicoureteral reflux (VUR) is one of the most common ailments in children. Evidence-based guidelines recommend conservative treatment in children with VUR, followed by endoscopic surgery in those with breakthrough febrile urinary tract infections (UTIs). Despite this fact, the management of VUR is still controversial. Our objective is to evaluate the conservative strategy in children with primary VUR in terms of renal function and scarring, and identify factors associated with poor prognosis in those children. A retrospective study was carried out in a tertiary center in children with primary VUR under conservative strategy treatment from 1989 to 2015. Data extracted included age of presentation, family and prenatal backgrounds, radiographic evaluation including ultrasound (US), dimercaptosuccinic acid (DMSA) scans and voiding cystourethrogram (VCUG). The SPSS program was used for statistical analysis. Two-hundred and five patients were diagnosed and followed a conservative therapy scheme (49.8% males, 50.2% females) after febrile UTI (73.17%) or prenatal diagnosis (26.83%). VCUG showed 53.20% of low-moderate VUR grade, 46.80% high VUR grade. Renal damage was present at diagnosis in 40.89%. Mean follow-up reakthrough recurrent febrile UTIs and underwent surgery. Conservative therapy was followed in 189 patients. Renal scarring or decreased kidney function were shown in 15.12% respectively. Renal damage was identified as a risk factor for poor prognosis (p-value <0.005) only for renal function deterioration. Patients with high-grade VUR required surgery in a significantly greater proportion (p <0.005) due to recurrent febrile UTIs. Conservative strategy is a feasible treatment for primary VUR in children. The majority of cases could be managed conservatively with good outcomes after long-term follow-up. Decreased renal function is more frequent in patients with high-grade VUR. Renal damage at diagnosis increases the risk for surgical treatment.

Simple noninvasive measurement of skin autofluorescence.

PubMed

Meerwaldt, Robbert; Links, Thera; Graaff, Reindert; Thorpe, Suzannne R; Baynes, John W; Hartog, Jasper; Gans, Reinold; Smit, Andries

2005-06-01

Accumulation of advanced glycation end products (AGEs) is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. Several studies indicate that AGE accumulation in tissue may reflect the cumulative effect of hyperglycemia and oxidative stress over many years. Simple quantitation of AGE accumulation in tissue could provide a tool for assessing the risk of long-term complications. Because several AGEs exhibit autofluorescence, we developed a noninvasive autofluorescence reader (AFR). Skin autofluorescence measured with the AFR correlates with collagen-linked fluorescence and specific skin AGE levels from skin biopsy samples. Furthermore, skin autofluorescence correlates with long-term glycemic control and renal function, and preliminary results show correlations with the presence of long-term complications in diabetes. The AFR may be useful as a clinical tool for rapid assessment of risk for AGE-related long-term complications in diabetes and in other conditions associated with AGE accumulation.

Long-term outcome of patients with multiple [corrected] myeloma-related advanced renal failure following auto-SCT.

PubMed

Glavey, S V; Gertz, M A; Dispenzieri, A; Kumar, S; Buadi, F; Lacy, M; Hayman, S R; Kapoor, P; Dingli, D; McCurdy, A; Hogan, W J; Gastineau, D A; Leung, N

2013-11-01

Renal failure commonly complicates multiple myeloma (MM) and is associated with reduced survival. It is not clear whether auto-SCT results in improved renal function or attainment of independence from dialysis in patients with advanced renal impairment due to MM. We conducted a retrospective cohort study of all patients who underwent auto-SCT for MM complicated by advanced renal failure at our institution over a 10-year period (2000-2010). We aimed to assess the association between auto-SCT and renal outcome in patients with serum creatinine (SCr) over 3 mg/dL, attributable to MM, including those who were dialysis dependent. Thirty patients (2.8% of all auto-SCT patients) met inclusion criteria. Fourteen of 15 patients who were dialysis dependent before auto-SCT remained dialysis dependent in the long term despite hematological response (HR). Of the remaining 15 patients with SCr >3 mg/dL, an improvement in glomerular filtration rate (GFR) from 15 to 19.4 mL/min/1.73 m(2) was noted post auto-SCT (P=0.035); however, neither HR post auto-SCT or pre-existing renal function were independently associated with renal outcome. Auto-SCT was not associated with independence from dialysis in patients with renal failure due to MM at our institution. Although auto-SCT was associated with an improvement in GFR in patients with SCr >3 mg/dL, this improvement was not related to HR.

Novel biomarkers of acute kidney injury: Evaluation and evidence in urologic surgery

PubMed Central

Schmid, Marianne; Dalela, Deepansh; Tahbaz, Rana; Langetepe, Jessica; Randazzo, Marco; Dahlem, Roland; Fisch, Margit; Trinh, Quoc-Dien; Chun, Felix K-H

2015-01-01

Patients undergoing urologic surgery are at risk of acute kidney injury (AKI) and consequently long-term deterioration in renal function. AKI is further associated with significantly higher odds of perioperative complications, prolonged hospital stay, higher mortality and costs. Therefore, better awareness and detection of AKI, as well as identification of AKI determinants in the urological surgery setting is warranted to pre-empt and mitigate further deterioration of renal function in patients at special risk. New consensus criteria provide precise definitions of diagnosis and description of the severity of AKI. However, they rely on serum creatinine (SCr), which is known to be an inaccurate marker of early changes in renal function. Therefore, several new urinary and serum biomarkers promise to address the gap associated with the use of SCr. Novel biomarkers may complement SCr measurement or most likely improve the diagnostic accuracy of AKI when used in combinations. However, novel biomarkers have to prove their clinical applicability, accuracy, and cost effectiveness prior to implementation into clinical practice. Most preferably, novel biomarkers should help to positively improve a patient’s long-term renal functional outcomes. The purpose of this review is to discuss currently available biomarkers and to review their clinical evidence within urologic surgery settings. PMID:25949930

Value of imaging studies after a first febrile urinary tract infection in young children: data from Italian renal infection study 1.

PubMed

Montini, Giovanni; Zucchetta, Pietro; Tomasi, Lisanna; Talenti, Enrico; Rigamonti, Waifro; Picco, Giorgio; Ballan, Alberto; Zucchini, Andrea; Serra, Laura; Canella, Vanna; Gheno, Marta; Venturoli, Andrea; Ranieri, Marco; Caddia, Valeria; Carasi, Carla; Dall'amico, Roberto; Hewitt, Ian

2009-02-01

We examined the diagnostic accuracy of routine imaging studies (ultrasonography and micturating cystography) for predicting long-term parenchymal renal damage after a first febrile urinary tract infection. This study addressed the secondary objective of a prospective trial evaluating different antibiotic regimens for the treatment of acute pyelonephritis. Data for 300 children < or =2 years of age, with normal prenatal ultrasound results, who completed the diagnostic follow-up evaluation (ultrasonography and technetium-99m-dimercaptosuccinic acid scanning within 10 days, cystography within 2 months, and repeat technetium-99m-dimercaptosuccinic acid scanning at 12 months to detect scarring) were analyzed. Outcome measures were sensitivity, specificity, and negative and positive predictive values for ultrasonography and cystography in predicting parenchymal renal damage on the 12-month technetium-99m-dimercaptosuccinic acid scans. The kidneys and urinary tracts were mostly normal. The acute technetium-99m-dimercaptosuccinic acid scans showed pyelonephritis in 54% of cases. Renal scarring developed in 15% of cases. The ultrasonographic and cystographic findings were poor predictors of long-term damage, showing minor sonographic abnormalities for 12 and reflux for 23 of the 45 children who subsequently developed scarring. The benefit of performing ultrasonography and scintigraphy in the acute phase or cystourethrography is minimal. Our findings support (1) technetium-99m-dimercaptosuccinic acid scintigraphy 6 months after infection to detect scarring that may be related to long-term hypertension, proteinuria, and renal function impairment (although the degree of scarring was generally minor and did not impair renal function) and (2) continued surveillance to identify recurrent urinary tract infections that may warrant further investigation.

Renal Angiomyolipoma: Mid- to Long-Term Results Following Embolization with Onyx.

PubMed

Thulasidasan, Narayanan; Sriskandakumar, Srividhiya; Ilyas, Shahzad; Sabharwal, Tarun

2016-12-01

Percutaneous transcatheter embolization is currently the preferred treatment for ruptured or enlarging renal angiomyolipoma (AML), although the optimum choice of embolic material has not yet been established. We present mid- to long-term outcomes following embolization of AMLs with Onyx. Ten AMLs in seven patients (including two with tuberous sclerosis) were embolized with Onyx. Patients were followed-up clinically, with tumour size and renal function measured pre- and post-procedure. Mean pre-treatment AML size was 63.4 mm (range 42-100). Mean clinical follow-up was 431.4 days (range 153-986) and imaging follow-up 284.2 days (range 30-741). There was no haemorrhage from treated lesions within the follow-up period. Of patients who had cross-sectional imaging pre- and post-procedure, mean decrease in AML size of 22 mm was seen after Onyx embolization (p = 0.0058, 95 % CI 9.13-34.87). No significant difference between serum creatinine was seen pre- and post-procedure (p = 0.54, 95 % CI 8.63-4.85). Onyx embolization of renal AMLs is effective in the medium to long term, with theoretical benefits in safety and durability of result.

COHORT PROFILE: The Complications of Long-Term Antiretroviral Therapy study in Uganda (CoLTART), a prospective clinical cohort.

PubMed

Mayanja, Billy Nsubuga; Kasamba, Ivan; Levin, Jonathan; Namakoola, Ivan; Kazooba, Patrick; Were, Jackson; Kaleebu, Pontiano; Munderi, Paula

2017-01-01

Antiretroviral therapy (ART) improves the survival and quality of life of HIV-positive individuals, but the effects of long-term ART use do eventually manifest. The Complications of Long-Term Antiretroviral Therapy cohort study in Uganda (CoLTART) was established to investigate the metabolic and renal complications of long-term ART use among Ugandan adults. We describe the CoLTART study set-up, aims, objectives, study methods, and also report some preliminary cross-sectional study enrolment metabolic and renal complications data analysis results. HIV-positive ART naïve and experienced adults (18 years and above) in Uganda were enrolled. Data on demographic, dietary, medical, social economic and behaviour was obtained; and biophysical measurements and a clinical examination were undertaken. We measured: fasting glucose and lipid profiles, renal and liver function tests, full blood counts, immunology, virology and HIV drug resistance testing. Plasma samples were stored for future studies. Between July 2013 and October 2014, we enrolled 1095 individuals, of whom 964 (88.0%) were ART experienced (6 months or more), with a median of 9.4 years (IQR 7.0-9.9) on ART. Overall, 968 (88.4%) were aged 35 years and above, 711 (64.9%) were females, 608 (59.6%) were or had ever been on a Tenofovir ART regimen and 236 (23.1%) on a Protease Inhibitor (PI) regimen. There were no differences in renal dysfunction between patients on Tenofovir and Non-Tenofovir containing ART regimens. Patients on PI regimens had higher total cholesterol, lower high density lipoprotein, higher low density lipoprotein, higher triglycerides, and a high atherogenic index for plasma than the non-PI regimen, p = 0.001 or < 0.001. Patients on Non-PI regimens had higher mean diastolic hypertension than patients on PI regimens, p < 0.001. Our finding of no differences in renal dysfunction between patients on Tenofovir and those on Non-Tenofovir containing ART regimens means that Tenofovir based first line ART can safely be initiated even in settings without routine renal function monitoring. However, integration of cardiovascular risk assessment, preventive and curative measures against cardiovascular disease are required. The CoLTART cohort is a good platform to investigate the complications of long-term ART use in Uganda.

Early renal function recovery and long-term graft survival in kidney transplantation.

PubMed

Wan, Susan S; Cantarovich, Marcelo; Mucsi, Istvan; Baran, Dana; Paraskevas, Steven; Tchervenkov, Jean

2016-05-01

Following kidney transplantation (KTx), renal function improves gradually until a baseline eGFR is achieved. Whether or not a recipient achieves the best-predicted eGFR after KTx may have important implications for immediate patient management, as well as for long-term graft survival. The aim of this cohort study was to calculate the renal function recovery (RFR) based on recipient and donor eGFR and to evaluate the association between RFR and long-term death-censored graft failure (DCGF). We studied 790 KTx recipients between January 1990 and August 2014. The last donor SCr prior to organ procurement was used to estimate donor GFR. Recipient eGFR was calculated using the average of the best three SCr values observed during the first 3 months post-KTx. RFR was defined as the ratio of recipient eGFR to half the donor eGFR. 53% of recipients had an RFR ≥1. There were 127 death-censored graft failures (16%). Recipients with an RFR ≥1 had less DCGF compared with those with an RFR <1 (HR 0.56; 95% CI 0.37-0.85; P = 0.006). Transplant era, acute rejection, ECD and DGF were also significant determinants of graft failure. Early recovery of predicted eGFR based on donor eGFR is associated with less DCGF after KTx. © 2016 Steunstichting ESOT.

Risk factors and co-morbidities associated with changes in renal function among antiretroviral treatment-naïve adults in South Africa: A chart review.

PubMed

Assaram, Shirelle; Mashamba-Thompson, Tivani P; Magula, Nombulelo P

2018-01-01

Our systematic scoping review has demonstrated a research gap in antiretroviral treatment (ART) nephrotoxicity as well as in the long-term outcomes of renal function for patients on ART in South Africa. Bearing in mind the high prevalence of human immunodeficiency virus (HIV) in South Africa, this is of great concern. To determine the risk factors and co-morbidities associated with changes in renal function in HIV-infected adults in South Africa. We conducted a retrospective study of 350 ART-naïve adult patients attending the King Edward VIII HIV clinic, Durban, South Africa. Data were collected at baseline (pre-ART) and at six, 12, 18 and 24 months on ART. Renal function was assessed in the 24-month period using the Modification of Diet in Renal Disease equation and was categorised into normal renal function (estimated glomerular filtration rate [eGFR] ≥ 60), moderate renal impairment (eGFR 30-59), severe renal impairment (eGFR 15-29) and kidney failure (eGFR < 15 mL/min/1.73 m 2 ). Generalised linear models for binary data were used to model the probability of renal impairment over the five time periods, controlling for repeated measures within participants over time. Risk ratios and 95% confidence intervals (CI) were reported for each time point versus baseline. The cohort was 64% female, and 99% were Black. The median age was 36 years. At baseline, 10 patients had hypertension (HPT), six had diabetes, 61 were co-infected with tuberculosis (TB) and 157 patients had a high body mass index (BMI) with 25.4% being categorised as overweight and 19.4% as obese. The majority of the patients (59.3%) were normotensive. At baseline, the majority of the patients (90.4%) had normal renal function (95% CI: 86% - 93%), 7.0% (CI: 5% - 10%) had moderate renal impairment, 1.3% (CI: 0% - 3%) had severe renal impairment and 1.3% (CI: 0% - 3%) had renal failure. As BMI increased by one unit, the risk of renal impairment increased by 1.06 (CI: 1.03-1.10) times. The association of HPT with abnormal renal function was found to be insignificant, p > 0.05. The vast majority of patients were initiated on tenofovir disoproxil fumarate (TDF) (90.6%), in combination with lamivudine (3TC) (100%) and either efavirenz (EFV) (56.6%) or nevirapine (NVP) (43.4%). This study reports a low prevalence of baseline renal impairment in HIV-infected ART-naïve outpatients. An improvement in renal function after the commencement of ART has been demonstrated in this population. However, the long-term outcomes of patients with HIV-related renal disease are not known.

Impact of Prophylactic Versus Preemptive Valganciclovir on Long-term Renal Allograft Outcomes

PubMed Central

Spinner, Michael L.; Saab, Georges; Casabar, Ed; Bowman, Lyndsey J.; Storch, Gregory A.; Brennan, Daniel C.

2010-01-01

Background Both prophylactic and preemptive oral valganciclovir therapy are effective for management of cytomegalovirus (CMV) post renal transplantation in the short-term. The long-term effect of either strategy is less well-defined. Methods We analyzed data on 115 adult recipients previously enrolled in a prospective randomized controlled trial of prophylaxis versus preemptive therapy for CMV. The primary outcome was a composite of freedom from acute rejection, graft loss, or death. Secondary outcomes included individual primary outcomes, post-transplant cardiovascular events, new-onset diabetes mellitus after transplant (NODAT), achievement of goal blood pressure, change in body mass index (BMI), interstitial fibrosis/tubular atrophy (IF/TA) and change in renal function. The analysis period was a 48-months post-transplant or date of death/graft loss, whichever was earlier. Results The primary outcome was similar between groups (83% prophylactic versus 81% preemptive, p = 0.754). The secondary outcomes showed similarities between the prophylactic and preemptive groups. Four patients in the prophylactic group (8%) compared to none in the preemptive group (0%) died with a functioning graft, p=0.043. Conclusions Within the limitations of sample size, our data suggest that either strategy for the management of CMV immediately post-transplantation appears effective for patient and graft survival in the long-term. CMV-management is one of many therapeutic strategies incorporated into a renal transplantation protocol which often differs among institutions, and the decision as to which approach to use remains center and resource specific. The increased incidence of death in the prophylactic group requires further investigation. PMID:20555305

Safety and Efficacy Endpoints for Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients.

PubMed

Bank, J R; Rabelink, T J; de Fijter, J W; Reinders, M E J

2015-01-01

Despite excellent short-term graft survival after renal transplantation, the long-term graft outcome remains compromised. It has become evident that a combination of sustained alloreactivity and calcineurin-inhibitor- (CNI-) related nephrotoxicity results in fibrosis and consequently dysfunction of the graft. New immunosuppressive regimens that can minimize or eliminate side effects, while maintaining efficacy, are required to improve long-term graft survival. In this perspective mesenchymal stromal cells (MSCs) are an interesting candidate, since MSCs have immunosuppressive and regenerative properties. The first clinical trials with MSCs in renal transplantation showed safety and feasibility and displayed promising results. Recently, the first phase II studies have been started. One of the most difficult and challenging aspects in those early phase trials is to define accurate endpoints that can measure safety and efficacy of MSC treatment. Since both graft losses and acute rejection rates declined, alternative surrogate markers such as renal function, histological findings, and immunological markers are used to measure efficacy and to provide mechanistic insight. In this review, we will discuss the current status of MSCs in renal transplantation with a focus on the endpoints used in the different experimental and clinical studies.

Renal function, renal volume, and blood pressure in infants with antecedent of antenatal steroids.

PubMed

Carballo-Magdaleno, Deyanira; Guízar-Mendoza, Juan M; Amador-Licona, Norma; Domínguez-Domínguez, Víctor

2011-10-01

Steroids have been used for more than 20 years in preterm infants to induce pulmonary maturity; however, some long-term effects have been reported, such as insulin resistance and elevation of blood pressure. The aim of our study was to compare renal volume, renal function, and blood pressure in infants between 12-36 months of age with and without antecedent of antenatal steroid treatment. This was a cross-sectional study comprised of three groups of infants (n = 30, respectively): preterm infants with and without antecedent of receiving antenatal steroids, respectively, and full-term infants. Blood pressure, renal volume, glomerular filtration rate, and tubular function were measured. Blood pressure and cystatin C levels and glomerular filtration rate were higher in both groups of preterm infants than in the control group (p < 0.01). However, no difference in any of the tested variables between the steroid and non-steroid group of preterm infants. Renal volume was similar in preterm and control infants. Based on these results, we conclude that prematurity independent of antenatal steroid use is associated with higher cystatin C and blood pressure levels and a higher glomerular filtration rate in infants between 12-36 months of age.

Randomized prospective study of the evolution of renal function depending on the anticalcineurin used.

PubMed

Moro, J A; Almenar Bonet, L; Martínez-Dolz, L; Raso, R; Sánchez-Lázaro, I; Agüero, J; Salvador, Antonio

2008-11-01

Renal failure is one of the primary medium- to long-term morbidities in heart transplant (HT) recipients. To a great extent, this renal deterioration is associated with calcineurin inhibitors, primarily cyclosporine A (CsA). It has been suggested that tacrolimus provides better renal function in these patients. We assessed the medium-term evolution of renal function depending on the calcineurin inhibitor used after HT. We assessed 40 consecutive HT recipients over one year. Patients were randomized to receive CsA (n = 20) or tacrolimus (n = 20) in combination with mycophenolate mofetil (1 g/12 h) and deflazacort in decreasing dosages. We analyzed demographic variables before HT, creatinine values before and six months after HT and incidence of acute rejection. No demographic, clinical, or analytical differences were observed were between the two groups before HT. Repeated measures analysis of variance of creatinine values showed no significant differences between the two groups (P = .98). Furthermore, no differences were observed in either the incidence of rejection (P = .02) or rejection-free survival (P = .14). There seems to be no difference in efficacy profile and renal tolerability between CsA and tacrolimus therapy during the first months after HT.

A proteinuria cut-off level of 0.7 g/day after 12 months of treatment best predicts long-term renal outcome in lupus nephritis: data from the MAINTAIN Nephritis Trial

PubMed Central

Tamirou, Farah; Lauwerys, Bernard R; Dall'Era, Maria; Mackay, Meggan; Rovin, Brad; Cervera, Ricard; Houssiau, Frédéric A

2015-01-01

Background Although an early decrease in proteinuria has been correlated with good long-term renal outcome in lupus nephritis (LN), studies aimed at defining a cut-off proteinuria value are missing, except a recent analysis performed on patients randomised in the Euro-Lupus Nephritis Trial, demonstrating that a target value of 0.8 g/day at month 12 optimised sensitivity and specificity for the prediction of good renal outcome. The objective of the current work is to validate this target in another LN study, namely the MAINTAIN Nephritis Trial (MNT). Methods Long-term (at least 7 years) renal function data were available for 90 patients randomised in the MNT. Receiver operating characteristic curves were built to test the performance of proteinuria measured within the 1st year as short-term predictor of long-term renal outcome. We calculated the positive and negative predictive values (PPV, NPV). Results After 12 months of treatment, achievement of a proteinuria <0.7 g/day best predicted good renal outcome, with a sensitivity and a specificity of 71% and 75%, respectively. The PPV was high (94%) but the NPV low (29%). Addition of the requirement of urine red blood cells ≤5/hpf as response criteria at month 12 reduced sensitivity from 71% to 41%. Conclusions In this cohort of mainly Caucasian patients suffering from a first episode of LN in most cases, achievement of a proteinuria <0.7 g/day at month 12 best predicts good outcome at 7 years and inclusion of haematuria in the set of criteria at month 12 undermines the sensitivity of early proteinuria decrease for the prediction of good outcome. The robustness of these conclusions stems from the very similar results obtained in two distinct LN cohorts. Trial registration number: NCT00204022. PMID:26629352

Embolization of renal angiomyolipomas: short-term and long-term outcomes, complications, and tumor shrinkage.

PubMed

Lee, Shen-Yang; Hsu, Hsiang-Hao; Chen, Yung-Chang; Huang, Chen-Chih; Wong, Yon-Cheong; Wang, Li-Jen; Chuang, Cheng-Keng; Yang, Chih-Wei

2009-11-01

This study retrospectively evaluated outcomes, complications, and tumor shrinkage in renal angiomyolipomas after transcatheter arterial embolization (TAE). All renal angiomyolipoma patients who underwent TAE between August 2000 and December 2008 and had short-term (6 months) follow-up images were evaluated. Complications and tumor relapse after TAE were reviewed. The sizes of embolized tumors were measured to calculate size reductions and reduction rates after TAE. Differences in tumor size, size reduction, and reduction rate between different time points (pre-TAE, short-term follow-up, and long-term follow-up) and groups (completely and incompletely embolized) were determined. Eleven renal angiomyolipoma patients who had undergone TAE were included. Seven (63.6%) patients had postembolization syndrome and one had abscess formation following TAE. Two patients had a tumor relapse (18.2%). The mean tumor size was 8.57+/-2.66 cm on pre-TAE images. The mean size reduction was 3.1 cm (33.3%) and 3.8 cm (43.0%) at short-term and long-term follow-up. Tumor sizes differed significantly between pre-TAE and short-term (p=0.004) or long-term images (p=0.022) but not between short-term and long-term images (p=0.059). Results stratified by the completeness of embolization indicate that only the short-term size reduction rate differed significantly (p=0.025), while the long-term reduction rate and short- and long-term follow-up tumor size and size reduction were comparable between the two groups. In conclusion, selective TAE is effective for tumor shrinkage in most renal angiomyolipomas, with acceptable complication and relapse rates. Tumor shrinkage occurring within 6 months after TAE may reflect the long-term effect of TAE.

Calcium phosphate stones during long-term acetazolamide treatment for epilepsy

PubMed Central

Paisley, K; Tomson, C

1999-01-01

We report a case of recurrent renal calculi containing calcium phosphate associated with long-term acetazolamide treatment for epilepsy. Unfortunately, the cause of stone formation was not recognised for many years, by which time irreversible renal damage had occurred.


Keywords: calcium phosphate renal calculi; renal failure; acetazolamide; adverse drug reaction PMID:10474731

Reversal deterioration of renal function accompanied with primary hypothyrodism.

PubMed

Dragović, Tamara

2012-02-01

Hypothyroidism is often accompanied with decline of kidney function, or inability to maintain electrolyte balance. These changes are usually overlooked in everyday practice. Early recognition of this association eliminates unnecessary diagnostic procedures that postpone the adequate treatment. Two patients with elevated serum creatinine levels due to primary autoimmune hypothyroidism, with complete recovery of creatinine clearance after thyroid hormone substitution therapy are presented. The first patient was a young male whose laboratory tests suggested acute renal failure, and the delicate clinical presentation of reduced thyroid function. The second patient was an elderly woman with a history of a long-term signs and symptoms attributed to ageing, including the deterioration of renal function, with consequently delayed diagnosis of hypothyroidism. Serum thyrotropin and thyroxin levels measurement should be done in all cases of renal failure with undefined renal desease, even if the typical clinical presentation of hypothyroidism is absent. Thyroid hormone assays sholud also be performed in all patients with chronic kidney disease whose kidney function is rapidly worsening.

Functional MRI detects perfusion impairment in renal allografts with delayed graft function.

PubMed

Hueper, Katja; Gueler, Faikah; Bräsen, Jan Hinrich; Gutberlet, Marcel; Jang, Mi-Sun; Lehner, Frank; Richter, Nicolas; Hanke, Nils; Peperhove, Matti; Martirosian, Petros; Tewes, Susanne; Vo Chieu, Van Dai; Großhennig, Anika; Haller, Hermann; Wacker, Frank; Gwinner, Wilfried; Hartung, Dagmar

2015-06-15

Delayed graft function (DGF) after kidney transplantation is not uncommon, and it is associated with long-term allograft impairment. Our aim was to compare renal perfusion changes measured with noninvasive functional MRI in patients early after kidney transplantation to renal function and allograft histology in biopsy samples. Forty-six patients underwent MRI 4-11 days after transplantation. Contrast-free MRI renal perfusion images were acquired using an arterial spin labeling technique. Renal function was assessed by estimated glomerular filtration rate (eGFR), and renal biopsies were performed when indicated within 5 days of MRI. Twenty-six of 46 patients had DGF. Of these, nine patients had acute rejection (including borderline), and eight had other changes (e.g., tubular injury or glomerulosclerosis). Renal perfusion was significantly lower in the DGF group compared with the group with good allograft function (231 ± 15 vs. 331 ± 15 ml·min(-1)·100 g(-1), P < 0.001). Living donor allografts exhibited significantly higher perfusion values compared with deceased donor allografts (P < 0.001). Renal perfusion significantly correlated with eGFR (r = 0.64, P < 0.001), resistance index (r = -0.57, P < 0.001), and cold ischemia time (r = -0.48, P < 0.01). Furthermore, renal perfusion impairment early after transplantation predicted inferior renal outcome and graft loss. In conclusion, noninvasive functional MRI detects renal perfusion impairment early after kidney transplantation in patients with DGF. Copyright © 2015 the American Physiological Society.

Renal Angiomyolipoma: Mid- to Long-Term Results Following Embolization with Onyx

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thulasidasan, Narayanan, E-mail: narayanant@doctors.net.uk; Sriskandakumar, Srividhiya; Ilyas, Shahzad

PurposePercutaneous transcatheter embolization is currently the preferred treatment for ruptured or enlarging renal angiomyolipoma (AML), although the optimum choice of embolic material has not yet been established. We present mid- to long-term outcomes following embolization of AMLs with Onyx.Materials and MethodsTen AMLs in seven patients (including two with tuberous sclerosis) were embolized with Onyx. Patients were followed-up clinically, with tumour size and renal function measured pre- and post-procedure.ResultsMean pre-treatment AML size was 63.4 mm (range 42–100). Mean clinical follow-up was 431.4 days (range 153–986) and imaging follow-up 284.2 days (range 30–741). There was no haemorrhage from treated lesions within the follow-up period. Ofmore » patients who had cross-sectional imaging pre- and post-procedure, mean decrease in AML size of 22 mm was seen after Onyx embolization (p = 0.0058, 95 % CI 9.13–34.87). No significant difference between serum creatinine was seen pre- and post-procedure (p = 0.54, 95 % CI 8.63–4.85).ConclusionsOnyx embolization of renal AMLs is effective in the medium to long term, with theoretical benefits in safety and durability of result.« less

Effect of complete or partial proteinuria recovery on long-term outcomes of lupus nephritis.

PubMed

Medina-Rosas, Jorge; Fung, William A; Su, Jiandong; Touma, Zahi

2018-02-01

We aimed to evaluate the effect of complete recovery (CR), partial recovery (PR), and no recovery (NR) of proteinuria at 2 years from the diagnosis of LN on long-term renal and extra-renal outcomes. Patients with LN and proteinuria attending the Lupus Center from 1970 to 2015 were analyzed. At 2 years from diagnosis of LN, patients were divided into three groups (CR, PR, and NR), and long-term outcomes were studied up to 15 years or last visit available. CR was defined as resolution of proteinuria, PR as a reduction ≥50% in baseline proteinuria, and NR as a reduction <50% compared to baseline. Long-term outcomes examined included renal outcomes [low eGFR, ESRD, and composite renal (low eGFR, ESRD, and dialysis/transplant)], cardiovascular outcomes, damage, and death. Kaplan-Meier plots, time-independent and time-dependent Cox proportional hazards models were applied to examine the effect of CR, PR, or NR on long-term outcomes. Of 277 patients, 71.8% achieved CR, 18.4% PR, and 9.8% NR at 2 years. CR compared to NR and CR compared to PR were protective against low eGFR and composite renal outcome in time-independent and time-dependent analyses. CR compared to PR protected against damage in the time-independent analysis. Overall, the comparison of CR and PR favored CR for long-term renal outcomes. CR at 2 years from diagnosis of LN protected against renal outcomes (low eGFR, ESRD/dialysis, and transplant). CR is more favorable compared to PR and clinicians should aim for CR to improve long-term outcomes in LN. Copyright © 2018 Elsevier Inc. All rights reserved.

Severe acute hypophosphatemia during renal replacement therapy adversely affects outcome of critically ill patients with acute kidney injury.

PubMed

Schiffl, Helmut; Lang, Susanne M

2013-02-01

Hypophosphatemia during renal replacement therapy (RRT) is common in critically ill patients with acute kidney injury (AKI). The clinical consequences of RRT-induced phosphate depletion are not well defined in this patient population, and there is no evidence that intravenous sodium phosphate supplementation (PS) prevents the clinical sequelae of acute hypophosphatemia. The purpose of this retrospective analysis of the Acute Renal Support Registry of the University of Munich was to examine the association between severe hypophosphatemia and severity of and recovery from AKI. 289 ICU patients with AKI on intermittent hemodialysis (IHD) were included in the study. One hundred and forty-nine patients received PS during IHD. Outcomes were short-term (at discharge) and long-term (at 1 year) recovery of renal function and mortality. The two patient groups did not differ in demographics, clinical features, renal characteristics, and frequency of hypophosphatemia at initiation of IHD. Without PS, the frequency of hypophosphatemia increased from 20 to 35%. Severe hypophosphatemia was found in 50% of these patients. By comparison, PS was not associated with an increased frequency of hypophosphatemia. Compared with patients with acute phosphate depletion, patients receiving PS developed less oliguria during IHD, had shorter duration of AKI, higher incidence of complete renal recovery at discharge, and a lower risk of de novo chronic kidney disease. Hypophosphatemia was associated with higher all-cause in-hospital mortality and higher risk of long-term mortality. This multicenter study indicates for the first time that hypophosphatemia during IHD adversely affects short- and long-term outcome of critically-ill patients with AKI. The clinical consequences of the acute hypophosphatemic syndrome may be prevented by PS.

Long-term success of combined kidney-lung transplantation in a patient with cystic fibrosis.

PubMed

Borro, José M; Rama, Pablo; Rey, Teresa; Fernández-Rivera, Constantino

2013-06-01

Advanced kidney disease is usually considered an absolute contraindication for lung transplantation due to the difficult management of these patients in the post-operative period. Combined lung-kidney transplantation, however, could offer an opportunity for selected patients with renal and pulmonary dysfunction. This study summarizes the long-term success of a double transplantation in a 38-year-old male patient with cystic fibrosis who presented respiratory and kidney failure. After a complicated post-operative period, the patient currently lives completely independently 46 months after the operation and he enjoys excellent pulmonary and renal function. Copyright © 2012 SEPAR. Published by Elsevier España, S.L. All rights reserved.

Renal function following long-term weight loss in individuals with abdominal obesity on a very-low-carbohydrate diet vs high-carbohydrate diet.

PubMed

Brinkworth, Grant D; Buckley, Jonathan D; Noakes, Manny; Clifton, Peter M

2010-04-01

A frequently cited concern of very-low-carbohydrate diets is the potential for increased risk of renal disease associated with a higher protein intake. However, to date, no well-controlled randomized studies have evaluated the long-term effects of very-low-carbohydrate diets on renal function. To study this issue, renal function was assessed in 68 men and women with abdominal obesity (age 51.5+/-7.7 years, body mass index [calculated as kg/m(2)] 33.6+/-4.0) without preexisting renal dysfunction who were randomized to consume either an energy-restricted ( approximately 1,433 to 1,672 kcal/day), planned isocaloric very-low-carbohydrate (4% total energy as carbohydrate [14 g], 35% protein [124 g], 61% fat [99 g]), or high-carbohydrate diet (46% total energy as carbohydrate [162 g], 24% protein [85 g], 30% fat [49 g]) for 1 year. Body weight, serum creatinine, estimated glomerular filtration rate and urinary albumin excretion were assessed before and after 1 year (April 2006-July 2007). Repeated measures analysis of variance was conducted. Weight loss was similar in both groups (very-low-carbohydrate: -14.5+/-9.7 kg, high-carbohydrate: -11.6+/-7.3 kg; P=0.16). By 1 year, there were no changes in either group in serum creatinine levels (very-low-carbohydrate: 72.4+/-15.1 to 71.3+/-13.8 mumol/L, high-carbohydrate: 78.0+/-16.0 to 77.2+/-13.2 mumol/L; P=0.93 time x diet effect) or estimated glomerular filtration rate (very-low-carbohydrate: 90.0+/-17.0 to 91.2+/-17.8 mL/min/1.73 m(2), high-carbohydrate: 83.8+/-13.8 to 83.6+/-11.8 mL/min/1.73 m(2); P=0.53 time x diet effect). All but one participant was classified as having normoalbuminuria at baseline, and for these participants, urinary albumin excretion values remained in the normoalbuminuria range at 1 year. One participant in high-carbohydrate had microalbuminuria (41.8 microg/min) at baseline, which decreased to a value of 3.1 microg/min (classified as normoalbuminuria) at 1 year. This study provides preliminary evidence that long-term weight loss with a very-low-carbohydrate diet does not adversely affect renal function compared with a high-carbohydrate diet in obese individuals with normal renal function. Copyright (c) 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

Does renal ageing affect survival?

PubMed

Razzaque, M Shawkat

2007-10-01

The effects of ageing on progressive deterioration of renal function, both in human and experimental animals, are described elsewhere, but the effect of renal damage on overall survival and longevity is not yet clearly established. The wild-type animals of various genetic backgrounds, fed with regular diet, overtime develop severe age-associated nephropathy, that include but not limited to inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis. Such renal damage significantly reduces their survival. Reducing renal damage, either by caloric restriction or by suppressing growth hormone (GH)/insulin-like growth factor-1 (IGF-1) activity could significantly enhance the longevity of these animals. Available survival studies using experimental animals clearly suggest that kidney pathology is one of the important non-neoplastic lesions that could affect overall survival, and that restoration of renal function by preventing kidney damage could significantly extend longevity. Careful long-term studies are needed to determine the human relevance of these experimental studies.

Renal transplantation in patients with hepatitis C virus antibody. A long national experience

PubMed Central

Morales, Jose María; Marcén, Roberto; Andres, Amado; Domínguez-Gil, Beatriz; Campistol, Josep María; Gallego, Roberto; Gutierrez, Alex; Gentil, Miguel Angel; Oppenheimer, Federico; Samaniego, María Luz; Muñoz-Robles, Jorge; Serón, Daniel

2010-01-01

Background. Renal transplantation is the best therapy for patients with hepatitis C virus (HCV) infection with end-stage renal disease. Patient and graft survival are lower in the long term compared with HCV-negative patients. The current study evaluated the results of renal transplantation in Spain in a long period (1990–2002), focusing on graft failure. Methods. Data on the Spanish Chronic Allograft Nephropathy Study Group including 4304 renal transplant recipients, 587 of them with HCV antibody, were used to estimate graft and patient survival at 4 years with multivariate Cox models. Results. Among recipients alive with graft function 1 year post-transplant, the 4-year graft survival was 92.8% in the whole group; this was significantly better in HCV-negative vs HCV-positive patients (94.4% vs 89.5%, P < 0.005). Notably, HCV patients showed more acute rejection, a higher degree of proteinuria accompanied by a diminution of renal function, more graft biopsies and lesions of de novo glomerulonephritis and transplant glomerulopathy. Serum creatinine and proteinuria at 1 year, acute rejection, HCV positivity and systolic blood pressure were independent risk factors for graft loss. Patient survival was 96.3% in the whole group, showing a significant difference between HCV-negative vs HCV-positive patients (96.6% vs 94.5%, P < 0.05). Serum creatinine and diastolic blood pressure at 1 year, HCV positivity and recipient age were independent risk factors for patient death. Conclusions. Renal transplantation is an effective therapy for HCV-positive patients with good survival but inferior than results obtained in HCV-negative patients in the short term. Notably, HCV-associated renal damage appears early with proteinuria, elevated serum creatinine showing chronic allograft nephropathy, transplant glomerulopathy and, less frequently, HCV-associated de novo glomerulonephritis. We suggest that HCV infection should be recognized as a true risk factor for graft failure, and preventive measures could include pre-transplant therapy with interferon. PMID:20508864

The science of Stewardship: due diligence for kidney donors and kidney function in living kidney donation--evaluation, determinants, and implications for outcomes.

PubMed

Poggio, Emilio D; Braun, William E; Davis, Connie

2009-10-01

Living kidney donor transplantation is now a common treatment for ESRD because it provides excellent outcomes to transplant recipients and is considered a safe procedure for prospective donors. The short- and long-term safety of prospective donors is paramount to the continued success of this procedure. Whereas the initial experiences with living kidney donors mostly included the healthiest, the increase in the need for organs and the changing demographic characteristics of the general population have subtly reshaped the suitability for donation. Kidney function assessment is a critical component of the evaluation of prospective donors; therefore, special emphasis is usually placed on this aspect of the evaluation. At the same time, consideration of kidney function after donation is important because it assists with the determination of renal health in donors. This review summarizes the process of predonation kidney function assessment, determinants of pre- and postdonation renal function, and, importantly, the potential implications of kidney function to the long-term outcomes of kidney donors.

Post-Discharge Worsening Renal Function in Patients with Type 2 Diabetes and Recent Acute Coronary Syndrome.

PubMed

Morici, Nuccia; Savonitto, Stefano; Ponticelli, Claudio; Schrieks, Ilse C; Nozza, Anna; Cosentino, Francesco; Stähli, Barbara E; Perrone Filardi, Pasquale; Schwartz, Gregory G; Mellbin, Linda; Lincoff, A Michael; Tardif, Jean-Claude; Grobbee, Diederick E

2017-09-01

Worsening renal function during hospitalization for an acute coronary syndrome is strongly predictive of in-hospital and long-term outcome. However, the role of post-discharge worsening renal function has never been investigated in this setting. We considered the placebo cohort of the AleCardio trial comparing aleglitazar with standard medical therapy among patients with type 2 diabetes mellitus and a recent acute coronary syndrome. Patients who had died or had been admitted to hospital for heart failure before the 6-month follow-up, as well as patients without complete renal function data, were excluded, leaving 2776 patients for the analysis. Worsening renal function was defined as a >20% reduction in estimated glomerular filtration rate from discharge to 6 months, or progression to macroalbuminuria. The Cox regression analysis was used to determine the prognostic impact of 6-month renal deterioration on the composite of all-cause death and hospitalization for heart failure. Worsening renal function occurred in 204 patients (7.34%). At a median follow-up of 2 years the estimated rates of death and hospitalization for heart failure per 100 person-years were 3.45 (95% confidence interval [CI], 2.46-6.36) for those with worsening renal function, versus 1.43 (95% CI, 1.14-1.79) for patients with stable renal function. At the adjusted analysis worsening renal function was associated with the composite endpoint (hazard ratio 2.65; 95% CI, 1.57-4.49; P <.001). Post-discharge worsening renal function is not infrequent among patients with type 2 diabetes and acute coronary syndromes with normal or mildly depressed renal function, and is a strong predictor of adverse cardiovascular events. Copyright © 2017 Elsevier Inc. All rights reserved.

Superiority of Serum Cystatin C Over Creatinine in Prediction of Long-Term Prognosis at Discharge From ICU.

PubMed

Ravn, Bo; Prowle, John R; Mårtensson, Johan; Martling, Claes-Roland; Bell, Max

2017-09-01

Renal outcomes after critical illness are seldom assessed despite strong correlation between chronic kidney disease and survival. Outside hospital, renal dysfunction is more strongly associated with mortality when assessed by serum cystatin C than by creatinine. The relationship between creatinine and longer term mortality might be particularly weak in survivors of critical illness. Retrospective observational cohort study. In 3,077 adult ICU survivors, we compared ICU discharge cystatin C and creatinine and their association with 1-year mortality. Exclusions were death within 72 hours of ICU discharge, ICU stay less than 24 hours, and end-stage renal disease. None. During ICU admission, serum cystatin C and creatinine diverged, so that by ICU discharge, almost twice as many patients had glomerular filtration rate less than 60 mL/min/1.73 m when estimated from cystatin C compared with glomerular filtration rate estimated from creatinine, 44% versus 26%. In 743 patients without acute kidney injury, where ICU discharge renal function should reflect ongoing baseline, discharge glomerular filtration rate estimated from creatinine consistently overestimated follow-up glomerular filtration rate estimated from creatinine, whereas ICU discharge glomerular filtration rate estimated from cystatin C well matched follow-up chronic kidney disease status. By 1 year, 535 (17.4%) had died. In survival analysis adjusted for age, sex, and comorbidity, cystatin C was near-linearly associated with increased mortality, hazard ratio equals to 1.78 (95% CI, 1.46-2.18), 75th versus 25th centile. Conversely, creatinine demonstrated a J-shaped relationship with mortality, so that in the majority of patients, there was no significant association with survival, hazard ratio equals to 1.03 (0.87-1.2), 75th versus 25th centile. After adjustment for both creatinine and cystatin C levels, higher discharge creatinine was then associated with lower long-term mortality. In contrast to creatinine, cystatin C consistently associated with long-term mortality, identifying patients at both high and low risk, and better correlated with follow-up renal function. Conversely, lower creatinine relative to cystatin C appeared to confer adverse prognosis, confounding creatinine interpretation in isolation. Cystatin C warrants further investigation as a more meaningful measure of renal function after critical illness.

Understanding the Risk Factors and Long-Term Consequences of Cisplatin-Associated Acute Kidney Injury: An Observational Cohort Study.

PubMed

Bhat, Zeenat Yousuf; Cadnapaphornchai, Pravit; Ginsburg, Kevin; Sivagnanam, Milani; Chopra, Shamit; Treadway, Corey K; Lin, Ho-Sheng; Yoo, George; Sukari, Ammar; Doshi, Mona D

2015-01-01

Acute kidney injury (AKI) is a well-known complication of cisplatin-based chemotherapy; however, its impact on long-term patient survival is unclear. We sought to determine the incidence and risk factors for development of cisplatin-associated AKI and its impact on long-term renal function and patient survival. We identified 233 patients who received 629 cycles of high-dose cisplatin (99±9mg/m2) for treatment of head and neck cancer between 2005 and 2011. These subjects were reviewed for development of AKI. Cisplatin nephrotoxicity (CN) was defined as persistent rise in serum creatinine, with a concomitant decline in serum magnesium and potassium, in absence of use of nephrotoxic agents and not reversed with hydration. All patients were hydrated per protocol and none had baseline glomerular filtration rate (GFR) via CKD-EPI<60mL/min/1.73m2. The patients were grouped based on development of AKI and were staged for levels of injury, per KDIGO-AKI definition. Renal function was assessed via serum creatinine and estimated glomerular filtration rate (eGFR) via CKD-EPI at baseline, 6- and 12-months. Patients with AKI were screened for the absence of nephrotoxic medication use and a temporal decline in serum potassium and magnesium levels. Logistic regression models were constructed to determine risk factors for cisplatin-associated AKI. Twelve-month renal function was compared among groups using ANOVA. Kaplan-Maier curves and Cox proportional hazard models were constructed to study its impact on patient survival. Of 233 patients, 158(68%) developed AKI; 77 (49%) developed stage I, 55 (35%) developed stage II, and 26 (16%) developed stage III AKI. Their serum potassium and magnesium levels correlated negatively with level of injury (p<0.05). African American race was a significant risk factor for cisplatin-associated AKI, OR 2.8 (95% CI 1.3 to 6.3) and 2.8 (95% CI 1.2 to 6.7) patients with stage III AKI had the lowest eGFR value at 12 months (p = 0.05) and long-term patient survival (HR 2.1; p<0.01) than patients with no or lower grades of AKI. Most common causes of death were recurrent cancer (44%) or secondary malignancy elsewhere (40%). Cisplatin-associated severe AKI occurs in 20% of the patients and has a negative impact on long-term renal function and patient survival. PEG tube placement may be protective and should be considered in high risk-patients.

Whole kidney engineering for clinical translation.

PubMed

Kim, Ick-Hee; Ko, In Kap; Atala, Anthony; Yoo, James J

2015-04-01

Renal transplantation is currently the only definitive treatment for end-stage renal disease; however, this treatment is severely limited by the shortage of implantable kidneys. To address this shortcoming, development of an engineered, transplantable kidney has been proposed. Although current advances in engineering kidneys based on decellularization and recellularization techniques have offered great promises for the generation of functional kidney constructs, most studies have been conducted using rodent kidney constructs and short-term in-vivo evaluation. Toward clinical translations of this technique, several limitations need to be addressed. Human-sized renal scaffolds are desirable for clinical application, and the fabrication is currently feasible using native porcine and discarded human kidneys. Current progress in stem cell biology and cell culture methods have demonstrated feasibility of the use of embryonic stem cells, induced pluripotent stem cells, and primary renal cells as clinically relevant cell sources for the recellularization of renal scaffolds. Finally, approaches to long-term implantation of engineered kidneys are under investigation using antithrombogenic strategies such as functional reendothelialization of acellular kidney matrices. In the field of bioengineering, whole kidneys have taken a number of important initial steps toward clinical translations, but many challenges must be addressed to achieve a successful treatment for the patient with end-stage renal disease.

Urinary tract infections in children after renal transplantation.

PubMed

John, Ulrike; Kemper, Markus J

2009-06-01

Urinary tract infections (UTI) after pediatric kidney transplantation (KTX) are an important clinical problem and occur in 15-33% of patients. Febrile UTI, whether occurring in the transplanted kidney or the native kidney, should be differentiated from afebrile UTI. The latter may cause significant morbidity and is usually associated with acute graft dysfunction. Risk factors for (febrile) UTI include anatomical, functional, and demographic factors as well as baseline immunosuppression and foreign material, such as catheters and stents. Meticulous surveillance, diagnosis, and treatment of UTI is important to minimize acute morbidity and compromise of long-term graft function. In febrile UTI, parenteral antibiotics are usually indicated, although controlled data are not available. As most data concerning UTI have been accumulated retrospectively, future prospective studies have to be performed to clarify pathogenetic mechanisms and risk factors, improve prophylaxis and treatment, and ultimately optimize long-term renal graft survival.

Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function.

PubMed

Perco, Paul; Heinzel, Andreas; Leierer, Johannes; Schneeberger, Stefan; Bösmüller, Claudia; Oberhuber, Rupert; Wagner, Silvia; Engler, Franziska; Mayer, Gert

2018-05-03

Donor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular features reported in scientific literature to be associated with chronic allograft nephropathy was created. Significantly enriched biological processes were identified and representative markers were selected. An independent kidney pre-implantation transcriptomics dataset of 76 organs was used to predict estimated glomerular filtration rate (eGFR) values twelve months after transplantation using available clinical data and marker expression values. The best-performing regression model solely based on the clinical parameters donor age, donor gender, and recipient gender explained 17% of variance in post-transplant eGFR values. The five molecular markers EGF, CD2BP2, RALBP1, SF3B1, and DDX19B representing key molecular processes of the constructed renal donor organ status molecular model in addition to the clinical parameters significantly improved model performance (p-value = 0.0007) explaining around 33% of the variability of eGFR values twelve months after transplantation. Collectively, molecular markers reflecting donor organ status significantly add to prediction of post-transplant renal function when added to the clinical parameters donor age and gender.

Effects of PEG-PLA-nano Artificial Cells Containing Hemoglobin on Kidney Function and Renal Histology in Rats

PubMed Central

Liu, Zun Chang; Chang, Thomas M.S.

2012-01-01

This study is to investigate the long-term effects of PEG-PLA nano artificial cells containing hemoglobin (NanoRBC) on renal function and renal histology after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: NanoRBC in Ringer lactate, Ringer lactate, stroma-free hemoglobin (SFHB), polyhemoglobin (PolyHb), autologous rat whole blood (rat RBC). Blood samples were taken before infusions and on days 1, 7 and 21 after infusions for biochemistry analysis. Rats were sacrificed on day 21 after infusions and kidneys were excised for histology examination. Infusion of SFHB induced significant decrease in renal function damage evidenced by elevated serum urea, creatinine and uric acid throughout the 21 days. Kidney histology in SFHb infusion group revealed focal tubular necrosis and intraluminal cellular debris in the proximal tubules, whereas the glomeruli were not observed damaged. In all the other groups, NanoRBC, PolyHb, Ringer lactate and rat RBC, there were no abnormalities in renal biochemistry or histology. In conclusion, injection of NanoRBC did not have adverse effects on renal function nor renal histology. PMID:18979292

The Effect of Patient and Surgical Characteristics on Renal Function After Partial Nephrectomy.

PubMed

Winer, Andrew G; Zabor, Emily C; Vacchio, Michael J; Hakimi, A Ari; Russo, Paul; Coleman, Jonathan A; Jaimes, Edgar A

2018-06-01

The purpose of the study was to identify patient and disease characteristics that have an adverse effect on renal function after partial nephrectomy. We conducted a retrospective review of 387 patients who underwent partial nephrectomy for renal tumors between 2006 and 2014. A line plot with a locally weighted scatterplot smoothing was generated to visually assess renal function over time. Univariable and multivariable longitudinal regression analyses incorporated a random intercept and slope to evaluate the association between patient and disease characteristics with renal function after surgery. Median age was 60 years and most patients were male (255 patients [65.9%]) and white (343 patients [88.6%]). In univariable analysis, advanced age at surgery, larger tumor size, male sex, longer ischemia time, history of smoking, and hypertension were significantly associated with lower preoperative estimated glomerular filtration rate (eGFR). In multivariable analysis, independent predictors of reduced renal function after surgery included advanced age, lower preoperative eGFR, and longer ischemia time. Length of time from surgery was strongly associated with improvement in renal function among all patients. Independent predictors of postoperative decline in renal function include advanced age, lower preoperative eGFR, and longer ischemia time. A substantial number of subjects had recovery in renal function over time after surgery, which continued past the 12-month mark. These findings suggest that patients who undergo partial nephrectomy can experience long-term improvement in renal function. This improvement is most pronounced among younger patients with higher preoperative eGFR. Copyright © 2017 Elsevier Inc. All rights reserved.

Serum aminoacylase-1 is a novel biomarker with potential prognostic utility for long-term outcome in patients with delayed graft function following renal transplantation

PubMed Central

Welberry Smith, Matthew P; Zougman, Alexandre; Cairns, David A; Wilson, Michelle; Wind, Tobias; Wood, Steven L; Thompson, Douglas; Messenger, Michael P; Mooney, Andrew; Selby, Peter J; Lewington, Andrew J P; Banks, Rosamonde E

2013-01-01

Early identification and prognostic stratification of delayed graft function following renal transplantation has significant potential to improve outcome. Mass spectrometry analysis of serum samples, before and on day 2 post transplant from five patients with delayed graft function and five with an uncomplicated transplant, identified aminoacylase-1 (ACY-1) as a potential outcome biomarker. Following assay development, analysis of longitudinal samples from an initial validation cohort of 55 patients confirmed that the ACY-1 level on day 1 or 2 was a moderate predictor of delayed graft function, similar to serum creatinine, complementing the strongest predictor cystatin C. A further validation cohort of 194 patients confirmed this association with area under ROC curves (95% CI) for day 1 serum (138 patients) of 0.74 (0.67–0.85) for ACY-1, 0.9 (0.84–0.95) for cystatin C, and 0.93 (0.88–0.97) for both combined. Significant differences in serum ACY-1 levels were apparent between delayed, slow, and immediate graft function. Analysis of long-term follow-up for 54 patients with delayed graft function showed a highly significant association between day 1 or 3 serum ACY-1 and dialysis-free survival, mainly associated with the donor–brain–dead transplant type. Thus, proteomic analysis provides novel insights into the potential clinical utility of serum ACY-1 levels immediately post transplantation, enabling subdivision of patients with delayed graft function in terms of long-term outcome. Our study requires independent confirmation. PMID:23739232

[Results of combined reconstructions of the renal arteries, abdominal aorta and its other branches in patients with atherosclerosis].

PubMed

Semenov, D V; Ignashov, A M; Turobova, E P; Martynenko, G I; Vakhitov, K M

2012-01-01

A comparative analysis was made of clinical indices and long-term survival in 20 patients (13 men and 7 women of mean age 62 +/- 2 years), having multifocal atherosclerosis of the renal arteries (RA), abdominal aorta and arteries of lower extremities (LE) (11 aneurysms, 7 occlusive lesions of the aorta and 3 of its unpaired branches) who underwent combined reconstructions, with patients having similar lesions, but not operated (12) or operated only on RA or on the arteries of LE (45). The groups of patients had no great differences except more pronounced renal dysfunction (RD) in the first of them. In spite of high postoperative lethality (20%) mainly due to acute renal failure (3), long-term survival proved to be significantly higher (14 from 16), than in not operated (3 from 12) (p = 0.00001) and had better tendency than in those operated on the same basin (35 from 45). In addition, the patients after combined operations had substantially decreased systolic and diastolic arterial pressure (159 +/- 13 vs. 132 +/- 9, p = 0.00001; 91 +/- 5 vs. 83 +/- 7, p = 0.010) and also stabilized renal function.

Long-term efficacy of anti-CD20 antibodies in refractory lupus nephritis.

PubMed

Arce-Salinas, C Alejandro; Rodríguez-García, Felipe; Gómez-Vargas, J Iván

2012-05-01

Eight patients with refractory lupus nephritis received rituximab after failing standard sequential therapy and were followed for 104 weeks after the infusion. One patient died secondary to a complicated pregnancy but had stable renal function. Three patients received a re-infusion of rituximab approximately 12 months apart due to a renal flare; during the second year of follow-up, those patients progressed toward ESRD. The four remaining patients demonstrated improvements in SLEDAI score, CrCl, and proteinuria with maintenance of their standard immunosuppressive therapy and did not require a re-infusion of rituximab. Although rituximab as induction therapy for refractory lupus nephritis has been shown to have a good response, its efficacy in long-term assessments demonstrates disappointing results.

Long term indwelling urethral catheterisation for congenital neuropathic bladder.

PubMed Central

Rickwood, A M; Philp, N H; Thomas, D G

1983-01-01

Long term urethral catheterisation remains an important and effective method of achieving dryness and maintaining renal function in children with congenital neuropathic bladders. Those most likely to require an indwelling catheter are girls who are severely disabled because of myelomeningocele. The management of such catheterisation and its consequences, in the light of our experience with a 100 children treated over a 12 year period, is described. Images Fig. 2 PMID:6847235

Which Frail Older People Are Dehydrated? The UK DRIE Study

PubMed Central

Bunn, Diane K.; Downing, Alice; Jimoh, Florence O.; Groves, Joyce; Free, Carol; Cowap, Vicky; Potter, John F.; Hunter, Paul R.; Shepstone, Lee

2016-01-01

Background: Water-loss dehydration in older people is associated with increased mortality and disability. We aimed to assess the prevalence of dehydration in older people living in UK long-term care and associated cognitive, functional, and health characteristics. Methods: The Dehydration Recognition In our Elders (DRIE) cohort study included people aged 65 or older living in long-term care without heart or renal failure. In a cross-sectional baseline analysis, we assessed serum osmolality, previously suggested dehydration risk factors, general health, markers of continence, cognitive and functional health, nutrition status, and medications. Univariate linear regression was used to assess relationships between participant characteristics and serum osmolality, then associated characteristics entered into stepwise backwards multivariate linear regression. Results: DRIE included 188 residents (mean age 86 years, 66% women) of whom 20% were dehydrated (serum osmolality >300 mOsm/kg). Linear and logistic regression suggested that renal, cognitive, and diabetic status were consistently associated with serum osmolality and odds of dehydration, while potassium-sparing diuretics, sex, number of recent health contacts, and bladder incontinence were sometimes associated. Thirst was not associated with hydration status. Conclusions: DRIE found high prevalence of dehydration in older people living in UK long-term care, reinforcing the proposed association between cognitive and renal function and hydration. Dehydration is associated with increased mortality and disability in older people, but trials to assess effects of interventions to support healthy fluid intakes in older people living in residential care are needed to enable us to formally assess causal direction and any health benefits of increasing fluid intakes. PMID:26553658

Donor age and delayed graft function as predictors of renal allograft survival in rejection-free patients.

PubMed

Moreso, F; Serón, D; Gil-Vernet, S; Riera, L; Fulladosa, X; Ramos, R; Alsina, J; Grinyó, J M

1999-04-01

Transplant recipients of kidneys harvested from old donors have a high incidence of delayed graft function (DGF) and a poor graft outcome. This result is partly explained by the increased incidence of acute rejection in patients suffering from DGF. However, the long-term impact of donor age and DGF in rejection free renal transplants is not well established. The aim of the present work is to evaluate the impact of donor age and DGF on long-term outcome in renal transplants with or without acute rejection. We review all cadaveric kidney transplants performed in our centre between April 1984 and December 1995 treated with a cyclosporin-based immunosuppression. Five hundred and ninety-five patients were included. The overall incidence of DGF was 29.1%, and this event was associated with an increased donor age and cold ischaemia time. Univariate and multivariate analysis showed that graft loss was associated with acute rejection (relative risk (RR) 2.24, 95% confidence interval (CI) 1.62-3.01); DGF (RR 1.83, 95% CI 1.32-2.54); donors >50 years (RR 1.65, 95% CI 1.13-2.38); and retransplantation (RR 1.52, 95% CI 1.01-2.31). In rejection-free patients there were two independent predictors of graft failure: donor >50 years (RR 2.40, 95% CI 1.45-4.01); and DGF (RR 2.42, 95% CI 1.53-3.84). Regardless of the presence of acute rejection, delayed graft function amplifies the detrimental effect of advanced donor age on long-term graft outcome.

Improvement in Renal Function and Symptoms of Patients Treated with Laparoscopic Pyeloplasty for Ureteropelvic Junction Obstruction with Less Than 20% Split Renal Function.

PubMed

Nishi, Morihiro; Matsumoto, Kazumasa; Fujita, Tetsuo; Iwamura, Masatsugu

2016-11-01

To evaluate the efficacy of laparoscopic pyeloplasty (LPP) for lower functioning kidney, we investigated the outcome of this procedure for patients with ureteropelvic junction obstruction with decreased renal function, defined as less than 20% split renal function. Between October 1998 and June 2015, we performed transperitoneal dismembered LPP in 224 patients. Among them, 15 patients with less than 20% split renal function were included in this study. Patient characteristics, perioperative split renal functions, complications, and surgical outcomes were retrospectively investigated. Fourteen of 15 patients had preoperative symptoms, including flank pain in 13 patients and gross hematuria in 1 patient. Preoperative 99mTc-mercaptoacetyltriglycine (MAG3) renogram revealed no response to diuretic injection and median split renal function was 16.5%. Median operative time and blood loss were 170 minutes and 20 mL, respectively. There were no complications during the perioperative period. Postoperative MAG3 renogram at 6 and 12 months after the operation revealed significantly increased split renal function (median: 23.8% and 23.7%, p = 0.001 and 0.008, respectively) and response to diuretic injection in all patients. Preoperative symptoms disappeared and no recurrence was seen during the follow-up period for all patients except for one who experienced flank pain again 4 months after the surgery. He subsequently underwent open pyeloplasty, and flank pain disappeared soon after. LPP for patients with low split renal function and flank pain significantly improved symptoms and split renal functions. Although the long-term clinical effects of LPP are unknown, we recommend performing LPP before considering nephrectomy for patients with lower functioning kidney.

Interaction between renal function and percutaneous edge-to-edge mitral valve repair using MitraClip.

PubMed

Kaneko, Hidehiro; Neuss, Michael; Schau, Thomas; Weissenborn, Jens; Butter, Christian

2017-02-01

MitraClip (MC; Abbott Vascular, Menlo Park, CA, USA) is a treatment option for mitral regurgitation. Renal dysfunction is closely associated with cardiovascular disease. However, the influence of renal function in MC remains not fully understood. In this study, we aimed to clarify the association between renal function and MC. We examined 206 consecutive patients who underwent MC and divided patients into 3 groups according to estimated glomerular filtration rate (eGFR), normal eGFR (≥60mL/min/1.73m 2 ) (n=70), mild chronic kidney disease (CKD) (30-59mL/min/1.73m 2 ) (n=106), and severe CKD (<30mL/min/1.73m 2 ) (n=30). N-terminal pro-B type natriuretic peptide (NT-pro BNP) levels increased with decreasing eGFR. Kaplan-Meier curves revealed that the long-term survival rate significantly decreased with eGFR. After adjustment with the covariates, severe CKD was still associated with mortality. Improved renal function was observed in 30% and associated with baseline lower NT-pro BNP levels. Patients with improved renal function had higher chronic phase survival rate. Renal dysfunction is common in MC patients and the survival rate decreased with eGFR in association with increased NT-pro BNP levels. MC may improve renal function in approximately 30% of MC patients. Improved renal function is associated with lower NT-pro BNP levels and results in satisfactory prognosis. These results implies a close association between renal function and MC treatment. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Long-term medical outcomes among Aboriginal living kidney donors.

PubMed

Storsley, Leroy J; Young, Ann; Rush, David N; Nickerson, Peter W; Ho, Julie; Suon, Vuthana; Karpinski, Martin

2010-08-27

It is unknown whether favorable long-term data on the safety of living kidney donation can be extrapolated to populations at higher risk of chronic kidney disease. Indigenous people (i.e., Aboriginals) have a high prevalence of risk factors for chronic kidney disease and Aboriginal living donor outcomes need to be defined. We performed a retrospective cohort study of all 38 Aboriginal donors donating at our center since 1970 and 76 randomly selected white donor controls to determine the long-term rates of hypertension, diabetes, and renal function postdonation. Follow-up was obtained for 91% of both Aboriginal and white donors (mean follow-up approximately 14 years). Hypertension has been diagnosed more frequently among Aboriginal donors (Ab 42% vs. white 19%, P=0.02). Notably, all 11 Aboriginal donors more than 20 years postdonation have developed hypertension. Diabetes has also been diagnosed more frequently among Aboriginal donors (Ab 19% vs. white 2%, P=0.005), including 5 of 11 (45%) more than 20 years postdonation. Follow-up estimated glomerular filtration rate was higher in Aboriginal donors (Ab 77+/-17 vs. white 67+/-13 mL/min/1.73 m, P=0.002) but not significantly different in adjusted analyses. One Aboriginal donor developed end-stage renal disease 14 years postdonation. Aboriginal living kidney donors at our center have high rates of hypertension and diabetes on long-term follow-up, although renal function is preserved to date. This profile is similar to that of the general unselected Aboriginal population despite detailed medical evaluation before donation. These findings have important implications for donor counseling and may have implications for other high-risk donor populations.

Rifaximin Decreases the Incidence and Severity of Acute Kidney Injury and Hepatorenal Syndrome in Cirrhosis.

PubMed

Dong, Tien; Aronsohn, Andrew; Gautham Reddy, K; Te, Helen S

2016-12-01

While the effects of rifaximin have been shown to be protective against acute kidney injury (AKI) and hepatorenal syndrome (HRS) in alcohol-induced cirrhosis, its long-term effects on the renal function of other cirrhotic patients are unknown. To examine the long-term effects of rifaximin on the renal function of patients with cirrhosis from various etiologies. In a retrospective study, we examined cirrhotic patients at the University of Chicago Liver Clinic from January 1, 2011, to December 31, 2014. The study enrolled patients on rifaximin for ≥90 days, who were then matched by age, gender, and MELD score to a control group. Patients with malignancy and renal replacement therapy (RRT) at baseline were excluded. Data were censored at the last follow-up, termination of rifaximin therapy, initiation of RRT, death, or liver transplant. Eighty-eight rifaximin cases were identified and matched to 88 control cases. Baseline characteristics were similar, with the exceptions of more prevalent long-term midodrine use (≥90 days) (17.0 vs 4.5 %, p = 0.01) and baseline ascites (37.5 vs 23.8 %, p = 0.05) in the rifaximin group. There was no difference in the frequency of infections, deaths, liver transplants, or hospitalizations. After controlling for cofounders, the incidence rate ratio of AKI (IRR 0.71, p = 0.02) and HRS (IRR 0.21, p = 0.02), as well as the risk of requiring RRT (OR 0.23, p = 0.01), was lower in the rifaximin group. Long-term use of rifaximin is associated with a decrease incidence of AKI and HRS and a decrease risk of requiring RRT in a general population of cirrhotic patients.

Predictive abilities of cardiovascular biomarkers to rapid decline of renal function in Chinese community-dwelling population: a 5-year prospective analysis.

PubMed

Fu, Shihui; Liu, Chunling; Luo, Leiming; Ye, Ping

2017-11-09

Predictive abilities of cardiovascular biomarkers to renal function decline are more significant in Chinese community-dwelling population without glomerular filtration rate (GFR) below 60 ml/min/1.73m 2 , and long-term prospective study is an optimal choice to explore this problem. Aim of this analysis was to observe this problem during the follow-up of 5 years. In a large medical check-up program in Beijing, there were 948 participants with renal function evaluated at baseline and follow-up of 5 years. Physical examinations were performed by well-trained physicians. Blood samples were analyzed by qualified technicians in central laboratory. Median rate of renal function decline was 1.46 (0.42-2.91) mL/min/1.73m 2 /year. Rapid decline of renal function had a prevalence of 23.5% (223 participants). Multivariate linear and Logistic regression analyses confirmed that age, sex, baseline GFR, homocysteine and N-terminal pro B-type natriuretic peptide (NT-proBNP) had independently predictive abilities to renal function decline rate and rapid decline of renal function (p < 0.05 for all). High-sensitivity cardiac troponin T (hs-cTnT), carotid femoral pulse wave velocity and central augmentation index had no statistically independent association with renal function decline rate and rapid decline of renal function (p > 0.05 for all). Homocysteine and NT-proBNP rather than hs-cTnT had independently predictive abilities to rapid decline of renal function in Chinese community-dwelling population without GFR below 60 ml/min/1.73m 2 . Baseline GFR was an independent factor predicting the rapid decline of renal function. Arterial stiffness and compliance had no independent effect on rapid decline of renal function. This analysis has a significant implication for public health, and changing the homocysteine and NT-proBNP levels might slow the rapid decline of renal function.

Effect of first myocardial ischemic event on renal function.

PubMed

Eijkelkamp, Wouter B A; de Graeff, Pieter A; van Veldhuisen, Dirk J; van Dokkum, Richard P E; Gansevoort, Ronald T; de Jong, Paul E; de Zeeuw, Dick; Hillege, Hans L

2007-07-01

Effects of cardiovascular dysfunction on renal function have been poorly characterized. Therefore, we investigated the relation between a first ischemic cardiac event and long-term renal function changes in the general population from the PREVEND study. We studied 6,360 subjects with a total follow-up duration of 27.017 subject-years. The estimated mean proportional increase in serum creatinine after a first ischemic cardiac event was 3.1% compared with 0.4% per year of follow-up in subjects without such an event (p = 0.005). This represented a significantly larger decrease in estimated glomerular filtration rate after the event in subjects with an event versus the decrease in subjects without a first ischemic cardiac event (2.2 vs 0.5 ml/min/1.73 m(2)/year of follow-up, p = 0.006). In multivariate analysis with adjustment for renal risk factors, this event showed an independent association with serum creatinine change. In conclusion, a first ischemic cardiac event appears to enhance the natural decrease in renal function. Because even mild renal dysfunction should be considered a major cardiovascular risk factor after myocardial infarction, increased renal function loss after an ischemic cardiac event could add to the risk for subsequent cardiovascular morbidity, thus closing a vicious circle.

Recovery from AKI and short- and long-term outcomes after lung transplantation.

PubMed

Wehbe, Edgard; Duncan, Andra E; Dar, Gohar; Budev, Marie; Stephany, Brian

2013-01-01

Patients with AKI after lung transplantation are at increased risk for CKD and death. Whether patients who completely recover from AKI have improved long-term outcome compared with patients who do not completely recover remains unknown. This study retrospectively evaluated data on 657 patients who underwent lung transplantation from 1997 to 2009. Outcomes analyzed were the incidence of renal recovery after AKI and the association of this recovery with short- and long-term mortality. AKI was defined by an absolute increase in serum creatinine of ≥0.3 mg/dl or a percent increase in serum creatinine of ≥50% from baseline at any time during the first 2 weeks after transplantation. Four hundred twenty-four (65%) patients experienced AKI in the first 2 weeks after transplantation. Of these patients, complete renal recovery occurred in 142 (33%) patients. The incidence of in-hospital complications was similar between patients who recovered renal function and patients without recovery. At 1 year, the cumulative incidence of CKD was 14% and 22% (P=0.10) and patient survival rate was 81% and 76% (P=0.20) in patients with complete recovery from AKI and patients without recovery, respectively. Patients with completely recovered AKI had similar risk-adjusted long-term mortality compared with patients who did not recover (hazard ratio [95% confidence interval]=1.42 [1.15-2.05] versus 1.53 [1.01-2.00]). Patients who recover completely from early AKI after lung transplantation have a similar risk for CKD and long-term mortality compared with patients who do not recover.

Effects of cyclosporine A pretreatment of deceased organ donors on kidney graft function (Cis-A-rein): study protocol for a randomized controlled trial.

PubMed

Orban, Jean-Christophe; Fontaine, Eric; Cassuto, Elisabeth; Baumstarck, Karine; Leone, Marc; Constantin, Jean-Michel; Ichai, Carole

2018-04-17

Renal transplantation represents the treatment of choice of end-stage kidney disease. Delayed graft function (DGF) remains the most frequent complication after this procedure, reaching more than 30%. Its prevention is essential as it impedes early- and long-term prognosis of transplantation. Numerous pharmacological interventions aiming to prevent ischemia-reperfusion injuries failed to reduce the rate of DGF. We hypothesize that cyclosporine as an early preconditioning procedure in donors would be associated with decreased DGF. The Cis-A-rein study is an investigator-initiated, prospective, multicenter, double-blind, randomized, controlled study performed to assess the effects of a donor preconditioning with cyclosporine A on kidney grafts function in transplanted patients. After randomization, a brain dead donor will receive 2.5 mg kg -1 of cyclosporine A or the same volume of 5% glucose solution. The primary objective is to compare the rate of DGF, defined as the need for at least one dialysis session within the 7 days following transplantation, between both groups. The secondary objectives include rate of slow graft function, mild and severe DGF, urine output and serum creatinine during the first week after transplantation, rate of primary graft dysfunction, renal function and mortality at 1 year. The sample size (n = 648) was determined to obtain 80% power to detect a 10% difference for rate of DGF at day 7 between the two groups (30% of the patients in the placebo group and 20% of the patients in the intervention group). Delayed graft function is a major issue after renal transplantation, impeding long-term prognosis. Cyclosporine A pretreatment in deceased donors could improve the outcome of patients after renal transplantation. ClinicalTrials.gov, ID: NCT02907554 Registered on 20 September 2016.

HRV Influence During Renal Transplantation Procedure on Long-Term Mortality.

PubMed

Biernawska, J; Kotfis, K; Kaczmarczyk, M; Błaszczyk, W; Barnik, E; Żukowski, M

2016-06-01

The autonomic nervous system plays an important role in heart function regulation. One of the most acknowledged methods for noninvasive measurement of autonomic system activity is to determine heart rate variability (HRV). Reduced HRV parameters-heart rate rigidity/stiffness-are an independent prognostic factor of sudden cardiac death risk because of arrhythmia. Renal transplantation is an important factor in HRV changes because of hemodynamic and ion disturbances. The main purpose of this study was to determine the influence of HRV disturbances during renal transplantation procedures on long-term mortality in patients with chronic kidney disease. A prospective observation study was performed in the Department of Anesthesiology, Intensive Care, and Acute Poisoning, Pomeranian Medical University, Szczecin, Poland. There were 75 patients (mean age, 47 ± 12 years; 42 men) treated with renal transplantation between 2008 and 2010. Patients were monitored with electrocardiographic tracing with the use of 7 electrodes in position type B. The final stage of analysis was to determine the possible relationship between HRV parameters during the perioperative period and the number of deaths within a 5-year follow-up. HRV parameters during the perioperative period of renal transplantation and the number of deaths within a 5-year follow-up, measured by use of the Holter method, did not differ among patients in the studied population. HRV is a noninvasive and confirmed tool used for the evaluation of autonomic function and mortality risk in patients with end-stage renal disease. HRV parameters recorded in the perioperative period are not optimal stratification tools for estimating the risk of cardiac deaths in patients with end-stage renal disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Hypertension: physiology and pathophysiology.

PubMed

Hall, John E; Granger, Joey P; do Carmo, Jussara M; da Silva, Alexandre A; Dubinion, John; George, Eric; Hamza, Shereen; Speed, Joshua; Hall, Michael E

2012-10-01

Despite major advances in understanding the pathophysiology of hypertension and availability of effective and safe antihypertensive drugs, suboptimal blood pressure (BP) control is still the most important risk factor for cardiovascular mortality and is globally responsible for more than 7 million deaths annually. Short-term and long-term BP regulation involve the integrated actions of multiple cardiovascular, renal, neural, endocrine, and local tissue control systems. Clinical and experimental observations strongly support a central role for the kidneys in the long-term regulation of BP, and abnormal renal-pressure natriuresis is present in all forms of chronic hypertension. Impaired renal-pressure natriuresis and chronic hypertension can be caused by intrarenal or extrarenal factors that reduce glomerular filtration rate or increase renal tubular reabsorption of salt and water; these factors include excessive activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, increased formation of reactive oxygen species, endothelin, and inflammatory cytokines, or decreased synthesis of nitric oxide and various natriuretic factors. In human primary (essential) hypertension, the precise causes of impaired renal function are not completely understood, although excessive weight gain and dietary factors appear to play a major role since hypertension is rare in nonobese hunter-gathers living in nonindustrialized societies. Recent advances in genetics offer opportunities to discover gene-environment interactions that may also contribute to hypertension, although success thus far has been limited mainly to identification of rare monogenic forms of hypertension. © 2012 American Physiological Society

Late-onset renal vein thrombosis: A case report and review of the literature

PubMed Central

Hogan, Jessica L.; Rosenthal, Stanton J.; Yarlagadda, Sri G.; Jones, Jill A.; Schmitt, Timothy M.; Kumer, Sean C.; Kaplan, Bruce; Deas, Shenequa L.; Nawabi, Atta M.

2014-01-01

INTRODUCTION Renal vein thrombosis, a rare complication of renal transplantation, often causes graft loss. Diagnosis includes ultrasound with Doppler, and it is often treated with anticoagulation or mechanical thrombectomy. Success is improved with early diagnosis and institution of treatment. PRESENTATION OF CASE We report here the case of a 29 year-old female with sudden development of very late-onset renal vein thrombosis after simultaneous kidney pancreas transplant. This resolved initially with thrombectomy, stenting and anticoagulation, but thrombosis recurred, necessitating operative intervention. Intraoperatively the renal vein was discovered to be compressed by a large ovarian cyst. DISCUSSION Compression of the renal vein by a lymphocele or hematoma is a known cause of thrombosis, but this is the first documented case of compression and thrombosis due to an ovarian cyst. CONCLUSION Early detection and treatment of renal vein thrombosis is paramount to restoring renal allograft function. Any woman of childbearing age may have thrombosis due to compression by an ovarian cyst, and screening for this possibility may improve long-term graft function in this population. PMID:25528029

Late-onset renal vein thrombosis: A case report and review of the literature.

PubMed

Hogan, Jessica L; Rosenthal, Stanton J; Yarlagadda, Sri G; Jones, Jill A; Schmitt, Timothy M; Kumer, Sean C; Kaplan, Bruce; Deas, Shenequa L; Nawabi, Atta M

2015-01-01

Renal vein thrombosis, a rare complication of renal transplantation, often causes graft loss. Diagnosis includes ultrasound with Doppler, and it is often treated with anticoagulation or mechanical thrombectomy. Success is improved with early diagnosis and institution of treatment. We report here the case of a 29 year-old female with sudden development of very late-onset renal vein thrombosis after simultaneous kidney pancreas transplant. This resolved initially with thrombectomy, stenting and anticoagulation, but thrombosis recurred, necessitating operative intervention. Intraoperatively the renal vein was discovered to be compressed by a large ovarian cyst. Compression of the renal vein by a lymphocele or hematoma is a known cause of thrombosis, but this is the first documented case of compression and thrombosis due to an ovarian cyst. Early detection and treatment of renal vein thrombosis is paramount to restoring renal allograft function. Any woman of childbearing age may have thrombosis due to compression by an ovarian cyst, and screening for this possibility may improve long-term graft function in this population. Published by Elsevier Ltd.

Long term outcome of treatment of end stage renal failure.

PubMed

Henning, P; Tomlinson, L; Rigden, S P; Haycock, G B; Chantler, C

1988-01-01

The most common causes of end stage renal failure in 46 children (mean age 11 years, range 4-14) treated between January 1972 and June 1977 were: reflux nephropathy (n = 12), cystinosis (n = 7), focal and segmental glomerulosclerosis (n = 6), and Schönlein-Henoch disease (n = 5). The quality of life, degree of renal function, and height attainment of the 31 survivors were assessed in June 1985, when their mean age was 22 years (range 14-27), using hospital records and a questionnaire designed to highlight social and psychological problems. Twenty six patients had a functioning transplanted kidney. Average growth during treatment for all survivors was normal, but most were disappointed with their 'final height'. Though five patients had some form of disabling bone disease, all 31 could walk and 27 could run. Sixteen (67%) were in full or part time employment and nine were living independently. A group of 32 patients with juvenile onset diabetes treated at this hospital for at least five years were also asked to complete the questionnaire and of these, 17 responded. On average, their data could usefully be compared with those of cases of end stage renal failure. More of the diabetics had jobs, but most sexually mature patients with renal disease were concerned about their physical appearance and had not achieved any stable long term sexual relationships. We suggest that a poor body image resulting in low self esteem may be responsible for the deficiency and believe that further study in this group is warranted.

Combined predictive value of the expanded donor criteria for long-term graft survival of kidneys from donors after cardiac death: A single-center experience over three decades.

PubMed

Kusaka, Mamoru; Kubota, Yusuke; Sasaki, Hitomi; Fukami, Naohiko; Fujita, Tamio; Hirose, Yuichi; Takahashi, Hiroshi; Kenmochi, Takashi; Shiroki, Ryoichi; Hoshinaga, Kiyotaka

2016-04-01

Kidneys procured from the deceased hold great potential for expanding the donor pool. The aims of the present study were to investigate the post-transplant outcomes of renal allografts recovered from donors after cardiac death, to identify risk factors affecting the renal prognosis and to compare the long-term survival from donors after cardiac death according to the number of risk factors shown by expanded criteria donors. A total of 443 grafts recovered using an in situ regional cooling technique from 1983 to 2011 were assessed. To assess the combined predictive value of the significant expanded criteria donor risk criteria, the patients were divided into three groups: those with no expanded criteria donor risk factors (no risk), one expanded criteria donor risk factor (single-risk) and two or more expanded criteria donor risk factors (multiple-risk). Among the donor factors, age ≥50 years, hypertension, maximum serum creatinine level ≥1.5 mg/dL and a warm ischemia time ≥30 min were identified as independent predictors of long-term graft failure on multivariate analysis. Regarding the expanded criteria donors criteria for marginal donors, cerebrovascular disease, hypertension and maximum serum creatinine level ≥1.5 mg/dL were identified as significant predictors on univariate analysis. The single- and multiple-risk groups showed 2.01- and 2.40-fold higher risks of graft loss, respectively. Renal grafts recovered from donors after cardiac death donors have a good renal function with an excellent long-term graft survival. However, an increased number of expanded criteria donors risk factors increase the risk of graft loss. © 2016 The Japanese Urological Association.

Intermediate Volume on Computed Tomography Imaging Defines a Fibrotic Compartment that Predicts Glomerular Filtration Rate Decline in Autosomal Dominant Polycystic Kidney Disease Patients

PubMed Central

Caroli, Anna; Antiga, Luca; Conti, Sara; Sonzogni, Aurelio; Fasolini, Giorgio; Ondei, Patrizia; Perico, Norberto; Remuzzi, Giuseppe; Remuzzi, Andrea

2011-01-01

Total kidney and cyst volumes have been used to quantify disease progression in autosomal dominant polycystic kidney disease (ADPKD), but a causal relationship with progression to renal failure has not been demonstrated. Advanced image processing recently allowed to quantify extracystic tissue, and to identify an additional tissue component named “intermediate,” appearing hypoenhanced on contrast-enhanced computed tomography (CT). The aim of this study is to provide a histological characterization of intermediate volume, investigate its relation with renal function, and provide preliminary evidence of its role in long-term prediction of functional loss. Three ADPKD patients underwent contrast-enhanced CT scans before nephrectomy. Histological samples of intermediate volume were drawn from the excised kidneys, and stained with hematoxylin and eosin and with saturated picrosirius solution for histological analysis. Intermediate volume showed major structural changes, characterized by tubular dilation and atrophy, microcysts, inflammatory cell infiltrate, vascular sclerosis, and extended peritubular interstitial fibrosis. A significant correlation (r = −0.69, P < 0.001) between relative intermediate volume and baseline renal function was found in 21 ADPKD patients. Long-term prediction of renal functional loss was investigated in an independent cohort of 13 ADPKD patients, followed for 3 to 8 years. Intermediate volume, but not total kidney or cyst volume, significantly correlated with glomerular filtration rate decline (r = −0.79, P < 0.005). These findings suggest that intermediate volume may represent a suitable surrogate marker of ADPKD progression and a novel therapeutic target. PMID:21683674

Two-year outcomes after diagnostic and therapeutic fetal cystoscopy for lower urinary tract obstruction.

PubMed

Sananes, Nicolas; Cruz-Martinez, Rogelio; Favre, Romain; Ordorica-Flores, Ricardo; Moog, Raphaël; Zaloszy, Ariane; Giron, Amilcar Martins; Ruano, Rodrigo

2016-04-01

Our objective is to report long-term outcome after fetal cystoscopy for lower urinary tract obstruction (LUTO), as well as to investigate the accuracy of fetal cystoscopy in diagnosing the cause of bladder outlet obstruction. This is a retrospective cohort study of all fetuses who underwent cystoscopy for prenatal diagnosis of LUTO in three tertiary referral centers. Fetal diagnostic cystoscopy was performed to determine prenatally the cause of LUTO and to ablate the posterior urethral valves (PUV). A total of 50 fetal cystoscopies were performed, revealing PUV in 31 (62%) fetuses, urethral atresia (UA) in 14 (28%) fetuses, and urethral stenosis (US) in 5 (10%) fetuses. Two fetuses had trisomy 18 diagnosed after fetal cystoscopy and were excluded from the present analysis. Fetal cystoscopy was accurate in the diagnosis of the etiology of LUTO in 32/35 (91.4%). There were no survivors in the UA group. One fetus with US underwent urethral stenting and survived with normal renal function at 2 years of life. Among the infants with PUV, 17/30 (56.7%) infants survived, and 13/17 (76.5%) had normal renal function at 1 year of life; 15/28 (53.6%) infants survived, and 11/15 (73.3%) had normal renal function at 2 years. Fetal cystoscopy is accurate in the diagnosis of the etiology of LUTO and serves as a guide to the specific prenatal treatment. This procedure is associated with modest long-term survival (54%) but with adequate preserved normal renal function in two thirds of the infants among fetuses with PUV. © 2016 John Wiley & Sons, Ltd.

Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient.

PubMed

Azar, Ibrahim; Esfandiarifard, Saghi; Sinai, Pedram; Wazir, Ali; Foulke, Llewellyn; Mehdi, Syed

2017-01-01

Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN), in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib) or antibodies (bevacizumab) suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.

Vesico-ureteric reflux: occurrence and long-term risks.

PubMed

Jacobson, S H; Hansson, S; Jakobsson, B

1999-11-01

The prevalence of vesico-ureteric reflux in the general population is unknown, but it is increased in risk groups, such as children with symptomatic urinary tract infection, schoolgirls with asymptomatic bacteriuria, first-degree relatives of patients with reflux and children with prenatal dilatation of their upper urinary tract. Children and adults with pyelonephritic renal scarring are at risk of serious long-term complications, e.g. hypertension and renal failure. Modern paediatric care, with early detection and treatment of urinary tract infections and reflux during childhood and adolescence, may improve long-term prognosis. In the adult patient with established pyelonephritic renal scarring, careful control of hypertension may retard the rate of progression, and angiotensin converting enzyme inhibitors may have renal protective properties.

Safety and Efficacy of Teneligliptin in Patients with Type 2 Diabetes Mellitus and Impaired Renal Function: Interim Report from Post-marketing Surveillance.

PubMed

Haneda, Masakazu; Kadowaki, Takashi; Ito, Hiroshi; Sasaki, Kazuyo; Hiraide, Sonoe; Ishii, Manabu; Matsukawa, Miyuki; Ueno, Makoto

2018-06-01

Teneligliptin is a novel oral dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes mellitus (T2DM). Safety and efficacy of teneligliptin have been demonstrated in clinical studies; however, data supporting its use in patients with moderate or severe renal impairment are limited. This interim analysis of a post-marketing surveillance of teneligliptin, exploRing the long-term efficacy and safety included cardiovascUlar events in patients with type 2 diaBetes treated bY teneligliptin in the real-world (RUBY), aims to verify the long-term safety and efficacy of teneligliptin in Japanese patients with T2DM and impaired renal function. For this analysis, we used the data from case report forms of the RUBY surveillance between May 2013 and June 2017. The patients were classified into G1-G5 stages of chronic kidney disease according to estimated glomerular filtration rate (eGFR) at initiation of teneligliptin treatment. Safety and efficacy were evaluated in these subgroups. Patients on dialysis were also assessed. Safety was assessed from adverse drug reactions (ADRs). Glycemic control was evaluated up to 2 years after teneligliptin initiation. A total of 11,677 patients were enrolled in the surveillance and 11,425 patient case-report forms were collected for the interim analysis. The incidence of ADRs in each subgroup was 2.98-6.98% of patients, with no differences in the ADR profile (including hypoglycemia and renal function ADRs) between subgroups. At 1 and 2 years after starting teneligliptin, the least-squares mean change in HbA1c adjusted to the baseline was - 0.68 to - 0.85% and - 0.71 to - 0.85% across the eGFR groups, respectively. Treatment with teneligliptin in patients on dialysis reduced or tended to reduce glycated albumin levels [- 2.29%, (p < 0.001) after 1 year; - 1.64%, (p = 0.064) after 2 years]. During long-term treatment, teneligliptin was generally well tolerated in patients with any stage of renal impairment from normal to end-stage renal disease, including those on dialysis, and improved glycemic control. Japic CTI-153047. Mitsubishi Tanabe Pharma Corporation and Daiichi Sankyo Co, Ltd.

Efficacy of Intravenous Cyclophosphamide Pulse Therapy for P-Glycoprotein-expressing B Cell-associated Active True Renal Lupus Vasculitis in Lupus Nephritis

PubMed Central

Kawabe, Akio; Tsujimura, Shizuyo; Saito, Kazuyoshi; Tanaka, Yoshiya

2017-01-01

True renal lupus vasculitis (TRLV), a vascular lesion usually associated with proliferative lupus nephritis (LN), is resistant to conventional treatments. The expression of P-glycoprotein (P-gp) on activated lymphocytes causes drug resistance. We herein report a patient with TRLV, minimal change LN, overexpression of P-gp on peripheral B cells, and accumulation of P-gp+ B cells at the site of TRLV. High-dose corticosteroids combined with intravenous cyclophosphamide pulse therapy resulted in clinical remission and the long-term normal renal function. PMID:28626187

Commercial cadaveric renal transplant: an ethical rather than medical issue.

PubMed

Sun, Chiao-Yin; Lee, Chin-Chan; Chang, Chiz-Tzung; Hung, Cheng-Chih; Wu, Mai-Szu

2006-01-01

Donor organ shortage is a universal problem. The organ source has been extended to controversial death-penalty outlaws in certain countries. It was claimed that commercial transplant had a worse short-term clinical outcome. The aim of this study is to investigate the long-term outcome of patients receiving commercial cadaveric renal transplant. Seventy-five renal transplant recipients receiving long-term follow-up were included. Thirty-one patients received overseas commercial cadaveric transplant. Forty-four patients had legal domestic transplant in Taiwan. The age of the patients receiving the commercial cadaveric transplant was significantly older than those with legal domestic transplant (commerical vs. legal: 46.1 +/- 11.4 vs. 35.6 +/- 9.0 yr old, p < 0.001). The renal function estimated by creatinine and 1/creatinine up to eight yr showed no significant difference between the two groups. The graft survivals of the two groups were not different. The mortality rate between the two groups was comparable in 10 yr (91.1% in domestic and 88.9% in overseas). There was no significant difference in de novo viral hepatitis, cytomegalovirus infection, and acute rejection. The clinical outcome of overseas commercial cadaveric transplant was not different from the domestic legal transplant. To stop the unethical procedure, ethnicity and humanity are the major concerns.

Which Frail Older People Are Dehydrated? The UK DRIE Study.

PubMed

Hooper, Lee; Bunn, Diane K; Downing, Alice; Jimoh, Florence O; Groves, Joyce; Free, Carol; Cowap, Vicky; Potter, John F; Hunter, Paul R; Shepstone, Lee

2016-10-01

Water-loss dehydration in older people is associated with increased mortality and disability. We aimed to assess the prevalence of dehydration in older people living in UK long-term care and associated cognitive, functional, and health characteristics. The Dehydration Recognition In our Elders (DRIE) cohort study included people aged 65 or older living in long-term care without heart or renal failure. In a cross-sectional baseline analysis, we assessed serum osmolality, previously suggested dehydration risk factors, general health, markers of continence, cognitive and functional health, nutrition status, and medications. Univariate linear regression was used to assess relationships between participant characteristics and serum osmolality, then associated characteristics entered into stepwise backwards multivariate linear regression. DRIE included 188 residents (mean age 86 years, 66% women) of whom 20% were dehydrated (serum osmolality >300 mOsm/kg). Linear and logistic regression suggested that renal, cognitive, and diabetic status were consistently associated with serum osmolality and odds of dehydration, while potassium-sparing diuretics, sex, number of recent health contacts, and bladder incontinence were sometimes associated. Thirst was not associated with hydration status. DRIE found high prevalence of dehydration in older people living in UK long-term care, reinforcing the proposed association between cognitive and renal function and hydration. Dehydration is associated with increased mortality and disability in older people, but trials to assess effects of interventions to support healthy fluid intakes in older people living in residential care are needed to enable us to formally assess causal direction and any health benefits of increasing fluid intakes. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Long-term effects of moderate protein diet on renal function and low-grade inflammation in older adults with type 2 diabetes and chronic kidney disease.

PubMed

Giordano, Mauro; Ciarambino, Tiziana; Castellino, Pietro; Cataliotti, Alessandro; Malatino, Lorenzo; Ferrara, Nicola; Politi, Cecilia; Paolisso, Giuseppe

2014-09-01

The aim of this study was to determine the long-term effects of a moderate protein diet (MPD) on renal function, low-grade inflammation, and oxidative stress in older adults with type 2 diabetes, which to date are unclear. Seventy-four older adults with type 2 diabetes and chronic kidney disease (stage G3b-G4) were enrolled in the study. During the 4-wk baseline period (T0), all patients were asked to follow a normal protein diet regimen, providing 1.1 g/kg daily. Successively, all patients were asked to follow an MPD, for 36 mo, providing 0.7 g/kg daily, for only 6 d/wk. Patients who refused to follow an MPD treatment were included in the control (NPD [normal protein diet] group). During the 36 mo of the study, creatinine clearance, blood urea nitrogen, proteinuria, blood pressure, glycated hemoglobin (Hb)A1c, fat-free mass, low-grade inflammation (interleukin-6 and C-reactive protein) were evaluated monthly and oxidative stress (urinary 8-epiprostaglandin [Epi-PG]F2α) was evaluated every 3 mo. During T0, mean creatinine clearance, proteinuria, blood urea nitrogen, blood pressure, HbA1c, fat free mass, low-grade inflammation, and oxidative stress were similar in both groups. After 36 mo, a significant reduction in decline of renal function was observed in the MPD group but not in controls (2.4 ± 0.2 versus 5.7 ± 0.5 mL·min·y, respectively; P < 0.05 versus control). Similarly, a significant reduction in proteinuria, serum interleukin-6, serum C-reactive protein, and urinary 8-Epi-PGF2α excretion, was observed in the MPD group (P < 0.05 versus NPD). In older adults with type 2 diabetes, long-term effects of an MPD regimen are associated with a significant decline of renal function, proteinuria, low-grade inflammation, and oxidative stress without a change in fat-free mass. Copyright © 2014 Elsevier Inc. All rights reserved.

Low Birth Weight due to Intrauterine Growth Restriction and/or Preterm Birth: Effects on Nephron Number and Long-Term Renal Health

PubMed Central

Zohdi, Vladislava; Sutherland, Megan R.; Lim, Kyungjoon; Gubhaju, Lina; Zimanyi, Monika A.; Black, M. Jane

2012-01-01

Epidemiological studies have clearly demonstrated a strong association between low birth weight and long-term renal disease. A potential mediator of this long-term risk is a reduction in nephron endowment in the low birth weight infant at the beginning of life. Importantly, nephrons are only formed early in life; during normal gestation, nephrogenesis is complete by about 32–36 weeks, with no new nephrons formed after this time during the lifetime of the individual. Hence, given that a loss of a critical number of nephrons is the hallmark of renal disease, an increased severity and acceleration of renal disease is likely when the number of nephrons is already reduced prior to disease onset. Low birth weight can result from intrauterine growth restriction (IUGR) or preterm birth; a high proportion of babies born prematurely also exhibit IUGR. In this paper, we describe how IUGR and preterm birth adversely impact on nephrogenesis and how a subsequent reduced nephron endowment at the beginning of life may lead to long-term risk of renal disease, but not necessarily hypertension. PMID:22970368

Impact of pretransplant renal function on survival after liver transplantation.

PubMed

Gonwa, T A; Klintmalm, G B; Levy, M; Jennings, L S; Goldstein, R M; Husberg, B S

1995-02-15

To determine the effect of pretransplant liver function on survival following orthotopic liver transplantation and to quantify the effects of cyclosporine administration on long-term renal function in patients undergoing liver transplant, we performed an analysis of a prospectively maintained database. Data from 569 consecutive patients undergoing liver transplantation alone who were treated with CsA for immunosuppression were used for this study. Actuarial graft and patient survival rates were calculated using Kaplan-Meier statistics. Glomerular filtration rates, serum creatinine, and the use of various immunosuppressives were analyzed for this study. The initial analysis demonstrated that patients presenting for liver transplant with hepatorenal syndrome have a significantly decreased acturial patient survival after liver transplant at 5 years compared with patients without hepatorenal syndrome (60% vs. 68%, P < 0.03). Patients with hepatorenal syndrome recovered their renal function after liver transplant. Patients who had hepatorenal syndrome were sicker and required longer stays in the intensive care unit, longer hospitalizations, and more dialysis treatments after transplantation compared with patients who did not have hepatorenal syndrome. The incidence of end-stage renal disease after liver transplantation in patients who had hepatorenal syndrome was 7%, compared with 2% in patients who did not have hepatorenal syndrome. To more fully examine the effect of pretransplant renal function on posttransplant survival, the non-hepatorenal syndrome patients were divided into quartiles depending upon their pretransplant renal function. The patients with the lowest pretransplant renal function had the same survival as the patients with the highest pretransplant renal function. In addition, there was no increased incidence of acute or chronic rejection in any of the groups. The patients with the lower pretransplant renal function were treated with more azathioprine to maintain renal function and had a negligible decrease in glomerular filtration rate following transplant. Conversely, patients with the highest level of renal function pretransplant had a 40% decline in renal function in the first year, but maintained stable renal function up to 4 years after transplant. We conclude that pretransplant renal function other than hepato-renal syndrome has no effect on patient survival after orthotopic liver transplant. Renal function after liver transplant is stable after an initial decline, despite continued administration of CsA.(ABSTRACT TRUNCATED AT 400 WORDS)

Impact of Continuous Administration of Tolvaptan on Preventing Medium-Term Worsening Renal Function and Long-Term Adverse Events in Heart Failure Patients with Chronic Kidney Disease.

PubMed

Nakano, Yusuke; Mizuno, Tomofumi; Niwa, Toru; Mukai, Kentaro; Wakabayashi, Hirokazu; Watanabe, Atsushi; Ando, Hirohiko; Takashima, Hiroaki; Murotani, Kenta; Waseda, Katsuhisa; Amano, Tetsuya

2018-01-27

Tolvaptan (TLV) has an inhibiting effect for worsening renal function (WRF) in acute decompensated heart failure (HF) patients. However, there are limited data regarding the effect of continuous TLV administration on medium-term WRF.This was a retrospective observational study in hospitalized HF patients with chronic kidney disease (CKD). TLV was administered to those patients with fluid retention despite standard HF therapy. We compared 34 patients treated with TLV (TLV group) to 33 patients treated with conventional HF therapy with high-dose loop diuretics (furosemide ≥ 40 mg) (Loop group). Clinical outcomes, including the incidence of medium-term WRF, defined as increase of serum creatinine > 0.3 mg/dL, at 6 months after discharge and adverse events rate, were evaluated.Baseline patient characteristics were not different between the TLV and Loop group. The TLV group consisted of less frequent use of loop diuretics and carperitide compared with the Loop group. The incidence of medium-term WRF was significantly lower in the TLV group than in the Loop group (3.2% versus 31.0%, P = 0.002). Multivariate logistic analysis showed that the TLV non-user was an independent predictor of medium-term WRF. Kaplan-Meier analysis revealed that the long-term event-free survival was significantly higher in the TLV group (log-rank P = 0.01).Continuous administration of TLV may reduce the risk of medium-term WRF, resulting possibility in improvement of long-term adverse outcomes in HF patients with CKD.

Effects of Bosutinib Treatment on Renal Function in Patients With Philadelphia Chromosome-Positive Leukemias.

PubMed

Cortes, Jorge E; Gambacorti-Passerini, Carlo; Kim, Dong-Wook; Kantarjian, Hagop M; Lipton, Jeff H; Lahoti, Amit; Talpaz, Moshe; Matczak, Ewa; Barry, Elly; Leip, Eric; Brümmendorf, Tim H; Khoury, H Jean

2017-10-01

The purpose of the study was to assess renal function in patients with Philadelphia chromosome-positive leukemias receiving bosutinib or imatinib. Patients received first-line bosutinib (n = 248) or imatinib (n = 251; phase III trial), or second-line or later bosutinib (phase I/II trial; n = 570). Adverse events (AEs) and changes from baseline in estimated glomerular filtration rate (eGFR) and serum creatinine were assessed. Time from the last patient's first dose to data cutoff was ≥ 48 months. Renal AEs were reported in 73/570 patients (13%) receiving second-line or later bosutinib, and in 22/248 (9%) and 16/251 (6%) receiving first-line bosutinib and imatinib, respectively. eGFR in patients receiving bosutinib declined over time with more patients developing Grade ≥ 3b eGFR (< 45 mL/min/1.73 m 2 according to the Modification of Diet in Renal Disease method) with second-line or later bosutinib (139/570, 24%) compared with first-line bosutinib (26/248, 10%) and imatinib (25/251, 10%); time to Grade ≥ 3b eGFR was shortest with second-line or later bosutinib. Similar proportions of patients receiving second-line or later bosutinib (74/139, 53%), first-line bosutinib (15/26, 58%), and first-line imatinib (15/25, 60%) improved to ≥ 45 mL/min/1.73 m 2 eGFR as of the last follow-up. In a regression analysis, first-line treatment with bosutinib versus imatinib was not a significant predictor of Grade ≥ 3b eGFR. Long-term bosutinib treatment is associated with an apparently reversible decline in renal function with frequency and characteristics similar to renal decline observed with long-term imatinib treatment. Patients with risk factors for Grade ≥ 3b eGFR should be monitored closely. Copyright © 2017 Elsevier Inc. All rights reserved.

Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats.

PubMed

Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

2015-01-01

Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography-tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney.

Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats

PubMed Central

Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

2015-01-01

Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography–tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney. PMID:26485038

Comparing renal function preservation after laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for clinical T1a renal tumor: using a 3D parenchyma measurement system.

PubMed

Zhu, Liangsong; Wu, Guangyu; Huang, Jiwei; Wang, Jianfeng; Zhang, Ruiyun; Kong, Wen; Xue, Wei; Huang, Yiran; Chen, Yonghui; Zhang, Jin

2017-05-01

To compare the renal function preservation between laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy. Data were analyzed from 246 patients who underwent laparoscopic radio frequency ablation assisted tumor enucleation and laparoscopic partial nephrectomy for solitary cT1a renal cell carcinoma from January 2013 to July 2015. To reduce the intergroup difference, we used a 1:1 propensity matching analysis. The functional renal parenchyma volume preservation were measured preoperative and 12 months after surgery. The total renal function recovery and spilt GFR was compared. Multivariable logistic analysis was used for predictive factors for renal function decline. After 1:1 propensity matching, each group including 100 patients. Patients in the laparoscopic radio frequency ablation assisted tumor enucleation had a smaller decrease in estimate glomerular filtration rate at 1 day (-7.88 vs -20.01%, p < 0.001), 3 months (-2.31 vs -10.39%, p < 0.001), 6 months (-2.16 vs -7.99%, p = 0.015), 12 months (-3.26 vs -8.03%, p = 0.012) and latest test (-3.24 vs -8.02%, p = 0.040), also had better functional renal parenchyma volume preservation (89.19 vs 84.27%, p < 0.001), lower decrease of the spilt glomerular filtration rate (-9.41 vs -17.13%, p < 0.001) at 12 months. The functional renal parenchyma volume preservation, warm ischemia time and baseline renal function were the important independent factors in determining long-term functional recovery. The laparoscopic radio frequency ablation assisted tumor enucleation technology has unique advantage and potential in preserving renal parenchyma without ischemia damage compared to conventional laparoscopic partial nephrectomy, and had a better outcome, thus we recommend this technique in selected T1a patients.

Xenon treatment attenuates early renal allograft injury associated with prolonged hypothermic storage in rats.

PubMed

Zhao, Hailin; Yoshida, Akira; Xiao, Wei; Ologunde, Rele; O'Dea, Kieran P; Takata, Masao; Tralau-Stewart, Catherine; George, Andrew J T; Ma, Daqing

2013-10-01

Prolonged hypothermic storage elicits severe ischemia-reperfusion injury (IRI) to renal grafts, contributing to delayed graft function (DGF) and episodes of acute immune rejection and shortened graft survival. Organoprotective strategies are therefore needed for improving long-term transplant outcome. The aim of this study is to investigate the renoprotective effect of xenon on early allograft injury associated with prolonged hypothermic storage. Xenon exposure enhanced the expression of heat-shock protein 70 (HSP-70) and heme oxygenase 1 (HO-1) and promoted cell survival after hypothermia-hypoxia insult in human proximal tubular (HK-2) cells, which was abolished by HSP-70 or HO-1 siRNA. In the brown Norway to Lewis rat renal transplantation, xenon administered to donor or recipient decreased the renal tubular cell death, inflammation, and MHC II expression, while delayed graft function (DGF) was therefore reduced. Pathological changes associated with acute rejection, including T-cell, macrophage, and fibroblast infiltration, were also decreased with xenon treatment. Donors or recipients treated with xenon in combination with cyclosporin A had prolonged renal allograft survival. Xenon protects allografts against delayed graft function, attenuates acute immune rejection, and enhances graft survival after prolonged hypothermic storage. Furthermore, xenon works additively with cyclosporin A to preserve post-transplant renal function.

Exercise as an anabolic intervention in patients with end-stage renal disease.

PubMed

Ikizler, T Alp

2011-01-01

Muscle wasting and accompanying structural derangements leading to abnormalities in muscle function, exercise performance, and physical activity are common in patients with end-stage renal disease. Therefore, several studies have been performed examining the effects of exercise in this particular patient population. Most of the studies have assessed the effects of cardiopulmonary fitness training, whereas a few have examined the role of resistance (i.e., strength) training. Despite the proven efficacy of resistance exercise as an anabolic intervention in the otherwise healthy elderly population and certain chronic disease states, recent studies in patients on maintenance hemodialysis have not been encouraging in terms of long-term improvements in markers of muscle mass. Preliminary studies indicated that a combination of simultaneous exercise and nutritional supplementation could augment the anabolic effects of exercise, at least in the acute setting. However, a recent randomized clinical trial failed to show further benefits of additional resistance exercise on long-term somatic protein accretion above and beyond nutritional supplementation alone. Further research is necessary to both understand the observed lack of obvious benefits and strategies to improve the exercise regimens in patients with end-stage renal disease. Published by Elsevier Inc.

Robotic Partial Nephrectomy in Patients with Chronic Kidney Disease: Objective Measurement of Short- and Long-term Renal Functional Outcomes.

PubMed

Chalouhy, Charbel; Ruck, Jessica Moore; Zhou, Tian Cheng; Srivastava, Abhishek; Keehn, Aryeh; Watts, Kara L; Maria, Pedro; Ghavamian, Reza

2018-05-31

Minimal literature informs the use of robotic partial nephrectomy (RPN) in patients with chronic kidney disease (CKD). Therefore, we evaluated the renal functional outcomes in CKD patients undergoing RPN. We reviewed a prospective database of patients undergoing RPN 2010-2015 and identified 182 patients who had preoperative and postoperative nuclear renal scintigraphy (at 2 and 12 months postop). Pre-operative and 12-month post-operative eGFR (mL/min/1.73m2, by MDRD) were calculated. CKD was defined as eGFR <60mL/min/1.73m2 (CKD stages III&IV). Changes in creatinine, eGFR and split function on Mercaptuacetyltriglycine (MAG) 3 scan were compared by baseline CKD status. Correlations between pre- and post-operative eGFR were calculated. Of 182 patients, 30 (16.5%) had baseline CKD. Preoperative eGFR was 48.5 and 99.0 in CKD and non-CKD patients, respectively (p<0.001). From pre-operation to 12 months post-operation, eGFR decreased by 2.8 and 1.1 mL/min/1.73m2, respectively (p=0.6). On MAG-3 scan, the contribution of the surgical kidney to overall renal function decreased by 5.0% and 4.8% (p = 0.9) in the CKD and non-CKD cohorts, respectively. When comparing renal scans at 2 and 12 months post-operation, in both groups the surgical kidney significantly recovered (both p<0.001) and the patterns of kidney function recovery was similar in both groups (CKD +2.0%, non-CKD +1.4%, p=0.6). On long-term follow-up (>2years), eGFR did not change significantly in either the CKD or non-CKD group (-2.8 vs -1.1 mL/min/1.73m2, p=0.6). On pathology, tumors were more frequently malignant in CKD vs. non-CKD patients (93.3% vs 73.2%, p=0.02) and of higher Fuhrman Grade (grade >3: 49.7% vs 28.1%, p<0.001). RPN is a reasonable treatment option in patients with CKD, as it did not lead to a greater decline in renal function contributed by the surgical kidney. The patterns of kidney function recovery after surgery are similar between patients with and without CKD.

Developmental Programming of Renal Function and Re-Programming Approaches.

PubMed

Nüsken, Eva; Dötsch, Jörg; Weber, Lutz T; Nüsken, Kai-Dietrich

2018-01-01

Chronic kidney disease affects more than 10% of the population. Programming studies have examined the interrelationship between environmental factors in early life and differences in morbidity and mortality between individuals. A number of important principles has been identified, namely permanent structural modifications of organs and cells, long-lasting adjustments of endocrine regulatory circuits, as well as altered gene transcription. Risk factors include intrauterine deficiencies by disturbed placental function or maternal malnutrition, prematurity, intrauterine and postnatal stress, intrauterine and postnatal overnutrition, as well as dietary dysbalances in postnatal life. This mini-review discusses critical developmental periods and long-term sequelae of renal programming in humans and presents studies examining the underlying mechanisms as well as interventional approaches to "re-program" renal susceptibility toward disease. Clinical manifestations of programmed kidney disease include arterial hypertension, proteinuria, aggravation of inflammatory glomerular disease, and loss of kidney function. Nephron number, regulation of the renin-angiotensin-aldosterone system, renal sodium transport, vasomotor and endothelial function, myogenic response, and tubuloglomerular feedback have been identified as being vulnerable to environmental factors. Oxidative stress levels, metabolic pathways, including insulin, leptin, steroids, and arachidonic acid, DNA methylation, and histone configuration may be significantly altered by adverse environmental conditions. Studies on re-programming interventions focused on dietary or anti-oxidative approaches so far. Further studies that broaden our understanding of renal programming mechanisms are needed to ultimately develop preventive strategies. Targeted re-programming interventions in animal models focusing on known mechanisms will contribute to new concepts which finally will have to be translated to human application. Early nutritional concepts with specific modifications in macro- or micronutrients are among the most promising approaches to improve future renal health.

Developmental Programming of Renal Function and Re-Programming Approaches

PubMed Central

Nüsken, Eva; Dötsch, Jörg; Weber, Lutz T.; Nüsken, Kai-Dietrich

2018-01-01

Chronic kidney disease affects more than 10% of the population. Programming studies have examined the interrelationship between environmental factors in early life and differences in morbidity and mortality between individuals. A number of important principles has been identified, namely permanent structural modifications of organs and cells, long-lasting adjustments of endocrine regulatory circuits, as well as altered gene transcription. Risk factors include intrauterine deficiencies by disturbed placental function or maternal malnutrition, prematurity, intrauterine and postnatal stress, intrauterine and postnatal overnutrition, as well as dietary dysbalances in postnatal life. This mini-review discusses critical developmental periods and long-term sequelae of renal programming in humans and presents studies examining the underlying mechanisms as well as interventional approaches to “re-program” renal susceptibility toward disease. Clinical manifestations of programmed kidney disease include arterial hypertension, proteinuria, aggravation of inflammatory glomerular disease, and loss of kidney function. Nephron number, regulation of the renin–angiotensin–aldosterone system, renal sodium transport, vasomotor and endothelial function, myogenic response, and tubuloglomerular feedback have been identified as being vulnerable to environmental factors. Oxidative stress levels, metabolic pathways, including insulin, leptin, steroids, and arachidonic acid, DNA methylation, and histone configuration may be significantly altered by adverse environmental conditions. Studies on re-programming interventions focused on dietary or anti-oxidative approaches so far. Further studies that broaden our understanding of renal programming mechanisms are needed to ultimately develop preventive strategies. Targeted re-programming interventions in animal models focusing on known mechanisms will contribute to new concepts which finally will have to be translated to human application. Early nutritional concepts with specific modifications in macro- or micronutrients are among the most promising approaches to improve future renal health. PMID:29535992

Acute renal failure induced by markedly decreased appetite secondary to a depressive episode after discontinuation of long-term lithium therapy in an elderly patient with bipolar disorder.

PubMed

Okada, Akira

2014-05-16

Some elderly patients on chronic lithium therapy for bipolar disorder and their doctors may be faced with a therapeutic dilemma over whether or not to continue prescribing/taking lithium given their increased risk of reduced renal function. We present the case of a 78-year-old woman with bipolar disorder who discontinued lithium therapy due to increased risk factors for renal injury. After discontinuation, she experienced markedly decreased appetite secondary to a depressive episode, and developed acute renal failure, which subsequently progressed to a more advanced stage of chronic kidney disease. This case suggests that extreme care must be taken to prevent the recurrence of depression in elderly patients with bipolar disorder who discontinue lithium therapy, even when they had been emotionally stable for a long time while receiving lithium. Medications other than lithium for bipolar disorder may be needed at the time lithium therapy is discontinued. 2014 BMJ Publishing Group Ltd.

Can quantity of amniotic fluid reliably predict postnatal renal function in boys with posterior urethral valves: a decision curve analysis.

PubMed

Harper, Luke; Waubant, Alice; Vignes, Julien; Amat, Sara; Dobremez, Eric; Lefevre, Yan; Ferdynus, Cyril

2017-09-01

Prenatal management of male fetuses with suspected posterior urethral valves depends on reliable markers for postnatal long-term renal function. Whether ultrasound parameters, including the presence or absence of oligohydramnios, are reliable remains the subject of debate. We decided to evaluate the reliability of quantity of amniotic fluid to predict postnatal renal function using decision curve analysis (DCA), a method for evaluating the clinical utility of a diagnostic test. We analyzed retrospectively 51 male fetuses born with prenatally suspected posterior urethral valves between 2009 and 2012. We studied the relationship between quantity of amniotic fluid on prenatal ultrasound and the nadir creatinine during the first year of life as a proxy of postnatal renal function using DCA. Twelve fetuses presented with prenatal oligohydramnios. Thirty-one children had a normal nadir creatinine, of which one had prenatal oligohydramnios (3.2%). Thirteen had a nadir creatinine between 35 and 75 μmol/L, of which four had prenatal oligohydramnios (30.8%). Seven had a nadir creatinine >75 μmol/L, all of them had prenatal oligohydramnios. In this retrospective study, DCA confirms the relationship between prenatal quantity of amniotic fluid volume and postnatal renal function. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

Transient prehypertensive treatment in spontaneously hypertensive rats: a comparison of losartan and amlodipine regarding long-term blood pressure, cardiac and renal protection.

PubMed

Peng, Feng; Lin, Jinxiu; Lin, Liming; Tang, Hong

2012-12-01

The aim of this study was to compare the effectiveness of transient prehypertensive treatment with losartan compared with amlodipine in spontaneously hypertensive rats (SHRs) on long-term blood pressure (BP), cardiac and renal protection. SHRs were prehypertensively treated with losartan, amlodipine or saline. Rats were followed up until 46 weeks of age. The left ventricular (LV) geometry and function were assessed by echocardiography. Angiotensin II (Ang II) and aldosterone (Aldo) were measured by radioimmunoassay. Ang II type 1 (AT1R) and type 2 (AT2R) receptor protein expression was determined by western blotting. The systolic blood pressure (SBP) in losartan-treated SHRs (SHR-Los) was persistently reduced until 46 weeks of age, but returned to untreated SHR levels in amlodipine-treated SHRs (SHR-Aml) from 30 weeks onwards. Compared to untreated SHRs, the albuminuria excretion in SHR-Los at week 46 was markedly decreased, the plasma, myocardium and renal tissue Ang II and Aldo levels in SHR-Los at week 46 were markedly decreased; AT1R and TGF-β1 protein expression was downregulated and AT2R protein was upregulated. Compared to untreated SHRs, the left ventricular mass index (LVMI) and collagen volume fraction (CVF) in SHR-Los were markedly decreased until week 46, and the left ventricular ejection fraction (LVEF) and cardiac brain natriuretic peptide mRNA expression were improved, whereas similar LVMI and elevated CVF were observed in SHR-Aml, and the LVEF decreased significantly below that of untreated SHRs at week 46, with cardiac BNP mRNA expression increasing slightly. Prehypertensive treatment with losartan was more effective than amlodipine on delaying long-term BP increase and ameliorating cardiac, renal structure and function, which may be related to the permanent attenuation of the circulating and local renin-angiotensin systems.

Long-term exposure to tenofovir continuously decrease renal function in HIV-1-infected patients with low body weight: results from 10 years of follow-up.

PubMed

Nishijima, Takeshi; Kawasaki, Yohei; Tanaka, Noriko; Mizushima, Daisuke; Aoki, Takahiro; Watanabe, Koji; Kinai, Ei; Honda, Haruhito; Yazaki, Hirohisa; Tanuma, Junko; Tsukada, Kunihisa; Teruya, Katsuji; Kikuchi, Yoshimi; Gatanaga, Hiroyuki; Oka, Shinichi

2014-08-24

To investigate the effect of long-term tenofovir disoproxil fumarate (TDF) use on renal function, especially in patients with low body weight who are vulnerable to TDF nephrotoxicity. A single-center, observational study in Tokyo, Japan. We performed a 10 years cohort study of 792 HIV-1-infected patients. The effect of long-term TDF use on estimated glomerular filtration rate (eGFR) was investigated on treatment-naive patients who started TDF-containing antiretroviral therapy (n = 422) and those who started abacavir-containing antiretroviral therapy as control (n = 370). Three renal endpoints were examined by the logistic regression model: decrement in eGFR of higher than 10 ml/min per 1.73 m relative to the baseline, more than 25% decrement in eGFR, and eGFR lower than 60 ml/min per 1.73 m at least 3 months apart. The loss in eGFR was estimated using linear mixed models for repeated measures. The median weight at baseline was 63 kg. TDF use increased the risk of all three renal outcomes compared with the control group: higher than 10 ml/min per 1.73 m decrement in eGFR [adjusted odds ratio (OR) = 2.1, 95% confidence interval (CI) 1.45-3.14, P < 0.001], more than 25% decrement (adjusted OR = 2.1, 95% CI 1.50-2.90, P < 0.001), and eGFR lower than 60 ml/min per 1.73 m at least 3 months apart (adjusted OR = 3.9, 95% CI 1.62-9.36, P = 0.002). The cumulative mean loss relative to the control after 1, 2, 3, 4, and 5 years of TDF exposure was -3.8, -3.6, -5.5, -6.6, and -10.3 ml/min per 1.73 m, respectively, indicating that the loss in eGFR increased over time (P < 0.001). In this cohort of patients with low body weight, TDF exposure increased the risk of renal dysfunction. Furthermore, the loss in eGFR relative to the control increased continuously up to 5 years.

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

PubMed Central

Wang, Xuexiang; Johnson, Ashley C.; Williams, Jan M.; White, Tiffani; Chade, Alejandro R.; Zhang, Jie; Liu, Ruisheng; Roman, Richard J.; Lee, Jonathan W.; Kyle, Patrick B.; Solberg-Woods, Leah

2015-01-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%–75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. PMID:25349207

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.

PubMed

Wang, Xuexiang; Johnson, Ashley C; Williams, Jan M; White, Tiffani; Chade, Alejandro R; Zhang, Jie; Liu, Ruisheng; Roman, Richard J; Lee, Jonathan W; Kyle, Patrick B; Solberg-Woods, Leah; Garrett, Michael R

2015-07-01

Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney. Copyright © 2015 by the American Society of Nephrology.

One-year renal and cardiac effects of bisoprolol versus losartan in recently diagnosed hypertensive patients: a randomized, double-blind study.

PubMed

Parrinello, Gaspare; Paterna, Salvatore; Torres, Daniele; Di Pasquale, Pietro; Mezzero, Manuela; La Rocca, Gabriella; Cardillo, Mauro; Trapanese, Caterina; Caradonna, Mario; Licata, Giuseppe

2009-01-01

Hypertension is a significant cause of chronic renal injury and its effective treatment is capable of reducing the rate of renal failure. beta-Adrenoceptor antagonists (beta-blockers) have been reported to induce a deterioration in renal function, while several data have indicated a renoprotective effect of treatment with the angiotensin II type 1 receptor antagonist losartan. Previous studies of the interaction between the selective beta(1)-blocker bisoprolol and kidney function were performed only for short- and medium-term periods. The aim of this study was to compare the antihypertensive efficacy and renal and cardiac haemodynamic effects of bisoprolol with those of losartan over a 1-year time period in patients with essential hypertension. Seventy-two patients (40 males) with recently diagnosed uncomplicated (European Society of Hypertension [ESH] criteria stage 1-2) hypertension (mean +/- SD age 52 +/- 12 years) were enrolled in the study. After a run-in period of 14 days on placebo, the patients were randomized in a double-blind, prospective study to receive either bisoprolol 5 mg or losartan 50 mg, administered once daily for 1 year. At recruitment and 12 months after treatment, cardiac output and renal haemodynamics and function were evaluated by echocardiography and radionuclide studies, respectively. There were no significant differences in baseline clinical data, including glomerular filtration rate and blood pressure, between the two treatment groups. At 1 year, blood pressure had decreased significantly (p < 0.001) with both treatments, and heart rate was reduced only in the group taking bisoprolol. The long-term effects on renal haemodynamics and cardiac function were similar with both drugs, the only change being a significant reduction in the filtration fraction for each group. These data suggest that both bisoprolol and losartan are effective agents for the treatment of patients with recently diagnosed ESH stage 1-2 hypertension. Over a 1-year period, both agents maintained good renal and cardiac performance and haemodynamics.

Current Insights into Long Non-Coding RNAs in Renal Cell Carcinoma

PubMed Central

Seles, Maximilian; Hutterer, Georg C.; Kiesslich, Tobias; Pummer, Karl; Berindan-Neagoe, Ioana; Perakis, Samantha; Schwarzenbacher, Daniela; Stotz, Michael; Gerger, Armin; Pichler, Martin

2016-01-01

Renal cell carcinoma (RCC) represents a deadly disease with rising mortality despite intensive therapeutic efforts. It comprises several subtypes in terms of distinct histopathological features and different clinical presentations. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts in the genome which vary in expression levels and length and perform diverse functions. They are involved in the inititation, evolution and progression of primary cancer, as well as in the development and spread of metastases. Recently, several lncRNAs were described in RCC. This review emphasises the rising importance of lncRNAs in RCC. Moreover, it provides an outlook on their therapeutic potential in the future. PMID:27092491

Cutting Balloon Angioplasty (CBA) for the Treatment of Renal Artery Fibromuscular Dysplasia (FMD) in Six Patients: 5-Year Long-Term Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cotroneo, Antonio Raffaele; Amoroso, Luigi; Giammarino, Alberto

PurposeTo evaluate long-term outcomes in terms of hypertension control, recurrent stenosis, and reinterventions from patients who underwent cutting balloon angioplasty (CBA) for symptomatic renal artery fibromuscular dysplasia (FMD).Materials and MethodsFrom 2011, six consecutive renal artery FMD women underwent CBA for poorly controlled hypertension, despite antihypertensive therapy. Follow-up consisted of blood pressure monitoring and duplex ultrasonography at 1, 6, and 12 months and thereafter annually for 5 years.ResultsAll treatments were technically successful. Recurrence of hypertension was found in two patients within 12 months, and reinterventions were performed using CBA.ConclusionResults show the efficacy of CBA for renal artery FMD.

The cost effectiveness of tacrolimus versus microemulsified cyclosporin: a 10-year model of renal transplantation outcomes.

PubMed

Orme, Michelle E; Jurewicz, Wieslaw A; Kumar, Nagappan; McKechnie, Tracy L

2003-01-01

In 1983, the launch of cyclosporin was a significant clinical advance for organ transplant recipients. Subsequent drug research led to further advances with the introduction of cyclosporin microemulsion (cyclosporin ME) and tacrolimus. This paper presents the results from a long-term model comparing the clinical and economic outcomes associated with cyclosporin ME and tacrolimus immunosuppression for the prevention of graft rejection following renal transplantation. A model was developed to project the costs and outcomes over a 10-year period following transplantation. The model was based on the results of a prospective, randomised study of 179 renal transplantation recipients receiving either cyclosporin ME or tacrolimus, which was conducted by the Welsh Transplantation Research Group (median follow-up: 2.7 years). The short-term costs and outcomes were the averages from the actual head-to-head trial data. From this, the long-term costs and outcomes were extrapolated based on the rate of change in patient and graft survival at 3, 5 and 10 years post transplant, as reported in the 1995 United Kingdom Transplant Support Service Authority Renal Transplant Audit. PERSPECTIVE AND YEAR OF COST DATA: The analysis was conducted from the perspective of a UK transplant unit. Costs were at 1999 prices (pounds sterling 1 = dollars US 1.42 = Euro 1.5) and costs and outcomes were discounted at 6% and 1.5%, respectively. The model estimated that 10 years after transplantation, the proportion of patients surviving was 56% of the cyclosporin ME cohort and 64% of the tacrolimus cohort. The cumulative cost of maintenance therapy at 10 years was pounds sterling 23204 per patient maintained on cyclosporin ME versus pounds sterling 23803 per patient on tacrolimus. The cost per survivor at 10 years was pounds sterling 37000 (tacrolimus) versus pounds sterling 41000 (cyclosporin ME) and the cost per patient with a functioning graft was pounds sterling 39000 versus pounds sterling 45000. A Monte Carlo simulation of the model (10000 simulations) gave an average cost at 10 years of pounds sterling 23279 (SD pounds sterling 3457) for cyclosporin ME and pounds sterling 22841 (SD pounds sterling 3590) for tacrolimus. A (second order) probabilistic sensitivity analysis was also performed. The average cost at 10 years from a simulated cohort of 1000 was pounds sterling 23473 (SD pounds sterling 2154) for cyclosporin ME and pounds sterling 24087 (SD pounds sterling 2025) for tacrolimus. Renal transplant recipients maintained on tacrolimus have better short- and long-term outcomes than patients maintained on cyclosporin ME. The long-term use of tacrolimus is a more cost-effective solution in terms of the number of survivors, patients with a functioning graft and rejection-free patients.

Personality traits and long-term health status. The influence of neuroticism and conscientiousness on renal deterioration in type-1 diabetes.

PubMed

Brickman, A L; Yount, S E; Blaney, N T; Rothberg, S T; De-Nour, A K

1996-01-01

Stringent long-term control of blood glucose concentration in patients with insulin-dependent diabetes mellitus (IDDM) can decrease albuminuria, presumably forestalling development of renal insufficiency. Personality characteristics may influence a diabetic patient's ability and willingness to follow a prescribed regimen to achieve glycemic control. This study investigated the relationship of 2 personality factors to renal deterioration time (from initiation of insulin therapy to renal failure) in 85 patients with IDDM and end-stage renal disease. Persons moderate in the personality trait of neuroticism and high in conscientiousness had renal deterioration times that were 12 years longer than persons with either high or low neuroticism and low conscientiousness, presumably because of better self-care. The implications of this study's findings are discussed.

Optimising the use of mTOR inhibitors in renal transplantation.

PubMed

Russ, Graeme R

2013-11-20

Renal transplantation is the treatment of choice for end-stage renal failure. Although advances in immunosuppression have led to improvements in short-term outcomes, graft survival beyond 5 to 10 years has not improved. One of the major causes of late renal allograft failure is chronic allograft nephropathy, a component of which is nephrotoxicity from the use of calcineurin inhibitors (CNIs). In addition, premature patient death is a major limitation of renal transplantation and the major causes are cancer, cardiovascular disease and infection. CNI-free immunosuppressive regimens based on mammalian target of rapamycin (mTOR) inhibitors have been trial led over the last few years and have defined the rational use of these agents. Conversion from a CNI-based to an mTOR-inhibitor-based regimen has been successful at improving renal function for a number of years after conversion, although long-term survival outcomes are still awaited. The studies suggest that the safest and most effective time to convert is between 1 and 6 months after transplant. In addition, mTOR-inhibitor-based regimens have been shown to be associated with lower rates of post-transplant malignancy and less cytomegalovirus infection, which may add further to the appeal of this approach.

Serum uric acid is a GFR-independent long-term predictor of acute and chronic renal insufficiency: the Jerusalem Lipid Research Clinic cohort study

PubMed Central

Kark, Jeremy D.

2011-01-01

Background. Kidney disease is commonly accompanied by hyperuricemia. However, the contribution of serum uric acid (SUA) to kidney injury is debated. Our objective was to assess the long-term prediction of renal failure by SUA. Methods. Visit 2 participants in the Jerusalem Lipid Research Clinic cohort with normal baseline kidney function were followed for 24–28 years. SUA levels were assessed for associations with acute renal failure (ARF) and chronic renal failure (CRF) as defined by hospital discharge records, and mortality, ascertained through linkage with the national population registry. Results. Among 2449 eligible participants (1470 men, 979 women aged 35–78 years in 1976–79), SUA was positively linked with male sex, serum creatinine and components of the metabolic syndrome but was lower in smokers and in diabetic subjects. The 22- to 25-year incidence of hospital-diagnosed kidney failure (145 first events, 67% CRF) and the 24- to 28-year mortality (587 events) were higher in subject with hyperuricemia (>6.5 mg/dL in men and >5.3 mg/dL in women, reflecting the upper quintiles), independent of baseline kidney function and covariates. Hyperuricemia conferred adjusted hazard ratios of 1.36 (P = 0.003), 2.14 (P < 0.001) and 2.87 (P = 0.003) for mortality, CRF and ARF, respectively. Conclusions. SUA predicts renal failure incidence and all-cause mortality independently of demographic and clinical covariates. These results lend support to the undertaking of clinical trials to examine the effect of uric acid-lowering strategies on kidney outcomes. PMID:21220750

Colchicine triggered severe rhabdomyolysis after long-term low-dose simvastatin therapy: a case report.

PubMed

Frydrychowicz, Clara; Pasieka, Bastian; Pierer, Matthias; Mueller, Wolf; Petros, Sirak; Weidhase, Lorenz

2017-01-04

Rhabdomyolysis is a widely recognized yet rare complication in statin use. Rhabdomyolysis might be triggered by the prescription of high doses of statins or by statin accumulation due to interactions with concomitant medication. Muscle cell destruction as evidenced by myoglobin elevation can induce potentially life-threatening acute renal failure. We report a case of a 70-year-old obese white man with sudden onset of severe rhabdomyolysis with consecutive renal failure. His medication included low-dose simvastatin, which he had taken for 6 years up until the event. The statin was withdrawn immediately. After 3 days of veno-venous hemofiltration his renal function was completely restored. Clinicians in both primary and special care might be unaware that side effects of statins do occur even after a long uneventful statin medication; they should be advised not to exclude that possibility upfront, even if a patient has tolerated the medication for years.

Congenital renal arteriovenous fistula during the first trimester diagnosed with ultrasonography.

PubMed

Yao, Mengyun; Zhang, Qiuyan; Wang, Jing; Xiang, Feixiang; Yu, Cheng; Lv, Qing; Xie, Mingxing; Zhang, Yanrong

2017-01-01

A case of congenital renal arteriovenous fistula (AVF) complicating pregnancy with gross hematuria was managed successfully by superselective embolization with metallic coils. The patient was in the first trimester of her pregnancy at 12 weeks of gestation. The AVF was detected by color Doppler sonography and confirmed by renal arteriography. Because of its easy accessibility and absence of irradiation, ultrasound is the first choice for pregnant patients. Color Doppler ultrasound is effective in diagnosing AVF, and it is also helpful in the long-term followup after treatment. The cirsoid-type renal congenital arteriovenous fistula has a characteristic sonographic appearance with a cluster of tubular anechoic structures in the kidney, which produce continuous turbulent high-velocity flow signals and a burr-like boundary flow spectrum. When the sonographic features are present, the diagnosis of renal AVF should be made, after which renal arteriography can be performed to confirm it. Selective embolization provided a safe and effective treatment with minimal damage to the parenchyma and without compromising renal function.

The natural history of renal function after surgical management of renal cell carcinoma: Results from the Canadian Kidney Cancer Information System.

PubMed

Mason, Ross; Kapoor, Anil; Liu, Zhihui; Saarela, Olli; Tanguay, Simon; Jewett, Michael; Finelli, Antonio; Lacombe, Louis; Kawakami, Jun; Moore, Ronald; Morash, Christopher; Black, Peter; Rendon, Ricardo A

2016-11-01

Patients who undergo surgical management of renal cell carcinoma (RCC) are at risk for chronic kidney disease and its sequelae. This study describes the natural history of renal function after radical and partial nephrectomy and explores factors associated with postoperative decline in renal function. This is a multi-institutional cohort study of patients in the Canadian Kidney Cancer Information System who underwent partial or radical nephrectomy for RCC. Estimated glomerular filtration rate (eGFR) and stage of chronic kidney disease were determined preoperatively and at 3, 12, and 24 months postoperatively. Linear regression was used to determine the association between postoperative eGFR and type of surgery (radical vs. partial), duration of ischemia, ischemia type (warm vs. cold), and tumor size. With a median follow-up of 26 months, 1,379 patients were identified from the Canadian Kidney Cancer Information System database including 665 and 714 who underwent partial and radical nephrectomy, respectively. Patients undergoing radical nephrectomy had a lower eGFR (mean = 19ml/min/1.73m 2 lower) at 3, 12, and 24 months postoperatively (P<0.001). Decline in renal function occurred early and remained stable throughout follow-up. A lower preoperative eGFR and increasing age were also associated with a lower postoperative eGFR (P<0.01). Ischemia type and duration were not predictive of postoperative decline in eGFR (P>0.05). Severe renal failure (eGFR<30ml/min/1.73m 2 ) developed postoperatively in 12.5% and 4.1% of radical and partial nephrectomy patients, respectively (P<0.001). After the initial postoperative decline, renal function remains stable in patients undergoing surgery for RCC. Patients undergoing radical nephrectomy have a greater long-term reduction in renal function compared with those undergoing partial nephrectomy. Ischemia duration and type are not predictive of postoperative renal function when adhering to generally short ischemia durations. Copyright © 2016 Elsevier Inc. All rights reserved.

Ischemia and reperfusion injury in renal transplantation: hemodynamic and immunological paradigms

PubMed Central

Requião-Moura, Lúcio Roberto; Durão, Marcelino de Souza; de Matos, Ana Cristina Carvalho; Pacheco-Silva, Alvaro

2015-01-01

Ischemia and reperfusion injury is an inevitable event in renal transplantation. The most important consequences are delayed graft function, longer length of stay, higher hospital costs, high risk of acute rejection, and negative impact of long-term follow-up. Currently, many factors are involved in their pathophysiology and could be classified into two different paradigms for education purposes: hemodynamic and immune. The hemodynamic paradigm is described as the reduction of oxygen delivery due to blood flow interruption, involving many hormone systems, and oxygen-free radicals produced after reperfusion. The immune paradigm has been recently described and involves immune system cells, especially T cells, with a central role in this injury. According to these concepts, new strategies to prevent ischemia and reperfusion injury have been studied, particularly the more physiological forms of storing the kidney, such as the pump machine and the use of antilymphocyte antibody therapy before reperfusion. Pump machine perfusion reduces delayed graft function prevalence and length of stay at hospital, and increases long-term graft survival. The use of antilymphocyte antibody therapy before reperfusion, such as Thymoglobulin™, can reduce the prevalence of delayed graft function and chronic graft dysfunction. PMID:25993079

Preventing Contrast-induced Renal Failure: A Guide.

PubMed

Faggioni, Michela; Mehran, Roxana

2016-10-01

Contrast-induced acute kidney injury (CI-AKI) is characterised by a rapid deterioration of renal function within a few days of parenteral administration of contrast media (CM) in the absence of alternative causes. CI-AKI is the most common form of iatrogenic kidney dysfunction with an estimated prevalence of 12 % in patients undergoing percutaneous coronary intervention. Although usually self-resolving, in patients with pre-existing chronic kidney disease (CKD) or concomitant risk factors for renal damage, CI-AKI is associated with increased short-and long-term morbidity and mortality. Therefore, risk stratification based on clinical and peri-procedural characteristics is crucial in selecting patients at risk of CI-AKI who would benefit the most from implementation of preventive measures.

[Safety and short-term efficacy of renal sympathetic denervation in the treatment of resistant hypertension].

PubMed

Jiang, Xiong-jing; Liang, Tuo; Dong, Hui; Peng, Meng; Ma, Wen-jun; Guan, Ting; Zhang, Hui-min; Bian, Jin; Xu, Bo; Gao, Run-lin

2012-12-11

Transcatheter renal sympathetic denervation (RDN) is a novel technology/therapy in treating resistant hypertension. The present study aims to evaluate the safety and short-term efficacy of RDN for the treatment of resistant hypertension in a Chinese population. This prospective single-center pilot study was the first one conducted in China with Medtronic Ardian Symplicity Catheter System. Eight patients (6 males and 2 females) with resistant hypertension underwent RDN at our hospital from February to April 2012. All patients were followed up at one month and three months post-RDN. Blood pressure, use of antihypertensive medications, renal function and complications were recorded and analyzed. At one month and three months post-RDN, 24-hour ambulatory blood pressure monitoring showed mean systolic blood pressure and diastolic blood pressure decreased 10 (0 - 18) 13 (3 - 19) and 8 (-2 - 15), 9 (2 - 16) mm Hg throughout 24 hours respectively (P < 0.05, vs baseline). The number of drugs decreased from 4.3 ± 0.5 to 2.8 ± 0.9 and 2.5 ± 0.7 post-RSD respectively (P < 0.01). There was no significant change of renal function (P > 0.05). No complications were observed. The preliminary results revealed that RDN was safe and effective for the treatment of resistant hypertension in the Chinese population during a 3-month follow-up. Further large and long-term studies are warranted.

Anatomic partial nephrectomy: technique evolution.

PubMed

Azhar, Raed A; Metcalfe, Charles; Gill, Inderbir S

2015-03-01

Partial nephrectomy provides equivalent long-term oncologic and superior functional outcomes as radical nephrectomy for T1a renal masses. Herein, we review the various vascular clamping techniques employed during minimally invasive partial nephrectomy, describe the evolution of our partial nephrectomy technique and provide an update on contemporary thinking about the impact of ischemia on renal function. Recently, partial nephrectomy surgical technique has shifted away from main artery clamping and towards minimizing/eliminating global renal ischemia during partial nephrectomy. Supported by high-fidelity three-dimensional imaging, novel anatomic-based partial nephrectomy techniques have recently been developed, wherein partial nephrectomy can now be performed with segmental, minimal or zero global ischemia to the renal remnant. Sequential innovations have included early unclamping, segmental clamping, super-selective clamping and now culminating in anatomic zero-ischemia surgery. By eliminating 'under-the-gun' time pressure of ischemia for the surgeon, these techniques allow an unhurried, tightly contoured tumour excision with point-specific sutured haemostasis. Recent data indicate that zero-ischemia partial nephrectomy may provide better functional outcomes by minimizing/eliminating global ischemia and preserving greater vascularized kidney volume. Contemporary partial nephrectomy includes a spectrum of surgical techniques ranging from conventional-clamped to novel zero-ischemia approaches. Technique selection should be tailored to each individual case on the basis of tumour characteristics, surgical feasibility, surgeon experience, patient demographics and baseline renal function.

History of Childhood Kidney Disease and Risk of Adult End-Stage Renal Disease.

PubMed

Calderon-Margalit, Ronit; Golan, Eliezer; Twig, Gilad; Leiba, Adi; Tzur, Dorit; Afek, Arnon; Skorecki, Karl; Vivante, Asaf

2018-02-01

The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease (ESRD) among adolescents who had normal renal function and a history of childhood kidney disease. We conducted a nationwide, population-based, historical cohort study of 1,521,501 Israeli adolescents who were examined before compulsory military service in 1967 through 1997; data were linked to the Israeli ESRD registry. Kidney diseases in childhood included congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease; all participants included in the primary analysis had normal renal function and no hypertension in adolescence. Cox proportional-hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease. During 30 years of follow-up, ESRD developed in 2490 persons. A history of any childhood kidney disease was associated with a hazard ratio for ESRD of 4.19 (95% confidence interval [CI], 3.52 to 4.99). The associations between each diagnosis of kidney disease in childhood (congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease) and the risk of ESRD in adulthood were similar in magnitude (multivariable-adjusted hazard ratios of 5.19 [95% CI, 3.41 to 7.90], 4.03 [95% CI, 3.16 to 5.14], and 3.85 [95% CI, 2.77 to 5.36], respectively). A history of kidney disease in childhood was associated with younger age at the onset of ESRD (hazard ratio for ESRD among adults <40 years of age, 10.40 [95% CI, 7.96 to 13.59]). A history of clinically evident kidney disease in childhood, even if renal function was apparently normal in adolescence, was associated with a significantly increased risk of ESRD, which suggests that kidney injury or structural abnormality in childhood has long-term consequences.

Maintenance immunosuppression with intermittent intravenous IL-2 receptor antibody therapy in renal transplant recipients.

PubMed

Gabardi, Steven; Catella, Jennifer; Martin, Spencer T; Perrone, Ronald; Chandraker, Anil; Magee, Colm C; McDevitt-Potter, Lisa M

2011-09-01

To report what we believe to be the first 2 cases of long-term (>24 months) intermittent intravenous interleukin-2 receptor antibody (IL-2RA) therapy for maintenance immunosuppression following renal transplantation. The first patient is a 52-year-old female with a history of intolerance to calcineurin inhibitors (CNIs) and sirolimus. Following her second transplant, the patient received mycophenolate mofetil 100 mg twice daily, a tapering corticosteroid regimen (initial dose of methylprednisolone 500 mg tapered over 1 week to prednisone 30 mg/day), and biweekly intravenous daclizumab 1-1.2 mg/kg/dose; 33 months after transplant the IL-2RA was changed to intravenous basiliximab 40 mg once a month. At 40 months after transplant, the patient continued to have stable renal function (estimated glomerular filtration rate 48 mL/min/1.73 m²) with excellent tolerability. The second patient is a 59-year-old female also intolerant to CNIs and sirolimus who required intermittent maintenance therapy with intravenous basiliximab 20 mg/dose. Despite an initial rejection episode, the patient tolerated more than 2 years of basiliximab therapy with good renal function (estimated glomerular filtration rate 103 months after transplant 69 mL/min/1.73 m²) and no adverse events. The IL-2RAs basiliximab and daclizumab possess several characteristics of ideal maintenance immunosuppressive agents (ie, nondepleting, long half-lives, limited adverse events). Based on a MEDLINE search (through December 31, 2010) using the search terms basiliximab, daclizumab, organ transplant, immunosuppression, and/or maintenance immunosuppression, and an advanced search in the published abstracts from the American Transplant Congress and World Transplant Congress (2000-2010), it appears that IL-2RAs have been used successfully as short-term therapy in both renal and extrarenal transplant recipients to allow for renal recovery following CNI-induced nephrotoxicity. In heart transplant recipients, the IL-2RAs have been used for <24 months as maintenance immunosuppression in patients intolerant of CNIs or sirolimus. To the best of our knowledge, these 2 cases are the first to demonstrate that IL-2RAs can be used as an alternative to a CNI in a de novo immunosuppressive regimen. Also, this is the first report to illustrate successful long-term use of IL-2RAs in renal transplant recipients. This alternative approach was well tolerated by our patients, with no apparent adverse events. Although the efficacy of such regimens cannot be determined with 2 case reports, the fact that intermittent intravenous IL-2RA administration was successfully accomplished in these patients provides impetus to evaluate this treatment modality in prospective studies.

Stability of renal allograft recipients after conversion from cyclosporine to azathioprine.

PubMed

Carpenter, C B; Milford, E L; Kirkman, R L; Strom, T B; Lazarus, J M; Tilney, N L

1985-08-01

Forty-eight patients with stable renal function after allotransplantation have been converted from CsA/prednisone to azathioprine/prednisone to assess the short- and long-term effects upon renal function. Virtually all patients show an initial improvement in serum creatinine levels. Three patients developed chronic renal failure after 12 to 21 months, and three died of pneumonia 7, 12, and 19 months later. The mean serum creatinine level at latest follow-up (seven to 36 months) was 2.5 +/- 1.5 mg/dL for all 48 patients. Of interest, a control group of 21 patients not converted to azathioprine had serum creatinine levels of 2.5 +/- 0.8 mg/dL, over a follow-up period of five to 25 months. It is not immediately apparent that either group will have a superior overall outcome, although patients on azathioprine seem to have more of a risk for graft loss. More data are needed with various dosage schedules, and with randomized controls.

Reduced nephron endowment in the neonates of Indigenous Australian peoples.

PubMed

Kandasamy, Y; Smith, R; Wright, I M R; Lumbers, E R

2014-02-01

Rates of chronic kidney disease (CKD) among Indigenous groups in Australia exceed non-Indigenous rates eight-fold. Using kidney volume as a surrogate for nephron number, we carried out a study to determine if Indigenous neonates have a smaller kidney volume (and thus a reduced nephron number) from birth compared with non-Indigenous neonates. We recruited term and preterm neonates (<32 weeks) at a tertiary care neonatal unit over a 12 months period. Preterm neonates were assessed (renal sonography and renal function measurement) at 32 weeks corrected age (CA) and again at 38 weeks CA when blood pressure was also measured. All term neonates were assessed in the first post-natal week, including renal sonography, renal function and blood pressure measurement. The primary outcome measured was total kidney volume (TKV) and estimated glomerular filtration rate (eGFR) was a secondary outcome. Data was available for 44 preterm (11 Indigenous) and 39 term (13 Indigenous) neonates. TKV of Indigenous neonates was significantly lower at 32 weeks [12.0 (2.0) v. 15.4 (5.1) ml; P=0.03] and 38 weeks CA [18.6 (4.0) v. 22.6 (5.9) ml; P=0.04] respectively. Term Indigenous neonates also had smaller kidney volumes compared with non-Indigenous neonates. Despite a smaller kidney volume (and reduced nephron number), Indigenous neonates did not have a significantly lower eGFR. Indigenous neonates achieve similar eGFRs to Non-Indigenous neonates, presumably through a higher single nephron filtration rate. This places Indigenous neonates at a greater risk of long-term kidney damage later in life.

Long-term safety of left renal vein division and ligation to expedite complex abdominal aortic surgery.

PubMed

Samson, Russell H; Lepore, Michael R; Showalter, David P; Nair, Deepak G; Lanoue, Julien B

2009-09-01

Left renal vein division and ligation (LRVDAL) is performed to facilitate complex abdominal aortic surgery. Surgeons restore continuity of the vein due to concern that ligation could cause renal compromise or hematuria. However, we report the short and long-term safety of left renal vein division and ligation. Between 1992 and 2007, we divided the left renal vein in 56 patients (40 males, 16 females) ages 57 to 84 (average 74-years-old) who were treated for aortic occlusive disease (9) or abdominal aortic aneurysm (47). Patients requiring concomitant renal artery reconstruction were excluded from this review. Suprarenal cross-clamp was used in 51 patients with temporary vessel-loop control of the renal arteries. Creatinine (Cr) and glomerular filtration rates (eGFR) were measured pre-, post-, and long-term after surgery. Outpatient records of all patients that had survived more than 12 months were also reviewed in order to evaluate the late effects on renal function or symptoms possibly related to LRVDAL. Median procedure duration was 157 (61-375) minutes. Median cross-clamp time was 16 (10-45) minutes. Median intensive care unit (ICU) and hospital length of stays were 2 (1-11) days and 7 (4-58) days, respectively. There were no deaths. There were no complications directly related to renal vein ligation. Hematuria, seen in 2 patients, was a result of traumatic insertion of a Foley catheter. Median pre-op and discharge Cr levels were 1.1 mg/dL (0.7-2.4 mg/dL) and 1.1 mg/dL (0.6-2.1 mg/dL), respectively (P < .5). Median change in Cr was 0.0 mg/dL and only increased in 14 patients (maximum increase 0.9 mg/dL). Median pre-op and discharge eGFR was 61 mL/minute (28-137 mL/minute/1.73 m2) and 67 mL/minute (32-138 mL/minute/1.73 m2), respectively (P < .5). Cr and eGFR in the 2 patients with a Cr of >2.0 mg/dL remained unchanged post-op. Only 2 patients with a Cr of <2.0 mg/dL had a post-op Cr >2.0 mg/dL and both returned to normal by day 3 post-op. Thirty-six patients have been followed for more than a year (median 34.5 months, maximum 144 months) and Cr has remained stable in all but 2 patients. These 2 patients, both with a pre-op Cr of 1.5 mg/dL, subsequently developed Cr levels of 2.1 mg/dL and 2.4 mg/dL but maintained baseline Cr levels for 25 and 34 months, respectively, before demonstrating these elevated levels which have proven to be unrelated to renal vein ligation. Hematuria and flank pain have never been recorded after discharge. Restoration of left renal vein continuity after LRVDAL may be unnecessary since renal compromise and hematuria was not encountered in this long-term analysis.

Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with (177)Lu-octreotate.

PubMed

Sabet, Amir; Ezziddin, Khaled; Pape, Ulrich-Frank; Reichman, Karl; Haslerud, Torjan; Ahmadzadehfar, Hojjat; Biersack, Hans-Jürgen; Nagarajah, James; Ezziddin, Samer

2014-03-01

Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine-allowing only approximate estimates of GFR-the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement. Nephrotoxicity was analysed using (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with (177)Lu-octreotate. The mean follow-up period was 21 months (range 12-50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by (99m)Tc-DTPA clearance versus serum creatinine. The alteration in GFR differed widely among the patients (mean -2.1 ± 13.1 ml/min/m(2) per year, relative yearly reduction -1.8 ± 18.9%). Fifteen patients (21%) experienced a mild (2-10 ml/min/m(2) per year) and 16 patients (22%) a significant (>10 ml/min/m(2) per year) decline of GFR following PRRT. However, 11 patients (15%) showed an increase of >10 ml/min/m(2) per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3%) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15% of the assessments and led to underestimation in 12% of patients. None of the investigated factors including cumulative administered activity contributed to the decline of renal function. Serious nephrotoxicity after PRRT with (177)Lu-octreotate is rare (1.3%). However, slight renal impairment (GFR loss >2 ml/min/m(2) per year) can frequently (43%) be detected by (99m)Tc-DTPA clearance assessments. Cumulative administered activity of (177)Lu-octreotate is not a major determinant of renal impairment in our study.

Outcome of heart transplants 15 to 20 years ago: graft survival, post-transplant morbidity, and risk factors for mortality.

PubMed

Roussel, Jean C; Baron, Olivier; Périgaud, Christian; Bizouarn, Philippe; Pattier, Sabine; Habash, Oussama; Mugniot, Antoine; Petit, Thierry; Michaud, Jean L; Heymann, Marie Françoise; Treilhaud, Michèle; Trochu, Jean N; Gueffet, Jean P; Lamirault, Guillaume; Duveau, Daniel; Despins, Philippe

2008-05-01

The study was conducted to determine the long-term outcome of patients who underwent heart transplantation 15 to 20 years ago, in the cyclosporine era, and identify risk factors for death. A retrospective analysis was done of 148 patients who had undergone heart transplantation between 1985 and 1991 at a single center. Operative technique and immunosuppressive treatment were comparable in all patients. Actuarial survival rates were 75% (n = 111), 58% (n = 86), and 42% (n = 62) at 5, 10, and 15 years, respectively. The mean follow-up period was 12.1 +/- 5.6 years for patients who survived more than 3 months after transplantation (n = 131). The major causes of death were malignancy (35.8%) and cardiac allograft vasculopathy (24.7%). No death related to acute rejection was reported after the first month of transplantation. Graft coronary artery disease was detected on angiography in 66 (50.3%), and 7 (5.3%) had retransplantation. Malignancies developed in 131 patients (48.1%), including skin cancers in 31 (23.6%), solid tumors in 26 (19.8%), and hematologic malignancies in 14 (10.6%). Severe renal function requiring dialysis or renal transplantation developed in 27 patients (20.6%). By multivariable analysis, the only pre-transplant risk factor found to affect long-term survival was a history of cigarette use (p < 0.0004). Long-term survival at 15 years after cardiac transplantation remains excellent in the cyclosporine era. Controlling acute allograft rejection can be achieved but seems to carry a high rate of cancers and renal dysfunction. History of cigarette use affects significantly long-term survival in our study.

Diabetes and Age-Related Differences in Vascular Function of Renal Artery: Possible Involvement of Endoplasmic Reticulum Stress.

PubMed

Matsumoto, Takayuki; Watanabe, Shun; Ando, Makoto; Yamada, Kosuke; Iguchi, Maika; Taguchi, Kumiko; Kobayashi, Tsuneo

2016-02-01

To study the time-course relationship between vascular functions and endoplasmic reticulum (ER) stress in type 2 diabetes, we investigated vascular function and associated protein expression, including cyclo-oxygenase (COX), ER stress, and apoptotic markers, in renal arteries (RA) from type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats at the young adult (4 months old) and aged (18 months old) stages. In the RA of aged OLETF (vs. young OLETF), we found: (1) Increased contractions induced by uridine adenosine tetraphosphate (Up4A) and phenylephrine, (2) decreased relaxation and increased contraction induced by acetylcholine (ACh) at lower and higher concentrations, respectively, and (3) increased expression of COX-1 and C/EBP-homologous protein (CHOP, a pro-apoptotic protein). In aged rats, the expression of COX-1, COX-2, PDI (an ER protein disulfide isomerase), Bax (a proapoptotic marker), and CHOP were increased in RA from OLETF rats (vs. age-matched control Long-Evans Tokushima Otsuka [LETO] rats). Up-regulation of PDI and Bax were seen in the RA from young OLETF (vs. young LETO) rats. No age-related alterations were apparent in the above changes in RA from LETO rats, excluding ACh-induced contraction. Short-term treatment with the ER stress inhibitor tauroursodeoxycholic acid (TUDCA, 100 mg/kg per day, intraperitoneally for 1 week) to OLETF rats at the chronic stage of the disease (12 months old) could suppress renal arterial contractions induced by Up4A and ACh. These results suggest that a long-term duration of disease may be important for the development of vascular dysfunction rather than aging per se. The early regulation of ER stress may be important against the development of diabetes-associated vascular dysfunction.

Effect of renal sympathetic denervation on the progression of paroxysmal atrial fibrillation in canines with long-term intermittent atrial pacing.

PubMed

Wang, Xule; Huang, Congxin; Zhao, Qingyan; Huang, He; Tang, Yanhong; Dai, Zixuan; Wang, Xiaozhan; Guo, Zongwen; Xiao, Jinping

2015-04-01

The aim of the present study was to explore the effect of renal sympathetic denervation (RSD) on the progression of paroxysmal atrial fibrillation (AF) in canines with long-term intermittent atrial pacing. Nineteen beagles were randomly divided into sham-operated group (six dogs), control group (six dogs), and RSD group (seven dogs). Sham-operated group were implanted with pacemakers without pacing; control group were implanted with pacemakers with long-term intermittent atrial pacing; and RSD group underwent catheter-based RSD bilaterally and were simultaneously implanted with pacemakers. Atrial pacing was maintained for 8 h a day and a total of 12 weeks in the control group and RSD group. Echocardiography showed that the left atrial structure and function were significantly improved in the RSD group compared with the control group (P < 0.05). Compared with the control group, the RSD group had fewer incidences of AF and a shorter duration of AF (P < 0.05) after long-term intermittent atrial pacing. In addition to increased atrial effective refractory period (AERP) and AF cycle length, AERP dispersion and P-wave duration and dispersion were significantly decreased in the RSD group compared with the control group (P < 0.05). Atrial morphological evaluation suggested that fibrosis and ultrastructural changes induced by long-term intermittent atrial pacing were markedly suppressed in the RSD dogs compared with controls (P < 0.05). Immunohistochemistry results showed that connexin 43 distribution in RSD mid-myocardial was significantly fewer heterogeneous than that in control mid-myocardial (P < 0.05). Renal denervation inhibits the progression of paroxysmal AF, which might be related to the suppression of atrial electrophysiology and structural heterogeneity. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

Prognosis of clinical renal disease and incidence of new renal findings in patients with rheumatoid arthritis: follow-up of a population-based study.

PubMed

Karstila, K; Korpela, M; Sihvonen, S; Mustonen, J

2007-12-01

The objective of this study was to assess the long-term prognosis of nephropathy findings and the incidence of new abnormal clinical renal findings in patients with rheumatoid arthritis (RA). The original population-based cross-sectional study of 604 RA patients was carried out in 1988, 103 nephropathy patients being found. Controls matched for age, sex, and duration of RA were selected from among RA patients with normal renal function and urinalysis in 1988. In 2003, a follow-up study was made of the 103 nephropathy patients and 102 controls, and the median follow-up time was 13 years. In the original nephropathy group, serum creatinine exceeded 200 mumol/l in 8% of the original isolated hematuria patients, in 30% of the isolated proteinuria patients, in 57% of the combined hematuria and proteinuria patients, but in none of the isolated chronic renal failure (CRF) patients (p = 0.001 for the difference). Probable or definitive renal amyloidosis was diagnosed in 19% of the nephropathy patients. Dialysis therapy was given to 10 out of the 103 nephropathy patients, nine of them belonging to the original isolated proteinuria or combined hematuria and proteinuria groups. There were six renal deaths among the nephropathy patients, and none in the controls. In the control group, new abnormal renal findings, in most cases mild, were detected in 28%. Serum creatinine exceeded 200 mumol/l in 4% of the controls, and dialysis therapy was given to 2% of the controls. Probable or definitive renal amyloidosis was diagnosed in 4% of this group. With regards to the development or progression of chronic renal failure, the long-term clinical prognosis of isolated hematuria and isolated CRF was found to be favorable. Proteinuria alone or combined with hematuria or CRF was related to evidently poorer prognosis.

Renal dysfunction and hypophosphatemia during long-term lamivudine plus adefovir dipivoxil therapy in patients with chronic hepatitis B.

PubMed

Tanaka, Mio; Suzuki, Fumitaka; Seko, Yuya; Hara, Tasuku; Kawamura, Yusuke; Sezaki, Hitomi; Hosaka, Tetsuya; Akuta, Norio; Kobayashi, Masahiro; Suzuki, Yoshiyuki; Saitoh, Satoshi; Arase, Yasuji; Ikeda, Kenji; Kobayashi, Mariko; Kumada, Hiromitsu

2014-03-01

Renal dysfunction and Fanconi's syndrome associated with hypophosphatemia caused by long-term administration of low-dose adefovir dipivoxil (ADV) has been reported in recent years. The aim of this retrospective study was to determine the incidence and factors associated with renal dysfunction and hypophosphatemia in patients with hepatitis B infection on long-term treatment with ADV and lamivudine (LAM). The study subjects were 292 patients treated with 10 mg/day ADV and 100 mg/day LAM for more than 6 months. We evaluated estimated glomerular filtration rate (eGFR), serum creatinine and serum phosphate level at the start of ADV and every 6 months. During a median treatment duration of 64 months, 28 (9.6 %) patients developed renal impairment (defined as eGFR < 50 ml/min/1.73 m(2)), and 73 (27.1 %) developed hypophosphatemia, including 14 with persistent hypophosphatemia. The cumulative incidences of renal impairment at 1, 3, and 5 years were 1.4, 7.5, 10.5 %, respectively, and those of hypophosphatemia were 6.8, 20.6, 26.7 %, respectively. Multivariate analysis identified old age, liver cirrhosis and hypertension as determinants of renal impairment, and male sex, HCC, low baseline serum phosphate as determinants of hypophosphatemia. Three of the 14 patients with persistent hypophosphatemia developed Fanconi's syndrome; their serum creatinine level remained normal, but eGFR was lower than at baseline. Long-term treatment of hepatitis B with low-dose (10 mg/day) ADV and LAM can potentially cause renal impairment and hypophosphatemia. We advocate regular monitoring of serum phosphate and evaluation of eGFR, in addition to serum creatinine, in such patients.

Pregnancy in renal transplant recipients.

PubMed

Bouattar, T; Hakim, H; Rhou, H; Benamar, L; Bayahia, R; Ouzeddoun, N

2009-06-01

Renal transplantation with a well-functioning graft leads to a rapid restoration of endocrine and sexual functions. The aim of this study was to examine our experience with pregnancies among renal transplant patients, particularly with regard to their impact on graft function. We analyzed 10 pregnancies in 7 renal transplant recipients for long-term graft outcomes in terms of clinical and biological data. The mean patient age was 28.5 +/- 4 years. They all received a living donor kidney. The time between transplantation and the onset of pregnancy was 33.4 +/- 23.2 months. Regarding the immunosuppressive therapy, all patients received steroids and cyclosporine; 4 patients received in addition azathioprine and 2 received mycophenolate mofetil that was changed at 1 month before conception to azathioprine. There was no significant difference between the serum creatinine before and during pregnancy. We did not observe any acute rejection episode. Pregnancy complications were preclampsia in 1 case, hypertension in 1 case, urinary tract infection in 2 cases, and anemia in 80% of patients during the third trimester. Premature rupture of membranes occurred in 1 case and preterm delivery in 2 cases. Two cases of neonatal death were registered. Cesarean section was performed in 50% of cases. The follow-up revealed 2 cases of chronic rejection. A multidisciplinary approach is necessary for pregnancy which generally occurs at 2 years after kidney transplantation.

Clinical Features and Long-Term Outcome of Nephrotic Syndrome Associated with Heterozygous NPHS1 and NPHS2 Mutations

PubMed Central

Caridi, Gianluca; Gigante, Maddalena; Ravani, Pietro; Trivelli, Antonella; Barbano, Giancarlo; Scolari, Francesco; Dagnino, Monica; Murer, Luisa; Murtas, Corrado; Edefonti, Alberto; Allegri, Landino; Amore, Alessandro; Coppo, Rosanna; Emma, Francesco; De Palo, Tommaso; Penza, Rosa; Gesualdo, Loreto; Ghiggeri, Gian Marco

2009-01-01

Background and objectives: Mutations in nephrin (NPHS1) and podocin (NPHS2) genes represent a major cause of idiopathic nephrotic syndrome (NS) in children. It is not yet clear whether the presence of a single mutation acts as a modifier of the clinical course of NS. Design, setting, participants, & measurements: We reviewed the clinical features of 40 patients with NS associated with heterozygous mutations or variants in NPHS1 (n = 7) or NPHS2 (n = 33). Long-term renal survival probabilities were compared with those of a concurrent cohort with idiopathic NS. Results: Patients with a single mutation in NPHS1 received a diagnosis before those with potentially nongenetic NS and had a good response to therapies. Renal function was normal in all cases. For NPHS2, six patients had single heterozygous mutations, six had a p.P20L variant, and 21 had a p.R229Q variant. Age at diagnosis and the response to drugs were comparable in all NS subgroups. Overall, they had similar renal survival probabilities as non-NPHS1/NPHS2 cases (log-rank χ2 0.84, P = 0.656) that decreased in presence of resistance to therapy (P < 0.001) and in cases with renal lesions of glomerulosclerosis and IgM deposition (P < 0.001). Cox regression confirmed that the only significant predictor of dialysis was resistance to therapy. Conclusions: Our data indicate that single mutation or variant in NPHS1 and NPHS2 does not modify the outcome of primary NS. These patients should be treated following consolidated schemes and have good chances for a good long-term outcome. PMID:19406966

Cross talk between primary human renal tubular cells and endothelial cells in cocultures.

PubMed

Tasnim, Farah; Zink, Daniele

2012-04-15

Interactions between renal tubular epithelial cells and adjacent endothelial cells are essential for normal renal functions but also play important roles in renal disease and repair. Here, we investigated cocultures of human primary renal proximal tubular cells (HPTC) and human primary endothelial cells to address the cross talk between these cell types. HPTC showed improved proliferation, marker gene expression, and enzyme activity in cocultures. Also, the long-term maintenance of epithelia formed by HPTC was improved, which was due to the secretion of transforming growth factor-β1 and its antagonist α2-macroglobulin. HPTC induced endothelial cells to secrete increased amounts of these factors, which balanced each other functionally and only displayed in combination the observed positive effects. In addition, in the presence of HPTC endothelial cells expressed increased amounts of hepatocyte growth factor and vascular endothelial growth factor, which have well-characterized effects on renal tubular epithelial cells as well as on endothelial cells. Together, the results showed that HPTC stimulated endothelial cells to express a functionally balanced combination of various factors, which in turn improved the performance of HPTC. The results give new insights into the cross talk between renal epithelial and endothelial cells and suggest that cocultures could be also useful models for the analysis of cellular communication in renal disease and repair. Furthermore, the characterization of defined microenvironments, which positively affect HPTC, will be helpful for improving the performance of this cell type in in vitro applications including in vitro toxicology and kidney tissue engineering.

Sympathetic nervous system and the kidney in hypertension.

PubMed

DiBona, Gerald F

2002-03-01

Long-term control of arterial pressure has been attributed to the kidney by virtue of its ability to couple the regulation of blood volume to the maintenance of sodium and water balance by the mechanisms of pressure natriuresis and diuresis. In the presence of a defect in renal excretory function, hypertension arises as the consequence of the need for an increase in arterial pressure to offset the abnormal pressure natriuresis and diuresis mechanisms, and to maintain sodium and water balance. There is growing evidence that an important cause of the defect in renal excretory function in hypertension is an increase in renal sympathetic nerve activity (RSNA). First, increased RSNA is found in animal models of hypertension and hypertensive humans. Second, renal denervation prevents or alleviates hypertension in virtually all animal models of hypertension. Finally, increased RSNA results in reduced renal excretory function by virtue of effects on the renal vasculature, the tubules, and the juxtaglomerular granular cells. The increase in RSNA is of central nervous system origin, with one of the stimuli being the action of angiotensin II, probably of central origin. By acting on brain stem nuclei that are important in the control of peripheral sympathetic vasomotor tone (e.g. rostral ventrolateral medulla), angiotensin II increases the basal level of RSNA and impairs its arterial baroreflex regulation. Therefore, the renal sympathetic nerves may serve as the link between central sympathetic nervous system regulatory sites and the kidney in contributing to the renal excretory defect in the development of hypertension.

Adrenal, metabolic and cardio-renal dysfunction develops after pregnancy in rats born small or stressed by physiological measurements during pregnancy.

PubMed

Cheong, Jean N; Cuffe, James S M; Jefferies, Andrew J; Moritz, Karen M; Wlodek, Mary E

2016-10-15

Women born small are at an increased risk of developing pregnancy complications. Stress may further increase a woman's likelihood for an adverse pregnancy. Adverse pregnancy adaptations can lead to long-term diseases even after her pregnancy. The current study investigated the effects of stress during pregnancy on the long-term adrenal, metabolic and cardio-renal health of female rats that were born small. Stress programmed increased adrenal Mc2r gene expression, a higher insulin secretory response to glucose during intraperitoneal glucose tolerance test (+36%) and elevated renal creatinine clearance after pregnancy. Females that were born small had increased homeostatic model assessment-insulin resistance and elevated systolic blood pressure after pregnancy, regardless of stress exposure. These findings suggest that being born small or being stressed during pregnancy programs long-term adverse health outcomes after pregnancy. However, stress in pregnancy does not exacerbate the long-term adverse health outcomes for females that were born small. Females born small are more likely to experience complications during their pregnancy, including pregnancy-induced hypertension, pre-eclampsia and gestational diabetes. The risk of developing complications is increased by stress exposure during pregnancy. In addition, pregnancy complications may predispose the mother to diseases after pregnancy. We determined whether stress during pregnancy would exacerbate the adrenal, metabolic and cardio-renal dysfunction of growth-restricted females in later life. Late gestation bilateral uterine vessel ligation was performed in Wistar Kyoto rats to induce growth restriction. At 4 months, growth-restricted and control female offspring were mated with normal males. Those allocated to the stressed group had physiological measurements [metabolic cage, tail cuff blood pressure, intraperitoneal glucose tolerance test (IPGTT)] conducted during pregnancy whilst the unstressed groups were unhandled. After the completion of pregnancy, dams were aged to 12 months and blood pressure, and metabolic and renal function were assessed. At 13 months, adrenal glands, pancreases and plasma were collected at post-mortem. Females stressed during pregnancy had increased adrenal Mc2r gene expression (+22%), higher insulin secretory response to glucose during IPGTT (+36%) and higher creatinine clearance (+29%, indicating increased estimated glomerular filtration rate). In contrast, females that were born small had increased homeostatic model assessment-insulin resistance (+54%), increased water intake (+23%), urine output (+44%) and elevated systolic blood pressure (+7%) regardless of exposure to stress. Our findings suggest that low maternal birth weight and maternal stress exposure during pregnancy are both independently detrimental for long-term adrenal, metabolic and cardio-renal health of the mother, although their effects were not exacerbated. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

International expert consensus statement: Percutaneous transluminal renal denervation for the treatment of resistant hypertension.

PubMed

Schlaich, Markus P; Schmieder, Roland E; Bakris, George; Blankestijn, Peter J; Böhm, Michael; Campese, Vito M; Francis, Darrel P; Grassi, Guido; Hering, Dagmara; Katholi, Richard; Kjeldsen, Sverre; Krum, Henry; Mahfoud, Felix; Mancia, Giuseppe; Messerli, Franz H; Narkiewicz, Krzysztof; Parati, Gianfranco; Rocha-Singh, Krishna J; Ruilope, Luis M; Rump, Lars C; Sica, Domenic A; Sobotka, Paul A; Tsioufis, Costas; Vonend, Oliver; Weber, Michael A; Williams, Bryan; Zeller, Thomas; Esler, Murray D

2013-12-03

Catheter-based radiofrequency ablation technology to disrupt both efferent and afferent renal nerves has recently been introduced to clinical medicine after the demonstration of significant systolic and diastolic blood pressure reductions. Clinical trial data available thus far have been obtained primarily in patients with resistant hypertension, defined as standardized systolic clinic blood pressure ≥ 160 mm Hg (or ≥ 150 mm Hg in patients with type 2 diabetes) despite appropriate pharmacologic treatment with at least 3 antihypertensive drugs, including a diuretic agent. Accordingly, these criteria and blood pressure thresholds should be borne in mind when selecting patients for renal nerve ablation. Secondary forms of hypertension and pseudoresistance, such as nonadherence to medication, intolerance of medication, and white coat hypertension, should have been ruled out, and 24-h ambulatory blood pressure monitoring is mandatory in this context. Because there are theoretical concerns with regard to renal safety, selected patients should have preserved renal function, with an estimated glomerular filtration rate ≥ 45 ml/min/1.73 m(2). Optimal periprocedural management of volume status and medication regimens at specialized and experienced centers equipped with adequate infrastructure to cope with potential procedural complications will minimize potential patient risks. Long-term safety and efficacy data are limited to 3 years of follow-up in small patient cohorts, so efforts to monitor treated patients are crucial to define the long-term performance of the procedure. Although renal nerve ablation could have beneficial effects in other conditions characterized by elevated renal sympathetic nerve activity, its potential use for such indications should currently be limited to formal research studies of its safety and efficacy. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Use of Everolimus in Liver Transplantation: Recommendations From a Working Group

PubMed Central

De Simone, Paolo; Fagiuoli, Stefano; Cescon, Matteo; De Carlis, Luciano; Tisone, Giuseppe; Volpes, Riccardo; Cillo, Umberto

2017-01-01

Abstract Immunosuppression after liver transplantation (LT) is presently based on use of calcineurin inhibitors (CNI), although they are associated with an increased incidence of renal dysfunction, cardiovascular complications, and de novo and recurrent malignancies. Over the past decade, mammalian target of rapamycin inhibitors have received considerable attention as immunosuppressants because they are associated with a more favorable renal profile versus CNI, as well as antiproliferative activity in clinical studies. Comprehensive guidelines on use of everolimus (EVR) in LT are still lacking. In Italy, a project, named Everolimus: the road to long-term functioning, was initiated to collect the experience on EVR after LT with the aim of providing guidance for transplant clinicians. Herein, recommendations by this national consensus group, based on Delphi methodology, are presented. Consensus was reached on 20 of the 23 statements proposed, and their level of evidence, grade of recommendation, and percent of agreement are reported. Statements are grouped into 4 areas: (A) renal function; (B) time of EVR introduction, CNI reduction and elimination, and risk for graft rejection; (C) antiproliferative effects of EVR; and (D) management of EVR-related adverse events. The high level of consensus shows that there is good agreement on the routine use of EVR in predefined clinical scenarios, especially in light of posttransplant nephrotoxicity and other adverse events associated with long-term administration of CNIs. PMID:27495768

Renal Perfusion and Function during Pneumoperitoneum: A Systematic Review and Meta-Analysis of Animal Studies

PubMed Central

Warlé, Michiel C.; Hooijmans, Carlijn R.

2016-01-01

Both preclinical and clinical studies indicate that raised intra-abdominal pressure (IAP) associated with pneumoperitoneum during laparoscopic surgical procedures can cause renal damage, the severity of which may be influenced by variables such as pressure level and duration. Several of these variables have been investigated in animal studies, but synthesis of all preclinical data has not been performed. This systematic review summarizes all available pre-clinical evidence on this topic, including an assessment of its quality and risk of bias. We performed meta-analysis to assess which aspects of the pneumoperitoneum determine the severity of its adverse effects. A systematic search in two databases identified 55 studies on the effect of pneumoperitoneum on renal function which met our inclusion criteria. There was high heterogeneity between the studies regarding study design, species, sex, pressure and duration of pneumoperitoneum, and type of gas used. Measures to reduce bias were poorly reported, leading to an unclear risk of bias in the majority of studies. Details on randomisation, blinding and a sample size calculation were not reported in ≥80% of the studies. Meta-analysis showed an overall increase in serum creatinine during pneumoperitoneum, and a decrease in urine output and renal blood flow. Subgroup analysis indicated that for serum creatinine, this effect differed between species. Subgroup analysis of pressure level indicated that urine output decreased as IAP level increased. No differences between types of gas were observed. Data were insufficient to reliably assess whether sex or IAP duration modulate the effect of pneumoperitoneum. Four studies assessing long-term effects indicated that serum creatinine normalized ≥24 hours after desufflation of pneumoperitoneum at 15mmHg. We conclude that harmful effects on renal function and perfusion during pneumoperitoneum appear to be robust, but evidence on long-term effects is very limited. The reliability and clinical relevance of these findings for healthy patients and patients at high risk of renal impairment remain uncertain. We emphasize the need for rigorous reporting of preclinical research methodology, which is of vital importance for clinical translation of preclinical data. PMID:27657740

Improved long-term survival and renal recovery after acute kidney injury in hospitalized patients: A 20 year experience.

PubMed

Long, Thorir E; Sigurdsson, Martin I; Sigurdsson, Gisli H; Indridason, Olafur S

2016-12-01

Acute kidney injury (AKI) is a common complication of medical and surgical interventions in hospitalized patients and associates with high mortality. Our aim was to examine renal recovery and long-term survival and time trends in AKI survival. Changes in serum creatinine (SCr) were used to define AKI in patients at Landspitali University Hospital in Iceland from 1993 to 2013. Renal recovery was defined as SCr < 1.5× baseline. Out of 25 274 individuals who had their highest measured SCr during hospitalization and an available baseline SCr, 10,419 (41%) had AKI during hospitalization (H-AKI), 19%, 11% and 12% with Stage 1, 2 and 3, respectively. The incidence of H-AKI increased from 18.6 (95% CI, 14.7-22.5) to 29.9 (95% CI, 26.7-33.1) per 1000 admissions/year over the study period. Survival after H-AKI was 61% at 90-days and 51% at one year. Comparing H-AKI patients to propensity score matched individuals the hazard ratio for death was 1.49 (1.36-1.62), 2.17 (1.95-2.41) and 2.95 (2.65-3.29) for Stage 1, 2 and 3, respectively. One-year survival of H-AKI patients improved from 47% in 1993-1997 to 57% in 2008-2013 and the adjusted hazard ratio for mortality improved, compared to the first 5-year period, 0.85 (0.81-0.89), 0.67 (0.64-0.71), and 0.57 (0.53-0.60) for each subsequent 5-year interval. Recovery of renal function was achieved in 88%, 58% and 44% of patients in Stages 1, 2 and 3, respectively, improving with time. Acute kidney injury is an independent predictor of long-term mortality in hospitalized patients but there has been a marked improvement in survival and renal recovery over the past two decades. © 2015 Asian Pacific Society of Nephrology.

Long-term administration of advanced glycation end-product stimulates the activation of NLRP3 inflammasome and sparking the development of renal injury.

PubMed

Yeh, Wan-Ju; Yang, Hsin-Yi; Pai, Man-Hui; Wu, Chi-Hao; Chen, Jiun-Rong

2017-01-01

The accumulation of advanced glycation end-products (AGEs) and the enhanced interaction of AGE with their cellular receptor (RAGE) have been implicated in the progression of chronic kidney disease. The purpose of this study was to examine whether the AGE/RAGE-induced nephrotoxic effects are associated with inflammasome activation and endothelial dysfunction. Chronic renal injury was examined in BALB/c mice by the long-term administration of carbonyl-AGE for 16 weeks. Endothelial dysfunction was detected by measuring the number of circulating endothelial progenitor cells (EPCs) and the levels of nitric oxide synthase (eNOS) and nitric oxide (NO) in kidneys. Results showed that administration of methylglyoxal-bovine serum albumin (MG-BSA) AGE accelerated renal MG, carboxyethyl lysine, carboxymethyl lysine and malondialdehyde formation and, in parallel, the levels of serum creatinine and blood urea nitrogen (BUN) were significantly increased. Expression of RAGE and NLRP3 inflammasome-related proteins (TXNIP, NLRP3, procaspase-1 and caspase-1) and IL (interleukin)-1β secretion were upregulated, whereas the levels of EPCs, eNOS and NO were lower in MG-BSA-treated mice. This induction by MG-BSA was significantly inhibited by RAGE antagonist. Our results firstly reveal a possible mechanism of AGE-mediated renal dysfunction upon NLRP3 inflammasome activation. Therapeutic blockade of RAGE may ameliorate renal and endothelial functions in subjects under high AGE burden. Copyright © 2016 Elsevier Inc. All rights reserved.

Exploration of Fecal Microbiota Transplantation in the Treatment of Refractory Diarrhea After Renal Transplantation.

PubMed

Gu, B; Bo, G Z; Ke, C

2018-06-01

Exploration of fecal microbiota transplantation in the treatment of refractory diarrhea after renal transplantation. Summarize the etiology of 120 cases with diarrhea after renal transplantation from 2014 to 2017 in our hospital. There were 4 recipients of refractory diarrhea who accepted fecal microbiota transplantation with informed consent, and we collected clinical data of stool and bacterial culture, gut microbiota analysis, graft function, electrolytes, immunosuppressant concentrations of prognostic evaluation of patients with fecal transplantation. The absorption of electrolyte is slightly higher and concentration of tacrolimus and creatinine were not significantly changed compared with before. Fecal microbiota transplantation provides a new choice to refractory diarrhea after renal transplantation as an innovative treatment, but the effectiveness of fecal microbiota transplantation needs long-term observation and further evaluation through large sample data. Copyright © 2018. Published by Elsevier Inc.

Renal and blood pressure effects from environmental cadmium exposure in Thai children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaddiwudhipong, Witaya, E-mail: swaddi@hotmail.com; Mahasakpan, Pranee; Jeekeeree, Wanpen

Very few studies have shown renal and blood pressure effects from environmental cadmium exposure in children. This population study examined associations between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and renal dysfunctions and blood pressure in environmentally exposed Thai children. Renal functions including urinary excretion of β{sub 2}-microglobulin, calcium (early renal effects), and total protein (late renal effect), and blood pressure were measured in 594 primary school children. Of the children studied, 19.0% had urinary cadmium ≥1 μg/g creatinine. The prevalence of urinary cadmium ≥1 μg/g creatinine was significantly higher in girls and in those consuming ricemore » grown in cadmium-contaminated areas. The geometric mean levels of urinary β{sub 2}-microglobulin, calcium, and total protein significantly increased with increasing tertiles of urinary cadmium. The analysis did not show increased blood pressure with increasing tertiles of urinary cadmium. After adjusting for age, sex, and blood lead levels, the analysis showed significant positive associations between urinary cadmium and urinary β{sub 2}-microglobulin and urinary calcium, but not urinary total protein nor blood pressure. Our findings provide evidence that environmental cadmium exposure can affect renal functions in children. A follow-up study is essential to assess the clinical significance and progress of renal effects in these children. - Highlights: • Few studies show renal effects from environmental cadmium exposure in children. • We report renal and blood pressure effects from cadmium exposure in Thai children. • Urinary β{sub 2}-microglobulin and calcium increased with increasing urinary cadmium. • The study found no association between urinary cadmium levels and blood pressure. • Environmental cadmium exposure can affect renal functions in children.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wendler, J. J., E-mail: johann.wendler@med.ovgu.de; Porsch, M.; Huehne, S.

Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histologicalmore » follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.« less

Long-Term Outcomes of Renal Transplant in Recipients With Lower Urinary Tract Dysfunction.

PubMed

Wilson, Rebekah S; Courtney, Aisling E; Ko, Dicken S C; Maxwell, Alexander P; McDaid, James

2018-01-02

Lower urinary tract dysfunction can lead to chronic kidney disease, which, despite surgical intervention, will progress to end-stage renal disease, requiring dialysis. Urologic pathology may damage a transplanted kidney, limiting patient and graft survival. Although smaller studies have suggested that urinary tract dysfunction does not affect graft or patient survival, this is not universally accepted. Northern Ireland has historically had the highest incidence of neural tube defects in Europe, giving rich local experience in caring for patients with lower urinary tract dysfunction. Here, we analyzed outcomes of renal transplant recipients with lower urinary tract dysfunction versus control recipients. We identified 3 groups of kidney transplant recipients treated between 2001 and 2010; those in group 1 had end-stage renal disease due to lower urinary tract dysfunction with prior intervention (urologic surgery, long-term catheter, or intermittent self-catheterization), group 2 had end-stage renal disease secondary to lower urinary tract dysfunction without intervention, and group 3 had end-stage renal disease due to polycystic kidney disease (chosen as a relatively healthy control cohort without comorbid burden of other causes of end-stage renal disease such as diabetes). The primary outcome measured, graft survival, was death censored, with graft loss defined as requirement for renal replacement therapy or retransplant. Secondary outcomes included patient survival and graft function. In 150 study patients (16 patients in group 1, 64 in group 2, and 70 in group 3), 5-year death-censored graft survival was 93.75%, 90.6%, and 92.9%, respectively, with no significant differences in graft failure among groups (Cox proportional hazards model). Five-year patient survival was 100%, 100%, and 94.3%, respectively. Individuals with a history of lower urinary tract dysfunction had graft and patient survival rates similar to the control group. When appropriately treated, lower urinary tract dysfunction is not a barrier to successful renal transplant.

Distress due to lithium-induced polyuria: exploratory study.

PubMed

Pradhan, Basant K; Chakrabarti, Subho; Irpati, Anand S; Bhardwaj, Rahul

2011-06-01

Lithium-induced polyuria, although common, often goes unrecognized. The purpose of the present study was therefore to investigate the complaints of polyuria, and distress and functional impairment associated with polyuria, in 56 patients with bipolar disorder on long-term lithium treatment. All participants underwent 24-h urine collection, and renal function tests. Polyuria (24-h urine volume > 3 L) was found in 70% of subjects. Unless directly enquired about, polyuria was underreported. Impairment in work and daily routine due to increased urine output/frequency was associated with 24-h urine volumes. Polyuria is a highly prevalent, distressing and impairing side-effect of long-term lithium treatment, requiring due attention. © 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.

Kidney transplantation in the context of renal replacement therapy.

PubMed

Pesavento, Todd E

2009-12-01

Kidney transplantation has dramatically evolved from a life-saving yet unproven therapy for patients with renal failure to a mature field that is the preferred treatment for those suffering from ESRD. Patients who receive a transplant experience a 68% lower risk of death compared with those waiting on dialysis for a transplant. This benefit is afforded to all patient subgroups including the elderly (> or =70 yr), and diabetics, who can gain 11 yr of extra life with transplantation. Prolonged transplant wait times result in a higher risk of death but this can be ameliorated with preemptive transplantation. Future challenges will focus on appropriate organ allocation and addressing long-term renal function and comorbid conditions so patients can enjoy the full benefits of transplantation.

Long-term changes of renal function in relation to ace inhibitor/angiotensin receptor blocker dosing in patients with heart failure and chronic kidney disease.

PubMed

Fröhlich, Hanna; Nelges, Christoph; Täger, Tobias; Schwenger, Vedat; Cebola, Rita; Schnorbach, Johannes; Goode, Kevin M; Kazmi, Syed; Katus, Hugo A; Cleland, John G F; Clark, Andrew L; Frankenstein, Lutz

2016-08-01

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have become cornerstones of therapy for chronic heart failure (CHF). Guidelines advise high target doses for ACEIs/ARBs, but fear of worsening renal function may limit dose titration in patients with concomitant chronic kidney disease (CKD). In this retrospective observational study, we identified 722 consecutive patients with systolic CHF, stable CKD stage III/IV (estimated glomerular filtration rate [eGFR] 15-60 mL min(-1) 1.73 m(-2)) and chronic ACEI/ARB treatment from the outpatient heart failure clinics at the Universities of Hull, UK, and Heidelberg, Germany. Change of renal function, worsening CHF, and hyperkalemia at 12-month follow-up were analyzed as a function of both baseline ACEI/ARB dose and dose change from baseline. ΔeGFR was not related to baseline dose of ACEI/ARB (P = .58), or to relative (P = .18) or absolute change of ACEI/ARB dose (P = .21) during follow-up. Expressing change of renal function as a categorical variable (improved/stable/decreased) as well as subgroup analyses with respect to age, sex, New York Heart Association functional class, left ventricular ejection fraction, diabetes, concomitant aldosterone antagonists, CKD stage, hypertension, ACEI vs ARB, and congestion status yielded similar results. There was no association of dose/dose change with incidence of either worsening CHF or hyperkalemia. In patients with systolic CHF and stable CKD stage III/IV, neither continuation of high doses of ACEI/ARB nor up-titration was related to adverse changes in longer-term renal function. Conversely, down-titration was not associated with improvement in eGFR. Use of high doses of ACEI/ARB and their up-titration in patients with CHF and CKD III/IV may be appropriate provided that the patient is adequately monitored. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-Term Efficacy and Safety of Linagliptin in Patients With Type 2 Diabetes and Severe Renal Impairment

PubMed Central

McGill, Janet B.; Sloan, Lance; Newman, Jennifer; Patel, Sanjay; Sauce, Christophe; von Eynatten, Maximilian; Woerle, Hans-Juergen

2013-01-01

OBJECTIVE This placebo-controlled study assessed long-term efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with type 2 diabetes and severe renal impairment (RI). RESEARCH DESIGN AND METHODS In this 1-year, double-blind study, 133 patients with type 2 diabetes (HbA1c 7.0–10.0%) and severe RI (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) at screening were randomized to linagliptin 5 mg (n = 68) or placebo (n = 65) once daily, added to existing background therapy. The primary efficacy end point was HbA1c change from baseline to week 12. Efficacy and safety end points were assessed after 1 year. RESULTS At week 12, adjusted mean HbA1c decreased by −0.76% with linagliptin and −0.15% with placebo (treatment difference, −0.60%; 95% CI −0.89 to −0.31; P < 0.0001). HbA1c improvements were sustained with linagliptin (−0.71%) over placebo (0.01%) at 1 year (treatment difference −0.72%, −1.03 to −0.41; P < 0.0001). Mean insulin doses decreased by −6.2 units with linagliptin and −0.3 units with placebo. Overall adverse event incidence was similar over 1 year (94.1 vs. 92.3%). Incidence of severe hypoglycemia with linagliptin and placebo was comparably low (three patients per group). Linagliptin and placebo had little effect on renal function (median change in eGFR, −0.8 vs. −2.2 mL/min/1.73 m2), and no drug-related renal failure occurred. CONCLUSIONS In patients with type 2 diabetes and severe RI, linagliptin provided clinically meaningful improvements in glycemic control with very low risk of severe hypoglycemia, stable body weight, and no cases of drug-related renal failure. The potential for linagliptin to spare insulin and provide long-term renal safety warrants further investigations. PMID:23033241

Long-term safety of tiotropium/olodaterol Respimat® in patients with moderate-to-very severe COPD and renal impairment in the TONADO® studies.

PubMed

LaForce, Craig; Derom, Eric; Bothner, Ulrich; Kloer, Isabel M; Trampisch, Matthias; Buhl, Roland

2018-01-01

The safety, lung function efficacy, and symptomatic benefits of combined tiotropium and olodaterol in patients with COPD were established in the 1-year TONADO ® studies (NCT01431274; NCT01431287). As tiotropium is predominantly excreted by the kidneys, the long-term safety profile of tiotropium/olodaterol was investigated in patients with renal impairment in a prespecified safety analysis of the TONADO studies. These were 2 replicate, randomized, double-blind, parallel-group, 52-week Phase III studies that assessed tiotropium/olodaterol compared with tiotropium or olodaterol alone (all via Respimat ® ) in patients with moderate-to-very severe COPD. In this analysis, renal impairment was defined as mild (creatinine clearance [CLcr] 60-89 mL/min), moderate (CLcr 30-59 mL/min) or severe (CLcr 15-29 mL/min). Adverse events (AEs) were pooled from both studies. Of 3,041 patients included in this analysis, 1,333 (43.8%) had mild, 404 (13.3%) had moderate, and 5 (0.2%) had severe renal impairment; these were distributed equally between treatment groups. Almost one-quarter of all treated patients (23.4%) had a history of cardiac disorder, 45.6% had hypertension, and 13.3% had glucose metabolism disorders, including diabetes. AEs with olodaterol, tiotropium, and tiotropium/olodaterol occurred in 75.1%, 70.8%, and 72.0% of patients with no renal impairment, 75.7%, 74.0%, and 73.3% with mild renal impairment, and 84.3%, 79.5%, and 79.7% with moderate renal impairment, respectively. There was no notable effect of renal impairment on the proportion of patients with an AE, and no differences were observed between tiotropium/olodaterol versus the monocomponents. There was no difference in the incidence of major adverse cardiac events, renal and urinary tract AEs, or potential anticholinergic effects with increasing severity of renal impairment. Over half the patients enrolled in the TONADO studies had renal impairment, and there was a high level of pre-existing cardiovascular comorbidity. The safety and tolerability of tiotropium/olodaterol is comparable to the monocomponents, irrespective of the level of renal impairment.

Benefits and Safety of Long-Term Fenofibrate Therapy in People With Type 2 Diabetes and Renal Impairment

PubMed Central

Ting, Ru-Dee; Keech, Anthony C.; Drury, Paul L.; Donoghoe, Mark W.; Hedley, John; Jenkins, Alicia J.; Davis, Timothy M.E.; Lehto, Seppo; Celermajer, David; Simes, R. John; Rajamani, Kushwin; Stanton, Kim

2012-01-01

OBJECTIVE Diabetic patients with moderate renal impairment (estimated glomerular filtration rate [eGFR] 30–59 mL/min/1.73 m2) are at particular cardiovascular risk. Fenofibrate’s safety in these patients is an issue because it may elevate plasma creatinine. Furthermore, guidelines regarding fenofibrate dosing in renal impairment vary internationally. We investigated fenofibrate’s effects on cardiovascular and end-stage renal disease (ESRD) events, according to eGFR, in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. RESEARCH DESIGN AND METHODS Type 2 diabetic patients (aged 50–75 years) with eGFR ≥30 mL/min/1.73 m2 were randomly allocated to a fixed dose of fenofibrate (200 mg daily) (n = 4,895) or placebo (n = 4,900) for 5 years. Baseline renal function (Modification of Diet in Renal Disease equation) was grouped by eGFR (30–59, 60–89, and ≥90 mL/min/1.73 m2). The prespecified outcome was total cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, and coronary/carotid revascularization). Serious adverse events and instances of ESRD (plasma creatinine >400 μmol/L, dialysis, renal transplant, or renal death) were recorded. Analysis was by intention to treat. RESULTS Overall, fenofibrate reduced total cardiovascular events, compared with placebo (hazard ratio 0.89 [95% CI 0.80–0.99]; P = 0.035). This benefit was not statistically different across eGFR groupings (P = 0.2 for interaction) (eGFR 30–59 mL/min/1.73 m2: 0.68 [0.47–0.97], P = 0.035; eGFR ≥90 mL/min/1.73 m2: 0.85 [0.70–1.02], P = 0.08). ESRD rates were similar between treatment arms, without adverse safety signals of fenofibrate use in renal impairment. CONCLUSIONS Patients with type 2 diabetes and moderate renal impairment benefit from long-term fenofibrate, without excess drug-related safety concerns compared with those with no or mild renal impairment. Fenofibrate treatment should not be contraindicated in moderate renal impairment, suggesting that current guidelines may be too restrictive. PMID:22210576

Effect of whole soy and purified isoflavone daidzein on renal function--a 6-month randomized controlled trial in equol-producing postmenopausal women with prehypertension.

PubMed

Liu, Zhao-min; Ho, Suzanne C; Chen, Yu-ming; Tang, Nelson; Woo, Jean

2014-09-01

The aim of the study was to examine the long-term effect of commonly used whole soy foods (soy flour) and purified daidzein (one major isoflavone and the precursor of equol) on renal function among prehypertensive postmenopausal women who are also equol producers, a population most likely to benefit from soy intervention. This was a 6-month double-blind, randomized, placebo-controlled trial. Two hundred seventy eligible Chinese women were randomized to either one of the three treatments: 40 g soy flour (whole soy group), 40 g low-fat milk powder + 63 mg daidzein (daidzein group) or 40 g low-fat milk powder (placebo group) daily each for 6 months. Fasting blood and 24-h urine samples were collected at the beginning and end of trial. Serum creatinine, cystatin C, urea, angiotensin-converting enzyme, minerals and 24-h urinary creatinine and minerals were analyzed. Estimated glomerular filtration rate (eGFR) was calculated with the Cockcroft-Gault and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Two hundred fifty-three subjects completed the study according to the protocol. Urinary isoflavones indicated good compliance of participants. No significant changes were observed in most of renal parameters, however, there was a less decrease in eGFRcockcroft in 6-month change (p=0.044) and %change (p=0.031) with whole soy intake relative to milk placebo. Subgroup analysis among women with lowered renal function suggested whole soy consumption tended to improve markers of renal function relative to control. Six-month consumption of whole soy tended to have a modest improvement of renal function in prehypertensive postmenopausal women with lowered renal function. Future trials in subjects with more declined renal function are necessary. The trial was registered in ClinicalTrials.gov with identifier of NCT01270737. (URL: http://clinicaltrials.gov/ct2/show/NCT01270737). Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

A population-based cohort study defines prognoses in severe chronic kidney disease.

PubMed

Tonelli, Marcello; Wiebe, Natasha; James, Matthew T; Klarenbach, Scott W; Manns, Braden J; Ravani, Pietro; Strippoli, Giovanni F M; Hemmelgarn, Brenda R

2018-05-01

In older people with chronic kidney disease (CKD) and comorbidities, the risk of death or disability may overshadow the risk of kidney failure. To help refine this we did a retrospective population-based cohort study to evaluate the relative likelihood of adverse outcomes as functions of age and comorbidity burden among 47,228 adults with severe non-dialysis dependent CKD. We identified comorbidities using 29 validated algorithms applied to administrative data and assessed death, end-stage renal disease (ESRD), cardiovascular disease (CVD) events, and long-term care. Over five years of follow-up, 53.4% of participants died, 24.1% had a CVD event, 14.3% were placed into long-term care and 5.3% developed ESRD. Death was 145 times more likely and 11 times more likely than ESRD for participants aged 80 years or more and 60-79 years, respectively; long-term care was 30 times more likely and 1.7 times as likely as ESRD for participants aged 80 years or more and 60-79 years, respectively. Increasing comorbidity burden was similarly associated with increased risk of death and long-term care placement but reduced the likelihood of ESRD, and the risks of increasing age were similarly incremental. Thus, among patients with severe CKD, older age and/or higher comorbidity burden, death and long-term care placement are markedly more likely than ESRD. Hence, clinicians, patients and families should all consider the relative magnitude of these risks when making decisions about renal replacement. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Health effects of long-term mercury exposure among chloralkali plant workers.

PubMed

Frumkin, H; Letz, R; Williams, P L; Gerr, F; Pierce, M; Sanders, A; Elon, L; Manning, C C; Woods, J S; Hertzberg, V S; Mueller, P; Taylor, B B

2001-01-01

Inorganic mercury is toxic to the nervous system, kidneys, and reproductive system. We studied the health effects of mercury exposure among former employees of a chloralkali plant that operated from 1955 to 1994 in Georgia. Former plant workers and unexposed workers from nearby employers were studied. Exposure was assessed with a job-exposure matrix based on historical measurements and personnel records. Health outcomes were assessed with interviews, physical examinations, neurological and neurobehavioral testing, renal function testing, and urinary porphyrin measurements. Exposure-disease associations were assessed with multivariate modeling. Exposed workers reported more symptoms, and tended toward more physical examination abnormalities, than unexposed workers. Exposed workers performed worse than unexposed subjects on some quantitative tests of vibration sense, motor speed and coordination, and tremor, and on one test of cognitive function. Few findings remained significant when exposure was modeled as a continuous variable. Neither renal function nor porphyrin excretion was associated with mercury exposure. Mercury-exposed chloralkali plant workers reported more symptoms than unexposed controls, but no strong associations were demonstrated with neurological or renal function or with porphyrin excretion. Copyright 2001 Wiley-Liss, Inc.

Biphasic decline in renal function after radical cystectomy with urinary diversion.

PubMed

Makino, Katsuhiro; Nakagawa, Tohru; Kanatani, Atsushi; Kawai, Taketo; Taguchi, Satoru; Otsuka, Masafumi; Matsumoto, Akihiko; Miyazaki, Hideyo; Fujimura, Tetsuya; Fukuhara, Hiroshi; Kume, Haruki; Homma, Yukio

2017-04-01

We evaluated short- and long-term renal function in patients after radical cystectomy with urinary diversion and identified risk factors for the deterioration of renal function. This retrospective study comprised 91 patients who underwent radical cystectomy and urinary diversion for bladder cancer and survived ≥3 years after surgery. The estimated glomerular filtration rate (eGFR) was calculated, and longitudinal changes of eGFR were assessed. Deterioration in renal function in early and late postoperative years was defined as a ≥25 % decrease in the eGFR from preoperative to postoperative year one, and a reduction in the eGFR of >1 mL/min/1.73 m 2 annually in subsequent years, respectively. Univariate and multivariate logistic regression analyses were used to evaluate its association with clinicopathologic features. The median follow-up period after surgery was 7 years (range 3-26). The mean eGFR decreased from preoperative 65.1 to 58.9 mL/min/1.73 m 2 1 year after the surgery, followed by a continuous decline of ~1.0 mL/min/1.73 m 2 per year thereafter. Multivariate analyses identified ureteroenteric stricture as the sole risk factor associated with early renal function deterioration [odds ratio (OR) 4.22, p = 0.037]. Diabetes mellitus (OR 8.24, p = 0.015) and episodes of pyelonephritis (OR 4.89, p = 0.038) were independently associated with the gradual decline in the late postoperative period. In cystectomy patients with urinary diversion, the rapid deterioration of renal function observed during the first year after surgery and the gradual but continuous decline in function thereafter were found to be associated with different risk factors.

The Role of mTOR Inhibitors in Liver Transplantation: Reviewing the Evidence

PubMed Central

Klintmalm, Goran B.; Nashan, Björn

2014-01-01

Despite the success of liver transplantation, long-term complications remain, including de novo malignancies, metabolic syndrome, and the recurrence of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC). The current mainstay of treatment, calcineurin inhibitors (CNIs), can also worsen posttransplant renal dysfunction, neurotoxicity, and diabetes. Clearly there is a need for better immunosuppressive agents that maintain similar rates of efficacy and renal function whilst minimizing adverse effects. The mammalian target of rapamycin (mTOR) inhibitors with a mechanism of action that is different from other immunosuppressive agents has the potential to address some of these issues. In this review we surveyed the literature for reports of the use of mTOR inhibitors in adult liver transplantation with respect to renal function, efficacy, safety, neurological symptoms, de novo tumors, and the recurrence of HCC and HCV. The results of our review indicate that mTOR inhibitors are associated with efficacy comparable to CNIs while having benefits on renal function in liver transplantation. We also consider newer dosing schedules that may limit side effects. Finally, we discuss evidence that mTOR inhibitors may have benefits in the oncology setting and in relation to HCV-related allograft fibrosis, metabolic syndrome, and neurotoxicity. PMID:24719752

Renal impairment in HIV-infected patients initiating tenofovir-containing antiretroviral therapy regimens in a Primary Healthcare Setting in South Africa.

PubMed

Kamkuemah, Monika; Kaplan, Richard; Bekker, Linda-Gail; Little, Francesca; Myer, Landon

2015-04-01

Long-term use of tenofovir disoproxil fumarate is associated with declines in glomerular function and chronic kidney disease in HIV-infected patients. We aimed to assess the prevalence and incidence of renal impairment in a primary care setting in sub-Saharan Africa. We analysed data from 1092 HIV-infected patients initiating tenofovir at a primary care clinic in Cape Town, South Africa. Renal function was assessed for the first 12 months on ART by estimating glomerular filtration rate (eGFR) calculated using the Cockroft-Gault equation categorised into normal, mild, moderate and severe reduction in renal function based on values >90, 60-89, 30-59 and <30 ml/min/1.73 m(2) , respectively. Associations were assessed using logistic regression, and average GFR trajectory over time was modelled using linear mixed-effects models. The cohort consisted of 62% women; median age was 34 years (IQR 29; 41 years). The majority had normal renal function pre-ART (79%), 19% had mildly reduced GFR, and 2% had moderate renal impairment. Older age, more advanced WHO stage and anaemia were independently associated with prevalent renal impairment. On average, estimated glomerular function improved over the first year on tenofovir [1.10 ml/min/1.73 m(2) average increase over 12 months (95% CI: 0.80; 1.40)]. Male gender, anaemia and immunosuppression (WHO Stage III/IV and CD4 cell counts <100 cells/mm(3) ) were associated with lower average eGFR levels over time. Overall, 3% developed eGFR <50 ml/min/1.73 m(2) during this period. Serum creatinine tests conducted before 4 months on ART had low predictive value for predicting change in eGFR after a year on ART. Generally, renal function improved in HIV-infected adults initiating ART in this primary healthcare setting during the first year on ART. While monitoring of renal function is recommended in the first 4 months on ART, renal impairment appears uncommon during the first 12 months of tenofovir-containing ART in primary care populations. © 2014 John Wiley & Sons Ltd.

Idiopathic membranous nephropathy: outline and rationale of a treatment strategy.

PubMed

du Buf-Vereijken, Peggy W G; Branten, Amanda J W; Wetzels, Jack F M

2005-12-01

Idiopathic membranous nephropathy is a common cause of nephrotic syndrome. The treatment of patients with idiopathic membranous nephropathy is heavily debated. Based on literature data and our own experience, we propose a rational treatment strategy. Patients with renal insufficiency (serum creatinine level > 1.5 mg/dL [> 135 micromol/L]) are at greatest risk for the development of end-stage renal disease and should receive immunosuppressive therapy. In patients with normal renal function (serum creatinine level < 1.5 mg/dL [< 135 micromol/L]), risk for developing end-stage renal disease can be estimated by measuring urinary excretion of beta2-microglobulin or alpha1-microglobulin and immunoglobulin G. For low-risk patients, a wait-and-see policy is advised. High-risk patients likely benefit from immunosuppressive therapy. Currently, combinations of steroids with chlorambucil or cyclophosphamide are the best studied. We prefer cyclophosphamide in view of its fewer side effects. Cyclosporine may be an alternative option in patients with well-preserved renal function, although long-term data are lacking. Other immunosuppressive agents, such as mycophenolate mofetil or rituximab, currently are under study; however, data are insufficient to support their routine use.

Long-term outcomes and management of the heart transplant recipient.

PubMed

McCartney, Sharon L; Patel, Chetan; Del Rio, J Mauricio

2017-06-01

Cardiac transplantation remains the gold standard in the treatment of advanced heart failure. With advances in immunosuppression, long-term outcomes continue to improve despite older and higher risk recipients. The median survival of the adult after heart transplantation is currently 10.7 years. While early graft failure and multiorgan system dysfunction are the most important causes of early mortality, malignancy, rejection, infection, and cardiac allograft vasculopathy contribute to late mortality. Chronic renal dysfunction is common after heart transplantation and occurs in up to 68% of patients by year 10, with 6.2% of patients requiring dialysis and 3.7% undergoing renal transplant. Functional outcomes after heart transplantation remain an area for improvement, with only 26% of patients working at 1-year post-transplantation, and are likely related to the high incidence of depression after cardiac transplantation. Areas of future research include understanding and managing primary graft dysfunction and reducing immunosuppression-related complications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nephrotoxicity in rabbits after long-term nandrolone decanoate administration.

PubMed

Tsitsimpikou, Christina; Vasilaki, Fotini; Tsarouhas, Konstantinos; Fragkiadaki, Persefoni; Tzardi, Maria; Goutzourelas, Nikolaos; Nepka, Charitini; Kalogeraki, Alexandra; Heretis, Ioannis; Epitropaki, Zoi; Kouretas, Dimitrios; Tsatsakis, Aristidis M

2016-09-30

Among the various side effects of supra-physiological dose of anabolic androgenic steroids that are described, renal toxicity remains the least evaluated. The present study provides evidence that long-term administration of nandrolone decanoate could lead to alterations of renal function and structure in the experimental rabbit model. A pronounced increase in serum urea, creatinine, SGOT and SGPT is observed in the treated animals, with intramuscular administration being more detrimental. Histopathological evaluation of kidneys indicated hyperaemia, fibrosis and focal inflammation. Furthermore, the significantly increased telomerase activity found in the kidneys of the intramuscularly treated animals could possibly represent a counteracting survival mechanism. Oxidative stress markers that were influenced the most were TBARS, indicating lipid peroxidation, and GSH. An interesting finding in our study though, was that while intramuscular administration showed the highest biochemical derangement, oxidative stress markers provided mixed results between intramuscularly and subcutaneously treated rabbits. In conclusion, nephrotoxicity of nandrolone decanoate remains a multi-factorial, partly irreversible effect that involves augmented tissue oxidative status. Copyright © 2016. Published by Elsevier Ireland Ltd.

[Kidney stone formation during space flight and long-term bed rest].

PubMed

Okada, Atsushi; Ichikawa, Jun; Tozawa, Keiichi

2011-10-01

Microgravity environment like space flight or a condition requiring long-term bed-rest increase bone resorption and decrease bone formation, inducing the rapid decrease of bone minerals to osteoporosis. Bone mineral loss increases urinary calcium excretion and the risk of urinary stone formation. To clarify the influence of the conditions on renal stone formation, a 90-day bed rest test was performed to analyze the mechanism of microgravity or bed rest-induced stone formation and prevention by bisphosphonate medication and bed-rest exercise. As the results, renal stone formation was observed in control and exercise groups and no stone was seen in the medication group. In the medication group, urinary calcium excretion and relative supersaturation of calcium oxalate were lower than in the control group throughout the bed-rest and recovery period. Bisphosphonate is useful for the prevention of renal stone formation during space flight and long-term bed-rest.

Examination of the effect of changing to azilsartan from candesartan in renal transplant patients.

PubMed

Ishii, T; Yasuda, M; Saito, Y; Mori, Y; Hayashi, T; Uemura, H; Nose, K; Nishioka, T

2014-01-01

Azilsartan, an angiotensin receptor blocker (ARB), was administered to renal transplant recipients to investigate the safety and antihypertensive effect in addition to its ARB-characteristic organ-protective effect. The subjects were 20 patients (18 males, 2 females; baseline serum creatinine 2.39 ± 1.33 mg/dL) responding poorly to candesartan, who suffered albuminuria (>0.3 g/g creatinine) and hypertension (>140/90 mm Hg) following renal transplantation. Three months after candesartan was switched to azilsartan 20 mg/d, blood pressure, creatinine-corrected urinary albumin excretion, urinary L-type acid binding protein, urinary 8-hydroxydeoxyguano-sine, serum creatinine, and estimated glomerular filtration rate were evaluated. Thirteen patients received cyclosporine (65.0%) and 7 received tacrolimus (35.0%). Another hypertensive (calcium antagonist) agent was combined in 7 (35.0%). Systolic blood pressure significantly decreased from 139.5 mm Hg (baseline) from 128.7 mm Hg (at 3 months), whereas no significant changes were observed for diastolic blood pressure. The percentage of patients achieving the target level of antihypertensive effect (blood pressure < 130/80 mm Hg) significantly improved from 30.0% (baseline) to 70.0% (at 3 months). No significant changes were observed in renal graft function, oxidative stress marker level, or biochemical examination findings. Sufficient antihypertensive effect was demonstrated soon after switching to azilsartan. However, no significant change was found in renal damage markers. Long-term study must be conducted to confirm the protective effect azilsartan on the transplanted kidney, as found with candesartan. The safety of azilsartan was demonstrated. If the transplanted kidney protection is demonstrated, this drug is expected to contribute to the improved long-term prognosis of renal transplant recipients. Copyright © 2014 Elsevier Inc. All rights reserved.

Long-term survival in an adolescent with widely metastatic renal cell carcinoma with rhabdoid features.

PubMed

Ettinger, L J; Goodell, L A; Javidian, P; Hsieh, Y; Amenta, P

2000-01-01

Renal cell carcinoma is rarely seen in children and adolescents. Patients with widespread disease at diagnosis have a particularly poor survival rate. Currently, all known chemotherapy has been ineffective in improving the median survival in patients with advanced disease. A 13-year-old black boy with stage IV renal cell carcinoma with rhabdoid features is a long-term disease-free survivor after aggressive multiagent chemotherapy. After the initial evaluation and histologic diagnosis of renal cell carcinoma, the patient received three courses of an aggressive chemotherapy regimen consisting of vincristine, doxorubicin, cyclophosphamide with mesna uroprotection, granulocyte colony-stimulating factor and erythropoietin (Epogen). After an almost complete response, a radical nephrectomy was performed and results demonstrated a solitary small nodule with viable tumor. After surgery, he received floxuridine infusion for 14 days by circadian schedule at 28-day intervals for a total of 1 year. The patient is well and free of disease 5 years after initial presentation. The dramatic response to treatment and long-term disease-free survival of this patient suggest this chemotherapeutic approach warrants additional investigation.

Genotype-Phenotype Analysis in Pediatric Patients with Distal Renal Tubular Acidosis.

PubMed

Park, Eujin; Cho, Myung Hyun; Hyun, Hye Sun; Shin, Jae Il; Lee, Joo Hoon; Park, Young Seo; Choi, Hyun Jin; Kang, Hee Gyung; Cheong, Hae Il

2018-01-01

Primary distal renal tubular acidosis (dRTA) in children is a rare genetic disorder, and three causative mutated genes have been identified: SLC4A1, ATP6V1B1, and ATP6V0A4. We analyzed the prevalence and phenotypic differences of genetic mutations in children with dRTA. A total of 17 children with dRTA were enrolled in the study. All patients underwent genetic testing for all three candidate genes. Pathogenic mutations, including six novel mutations, were detected in 15 (88.2%) patients: dominant SLC4A1 mutations in ten (58.8%) patients, recessive ATP6V0A4 mutations in three (17.6%) patients, and recessive ATP6V1B1 mutations in two (11.8%) patients. Compared to other patients, patients with SLC4A1 mutations showed an older age of onset (3.7 ± 2.6 years) and less severe metabolic acidosis at initial presentation. All patients developed nephrocalcinosis, and sensorineural hearing loss was observed in two patients with ATP6V1B1 mutations. Three (17.6%) patients had decreased renal function (chronic kidney disease stage 2), and five (29.4%) patients had persistent growth retardation at the last follow-up. Long-term prognosis showed no genotype-phenotype correlation. SLC4A1 is the most common defective gene in Korean children with dRTA. Patients with SLC4A1 mutations show later onset and milder disease severity. Long-term follow-up of hearing ability, renal function, and growth is necessary for patients with dRTA. © 2018 The Author(s). Published by S. Karger AG, Basel.

Macrophage Phenotype Controls Long-Term AKI Outcomes—Kidney Regeneration versus Atrophy

PubMed Central

Gröbmayr, Regina; Ryu, Mi; Lorenz, Georg; Hartter, Ingo; Mulay, Shrikant R.; Susanti, Heni Eka; Kobayashi, Koichi S.; Flavell, Richard A.; Anders, Hans-Joachim

2014-01-01

The mechanisms that determine full recovery versus subsequent progressive CKD after AKI are largely unknown. Because macrophages regulate inflammation as well as epithelial recovery, we investigated whether macrophage activation influences AKI outcomes. IL-1 receptor–associated kinase-M (IRAK-M) is a macrophage-specific inhibitor of Toll-like receptor (TLR) and IL-1 receptor signaling that prevents polarization toward a proinflammatory phenotype. In postischemic kidneys of wild-type mice, IRAK-M expression increased for 3 weeks after AKI and declined thereafter. However, genetic depletion of IRAK-M did not affect immunopathology and renal dysfunction during early postischemic AKI. Regarding long-term outcomes, wild-type kidneys regenerated completely within 5 weeks after AKI. In contrast, IRAK-M−/− kidneys progressively lost up to two-thirds of their original mass due to tubule loss, leaving atubular glomeruli and interstitial scarring. Moreover, M1 macrophages accumulated in the renal interstitial compartment, coincident with increased expression of proinflammatory cytokines and chemokines. Injection of bacterial CpG DNA induced the same effects in wild-type mice, and TNF-α blockade with etanercept partially prevented renal atrophy in IRAK-M−/− mice. These results suggest that IRAK-M induction during the healing phase of AKI supports the resolution of M1 macrophage– and TNF-α–dependent renal inflammation, allowing structural regeneration and functional recovery of the injured kidney. Conversely, IRAK-M loss-of-function mutations or transient exposure to bacterial DNA may drive persistent inflammatory mononuclear phagocyte infiltrates, which impair kidney regeneration and promote CKD. Overall, these results support a novel role for IRAK-M in the regulation of wound healing and tissue regeneration. PMID:24309188

Direct renal effects of a fructose-enriched diet: interaction with high salt intake

PubMed Central

Ares, Gustavo R.

2015-01-01

Consumption of fructose has increased during the last 50 years. Excessive fructose consumption has a detrimental effect on mammalian health but the mechanisms remain unclear. In humans, a direct relationship exists between dietary intake of added sugars and increased risk for cardiovascular disease mortality (52). While the causes for this are unclear, we recently showed that fructose provided in the drinking water induces a salt-dependent increase in blood pressure in Sprague-Dawley rats in a matter of days (6). However, little is known about the effects of fructose in renal salt handling and whether combined intake of high fructose and salt can lead to salt-sensitive hypertension before the development of metabolic abnormalities. The long-term (more than 4 wk) adverse effects of fructose intake on renal function are not just due to fructose but are also secondary to alterations in metabolism which may have an impact on renal function. This minireview focuses on the acute effect of fructose intake and its effect on salt regulation, as they affect blood pressure. PMID:26447210

Acute kidney injury and disease: Long-Term consequences and management.

PubMed

Rangaswamy, Dharshan; Sud, Kamal

2018-05-27

With increasing longevity and presence of multiple co-morbidities, a significant proportion of hospitalized patients and an even larger population in the community is at increased risk for developing an episode of acute kidney injury (AKI). Because of improvements in short term outcomes following an episode of AKI, survivors of an episode of AKI are now predisposed to develop its long-term sequel. Identification of risk for progression to chronic kidney disease (CKD) is complicated by the absence of good biomarkers that identify this risk and the variability of risk associated with clinical factors including, but not limited to number of AKI episodes, severity, duration of previous AKI and pre-existing chronic kidney disease that has made prediction for long-term outcomes in survivors of AKI more difficult. Being a significant contributor for the growing incidence of CKD, there is a need to implement measures to prevent AKI both in the community and hospital settings, target interventions to treat AKI that are also associated with better long-term outcomes, accurately identify patients at risk for adverse consequences following an episode of AKI and institute therapeutic strategies to improve these long-term outcomes. We discuss the lasting renal and non-renal consequences following an episode of AKI, available biomarkers and non-invasive testing to identify ongoing intra-renal pathology and review the currently available and future treatment strategies to help reduce these adverse long-term outcomes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Tailored dialysis start may allow persistence of residual renal function after graft failure: a case report.

PubMed

Piccoli, G B; Motta, D; Gai, M; Mezza, E; Maddalena, E; Bravin, M; Tattoli, F; Consiglio, V; Burdese, M; Bilucaglia, D; Ferrari, A; Segoloni, G P

2004-11-01

Restarting dialysis after kidney transplantation is a critical step with psychological and clinical implications. Maintenance of residual renal function a known factor affecting survival in chronic kidney disease, has so far not been investigated after a kidney transplantation. A 54-year-old woman who started dialysis in 1974 (first graft, 1975-1999) received a second "marginal" kidney graft in February 2001 (donor age, 65 years). Her chronic therapy was tacrolimus and steroids. She had a clinical history as follows: nadir creatinine level of 1.5 mg/dL, moderate-severe hypertension, progressive graft dysfunction, nonresponsiveness to addition of mycophenolate, tapering FK levels, and a rescue switch from tacrolimus to rapamycin. From October to December 2003, the creatinine level increased from 2-2.8 to 7 mg/dL. Biopsy specimen showed malignant and "benign" nephrosclerosis, posttransplantation glomerulopathy, and tacrolimus toxicity. Chronic dialysis was started (GFR <3 mL/min). Rapamycin was discontinued. Dialysis was tailored to reach an equivalent renal clearance of >15 mL/min (2 sessions/wk). Blood pressure control improved, nephrotoxic drugs were avoided, and fluid loss was minimized (maximum 500 mL/hr). By this policy, renal function progressively increased to GFR >10 mL/min in May 2004, allowing a once or twice weekly dialysis schedule, with good clinical balance, and obvious advantages for the quality of life. This long-term patient, who restarted dialysis with severely reduced renal function, regained sufficient renal function to allow once weekly dialysis. Thus, careful tailoring of dialysis sessions at the restart of dialysis may allow preservation of residual kidney function, at least in individuals for whom a subsequent graft is unlikely.

Diabetes-Induced Decrease in Renal Oxygen Tension: Effects of an Altered Metabolism

NASA Astrophysics Data System (ADS)

Palm, Fredrik; Carlsson, Per-Ola; Fasching, Angelica; Hansell, Peter; Liss, Per

During conditions with experimental diabetes mellitus, it is evident that several alterations in renal oxygen metabolism occur, including increased mitochondrial respiration and increased lactate accumulation in the renal tissue. Consequently, these alterations will contribute to decrease the interstitial pO2, preferentially in the renal medulla of animals with sustained long-term hyperglycemia.

Long-term tolerance to kidney allografts in a preclinical canine model.

PubMed

Kuhr, Christian S; Yunusov, Murad; Sale, George; Loretz, Carol; Storb, Rainer

2007-08-27

Durable immune tolerance supporting vascularized allotransplantation offers the possibility of extending graft survival and avoiding harmful complications of chronic immunosuppression. Immune tolerance to renal allografts was induced in a preclinical canine model through engraftment of donor hematopoietic cells using a combination of low-dose total body irradiation and a short course of immunosuppression. Subsequently, donor renal allografts were transplanted accompanied by bilateral native nephrectomies. With 5-year follow up, we found normal renal function in all recipients and no histological evidence of acute or chronic rejection. This tolerance does not extend universally to donor skin grafts, however, with two of four animals rejecting delayed donor skin grafts. Hematopoietic chimerism produces durable and robust immune tolerance to kidney allografts, although incomplete tolerance to donor skin grafting.

Systematic review of kidney transplantation functional predictors.

PubMed

Miret Alomar, E; Trilla Herrera, E; Lorente Garcia, D; Regis Placido, L; López Del Campo, R; Cuadras Solé, M; Pont Castellana, T; Moreso Mateos, F; Serón Micas, D; Morote Robles, J

2018-05-01

Kidney transplantation from donors with expanded criteria has increased the pool of kidneys at the cost of a higher risk of short and long-term graft dysfunction. The main issue lies in determining which kidneys will offer acceptable function and survival compared with the risk represented by surgery and subsequent immunosuppression. The objective of our article is to review the current evidence on the tools for predicting the functionality of kidney transplantation from cadaveric donors with expanded criteria and determining the validity for their use in standard practice. We conducted a systematic literature review according to the PRISM criteria, through Medline (http://www.ncbi.nlm.nih.gov) and using the keywords (in isolation or in conjunction) "cadaveric renal transplantation; kidney graft function appraisal, graft function predictors". We selected prospective and retrospective series and review articles. A total of 375 articles were analysed, 39 of which were ultimately selected for review. The predictors of functionality include the following: The donor risk indices; the calculation of the renal functional weight or the assessment of the nephronic mass; the measurement of vascular resistances during perfusion in hypothermia; the measurement of the donor's biomarkers in urine and in the perfusion liquid; the measurement of functional and reperfusion parameters in normothermia; and the measurement of morphological parameters (microscopic and macroscopic) of the target organ. In this article, we present an explanatory summary of each of these parameters, as well as their most recent evidence on this issue. None of the reviewed parameters in isolation could reliably predict renal function and graft survival. There is a significant void in terms of the macroscopic assessment of kidney transplantation. We need to continue developing predictors of renal functionality to accurately define the distribution of each currently available donor kidney. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Preoperative hydronephrosis is associated with less decline in renal function after radical nephroureterectomy for upper tract urothelial carcinoma.

PubMed

Singla, Nirmish; Hutchinson, Ryan; Haddad, Ahmed; Sagalowsky, Arthur; Lotan, Yair; Margulis, Vitaly

2016-08-01

To compare renal function changes after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) based on the presence of preoperative hydronephrosis. Clinicopathologic data of 208 patients with UTUC treated surgically from 1998 to 2013 were compiled. Patients with bilateral disease, less than 1 month follow up, missing hydronephrosis data, or who underwent nephron-sparing approaches were excluded. Estimated glomerular filtration rate (eGFR) was calculated preoperatively, at first follow up (within 3 months) and at last follow up using the Modification of Diet in Renal Disease equation. Events were defined as new-onset stage III chronic kidney disease (CKD) or worsening of CKD stage in preexisting CKD. Kaplan-Meier event-free survival was assessed. Cox regression was performed to identify predictors of events. A total of 132 patients were analyzed, including 62 (47.0%) with hydronephrosis. Median follow up was 28.6 months. Patients with hydronephrosis had larger tumors (p = 0.045) and higher pathologic stage (p = 0.010) than those without hydronephrosis. Baseline eGFR was comparable between groups (p = 0.088). Patients without hydronephrosis experienced greater declines in eGFR following surgery (p < 0.001) and higher event rates at first (42.8% versus 24.2%, p = 0.028) and last (54.2% versus 30.6%, p = 0.008) follow up. On Cox regression, hydronephrosis predicted lower event likelihood in the long term (univariate HR 0.54, p = 0.033), while ureteral tumor location predicted lower event likelihood in the short term (HR 0.52, p = 0.030). Patients with hydronephrosis undergoing RNU for UTUC experience less decline in renal function than those without hydronephrosis. Given the prevalence of renal dysfunction in patients with UTUC, our results may help inform preoperative counseling.

Management of bladder dysfunction in Wolfram syndrome with Mitrofanoff appendicovesicostomy: long-term follow-up.

PubMed

Mozafarpour, Sarah; Kajbafzadeh, Abdol-Mohammad; Mojtahed, Ali; Mojtahed, Mohammad; Mahboubi, Hossein; Shalileh, Keivan

2015-07-01

To present the long-term outcomes of appendicovesicostomy using the Mitrofanoff principle for end-stage Wolfram bladder dysfunction as an alternative to clean intermittent self-catheterization (CIC) per urethra mainly following blindness. Twelve Wolfram patients presenting with bilateral hydroureteronephrosis and advanced bladder dysfunction were included in this study. All patients were managed initially by CIC per urethra. All of these patients became blind during follow-up and were unable to perform urethral CIC independently. Out of these patients, six patients agreed to proceed to appendicovesicostomy. Appendicovesicostomy urinary diversion using the Mitrofanoff principle was performed in these six blind patients. The rest of the patients stopped CIC or performed CIC irregularly. Severe hydroureteronephrosis and large bladders were found in all patients prior to intervention. All patients were able to conduct CIC independently through the stoma and maintained overnight bladder free drainage. In all patients with urinary diversion and CIC, the hydroureteronephrosis was reduced and renal function returned to normal. However, the non-intervention group ended with different degrees of progressive renal failure with three mortalities during the follow-up. We suggest appendicovesicostomy as a safe and lifesaving procedure for long-term management of bladder dysfunction in Wolfram syndrome particularly after progression to blindness. Copyright © 2015 Elsevier Inc. All rights reserved.

A Randomized 2x2 Factorial Clinical Trial of Renal Transplantation: Steroid-Free Maintenance Immunosuppression with Calcineurin Inhibitor Withdrawal after Six Months Associates with Improved Renal Function and Reduced Chronic Histopathology.

PubMed

Stevens, R Brian; Foster, Kirk W; Miles, Clifford D; Kalil, Andre C; Florescu, Diana F; Sandoz, John P; Rigley, Theodore H; Malik, Tamer; Wrenshall, Lucile E

2015-01-01

The two most significant impediments to renal allograft survival are rejection and the direct nephrotoxicity of the immunosuppressant drugs required to prevent it. Calcineurin inhibitors (CNI), a mainstay of most immunosuppression regimens, are particularly nephrotoxic. Until less toxic antirejection agents become available, the only option is to optimize our use of those at hand. To determine whether intensive rabbit anti-thymocyte globulin (rATG) induction followed by CNI withdrawal would individually or combined improve graft function and reduce graft chronic histopathology-surrogates for graft and, therefore, patient survival. As previously reported, a single large rATG dose over 24 hours was well-tolerated and associated with better renal function, fewer infections, and improved patient survival. Here we report testing whether complete CNI discontinuation would improve renal function and decrease graft pathology. Between April 20, 2004 and 4-14-2009 we conducted a prospective, randomized, non-blinded renal transplantation trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment = 180). Subsequent maintenance immunosuppression consisted of tacrolimus, a CNI, and sirolimus, a mammalian target of rapamycin inhibitor. We report here the outcome of converting patients after six months either to minimized tacrolimus/sirolimus or mycophenolate mofetil/sirolimus. Primary endpoints were graft function and chronic histopathology from protocol kidney biopsies at 12 and 24 months. CNI withdrawal (on-treatment analysis) associated with better graft function (p <0.001) and lower chronic histopathology composite scores in protocol biopsies at 12 (p = 0.003) and 24 (p = 0.013) months, without affecting patient (p = 0.81) or graft (p = 0.93) survival, or rejection rate (p = 0.17). CNI (tacrolimus) withdrawal at six months may provide a strategy for decreased nephrotoxicity and improved long-term function in steroid-free low immunological risk renal transplant patients. ClinicalTrials.gov NCT00556933.

Practical recommendations for the early use of m-TOR inhibitors (sirolimus) in renal transplantation.

PubMed

Campistol, Josep M; Cockwell, Paul; Diekmann, Fritz; Donati, Donato; Guirado, Luis; Herlenius, Gustaf; Mousa, Dujanah; Pratschke, Johann; San Millán, Juan Carlos Ruiz

2009-07-01

m-TOR inhibitors (e.g. sirolimus) are well-tolerated immunosuppressants used in renal transplantation for prophylaxis of organ rejection, and are associated with long-term graft survival. Early use of sirolimus is often advocated by clinicians, but this may be associated with a number of side-effects including impaired wound-healing, lymphoceles and delayed graft function. As transplant clinicians with experience in the use of sirolimus, we believe such side-effects can be limited by tailored clinical management. We present recommendations based on published literature and our clinical experience. Furthermore, guidance is provided on sirolimus use during surgery, both at transplantation and for subsequent operations.

Improving the efficacy of RAAS blockade in patients with chronic kidney disease.

PubMed

Lambers Heerspink, Hiddo J; de Borst, Martin H; Bakker, Stephan J L; Navis, Gerjan J

2013-02-01

Reduction of blood pressure and proteinuria by blockade of the renin-angiotensin-aldosterone system (RAAS) has been the cornerstone of renoprotective intervention for patients with chronic kidney disease (CKD) for many years. Despite the proven efficacy of RAAS blockade, however, the reduction in proteinuria is insufficient in many patients, and does not prevent further deterioration of renal function. Short-term studies have shown that a variety of treatment intensification strategies have a beneficial effect on blood pressure and proteinuria, including RAAS blockade using either dose escalation or multiple drugs, and restriction of dietary sodium. Large clinical trials have shown that RAAS blockade with multiple drugs does not improve patients' long-term renal or cardiovascular outcome. By contrast, two post-hoc analyses of landmark trials in nephrology show beneficial renal and cardiovascular effects from avoiding excessive dietary sodium intake during single-agent RAAS blockade therapy. The effects of dietary sodium restriction on renal or cardiovascular outcome still require prospective confirmation. However, current data support the implementation of lifestyle changes to reduce dietary sodium intake in combination with single-agent RAAS blockade, rather than dual-agent RAAS blockade, as a potent and feasible strategy to mitigate the burden of renal and cardiovascular disease in patients with CKD.

The recovery status from delayed graft function can predict long-term outcome after deceased donor kidney transplantation.

PubMed

Lee, Juhan; Song, Seung Hwan; Lee, Jee Youn; Kim, Deok Gie; Lee, Jae Geun; Kim, Beom Seok; Kim, Myoung Soo; Huh, Kyu Ha

2017-10-20

The effect of delayed graft function (DGF) recovery on long-term graft outcome is unclear. The aim of this study was to examine the association of DGF recovery status with long-term outcome. We analyzed 385 recipients who underwent single kidney transplantation from brain-dead donors between 2004 and 2015. Patients were grouped according to renal function at 1 month post-transplantation: control (without DGF); recovered DGF (glomerular filtration rate [GFR] ≥ 30 mL/min/1.73 m 2 ); and incompletely recovered DGF group (GFR < 30 mL/min/1.73 m 2 ). DGF occurred in 104 of 385 (27%) recipients. Of the DGF patients, 70 recovered from DGF and 34 incompletely recovered from DGF. Death-censored graft survival rates for control, recovered DGF, and incompletely recovered DGF groups were 95.3%, 94.7%, and 80.7%, respectively, at 5 years post-transplantation (P = 0.003). Incompletely recovered DGF was an independent risk factor for death-censored graft loss (HR = 3.410, 95%CI, 1.114-10.437). DGF was associated with increased risk for patient death regardless of DGF recovery status. Mean GFRs at 5 years were 65.5 ± 20.8, 62.2 ± 27.0, and 45.8 ± 15.4 mL/min/1.73 m 2 for control, recovered, and incompletely recovered DGF groups, respectively (P < 0.001). Control group and recovered DGF patients had similar renal outcomes. However, DGF was associated with increased risk for patient death regardless of DGF recovery status.

Short-term and long-term effects of dipeptidyl peptidase-4 inhibitors in type 2 diabetes mellitus patients with renal impairment: a meta-analysis of randomized controlled trials.

PubMed

Li, Ruifei; Wang, Rui; Li, Haixia; Sun, Sihao; Zou, Meijuan; Cheng, Gang

2016-09-01

To assess the short-term and long-term effects of dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes mellitus patients with renal impairment, a meta-analysis of randomized clinical trials of DPP-4 inhibitor interventions in type 2 diabetes mellitus patients with renal impairment was performed. PubMed, Embase, Cochrane Library and ClinicalTrials.gov were searched through the end of March 2015. Randomized clinical trials were selected if (1) DPP-4 inhibitors were compared with a placebo or other active-comparators, (2) the treatment duration was ≥12 weeks and (3) data regarding changes in haemoglobin A1c (HbA1c ), changes in fasting plasma glucose or hypoglycaemia and other adverse events were reported. Of 790 studies, ten studies on eight randomized clinical trials were included. Compared with the control group, DPP-4 inhibitors were associated with a greater HbA1c reduction in both the short-term [mean differences (MD) = -0.45, 95% confidence intervals (-0.57, -0.33), p < 0.0001] and long-term [MD = -0.33, 95% confidence intervals (-0.63, -0.03), p = 0.03] treatments. However, the long-term greater reduction in HbA1c with DPP-4 inhibitor treatment was only significant when the control treatment comprised placebo plus stable background treatment, but not glipizide plus stable background treatment. DPP-4 inhibitors were associated with a greater fasting plasma glucose reduction [MD = -12.59, 95% confidence intervals (-22.01, -3.17), p = 0.009] over the short-term; however, this effect was not present over the long-term. Regarding the hypoglycaemia adverse events assessment, the long-term treatment data indicated there was no increased risk of hypoglycaemia compared with placebo or active-controlled anti-diabetic drugs. The present meta-analysis confirms that DPP-4 inhibitors are effective and equivalent to other agents in type 2 diabetes mellitus patients with renal impairment. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

A review of the evidence for use of thymoglobulin induction in renal transplantation.

PubMed

Gaber, A Osama; Knight, R J; Patel, S; Gaber, L W

2010-06-01

Depleting antilymphocyte, or antithymocyte antibodies, have long been an integral part of induction regimens and continue today to be used in the management of patients at risk of early rejection or those in whom the introduction of calcineurins or other immune suppressants must be delayed. Registry data demonstrate that the most commonly used depleting antibody, rabbit anti-human thymocyte globulin (rATG), is associated with improved outcomes following renal transplantation in high-risk patients, particularly in conjunction with steroid-avoidance regimens. Two prospective randomized trials in high-risk renal allograft patients have also demonstrated an advantage of r-ATG induction compared to the nondepleting interleukin receptor (IL2RA) antibodies. In low-immunologic-risk patients, however, r-ATG induction and IL2RA induction appear to be equivalent in terms of rejection prophylaxis and long-term function. Other studies have shown that sequential rATG-containing regimens were superior to no induction and allowed for successful late introduction of calcineurin inhibitors. The side effect profile of the depleting antibody included increased incidence of fever, hematologic abnormalities, cytomegalovirus infections when prophylaxis was not employed, and in some studies, increased incidence of posttransplant lymphoproliferative disease. This review describes the evidence supporting the use of depleting ATGs in kidney transplantation.

The pathogenesis and management of hypertension in diabetic kidney disease.

PubMed

Van Buren, Peter N; Toto, Robert D

2013-01-01

Hypertension commonly coexists with diabetes, and its prevalence is even higher in the presence of diabetic kidney disease. The pathogenesis of hypertension in this population stems from increased extracellular volume and increased vasoconstriction that results from mechanisms that may be attributed to both diabetes and the eventual impairment of renal function. Antihypertensive therapy aimed at reducing blood pressure remains a primary goal in preventing the incidence of diabetic kidney and slowing its progression. Initial therapy should consist of an ACE inhibitor or ARB titrated to the maximally tolerated dose. Using combination RAAS therapy further reduces proteinuria, but the benefits of this strategy compared with the potential risks of hyperkalemia and acute deterioration of renal function are still unknown. Endothelin receptor antagonists also lower proteinuria, but these can be associated with volume overload and edema with no clear long-term benefit on renal function yet identified. Further large clinical trials are needed to better understand how progression to ESRD can be slowed or halted in patients with diabetic kidney disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Renal function alterations during skeletal muscle disuse in simulated microgravity

NASA Technical Reports Server (NTRS)

Tucker, Bryan J.

1992-01-01

This project was to examine the alterations in renal functions during skeletal muscle disuse in simulated microgravity. Although this area could cover a wide range of investigative efforts, the limited funding resulted in the selection of two projects. These projects would result in data contributing to an area of research deemed high priority by NASA and would address issues of the alterations in renal response to vasoactive stimuli during conditions of skeletal muscle disuse as well as investigate the contribution of skeletal muscle disuse, conditions normally found in long term human exposure to microgravity, to the balance of fluid and macromolecules within the vasculature versus the interstitium. These two projects selected are as follows: investigate the role of angiotensin 2 on renal function during periods of simulated microgravity and skeletal muscle disuse to determine if the renal response is altered to changes in circulating concentrations of angiotensin 2 compared to appropriate controls; and determine if the shift of fluid balance from vasculature to the interstitium, the two components of extracellular fluid volume, that occur during prolonged exposure to microgravity and skeletal muscle disuse is a result, in part, to alterations in the fluid and macromolecular balance in the peripheral capillary beds, of which the skeletal muscle contains the majority of recruitment capillaries. A recruitment capillary bed would be most sensitive to alterations in Starling forces and fluid and macromolecular permeability.

Vascular and renal function in experimental thyroid disorders.

PubMed

Vargas, Félix; Moreno, Juan Manuel; Rodríguez-Gómez, Isabel; Wangensteen, Rosemary; Osuna, Antonio; Alvarez-Guerra, Miriam; García-Estañ, Joaquín

2006-02-01

This review focuses on the effects of thyroid hormones in vascular and renal systems. Special emphasis is given to the mechanisms by which thyroid hormones affect the regulation of body fluids, vascular resistance and, ultimately, blood pressure. Vascular function is markedly affected by thyroid hormones that produce changes in vascular reactivity and endothelial function in hyper- and hypothyroidism. The hypothyroid state is accompanied by a marked decrease in sensitivity to vasoconstrictors, especially to sympathetic agonists, alteration that may play a role in the reduced blood pressure of hypothyroid rats, as well as in the preventive effects of hypothyroidism on experimental hypertension. Moreover, in hypothyroid rats, the endothelium-dependent and nitric oxide donors vasodilation is reduced. Conversely, the vessels from hyperthyroid rats showed an increased endothelium-dependent responsiveness that may be secondary to the shear-stress induced by the hyperdynamic circulation, and that may contribute to the reduced vascular resistance characteristic of this disease. Thyroid hormones also have important effects in the kidney, affecting renal growth, renal haemodynamics, and salt and water metabolism. In hyperthyroidism, there is a resetting of the pressure-natriuresis relationship related to hyperactivity of the renin-angiotensin system, which contributes to the arterial hypertension associated with this endocrine disease. Moreover, thyroid hormones affect the development and/or maintenance of various forms of arterial hypertension. This review also describes recent advances in our understanding of thyroid hormone action on nitric oxide and oxidative stress in the regulation of cardiovascular and renal function and in the long-term control of blood pressure.

Chromium-induced kidney disease.

PubMed

Wedeen, R P; Qian, L F

1991-05-01

Kidney disease is often cited as one of the adverse effects of chromium, yet chronic renal disease due to occupational or environmental exposure to chromium has not yet been reported. Occasional cases of acute tubular necrosis (ATN) following massive absorption of chromate have been described. Chromate-induced ATN has been extensively studied in experimental animals following parenteral administration of large doses of potassium chromate (hexavalent) (15 mg/kg body weight). The chromate is selectively accumulated in the convoluted proximal tubule where necrosis occurs. An adverse long-term effect of low-dose chromium exposure on the kidneys is suggested by reports of low molecular weight (LMW) proteinuria in chromium workers. Excessive urinary excretion of beta 2-microglobulin, a specific proximal tubule brush border protein, and retinol-binding protein has been reported among chrome platers and welders. However, LMW proteinuria occurs after a variety of physiologic stresses, is usually reversible, and cannot by itself be considered evidence of chronic renal disease. Chromate-induced ATN and LMW proteinuria in chromium workers, nevertheless, raise the possibility that low-level, long-term exposure may produce persistent renal injury. The absence of evidence of chromate-induced exposure may produce persistent renal injury. The absence of evidence of chromate-induced chronic renal disease cannot be interpreted as evidence of the absence of such injury. Rather, it must be recognized that no prospective cohort or case-control study of the delayed renal effects of low-level, long-term exposure to chromium has been published.

[Hybrid operating room: For what?

PubMed

Benoit, M; Bouvier, A; Bigot, P

2017-11-01

Hybrid operating rooms (HOR) are rooms that mix interventional radiology and surgical equipments. They are usually used in heart, vascular, orthopedic and neurosurgery, and make it possible to consider new minimally invasive procedures in urology. Thanks to these, we developed a new partial nephrectomy technique without renal pedicle clamping and without ischemia. Renal cancer is now diagnosed at localized stage in most of the cases, and its treatment is mostly based on nephron sparing surgery. However, the hemorrhagic character of this intervention requires a renal pedicle clamping whose long-term consequences on renal function are discussed. It also exposes to a classical complication: the renal artery pseudoaneurysm. Therefore, we developed a new laparoscopic partial nephrectomy technique without clamping or approach of renal pedicle, by a selective embolization of tumor vessels through an endovascular route, immediately before the surgery. HOR allowed the combination of the two procedures in the same time and space unit. Tumor staining by Bleu Patenté also aids the surgeon in its spotting. HOR allow a new approach in localized renal cancer management, and should be used in many other urologic surgeries in years to come. They represent a technological advancement by combining interventional radiologists and surgeons' expertise. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Assessment of lead health hazards in a body shop of an automobile assembly plant.

PubMed

Lilis, R; Valciukas, J A; Kon, S; Sarkosi, L; Campbell, C; Selikoff, I J

1982-01-01

This study of an occupationally lead-exposed group in the automobile assembly industry (body shop employees) has provided information with regard to current and recent lead-exposure levels characteristic for these operations. Comparison with findings in other, previously studied occupational groups (secondary smelter workers) indicated that current and recent lead exposure was significantly lower in the autobody shop employees. Prevalence of symptoms was found to be higher than in a control, non-lead-exposed group of maintenance workers in the same plant, but the differences reached the level of statistical significance only sporadically. Long-term effects on renal function, as reflected in blood urea nitrogen (BUN) and creatinine levels, were documented to be significant in this group of autobody shop employees. When compared with two secondary lead smelter populations previously studied, correlations between indicators of renal function, BUN and creatinine, and duration of lead exposure were consistently higher in the secondary lead smelter populations than in the group of autobody shop employees, although duration of lead exposure was greater in the latter. These findings are consistent with a dose-response relationship with regard to renal function impairment due to lead absorption. An increased prevalence of hypertension, especially diastolic, was also found, probably the consequence of renal effect.

Thermal Versus Impedance-Based Ablation of Renal Cell Carcinoma: A Meta-analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Modabber, Milad, E-mail: mmodabber@gmail.com; Martin, Jason, E-mail: jason.martin@medportal.ca; Athreya, Sriharsha, E-mail: sathreya@stjosham.on.ca

2013-10-04

BackgroundPercutaneous radiofrequency ablation (RFA) of renal carcinoma has become an established treatment modality. However, thermal (TB) versus impedance-based (IB)-RF generators have not been previously compared.MethodsA literature search on the application of RFA for renal masses using TB or IB-RF generators was performed. The safety, efficacy, and long-term outcomes of TB versus IB-based RFA were assessed using the outcome measures of technical success, local recurrence rate, complications, and preservation of renal function.ResultsAcross the 27 included studies, pooled results suggested comparable results for technical success (TB-RFA 98.53 % vs. IB-RFA 98.78 %, P = 0.9813). Clinical efficacy results were also similar across both generators (91.0 % TB-RFAmore » vs. 91.5 % IB-RFA; P = 0.73). At follow-up, no differences in renal function (relative risk [RR] 0.5, 95 % confidence interval [CI] 0.45–5.48), and local recurrence (RR 0.717, 95 % CI 0.49–1.50) were observed. The pooled proportion of overall complication rates was 13.1 % for TB-RFA and 11.5 % for IB-RFA.ConclusionNo differences in the observed parameters were found either during surgery or at follow-up.« less

A computational analysis of the long-term regulation of arterial pressure

PubMed Central

Beard, Daniel A.

2013-01-01

The asserted dominant role of the kidneys in the chronic regulation of blood pressure and in the etiology of hypertension has been debated since the 1970s. At the center of the theory is the observation that the acute relationships between arterial pressure and urine production—the acute pressure-diuresis and pressure-natriuresis curves—physiologically adapt to perturbations in pressure and/or changes in the rate of salt and volume intake. These adaptations, modulated by various interacting neurohumoral mechanisms, result in chronic relationships between water and salt excretion and pressure that are much steeper than the acute relationships. While the view that renal function is the dominant controller of arterial pressure has been supported by computer models of the cardiovascular system known as the “Guyton-Coleman model”, no unambiguous description of a computer model capturing chronic adaptation of acute renal function in blood pressure control has been presented. Here, such a model is developed with the goals of: 1. representing the relevant mechanisms in an identifiable mathematical model; 2. identifying model parameters using appropriate data; 3. validating model predictions in comparison to data; and 4. probing hypotheses regarding the long-term control of arterial pressure and the etiology of primary hypertension. The developed model reveals: long-term control of arterial blood pressure is primarily through the baroreflex arc and the renin-angiotensin system; and arterial stiffening provides a sufficient explanation for the etiology of primary hypertension associated with ageing. Furthermore, the model provides the first consistent explanation of the physiological response to chronic stimulation of the baroreflex. PMID:24555102

A computational analysis of the long-term regulation of arterial pressure.

PubMed

Beard, Daniel A; Pettersen, Klas H; Carlson, Brian E; Omholt, Stig W; Bugenhagen, Scott M

2013-01-01

The asserted dominant role of the kidneys in the chronic regulation of blood pressure and in the etiology of hypertension has been debated since the 1970s. At the center of the theory is the observation that the acute relationships between arterial pressure and urine production-the acute pressure-diuresis and pressure-natriuresis curves-physiologically adapt to perturbations in pressure and/or changes in the rate of salt and volume intake. These adaptations, modulated by various interacting neurohumoral mechanisms, result in chronic relationships between water and salt excretion and pressure that are much steeper than the acute relationships. While the view that renal function is the dominant controller of arterial pressure has been supported by computer models of the cardiovascular system known as the "Guyton-Coleman model", no unambiguous description of a computer model capturing chronic adaptation of acute renal function in blood pressure control has been presented. Here, such a model is developed with the goals of: 1. representing the relevant mechanisms in an identifiable mathematical model; 2. identifying model parameters using appropriate data; 3. validating model predictions in comparison to data; and 4. probing hypotheses regarding the long-term control of arterial pressure and the etiology of primary hypertension. The developed model reveals: long-term control of arterial blood pressure is primarily through the baroreflex arc and the renin-angiotensin system; and arterial stiffening provides a sufficient explanation for the etiology of primary hypertension associated with ageing. Furthermore, the model provides the first consistent explanation of the physiological response to chronic stimulation of the baroreflex.

(131)I treatment in Differentiated Thyroid Cancer and End-Stage Renal Disease.

PubMed

Ortega, A J M; Vázquez, R G; Cuenca, J I C; Brocca, M A M; Castilla, J; Martínez, J M M; González, E N

2016-01-01

Radioiodine (RAI) is a cornerstone in the treatment of Differentiated Thyroid Cancer (DTC). In patients on haemodialysis due to End-Stage Renal Disease (ESRD), it must be used cautiously, considering the renal clearance of this radionuclide. Also, the safety of the procedure and subsequent long-term outcome is still not well defined. In 2001, we described a dosimetric method and short-term results in three patients, with a good safety profile. We hypothesize that our method is safe in a long-term scenario without compromising the prognosis of both renal and thyroid disease. Descriptive-retrospective study. A systematic search was carried out using our clinical database from 2000 to 2014. DTC and radioiodine treatment while on haemodialysis. peritoneal dialysis. Final sample n=9 patients (n=5 males), age 48 years (median age 51 years males, 67 years female group); n=8 papillary thyroid cancer, n=1 follicular thyroid cancer; n=5 lymph node invasion; n=1 metastatic disease. Median RAI dose administered on haemodialysis 100mCi. 7.5 years after radioiodine treatment on haemodialysis, n=7 deemed free of thyroid disease, n=1 persistent non-localised disease. No complications related to the procedure or other target organs were registered. After 3.25 years, n=4 patients underwent successful renal transplantation; n=4 patients did not meet transplantation criteria due to other conditions unrelated to the thyroid disease or its treatment. One patient died due to ischemic cardiomyopathy (free of thyroid disease). Radioiodine treatment during haemodialysis is a long-term, safe procedure without worsening prognosis of either renal or thyroid disease. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Exploring the effect and mechanism of Hibiscus sabdariffa on urinary tract infection and experimental renal inflammation.

PubMed

Chou, Shun-Ting; Lo, Hsin-Yi; Li, Chia-Cheng; Cheng, Lu-Chen; Chou, Pei-Chi; Lee, Yu-Chen; Ho, Tin-Yun; Hsiang, Chien-Yun

2016-12-24

Hibiscus sabdariffa Linn., also known as roselle, is used in folk medicine as an anti-inflammatory agent. Urinary tract infection (UTI) is a common problem in long-term care facilities. However, effects of roselle on UTI and renal inflammation remained to be analyzed. Here we surveyed the effect of roselle drink on the prevention of UTI in long-term care facilities and analyzed the anti-inflammatory potential of roselle on lipopolysaccharide (LPS)-induced renal inflammation in mice. Survey questionnaires and clinical observation were applied to evaluate the use of roselle and the incidence of UTI in long-term care facilities. Mice were administrated roselle orally for 7 consecutive days and then challenged with LPS. Anti-renal inflammatory effects of roselle were analyzed by microarray and immunohistochemical staining. Clinical observation showed that taking roselle drink in residents with urinary catheters reduced the incidence of UTI in long-term care facilities. Renal inflammation is a key event of UTI. Roselle suppressed LPS-induced nuclear factor-κB (NF-κB) activation in cells and LPS-induced interleukin-1β production in mice a dose-dependent manner. Immunohistochemical staining showed that roselle inhibited LPS-induced NF-κB activation and inflammatory cell infiltration in kidney. Gene expression profiling further showed that roselle suppressed the expression of pro-inflammatory cytokine genes and enzyme genes involved in the production of prostaglandin and nitric oxide. In addition, NF-κB was the main transcription factor involved in the regulation of roselle-regulated gene expression in kidney. This is the first report applying clinical observation-guided transcriptomic study to explore the application and mechanism of roselle on UTI. Our findings suggested that roselle drink ameliorated LPS-induced renal inflammation via downregulation of cytokine network, pro-inflammatory product production, and NF-κB pathway. Moreover, this report suggested the potential benefit of roselle drink on UTI. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Internist, anesthesiologist and surgeon use of ketogenic diet.

PubMed

Cenci, Lorenzo; Paoli, Antonio; Omar, Hesham R; Dalvi, Prachiti; Camporesi, Enrico M; Mangar, Devanand; Quartesan, Silvia; Fiorito, Alberto; Bosco, Gerardo

2018-03-01

Ketogenic diet is being increasingly utilized in recent decades because of its success as an effective tool for short and intermediate-term weight loss. Promoting physiological ketosis from a drastically low carbohydrate diet is the fundamental basis for this diet regime. Though debated, these diets have been demonstrated to be effective, at least in the short- to medium terms, to manage excess weight, hyperlipidemia, and other cardiovascular risk factors. We reviewed the cardiovascular, metabolic, anesthetic, and postsurgical profiles in the literature and summarized technical issues of anesthesia and surgery along with long-term changes from published papers. Doubts with ketogenic diet were raised due to possible renal damage caused by significant excretion of nitrogen found in animal models, the effects of acidosis, and the concerns of increasing triglycerides and cholesterol levels. Though current literature supports the efficacy of very low carbohydrate keto-diets their potential negative effects on renal function and acidosis are debated. An increase in nitrogen excretion during protein metabolism in the postoperative period could lead to renal damage. Research on the value of ketogenic diets is emerging because of its value in weight loss and in managing other pathologies.

Long-term outcomes of urinary tract reconstruction in patients with neurogenic urinary tract dysfunction

PubMed Central

Johnson, E. U.; Singh, Gurpreet

2013-01-01

The advent of specialized spinal units and better understanding of the pathophysiology of neurogenic urinary tract dysfunction has made long-term survival of these patients a reality. This has, in turn, led to an increase in quality and choice of management modalities offered to these patients including complex anatomic urinary tract reconstructive procedures tailored to the unique needs of each individual with variable outcomes. We performed a literature review evaluating the long-term outcomes of these reconstructive procedures. To achieve this, we conducted a world-wide electronic literature search of long-term outcomes published in English. As the premise of this review is long-term outcomes, we have focused on pathologies where evidence of long-term outcome is available such as patients with spinal injuries and spina bifida. Therapeutic success following urinary tract reconstruction is usually measured by preservation of renal function, improvement in quality-of-life, the satisfactory achievement of agreed outcomes and the prevention of serious complications. Prognostic factors include neuropathic detrusor overactivity; sphincter dyssynergia; bladder over distension; high pressure storage and high leak point pressures; vesicoureteric reflex, stone formation and urinary tract infections. Although, the past decade has witnessed a reduction in the total number of bladder reconstructive surgeries in the UK, these procedures are essentially safe and effective; but require long-term clinical and functional follow-up/monitoring. Until tissue engineering and gene therapy becomes more mainstream, we feel there is still a place for urinary tract reconstruction in patients with neurogenic lower urinary tract dysfunction. PMID:24235796

Xenon Treatment Protects Against Cold Ischemia Associated Delayed Graft Function and Prolongs Graft Survival in Rats

PubMed Central

Zhao, H; Watts, H R; Chong, M; Huang, H; Tralau-Stewart, C; Maxwell, P H; Maze, M; George, A J T; Ma, D

2013-01-01

Prolonged hypothermic storage causes ischemia-reperfusion injury (IRI) in the renal graft, which is considered to contribute to the occurrence of the delayed graft function (DGF) and chronic graft failure. Strategies are required to protect the graft and to prolong renal graft survival. We demonstrated that xenon exposure to human proximal tubular cells (HK-2) led to activation of range of protective proteins. Xenon treatment prior to or after hypothermia–hypoxia challenge stabilized the HK-2 cellular structure, diminished cytoplasmic translocation of high-mobility group box (HMGB) 1 and suppressed NF-κB activation. In the syngeneic Lewis-to-Lewis rat model of kidney transplantation, xenon exposure to donors before graft retrieval or to recipients after engraftment decreased caspase-3 expression, localized HMGB-1 within nuclei and prevented TLR-4/NF-κB activation in tubular cells; serum pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced and renal function was preserved. Xenon treatment of graft donors or of recipients prolonged renal graft survival following IRI in both Lewis-to-Lewis isografts and Fischer-to-Lewis allografts. Xenon induced cell survival or graft functional recovery was abolished by HIF-1α siRNA. Our data suggest that xenon treatment attenuates DGF and enhances graft survival. This approach could be translated into clinical practice leading to a considerable improvement in long-term graft survival. PMID:23710625

Long-term outcome of patients treated with prophylactic nesiritide for the prevention of acute kidney injury following cardiovascular surgery.

PubMed

Lingegowda, Vijaykumar; Van, Quoc C; Shimada, Michiko; Beaver, Thomas M; Dass, Bhagwan; Sood, Puneet; Ejaz, A Ahsan

2010-04-01

Previously, we reported that the prophylactic use of nesiritide did not reduce the incidence of dialysis or death following cardiovascular (CV) surgery despite reducing the incidence of acute kidney injury (AKI) in the immediate postoperative period. Therefore, we investigated whether the observed renal benefits of nesiritide had any long-term impact on cumulative patient survival and renal outcomes. Participants of the Nesiritide Study, a previously reported prospective, double-blind, placebo-controlled, randomized clinical trial investigating the effect of nesiritide on the incidence of dialysis or death at 21 days in adult patients undergoing high-risk CV surgery, were included in the study. Data of the participants' most recent health and renal function status were obtained using institutional review board-approved patient questionnaires, medical records, and the database of the Social Security Administration. Data on all 94 patients from the Nesiritide Study were obtained. The mean follow-up period was 20.8 +/- 10.4 months. No differences in cumulative survival between the groups were noted at follow-up (nesiritide 77.7% vs placebo 81.6%, P = 0.798). Patients with in-hospital incidence of AKI had a higher rate of mortality than those with no AKI (AKI 41.4% vs no AKI 10.7%, P = 0.002). However, differences in survival time were not significant between the groups when the analysis was restricted to patients with AKI (nesiritide 16.8 +/- 4 months vs placebo 18.5 +/- 2.3 months, P = 0.729). Renoprotection provided by nesiritide in the immediate postoperative period was not associated with improved long-term survival in patients undergoing high-risk CV surgery. Copyright 2010 Wiley Periodicals, Inc.

Controlled-release oxycodone-induced seizures.

PubMed

Klein, Moti; Rudich, Zvia; Gurevich, Boris; Lifshitz, Matityahu; Brill, Silviu; Lottan, Michael; Weksler, Natan

2005-11-01

The use of the opioid oxycodone hydrochloride in the management of chronic pain is gaining popularity principally because of its tolerability. However, opioid-related seizure in patients with epilepsy or other conditions that may decrease seizure threshold has been described in the literature; in particular, oxycodone has been associated with seizure in a patient with acute renal failure. The aim of this article was to report a patient with a history of seizures but normal renal and hepatic function who developed seizure on 2 occasions after oxycodone ingestion. A 54-year-old male patient presented with a history of tonic-clonic seizures that developed immediately after intracranial surgery. Long-term treatment with carbamazepine 400 mg QD was started, and the patient was free of convulsions for approximately 7 years. The patient presented to us with severe headache that was nonresponsive to an NSAID and the opiate agonist tramadol. Treatment with controlled-release (CR) oxycodone and tramadol drops (50 mg QID if necessary) was started, and tonic-clonic seizures developed 3 days later. Based on laboratory analysis, the patient had normal renal and hepatic function. On discontinuation of oxycodone treatment, the seizures resolved. However, due to effective pain relief with oxycodone, the patient decided to continue treatment, and seizures recurred. Carbamazepine was then administered 4 hours before oxycodone dosing, which allowed continuation of treatment without seizure. A patient with a history of seizures controlled with long-term carbamazepine therapy developed seizures when he started treatment with oxycodone CR at recommended doses. Oxycodone CR should be used with extreme caution in patients with epilepsy or other conditions that may decrease seizure threshold.

Renal artery and vein injury following blunt trauma.

PubMed Central

Sturm, J T; Perry, J F; Cass, A S

1975-01-01

Blunt injuries of the renal vascular pedicle occur infrequently. The experience with fourteen cases of blunt renal vascular trauma is presented. Most patients were injured in motor vehicle accidents. The diagnosis was made immediately after admission in 6 patients, delayed in 5, and at autopsy in 3. Most patients presented with gross or microscopic hematuria. The diagnosis of renal vascular injury was suggested by IVP in most instances. Surgical management was used in the 6 patients in whom the immediate diagnosis of renal pedicle injury was made; primary vascular repair was carried out in 4 patients and nephrectomy in two. Conservative management was used in 4 of the 5 patients with delayed diagnosis, and nephrectomy was required in the fifth. Three patients received no treatment as two were dead on arrival and one die during laparotomy. Seven patients died (50%). One of the 7 survivors has a functioning kidney following repair of a renal vein laceration. Three patients with devascularized kidneys have been followed long term and have not developed hypertension. An IVP should be mandatory following severe blunt trauma, especially when hematuria is present. Renal arteriography is indicated with distortion of calyces, extravasation or nonfunction seen on IVP and allows a definitive diagnosis of renal vessel injury to be made. PMID:1190872

Intraoperative double-J stent insertion in children with scintigraphic impaired renal function and obstructive urinary tract malformation.

PubMed

Erculiani, E; Zampieri, N; Cecchetto, M; Camoglio, F S; Giacomello, L

2008-03-01

Ureteral double-J (DJ) stents are frequently used in modern urologic practice. At present the role of stents in urological and surgical practice and their efficacy in paediatric age are not yet clear. The aim of this study is to evaluate advantages and efficacy of ureteral stents, correlating clinical and radiological data with the permanence of stent in situ. Between July 1999 and July 2004 surgery with ureteral stenting was performed on 24 consecutive patients aged between 2 and 13.5 months with scintigraphic impaired renal function due to an obstructive urinary tract malformation. During the study the performance and the efficacy of indwelling stent have been evaluated through clinical and radiological variables: pre-, intra-, and post stenting blood tests, ultrasonographic and scintigraphic parameters were also evaluated. The stent insertion was useful to improve renal parenchymal thickness and renal growth. No correlation was found between improved blood tests and scintigraphic values. The improvements of clinical and radiological data were strictly correlated with the time of stenting (>3 months). The insertion of DJ stents as long-term internal urinary diversion is useful and safe. Late complications related to the use of stents are not frequent.

[Expert consensus statement on interventional renal sympathetic denervation for hypertension treatment].

PubMed

Mahfoud, F; Vonend, O; Bruck, H; Clasen, W; Eckert, S; Frye, B; Haller, H; Hausberg, M; Hoppe, U C; Hoyer, J; Hahn, K; Keller, T; Krämer, B K; Kreutz, R; Potthoff, S A; Reinecke, H; Schmieder, R; Schwenger, V; Kintscher, U; Böhm, M; Rump, L C

2011-11-01

This commentary summarizes the expert consensus and recommendations of the working group 'Herz und Niere' of the German Society of Cardiology (DGK), the German Society of Nephrology (DGfN) and the German Hypertension League (DHL) on renal denervation for antihypertensive treatment. Renal denervation is a new, interventional approach to selectively denervate renal afferent and efferent sympathetic fibers. Renal denervation has been demonstrated to reduce office systolic and diastolic blood pressure in patients with resistant hypertension, defined as systolic office blood pressure ≥ 160 mm Hg and ≥ 150 mm Hg in patients with diabetes type 2, which should currently be used as blood pressure thresholds for undergoing the procedure. Exclusion of secondary hypertension causes and optimized antihypertensive drug treatment is mandatory in every patient with resistant hypertension. In order to exclude pseudoresistance, 24-hour blood pressure measurements should be performed. Preserved renal function was an inclusion criterion in the Symplicity studies, therefore, renal denervation should be only considered in patients with a glomerular filtration rate > 45 ml/min. Adequate centre qualification in both, treatment of hypertension and interventional expertise are essential to ensure correct patient selection and procedural safety. Long-term follow-up after renal denervation and participation in the German Renal Denervation (GREAT) Registry are recommended to assess safety and efficacy after renal denervation over time. © Georg Thieme Verlag KG Stuttgart · New York.

Large Renal Corpuscle: Clinical Significance of Evaluation of the Largest Renal Corpuscle in Kidney Biopsy Specimens.

PubMed

Kataoka, Hiroshi; Mochizuki, Toshio; Nitta, Kosaku

2018-01-01

Renal prognostic factors of chronic kidney disease are important concerns for patients. Kidney biopsy can be used to evaluate not only the activity of the original disease but also various risk factors related to the lifestyle of patients. Considering that lifestyle-related factors, including obesity and metabolic syndrome, are crucial prognostic risk factors of kidney disease progression and all-cause mortality, evaluation of lifestyle-related prognostic factors in kidney biopsy of all kidney diseases is important. Renal corpuscle size (glomerular size) is an easily measured parameter and potentially acts as a predictor of long-term renal function. Large renal corpuscle found on kidney biopsy is a classic and simple indicator, and has merit owing to its quantitative nature, but it has yet to be used to its full potential in clinical settings. Large renal corpuscle is an index that includes not only the activity of the original disease but also the damage of various metabolic risk states as represented by obesity, diabetes, and metabolic syndrome. Large renal corpuscles could be used to guide therapy. In this review, after identifying the pitfalls regarding the assessment of mean values in medical research, we propose that measurement of the maximum renal corpuscle profile (glomerular profile) in renal biopsies would provide valuable insights into the diagnosis, prognosis, and management of kidney diseases. © 2018 S. Karger AG, Basel.

Effects of short-term addition of NSAID to diuretics and/or RAAS-inhibitors on blood pressure and renal function.

PubMed

Nygård, Peder; Jansman, Frank G A; Kruik-Kollöffel, Willemien J; Barnaart, Alex F W; Brouwers, Jacobus R B J

2012-06-01

The combined post-operative use of diuretics and/or renin-angiotensin-aldosterone system (RAAS) inhibitors may increase the risk of nonsteroidal anti-inflammatory drug (NSAID) associated renal failure because of a drug-drug interaction. The aim of this study was to investigate the effect of the short-term (<4 days) post-operative combined use of NSAIDs with diuretics and/or RAAS inhibitors on renal function and blood pressure. One teaching hospital in the Netherlands. The study-design was a prospective, observational cohort-study. Based on postoperative treatment with NSAIDs, the intervention-group was compared to a control-group (no NSAIDs treatment). Systolic blood pressure and renal function expressed by the estimated glomular filtration rate (eGFR) calculated with the modification of renal desease formula. 97 patients were included in the intervention-group, 53 patients in the control-group. Patient characteristics were comparable except for one variable: 'combined use of a diuretic with a RAAS inhibitor' which was higher in the control-group (62 vs. 43 %, p = 0.046). Odds ratio for clinically relevant increase in systolic blood pressure was 0.66 (CI95 % 0.3-1.5). Odds ratio for clinical relevant decrease in renal function was 2.44 (CI95 % 1.1-5.2). On day 4 eGFR of 3 patients in the intervention- and 1 in the control-group was <50 ml/min/1.73 m(2). Odds ratios showed no significant difference of a clinically relevant increase in systolic blood pressure but showed a higher risk for a clinically relevant decrease in renal function in the intervention group. However this decrease resulted in a relevant impaired renal function (<50 ml/min/1.73 m(2)) in only 3 patients in the interventiongroup and 1 patient in the control-group. In the post-operative patient, without preexisting impaired renal function, concurrent diuretics and/or renin-angiotensinaldosterone system inhibitor therapy can be combined with short-term NSAID treatment.

Early Gains in Renal Function Following Implantation of HeartMate II Left Ventricular Assist Devices May Not Persist to One Year.

PubMed

Hasin, Tal; Grupper, Avishay; Dillon, John J; Maleszewski, Joseph J; Li, Zhuo; Topilsky, Yan; Frantz, Robert P; Edwards, Brooks S; Pereira, Naveen L; Maltais, Simon; Stulak, John M; Joyce, Lyle; Daly, Richard; Park, Soon J; Kushwaha, Sudhir S

Renal function improves early after left ventricular assist device (LVAD) implantation but later decline has been observed. We sought to determine the occurrence and evaluate possible causes for this decline. In 62 consecutive patients with HeartMateII LVAD with available calculated glomerular filtration rate (GFR, ml/min/1.73 m) 1 year after implant, GFR was assessed repeatedly and possible predictors for decline from 3 to 12 months were investigated. Post-mortem renal specimens for patients supported with an LVAD were evaluated. GFR 54.5 ± 19.5 at admission increased to 66.4 ± 22.3 preoperatively and to 79.2 ± 30.1 ~1 month after implantation. Subsequently at ~3 months GFR declined to 74.7 ± 25.4, at ~6 months to 68.8 ± 23.1, and ~1 year after implant to 63.9 ± 17.7. Glomerular filtration rate at 1 year was significantly lower (p < 0.0001, p < 0.0001, p = 0.005) than GFR 1, 3, and 6 months after implant. Early rise in GFR after surgery was not associated with late decline. Shorter bypass time (β = -0.09, p = 0.048) and higher albumin 3 months after LVAD (β = 14.4, p = 0.025) were significantly associated with less later decline in GFR. Arteriosclerosis was identified in autopsy renal specimens. In conclusion, early gains in renal function after LVAD implant are not sustained in many patients. Patient, device, and operative factors may influence long-term renal function in these patients.

Fanconi syndrome induced by tenofovir: A case report.

PubMed

Lify, Bouchra; Dabo, G; Nascimento, O; Iraqui, S; Elkhayat, S; Zamd, M; Medkouri, G; Benghanem, M; Ramdani, B; Sodqi, M M; Marih, L; Chakib, A; El FilaliMarhoum, K

2016-01-01

Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor discovered in the USA in 2001. It is currently the treatment of choice for patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus. Its antiretroviral efficacy and good tolerance are responsible for the higher frequency of prescriptions compared with other nucleoside analogs. However, it can induce acute renal toxicity causing impairment of the proximal tubular function of the kidney. This is highly dependent on factors such as associated co-prescription didanosine or a protease inhibitor "boosted" with ritonavir, preexisting renal insufficiency, low body weight, or presence of associated diabetes. In contrast, long-term renal toxicity remains highly debated. Some studies describe a decrease in estimated glomerular filtration rate during prolonged treatment with TDF. Others reported renal safety even during prolonged use. The differences between patients enrolled in the different studies, the measured parameters and their interpretation could explain these discrepancies. We describe a case of a patient infected with HIV, who presented with Fanconi syndrome with acute renal failure six months after starting antiretroviral treatment including tenofovir.

The Mitochondria-Targeted Antioxidant Mitoquinone Protects against Cold Storage Injury of Renal Tubular Cells and Rat Kidneys

PubMed Central

Mitchell, Tanecia; Rotaru, Dumitru; Saba, Hamida; Smith, Robin A. J.; Murphy, Michael P.

2011-01-01

The majority of kidneys used for transplantation are obtained from deceased donors. These kidneys must undergo cold preservation/storage before transplantation to preserve tissue quality and allow time for recipient selection and transport. However, cold storage (CS) can result in tissue injury, kidney discardment, or long-term renal dysfunction after transplantation. We have previously determined mitochondrial superoxide and other downstream oxidants to be important signaling molecules that contribute to CS plus rewarming (RW) injury of rat renal proximal tubular cells. Thus, this study's purpose was to determine whether adding mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to University of Wisconsin (UW) preservation solution could offer protection against CS injury. CS was initiated by placing renal cells or isolated rat kidneys in UW solution alone (4 h at 4°C) or UW solution containing MitoQ or its control compound, decyltriphenylphosphonium bromide (DecylTPP) (1 μM in vitro; 100 μM ex vivo). Oxidant production, mitochondrial function, cell viability, and alterations in renal morphology were assessed after CS exposure. CS induced a 2- to 3-fold increase in mitochondrial superoxide generation and tyrosine nitration, partial inactivation of mitochondrial complexes, and a significant increase in cell death and/or renal damage. MitoQ treatment decreased oxidant production ∼2-fold, completely prevented mitochondrial dysfunction, and significantly improved cell viability and/or renal morphology, whereas DecylTPP treatment did not offer any protection. These findings implicate that MitoQ could potentially be of therapeutic use for reducing organ preservation damage and kidney discardment and/or possibly improving renal function after transplantation. PMID:21159749

The mitochondria-targeted antioxidant mitoquinone protects against cold storage injury of renal tubular cells and rat kidneys.

PubMed

Mitchell, Tanecia; Rotaru, Dumitru; Saba, Hamida; Smith, Robin A J; Murphy, Michael P; MacMillan-Crow, Lee Ann

2011-03-01

The majority of kidneys used for transplantation are obtained from deceased donors. These kidneys must undergo cold preservation/storage before transplantation to preserve tissue quality and allow time for recipient selection and transport. However, cold storage (CS) can result in tissue injury, kidney discardment, or long-term renal dysfunction after transplantation. We have previously determined mitochondrial superoxide and other downstream oxidants to be important signaling molecules that contribute to CS plus rewarming (RW) injury of rat renal proximal tubular cells. Thus, this study's purpose was to determine whether adding mitoquinone (MitoQ), a mitochondria-targeted antioxidant, to University of Wisconsin (UW) preservation solution could offer protection against CS injury. CS was initiated by placing renal cells or isolated rat kidneys in UW solution alone (4 h at 4°C) or UW solution containing MitoQ or its control compound, decyltriphenylphosphonium bromide (DecylTPP) (1 μM in vitro; 100 μM ex vivo). Oxidant production, mitochondrial function, cell viability, and alterations in renal morphology were assessed after CS exposure. CS induced a 2- to 3-fold increase in mitochondrial superoxide generation and tyrosine nitration, partial inactivation of mitochondrial complexes, and a significant increase in cell death and/or renal damage. MitoQ treatment decreased oxidant production ~2-fold, completely prevented mitochondrial dysfunction, and significantly improved cell viability and/or renal morphology, whereas DecylTPP treatment did not offer any protection. These findings implicate that MitoQ could potentially be of therapeutic use for reducing organ preservation damage and kidney discardment and/or possibly improving renal function after transplantation.

Response of urinary liver-type fatty acid-binding protein to contrast media administration has a potential to predict one-year renal outcome in patients with ischemic heart disease.

PubMed

Fujita, Daishi; Takahashi, Masao; Doi, Kent; Abe, Mitsuru; Tazaki, Junichi; Kiyosue, Arihiro; Myojo, Masahiro; Ando, Jiro; Fujita, Hideo; Noiri, Eisei; Sugaya, Takeshi; Hirata, Yasunobu; Komuro, Issei

2015-05-01

Urinary liver-type fatty acid-binding proteins (uL-FABP) have recently been recognized as a useful biomarker for predicting contrast-induced nephropathy. Although accumulating studies have evaluated short-term outcomes, its prognostic value for long-term renal prognosis in patients undergoing coronary angiography (CAG) has not been fully examined. This study aimed to evaluate the predictive value of uL-FABP for long-term renal outcome in patients with ischemic heart disease (IHD). Consecutive 24 patients with impaired renal function (serum creatinine >1.2 mg/dL) who underwent CAG were enrolled. uL-FABP was measured before CAG, 24 and 48 h after CAG. The changes in estimated glomerular filtration rate (eGFR) throughout CAG and at 1 year later were compared with the uL-FABP levels. The patients with a greater decrease in eGFR 1 year later had higher uL-FABP levels at all points, but only the value at 48 h after CAG reached statistical significance (lower vs. higher decreased eGFR group, 4.61 ± 3.87 vs. 17.71 ± 12.96; P < 0.01). Measurement of uL-FABP at 48 h after CAG (48h-uL-FABP) showed better correlation with the change in eGFR (pre-CAG uL-FABP vs. 48h-uL-FABP: R = 0.27, P = 0.20 vs. R = 0.65, P < 0.01). Moreover, the high-pre and high-48h-uL-FABP group showed a significantly larger decrease in eGFR compared with the high-pre and low-48h-uL-FABP group (change in eGFR; 8.12 ± 4.06 vs. 1.25 ± 2.23 mL/min/1.73 m2, P < 0.01), although the baseline eGFR levels were similar between these two groups. In this pilot study, measurement of uL-FABP levels at 48 h after CAG may be useful in detecting renal damage, and in predicting 1-year renal outcome in IHD patients undergoing CAG.

Long-term Renal Function in Living Kidney Donors Who Had Histological Abnormalities at Donation.

PubMed

Fahmy, Lara M; Massie, Allan B; Muzaale, Abimereki D; Bagnasco, Serena M; Orandi, Babak J; Alejo, Jennifer L; Boyarsky, Brian J; Anjum, Saad K; Montgomery, Robert A; Dagher, Nabil N; Segev, Dorry L

2016-06-01

Recent evidence suggests that living kidney donors are at an increased risk of end-stage renal disease. However, predicting which donors will have renal dysfunction remains challenging, particularly among those with no clinical evidence of disease at the time of donation. Although renal biopsies are not routinely performed as part of the donor evaluation process, they may yield valuable information that improves the ability to predict renal function in donors. We used implantation protocol biopsies to evaluate the association between histological abnormalities in the donated kidney and postdonation renal function (estimated glomerular filtration rate, eGFR) of the remaining kidney in living kidney donors. Longitudinal analysis using mixed-effects linear regression was used to account for multiple eGFR measures per donor. Among 310 donors between 1997 and 2012, median (IQR) follow-up was 6.2 (2.5-8.7; maximum 14.0) years. In this cohort, the overall prevalence of histological abnormalities was 65.8% (19.7% abnormal glomerulosclerosis, 23.9% abnormal interstitial fibrosis and tubular atrophy (IFTA), 4.8% abnormal mesangial matrix increase, 32.0% abnormal arteriolar hyalinosis, and 32.9% abnormal vascular intimal thickening). IFTA was associated with a 5-mL/min/1.73 m decrease of postdonation eGFR after adjusting for donor age at donation, sex, race, preoperative systolic blood pressure, preoperative eGFR, and time since donation (P < 0.01). In this single-center study, among healthy individuals cleared for living donation, IFTA was associated with decreased postdonation eGFR, whereas no other subclinical histological abnormalities provided additional information.

Long-Term Renal Function in Living Kidney Donors who had Histological Abnormalities at Donation

PubMed Central

Fahmy, Lara M.; Massie, Allan B.; Muzaale, Abimereki D.; Bagnasco, Serena M.; Orandi, Babak J.; Alejo, Jennifer L.; Boyarsky, Brian J.; Anjum, Saad K.; Montgomery, Robert A.; Dagher, Nabil N.; Segev, Dorry L.

2016-01-01

Background Recent evidence suggests that living kidney donors are at an increased risk of end-stage renal disease. However, predicting which donors will have renal dysfunction remains challenging, particularly among those with no clinical evidence of disease at the time of donation. Although renal biopsies are not routinely performed as part of the donor evaluation process, they may yield valuable information that improves the ability to predict renal function in donors. Methods We used implantation protocol biopsies to evaluate the association between histological abnormalities in the donated kidney and postdonation renal function (estimated glomerular filtration rate, eGFR) of the remaining kidney in living kidney donors. Longitudinal analysis using mixed-effects linear regression was used to account for multiple eGFR measures per donor. Results Among 310 donors between 1997 and 2012, median (IQR) follow-up was 6.2 (2.5–8.7; maximum 14.0) years. In this cohort, the overall prevalence of histological abnormalities was 65.8% (19.7% abnormal glomerulosclerosis, 23.9% abnormal interstitial fibrosis and tubular atrophy (IFTA), 4.8% abnormal mesangial matrix increase, 32.0% abnormal arteriolar hyalinosis, and 32.9% abnormal vascular intimal thickening). IFTA was associated with a 5-mL/min/1.73m2 decrease of postdonation eGFR after adjusting for donor age at donation, sex, race, preoperative systolic blood pressure, preoperative eGFR, and time since donation (p<0.01). Conclusions In this single-center study, among healthy individuals cleared for living donation, IFTA was associated with decreased postdonation eGFR, while no other subclinical histological abnormalities provided additional information. PMID:27152920

PLUTO trial protocol: percutaneous shunting for lower urinary tract obstruction randomised controlled trial.

PubMed

Kilby, Mark; Khan, Khalid; Morris, Katie; Daniels, Jane; Gray, Richard; Magill, Laura; Martin, Bill; Thompson, Peter; Alfirevic, Zarko; Kenny, Simon; Bower, Sarah; Sturgiss, Stephen; Anumba, Dilly; Mason, Gerald; Tydeman, Graham; Soothill, Peter; Brackley, Karen; Loughna, Pamela; Cameron, Alan; Kumar, Sailesh; Bullen, Phil

2007-07-01

The primary objective is to determine whether intrauterine vesicoamniotic shunting for fetal bladder outflow obstruction, compared with conservative, noninterventional care, improves prenatal and perinatal mortality and renal function. The secondary objectives are to determine if shunting for fetal bladder outflow obstruction improves perinatal morbidity, to determine if improvement in outcomes is related to prognostic assessment at diagnosis and, if possible, derive a prognostic risk index and to determine the safety and long-term efficacy of shunting. A multicentre randomised controlled trial (RCT). Fetal medicine units. Pregnant women with singleton, male fetus with isolated lower urinary tract obstruction (LUTO). Following ultrasound diagnosis of LUTO in a male fetus and exclusion of other structural and chromosomal anomalies, participation in the trial will be discussed with the mother and written information given. Consent for participation in the trial will be taken and the mother randomised via the internet to either insertion of a vesicoamniotic shunt or expectant management. During pregnancy, both groups will be followed with regular ultrasound scans looking at viability, renal measurements and amniotic fluid volume. Following delivery, babies will be followed up by paediatric nephrologists/urologists at 4-6 weeks, 12 months and 3 and 5 years to assess renal function via serum creatinine, renal ultrasound and need for dialysis/transplant. The main outcome measures will be perinatal mortality rates and renal function at 4-6 weeks and 12 months measured via serum creatinine, renal ultrasound and need for dialysis/transplant. Wellbeing of Women. ESTIMATED COMPLETION DATE: September 2010. TRIAL ALGORITHM: [flowchart: see text].

Chronic Kidney Disease and Related Long-term Complications Following Liver Transplantation

PubMed Central

Sharma, Pratima; Bari, Khurram

2015-01-01

Liver transplantation (LT) is the standard of care for patients with decompensated cirrhosis. LT recipients have excellent short-term and long-term outcomes including patient and graft survival. Since the adoption of model for end-stage liver disease (MELD) - based allocation policy, the incidence of post-transplant end stage renal disease has risen significantly. Occurrence of stage 4 chronic kidney disease and end stage renal disease substantially increase the risk of post-transplant deaths. Since majority of late post-transplant mortality is due to non-hepatic post-transplant comorbidities, personalized care directed towards risk factor modification may further improve post-transplant survival. PMID:26311603

Study of Histopathological and Molecular Changes of Rat Kidney under Simulated Weightlessness and Resistance Training Protective Effect

PubMed Central

Li, Zhili; Tian, Jijing; Abdelalim, Saed; Du, Fang; She, Ruiping; Wang, Desheng; Tan, Cheng; Wang, Huijuan; Chen, Wenjuan; Lv, Dongqiang; Chang, Lingling

2011-01-01

To explore the effects of long-term weightlessness on the renal tissue, we used the two months tail suspension model to simulate microgravity and investigated the simulated microgravity on the renal morphological damages and related molecular mechanisms. The microscopic examination of tissue structure and ultrastructure was carried out for histopathological changes of renal tissue morphology. The immunohistochemistry, real-time PCR and Western blot were performed to explore the molecular mechanisms associated the observations. Hematoxylin and eosin (HE) staining showed severe pathological kidney lesions including glomerular atrophy, degeneration and necrosis of renal tubular epithelial cells in two months tail-suspended rats. Ultrastructural studies of the renal tubular epithelial cells demonstrated that basal laminas of renal tubules were rough and incrassate with mitochondria swelling and vacuolation. Cell apoptosis in kidney monitored by the expression of Bax/Bcl-2 and caspase-3 accompanied these pathological damages caused by long-term microgravity. Analysis of the HSP70 protein expression illustrated that overexpression of HSP70 might play a crucial role in inducing those pathological damages. Glucose regulated protein 78 (GRP78), one of the endoplasmic reticulum (ER) chaperones, was up-regulated significantly in the kidney of tail suspension rat, which implied that ER-stress was associated with apoptosis. Furthermore, CHOP and caspase-12 pathways were activated in ER-stress induced apoptosis. Resistance training not only reduced kidney cell apoptosis and expression of HSP70 protein, it also can attenuate the kidney impairment imposed by weightlessness. The appropriate optimization might be needed for the long term application for space exploration. PMID:21625440

Long-term outcome of anti-glomerular basement membrane antibody disease treated with immunoadsorption.

PubMed

Biesenbach, Peter; Kain, Renate; Derfler, Kurt; Perkmann, Thomas; Soleiman, Afschin; Benharkou, Alexandra; Druml, Wilfred; Rees, Andrew; Säemann, Marcus D

2014-01-01

Anti-glomerular basement membrane (GBM) antibody disease may lead to acute crescentic glomerulonephritis with poor renal prognosis. Current therapy favours plasma exchange (PE) for removal of pathogenic antibodies. Immunoadsorption (IAS) is superior to PE regarding efficiency of antibody-removal and safety. Apart from anecdotal data, there is no systemic analysis of the long-term effects of IAS on anti-GBM-disease and antibody kinetics. To examine the long-term effect of high-frequency IAS combined with standard immunosuppression on patient and renal survival in patients with anti-GBM-disease and to quantify antibody removal and kinetics through IAS. Retrospective review of patients treated with IAS for anti-GBM-antibody disease confirmed by biopsy and/or anti-GBM-antibodies. University Hospital of Vienna, Austria. 10 patients with anti-GBM-disease treated with IAS. Patient and renal survival, renal histology, anti-GBM-antibodies. Anti-GBM-antibodies were reduced by the first 9 IAS treatments (mean number of 23) to negative levels in all patients. Renal survival was 40% at diagnosis, 70% after the end of IAS, 63% after one year and 50% at the end of observation (mean 84 months, range 9 to 186). Dialysis dependency was successfully reversed in three of six patients. Patient survival was 90% at the end of observation. IAS efficiently eliminates anti-GBM-antibodies suggesting non-inferiority to PE with regard to renal and patient survival. Hence IAS should be considered as a valuable treatment option for anti-GBM-disease, especially in patients presenting with a high percentage of crescents and dialysis dependency due to an unusual high proportion of responders.

Morbidity, mortality and economic burden of renal impairment in cardiac intensive care.

PubMed

Chew, D P; Astley, C; Molloy, D; Vaile, J; De Pasquale, C G; Aylward, P

2006-03-01

Moderate to severe impairment of renal function has emerged as a potent risk factor for adverse short- and long-term outcomes among patients presenting with cardiac disease. We sought to define the clinical, late mortality and economic burden of this risk factor among patients presenting to cardiac intensive care. A clinical audit of patients presenting to cardiac intensive care was undertaken between July 2002 and June 2003. All patients presenting with cardiac diagnoses were included in the study. Baseline creatinine levels were assessed in all patients. Late mortality was assessed by the interrogation of the National Death Register. Renal impairment was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2, as calculated by the Modified Diet in Renal Disease formula. In-hospital and late outcomes were compared by Cox proportional hazards modelling, adjusting for known confounders. A matched analysis and attributable risk calculation were undertaken to assess the proportion of late mortality accounted for by impairment of renal function and other known negative prognostic factors. The in-hospital total cost associated with renal impairment was assessed by linear regression. Glomerular filtration rate <60 mL/min per 1.73 m2 was evident in 33.0% of this population. Among these patients, in-hospital and late mortality were substantially increased: risk ratio 13.2; 95% CI 3.0-58.1; P < 0.001 and hazard ratio 6.2; 95% CI 3.6-10.7; P < 0.001, respectively. In matched analysis, renal impairment to this level was associated with 42.1% of all the late deaths observed. Paradoxically, patients with renal impairment were more conservatively managed, but their hospitalizations were associated with an excess adjusted in-hospital cost of $A1676. Impaired renal function is associated with a striking clinical and economic burden among patients presenting to cardiac intensive care. As a marker for future risk, renal function accounts for a substantial proportion of the burden of late mortality. The burden of risk suggests a greater potential opportunity for improvement of outcomes through optimisation of therapeutic strategies.

Successful angioplasty of tripolar renal arteries in a single setting: a case report.

PubMed

Sharma, Gyarsi Lal; Morice, Marie-Claude; Catineau, Patrick

2002-08-01

Renal artery stenosis (RAS) is one of the important causes of correctable hypertension. There are various modes of therapy for RAS, including percutaneous transluminal renal angioplasty (PTRA) and surgery. PTRA has emerged as the treatment of choice in cases of renal artery stenosis. PTRA combined with stenting is associated with good immediate and long-term results. This case report describes successful angioplasty of bilateral multiple renal arteries in a single setting with good immediate and follow-up results.

Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats

PubMed Central

Berger, Rebeca Caldeira Machado; Vassallo, Paula Frizera; Crajoinas, Renato de Oliveira; Oliveira, Marilene Luzia; Martins, Flávia Letícia; Nogueira, Breno Valentim; Motta-Santos, Daisy; Araújo, Isabella Binotti; Forechi, Ludimila; Girardi, Adriana Castello Costa; Santos, Robson Augusto Souza; Mill, José Geraldo

2015-01-01

Several evidences have shown that salt excess is an important determinant of cardiovascular and renal derangement in hypertension. The present study aimed to investigate the renal effects of chronic high or low salt intake in the context of hypertension and to elucidate the molecular mechanisms underlying such effects. To this end, newly weaned male SHR were fed with diets only differing in NaCl content: normal salt (NS: 0.3%), low salt (LS: 0.03%), and high salt diet (HS: 3%) until 7 months of age. Analysis of renal function, morphology, and evaluation of the expression of the main molecular components involved in the renal handling of albumin, including podocyte slit-diaphragm proteins and proximal tubule endocytic receptors were performed. The relationship between diets and the balance of the renal angiotensin-converting enzyme (ACE) and ACE2 enzymes was also examined. HS produced glomerular hypertrophy and decreased ACE2 and nephrin expressions, loss of morphological integrity of the podocyte processes, and increased proteinuria, characterized by loss of albumin and high molecular weight proteins. Conversely, severe hypertension was attenuated and renal dysfunction was prevented by LS since proteinuria was much lower than in the NS SHRs. This was associated with a decrease in kidney ACE/ACE2 protein and activity ratio and increased cubilin renal expression. Taken together, these results suggest that LS attenuates hypertension progression in SHRs and preserves renal function. The mechanisms partially explaining these findings include modulation of the intrarenal ACE/ACE2 balance and the increased cubilin expression. Importantly, HS worsens hypertensive kidney injury and decreases the expression nephrin, a key component of the slit diaphragm. PMID:26495970

Longitudinal assessment of renal size and function in extremely low birth weight children at 7 and 11 years of age.

PubMed

Starzec, Katarzyna; Klimek, Małgorzata; Grudzień, Andrzej; Jagła, Mateusz; Kwinta, Przemko

2016-11-01

There are a lack of studies describing a longitudinal association between preterm delivery and renal complications later in life. We assessed renal size and function in preterm infants born with extremely low birth weight (ELBW) during 4 years of follow-up, comparing these parameters to age-matched children born full term (term controls). The results of selected renal laboratory tests [levels of cystatin C, creatinine, blood urea nitrogen (BUN)] and of renal ultrasound evaluations were compared between the ELBW group and the term control group at age 7 and 11 years. The study population consisted of 64 children born with ELBW (ELBW children) who had been recruited at birth and 36 children born at term (term children) who took part in both follow-up assessments. Renal ultrasound examination revealed a significantly smaller renal volume in the 7- and 11-year-old ELBW children compared to the term controls [right kidney volume: 50.8 vs. 61.2 ml/m(2), respectively, at 7 years (p <0.01) and 51.4 vs. 58.2 ml/m(2), respectively, at 11 years (p <0.01); left kidney volume: 51.4 vs. 60.3 ml/m(2), respectively, at 7 years (p <0.01) and 55.2 vs. 60.7 ml/m(2), respectively, at 11 years (p = 0.02)]. Renal function in ELBW children was also affected. Serum cystatin C levels were significantly higher in ELBW children than in the controls at 7 years of age, and this difference remained statistically significant at 11 years of age [0.63 vs. 0.59 mg/l, respectively, at 7 years (p = 0.02) and 0.72 vs. 0.61 mg/l, respectively, at 11 years (p = 0.01)]. Six ELBW children also had elevated cystatin C levels (0.97-1.11 mg/l) at 11 years of age. Cystatin C levels were within normal range in the ELBW children at age 7 years and in term children in both follow-up studies. BUN levels were higher in ELBW children at the age of 11 years (4.49 vs. 4.15 mmol/l; p = 0.028). Continued follow-up of these patients will reveal whether the observed worsening in renal function will persist into adulthood.

Sustained ELABELA Gene Therapy in High-salt Diet-induced Hypertensive Rats.

PubMed

Schreiber, Claire A; Holditch, Sara J; Generous, Alex; Ikeda, Yasuhiro

2017-01-01

Elabela (ELA) is a recently identified apelin receptor agonist essential for cardiac development, but its biology and therapeutic potential are unclear. In humans, ELA transcripts are detected in embryonic stem cells, induced pluripotent stem cells, kidney, heart and blood vessels. ELA through the apelin (APJ) receptor promotes angiogenesis in vitro, relaxes murine aortic blood vessels and attenuates high blood pressure in vivo. The APJ receptor when bound to its original ligand, apelin, exerts peripheral vasodilatory and positive inotropic effects, conferring cardioprotection in vivo. This study initially assessed endogenous ELA expression in normal and diseased rats and then characterized the effects of long-term ELA gene delivery by adeno-associated virus serotype 9 (AAV9) vectors on cardiorenal function in Dahl salt-sensitive rats (DS) on a high-salt diet over 3 months. Endogenous ELA was predominantly expressed in the kidneys, especially in the renal collecting duct cells and was not affected by disease. Rat ELA was overexpressed in the heart via AAV9 vector by a single intravenous injection. ELA-treated animals showed delayed onset of blood pressure elevation. Prior to high-salt diet, a reduction in the fractional sodium and chloride excretion was observed in rats given the AAV9-ELA vector. After three months on a high-salt diet, ELA preserved glomerular architecture, decreased renal fibrosis and suppressed expression of fibrosis-associated genes in the kidneys. ELA is constitutively expressed in renal collecting ducts in rats. Sustained AAV-ELA expression may offer a potential long-term therapy for hypertension and renal remodeling. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Post-discharge kidney function is associated with subsequent ten-year renal progression risk among survivors of acute kidney injury.

PubMed

Sawhney, Simon; Marks, Angharad; Fluck, Nick; Levin, Adeera; McLernon, David; Prescott, Gordon; Black, Corri

2017-08-01

The extent to which renal progression after acute kidney injury (AKI) arises from an initial step drop in kidney function (incomplete recovery), or from a long-term trajectory of subsequent decline, is unclear. This makes it challenging to plan or time post-discharge follow-up. This study of 14651 hospital survivors in 2003 (1966 with AKI, 12685 no AKI) separates incomplete recovery from subsequent renal decline by using the post-discharge estimated glomerular filtration rate (eGFR) rather than the pre-admission as a new reference point for determining subsequent renal outcomes. Outcomes were sustained 30% renal decline and de novo CKD stage 4, followed from 2003-2013. Death was a competing risk. Overall, death was more common than subsequent renal decline (37.5% vs 11.3%) and CKD stage 4 (4.5%). Overall, 25.7% of AKI patients had non-recovery. Subsequent renal decline was greater after AKI (vs no AKI) (14.8% vs 10.8%). Renal decline after AKI (vs no AKI) was greatest among those with higher post-discharge eGFRs with multivariable hazard ratios of 2.29 (1.88-2.78); 1.50 (1.13-2.00); 0.94 (0.68-1.32) and 0.95 (0.64-1.41) at eGFRs of 60 or more; 45-59; 30-44 and under 30, respectively. The excess risk after AKI persisted over ten years of study, irrespective of AKI severity, or post-episode proteinuria. Thus, even if post-discharge kidney function returns to normal, hospital admission with AKI is associated with increased renal progression that persists for up to ten years. Follow-up plans should avoid false reassurance when eGFR after AKI returns to normal. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

[Cardio-renal syndrome: the challenge in heart failure treatment].

PubMed

Martins, Hélia; Pedro, Nelson; Castellano, Maria; Monteiro, Pedro; Moura, José Júlio; Providência, Luís A

2011-01-01

Heart failure is a chronic and progressive disease that is estimated to affect approximately 20 million people worldwide and is one of the major public health problems. Its prevalence is reaching epidemic levels with about 550,000 new cases diagnosed annually, partly due to increased life expectancy in developed countries. And as it is a systemic disease, it can cause dysfunction in various organs, but especially in the kidney. The renal failure is often associated with heart failure and, when present together, make the treatment more complex and the prognosis is worse. This is the cardio-renal syndrome. The definition of cardio-renal syndrome varies according to the working groups, and there isn't a consensus. The exact cause of deterioration of renal function and the mechanism behind this interaction are complex, multifactorial in nature and not fully known at present. The treatment available is the one used for the treatment of heart failure. It is necessary to maintain the normal function of filtration, secretion and reabsorption in kidney to have a real improvement of the clinical condition of the patient. Patients with higher risk of developing nephropathy and those who have diagnosed renal failure should have prescribed drugs that are handled very carefully. But as in many other clinical situations, there aren't perfect drugs available to treat cardio-renal syndrome and the existing ones may have serious side effects in medium/long term causing the deterioration of renal function and possibly an increased mortality. The treatment is truly challenging in patients with severe fluid overload that is refractory to diuretics. This article aims to present the existing definitions of cardio-renal syndrome, its epidemiology, describe the current knowledge about the pathophysiology and its relationship to therapeutic interventions, some actual strategies and future technologies in an attempt to preserve the kidney, mainly during the decompensation of chronic heart failure.

Retrograde Intrarenal Surgery for Symptomatic Renal Sinus Cysts: Long-Term Results and Literature Review.

PubMed

Mancini, Vito; Cormio, Luigi; d'Altilia, Nicola; Benedetto, Giuseppe; Ferrarese, Paolo; Balzarro, Matteo; Defidio, Lorenzo; Carrieri, Giuseppe

2018-05-02

To report the long-term multicenter experience with retrograde intrarenal holmium-laser incision (RIR-HoLI) in the management of symptomatic renal sinus cysts (RSCs). In the literature, RIR-HoLI has been shown to be a safe and effective treatment, but there are only a few reports regarding long-term results and reproducibility of this procedure. From June 2010 to June 2015, 14 patients with symptomatic RSCs underwent RIR-HoLI. The mean age was 52.1 ± 11.28 years (range 28-77) and the mean cyst size was 53.2 ± 14.23 mm (range 35-90). In all cases, contrast-enhanced computer tomography (CT) showed compression of the renal pelvis by the cyst (no malignancy). Surgical outcome was assessed in terms of symptoms improvement (measured by Visual Analogue Scale [VAS] for pain) and renal ultrasound findings at 3-6-12 months postoperatively and then yearly. CT scan was carried out at 12 months follow-up. RIR-HoLI was successful in all patients. The mean operative time was 47.8 ± 13.54 min (range 30-80) and mean hospital stay was 3.5 days (range 2-5). There were 2 Clavien grade II complications (flank pain and urgency delaying discharge). After surgery, all patients -became asymptomatic (VAS score change, p = 0.0001). One patient had persistence of a small cyst (10 mm). Mean follow-up is 44 ± 17.24 months (range 24-84); all patients remained asymptomatic, with no signs of recurrence. RIR-HoLI proved to be a safe and effective treatment for symptomatic RSCs. In our experience, it provided excellent long-term results and was reproducible at 4 different -institutions. © 2018 S. Karger AG, Basel.

Long-term outcome of pediatric renal transplantation: a single center study in Japan.

PubMed

Yamada, Akio; Tashiro, Atsushi; Hiraiwa, Tomoko; Komatsu, Tomonori; Kinukawa, Tsuneo; Ueda, Norishi

2014-08-01

Little is known about the risk factors for long-term poor outcome in pediatric renal transplantation. Between 1973 and 2010, 111 renal transplants (92 living donations) were performed in 104 children (56 males, mean age, 12.5 yr) at the Social Insurance Chukyo Hospital, and followed-up for a mean period of 13.6 yr. The patient survival at 1, 5, 10, 15, 20 (living- and deceased-donor transplants), and 30 yr (living-donor transplants only) was 98.1%, 92.8%, 87.8%, 84.9%, 82.6%, and 79.3%. The graft survival at 1, 5, 10, 15, 20, and 30 yr was 92.0%, 77.3%, 58.4%, 50.8%, 38.5%, and 33.3%. The most common cause of graft loss was CAI, AR, death with functioning, recurrent primary disease, ATN, and malignancy. Donor gender, ATN, malignancy/cardiovascular events, and eras affected patient survival. AR and CAI were the risk factors for graft loss. The evolved immunosuppression protocols improved the outcome by reducing AR episodes and ATN but not CAI, suggesting CAI as the major risk factor for graft loss. CAI was correlated with AR episodes, CMV infection, and post-transplant hypertension. Strategies for preventing the risk factors for malignancy/cardiovascular events and CAI, including hypertension/infection, are crucial for better outcomes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Asymptomatic Kidney Stones in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia

PubMed Central

Thomas, Nicole A.; Rai, Shesh N.; Cheon, Kyeongmi; McCammon, Elizabeth; Chesney, Russell; Jones, Deborah; Pui, Ching-Hon; Hudson, Melissa M.

2009-01-01

We hypothesized an association between renal calculi and bone mineral density (BMD) deficits, shown in adults, exists in survivors of childhood ALL. Thus, we analyzed associations between quantitative computed tomography (QCT)-determined renal calcifications and clinical parameters (gender, race, age at diagnosis, age at time of QCT), BMD, treatment exposures, Tanner stage. We investigated associations between stone formation and nutritional intake, serum and urinary calcium and creatinine levels, and urinary calcium/creatinine ratio. Exact Chi-square test was used to compare categorical patient characteristics and Wilcoxon-Mann-Whitney test to compare continuous measurements. Of 424 participants, 218 (51.4%) were male; 371 (87.5%) were non-black. Most (n=270; 63.7%) were ≥ 3.5 years at ALL diagnosis. Mean (SD) and median (range) BMD Z-scores of the entire cohort was -0.4 (1.2) and -0.5 (-3.9 to 5.1), respectively. Nineteen (10 males; 10 Caucasians) had kidney stones (observed prevalence of 4.5 %; 19/424) with significant negative association between stone formation and body habitus (BMI, p=0.003). Stone formation was associated with treatment protocol (p=0.009) and treatment group (0.007). Thus, kidney stones in childhood ALL survivors could herald future deterioration of renal function and development of hypertension. Long-term follow-up imaging may be warranted in these patients to monitor for progressive morbidity. PMID:18830261

A Randomized 2x2 Factorial Clinical Trial of Renal Transplantation: Steroid-Free Maintenance Immunosuppression with Calcineurin Inhibitor Withdrawal after Six Months Associates with Improved Renal Function and Reduced Chronic Histopathology

PubMed Central

Stevens, R. Brian; Foster, Kirk W.; Miles, Clifford D.; Kalil, Andre C.; Florescu, Diana F.; Sandoz, John P.; Rigley, Theodore H.; Malik, Tamer; Wrenshall, Lucile E.

2015-01-01

Introduction The two most significant impediments to renal allograft survival are rejection and the direct nephrotoxicity of the immunosuppressant drugs required to prevent it. Calcineurin inhibitors (CNI), a mainstay of most immunosuppression regimens, are particularly nephrotoxic. Until less toxic antirejection agents become available, the only option is to optimize our use of those at hand. Aim To determine whether intensive rabbit anti-thymocyte globulin (rATG) induction followed by CNI withdrawal would individually or combined improve graft function and reduce graft chronic histopathology–surrogates for graft and, therefore, patient survival. As previously reported, a single large rATG dose over 24 hours was well-tolerated and associated with better renal function, fewer infections, and improved patient survival. Here we report testing whether complete CNI discontinuation would improve renal function and decrease graft pathology. Methods Between April 20, 2004 and 4-14-2009 we conducted a prospective, randomized, non-blinded renal transplantation trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment = 180). Subsequent maintenance immunosuppression consisted of tacrolimus, a CNI, and sirolimus, a mammalian target of rapamycin inhibitor. We report here the outcome of converting patients after six months either to minimized tacrolimus/sirolimus or mycophenolate mofetil/sirolimus. Primary endpoints were graft function and chronic histopathology from protocol kidney biopsies at 12 and 24 months Results CNI withdrawal (on-treatment analysis) associated with better graft function (p <0.001) and lower chronic histopathology composite scores in protocol biopsies at 12 (p = 0.003) and 24 (p = 0.013) months, without affecting patient (p = 0.81) or graft (p = 0.93) survival, or rejection rate (p = 0.17). Conclusion CNI (tacrolimus) withdrawal at six months may provide a strategy for decreased nephrotoxicity and improved long-term function in steroid-free low immunological risk renal transplant patients. Trial Registration ClinicalTrials.gov NCT00556933 PMID:26465152

Renal insufficiency, a frequent complication with age in oral-facial-digital syndrome type I.

PubMed

Saal, S; Faivre, L; Aral, Bernard; Gigot, N; Toutain, A; Van Maldergem, L; Destree, A; Maystadt, I; Cosyns, J-P; Jouk, P-S; Loeys, B; Chauveau, D; Bieth, E; Layet, V; Mathieu, M; Lespinasse, J; Teebi, A; Franco, B; Gautier, E; Binquet, C; Masurel-Paulet, A; Mousson, C; Gouyon, J-B; Huet, F; Thauvin-Robinet, C

2010-03-01

The oral-facial-digital syndrome type I (OFD I) is characterized by multiple congenital malformations of the face, oral cavity and digits. A polycystic kidney disease (PKD) is found in about one-third of patients but long-term outcome and complications are not well described in the international literature. Renal findings have been retrospectively collected in a cohort of 34 females all carrying a pathogenic mutation in the OFD1 gene with ages ranging from 1 to 65 years. Twelve patients presented with PKD - 11/16 (69%) if only adults were considered -with a median age at diagnosis of 29 years [IQR (interquartile range) = (23.5-38)]. Among them, 10 also presented with renal impairment and 6 were grafted (median age = 38 years [IQR = (25-48)]. One grafted patient under immunosuppressive treatment died from a tumor originated from a native kidney. The probability to develop renal failure was estimated to be more than 50% after the age of 36 years. Besides, neither genotype-phenotype correlation nor clinical predictive association with renal failure could be evidenced. These data reveal an unsuspected high incidence rate of the renal impairment outcome in OFD I syndrome. A systematic ultrasound (US) and renal function follow-up is therefore highly recommended for all OFD I patients.

Heart Failure Increases the Risk of Adverse Renal Outcomes in Patients With Normal Kidney Function.

PubMed

George, Lekha K; Koshy, Santhosh K G; Molnar, Miklos Z; Thomas, Fridtjof; Lu, Jun L; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

2017-08-01

Heart failure (HF) is associated with poor cardiac outcomes and mortality. It is not known whether HF leads to poor renal outcomes in patients with normal kidney function. We hypothesized that HF is associated with worse long-term renal outcomes. Among 3 570 865 US veterans with estimated glomerular filtration rate (eGFR) ≥60 mL min -1 1.73 m -2 during October 1, 2004 to September 30, 2006, we identified 156 743 with an International Classification of Diseases , Ninth Revision , diagnosis of HF. We examined the association of HF with incident chronic kidney disease (CKD), the composite of incident CKD or mortality, and rapid rate of eGFR decline (slopes steeper than -5 mL min -1 1.73 m -2 y -1 ) using Cox proportional hazard analyses and logistic regression. Adjustments were made for various confounders. The mean±standard deviation baseline age and eGFR of HF patients were 68±11 years and 78±14 mL min -1 1.73 m -2 and in patients without HF were 59±14 years and 84±16 mL min -1 1.73 m -2 , respectively. HF patients had higher prevalence of hypertension, diabetes mellitus, cardiac, peripheral vascular and chronic lung diseases, stroke, and dementia. Incidence of CKD was 69.0/1000 patient-years in HF patients versus 14.5/1000 patient-years in patients without HF, and 22% of patients with HF had rapid decline in eGFR compared with 8.5% in patients without HF. HF patients had a 2.12-, 2.06-, and 2.13-fold higher multivariable-adjusted risk of incident CKD, composite of CKD or mortality, and rapid eGFR decline, respectively. HF is associated with significantly higher risk of incident CKD, incident CKD or mortality, and rapid eGFR decline. Early diagnosis and management of HF could help reduce the risk of long-term renal complications. © 2017 American Heart Association, Inc.

Results of transurethral resection of the prostate in renal transplant recipients: a single center experience.

PubMed

Sarier, Mehmet; Tekin, Sabri; Duman, İbrahim; Yuksel, Yucel; Demir, Meltem; Alptekinkaya, Furkan; Guler, Mehmet; Yavuz, Asuman Havva; Kosar, Alim

2018-01-01

The aim of this study was to retrospectively evaluate the early and long-term results of renal transplantation (RT) patients undergoing transurethral resection of the prostate (TURP) due to benign prostate hyperplasia (BPH). Eighty-nine patients with RT performed in our hospital underwent TURP between November 2008 and March 2016. Results were evaluated along with early and long-term complications. Patients were followed up for a minimum of 12 months. The mean age of the patients was 61.4 ± 7.4 years. The median duration of dialysis was 28 (0-180) months. The median duration between transplantation and TURP was 13 (0-84) months. Before TURP, the mean serum creatinine (sCr) was 1.99 ± 0.83 mg/dL and the mean prostate volume was 33.3 ± 14.6 cm 3 . The mean Q max , Q ave and PVR values were 9.5 ± 3.7, 5.2 ± 2.2 ml/s and 85(5-480) mL, respectively. None of the patients developed perioperative and postoperative major complications. Twelve patients (13.4%) developed urinary tract infections in the postoperative period. The sCr, IPSS and PVR values significantly decreased, while Q max and Q ave significantly increased at the 1-month follow-up. At the 6-month follow-up, 63 (70.8%) patients had retrograde ejaculation. Patients were followed up for a median of 42 (12-96) months. Three patients (3.3%) were re-operated for bladder neck contracture and eight (8.9%) patients were re-operated for urethral stricture. TURP can be safely and successfully applied for the treatment of BPH after RT. LUTS and renal functions significantly improve after the operation. Patients should be followed up for UTIs in the short term and for urethral stricture in the long term.

Long-term survival in patients with septic acute kidney injury is strongly influenced by renal recovery.

PubMed

Fiorentino, Marco; Tohme, Fadi A; Wang, Shu; Murugan, Raghavan; Angus, Derek C; Kellum, John A

2018-01-01

Several studies have shown that long-term survival after acute kidney injury (AKI) is reduced even if there is clinical recovery. However, we recently reported that in septic shock patients those that recover from AKI have survival similar to patients without AKI. Here, we studied a cohort with less severe sepsis to examine the effects of AKI on longer-term survival as a function of recovery by discharge. We analyzed patients with community-acquired pneumonia from the Genetic and Inflammatory Markers of Sepsis (GenIMS) cohort. We included patients who developed AKI (KDIGO stages 2-3) and defined renal recovery as alive at hospital discharge with return of SCr to within 150% of baseline without dialysis. Our primary outcome was survival up to 3 years analyzed using Gray's model. Of the 1742 patients who survived to hospital discharge, stage 2-3 AKI occurred in 262 (15%), of which 111 (42.4%) recovered. Compared to recovered patients, patients without recovery were older (75 ±14 vs 69 ±15 years, p<0.001) and were more likely to have at least stage 1 AKI on day 1 (83% vs 52%, p<0.001). Overall, 445 patients (25.5%) died during follow-up, 23.4% (347/1480) for no AKI, 28% (31/111) for AKI with recovery and 44.3% (67/151) for AKI without recovery. Patients who did not recover had worse survival compared to no AKI (HR range 1.05-2.46, p = 0.01), while recovering patients had similar survival compared to no AKI (HR 1.01, 95%CI 0.69-1.47, p = 0.96). Absence of AKI on day 1, no in-hospital renal replacement therapy (RRT), higher Apache III score and higher baseline SCr were associated with recovery after AKI. In patients with sepsis, recovery by hospital discharge is associated with long-term survival similar to patients without AKI.

Treatment of multiple synchronous misdiagnosed renal cell cancers in a young patient affected by a "de novo" Von Hippel-Lindau syndrome.

PubMed

Allasia, Marco; Battaglia, Antonino; Pasini, Barbara; Gazzera, Carlo; Calandri, Marco; Bosio, Andrea; Gontero, Paolo; Destefanis, Paolo

2017-02-28

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited syndrome occurring in one out of 36,000 live births. Diagnosis could be a challenge in patients with no familial VHL history. Renal cancer (RCC) represents one of the most important manifestations. RCC is usually recurrent and multifocal. Actually treating RCC in VHL patients represent a clinical dilemma: the oncological outcomes must be balanced against renal function preservation. A young man with a negative familial history was referred to our department with seven misdiagnosed renal masses. VHL disease was determined through genetic test. The multiple RCCs were treated by surgery and percutaneous thermal ablation by radiofrequency ablation (RFA) with complete control of RCC and no impairment of renal function. This case history confirms that VHL disease has to be suspected in young patients with evidence of synchronous multiple renal masses and in presence of specific clinical criteria.RFA appears to be safe in terms of oncological radicalism and in renal function preservation.In hereditary RCC, we should purpose, whenever it is possible, minimally invasive treatment in terms of low hospital stay and a minimal loss of renal tissue.

Effect of conservative treatment on the renal outcome of children with primary hyperoxaluria type 1.

PubMed

Fargue, Sonia; Harambat, Jérôme; Gagnadoux, Marie-France; Tsimaratos, Michel; Janssen, Françoise; Llanas, Brigitte; Berthélémé, Jean-Pierre; Boudailliez, Bernard; Champion, Gérard; Guyot, Claude; Macher, Marie-Alice; Nivet, Hubert; Ranchin, Bruno; Salomon, Rémi; Taque, Sophie; Rolland, Marie-Odile; Cochat, Pierre

2009-10-01

Primary hyperoxaluria type 1 results from alanine:glyoxylate aminotransferase deficiency. Due to genotype/phenotype heterogeneity in this autosomal recessive disorder, the renal outcome is difficult to predict in these patients and the long-term impact of conservative management in children is unknown. We report here a multicenter retrospective study on the renal outcome in 27 affected children whose biological diagnosis was based on either decreased enzyme activity or identification of mutations in the patient or his siblings. The median age at first symptoms was 2.4 years while that at initiation of conservative treatment was 4.1 years; 6 children were diagnosed upon family screening. The median follow-up was 8.7 years. At diagnosis, 15 patients had an estimated glomerular filtration rate (eGFR) below 90, and 7 children already had stage 2-3 chronic kidney disease. The median baseline eGFR was 74, which rose to 114 with management in the 22 patients who did not require renal replacement therapy. Overall, 20 patients had a stable eGFR, however, 7 exhibited a decline in eGFR of over 20 during the study period. In a Cox regression model, the only variable significantly associated with deterioration of renal function was therapeutic delay with a relative risk of 1.7 per year. Our study strongly suggests that early and aggressive conservative management may preserve renal function of compliant children with this disorder, thereby avoiding dialysis and postponing transplantation.

Long-Term Outcomes of Kidney Transplantation in Fabry Disease.

PubMed

Ersözlü, Sara; Desnick, Robert J; Huynh-Do, Uyen; Canaan-Kühl, Sima; Barbey, Frédéric; Genitsch, Vera; Müller, Thomas; Cheetham, Marcus; Flammer, Andreas; Schaub, Stefan; Nowak, Albina

2018-04-24

Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene that obliterate or markedly reduce α-galactosidase A activity. This results in the systemic accumulation of its glycosphingolipid substrates in body fluids and organs, including the kidney. Fabry nephropathy can lead to end-stage renal disease requiring kidney transplantation. Little is known about its long-term outcomes and the overall patient survival after kidney transplantation. Here, we report 17 Fabry patients (15 males, 2 females) who received kidney transplants and their long-term treatment and follow-up at 4 specialized Fabry centers. The posttransplant follow-up ranged to 25 years, with a median of 11.5 [range 0.8-25.5] years. Graft survival was similar and death-censored graft survival was superior to matched controls. Fabry patients died with functioning kidneys, mostly from cardiac causes. In 2 males 14 and 23 years posttransplant, the grafts had a few typical FD lamellar inclusions, presumably originating from invading host macrophages and vascular endothelial cells. We conclude that kidney transplantation has an excellent long-term outcome in Fabry disease.

Extracorporeal shock-wave lithotripsy monotherapy of partial staghorn calculi. Prognostic factors and long-term results.

PubMed

El-Assmy, Ahmed; El-Nahas, Ahmed R; Madbouly, Khaled; Abdel-Khalek, Mohamed; Abo-Elghar, Mohamed E; Sheir, Khaled Z

2006-01-01

To define factors affecting the success and long-term outcome of extracorporeal shock-wave lithotripsy (ESWL) monotherapy of partial staghorn calculi. We retrospectively reviewed 92 patients with partial staghorn calculi who were treated with ESWL monotherapy. The outcome of the treatment was evaluated after 3 months. Long-term follow-up data (>24 months) were available for 49 patients. These data were further analyzed to determine long-term outcome. At 3 months, the overall stone-free rate was 59.8%. Multiple ESWL sessions were required in 85.8% of patients. Stone surface area>500 mm2 was the only factor that significantly decreased the stone-free rate. Post-ESWL complications occurred in 12 patients (13%), among whom renal obstruction was observed in 10.8%. Secondary procedures were needed in 17 cases (18.4%). After a mean follow-up period of 7.5 years, the stone-free rate was 59.2% (29/49) and one-third of patients developed recurrence. In the long term, clinically insignificant residual fragments (CIRFs) passed spontaneously in 23% of patients, remained stable in 38.5% and became bigger in 38.5%. Regrowth of CIRFs was related to a history of stone recurrence. No patients showed deterioration of kidney function on the treated side and an improvement in pre-ESWL hydronephrosis was observed in 73.3% of patients. ESWL is suitable for staghorn stones

Post-partum trend in blood pressure levels, renal function and proteinuria in women with severe preeclampsia and eclampsia in Sub-Saharan Africa: a 6-months cohort study.

PubMed

Kaze, Francois Folefack; Njukeng, Francis A; Kengne, Andre-Pascal; Ashuntantang, Gloria; Mbu, Robinson; Halle, Marie Patrice; Asonganyi, Tazoacha

2014-04-09

Preeclampsia and eclampsia, which are the most frequent hypertensive disorders in pregnancy, are associated with renal involvements. We aimed to assess the time trend in blood pressure levels, renal function and proteinuria after delivery, and investigate their determinants in Cameroonian women with severe preeclampsia and eclampsia. This was a prospective cohort study involving 54 women with severe preeclampsia and eclampsia, conducted between July 2010 and February 2012 at the central maternity unit of the Yaoundé Central Hospital. Clinical and laboratory parameters were recorded from day-1 to 6 months after delivery. Mixed-linear and logistic regression models were used to relate baseline and within follow-up levels of covariates, with changes in blood pressure levels, renal function and proteinuria, as well as persisting hypertension, renal failure and proteinuria. During follow-up, a significant improvement was observed in blood pressure, renal function and proteinuria (all p < 0.002). Thirteen (24.1%) patients with renal failure at delivery recovered completely within six weeks. Twenty-six (48.1%), 17 (31.5%) and 1 (1.8%) patients had persisting proteinuria at 6 weeks, 3 months and 6 months post-delivery, respectively. Corresponding figures for persisting hypertension were 23 (42.6%), 15 (27.8%) and 8 (14.8%). Advanced age, higher body mass index, low gestational age at delivery, low fetal birth weight, and proteinuria at delivery were the main risk factors for persisting hypertension at 3 months, meanwhile low fetal birth weight, severe preeclampsia and proteinuria at delivery were correlated with persisting proteinuria at 3 months. Advanced age and higher body mass index were the only determinants of the composite outcome of persisting hypertension or proteinuria at three and six months. Hypertension and proteinuria are very common beyond the postpartum period in Cameroonian women with severe preeclampsia and eclampsia. Long-term follow-up of these women will help preventing and controlling related complications.

Human Urine-Derived Renal Progenitors for Personalized Modeling of Genetic Kidney Disorders

PubMed Central

Ronconi, Elisa; Angelotti, Maria Lucia; Peired, Anna; Mazzinghi, Benedetta; Becherucci, Francesca; Conti, Sara; Sansavini, Giulia; Sisti, Alessandro; Ravaglia, Fiammetta; Lombardi, Duccio; Provenzano, Aldesia; Manonelles, Anna; Cruzado, Josep M.; Giglio, Sabrina; Roperto, Rosa Maria; Materassi, Marco; Lasagni, Laura

2015-01-01

The critical role of genetic and epigenetic factors in the pathogenesis of kidney disorders is gradually becoming clear, and the need for disease models that recapitulate human kidney disorders in a personalized manner is paramount. In this study, we describe a method to select and amplify renal progenitor cultures from the urine of patients with kidney disorders. Urine-derived human renal progenitors exhibited phenotype and functional properties identical to those purified from kidney tissue, including the capacity to differentiate into tubular cells and podocytes, as demonstrated by confocal microscopy, Western blot analysis of podocyte-specific proteins, and scanning electron microscopy. Lineage tracing studies performed with conditional transgenic mice, in which podocytes are irreversibly tagged upon tamoxifen treatment (NPHS2.iCreER;mT/mG), that were subjected to doxorubicin nephropathy demonstrated that renal progenitors are the only urinary cell population that can be amplified in long-term culture. To validate the use of these cells for personalized modeling of kidney disorders, renal progenitors were obtained from (1) the urine of children with nephrotic syndrome and carrying potentially pathogenic mutations in genes encoding for podocyte proteins and (2) the urine of children without genetic alterations, as validated by next-generation sequencing. Renal progenitors obtained from patients carrying pathogenic mutations generated podocytes that exhibited an abnormal cytoskeleton structure and functional abnormalities compared with those obtained from patients with proteinuria but without genetic mutations. The results of this study demonstrate that urine-derived patient-specific renal progenitor cultures may be an innovative research tool for modeling of genetic kidney disorders. PMID:25568173

Two-year analysis for predicting renal function and contralateral hypertrophy after robot-assisted partial nephrectomy: A three-dimensional segmentation technology study.

PubMed

Kim, Dae Keun; Jang, Yujin; Lee, Jaeseon; Hong, Helen; Kim, Ki Hong; Shin, Tae Young; Jung, Dae Chul; Choi, Young Deuk; Rha, Koon Ho

2015-12-01

To analyze long-term changes in both kidneys, and to predict renal function and contralateral hypertrophy after robot-assisted partial nephrectomy. A total of 62 patients underwent robot-assisted partial nephrectomy, and renal parenchymal volume was calculated using three-dimensional semi-automatic segmentation technology. Patients were evaluated within 1 month preoperatively, and postoperatively at 6 months, 1 year and continued up to 2-year follow up. Linear regression models were used to identify the factors predicting variables that correlated with estimated glomerular filtration rate changes and contralateral hypertrophy 2 years after robot-assisted partial nephrectomy. The median global estimated glomerular filtration rate changes were -10.4%, -11.9%, and -2.4% at 6 months, 1 and 2 years post-robot-assisted partial nephrectomy, respectively. The ipsilateral kidney median parenchymal volume changes were -24%, -24.4%, and -21% at 6 months, 1 and 2 years post-robot-assisted partial nephrectomy, respectively. The contralateral renal volume changes were 2.3%, 9.6% and 12.9%, respectively. On multivariable linear analysis, preoperative estimated glomerular filtration rate was the best predictive factor for global estimated glomerular filtration rate change on 2 years post-robot-assisted partial nephrectomy (B -0.452; 95% confidence interval -0.84 to -0.14; P = 0.021), whereas the parenchymal volume loss rate (B -0.43; 95% confidence interval -0.89 to -0.15; P = 0.017) and tumor size (B 5.154; 95% confidence interval -0.11 to 9.98; P = 0.041) were the significant predictive factors for the degree of contralateral renal hypertrophy on 2 years post-robot-assisted partial nephrectomy. Preoperative estimated glomerular filtration rate significantly affects post-robot-assisted partial nephrectomy renal function. Renal mass size and renal parenchyma volume loss correlates with compensatory hypertrophy of the contralateral kidney. Contralateral hypertrophy of the renal parenchyma compensates for the functional loss of the ipsilateral kidney. © 2015 The Japanese Urological Association.

Xenon treatment protects against cold ischemia associated delayed graft function and prolongs graft survival in rats.

PubMed

Zhao, H; Watts, H R; Chong, M; Huang, H; Tralau-Stewart, C; Maxwell, P H; Maze, M; George, A J T; Ma, D

2013-08-01

Prolonged hypothermic storage causes ischemia-reperfusion injury (IRI) in the renal graft, which is considered to contribute to the occurrence of the delayed graft function (DGF) and chronic graft failure. Strategies are required to protect the graft and to prolong renal graft survival. We demonstrated that xenon exposure to human proximal tubular cells (HK-2) led to activation of range of protective proteins. Xenon treatment prior to or after hypothermia-hypoxia challenge stabilized the HK-2 cellular structure, diminished cytoplasmic translocation of high-mobility group box (HMGB) 1 and suppressed NF-κB activation. In the syngeneic Lewis-to-Lewis rat model of kidney transplantation, xenon exposure to donors before graft retrieval or to recipients after engraftment decreased caspase-3 expression, localized HMGB-1 within nuclei and prevented TLR-4/NF-κB activation in tubular cells; serum pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced and renal function was preserved. Xenon treatment of graft donors or of recipients prolonged renal graft survival following IRI in both Lewis-to-Lewis isografts and Fischer-to-Lewis allografts. Xenon induced cell survival or graft functional recovery was abolished by HIF-1α siRNA. Our data suggest that xenon treatment attenuates DGF and enhances graft survival. This approach could be translated into clinical practice leading to a considerable improvement in long-term graft survival. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Long-term renal outcome in patients with malignant hypertension: a retrospective cohort study

PubMed Central

2012-01-01

Background Malignant hypertension is frequently complicated by renal insufficiency. Although the survival of this hypertensive emergency has improved, recent data on renal outcome and its predictors are lacking. We assessed renal outcome and its predictors in patients with malignant hypertension. Methods Retrospective analysis of patients admitted with malignant hypertension in Amsterdam, the Netherlands between August 1992–January 2010. Follow-up data on vital status, renal function and blood pressure (BP) were obtained from the outpatient department and from general practitioners. The primary composite endpoint was end-stage renal disease (ESRD) defined as the start of kidney replacement therapy (KRT) or ≥ 50% decline of estimated glomerular filtration rate (eGFR). The secondary endpoint was all cause mortality. Results A total of 120 patients admitted with malignant hypertension were included. After a median follow-up period of 67 months (IQR 28 to 108 months) the primary endpoint was reached by 37 (31%) patients, whereas 18 patients (15%) reached the secondary endpoint. Twenty-nine (24%) patients started KRT and 8 patients (7%) had an eGFR decline ≥ 50%. After the acute phase (> 3 months after admission), initial serum creatinine and follow-up BP were the main predictors of future ESRD with hazard ratios of 6.1 (95% CI, 2.2–17) for patients with initial serum creatinine ≥ 175 μmol /L and 4.3 (95% CI, 1.4–14) for patients with uncontrolled hypertension. Conclusions Progressive renal function decline leading to ESRD remains a major threat to patients with malignant hypertension. BP control during follow-up was an important modifiable predictor of renal outcome. PMID:22846257

Pharmacokinetics of Tedizolid in Subjects with Renal or Hepatic Impairment

PubMed Central

Minassian, S. L.; Morris, D.; Ponnuraj, R.; Marbury, T. C.; Alcorn, H. W.; Fang, E.; Prokocimer, P.

2014-01-01

Two open-label, single-dose, parallel-group studies were conducted to characterize the pharmacokinetics of the novel antibacterial tedizolid and the safety of tedizolid phosphate, its prodrug, in renally or hepatically impaired subjects. Tedizolid pharmacokinetics in subjects with severe renal impairment without dialysis support was compared with that of matched control subjects with normal renal function. Effects of hemodialysis on tedizolid pharmacokinetics were determined in a separate cohort of subjects undergoing long-term hemodialysis. Effects of hepatic impairment on tedizolid pharmacokinetics were determined in subjects with moderate or severe hepatic impairment and compared with those of matched control subjects with normal hepatic function. Each participant received a single oral (hepatic impairment) or intravenous (renal impairment) dose of tedizolid phosphate at 200 mg; hemodialysis subjects received two doses (separated by 7 days), before and after dialysis, in a crossover fashion. The pharmacokinetics of tedizolid was similar in subjects with severe renal impairment and controls (∼8% lower area under the concentration-time curve [AUC], with a nearly identical peak concentration) and in subjects undergoing hemodialysis before and after tedizolid phosphate administration (∼9% lower AUC, with a 15% higher peak concentration); <10% of the dose was removed during 4 h of hemodialysis. Tedizolid pharmacokinetics was only minimally altered in subjects with moderate or severe hepatic impairment; the AUC was increased approximately 22% and 34%, respectively, compared with that of subjects in the control group. Tedizolid phosphate was generally well tolerated in all participants. These results suggest that tedizolid phosphate dose adjustments are not necessary in patients with any degree of renal or hepatic impairment. (This study has been registered at ClinicalTrials.gov under registration numbers NCT01452828 [renal study] and NCT01431833 [hepatic study].) PMID:25136024

Is Long-Term Low-Dose Aspirin Therapy Associated with Renal Dysfunction in Patients with Type 2 Diabetes? JPAD2 Cohort Study

PubMed Central

Okada, Sadanori; Morimoto, Takeshi; Ogawa, Hisao; Sakuma, Mio; Soejima, Hirofumi; Nakayama, Masafumi; Jinnouchi, Hideaki; Waki, Masako; Akai, Yasuhiro; Ishii, Hitoshi; Saito, Yoshihiko

2016-01-01

Background Low-dose aspirin is widely recommended for patients at high risk for cardiovascular disease (CVD); however, it remains uncertain whether long-term treatment adversely affects renal function in patients with diabetes. We investigated whether long-term low-dose aspirin affects renal dysfunction in patients with diabetes. Methods We conducted a randomized controlled trial (RCT), the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, to evaluate low-dose aspirin as primary prevention for CVD in patients with type 2 diabetes. We followed the patients with negative urine dipstick albumin of the JPAD trial in a cohort study after the RCT period was completed. Patients were randomly allocated to receive aspirin (81 mg or 100 mg daily, aspirin group) or no aspirin (no aspirin group). After the RCT, the treating physician decided whether to administer aspirin. We evaluated the incidence of positive urine dipstick albumin and annual changes in estimated glomerular filtration rate (eGFR). Results Positive urine dipstick albumin developed in 297 patients in the aspirin group (n = 1,075) and 270 patients in the no aspirin group (n = 1,098) during follow-up (median, 8.5 years). Intention-to-treat analysis showed low-dose aspirin did not increase the incidence of positive urine dipstick albumin (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.995–1.38). On-treatment analysis yielded similar results (HR, 1.08; 95% CI, 0.92–1.28). Multivariable analysis showed the incidence of positive urine dipstick albumin was higher among the elderly and those with elevated serum creatinine, high hemoglobin A1c, or high blood pressure; however, low-dose aspirin did not increase the risk of positive urine dipstick albumin. There were no significant differences in annual changes in eGFR between the groups (aspirin, −0.8 ± 2.9; no aspirin, −0.9 ± 2.5 ml/min/1.73m2/year). Conclusion Long-term low-dose aspirin does not affect eGFR and positive urine dipstick albumin in patients with type 2 diabetes. PMID:26808136

Is Long-Term Low-Dose Aspirin Therapy Associated with Renal Dysfunction in Patients with Type 2 Diabetes? JPAD2 Cohort Study.

PubMed

Okada, Sadanori; Morimoto, Takeshi; Ogawa, Hisao; Sakuma, Mio; Soejima, Hirofumi; Nakayama, Masafumi; Jinnouchi, Hideaki; Waki, Masako; Akai, Yasuhiro; Ishii, Hitoshi; Saito, Yoshihiko

2016-01-01

Low-dose aspirin is widely recommended for patients at high risk for cardiovascular disease (CVD); however, it remains uncertain whether long-term treatment adversely affects renal function in patients with diabetes. We investigated whether long-term low-dose aspirin affects renal dysfunction in patients with diabetes. We conducted a randomized controlled trial (RCT), the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, to evaluate low-dose aspirin as primary prevention for CVD in patients with type 2 diabetes. We followed the patients with negative urine dipstick albumin of the JPAD trial in a cohort study after the RCT period was completed. Patients were randomly allocated to receive aspirin (81 mg or 100 mg daily, aspirin group) or no aspirin (no aspirin group). After the RCT, the treating physician decided whether to administer aspirin. We evaluated the incidence of positive urine dipstick albumin and annual changes in estimated glomerular filtration rate (eGFR). Positive urine dipstick albumin developed in 297 patients in the aspirin group (n = 1,075) and 270 patients in the no aspirin group (n = 1,098) during follow-up (median, 8.5 years). Intention-to-treat analysis showed low-dose aspirin did not increase the incidence of positive urine dipstick albumin (hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.995-1.38). On-treatment analysis yielded similar results (HR, 1.08; 95% CI, 0.92-1.28). Multivariable analysis showed the incidence of positive urine dipstick albumin was higher among the elderly and those with elevated serum creatinine, high hemoglobin A1c, or high blood pressure; however, low-dose aspirin did not increase the risk of positive urine dipstick albumin. There were no significant differences in annual changes in eGFR between the groups (aspirin, -0.8 ± 2.9; no aspirin, -0.9 ± 2.5 ml/min/1.73 m(2)/year). Long-term low-dose aspirin does not affect eGFR and positive urine dipstick albumin in patients with type 2 diabetes.

Renal function, cardiovascular disease risk factors' prevalence and 5-year disease incidence; the role of diet, exercise, lipids and inflammation markers: the ATTICA study.

PubMed

Chrysohoou, C; Panagiotakos, D B; Pitsavos, C; Skoumas, J; Toutouza, M; Papaioannou, I; Stefanadis, C

2010-06-01

We aimed to evaluate the association between renal function and various cardiovascular disease (CVD) risk factors, as well as 5-year incidence of CVD, in a sample of CVD free adults. (i) Cross-sectional information from n = 1975. Greek men and women (>18 years) without CVD and hypertension at baseline examination and (ii) 5-year (2001-06) survival data from n = 2101 individuals without CVD at baseline, all participants in the ATTICA study, were analysed in this work. Kidney function was quantified by the baseline estimated creatinine clearance rate (C(cr)), using the Cockcroft-Gault formula and the National Kidney Foundation recommendations. Outcome of interest was the development of CVD that was defined according to WHO-ICD-10 criteria. At baseline, the prevalence of moderate-to-severe renal dysfunction (i.e. C(cr) < 60) was 2.8% in males and 7.7% in females. Physical activity status, cigarette smoking, hypercholesterolemia and homocysteine levels and greater adherence to the Mediterranean diet were inversely associated with C(cr) rate (P < 0.05), while no association was found with history of diabetes. During the 5-year follow-up, people with moderate-to-severe renal dysfunction as compared with normal, had 3.21 times higher CVD risk [95% confidence interval (CI) 1.98-5.19], after adjusting for history of hypertension (hazard ratio = 2.15, 95% CI 1.48-3.11), hypercholesterolemia (1.37, 0.98-1.98), diabetes (3.28, 2.15-5.00), smoking habits (0.89, 0.60-1.32) and physical activity status (0.86, 0.56-1.21). Renal function seems to be associated with the levels of lifestyle and bio-clinical CVD risk factors and contribute to the long-term incidence of cardiac events. Public health care practitioners should take into account renal function in better preventing the burden of CVD at individual, and population level, as well.

Renal subcapsular rim sign. Radionuclide pattern

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howman-Giles, R.; Gett, M.; Roy, P.

1986-04-01

The renal cortical rim sign is a radiological term describing the thin peripheral nephrogram of 2-4 mm thick which is from the peri-renal capsular collateral circulation in an otherwise nonfunctioning kidney. Radionuclides are used frequently in the estimation of renal function. A neonate with renal vein thrombosis demonstrated a rim sign on renal scan with Technetium DTPA. The rim sign on renal scan can be differentiated from severe hydronephrosis or multicystic kidney both of which may have a peripheral thin cortex which functions late on the renal scan. The rim sign in renal vein thrombosis was best visualized during themore » early blood pool phase when there was a considerable amount of radioactivity in the blood pool.« less

Bladder versus renal bacteriuria during pregnancy: recurrence after treatment.

PubMed

Leveno, K J; Harris, R E; Gilstrap, L C; Whalley, P J; Cunningham, F G

1981-02-15

Localization of bacteriuria has been shown to correlate with the pattern of recurrence after treatment. The immunofluorescent technique was used to localize infection in 233 pregnant women with asymptomatic bacteriuria to determine whether this would identify those who were at greater risk for recurrence. In both an indigent and a military population, the incidence of renal bacteriuria was 42%. Regardless of the site of infection, after one course of short-term (10-day) or long-term (21-day) antimicrobial therapy, almost two thirds of these women were abacteriuric for the remainder of gestation. Women given short-term treatment were more likely to have a recurrence within 2 weeks of completion of therapy than were women given long-term therapy (P less than 0.001). Moreover, these early recurrences were more frequent in women given short-term treatment for renal bacteriuria (P less than 0.05). Conversely, recurrences 6 or more weeks after completion of therapy, and regardless of site of infection, were more common in women given long-term treatment (P less than 0.01). Although the timing of recurrence varied significantly in relation to duration of treatment and site of infection, the ultimate risk of recurrence was not related to either. The conclusion is that localization of asymptomatic bacteriuria does not contribute to the management of pregnant women, since overall recurrence rates are independent of the site of infection.

Design and rationale of the ATHENA study--A 12-month, multicentre, prospective study evaluating the outcomes of a de novo everolimus-based regimen in combination with reduced cyclosporine or tacrolimus versus a standard regimen in kidney transplant patients: study protocol for a randomised controlled trial.

PubMed

Sommerer, Claudia; Suwelack, Barbara; Dragun, Duska; Schenker, Peter; Hauser, Ingeborg A; Nashan, Björn; Thaiss, Friedrich

2016-02-17

Immunosuppression with calcineurin inhibitors remains the mainstay of treatment after kidney transplantation; however, long-term use of these drugs may be associated with nephrotoxicity. In this regard, the current approach is to optimise available immunosuppressive regimens to reduce the calcineurin inhibitor dose while protecting renal function without affecting the efficacy. The ATHENA study is designed to evaluate renal function in two regimens: an everolimus and reduced calcineurin inhibitor-based regimen versus a standard treatment protocol with mycophenolic acid and tacrolimus in de novo kidney transplant recipients. ATHENA is a 12-month, multicentre, open-label, prospective, randomised, parallel-group study in de novo kidney transplant recipients (aged 18 years or older) receiving renal allografts from deceased or living donors. Eligible patients are randomised (1:1:1) prior to transplantation to one of the following three treatment arms: everolimus (starting dose 1.5 mg/day; C0 3-8 ng/mL) with cyclosporine or everolimus (starting dose 3 mg/day; C0 3-8 ng/mL) with tacrolimus or mycophenolic acid (enteric-coated mycophenolate sodium at 1.44 g/day or mycophenolate mofetil at 2 g/day) with tacrolimus; in combination with corticosteroids. All patients receive induction therapy with basiliximab. The primary objective is to demonstrate non-inferiority of renal function (eGFR by the Nankivell formula) in one of the everolimus arms compared with the standard group at month 12 post transplantation. The key secondary objective is to assess the incidence of treatment failure, defined as biopsy-proven acute rejection, graft loss, or death, among the treatment groups. Other objectives include assessment of the individual components of treatment failure, incidence and severity of viral infections, incidence and duration of delayed graft function, incidence of indication biopsies, slow graft function and wound healing complications, and overall safety and tolerability. Exploratory objectives include evaluation of left ventricular hypertrophy assessed by the left ventricular mass index, evolution of human leukocyte antigen and non-human leukocyte antigen antibodies, and a cytomegalovirus substudy. As one of the largest European multicentre kidney transplant studies, ATHENA will determine whether a de novo everolimus-based regimen can preserve renal function versus the standard of care. This study further assesses a number of clinical issues which impact long-term outcomes post transplantation; hence, its results will have a major clinical impact. Clinicaltrials.gov: NCT01843348, date of registration--18 April 2013; EUDRACT number: 2011-005238-21, date of registration--20 March 2012.

Percutaneous nephrolithotomy for complex caliceal and staghorn stones in patients with solitary kidney.

PubMed

Resorlu, Berkan; Kara, Cengiz; Oguz, Ural; Bayindir, Mirze; Unsal, Ali

2011-06-01

Treatment of patients with solitary kidney having complex stones is one of the most challenging problem in urology. We present our experience with percutaneous nephrolithotomy (PCNL) in treating 16 patients with staghorn stones in a solitary kidney to determine long-term renal functional results. We retrospectively reviewed the records of 16 patients with complex caliceal or staghorn stones in a solitary kidney treated with PCNL. Demographic data, number and location of accesses, hemoglobin values, stone analyses, and complications were studied. Serum creatinine, glomerular filtration rate (GFR), systolic and diastolic blood pressure, new onset hypertension, and kidney morphology were determined preoperatively and postoperatively at 1 month and 1 year. Male to female ratio was 14:2 and mean age was 49.6 years (range 31-55). Of these, 10 (62.5%) patients required a single tract, while 6 (37.5%) required multiple tracts. The calculi were extracted or fragmented successfully in 13 (81.3%) patients and complete stone clearance was achieved after the first stage. In two patients with residual calculi, a double-J catheter was inserted and extracorporeal shock wave lithotripsy (SWL) was performed. There were no significant intraoperative problems except in one patient, who had bleeding from an infundibular tear attributable to torquing. During the 1-year study period, none of the patients progressed to end-stage renal disease requiring dialysis. We demonstrated a significant improvement in creatinine and GFR levels from preoperatively to 1-year follow-up. The number of patients with hypertension before PCNL was 5 and by the end of follow-up there was no new onset hypertension. The demonstrated effectiveness, small number of complications at short-term, not any poorly effect on renal function and blood pressure at the long-term follow-up confirm that PCNL is not only effective but is also safe in the solitary kidney with staghorn calculi.

Long Term Study of Protective Mechanisms of Human Adipose Derived Mesenchymal Stem Cells on Cisplatin Induced Kidney injury in Sprague-Dawley Rats.

PubMed

Elhusseini, Fatma M; Saad, Mohamed-Ahdy A A; Anber, Nahla; Elghannam, Doaa; Sobh, Mohamed-Ahmed; Alsayed, Aziza; El-Dusoky, Sara; Sheashaa, Hussein; Abdel-Ghaffar, Hassan; Sobh, Mohamed

2016-01-01

Long-term evaluation of cisplatin induced nephrotoxicity and the probable renal protective activities of stem cells are lacking up until now. We evaluated the early and long-term role of human adipose derived mesenchymal stem cells (ADMSCs) in prevention or amelioration of cisplatin induced acute kidney injury (AKI) in Sprague-Dawley rats. For this, we determined the kidney tissue level of oxidative stress markers in conjugation with a renal histopathological scoring system of both acute and chronic renal changes. This study used eighty Sprague-Dawley (SD) rats weighing 250-300g. They were assigned into four equal groups (each group n=20): (I) Negative control group, rats injected with single dose of 1 ml normal saline. (II) Positive control cisplatin, rats injected with a single dose of 5 mg/kg I.P in 1 ml saline. (III) Cisplatin and culture media group, rats injected with 0.5 ml of culture media single dose into the tail vein and (IV) Cisplatin and ADMSCs group, rats injected with a single dose of 0.5 ml of culture media containing 5 x10(6)ADMSCs into the tail vein one day after cisplatin administration. Each main group was further divided according to the timing of sacrifice into four subgroups (each subgroup n=5). Rats in the subgroup A were sacrificed after 4 days; subgroup B were sacrificed after 7 days; subgroup C were sacrificed after 11 days; and subgroup D were sacrificed after 30 days. Before sacrifice, 24 hrs.-urine was collected using a metabolic cage. Renal function was evaluated through blood urea nitrogen (BUN), serum creatinine and creatinine clearance. Kidney tissue homogenate oxidative stress parameters, Malondialdehyde (MDA), Superoxide dismutase (SOD) and Glutathione (GSH) were determined. In addition, histopathological analysis for active injury, regenerative and chronic changes was performed. ADMSCs were characterized and their capability of differentiation was proved. Cisplatin induced a significant increase in plasma creatinine and tissue MDA and induced a decrease in SOD, GSH and creatinine clearance. ADMSCs attenuated these changes. Cisplatin resulted in prominent histopathological changes in the term of tubular necrosis, atrophy, inflammatory cells infiltration and fibrosis. ADMSCs significantly lowered the injury score at day 4, 7, 11 and 30 with marked regenerative changes starting from day 4 and limited fibrotic score at day 30. ADMSCs have both protective and regenerative abilities with consequent limitation of the development of renal fibrosis after the cisplatin induced acute tubular necrosis, largely through an anti-oxidative activity.

Long-term risks of kidney living donation: review and position paper by the ERA-EDTA DESCARTES working group.

PubMed

Maggiore, Umberto; Budde, Klemens; Heemann, Uwe; Hilbrands, Luuk; Oberbauer, Rainer; Oniscu, Gabriel C; Pascual, Julio; Schwartz Sorensen, Soren; Viklicky, Ondrej; Abramowicz, Daniel

2017-02-01

Two recent matched cohort studies from the USA and Norway published in 2014 have raised some concerns related to the long-term safety of kidney living donation. Further studies on the long-term risks of living donation have since been published. In this position paper, Developing Education Science and Care for Renal Transplantation in European States (DESCARTES) board members critically review the literature in an effort to summarize the current knowledge concerning long-term risks of kidney living donation to help physicians for decision-making purposes and for providing information to the prospective live donors. Long-term risk of end-stage renal disease (ESRD) can be partially foreseen by trying to identify donors at risk of developing ‘de novo’ kidney diseases during life post-donation and by predicting lifetime ESRD risk. However, lifetime risk may be difficult to assess in young donors, especially in those having first-degree relatives with ESRD. The study from Norway also found an increased risk of death after living donor nephrectomy, which became visible only after >15 years of post-donation follow-up. However, these findings are likely to be largely the result of an overestimation due to the confounding effect related to a family history of renal disease. DESCARTES board members emphasize the importance of optimal risk–benefit assessment and proper information to the prospective donor, which should also include recommendations on health-promoting behaviour post-donation. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Congenital ureteropelvic junction obstruction: human disease and animal models

PubMed Central

Klein, Julie; Gonzalez, Julien; Miravete, Mathieu; Caubet, Cécile; Chaaya, Rana; Decramer, Stéphane; Bandin, Flavio; Bascands, Jean-Loup; Buffin-Meyer, Bénédicte; Schanstra, Joost P

2011-01-01

Ureteropelvic junction (UPJ) obstruction is the most frequently observed cause of obstructive nephropathy in children. Neonatal and foetal animal models have been developed that mimic closely what is observed in human disease. The purpose of this review is to discuss how obstructive nephropathy alters kidney histology and function and describe the molecular mechanisms involved in the progression of the lesions, including inflammation, proliferation/apoptosis, renin–angiotensin system activation and fibrosis, based on both human and animal data. Also we propose that during obstructive nephropathy, hydrodynamic modifications are early inducers of the tubular lesions, which are potentially at the origin of the pathology. Finally, an important observation in animal models is that relief of obstruction during kidney development has important effects on renal function later in adult life. A major short-coming is the absence of data on the impact of UPJ obstruction on long-term adult renal function to elucidate whether these animal data are also valid in humans. PMID:20681980

Renal Failure in Mice with Gsα Deletion in Juxtaglomerular Cells

PubMed Central

Chen, Limeng; Faulhaber-Walter, Robert; Wen, Yubing; Huang, Yuning; Mizel, Diane; Chen, Min; Sequeira Lopez, Maria Luisa; Weinstein, Lee S.; Gomez, R. Ariel; Briggs, Josephine P.; Schnermann, Jurgen

2010-01-01

Background Mice with deletion of Gsα in renin-producing cells (RC/FF mice) have been shown to have greatly reduced renin production and lack of responsiveness of renin secretion to acute stimuli. In addition, young RC/FF mice are hypotensive and have a vasopressin-resistant concentrating defect. In the present study we have determined the long-term effect on renal function, blood pressure, and renal pathology in this low renin and diuretic mouse model. Methods and Results Urine osmolarity of RC/FF mice was decreased in all age groups. GFR measured at 7, 14 and 20 weeks of age declined progressively. Single nephron GFR similarly declined while fractional proximal fluid absorption was maintained. Expression levels of extracellular matrix proteins (collagen I, IV and fibronectin) and α-smooth muscle actin were increased in kidneys of RC/FF mice at 20 weeks, and this was accompanied by focal segmental glomerulosclerosis and periglomerular interstitial fibrosis. RC/FF mice showed a progressive reduction of body weight, an increase in urine albumin excretion, and an increase of blood pressure with aging. Conclusion A chronic reduction of renin production in mice may be a risk factor in its own right, and does not protect renal function against the profibrotic influence of a chronically elevated urine flow. PMID:20551626

Albuminuria after renal transplantation: maintenance with sirolimus/low-dose tacrolimus vs. mycophenolate mofetil/high-dose tacrolimus.

PubMed

Miles, Clifford D; Skorupa, Jill Y; Sandoz, John P; Rigley, Theodore H; Nielsen, Kathleen J; Stevens, R Brian

2011-01-01

Maintenance immunosuppression with sirolimus (SRL) in renal transplantation has been associated with proteinuria. We report long-term outcomes of kidney transplant recipients maintained on steroid-free regimens, either SRL with low-dose tacrolimus (SRL/L-Tac) or mycophenolate mofetil (MMF) with high-dose tacrolimus (MMF/H-Tac). We conducted a case-matched study of 50 patients receiving MMF/H-Tac, matched 1:2 with 100 patients maintained on SRL/L-Tac. All patients were induced with rabbit antithymocyte globulin followed by early steroid withdrawal. Comparisons were made of patient and graft survival, graft function, acute rejection, and albuminuria. There were no significant differences between the SRL/L-Tac and MMF/H-Tac groups for patient survival, graft survival, occurrence of acute rejection, or graft function. There was no difference in the proportion of patients with albumin/creatinine ratio (ACR) ≥300 μg/mg (19% vs. 20%), but more patients in the SRL group were receiving renin-angiotensin system blocking agents (72% vs. 53%, p = 0.04). Only flushing the donor kidney with histidine-tryptophan-ketoglutarate solution (vs. UW solution) was predictive of albuminuria. Long-term outcomes are similar at our center for kidney transplant patients receiving either SRL/L-Tac or MMF/H-Tac. Although the occurrence of albuminuria was not different, significantly more SRL-treated patients were receiving antiproteinuric medications. © 2010 John Wiley & Sons A/S.

Abdominal wall dysfunction in adult bladder exstrophy: a treatable but under-recognized problem.

PubMed

Manahan, M A; Campbell, K A; Tufaro, A P

2016-08-01

Bladder exstrophy is defined by urogenital and skeletal abnormalities with cosmetic and functional deformity of the lower anterior abdominal wall. The primary management objectives have historically been establishment of urinary continence with renal function preservation, reconstruction of functional and cosmetically acceptable external genitalia, and abdominal wall closure of some variety. The literature has focused on the challenges of neonatal approaches to abdominal wall closure; however, there has been a paucity of long-term followup to identify the presence and severity of abdominal wall defects in adulthood. Our goal was to characterize the adult disease and determine effective therapy. A retrospective review of a consecutive series of six patients was performed. We report and characterize the presence of severe abdominal wall dysfunction in these adult exstrophy patients treated as children. We tailored an abdominal wall and pelvic floor reconstruction with long-term success to highlight a need for awareness of the magnitude of the problem and its solvability. The natural history of abdominal wall laxity and the long-term consequences of cloacal exstrophy closure have gone unexplored and unreported. Evaluation of our series facilitates understanding in this complex area and may be valuable for patients who are living limited lives thinking that no solution is available.

Bcıı--RFLP profiles for serum amiloid A1 and mutated MEFV gene prevalence in chronic renal failure patients requiring long-term hemodialysis.

PubMed

Ozdemir, Ozturk; Kayatas, Mansur; Cetinkaya, Selma; Yildirim, Malik Ejder; Silan, Fatma; Kurtulgan, Hande Kucuk; Koksal, Binnur; Urfali, Mine; Candan, Ferhan

2015-03-01

There is an increased mortality risk in long-term hemodialysis patients of renal failure due to the chronic inflammation. The relationship between the chronic renal failure (CRF) and the role of familial genetic markers remains incompletely understood. In the current study, it was aimed to find out the prevalence of common MEFV gene mutations and BcII polymorphism in serum amyloid A1 (SAA1) gene in chronic renal patients (CRF) who require long-term hemodialysis. Current cohort includes 242 CRF patients and 245 healthy individuals from the same population. Total genomic DNA was isolated from peripheral blood-EDTA samples and genotyping of target MEFV gene was carried out by reverse hybridization Strip Assay and real-time techniques. The SAA1 gene was genotyped by the BclI-RFLP method. Increased mutated MEFV genotypes were found in current CRF patients when compared with the control group from the same ethnicity and the difference was statistically significant (Table 2) (OR: 4.9401, 95% CI: 3.0694-7.9509), p<0.0001. The most frequent point mutations were M694V and E148Q. The mutated T allel frequency in the SAA1 gene was also different when compared with the healthy controls and the difference was found to be statistically significant (χ2: 13.18; p=0.000). The current results indicate the germ-line mutations in both genetic biomarkers (MEFV and SAA1 genes) that are related to inflammation and amyloidosis processes may play a crucial role in CRF pathogenesis due to the long-term chronic inflammation.

Ischemic acute kidney injury and klotho in renal transplantation.

PubMed

Panah, Fatemeh; Ghorbanihaghjo, Amir; Argani, Hassan; Asadi Zarmehri, Maryam; Nazari Soltan Ahmad, Saeed

2018-05-01

Post-transplant ischemic acute kidney injury (AKI), secondary to ischemia reperfusion injury (IRI), is a major problem influencing on the short and long term graft and patient survival. Many molecular and cellular modifications are observed during IRI, for example, tissue damage result production of reactive oxygen species (ROS), cytokines, chemokines, and leukocytes recruitment which are activated by NF-κB (nuclear factor kappa B) signaling pathway. Therefore, inhibiting these processes can significantly protect renal parenchyma from tissue damage. Klotho protein, mainly produced in distal convoluted tubules (DCT), is an anti-senescence protein. There is increasing evidence to confirm a relationship between Klotho levels and renal allograft function. Many studies have also demonstrated that expression of the Klotho gene would be down regulated with IRI, so it will be used as an early biomarker for acute kidney injury after renal transplantation. Other studies suggest that Klotho may have a renoprotective effect for attenuating of kidney injury. In this review, we will discuss pathophysiology of IRI-induced acute kidney injury and its relation with klotho level in renal transplantation procedure. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Transcatheter renal denervation for the treatment of resistant arterial hypertension: the Swiss expert consensus.

PubMed

Wuerzner, Gregoire; Muller, Olivier; Erne, Paul; Cook, Stéphane; Sudano, Isabella; Lüscher, Thomas F; Noll, Georg; Kaufmann, Urs; Rickli, Hans; Waeber, Bernard; Kaiser, Christophe; Sticherling, Christian; Pechère-Bertschi, Antoinette; Baumgartner, Iris; Jacob, Augustinus L; Burnier, Michel; Qanadli, Salah D

2014-03-20

Transcatheter (or percutaneous) renal denervation is a novel technique developed for the treatment of resistant hypertension. So far, only one randomised controlled trial has been published, which has shown a reduction of office blood pressure. The Swiss Society of Hypertension, the Swiss Society of Cardiology, The Swiss Society of Angiology and the Swiss Society of Interventional Radiology decided to establish recommendations to practicing physicians and specialists for good clinical practice. The eligibility of patients for transcatheter renal denervation needs (1.) confirmation of truly resistant hypertension, (2.) exclusion of secondary forms of hypertension, (3.) a multidisciplinary decision confirming the eligibility, (4.) facilities that guarantee procedural safety and (5.) a long-term follow-up of the patients, if possible in cooperation with a hypertension specialist. These steps are essential until long-term data on safety and efficacy are available.

Outcome after prenatal diagnosis of congenital anomalies of the kidney and urinary tract.

PubMed

Nef, Samuel; Neuhaus, Thomas J; Spartà, Giuseppina; Weitz, Marcus; Buder, Kathrin; Wisser, Josef; Gobet, Rita; Willi, Ulrich; Laube, Guido F

2016-05-01

Congenital anomalies of the kidney and urinary tract are common findings on fetal ultrasound. The aim of this prospective observational study was to describe outcome and risk factors in 115 patients born 1995-2001. All prenatally diagnosed children were stratified into low- and high-risk group and followed postnatally clinically and by imaging at defined endpoints. Risk factors were evaluated using odds ratios. Neonatal diagnosis included pelvi-ureteric junction obstruction (n = 33), vesicoureteral reflux (n = 27), solitary mild pelvic dilatation (postnatal anteroposterior diameter 5-10 mm; n = 25), and further diagnosis as primary obstructive megaureter, unilateral multicystic dysplastic kidney, renal dysplasia and posterior urethral valves. In 38 children with prenatal isolated hydronephrosis, ultrasound normalized at median age of 1.2 years (range 0.1-9). Surgery was performed in 34 children at median age of 0.4 years (0.1-10.8). Persistent renal anomalies without surgery were present in 43 children and followed in 36 for median time of 16 years (12.2-18). Oligohydramnios and postnatal bilateral anomalies were significantly associated with surgery and impaired renal function. The majority of children had a favourable postnatal outcome, in particular children with prenatally low risk, i.e. isolated uni- or bilateral hydronephrosis. Oligohydramnios and postnatal bilateral anomalies were risk factors for non-favourable outcome. • In congenital anomalies of the kidney and urinary tract significantly poorer outcome is known in patients with bilateral renal hypoplasia or solitary kidney associated with posterior urethral valves. • Other factors as proteinuria and vesicoureteral reflux were associated with a higher risk of progression to chronic renal failure in these patients. What is New: • Unlike other studies giving us above-mentioned information, we included all patients with any kind of prenatally diagnosed congenital anomalies of the kidney and urinary tract. Our study shows long-term follow up (median 16 years, range 12.2-18 years), especially in patients not needing surgery, but with persistent anomalies. • During postnatal long-term follow up (median 2.2 years, range 0.1-18 years) one third each showed normalization, need of surgery or persistence of anomalies without need of surgery. Our study revealed a good prognosis in the majority of these children, in particular with prenatally low risk, i.e. isolated uni- or bilateral hydronephrosis, and revealed oligohydramnios and postnatal bilateral anomalies as risk factors for a non-favourable outcome, defined as need of surgery, persistent anomalies with impaired renal function, end stage renal failure or death.

Multiple Renal Artery Pseudoaneurysms in Patients Undergoing Renal Artery Embolization Following Partial Nephrectomy: Correlation with RENAL Nephrometry Scores

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Nakul; Patel, Anish; Ensor, Joe

PurposeTo describe the incidence of multiple renal artery pseudoaneurysms (PSA) in patients referred for renal artery embolization following partial nephrectomy and to study its relationship to RENAL nephrometry scores.Materials and MethodsThe medical records of 25 patients referred for renal artery embolization after partial nephrectomy were retrospectively reviewed for the following parameters: size and number of tumors, RENAL nephrometry scores, angiographic abnormalities, technical and clinical outcomes, and estimated glomerular filtration rates (eGFRs) after embolization.ResultsTwenty-four patients had primary renal tumors, while 1 patient had a pancreatic tumor invading the kidney. Multiple tumors were resected in 4 patients. Most patients (92 %) were symptomatic,more » presenting with gross hematuria, flank pain, or both. Angiography revealed PSA with (n = 5) or without (n = 20) AV fistulae. Sixteen patients (64 %) had multiple PSA involving multiple renal vessels. Higher RENAL nephrometry scores were associated with an increasing likelihood of multiple PSA. Multiple vessels were embolized in 14 patients (56 %). Clinical success was achieved after one (n = 22) or two (n = 3) embolization sessions in all patients. Post-embolization eGFR values at different time points after embolization were not significantly different from the post-operative eGFR.ConclusionA majority of patients requiring renal artery embolization following partial nephrectomy have multiple pseudoaneurysms, often requiring selective embolization of multiple vessels. Higher RENAL nephrometry score is associated with an increasing likelihood of multiple pseudoaneurysms. We found transarterial embolization to be a safe and effective treatment option with no long-term adverse effect on renal function in all but one patient with a solitary kidney.« less

The behavior of renal-regulating hormones during hypogravic stress

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1985-01-01

The regulation of fluid and electrolyte behavior during space flight is believed to be under control, in large part, of a group of hormones which have their major effects on renal excretion. The hormones studied include renin-angitensin, aldosterone, and antidiuretic hormone (ADH). The regulatory systems of these renal-regulating hormones as they act individually and in concert with each other are analyzed. The analysis is based on simulations of the mathematical model of Guyton. A generalized theory is described which accounts for both short-term and long-term behavior of this set of hormones.

Acute kidney injury: not just acute renal failure anymore?

PubMed

Dirkes, Susan

2011-02-01

Until recently, no uniform standard existed for diagnosing and classifying acute renal failure. To clarify diagnosis, the Acute Dialysis Quality Initiative group stated its consensus on the need for a clear definition and classification system of renal dysfunction with measurable criteria. Today the term acute kidney injury has replaced the term acute renal failure, with an understanding that such injury is a common clinical problem in critically ill patients and typically is predictive of an increase in morbidity and mortality. A classification system, known as RIFLE (risk of injury, injury, failure, loss of function, and end-stage renal failure), includes specific goals for preventing acute kidney injury: adequate hydration, maintenance of renal perfusion, limiting exposure to nephrotoxins, drug protective strategies, and the use of renal replacement therapies that reduce renal injury.

Predictive Factors of Chronic Kidney Disease in Patients with Vesicoureteral Reflux Treated Surgically and Followed after Puberty.

PubMed

Kang, Minyong; Lee, Jung Keun; Im, Young Jae; Choi, Hwang; Park, Kwanjin

2016-04-01

We delineated clinical features and determined predictors of chronic kidney disease during long-term postpubertal followup in patients with vesicoureteral reflux treated surgically. We analyzed the data of 101 patients who were surgically treated for vesicoureteral reflux and had gone through puberty. Patients underwent preoperative and postoperative voiding cystourethrography to assess reflux status, and dimercaptosuccinic acid scan to assess renal cortical defects. We compared several variables preoperatively and postpubertally, including body mass index; blood urea nitrogen, creatinine and uric acid levels; estimated glomerular filtration rate; microalbuminuria; blood pressure; renal function and renal scarring. Kaplan-Meier analysis was used to predict chronic kidney disease-free survival rates throughout the followup periods. Cox regression model was adopted to identify independent predictors of chronic kidney disease. We defined chronic kidney disease as estimated glomerular filtration rate less than 60 ml/minute/1.73 m(2). Median followup was 100.0 months (IQR 69.0 to 136.5). Median age was 16 years at last followup (IQR 14 to 18). A total of 11 patients (10.9%) were diagnosed with de novo chronic kidney disease during postpubertal followup. It is noteworthy that serum uric acid levels (HR 1.96) and presence of high grade reflux (HR 7.40) were significant predictors of chronic kidney disease on multivariate analysis. In children who were treated surgically for vesicoureteral reflux preoperative uric acid levels and high grade reflux were independent predictors of de novo chronic kidney disease during postpubertal followup. Our results offer valuable information for predicting long-term renal outcomes in patients with vesicoureteral reflux treated surgically. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Effect of long-term high-fat diet intake on peripheral insulin sensibility, blood pressure, and renal function in female rats.

PubMed

Roza, Noemi A V; Possignolo, Luiz F; Palanch, Adrianne C; Gontijo, José A R

2016-01-01

This study determines whether 8-week high-fat diet (HFD) consumption alters insulin sensitivity, kidney function, and blood pressure (BP) in female rats when compared with standard rodent diet (ND) intake in gender- and age-matched rats. The present study investigates, in female Wistar HanUnib rats, the effect of long-term high-fat fed group (HFD) compared with standard chow on BP by an indirect tail-cuff method using an electrosphygmomanometer, insulin and glucose function, and kidney function by creatinine and lithium clearances. The current study shows glucose tolerance impairment, as demonstrated by increased fasting blood glucose (ND: 78±2.8 vs. HFD: 87±3.8 mg/dL) associated with reduced insulin secretion (ND: 0.58±0.07 vs. HFD: 0.40±0.03 ng/mL) in 8-week female HFD-treated rats. The incremental area under the curve (AUC, ND: 1,4558.0±536.0 vs. HFD: 1,6507.8±661.9), homeostasis model assessment of insulin resistance (HOMA-IR) index, and the first-order rate constant for the disappearance of glucose (Kitt) were significantly enhanced in 8-week HFD-treated rats compared with age-matched ND group (respectively, P=0.03, P=0.002, and P<0.0001). The current study also shows a significantly higher systolic BP measured in 5 and 8 weeks posttreatment in HFD (5-week HFD-treated: 155.25±10.54 mmHg and 8-week HFD-treated: 165±5.8 mmHg) (P=0.0001), when compared to BP values in 5-week ND, 137±4.24 mmHg and 8-week ND, 131.75±5.8 mmHg age-matched group. Otherwise, the glomerular filtration rate and renal sodium handling evaluated by FENa, FEPNa and FEPPNa, were unchanged in both groups. We may conclude that 8-week female HFD-fed rats compared with ND group stimulate harmful effects, such as BP rise and peripheral glucose intolerance. The increased BP occurs through insulin resistance and supposedly decreased vasodilatation response without any change on renal function.

Our paper 20 years later: from acute renal failure to acute kidney injury--the metamorphosis of a syndrome.

PubMed

Druml, Wilfred; Lenz, Kurt; Laggner, Anton N

2015-11-01

More than 20 years ago we reported an analysis of a case series of elderly critically ill patients with acute kidney injury (AKI)--then termed acute renal failure. At that time, AKI was regarded as a "simple" complication, but has since undergone a fundamental change and actually has become one of the central syndromes in the critically ill patient. We have analyzed elderly patients above 65 years of age with an AKI defined as serum creatinine above 3 mg/dl corresponding to modern KDIGO stage 3, most of them requiring renal replacement therapy (RRT). Using an extremely complete data set the diagnosis differentiated the underlying disease entity, the dominant cause of AKI, acute and chronic risk factors (comorbidities). Special aspects such as severity of disease, early AKI at admission versus late AKI, early versus later start of RRT, AKI not treated by RRT in spite of indication for RRT, various measures of short-term and long-term prognosis, renal outcome, patients dying with resolved AKI, and causes of death were evaluated. Crude mortality was 61% which corresponds to modern studies with gross variation among the different subgroups. Age per se was not a determinant of survival either within the group of elderly patients or as compared to younger age groups. Despite an increase in mean age and disease severity during the observation period prognosis improved. A total of 17% of patients developed a chronic kidney disease. Long-term survival as compared to the general population was low. A look back at the last two decades illustrates a remarkable evolution or rather metamorphosis of a syndrome. AKI has evolved as a central syndrome in intensive care patients, a systemic disease process associated with multiple systemic sequels and extra-renal organ injury and exerting a pronounced effect on the course of disease and short- and long-term prognosis not only of the patient but also of the kidney. Moreover, the "non-renal-naïve" elderly patient with multiple comorbidities has become the most frequent ICU patient in industrialized nations.

Renal denervation in the management of resistant hypertension: current evidence and perspectives.

PubMed

Jin, Yu; Persu, Alexandre; Staessen, Jan A

2013-09-01

Catheter-based renal denervation has emerged as a novel treatment modality for resistant hypertension. This review summarizes the current evidence on this procedure in treatment of resistant hypertension, limitations of available evidence and questions to be answered. The SYMPLICITY studies showed that renal denervation is feasible in treating resistant hypertension, but failed to provide conclusive evidence on the size and durability of the antihypertensive, renal and sympatholytic effects, as well as the long-term safety. The definition of resistant hypertension was loose in the SYMPLICITY studies and the management of resistant hypertension was suboptimal. Future studies should have a randomized design and enroll truly resistant hypertension patients by excluding secondary hypertension, white-coat hypertension and nonadherent patients. Questions to be addressed by the ongoing and future trials include the long-term efficacy and safety of this procedure, identification of responders and uncovering of the underlying mechanisms. Only well-designed, randomized clinical trials addressing the limitations of the SYMPLICITY studies will be able to demonstrate whether renal denervation is an efficacious treatment modality in resistant hypertension and in which patients. For now, renal denervation remains an experimental procedure and should only be offered to truly resistant hypertensive patients in a research context after careful selection.

Early Allograft Dysfunction After Liver Transplantation Is Associated With Short- and Long-Term Kidney Function Impairment.

PubMed

Wadei, H M; Lee, D D; Croome, K P; Mai, M L; Golan, E; Brotman, R; Keaveny, A P; Taner, C B

2016-03-01

Early allograft dysfunction (EAD) after liver transplantation (LT) is related to ischemia-reperfusion injury and may lead to a systemic inflammatory response and extrahepatic organ dysfunction. We evaluated the effect of EAD on new-onset acute kidney injury (AKI) requiring renal replacement therapy within the first month and end-stage renal disease (ESRD) within the first year post-LT in 1325 primary LT recipients. EAD developed in 358 (27%) of recipients. Seventy-one (5.6%) recipients developed AKI and 38 (2.9%) developed ESRD. Compared with those without EAD, recipients with EAD had a higher risk of AKI and ESRD (4% vs. 9% and 2% vs. 6%, respectively, p < 0.001 for both). Multivariate logistic regression analysis showed an independent relationship between EAD and AKI as well as ESRD (odds ratio 3.5, 95% confidence interval 1.9-6.4, and odds ratio 3.1, 95% confidence interval 11.9-91.2, respectively). Patients who experienced both EAD and AKI had inferior 1-, 3-, 5-, and 10-year patient and graft survival compared with those with either EAD or AKI alone, while those who had neither AKI nor EAD had the best outcomes (p < 0.001). Post-LT EAD is a risk factor for both AKI and ESRD and should be considered a target for future intervention to reduce post-LT short- and long-term renal dysfunction. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Characteristics and clinical outcomes of living renal donors in Hong Kong.

PubMed

Hong, Y L; Yee, C H; Leung, C B; Teoh, J Yc; Kwan, B Ch; Li, P Kt; Hou, S Sm; Ng, C F

2018-02-01

In Asia, few reports are available on the outcomes for living renal donors. We report the short- and long-term clinical outcomes of individuals following living donor nephrectomy in Hong Kong. We retrospectively reviewed the characteristics and clinical outcomes of all living renal donors who underwent surgery from January 1990 to December 2015 at a teaching hospital in Hong Kong. Information was obtained from hospital records and territory-wide electronic patient records. During the study period, 83 individuals underwent donor nephrectomy. The mean (± standard deviation) follow-up time was 12.0 ± 8.3 years, and the mean age at nephrectomy was 37.3 ± 10.0 years. A total of 44 (53.0%), four (4.8%), and 35 (42.2%) donors underwent living donor nephrectomy via an open, hand-port assisted laparoscopic, and laparoscopic approach, respectively. The overall incidence of complications was 36.6%, with most being grade 1 or 2. There were three (9.4%) grade 3a complications; all were related to open donor nephrectomy. The mean glomerular filtration rate was 96.0 ± 17.5 mL/min/1.73 m 2 at baseline and significantly lower at 66.8 ± 13.5 mL/min/1.73 m 2 at first annual follow-up (P<0.01). The latest mean glomerular filtration rate was 75.6% ± 15.1% of baseline. No donor died or developed renal failure. Of the donors, 14 (18.2%) developed hypertension, two (2.6%) had diabetes mellitus, and three (4.0%) had experienced proteinuria. The overall perioperative outcomes are good, with very few serious complications. The introduction of a laparoscopic approach has decreased perioperative blood loss and also shortened hospital stay. Long-term kidney function is satisfactory and no patients developed end-stage renal disease. The incidences of new-onset medical diseases and pregnancy-related complications were also low.

On the function of the mammalian renal papilla and the peristalsis of the surrounding pelvis.

PubMed

Schmidt-Nielsen, Bodil; Schmidt-Nielsen, Bent

2011-07-01

This is an informal personal review of the development over time of my ideas about the concentrating mechanism of the mammalian renal papilla. It had been observed that animals with a need to produce a concentrated urine have a long renal papilla. I saw the function of the long papilla in desert rodents as an elongation of the counter-current concentrating mechanism of the inner medulla. This model led me to overlook contrary evidence. For example, in many experiments, the final urine has a higher osmolality than that of the tissue at the tip of the papilla. In addition, we had observations of the peristalsis of the renal pelvis surrounding the papilla. The urine concentration falls if the peristalsis is stopped. I was wrong; together, these lines of evidence show that the renal papilla is not just an elongation of the inner medulla. We are left without a full explanation of the concentrating mechanism of the mammalian renal papilla. It is hoped that other researchers will tackle this interesting problem. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report.

PubMed

Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali

2015-09-01

Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.

Zonisamide and renal calculi in patients with epilepsy: how big an issue?

PubMed

Wroe, Stephen

2007-08-01

To determine the prevalence of renal calculi in patients treated with zonisamide during randomized, controlled and open-label clinical trials, and from post-marketing surveillance data. Reports of renal calculi from four placebo-controlled double-blind trials of zonisamide, their long-term open-label treatment extension phases, and the US/European zonisamide clinical trial programme were reviewed. One double-blind study and its extension included routine ultrasound screening to identify asymptomatic calculi. Post-marketing surveillance data were also investigated, as was concomitant treatment with topiramate. No symptomatic renal calculi were reported during four randomized double-blind, placebo-controlled trials involving 848 subjects (including 498 zonisamide recipients) treated for up to 3 months. In long-term extension studies with treatment for up to 24 months, symptomatic renal calculi were reported in 9/626 (1.4%) patients. Pooled safety data from all US/European clinical trials identified 15/1296 (1.2%) patients with symptomatic renal calculi during treatment for up to 8.7 years. Post-marketing surveillance revealed nine cases from 59 667 patient-years of exposure in the USA, and 14 from 709 294 patient-years of exposure in Japan; only one case occurred during concomitant topiramate and zonisamide treatment. No imbalance in electrolyte levels was found from 35 patients receiving such co-treatment in clinical trials. The available data suggest that the risk of developing renal calculi during zonisamide treatment is low. Data are insufficient to determine whether concomitant treatment with topiramate increases the risk of renal stones.

Vulval and Vaginal Rhabdomyosarcoma in Children: Update and Reappraisal of Institut Gustave Roussy Brachytherapy Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Magne, Nicolas; Oberlin, Odile; Martelli, Helene

2008-11-01

Purpose: To report the Institut Gustave Roussy brachytherapy (BT) experience in the management of vulval and vaginal rhabdomyosarcoma with special emphasis on long-term outcome. Patients and Methods: Between 1971 and 2005, the data concerning 39 girls who had undergone BT as a part of their treatment were retrospectively analyzed. Of the 39 girls, 20 had been treated before 1990, when the BT volume encompassed the initial tumor extension. After 1990, only residual disease was included in the BT volume. Side effects were classified using the Common Terminology Criteria for Adverse Events, version 3.0. Results: The median age was 16.3 monthsmore » at diagnosis. Vaginal or vulvar rhabdomyosarcoma was diagnosed in 26 and 6 patients, respectively. The median follow-up was 8.4 years. The 5-year overall survival rate was 91%. Of the 39 patients, 6 developed a relapse. Of the 20 patients treated before 1990, 6 experienced Grade 1-2 renal/genitourinary function symptoms and 75% developed sequelae, in the form of vaginal or urethral sclerosis or stenosis. Four patients received follow-up treatment for psychological disorders. Of the 19 patients treated after 1990, 2 developed acute side effects, with maximal Grade 1-2 renal/genitourinary function symptoms, and 20% developed vaginal or urethral sclerosis or stenosis. Two cases of psychological disturbances were also documented. Conclusion: Reducing the BT volume coverage, better indications for surgery, and more efficient chemotherapy, all combined within a multidisciplinary approach, tended to improve results in terms of both survival and long-term sequelae.« less

[Cardiac surgery in octogenarian patients: evaluation of predictive factors of mortality, long-term outcome and quality of life].

PubMed

Viana-Tejedor, Ana; Domínguez, Francisco J; Moreno Yangüela, Mar; Moreno, Raúl; López de Sá, Esteban; Mesa, José M; López-Sendón, José

2008-10-04

Increasing life expectancy in Western countries in the last decades has resulted in a significant gradual increasing number of octogenarians referred for cardiac surgery. There is a need for a critical evaluation of the long-term surgical outcome and quality of life in the elderly. The aim of this study is to identify risk factors of mortality in octogenarians undergoing cardiac surgery and to assess the long term survival and quality of life. Data were reviewed on 150 patients aged over 80 years--mean age (standard deviation): 82.7 (2.5) years--who underwent cardiac surgery at our institution in the last 26 years. We analyzed clinical and epidemiological variables included in the European System for Cardiac Operative Risk Evaluation (euroSCORE), in-hospital morbidity and mortality, long term survival and quality of life after cardiac surgery. The 30-day mortality rate was 30.1%, with a mean hospital stay of 16.5 days (13-27). Emergent procedure, reparation of postinfarction ventricular ruptures, New York Heart Association functional class IV, chronic renal failure and previous myocardial infarction were independent predictors of in-hospital mortality. Mean follow up was 72.2 (9.9) months with survival rates of 87.3% and 57% at 1 and 5 years, respectively. Late postoperative quality of life in our 53 long-term survivors was significantly better than prior to surgery. New York Heart Association functional class improved from 2.52 to 1.48. Most survivors (97.7%) were satisfied with present quality of life Cardiac surgery in octogenarians is associated with increased in-hospital mortality rate and longer hospital stay. Our findings support that cardiac surgery can be performed in a selected elderly population with good long-term survival and quality of life.

Late renal toxicity of treatment for childhood malignancy: risk factors, long-term outcomes, and surveillance.

PubMed

Skinner, Roderick

2018-02-01

Chronic glomerular and tubular nephrotoxicity is reported in 20-50% and 20-25%, respectively, of children and adolescents treated with ifosfamide and 60-80% and 10-30%, respectively, of those given cisplatin. Up to 20% of children display evidence of chronic glomerular damage after unilateral nephrectomy for a renal tumour. Overall, childhood cancer survivors have a ninefold higher risk of developing renal failure compared with their siblings. Such chronic nephrotoxicity may have multiple causes, including chemotherapy, radiotherapy exposure to kidneys, renal surgery, supportive care drugs and tumour-related factors. These cause a wide range of chronic glomerular and tubular toxicities, often with potentially severe clinical sequelae. Many risk factors for developing nephrotoxicity, mostly patient and treatment related, have been described, but we remain unable to predict all episodes of renal damage. This implies that other factors may be involved, such as genetic polymorphisms influencing drug metabolism. Although our knowledge of the long-term outcomes of chronic nephrotoxicity is increasing, there is still much to learn, including how we can optimally predict or achieve early detection of nephrotoxicity. Greater understanding of the pathogenesis of nephrotoxicity is needed before its occurrence can be prevented.

Embryonic kidney function in a chronic renal failure model in rodents.

PubMed

Fujimoto, Eisuke; Yamanaka, Shuichiro; Kurihara, Sho; Tajiri, Susumu; Izuhara, Luna; Katsuoka, Yuichi; Yokote, Shinya; Matsumoto, Kei; Kobayashi, Eiji; Okano, Hirotaka James; Chikaraishi, Tatsuya; Yokoo, Takashi

2017-08-01

Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p < 0.05), confirming that the grafts were functional. We also demonstrated the possibilities of an in vivo imaging system for determining the viability of transplanted embryonic kidney with bladder. The results of this study demonstrate that transplanted embryonic kidney and bladder can grow and function effectively, even under uremic conditions.

Renal dysfunction in early adulthood following birth asphyxia in male spiny mice, and its amelioration by maternal creatine supplementation during pregnancy.

PubMed

Ellery, Stacey J; LaRosa, Domenic A; Cullen-McEwen, Luise A; Brown, Russell D; Snow, Rod J; Walker, David W; Kett, Michelle M; Dickinson, Hayley

2017-04-01

Acute kidney injury affects ~70% of asphyxiated newborns, and increases their risk of developing chronic kidney disease later in life. Acute kidney injury is driven by renal oxygen deprivation during asphyxia, thus we hypothesized that creatine administered antenatally would protect the kidney from the long-term effects of birth asphyxia. Pregnant spiny mice were fed standard chow or chow supplemented with 5% creatine from 20-d gestation (midgestation). One day prior to term (37-d gestation), pups were delivered by caesarean or subjected to intrauterine asphyxia. Litters were allocated to one of two time-points. Kidneys were collected at 1 mo of age to estimate nephron number (stereology). Renal function (excretory profile and glomerular filtration rate) was measured at 3 mo of age, and kidneys then collected for assessment of glomerulosclerosis. Compared with controls, at 1 mo of age male (but not female) birth-asphyxia offspring had 20% fewer nephrons (P < 0.05). At 3 mo of age male birth-asphyxia offspring had 31% lower glomerular filtration rate (P < 0.05) and greater glomerular collagen IV content (P < 0.01). Antenatal creatine prevented these renal injuries arising from birth asphyxia. Maternal creatine supplementation during pregnancy may be an effective prophylactic to prevent birth asphyxia induced acute kidney injury and the emergence of chronic kidney disease.

Impact of augmenting dialysis frequency and duration on cardiovascular function.

PubMed

Ly, Joseph; Chan, Christopher T

2006-01-01

Conventional hemodialysis (CHD) only delivers 10% to 15% of renal function in a nonphysiological intermittent mode. Because it occurs nightly and is sustained over a longer dialysis time, the uremic clearance provided by nocturnal hemodialysis (NHD) far exceeds that of CHD. Increasing the dose and frequency of dialysis by NHD has been demonstrated, in both short- and long-term studies, to reverse several important risk factors for adverse cardiovascular events in patients with end-stage renal disease such as hypertension, left ventricular hypertrophy, systolic dysfunction, conduit artery stiffness, attenuated baroreflex regulation of heart rate, disturbed heart rate variability, sleep apnea, and endothelium-dependent vasodilation. In addition, the Toronto NHD experience has reported an emerging body of evidence demonstrating the benefits of NHD on anemia management, inflammation, and endothelial progenitor cell biology. The mechanism(s) by which nocturnal hemodialysis improves cardiovascular outcomes are under active investigation by our group. It is tempting to speculate that NHD has the potential to decrease endothelial/myocardial injury and restore simultaneously endothelial repair, thereby improving cardiovascular function in patients with end-stage renal disease. The objectives of the present document are (1) to review the mechanisms underlying dialysis-associated cardiovascular morbidity and (2) to describe the restorative potential of NHD on the cardiovascular system.

Iohexol clearance is superior to creatinine-based renal function estimating equations in detecting short-term renal function decline in chronic heart failure.

PubMed

Cvan Trobec, Katja; Kerec Kos, Mojca; von Haehling, Stephan; Anker, Stefan D; Macdougall, Iain C; Ponikowski, Piotr; Lainscak, Mitja

2015-12-01

To compare the performance of iohexol plasma clearance and creatinine-based renal function estimating equations in monitoring longitudinal renal function changes in chronic heart failure (CHF) patients, and to assess the effects of body composition on the equation performance. Iohexol plasma clearance was measured in 43 CHF patients at baseline and after at least 6 months. Simultaneously, renal function was estimated with five creatinine-based equations (four- and six-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Cockcroft-Gault adjusted for lean body mass, Chronic Kidney Disease Epidemiology Collaboration equation) and body composition was assessed using bioimpedance and dual-energy x-ray absorptiometry. Over a median follow-up of 7.5 months (range 6-17 months), iohexol clearance significantly declined (52.8 vs 44.4 mL/[min ×1.73 m2], P=0.001). This decline was significantly higher in patients receiving mineralocorticoid receptor antagonists at baseline (mean decline -22% of baseline value vs -3%, P=0.037). Mean serum creatinine concentration did not change significantly during follow-up and no creatinine-based renal function estimating equation was able to detect the significant longitudinal decline of renal function determined by iohexol clearance. After accounting for body composition, the accuracy of the equations improved, but not their ability to detect renal function decline. Renal function measured with iohexol plasma clearance showed relevant decline in CHF patients, particularly in those treated with mineralocorticoid receptor antagonists. None of the equations for renal function estimation was able to detect these changes. ClinicalTrials.gov registration number: NCT01829880.

Long-term low-dose glucocorticoid therapy associated with remission of overt renal tubular acidosis in Sjögren's syndrome.

PubMed

el-Mallakh, R S; Bryan, R K; Masi, A T; Kelly, C E; Rakowski, K J

1985-10-01

Renal tubular acidosis and focal interstitial inflammatory cell infiltrate secondary to Sjögren's syndrome remitted with low-dose glucocorticoid therapy over five and one half years in a patient with associated mild systemic lupus erythematosus. Such response has not been previously documented. This observation may have therapeutic applications for renal tubular acidosis associated with Sjögren's syndrome that deserve further investigation.

Long-term nebivolol administration reduces renal fibrosis and prevents endothelial dysfunction in rats with hypertension induced by renal mass reduction.

PubMed

Pires, María J; Rodríguez-Peña, Ana B; Arévalo, Miguel; Cenador, Begoña; Evangelista, Stefano; Esteller, Alejandro; Sánchez-Rodríguez, Angel; Colaço, Aura; López-Novoa, José M

2007-12-01

D/L-Nebivolol is a lypophilic beta1-adrenergic antagonist which is devoid of intrinsic sympathomimetic activity and can increase nitric oxide (NO) bioavailability with its subsequent vasodilating properties. The purpose of the present work was to assess the effect of long-term nebivolol administration on both renal damage and endothelial dysfunction induced by renal mass reduction (RMR) in rats. Atenolol, which does not increase NO bioavailability, was included in the study as a comparative beta-adrenoceptor antagonist. Rats were subjected to both right nephrectomy and surgical removal of two-thirds of the left kidney in order to retain approximately one-sixth of the total renal mass. One week after ablation, rats were distributed randomly according to the following experimental groups: control group containing RMR rats without treatment; RMR rats treated daily with nebivolol for 6 months (drinking water, 8 mg/kg per day); and RMR rats treated daily with atenolol for 6 months (drinking water, 80 mg/kg per day). A group of sham-operated animals was also included. Administration of either nebivolol or atenolol similarly reduced arterial pressure in comparison with RMR untreated animals; however, animals receiving nebivolol presented lower levels of collagen type I expression as well as lower glomerular and interstitial fibrosis than those receiving atenolol. Urinary excretion of oxidative stress markers were also lower in animals receiving nebivolol than in rats treated with atenolol. Furthermore, nebivolol prevented RMR-induced endothelial dysfunction more efficiently than atenolol. Nebivolol protects against renal fibrosis, oxidative stress and endothelial dysfunction better than equivalent doses, in terms of arterial pressure reduction, of atenolol in a hypertensive model of renal damage induced by RMR.

Lifestyle intervention to improve quality of life and prevent weight gain after renal transplantation: Design of the Active Care after Transplantation (ACT) randomized controlled trial.

PubMed

Klaassen, Gerald; Zelle, Dorien M; Navis, Gerjan J; Dijkema, Desie; Bemelman, Frederike J; Bakker, Stephan J L; Corpeleijn, Eva

2017-09-15

Low physical activity and reduced physical functioning are common after renal transplantation, resulting in a reduced quality of life. Another common post-transplantation complication is poor cardio-metabolic health, which plays a main role in long-term outcomes in renal transplant recipients (RTR). It is increasingly recognized that weight gain in the first year after transplantation, especially an increase in fat mass, is a highly common contributor to cardio-metabolic risk. The aim of this study is to compare the outcomes of usual care to the effects of exercise alone, and exercise combined with dietary counseling, on physical functioning, quality of life and post-transplantation weight gain in RTR. The Active Care after Transplantation study is a multicenter randomized controlled trial with three arms in which RTR from 3 Dutch hospitals are randomized within the first year after transplantation to usual care, to exercise intervention (3 months supervised exercise 2 times per week followed by 12 months active follow-up), or to an exercise + diet intervention, consisting of the exercise training with additional dietary counseling (12 sessions over 15 months by a renal dietician). In total, 219 participants (73 per group) will be recruited. The primary outcome is the subdomain physical functioning of quality of life, (SF-36 PF). Secondary outcomes include other evaluations of quality of life (SF-36, KDQOL-SF, EQ-5D), objective measures of physical functioning (aerobic capacity and muscle strength), level of physical activity, gain in adiposity (body fat percentage by bio-electrical impedance assessment, BMI, waist circumference), and cardiometabolic risk factors (blood pressure, lipids, glucose metabolism). Furthermore, data on renal function, medical history, medication, psychological factors (motivation, kinesiophobia, coping style), nutrition knowledge, nutrition intake, nutrition status, fatigue, work participation, process evaluation and cost-effectiveness are collected. Evidence on the effectiveness of an exercise intervention, or an exercise + diet intervention on physical functioning, weight gain and cardiometabolic health in RTR is currently lacking. The outcomes of the present study may help to guide future evidence-based lifestyle care after renal transplantation. Number: NCT01047410 .

Cigarette smoking causes epigenetic changes associated with cardiorenal fibrosis

PubMed Central

Haller, Steven T.; Fan, Xiaoming; Xie, Jeffrey X.; Kennedy, David J.; Liu, Jiang; Yan, Yanling; Hernandez, Dawn-Alita; Mathew, Denzil P.; Cooper, Christopher J.; Shapiro, Joseph I.; Tian, Jiang

2016-01-01

Clinical studies indicate that smoking combustible cigarettes promotes progression of renal and cardiac injury, leading to functional decline in the setting of chronic kidney disease (CKD). However, basic studies using in vivo small animal models that mimic clinical pathology of CKD are lacking. To address this issue, we evaluated renal and cardiac injury progression and functional changes induced by 4 wk of daily combustible cigarette smoke exposure in the 5/6th partial nephrectomy (PNx) CKD model. Molecular evaluations revealed that cigarette smoke significantly (P < 0.05) decreased renal and cardiac expression of the antifibrotic microRNA miR-29b-3 and increased expression of molecular fibrosis markers. In terms of cardiac and renal organ structure and function, exposure to cigarette smoke led to significantly increased systolic blood pressure, cardiac hypertrophy, cardiac and renal fibrosis, and decreased renal function. These data indicate that decreased expression of miR-29b-3p is a novel mechanism wherein cigarette smoke promotes accelerated cardiac and renal tissue injury in CKD. (155 words) PMID:27789733

Application of regenerative medicine for kidney diseases.

PubMed

Yokoo, Takashi; Fukui, Akira; Kobayashi, Eiji

2007-01-01

Following recent advancements of stem cell research, the potential for organ regeneration using somatic stem cells as an ultimate therapy for organ failure has increased. However, anatomically complicated organs such as the kidney and liver have proven more refractory to stem cell-based regenerative techniques. At present, kidney regeneration is considered to require one of two approaches depending on the type of renal failure, namely acute renal failure (ARF) and chronic renal failure (CRF).The kidney has the potential to regenerate itself provided that the damage is not too severe and the kidney's structure remains intact. Regenerative medicine for ARF should therefore aim to activate or support this potent. In cases of the irreversible damage to the kidney, which is most likely in patients with CRF undergoing long-term dialysis, self-renewal is totally lost. Thus, regenerative medicine for CRF will likely involve the establishment of a functional whole kidney de novo. This article reviews the challenges and recent advances in both approaches and discusses the potential approach of these novel strategies for clinical application.

Endovascular Techniques for the Treatment of Renal Artery Aneurysms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elaassar, Omar, E-mail: elaassaro@yahoo.com; Auriol, Julien; Marquez, Romero

2011-10-15

Purpose: Our goal was to analyze the indications and limitations of the different percutaneous endovascular approaches reported for the treatment of renal artery aneurysms (RAAs) and to develop a scientific approach for optimum selection of treatment strategy of RAAs through analyzing our experience and reviewing available literature. Methods: This retrospective study was designed to evaluate the treatment and follow-up of 13 consecutive patients who presented with 13 RAAs by using a variety of endovascular interventional techniques. Different combinations of coil embolization, liquid embolization, stenting, and stent-graft exclusion were used in correlation with variable-specific aneurysm criteria. Results: All patients were successfullymore » treated with no significant short- or long-term complications. Patients were followed for an average period of 43 (range 13-103) months. Conclusions: Ten different determinants were found to affect our decision making: shape, size, neck, position of aneurysm on artery, branches arising, artery involved, condition of the artery, age, general condition of the patient, and renal function.« less

Association of mGFR of the Remaining Kidney Divided by Its Volume before Donation with Functional Gain in mGFR among Living Kidney Donors.

PubMed

Courbebaisse, Marie; Gaillard, François; Tissier, Anne-Marie; Fournier, Catherine; Le Nestour, Alexis; Corréas, Jean-Michel; Slimani-Thevenet, Hind; Martinez, Frank; Léon, Carine; Eladari, Dominique; Timsit, Marc-Olivier; Otal, Philippe; Hignette, Chantal; Friedlander, Gérard; Méjean, Arnaud; Houillier, Pascal; Kamar, Nassim; Legendre, Christophe

2016-08-08

The predictors of long-term renal function in living kidney donors are currently discussed. Our objectives were to describe the predictors of functional gain of the remaining kidney after kidney donation. We hypothesized that GFR of the remaining kidney divided by volume of this kidney (rk-GFR/vol) would reflect the density of functional nephrons and be inversely associated with functional gain of the remaining kidney. We conducted a prospective monocentric study including 63 living donors (26 men; 50.3±11.8 years old) who had been evaluated for (51)Cr-EDTA and measured GFR, split renal function by scintigraphy before donation (between 2004 and 2009), and measured GFR at 5.7±0.5 years after donation. For 52 donors, volume of the remaining kidney (measured and estimated with the ellipsoid formula using renal computed tomography scannography) was determined before donation. We tested our hypothesis in an external validation cohort of 39 living donors (13 men; 51.0±9.4 years old) from another single center during the same time period. For the main cohort, the mean measured GFR was 97.6±13.0 ml/min per 1.73 m(2) before donation and 63.8±9.4 ml/min per 1.73 m(2) at 5 years. Functional gain averaged 16.2±7.2 ml/min per 1.73 m(2) (+35.3%±16.7%). Multivariate analysis showed that age, body mass index, and rk-GFR/vol at donation were negatively correlated with functional gain and had strong predictive power of the 5-year functional gain (adjusted 5-year functional gain for age: -0.4 [95% confidence interval (95% CI), -0.5 to -0.1]; body mass index: -0.3 [95% CI, -0.6 to -0.1]; rk-GFR/vol: -55.1 [95% CI, -92.3 to -17.9]). We tested this model in the external validation cohort (adjusted 5-year functional gain for age: -0.1 [95% CI, -0.5 to 0.3]; body mass index: -0.9 [95% CI, -1.8 to -0.1]; rk-GFR/vol: -97.6 [95% CI, -137.5 to -57.6]) and confirmed that rk-GFR/vol was inversely associated with 5-year functional gain. For given age and body mass index, the long-term functional gain of the remaining kidney is inversely associated with the new variable rk-GFR/vol at donation. Copyright © 2016 by the American Society of Nephrology.

Divergent Effects of Hypertonic Fluid Resuscitation on Renal Pathophysiological and Structural Parameters in Rat Model of Lower Body Ischemia/Reperfusion-Induced Sterile Inflammation.

PubMed

Ergin, Bulent; Zuurbier, Coert J; Kapucu, Aysegul; Ince, Can

2017-12-27

The pathogenesis of acute kidney injury (AKI) is characterized by the deterioration of tissue perfusion and oxygenation and enhanced inflammation. The purpose of this study was to investigate whether or not the hemodynamic and inflammatory effects of hypertonic saline (HS) protect the kidney by promoting renal microcirculatory oxygenation and possible deleterious effects of HS due to its high sodium content on renal functional and structural injury following ischemia/reperfusion. Mechanically ventilated and anesthetized rats were randomly divided into four groups (n = 6 per group): a sham-operated control group; a group subjected to renal ischemia for 45 min by supra-aortic occlusion followed by 2 h of reperfusion (I/R); and I/R group treated with a continuous i.v. infusion (5 mL/kg/h) of either % 0.9 NaCl (IR+NS) or %10 NaCl (I/R+HS) after releasing the clamp. Systemic and renal hemodynamic, renal cortical (CμPO2), and medullar microcirculatory pO2 (MμPO2) are measured by the oxygen-dependent quenching of the phosphorescence lifetime technique. Renal functional, inflammatory, and tissues damage parameters were also assessed. HS, but not NS, treatment restored I/R-induced reduced mean arterial pressure, CμPO2, renal oxygen deliver (DO2ren), and consumption (VO2ren). HS caused a decrease in tubular sodium reabsorption (TNa) that correlated with an elevation of fractional sodium excretion (EFNa) and urine output. HS had an anti-inflammatory effect by reducing the levels TNF-α, IL-6, and hyaluronic acid in the renal tissue samples as compared with the I/R and I/R+NS groups (P < 0.05). HS treatment was also associated with mild acidosis and an increased renal tubular damage. Despite HS resuscitation improving the systemic hemodynamics, microcirculatory oxygenation, and renal oxygen consumption as well as inflammation, it should be limited or strictly controlled for long-term use because of provoking widespread renal structural damage.

Renal sympathetic denervation for resistant hypertension.

PubMed

Froeschl, Michael; Hadziomerovic, Adnan; Ruzicka, Marcel

2013-05-01

Resistant hypertension is an increasingly prevalent health problem associated with important adverse cardiovascular outcomes. The pathophysiology that underlies this condition involves increased function of both the sympathetic nervous system and the renin-angiotensin II-aldosterone system. A crucial link between these 2 systems is the web of sympathetic fibres that course within the adventitia of the renal arteries. These nerves can be targeted by applying radiofrequency energy from the lumen of the renal arteries to renal artery walls (percutaneous renal sympathetic denervation [RSD]), an approach that has attracted great interest. This paper critically reviews the evidence supporting the use of RSD. Small studies suggest that RSD can produce dramatic blood pressure reductions: In the randomized Symplicity HTN-2 trial of 106 patients, the mean fall in blood pressure at 6 months in patients who received the treatment was 32/12 mm Hg. However, there are limitations to the evidence for RSD in the treatment of resistant hypertension. These include the small number of patients studied; the lack of any placebo-controlled evidence; the fact that blood pressure outcomes were based on office assessments, as opposed to 24-hour ambulatory monitoring; the lack of longer-term efficacy data; and the lack of long-term safety data. Some of these concerns are being addressed in the ongoing Renal Denervation in Patients With Uncontrolled Hypertension (Symplicity HTN-3) trial. The first percutaneous RSD system was approved by Health Canada in the spring of 2012. But until more and better-quality data are available, this procedure should generally be reserved for those patients whose resistant hypertension is truly uncontrolled. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients.

PubMed

McAdoo, Stephen P; Tanna, Anisha; Hrušková, Zdenka; Holm, Lisa; Weiner, Maria; Arulkumaran, Nishkantha; Kang, Amy; Satrapová, Veronika; Levy, Jeremy; Ohlsson, Sophie; Tesar, Vladimir; Segelmark, Mårten; Pusey, Charles D

2017-09-01

Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such 'double-positive' cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and 37 double-positive patients with ANCA and anti-GBM disease from four European centers. Double-positive patients shared characteristics of ANCA-associated vasculitis (AAV), such as older age distribution and longer symptom duration before diagnosis, and features of anti-GBM disease, such as severe renal disease and high frequency of lung hemorrhage at presentation. Despite having more evidence of chronic injury on renal biopsy compared to patients with anti-GBM disease, double-positive patients had a greater tendency to recover from being dialysis-dependent after treatment and had intermediate long-term renal survival compared to the single-positive patients. However, overall patient survival was similar in all three groups. Predictors of poor patient survival included advanced age, severe renal failure, and lung hemorrhage at presentation. No single-positive anti-GBM patients experienced disease relapse, whereas approximately half of surviving patients with AAV and double-positive patients had recurrent disease during a median follow-up of 4.8 years. Thus, double-positive patients have a truly hybrid disease phenotype, requiring aggressive early treatment for anti-GBM disease, and careful long-term follow-up and consideration for maintenance immunosuppression for AAV. Since double-positivity appears common, further work is required to define the underlying mechanisms of this association and define optimum treatment strategies. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Do the outcomes of living donor renal allograft recipients differ with peritoneal dialysis and hemodialysis as a bridge renal replacement therapy?

PubMed

Prasad, Narayan; Vardhan, Harsh; Baburaj, Vinod P; Bhadauria, Dharmendra; Gupta, Amit; Sharma, Raj K; Kaul, Anupama

2014-11-01

This study was undertaken to compare the outcomes of living donor renal transplant recipients using peritoneal dialysis (PD) and hemodialysis (HD) as a bridge modality for renal replacement therapy till renal transplantation. The demographic profiles of the recipients and donors, the patients' native kidney disease (diabetic versus non-diabetic), duration on dialysis, requirement of anti-hypertensive drugs, number of blood transfusions, human leukocyte antigen (HLA) mismatch status, pre- and post-transplant infectious complications, and post-transplant outcomes of patients were compared between the two groups. The demographic features of the study patients were similar in the two groups. The duration of dialysis prior to transplant was significantly longer in the PD group than in the HD group of patients. The anti-hypertensive drug requirement was lower and the hemoglobin level and residual urine volume at the time of transplant were relatively better in the PD patients compared to the HD patients. The number of acute rejection episodes, delayed graft function, surgical complications, glomerular filtration rate at one month and at the last follow-up, were also similar in both groups. The short-term and long-term graft survival was similar in both groups of patients. The one-, two-, five-, and eight-year death-censored graft survival rates of the PD patients were 98, 95, 85, and 73%, respectively, and in the HD group of patients, they were 100, 93, 84, and 79%, respectively. The one-, two-, five-, and eight-year patient survival rates in the PD group were 97, 92, 77, and 66%, respectively, and in the HD group, they were 97, 92, 79, and 69%, respectively. Our study suggests that the outcomes of the living donor renal allograft recipients did not differ between the groups of patients who used PD or HD as renal replacement therapy prior to renal transplantation.

Long-term Outcome of Lupus Nephritis Class II in Argentine Patients

PubMed Central

Collado, Maria Victoria; Dorado, Enrique; Rausch, Silvia; Gomez, Graciela; Khoury, Marina; Zazzetti, Federico; Gargiulo, María; Suarez, Lorena; Chaparro, Rafael; Paira, Sergio; Galvan, Laura; Juarez, Vicente; Pisoni, Cecilia; Garcia, Mercedes; Martinez, Liliana; Alvarez, Analia; Alvarez, Clarisa; Barreira, Juan; Sarano, Judith

2016-01-01

Background There is controversy in medical literature over the outcome of patients with lupus nephritis (LN) class II. The aim of this study was to explore the risk of histological transformation (HT) and possible factors related to negative response to treatment in patients with mesangial LN class II. Methods A retrospective and multicenter study was carried out that includes patients who had received a diagnosis of LN class II on their first renal biopsy. Creatinine, urine sediment, and proteinuria were recorded at the time of the first biopsy, 6 months, and 1, 2, and 5 years after the first biopsy. Response to treatment, HT, and long-term outcome were evaluated. Results Forty-one patients were included. The manifestation at first biopsy was proteinuria greater than 0.5 g/d in 28 patients (68.29%; 8 [28.57%] of 28 patients had nephrotic syndrome), hematuria in 18 patients (43.90%), and deterioration of renal function in 3 patients (7.31%). During the follow-up (median, 8 years; range, 1–35 years), a new biopsy was performed in 18 patients (43.90%), and in 17 patients (17/18 [94.44%]), there was HT. Median time at rebiopsy was 32 months (range, 11–305 months). Of the 18 patients who had a second biopsy, 10 (55.55%) were on hydroxychloroquine versus 100% (19/19) of patients who did not undergo the procedure (P = 0.001). A year after the first renal biopsy, there are data available from 34 patients; of them, 24 patients (70.58%) had achieved response, and 10 patients (29.41%) had no response (NR) (missing data in 7). A higher 24-hour urinary protein at 6 months was predictor of worse outcome at 1 year, with statistical significance difference for the nonresponder group (median proteinuria, 2.3 g/d [range, 0–4.7 g/d]) compared with responders (median proteinuria, 0.28 g/d [range, 0–1.7 g/d]) (P = 0.0133). In the long-term follow-up (5 years), HT was the main cause of unfavorable outcome and was measured in 78.57% of patients (11/14 patients). Conclusions This series shows a high rate of HT in long-term follow-up. Proteinuria at 6 months made it possible to set aside patients who will have an unfavorable outcome in the long term and who will thus benefit from a more aggressive treatment. The results suggest that hydroxychloroquine had a nephroprotective effect. PMID:27152693

Assessment of the Renal Function in Potential Donors of Living Kidney Transplants: Expanded Study.

PubMed

Macías, L B; Poblet, M S; Pérez, N N; Jerez, R I; Gonzalez Roncero, F M; Blanco, G B; Valdivia, M A P; Benjumea, A S; Gentil Govantes, M A

2015-11-01

It is very important to determine as accurately as possible the renal function in potential living renal transplant donors, especially those with limited renal function (CrCl <90 mL/m/1.73 m(2)), age older than 50 years, and cardiovascular risk factors that might favor the development of long-term kidney diseases. The objective of this study was to compare the direct measurement of glomerular filtration rate (GFR) using EDTA-Cr51 and the estimations based on creatinine (eGFR): Cr clearance (CCr) with 24-hour urine and estimated using Cockroft-Gault (adjusted by using body surface area-Mosteller formula-SC), MDRD-4, MDRD-6, and CKD-EPI to determine the usefulness of different methods from EDTA-Cr51to evaluate the kidney function. The kidney function evaluation has been made to 105 potential kidney donors using the EDTA-Cr51 method. The GFR obtained through the EDTA-Cr51 is compared with the CCr values in 24-hour urine and eGFR based on creatinine (Cockcroft-Gault, MDRD4, MDRD6, and CKD-EPI). Using the Bland Altman graphic we have observed that the most dispersed results are obtained with the eGFR using CCr in 24-hour urine and CKD-EPI. By means of Pasing & Bablock, we realized that MDRD-4 and MDRD-6 show the highest approximation to the reference method proposed to be substituted, whereas CCr shows a high dispersion. eGFR using MDRD-4 and MDRD-6 formulas reveal the best adjustment to the measure by EDTA-Cr51. This might represent the best option if a direct eGFR measure is not available. Copyright © 2015 Elsevier Inc. All rights reserved.

Amelioration of renal ischaemia–reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells

PubMed Central

Rogers, NM; Stephenson, MD; Kitching, AR; Horowitz, JD; Coates, PTH

2012-01-01

BACKGROUND AND PURPOSE Renal ischaemia–reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. EXPERIMENTAL APPROACH We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. KEY RESULTS Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. CONCLUSIONS AND IMPLICATIONS Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. PMID:21745189

Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.

PubMed

Rogers, N M; Stephenson, M D; Kitching, A R; Horowitz, J D; Coates, P T H

2012-05-01

Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Diffuse vascular damage in a transplanted kidney: an indication for nuclear magnetic resonance?

PubMed

Burdese, M; Consiglio, V; Mezza, E; Savio, D; Guarena, C; Rossetti, M; Messina, M; Soragna, G; Suriani, C; Rabbia, C; Segoloni, G P; Piccoli, G B

2005-06-01

Vascular lesions are an increasing challenge after renal transplantation due to the wider indications for recipients and acceptance criteria for donors. Diagnostic approach and prognostic interpretation are still matter of controversy. The case reported herein may summarize some of the issues in this regard. A 54-year-old woman, on renal replacement therapy since 1974, and a kidney graft recipient from 1975 to 1999, received a second graft in 2001. The donor age was 65 years (cold ischemia 22 hours; two mismatches). The early posttransplant follow-up was characterized by delayed graft function, hypertension, and diabetes. During the initial hypertension workup, renal graft ultrasound (US) Doppler demonstrated increased vascular resistances, stable over time (resistance index 0.74 to 0.77); renal scintiscan displayed homogeneously parenchymoa and angio-magnetic resonance imaging (MRI), an homogeneous parenchymal vascularization. Initial immunosuppression with tacrolimus and steroids was modulated by adding mycophenolate mofetil to taper tacrolimus (to reduce nephrotoxicity and hypertension). Despite this, kidney function slowly deteriorated; serum creatinine reached 3 to 3.5 mg/dL by the second year. After a severe hypertensive crisis with unchanged scintiscan and US doppler examinations, angio-MRI revealed the almost complete disappearance of parenchymal enhancement beyond the lobar arteries. A renal biopsy confirmed the severe vascular damage. The patient was switched to rapamycine and a low-dose of an angiotension converting enzyme (ACE) inhibitor. She did relatively well (serum creatinine 2.2 to 3 mg/dL) for 6 months, when rapid functional impairment forced her to restart hemodialysis. This case, almost paradigmatic of the problems occurring when the rigid vasculature of long-term dialysis patients is matched with "marginal kidneys," suggests that MRI may be a sensible good to define vascular damage in the grafted kidney.

Impact of warm ischaemia time on postoperative renal function after partial nephrectomy for clinical T1 renal cell carcinoma: a propensity score-matched study.

PubMed

Lee, Hakmin; Song, Byung D; Byun, Seok-Soo; Lee, Sang E; Hong, Sung K

2018-01-01

To analyse the effect of prolonged warm ischaemia time (WIT) on long-term renal function after partial nephrectomy (PN), as controversy still exists as to whether prolonged WIT adversely affects the incidence of chronic kidney disease (CKD) after PN. We reviewed data from 1816 patients who underwent PN for a clinical T1 renal tumour. The propensity scores for prolonged WIT were calculated with the shorter WIT group (<30 min) matched to the longer WIT group (≥30 min) in a 2:1 ratio. Multivariate analysis was used to determine independent predictors for occurrence of postoperative CKD [defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m 2 ] and major renal function deterioration (MRFD; defined as an eGFR decrease of ≥25% postoperatively). After propensity score matching, there was no significant difference in CKD-free survival between the two WIT groups (P = 0.787). Furthermore, longer WIT did not show any significant associations with postoperative CKD-free survival [hazard ratio (HR) 1.002, 95% confidence interval (CI) 0.989-1.015; P = 0.765) and MRFD-free survival (HR 1.014, 95% CI 1.000-1.028; P = 0.055). From further subgroup analyses using more specific WIT thresholds (≤20, 21-30, 31-40, 41-50, ≥50 min) and status of preoperative CKD, no significant differences were noted in CKD and MRFD-free survival amongst the subgroups (all P > 0.05). Prolonged WIT was not associated with increased incidence of CKD or MRFD after PN. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Safety and efficacy of skin patches containing loxoprofen sodium in diabetic patients with overt nephropathy.

PubMed

Araki, Hisazumi; Kuwagata, Shogo; Soumura, Mariko; Yamahara, Kosuke; Morita, Yoshikata; Kume, Shinji; Isshiki, Keiji; Araki, Shin-ichi; Kashiwagi, Atsunori; Maegawa, Hiroshi; Uzu, Takashi

2014-06-01

Because oral nonsteroidal anti-inflammatory drugs (NSAIDs) have adverse effects on kidney function, patients with kidney diseases are administered these drugs as transdermal patches. Little is known about the effects of NSAID patches on renal function. We therefore assessed the effects of topical loxoprofen sodium on kidney function in type 2 diabetic patients with overt nephropathy. Twenty patients with type 2 diabetes and overt proteinuria and with knee and/or low back pain were treated with skin patches containing 100 mg loxoprofen on the knee or back for 24 h per day for 5 consecutive days. The degree of pain was assessed using a visual analogue scale (VAS). Blood and 24-h urine samples were obtained at baseline and at the end of the study. Glomerular filtration rate (GFR) was estimated from serum creatinine and cystatin C concentrations. The 20 patients consisted of 11 males and 9 females, of mean age 61.6 ± 13.9 years. Loxoprofen-containing patches significantly reduced VAS pain without affecting blood pressure, GFR or urinary prostaglandin E2 concentration. Serum concentrations of loxoprofen and its active trans-OH metabolite did not correlate with GFR. Loxoprofen-containing patches do not affect renal function in type 2 diabetic patients with overt nephropathy over a short-term period. Long-term studies are needed to clarify the safety of loxoprofen-containing patches in patients with chronic kidney diseases.

Identification of a B cell signature associated with renal transplant tolerance in humans

PubMed Central

Newell, Kenneth A.; Asare, Adam; Kirk, Allan D.; Gisler, Trang D.; Bourcier, Kasia; Suthanthiran, Manikkam; Burlingham, William J.; Marks, William H.; Sanz, Ignacio; Lechler, Robert I.; Hernandez-Fuentes, Maria P.; Turka, Laurence A.; Seyfert-Margolis, Vicki L.

2010-01-01

Establishing long-term allograft acceptance without the requirement for continuous immunosuppression, a condition known as allograft tolerance, is a highly desirable therapeutic goal in solid organ transplantation. Determining which recipients would benefit from withdrawal or minimization of immunosuppression would be greatly facilitated by biomarkers predictive of tolerance. In this study, we identified the largest reported cohort to our knowledge of tolerant renal transplant recipients, as defined by stable graft function and receiving no immunosuppression for more than 1 year, and compared their gene expression profiles and peripheral blood lymphocyte subsets with those of subjects with stable graft function who are receiving immunosuppressive drugs as well as healthy controls. In addition to being associated with clinical and phenotypic parameters, renal allograft tolerance was strongly associated with a B cell signature using several assays. Tolerant subjects showed increased expression of multiple B cell differentiation genes, and a set of just 3 of these genes distinguished tolerant from nontolerant recipients in a unique test set of samples. This B cell signature was associated with upregulation of CD20 mRNA in urine sediment cells and elevated numbers of peripheral blood naive and transitional B cells in tolerant participants compared with those receiving immunosuppression. These results point to a critical role for B cells in regulating alloimmunity and provide a candidate set of genes for wider-scale screening of renal transplant recipients. PMID:20501946

Renal transplantation in Indo-Asian patients in the UK.

PubMed

Dooldeniya, M D; Dupont, P J; He, X; Johnson, R J; Joshi, T; Basra, R; Johnston, A; Warrens, A N

2006-04-01

Membership of some ethnic groups has an effect on renal transplant outcome but little is known about the impact of Indo-Asian ethnicity, despite this group's high incidence of renal disease. We compared outcomes in Indo-Asians and Caucasians at the Hammersmith Hospital (Indo-Asians, N = 46; Caucasians, N = 90), in the Long-Term Efficacy and Safety Surveillance (LOTESS) database of cyclosporin-treated renal transplant recipients (Indo-Asians, N = 254; Caucasians, N = 4262) and the National Transplant Database held by UK Transplant (Indo-Asians, N = 459; Caucasians, N = 4831). The baseline demographic and co-morbid characteristics of the two ethnic groups were comparable, save for more diabetes in the Indo-Asian community. Following transplantation, the incidence of delayed graft function and steroid-resistant acute rejection were also comparable, as were graft and patient survival (out to 5 years) and graft function. In addition, post-transplant blood pressure, levels of cholesterol and triglycerides and exposure to corticosteroids and cyclosporin were comparable. However, when patients who were not diabetic before transplantation were studied separately, there was an increased incidence of diabetes in the Indo-Asian community (Hammersmith data: Indo-Asians 10.9% vs. Caucasians 3.3%, p = 0.02; LOTESS data Indo-Asians 5.5% vs. Caucasians 1.6%, p < 0.0001). Subsequent management of this group should pursue immunosuppressive regimens less likely to impair post-transplant glucose tolerance.

Skin autofluorescence as a measure of advanced glycation endproduct deposition: a novel risk marker in chronic kidney disease.

PubMed

Smit, Andries J; Gerrits, Esther G

2010-11-01

Skin autofluorescence (SAF) is a new method to noninvasively assess accumulation of advanced glycation endproducts (AGEs) in a tissue with low turnover. Recent progress in the clinical application of SAF as a risk marker for diabetic nephropathy as well as cardiovascular disease in nondiabetic end-stage kidney disease, less advanced chronic kidney disease, and renal transplant recipients is reviewed. Experimental studies highlight the fundamental role of the interaction of AGEs with the receptor for AGEs (RAGEs), also called the AGE-RAGE axis, in the pathogenesis of vascular and chronic kidney disease. SAF predicts (cardiovascular) mortality in renal failure and also chronic renal transplant dysfunction. Long-term follow-up results from the Diabetes Control and Complications Trial and UK Prospective Diabetes Study suggest that AGE accumulation is a key carrier of metabolic memory and oxidative stress. Short-term intervention studies in diabetic nephropathy with thiamine, benfotiamine and angiotensin-receptor blockers aimed at reducing AGE formation have reported mixed results. SAF is a noninvasive marker of AGE accumulation in a tissue with low turnover, and thereby of metabolic memory and oxidative stress. SAF independently predicts cardiovascular and renal risk in diabetes, as well as in chronic kidney disease. Further long-term studies are required to assess the potential benefits of interventions to reduce AGE accumulation.

Extracorporeal shockwave lithotripsy in infants.

PubMed

Ramakrishnan, Prem A; Medhat, Mohammed; Al-Bulushi, Younis H; Nair, Priti; Al-Kindy, Ahmed

2007-10-01

Pediatric urolithiasis is relatively uncommon and limited information is available on the application of minimally invasive management modalities in young children. We present a single centre experience with extracorporeal shockwave lithotripsy (ESWL) for infants with upper urinary tract calculi. A total of 74 infants aged 3 months to 24 months with upper urinary tract calculi were treated with ESWL under general anesthesia using the Wolf 2500 and the 2501 Piezolith lithotriptors over a 14 and a half-year period. Patient and stone characteristics, risk factors for urolithiasis, treatment parameters, clinical outcomes and long-term follow-up were assessed and recorded. The mean patient age was 14.5 (range 3 to 24) months. The mean renal stone size was 18.2 (range 7 to 32) mm while the mean ureteral stone size was 9.4 (range 5 to 14) mm. Metabolic abnormalities, structural anomalies and urinary tract infections were identified as contributory factors for stone formation in 34% of the infants. At the 3-month follow-up there was an overall successful outcome in 72 infants (97%) that included 65 (88%) who were rendered stone-free and 7 (9%) who had clinically insignificant stone fragments. Retreatment was required in 27 (35%) patients, auxiliary procedures after ESWL were needed in 5 (7%) and secondary operative procedures were required in 2 (3%). Major complications were encountered in 5 (7%) patients that included complete ureteral obstruction with sepsis in 2, partial ureteral obstruction in 1 and febrile urinary tract infection in 2 other children. Long-term follow-up was recorded in 39 infants: 8 developed recurrent stones, 2 had stone regrowth and 1 developed mild hypertension but none had significant deterioration of renal function. ESWL is an effective treatment for upper urinary tract calculi in infants. In the short-term, complications are minimal but long-term follow-up is important.

Urinary tract infections in the infant.

PubMed

Arshad, Mehreen; Seed, Patrick C

2015-03-01

Urinary tract infection (UTI) in an infant may be the first indication of an underlying renal disorder. Early recognition and initiation of adequate therapy for UTI is important to reduce the risk of long-term renal scarring. Ampicillin and gentamicin are traditionally the empiric treatment of choice; however, local antibiotic resistance patterns should be considered. Maternal antibiotics during pregnancy also increase the risk of resistant pathogens during neonatal UTI. Long-term management after the first UTI in infants remains controversial because of lack of specific studies in this age group and the risk-benefit issues for antibiotic prophylaxis between reduced recurrent disease and emergent antibiotic resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

Iohexol clearance is superior to creatinine-based renal function estimating equations in detecting short-term renal function decline in chronic heart failure

PubMed Central

Cvan Trobec, Katja; Kerec Kos, Mojca; von Haehling, Stephan; Anker, Stefan D.; Macdougall, Iain C.; Ponikowski, Piotr; Lainscak, Mitja

2015-01-01

Aim To compare the performance of iohexol plasma clearance and creatinine-based renal function estimating equations in monitoring longitudinal renal function changes in chronic heart failure (CHF) patients, and to assess the effects of body composition on the equation performance. Methods Iohexol plasma clearance was measured in 43 CHF patients at baseline and after at least 6 months. Simultaneously, renal function was estimated with five creatinine-based equations (four- and six-variable Modification of Diet in Renal Disease, Cockcroft-Gault, Cockcroft-Gault adjusted for lean body mass, Chronic Kidney Disease Epidemiology Collaboration equation) and body composition was assessed using bioimpedance and dual-energy x-ray absorptiometry. Results Over a median follow-up of 7.5 months (range 6-17 months), iohexol clearance significantly declined (52.8 vs 44.4 mL/[min ×1.73 m2], P = 0.001). This decline was significantly higher in patients receiving mineralocorticoid receptor antagonists at baseline (mean decline -22% of baseline value vs -3%, P = 0.037). Mean serum creatinine concentration did not change significantly during follow-up and no creatinine-based renal function estimating equation was able to detect the significant longitudinal decline of renal function determined by iohexol clearance. After accounting for body composition, the accuracy of the equations improved, but not their ability to detect renal function decline. Conclusions Renal function measured with iohexol plasma clearance showed relevant decline in CHF patients, particularly in those treated with mineralocorticoid receptor antagonists. None of the equations for renal function estimation was able to detect these changes. ClinicalTrials.gov registration number NCT01829880 PMID:26718759

Losartan increases NO release in afferent arterioles during regression of L-NAME-induced renal damage.

PubMed

Helle, Frank; Iversen, Bjarne M; Chatziantoniou, Christos

2010-05-01

Inhibition of nitric oxide synthesis (NOS) induces hypertension and heavy proteinuria. Renal structure and function have shown striking improvement after interventions targeting ANG II or endothelin (ET) receptors in rats recovering after long-term NOS inhibition. To search for mechanisms underlying losartan-assisted regression of renal disease in rodents, we measured NO release and contractility to ET in afferent arterioles (AAs) from Sprague-Dawley rats recovering for 2 wk after 4 wk of N(G)-nitro-L-arginine methyl ester treatment. Losartan administration during the recovery period decreased blood pressure (113 ± 4 vs. 146 ± 5 mmHg, P < 0.01), reduced protein/creatinine ratio more (proteinuria decrease: Δ1,836 ± 214 vs. Δ1,024 ± 180 mg/mmol, P < 0.01), and normalized microvascular hypertrophy (AA media/lumen ratio: 1.74 ± 0.05 vs. 2.09 ± 0.08, P < 0.05) compared with no treatment. In diaminofluorescein-FM-loaded AAs from losartan-treated animals, NO release (% of baseline) was increased compared with untreated animals after stimulation with 10(-7) M ACh (118 ± 4 vs. 90 ± 7%, t = 560 s, P < 0.001) and 10(-9) M ET (123 ± 4 vs. 101 ± 5%, t = 560 s, P < 0.001). There was also a blunted contractile response to 10(-7) M ET in AAs from losartan-treated animals compared with untreated animals (Δ4.01 ± 2.9 vs. Δ14.6 ± 1.7 μm, P < 0.01), which disappeared after acute NOS inhibition (Δ10.7 ± 3.7 vs. Δ12.5 ± 2.9 μm, not significant). Contractile dose responses to ET (10(-9), 10(-8), 10(-7) M) were enhanced by NOS inhibition and blunted by exogenous NO (10(-2) mM S-nitroso-N-acetyl-penicillamine) in losartan-treated but not in untreated vessels. Reducing blood pressure similar to losartan with hydralazine did not improve AA hypertrophy, ET-induced contractility, ET-induced NO release, and NO sensitivity. In conclusion, blockade of the local action of ANG II improved endothelial function in AAs, a mechanism that is likely to contribute to the beneficial effects of AT(1a)R antagonism during the recovery of renal function after long-term NOS inhibition in rats.

Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling

PubMed Central

Yu, Hao; Yang, Tao; Gao, Peng; Wei, Xing; Zhang, Hexuan; Xiong, Shiqiang; Lu, Zongshi; Li, Li; Wei, Xiao; Chen, Jing; Zhao, Yu; Arendshorst, William J.; Shang, Qianhui; Liu, Daoyan; Zhu, Zhiming

2016-01-01

High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na+ channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC. PMID:27173481

Acute Kidney Injury Classification Underestimates Long-Term Mortality After Cardiac Valve Operations.

PubMed

Bouma, Hjalmar R; Mungroop, Hubert E; de Geus, A Fred; Huisman, Daniel D; Nijsten, Maarten W N; Mariani, Massimo A; Scheeren, Thomas W L; Burgerhof, Johannes G M; Henning, Robert H; Epema, Anne H

2018-03-01

Perioperative acute kidney injury (AKI) is an important predictor of long-term all-cause mortality after coronary artery bypass (CABG). However, the effect of AKI on long-term mortality after cardiac valve operations is hitherto undocumented. Perioperative renal injury and long-term all-cause mortality after valve operations were studied in a prospective cohort of patients undergoing solitary valve operations (n=2,806) or valve operations combined with CABG (n=1,260) with up to 18 years of follow-up. Postoperative serum creatinine increase was classified according to AKI 0-3. Patients undergoing solitary CABG (n=4,938) with cardiopulmonary bypass served as reference. In both valve and valve+CABG operations, postoperative renal injury of AKI stage 1 or higher was progressively associated with an increase in long-term mortality (HR 2.27, p<0.05 for valve; HR 1.65, p<0.05 for valve operations combined with CABG; HR 1.56, p<0.05 for CABG). Notably, the mortality risk increased already substantially at serum creatinine rises of 10-25%, i.e. far below the threshold for AKI stage 1 after valve operations (HR 1.39, p<0.05), but not after valve operations combined with CABG or CABG only. An increase in serum creatinine by more than 10%during the first week following valve operation is associated with an increased risk for long-term mortality following cardiac valve operation. Thus, AKI-classification clearly underestimates long-term mortality risk in patients undergoing valve operations. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Long-term maintenance of weight loss after lifestyle intervention in frail, obese older adults.

PubMed

Waters, D L; Vawter, R; Qualls, C; Chode, S; Armamento-Villareal, R; Villareal, D T

2013-01-01

To determine if long-term weight loss with associated improvement in physical and metabolic health can be maintained after lifestyle intervention in frail, obese older adults. Thirty-month follow-up pilot study of a 1-year lifestyle intervention trial. Community. Sixteen frail, obese (body mass index=36±2 kg/m2) older (71±1 yr.) adults. Body weight and composition, physical function, markers of the metabolic syndrome, glucose and insulin response to an oral glucose tolerance test, bone mineral density (BMD), liver and renal function tests, and food diaries. At 30-month follow-up, weight (101.5±3.8 vs. 94.5±3.9 kg) and BMI (36.0 ±1.7 vs. 33.5±1.7 kg/m2) remained significantly below baseline (all p<0.05). No significant change in fat-free mass (56.7±2.1 vs. 56.9±2.2 kg) or appendicular lean mass (24.1±1.0 vs. 24.1±1.1kg, all p>0.05) occurred between 12 months (end of trial) and 30 months. Improvements in the physical performance test (PPT 27±0.7 vs. 30.2±0.6), insulin sensitivity (4.1±0.8 vs. 3.0±0.6), and insulin area under the curve (12484±2042 vs. 9270±1139 min.mg/dl) remained at 30 months compared to baseline (all p<0.05). Waist circumference (116±3 vs. 109±3 cm) and systolic blood pressure (134±6 vs. 123±5 mm HG) remained decreased at 30 months compared to baseline (all p<0.05). Whole body and lumbar spine BMD did not change; however, total hip BMD progressively decreased at 30 months compared to baseline (0.985±.026 vs. 0.941±.024 g/cm2; p<0.05). There were no adverse effects on liver or renal function. Food frequency questionnaire data showed lower overall caloric intake (-619±157 kcal/day) at 30 months compared to baseline (p<0.05). These findings suggest that long-term maintenance of clinically important weight loss is possible in frail, obese older adults. Weight maintenance appears to be achieved through continued caloric restriction. Larger, long-term studies are needed to follow up on these findings and investigate mechanisms and behaviors underlying maintenance of weight loss and physical function.

A Short-Term Biological Indicator for Long-Term Kidney Damage after Radionuclide Therapy in Mice

PubMed Central

Pellegrini, Giovanni; Siwowska, Klaudia; Haller, Stephanie; Antoine, Daniel J.; Schibli, Roger; Kipar, Anja; Müller, Cristina

2017-01-01

Folate receptor (FR)-targeted radionuclide therapy using folate radioconjugates is of interest due to the expression of the FR in a variety of tumor types. The high renal accumulation of radiofolates presents, however, a risk of radionephropathy. A potential option to address this challenge would be to use radioprotectants, such as amifostine. Methods for early detection of kidney damage that—in this case—cannot be predicted based on dose estimations, would facilitate the development of novel therapies. The aim of this study was, therefore, to assess potentially changing levels of plasma and urine biomarkers and to determine DNA damage at an early stage after radiofolate application. The identification of an early indicator for renal damage in mice would be useful since histological changes become apparent only several months after treatment. Mice were injected with different quantities of 177Lu-folate (10 MBq, 20 MBq and 30 MBq), resulting in mean absorbed kidney doses of ~23 Gy, ~46 Gy and ~69 Gy, respectively, followed by euthanasia two weeks (>85% of the mean renal radiation dose absorbed) or three months later. Whereas all investigated biomarkers remained unchanged, the number of γ-H2AX-positive nuclei in the renal cortex showed an evident dose-dependent increase as compared to control values two weeks after treatment. Comparison with the extent of kidney injury determined by histological changes five to eight months after administration of the same 177Lu-folate activities suggested that the quantitative assessment of double-strand breaks can be used as a biological indicator for long-term radiation effects in the kidneys. This method may, thus, enable faster assessment of radiopharmaceuticals and protective measures by preventing logistically challenging long-term investigations to detect kidney damage. PMID:28635637

Metabolic and hemodynamic effects of sodium-dependent glucose cotransporter 2 inhibitors on cardio-renal protection in the treatment of patients with type 2 diabetes mellitus.

PubMed

Kashiwagi, Atsunori; Maegawa, Hiroshi

2017-07-01

The specific sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) inhibit glucose reabsorption in proximal renal tubular cells, and both fasting and postprandial glucose significantly decrease because of urinary glucose loss. As a result, pancreatic β-cell function and peripheral insulin action significantly improve with relief from glucose toxicity. Furthermore, whole-body energy metabolism changes to relative glucose deficiency and triggers increased lipolysis in fat cells, and fatty acid oxidation and then ketone body production in the liver during treatment with SGLT2 inhibitors. In addition, SGLT2 inhibitors have profound hemodynamic effects including diuresis, dehydration, weight loss and lowering blood pressure. The most recent findings on SGLT2 inhibitors come from results of the Empagliflozin, Cardiovascular Outcomes and Mortality in Type 2 Diabetes trial. SGLT2 inhibitors exert extremely unique and cardio-renal protection through metabolic and hemodynamic effects, with long-term durability on the reduction of blood glucose, bodyweight and blood pressure. Although a site of action of SGLT2 inhibitors is highly specific to inhibit renal glucose reabsorption, whole-body energy metabolism, and hemodynamic and renal functions are profoundly modulated during the treatment of SGLT2 inhibitors. Previous studies suggest multifactorial clinical benefits and safety concerns of SGLT2 inhibitors. Although ambivalent clinical results of this drug are still under active discussion, the present review summarizes promising recent evidence on the cardio-renal and metabolic benefits of SGLT2 inhibitors in the treatment of type 2 diabetes. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Personalized design and virtual evaluation of physician-modified stent grafts for juxta-renal abdominal aortic aneurysms

NASA Astrophysics Data System (ADS)

Sanathkhani, Soroosh; Shroff, Sanjeev G.; Menon, Prahlad G.

2017-02-01

Endovascular aneurysm repair (EVAR) of juxtarenal aortic aneurysms (JAA) is particularly challenging owing to the requirement of suprarenal EVAR graft fixation, which has been associated with significant declines in long term renal function. Therefore, the ability to design fenestrated EVAR grafts on a personalized basis in order to ensure visceral and renal perfusion, is highly desirable. The objectives of this study are: a) To demonstrate novel 3D geometric methods to virtually design and deploy EVAR grafts into a virtually designed JAA, by applying a custom surface mesh deformation tool to a patient-specific descending aortic model reconstructed from computed tomographic (CT) images; and b) To virtually evaluate patient-specific renal flow and wall stresses in these patient-specific virtually EVAR geometries, using computational fluid dynamics (CFD). The presented framework may provide the modern cardiovascular surgeon the ability to leverage non-invasive, pre-operative imaging equipment to personalize and guide EVAR therapeutic strategy. Our CFD studies revealed that virtual EVAR grafting of a patient-specific JAA, with optimal fenestration sites and renal stenting, led to a 179.67±15.95% and 1051.43±18.34% improvement in right and left renal flow rates, respectively, when compared with the baseline patient-specific aortic geometry with renal stenoses, whereas a right and left renal flow improved by 36.44±2.24% and 885.93±12.41%, respectively, relative to the equivalently modeled JAA with renal stenoses, considering averages across the three simulated inflow rate cases. The proposed framework have utility to iteratively optimize suprarenal EVAR fixation length and achieve normal renal wall shear stresses and streamlined juxtarenal hemodynamics.

Renal denervation after Symplicity HTN-3: an update.

PubMed

Persu, Alexandre; Jin, Yu; Fadl Elmula, Fadl Elmula Mohamed; Jacobs, Lotte; Renkin, Jean; Kjeldsen, Sverre

2014-08-01

After three years of excessive confidence, overoptimistic expectations and performance of 15 to 20,000 renal denervation procedures in Europe, the failure of a single well-designed US trial--Symplicity HTN-3--to meet its primary efficacy endpoint has cast doubt on renal denervation as a whole. The use of a sound methodology, including randomisation and blinded endpoint assessment was enough to see the typical 25-30 mmHg systolic blood pressure decrease observed after renal denervation melt down to less than 3 mmHg, the rest being likely explained by Hawthorne and placebo effects, attenuation of white coat effect, regression to the mean and other physician and patient-related biases. The modest blood pressure benefit directly assignable to renal denervation should be balanced with unresolved safety issues, such as potentially increased risk of renal artery stenosis after the procedure (more than ten cases reported up to now, most of them in 2014), unclear long-term impact on renal function and lack of morbidity-mortality data. Accordingly, there is no doubt that renal denervation is not ready for clinical use. Still, renal denervation is supported by a strong rationale and is occasionally followed by major blood pressure responses in at-risk patients who may otherwise have remained uncontrolled. Upcoming research programmes should focus on identification of those few patients with truly resistant hypertension who may derive a substantial benefit from the technique, within the context of well-designed randomised trials and independent registries. While electrical stimulation of baroreceptors and other interventional treatments of hypertension are already "knocking at the door", the premature and uncontrolled dissemination of renal denervation should remain an example of what should not be done, and trigger radical changes in evaluation processes of new devices by national and European health authorities.

Outcome of Renal Artery Reconstruction

PubMed Central

Darling, R. Clement; Kreienberg, Paul B.; Chang, Benjamin B.; Paty, Philip S. K.; Lloyd, William E.; Leather, Robert P.; Shah, Dhiraj M.

1999-01-01

Objective To evaluate the short- and long-term results of surgical reconstruction of the renal arteries, the authors review their experience with more than 600 reconstructions performed over a 12-year period. Summary Background Data Reconstruction of the renal arteries, whether for primary renal indications or concomitantly with aortic reconstruction, has evolved over the past 40 years. There is concern that renal artery reconstructions carry significant rates of mortality and morbidity and may fare poorly compared with less-invasive procedures. Methods From 1986 to 1998, 687 renal artery reconstructions were performed in 568 patients. Of these, 105 patients had simultaneous bilateral renal artery reconstructions. Fifty-six percent of the patients were male; 11% had diabetes; 35% admitted to smoking at the time of surgery. Mean age was 67 (range, 1 to 92). One hundred fifty-six (23%) were primary procedures and the remainder were adjunctive procedures with aortic reconstructions; 406 were abdominal aortic aneurysms and 125 were aortoiliac occlusive disease. Five hundred procedures were bypasses, 108 were endarterectomies, 72 were reimplantation, and 7 were patch angioplasties. There were 31 surgical deaths (elective and emergent) in the entire group for a mortality rate of 5.5%. Predictors of increased risk of death were patients with aortoiliac occlusive disease and patients undergoing bilateral simultaneous renal artery revascularization. Cause of death was primarily cardiac. Other nonfatal complications included bleeding (nine patients) and wound infection (three patients). There were 9 immediate occlusions (1.3%) and 10 late occlusions (1.5%). Thirty-three patients (4.8%) had temporary worsening of their renal function after surgery. Conclusion Renal artery revascularization is a safe and durable procedure. It can be performed in selected patients for primary renovascular pathology. It can also be an adjunct to aortic reconstruction with acceptable mortality and morbidity rates. PMID:10522722

Renal function and urological complications after radical hysterectomy with postoperative radiotherapy and platinum-based chemotherapy for cervical cancer.

PubMed

Okadome, Masao; Saito, Toshiaki; Kitade, Shoko; Ariyoshi, Kazuya; Shimamoto, Kumi; Kawano, Hiroyuki; Minami, Kazuhito; Nakamura, Motonobu; Shimokawa, Mototsugu; Okushima, Kazuhiro; Kubo, Yuichiro; Kunitake, Naonobu

2018-02-01

We aimed to clarify renal functional changes long term and serious urological complications in women with cervical cancer who undergo radical hysterectomy followed by pelvic radiotherapy and/or platinum-based chemotherapy to treat the initial disease. Data on 380 women who underwent radical hysterectomy at the National Kyushu Cancer Center from January 1997 to December 2013 were reviewed. Main outcome measures were the estimated glomerular filtration rate (eGFR) and monitored abnormal urological findings. Postoperative eGFR was significantly lower than preoperative eGFR in 179 women with surgery alone and in 201 women with additional pelvic radiotherapy and/or chemotherapy (both P < 0.01). Two types of univariate analyses for eGFR reduction in women after treatment showed that older age, advanced stage, pelvic radiotherapy, and platinum-based chemotherapy were significant variables on both analyses. Two types of multivariate analyses showed that platinum-based chemotherapy or pelvic radiotherapy were associated with impaired renal function (odds ratio 1.96, 95% confidence interval 1.08-3.54 and odds ratio 2.85, 95% confidence interval 1.12-7.24, for the respective analyses). There was a higher rate of bladder wall thickening in women with pelvic radiotherapy had than those without it (17.4% vs. 2.7%, P < 0.01). One serious urological complication (intraperitoneal rupture of the bladder) occurred among women who underwent pelvic radiotherapy (0.6% vs. 0%). Surgeons should be aware that eGFR is reduced after platinum-based chemotherapy and/or postoperative pelvic radiotherapy. Serious and life-threatening urological complications are rare, but surgeons should be aware of the possibility during the long follow-up. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Long-Term Outcomes in Idiopathic Membranous Nephropathy Using a Restrictive Treatment Strategy

PubMed Central

van Dijk, Peter R.; Hofstra, Julia M.; Wetzels, Jack F.M.

2014-01-01

Recently published Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend limiting the use of immunosuppressive drugs in idiopathic membranous nephropathy to patients at the highest risk of kidney failure. However, recommendations are based on natural history rather than direct assessment of a restrictive treatment strategy. Here, we describe the long-term outcomes of treating a large cohort of patients with idiopathic membranous nephropathy according to a restrictive treatment policy. We analyzed data for 254 patients who visited our outpatient clinic between 1995 and 2009. All patients were treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Immunosuppressive therapy was recommended in cases of deteriorating renal function or untreatable nephrotic syndrome. Primary outcomes for the present study were renal replacement therapy and death. Secondary outcomes included adverse events during follow-up and remission of proteinuria. In total, 124 patients (49%) received immunosuppressive therapy, which predominantly consisted of cyclophosphamide combined with steroids. Ten-year cumulative incidence rates were 3% for renal replacement therapy and 10% for death. Partial remission rates were 39%, 70%, and 83% after 1, 3, and 5 years, respectively; complete remission rates were 5%, 24%, and 38% at 1, 3, and 5 years, respectively. A serious adverse event occurred in 23% of all patients. The most notable complications were infections (17%), leukopenia (18%), cardiovascular events (13%), and malignancies (8%). In conclusion, the use of a restrictive treatment strategy in this cohort of patients with idiopathic membranous nephropathy yielded favorable outcomes while limiting the number of patients exposed to toxic drugs. These results support current KDIGO guidelines. PMID:24029426

Catheter-based renal denervation for treatment of resistant hypertension

PubMed Central

Hatipoglu, Emine; Ferro, Albert

2013-01-01

Hypertension is a common disease associated with important cardiovascular complications. Persistent blood pressure of 140/90 or higher despite combined use of a reninangiotensin system blocker, calcium channel blocker and a diuretic at highest tolerated doses constitutes resistant hypertension. Excess sympathetic activity plays an important pathogenic role in resistant hypertension in addition to contributing to the development of metabolic problems, in particular diabetes. Reduction of renal sympathetic activity by percutaneous catheter-based radiofrequency ablation via the renal arteries has been shown in several studies to decrease blood pressure in patients with resistant hypertension, and importantly is largely free of significant complications. However, longer term follow-up is required to confirm both long-term safety and efficacy. PMID:24175081

Obesity is not an independent risk factor for adverse perioperative and long-term clinical outcomes following open AAA repair or EVAR.

PubMed

Park, Brian; Dargon, Phong; Binette, Christopher; Babic, Bruna; Thomas, Tina; Divinagracia, Thomas; Dahn, Michael S; Menzoian, James O

2011-10-01

Moderate (body mass index [BMI] ≥30) and morbid obesity (BMI ≥35) is increasing at an alarming rate in vascular surgery patients. The objective of this study was to determine the impact of obesity on perioperative and long-term clinical outcomes following open abdominal aortic aneurysm (AAA) repair or endovascular aneurysm repair (EVAR). This review includes patients that underwent open AAA repair (n = 403) or EVAR (n = 223) from 1999 to 2009. Specific patient characteristics such as comorbid diseases, medications, and body mass index (BMI) were assessed. Specific perioperative outcomes such as length of stay, myocardial infarctions, and mortality were reviewed. In addition, long-term outcomes such as rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days were also assessed. The incidence of obesity in open AAA patients was 25.3% (documented incidence 1.5%) and for EVAR was 24.6% (documented incidence 4%). Moderate and morbid obesity was associated with longer intensive care unit (ICU) admissions for both open AAA or EVAR patients (P < .05). However, no significant differences in perioperative outcomes in terms of overall length of stay, myocardial infarction, acute renal failure, wound infections, or mortality were noted between obese and nonobese patients underoing open AAA repair or EVAR (P > .05). Similarly, moderate and morbid obesity was not associated with significant differences in rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days for patients undergoing open AAA repair or EVAR (P > .05). The results of this study indicate that moderate and morbid obesity are not independently associated with adverse perioperative and long-term clinical outcomes for patients undergoing open AAA repair or EVAR. Therefore, either open AAA repair or EVAR can be accomplished safely in moderately obese and morbidly obese patients.

Upper and Lower Urinary Tract Outcomes in Adult Myelomeningocele Patients: A Systematic Review

PubMed Central

Veenboer, Paul W.; Bosch, J. L. H. Ruud; van Asbeck, Floris W. A.; de Kort, Laetitia M. O.

2012-01-01

Background The introduction of sophisticated treatment of bladder dysfunction and hydrocephalus allows the majority of SB patients to survive into adulthood. However, no systematic review on urological outcome in adult SB patients is available and no follow-up schemes exist. Objectives To systematically summarize the evidence on outcome of urinary tract functioning in adult SB patients. Methods A literature search in PubMed and Embase databases was done. Only papers published in the last 25 years describing patients with open SB with a mean age >18 years were included. We focused on finding differences in the treatment strategies, e.g., clean intermittent catheterization and antimuscarinic drugs versus early urinary diversion, with regard to long-term renal and bladder outcomes. Results A total of 13 articles and 5 meeting abstracts on urinary tract status of adult SB patients were found describing a total of 1564 patients with a mean age of 26.1 years (range 3–74 years, with a few patients <18 years). All were retrospective cohort studies with relatively small and heterogeneous samples with inconsistent reporting of outcome; this precluded the pooling of data and meta-analysis. Total continence was achieved in 449/1192 (37.7%; range 8–85%) patients. Neurological level of the lesion and hydrocephalus were associated with incontinence. Renal function was studied in 1128 adult patients. In 290/1128 (25.7%; range 3–81.8%) patients some degree of renal damage was found and end-stage renal disease was seen in 12/958 (1.3%) patients. Detrusor-sphincter dyssynergy and detrusor-overactivity acted as adverse prognostic factors for the development of renal damage. Conclusions These findings should outline follow-up schedules for SB patients, which do not yet exist. Since renal and bladder deterioration continues beyond adolescence, follow-up of these individuals is needed. We recommend standardization in reporting the outcome of urinary tract function in adult SB patients. PMID:23119003

Mechanistic approach to the pathophysiology of target organ damage in hypertension from studies in a human model with characteristics opposite to hypertension: Bartter's and Gitelman's syndromes.

PubMed

Calò, L A; Maiolino, G

2015-07-01

Extensive studies using Bartter's/Gitelman's syndrome patients have provided insights into the angiotensin II (Ang II) signaling pathways involved in the regulation of vascular tone and cardiovascular-renal remodeling. The renin-angiotensin-aldosterone system is activated in these syndromes, however, patients do not develop hypertension and cardiovascular remodeling and clinically manifest conditions opposite to hypertension. The short- and the long-term signaling of Ang II remains an important matter of investigation to shed light on mechanisms responsible for the pathophysiology of hypertension and its long-term complications. The long-term signaling of Ang II is involved in the pathophysiology of cardiovascular-renal remodeling and inflammatory responses in which the balance between RhoA/Rho kinase pathway and NO system plays a crucial role. In this brief review, the results of our studies in Bartter's and Gitelman's syndromes are reported on these processes. The information obtained from these studies can clarify, confirm or be used to extend the biochemical mechanisms responsible for the pathophysiology of hypertension and its long-term complications and could offer further chances to identify additional potential significant targets of therapy.

Geometric Alteration of Renal Arteries After Fenestrated Grafting and the Impact on Renal Function.

PubMed

Ou, Jiale; Chan, Yiu-Che; Chan, Crystal Yin-Tung; Cheng, Stephen W K

2017-05-01

This study aims to investigate the degree of geometric change on renal arteries and its impact on renal function after fenestrated endovascular aortic repair (fEVAR). Twenty-five patients with fEVAR were included. There were 47 renal arteries target vessels, and 43 of these (22 left and 21 right vessels) stented successfully. Their preoperative and first postoperative follow-up computed tomography (CT) images were reconstructed using the Aquarius workstation (TeraRecon, San Mateo, CA, USA). The superior mesenteric artery (SMA) or celiac axis (if SMA was stented) was appointed as reference origin. The longitudinal orientation of a renal artery or a stent was represented by a takeoff angle (ToA) between the renal artery or stent and the distal abdominal aorta. The postoperative stent ToAs were compared with those of preoperative renal arteries. Preoperative and short-term postoperative serum creatinine levels were measured. Renal function impairment was indicated as a >30% or >2.0 mg/dL rise in serum creatinine compared to the preoperative level. The relationship between postoperative renal function impairment and the stent orientation or geometric changes in renal arteries was correlated. The patency rate of renal arteries was 100% at the first postoperative CT review. The average ToAs of both renal arteries were significantly enlarged after stenting (P < 0.05). Seven stent deformations (16.3%) in four patients (16.0%) were observed. They were attributed to caudal misalignment of the fenestrated stent graft (n = 6) or inaccurate graft sizing (n = 1). There was no stent fracture or target vessel loss. Postoperatively, nine patients (36.0%) at day 1 and 10 patients (41.7%) after 3 months suffered the renal function impairment. This was found not to be associated with the stent angulation or angular change of the renal arteries (both P > 0.05). The three patients with stent deformation due to misalignment suffered postoperative renal function impairment and continuing deterioration in renal function. Implanted renal stents could angulate renal arteries more cephalad after fenestrated stenting. Postoperative renal function impairment was not associated with the stent orientation and changes in vessel orientation. Accurate fenestrated alignment is important to maintain stent performance and preserve renal function. Copyright © 2017 Elsevier Inc. All rights reserved.

Hashimoto Thyroiditis and Nephrocalcinosis in a Child with Down Syndrome

PubMed Central

Spahiu, Lidvana; Jashari, Haki; Mulliqi-Kotori, Vjosa; Elezi-Rugova, Blerta; Merovci, Besart

2016-01-01

Introduction: Hypothyroidism has been reported to affect renal function and structure. However, the association of hypothyroidism with distal renal tubular acidosis (dRTA) is rarely reported in children. Case Presentation: We present a 6-year-boy with Down syndrome admitted in our department due to vomiting, weakness, polyuria, polydipsia, irritability and weight loss in the last few weeks. Investigations revealed features of hypokalemia, metabolic acidosis and alkaline urine consistent with dTRA. Abdominal ultrasound found nephrocalcinosis. In addition, Antithyroid peroxidase antibodies were positive, suggesting an autoimmune background for the pathogenesis of the tubular dysfunction. Treatment for dRTA and hypothyroidism was started and symptomatic improve was noticed. Conclusion: dRTA should be excluded in children with autoimmune disorders who develop weakness, polyuria, polydipsia or growth failure. Early diagnosis would reduce long-term complications. PMID:27147809

Factors affecting early and long-term outcomes after completion pneumonectomy.

PubMed

Chataigner, Olivier; Fadel, Elie; Yildizeli, Bedrettin; Achir, Abdallah; Mussot, Sacha; Fabre, Dominique; Mercier, Olaf; Dartevelle, Philippe G

2008-05-01

To identify factors that affect operative mortality and morbidity and long-term survival after completion pneumonectomy. We retrospectively reviewed the charts of consecutive patients who underwent completion pneumonectomy at our cardiothoracic surgery department from January 1996 to December 2005. We identified 69 patients, who accounted for 17.8% of all pneumonectomies during the study period; 22 had benign disease and 47 malignant disease (second primary lung cancer, n=19; local recurrence, n=17; or metastasis, n=11). There were 50 males and 19 females with a mean age of 60 years (range, 29-80 years). Postoperative mortality was 12% and postoperative morbidity 41%. Factors associated with postoperative mortality included obesity (p=0.005), coronary artery disease (p=0.03), removal of the right lung (p=0.02), advanced age (p=0.02), and renal failure (p<0.0001). Preoperative renal failure was the only significant risk factor for mortality by multivariate analysis (p=0.036). Bronchopleural fistula developed in seven patients (10%), with risk factors being removal of the right lung (p=0.04) and mechanical stump closure (p=0.03). Overall survival was 65% after 3 years and 46% after 5 years. Long-term survival was not affected by the reason for completion pneumonectomy. Although long-term survival was acceptable, postoperative mortality and morbidity rates remained high, confirming the reputation of completion pneumonectomy as a challenging procedure. Significant comorbidities and removal of the right lung were the main risk factors for postoperative mortality. Improved patient selection and better management of preoperative renal failure may improve the postoperative outcomes of this procedure, which offers a chance for prolonged survival.

Long-term treatment with EGFR inhibitor erlotinib attenuates renal inflammatory cytokines but not nephropathy in Alport syndrome mouse model.

PubMed

Omachi, Kohei; Miyakita, Rui; Fukuda, Ryosuke; Kai, Yukari; Suico, Mary Ann; Yokota, Tsubasa; Kamura, Misato; Shuto, Tsuyoshi; Kai, Hirofumi

2017-12-01

Alport syndrome (AS) is a hereditary kidney disease caused by mutation of type IV collagen. Loss of collagen network induces collapse of glomerular basement membrane (GBM) structure. The previous studies showed that upregulation of some tyrosine kinase receptors signaling accompanied GBM disorder in AS mouse model. EGFR signaling is one of the well-known receptor kinase signaling that is involved in glomerular diseases. However, whether EGFR signaling is relevant to AS progression is still uninvestigated. Here, we determined the involvement of EGFR in AS and the effect of suppressing EGFR signaling by erlotinib treatment on AS progression. Phosphorylated EGFR expression was investigated by Western blotting analysis and immunostaining of kidney tissues of Col4a5 mutant mice (a mouse model of X-linked AS). To check the effect of blocking EGFR signaling in AS, we administered erlotinib to AS mice once a day (10 mg/kg/day) orally for 18 weeks. Renal function parameters (proteinuria, serum creatinine, and BUN) and renal histology were assessed, and the gene expressions of inflammatory cytokines were analyzed in renal tissues. Phosphorylated EGFR expression was upregulated in AS mice kidney tissues. Erlotinib slightly reduced the urinary protein and suppressed the expression of renal injury markers (Lcn2, Lysozyme) and inflammatory cytokines (Il-6, Il-1β and KC). Erlotinib did not improve renal pathology, such as glomerular sclerosis and fibrosis. These findings suggest that EGFR signaling is upregulated in kidney, but although inhibiting this signaling pathway suppressed renal inflammatory cytokines, it did not ameliorate renal dysfunction in AS mouse model.

Renal denervation with a percutaneous bipolar radiofrequency balloon catheter in patients with resistant hypertension: 6-month results from the REDUCE-HTN clinical study.

PubMed

Sievert, Horst; Schofer, Joachim; Ormiston, John; Hoppe, Uta C; Meredith, Ian T; Walters, Darren L; Azizi, Michel; Diaz-Cartelle, Juan; Cohen-Mazor, Meital

2015-02-01

To evaluate the safety and efficacy of the balloon-based bipolar Vessix Renal Denervation System in treating patients with resistant hypertension. In this prospective, multicentre, single-arm study, 146 patients (age 58.6±10.5 years; 61% men) with office systolic blood pressure (BP) ≥160 mmHg despite ≥3 antihypertensive medications at maximally tolerated doses were treated with the Vessix System. Efficacy endpoints were reductions in office and 24-hour ambulatory systolic and diastolic BPs at six months. Acute and long-term safety, with a focus on the renal artery and estimated glomerular filtration rate (eGFR), were assessed. Baseline office and ambulatory BPs were 182.4±18.4/100.2±14.0 mmHg and 153.0±15.1/87.5±13.2 mmHg, respectively. No acute renal artery injury requiring intervention or serious periprocedural cardiovascular events occurred. At six months, office BP was reduced by 24.7±22.1/10.3±12.7 mmHg (p<0.0001) and ambulatory BP was reduced by 8.4±14.4/5.9±9.1 mmHg (N=69; p<0.0001). Twenty-six patients (18%) achieved an office systolic BP <140 mmHg. One patient had renal artery stenosis which required stenting. Mean eGFR remained stable. Renal artery denervation with the Vessix System reduced both office and ambulatory BP at six months in patients with resistant hypertension. Renal artery safety and renal function results are favourable.

Renal denervation prevents long-term sequelae of ischemic renal injury

PubMed Central

Kim, Jinu; Padanilam, Babu J.

2014-01-01

Signals that drive interstitial fibrogenesis after renal ischemia reperfusion injury remain undefined. Sympathetic activation is manifest even in the early clinical stages of chronic kidney disease and is directly related to disease severity. A role for renal nerves in renal interstitial fibrogenesis in the setting of ischemia reperfusion injury has not been studied. In male 129S1/SvImJ mice, ischemia reperfusion injury induced tubulointerstitial fibrosis as indicated by collagen deposition and profibrotic protein expression 4 to 16 days after the injury.. Leukocyte influx, proinflammatory protein expression, oxidative stress, apoptosis, and cell cycle arrest at G2/M phase were enhanced after ischemia reperfusion injury. Renal denervation at the time of injury or up to 1 day post-injury improved histology, decreased proinflammatory/profibrotic responses and apoptosis, and prevented G2/M cell cycle arrest in the kidney. Treatment with afferent nerve-derived calcitonin gene-related peptide (CGRP) or efferent nerve-derived norepinephrine in denervated and ischemia reperfusion injury-induced kidneys mimicked innervation, restored inflammation and fibrosis, induced G2/M arrest, and enhanced TGF-β1 activation. Blocking norepinephrine or CGRP function using respective receptor blockers prevented these effects. Consistent with the in vivo study, treatment with either norepinephrine or CGRP induced G2/M cell cycle arrest in HK-2 proximal tubule cells, whereas antagonists against their respective receptors prevented G2/M arrest. Thus, renal nerve stimulation is a primary mechanism and renal nerve-derived factors drive epithelial cell cycle arrest and the inflammatory cascade causing interstitial fibrogenesis after ischemia reperfusion injury. PMID:25207878

Outcomes of Renal Allograft Recipients With Hepatitis C.

PubMed

Carpio, R; Pamugas, G E; Danguilan, R; Que, E

2016-04-01

Studies on the effect of hepatitis C virus (HCV) infection showed decreased graft survival compared to HCV-negative matched patients. It was also identified as an independent risk factor for graft loss and mortality in kidney transplantation patients. This study was designed to evaluate the 10-year graft and patient outcomes of renal allograft recipients with HCV infection at the National Kidney and Transplant Institute. This is a retrospective study of patients who underwent renal transplantation with HCV infection and a group who were HCV-negative in the same post-transplantation period. Data were gathered from the in-patient and out-patient clinic records. Patient survival was significantly lower in the HCV-positive than in the HCV-negative group. The mean duration of patient survival was 154.95 (+4.95) months (12 years and 10 months) in HCV-negative patients compared to 141 (+6.52) months (11 years and 9 months) in the HCV-positive group (P = .05). Graft survival did not differ significantly between HCV-positive and HCV-negative recipients (P = .734). The mean duration of graft survival was 137 (+7.68) months (11 years and 5 months) in HCV-negative patients compared to 130 (+6.84) months (10 years and 10 months) in HCV-positive patients. Short- and long-term outcomes including biopsy-proven acute rejection, transplant glomerulopathy, chronic allograft nephropathy, renal function, and proteinuria were similar in both groups. Rejection, glomerulopathy, and renal function were similar in both groups. HCV progression was also observed in patients with detectable HCV-RNA 6 months before transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Review of the State of Renal Nerve Ablation for Patients with Severe and Resistant Hypertension

PubMed Central

Gulati, Vinay; White, William B.

2013-01-01

Through modulation of renin secretion, glomerular filtration rate and renal absorption of sodium, the sympathetic innervation of the kidneys plays an important role in the pathogenesis of hypertension. Renal nerve ablation technology is being developed for treatment of drug-treatment resistant hypertension worldwide. Preliminary research with the use of radiofrequency based renal denervation systems have demonstrated encouraging results with significant reduction of blood pressure in patients inadequately controlled despite nearly maximal drug therapy regimens. From work done thus far, the renal denervation procedure has not been associated with serious adverse effects. Long term efficacy and safety still needs to be established for renal nerve ablation. This review focuses on the impact of the renal sympathetic system on blood pressure regulation, the clinical rationale for renal nerve ablation in severe and drug-treatment resistant hypertension and current evidence from the more advanced renal denervation devices. PMID:23953998

Novel Approaches for the Treatment of the Patient with Resistant Hypertension: Renal Nerve Ablation

PubMed Central

Gulati, Vinay; White, William B.

2013-01-01

Sympathetic innervation of the kidneys plays a major role in the pathogenesis of hypertension through modulation of renin secretion, glomerular filtration rate and renal absorption of sodium. Targeted interventions for renal nerve ablation are being developed for treatment of drug resistant hypertension in the USA and rest of the world. Early studies with the use of radiofrequency based renal denervation systems have shown encouraging results with significant reduction of blood pressure in patients inadequately controlled despite nearly maximal drug therapy regimens. Thus far, the renal denervation procedure has been associated with minimal side effects. Long term efficacy and safety beyond 3 years needs to be determined for renal nerve ablation. This review focuses on the physiology of the renal sympathetic system, the rationale for renal nerve ablation and current evidence in support of the available therapeutic renal denervation systems. PMID:24244757

Impact of mycophenolate mofetil dose posttransplantation on 12-month renal function: analysis of the MOST database.

PubMed

Salvadori, M; Bock, A; Chapman, J; Dussol, B; Fritsche, L; Kliem, V; Lebranchu, Y; Oppenheimer, F; Pohanka, E; Tufveson, G; Rosati, A; Puig, X; Corbetta, G

2005-01-01

Mycophenolate mofetil (MMF) has greatly reduced the risk of acute rejection episodes (ARE) after renal transplantation, but dose reductions/withdrawals could jeopardize long-term results. The MOST database of "de novo" patients treated with MMF at month 1 and functioning grafts at month 12 were divided into 2 groups: groups 1, 2 g MMF at month 1 and month 12; and group 2, 2 g MMF at month 1 but MMF <2 g at month 12 to evaluate renal function glonerular filtration rate (GFR). In this study, 1136 patients were receiving 2 g MMF at month 1. On month 12, 645 were on 2 g (56.8%, group 1) and 431 were on <2 g (43.2%, group 2). Group 1 included younger recipients of younger donors with fewer patients with delayed graft function (DGF). Group 1 showed more ARE during month 1 and more patients who received induction. Mean Neoral daily doses at month 1/month 12 were 5.3/3.0 and 5.3/3.1 mg/kg in group 1 and group 2, respectively (P = .05 at month 12). GFR in group 1 and group 2 were 59.06 (CI 57.10-60.60) and 53.81 (CI 52-55.7) at month 1 (P < .001); 63.7 (CI 62.1-65.30) and 55.9 (CI 54.1-57.7) mL/min*1.73 m(2) at month 12 (P < .001). The mean increases in GFR between month 1 and month 12 were 4.64 and 1.94 mL/min*1.73 m(2), respectively (P < .05). A multivariate analysis also included 795 patients from the "maintenance" patient database with retrospective detailed information. The following parameters were highly predictive for good renal function at month 12: donor age younger than 60 years, recipient age younger than 60 years, immediate graft function, 12-month MMF dose = 2 g, absence of CMV infection, and 12-month Neoral dose <3 mg/kg/d. Maintenance of MMF dose at 2 g/d during the first year appears to facilitate the attainment of optimal renal function at 12-months after kidney transplantation.

Renal function during pregnancy may predict risk of future hospitalization due to atherosclerotic-related morbidity.

PubMed

Wolak, Talya; Shoham-Vardi, Ilana; Sergienko, Ruslan; Sheiner, Eyal

2016-02-01

This study aims to examine whether renal function during pregnancy can serve as a surrogate marker for the risk of developing atherosclerotic-related morbidity. A case-control study, including women who gave birth at a tertiary referral medical centre during 2000-2012. This population was divided into cases of women who were subsequently hospitalized for atherosclerotic morbidity during the study period and age-matched controls. From the study population, we retrieved two groups: the creatinine (Cr) group: women who had at least one Cr measurement (4945 women) and the urea group: women who had at least one urea measurement (4932 women) during their pregnancies. In the Cr and urea group, there were 572 and 571 cases and 4373 and 4361 controls, respectively. The mean follow-up period in the Cr and urea group was 61.7 ± 37.0 and 57.3 ± 36.0 months, respectively. Cox proportional hazards models (controlling for confounders: gestational hypertension, gestational diabetes, obesity, maternal age, creatinine level (for urea), and gestational week) were used to estimate the adjusted hazard ratios (HR) for hospitalizations. A significant association was documented between renal function during pregnancy and long-term atherosclerotic morbidity. Multivariate analysis, showed that Cr at pregnancy index of ≥89 μmol/L was associated with a significant increased risk for hospitalization due to cardiovascular (CVS) events (adjusted HR = 2.91 CI 1.37-6.19 P = 0.005) and urea level ≤7 mmol/L was independently associated with reduced prevalence of CVS hospitalization (adjusted HR = 0.62 CI 0.57-0.86 P = 0.001). Renal function abnormality during pregnancy may reveal occult predisposition to atherosclerotic morbidity years after childbirth. © 2015 Asian Pacific Society of Nephrology.

Effect of metoprolol administration on renal sodium handling in experimental congestive heart failure.

PubMed

DiBona, G F; Sawin, L L

1999-07-06

Long-term metoprolol therapy improves cardiac performance and decreases mortality in patients with chronic congestive heart failure (CHF). This study examined the effect of long-term metoprolol therapy on renal sodium handling in an experimental rat model of CHF. Rats with left coronary ligation and myocardial infarction-induced CHF were treated with metoprolol (1.5 mg. kg-1. h-1) or vehicle for 3 weeks by osmotic minipump. They were then evaluated for their ability to excrete a short-term sodium load (5% body weight isotonic saline infusion over 30 minutes) and a long-term sodium load (change from low- to high-sodium diet over 8 days). All CHF rats had left ventricular end-diastolic pressure >10 mm Hg, and heart weight/body weight ratios averaged 0.68+/-0.02% (versus control of approximately 0.40%). Compared with vehicle CHF rats (n=19), metoprolol CHF rats (n=18) had lower basal values of mean arterial pressure (122+/-3 versus 112+/-3 mm Hg) and heart rate (373+/-14 versus 315+/-9 bpm) and decreased heart rate responses to intravenous doses of isoproterenol. During short-term isotonic saline volume loading, metoprolol CHF rats excreted 54+/-4% more of the sodium load than vehicle CHF rats. During long-term dietary sodium loading, metoprolol CHF rats retained 28+/-3% less sodium than vehicle CHF rats. Metoprolol treatment of rats with CHF results in an improved ability to excrete both short- and long-term sodium loads.

Long-term outcomes of acute kidney injury.

PubMed

Coca, Steven G

2010-05-01

The goal of this review is to summarize the recent plethora of data that relate to long-term outcomes after acute kidney injury (AKI). Surviving patients with AKI are still at high risk for long-term adverse outcomes, even if serum creatinine returns to normal. After adjusting for potential confounders, many recent studies have demonstrated that AKI is independently associated with chronic kidney disease, end-stage renal disease, and premature death. Unfortunately, definitive evidence from randomized controlled trials demonstrating that prevention or treatment of AKI prevents long-term adverse outcomes is not yet available. AKI is clearly a prognostic marker for poor long-term outcomes, but more studies will be needed to determine whether AKI is truly causal and whether or not the risk is modifiable.

Role of renal sensory nerves in physiological and pathophysiological conditions

PubMed Central

2014-01-01

Whether activation of afferent renal nerves contributes to the regulation of arterial pressure and sodium balance has been long overlooked. In normotensive rats, activating renal mechanosensory nerves decrease efferent renal sympathetic nerve activity (ERSNA) and increase urinary sodium excretion, an inhibitory renorenal reflex. There is an interaction between efferent and afferent renal nerves, whereby increases in ERSNA increase afferent renal nerve activity (ARNA), leading to decreases in ERSNA by activation of the renorenal reflexes to maintain low ERSNA to minimize sodium retention. High-sodium diet enhances the responsiveness of the renal sensory nerves, while low dietary sodium reduces the responsiveness of the renal sensory nerves, thus producing physiologically appropriate responses to maintain sodium balance. Increased renal ANG II reduces the responsiveness of the renal sensory nerves in physiological and pathophysiological conditions, including hypertension, congestive heart failure, and ischemia-induced acute renal failure. Impairment of inhibitory renorenal reflexes in these pathological states would contribute to the hypertension and sodium retention. When the inhibitory renorenal reflexes are suppressed, excitatory reflexes may prevail. Renal denervation reduces arterial pressure in experimental hypertension and in treatment-resistant hypertensive patients. The fall in arterial pressure is associated with a fall in muscle sympathetic nerve activity, suggesting that increased ARNA contributes to increased arterial pressure in these patients. Although removal of both renal sympathetic and afferent renal sensory nerves most likely contributes to the arterial pressure reduction initially, additional mechanisms may be involved in long-term arterial pressure reduction since sympathetic and sensory nerves reinnervate renal tissue in a similar time-dependent fashion following renal denervation. PMID:25411364

Long-Term Effects of a Very Low Carbohydrate Compared With a High Carbohydrate Diet on Renal Function in Individuals With Type 2 Diabetes: A Randomized Trial.

PubMed

Tay, Jeannie; Thompson, Campbell H; Luscombe-Marsh, Natalie D; Noakes, Manny; Buckley, Jonathan D; Wittert, Gary A; Brinkworth, Grant D

2015-11-01

To compare the long-term effects of a very low carbohydrate, high-protein, low saturated fat (LC) diet with a traditional high unrefined carbohydrate, low-fat (HC) diet on markers of renal function in obese adults with type 2 diabetes (T2DM), but without overt kidney disease.One hundred fifteen adults (BMI 34.6 ± 4.3 kg/m, age 58 ± 7 years, HbA1c 7.3 ± 1.1%, 56 ± 12 mmol/mol, serum creatinine (SCr) 69 ± 15 μmol/L, glomerular filtration rate estimated by the Chronic Kidney Disease Epidemiology Collaboration formula (eGFR 94 ± 12 mL/min/1.73 m)) were randomized to consume either an LC (14% energy as carbohydrate [CHO < 50 g/day], 28% protein [PRO], 58% fat [<10% saturated fat]) or an HC (53% CHO, 17% PRO, 30% fat [<10% saturated fat]) energy-matched, weight-loss diet combined with supervised exercise training (60 min, 3 day/wk) for 12 months. Body weight, blood pressure, and renal function assessed by eGFR, estimated creatinine clearance (Cockcroft-Gault, Salazar-Corcoran) and albumin excretion rate (AER), were measured pre- and post-intervention.Both groups achieved similar completion rates (LC 71%, HC 65%) and reductions in weight (mean [95% CI]; -9.3 [-10.6, -8.0] kg) and blood pressure (-6 [-9, -4]/-6[-8, -5] mmHg), P ≥ 0.18. Protein intake calculated from 24 hours urinary urea was higher in the LC than HC group (LC 120.1 ± 38.2 g/day, 1.3 g/kg/day; HC 95.8 ± 27.8 g/day, 1 g/kg/day), P < 0.001 diet effect. Changes in SCr (LC 3 [1, 5], HC 1 [-1, 3] μmol/L) and eGFR (LC -4 [-6, -2], HC -2 [-3, 0] mL/min/1.73 m) did not differ between diets (P = 0.25). AER decreased independent of diet composition (LC --2.4 [-6, 1.2], HC -1.8 [-5.4, 1.8] mg/24 h, P = 0.24); 6 participants (LC 3, HC 3) had moderately elevated AER at baseline (30-300 mg/24 h), which normalized in 4 participants (LC 2, HC 2) after 52 weeks.Compared with a traditional HC weight loss diet, consumption of an LC high protein diet does not adversely affect clinical markers of renal function in obese adults with T2DM and no preexisting kidney disease.

How botulinum toxin in neurogenic detrusor overactivity can reduce upper urinary tract damage?

PubMed Central

Baron, Maximilien; Grise, Philippe; Cornu, Jean-Nicolas

2016-01-01

Intradetrusor injections of botulinum toxin are the cornerstone of medical treatment of neurogenic detrusor overactivity. The primary aim of this treatment is to ensure a low pressure regimen in the urinary bladder, but the mechanisms leading to long-term protection of the urinary tract remain poorly understood. In this paper, we highlight the potential benefits of intradetrusor injections of botulinum toxin regarding local effects on the bladder structures, urinary tract infections, stone disease, vesico ureteral reflux, hydronephrosis, renal function based on a comprehensive literature review. PMID:26981445

Hepatoblastoma and hypoplastic kidneys: a new association.

PubMed

Chan, Randall; Mascarenhas, Leo; Venkatramani, Rajkumar

2014-08-01

Both hepatoblastoma and hypoplastic kidneys are rare in children. A review of all patients with hepatoblastoma treated at our institution between 1993 and 2011 revealed three cases of hepatoblastoma occurring in children with hypoplastic kidneys and significantly impaired renal function. Two patients were treated with doxorubicin-based therapy without cisplatin. One was treated with carboplatin. The former two are long-term survivors while the third patient died of sepsis following chemotherapy. This association is unlikely due to chance alone and chemotherapy regimens without cisplatin may be effective in treating these children. © 2014 Wiley Periodicals, Inc.

Two distinct clinical courses of renal involvement in rheumatoid patients with AA amyloidosis.

PubMed

Uda, Hiroshi; Yokota, Akira; Kobayashi, Kumiko; Miyake, Tadao; Fushimi, Hiroaki; Maeda, Akira; Saiki, Osamu

2006-08-01

We conducted a prospective study to investigate whether a correlation exists between the clinical course of renal involvement and the pathological findings of renal amyloidosis in patients with rheumatoid arthritis (RA). Patients with RA of more than 5 years' duration and who did not show renal manifestations were selected and received a duodenal biopsy for the diagnosis of amyloidosis. After the diagnosis of AA amyloidosis, patients received a renal biopsy, and patterns of amyloid deposition were examined. We followed the renal functions (serum levels of blood urea nitrogen and creatinine) of patients diagnosed with AA amyloidosis for 5 years. We diagnosed 53 patients with AA amyloidosis and monitored the renal function of 38 of them for > 5 years. The histological patterns were examined; in the 38 patients there were appreciable variations in the patterns of amyloid deposition. In 27 patients, amyloid deposits were found exclusively in the glomerulus (type 1). In the other 11 patients, however, amyloid deposits were found selectively around blood vessels and were totally absent in the glomerulus (type 2). In type 1 patients with glomerular involvement, renal function deteriorated rapidly regardless of disease state; most patients received hemodialysis. In type 2 patients with purely vascular involvement, however, renal function did not deteriorate significantly. In patients with RA and AA amyloidosis, 2 distinct clinical courses in terms of renal involvement were identified. It is suggested that renal function does not deteriorate when amyloid deposition is totally lacking in the glomerulus.

Renal Replacement Therapy: Purifying Efficiency of Automated Peritoneal Dialysis in Diabetic versus Non-Diabetic Patients

PubMed Central

Vega-Diaz, Nicanor; Gonzalez-Cabrera, Fayna; Marrero-Robayna, Silvia; Santana-Estupiñan, Raquel; Gallego-Samper, Roberto; Henriquez-Palop, Fernando; Perez-Borges, Patricia; Rodriguez-Perez, José Carlos

2015-01-01

Background: In order to reduce the cardiovascular risk, morbidity and mortality of peritoneal dialysis (PD), a minimal level of small-solute clearances as well as a sodium and water balance are needed. The peritoneal dialysis solutions used in combination have reduced the complications and allow for a long-time function of the peritoneal membrane, and the preservation of residual renal function (RRF) in patients on peritoneal dialysis (PD) is crucial for the maintenance of life quality and long-term survival. This retrospective cohort study reviews our experience in automatic peritoneal dialysis (APD) patients, with end-stage renal disease (ESRD) secondary to diabetic nephropathy (DN) in comparison to non-diabetic nephropathy (NDN), using different PD solutions in combination. Design: Fifty-two patients, 29 diabetic and 23 non-diabetic, were included. The follow-up period was 24 months, thus serving as their own control. Results: The fraction of renal urea clearance (Kt) relative to distribution volume (V) (or total body water) (Kt/V), or creatinine clearance relative to the total Kt/V or creatinine clearance (CrCl) decreases according to loss of RRF. The loss of the slope of RRF is more pronounced in DN than in NDN patients, especially at baseline time interval to 12 months (loss of 0.29 mL/month vs. 0.13 mL/month, respectively), and is attenuated in the range from 12 to 24 months (loss of 0.13 mL/month vs. 0.09 mL/month, respectively). Diabetic patients also experienced a greater decrease in urine output compared to non-diabetic, starting from a higher baseline urine output. The net water balance was adequate in both groups during the follow up period. Regarding the balance sodium, no inter-group differences in sodium excretion over follow up period was observed. In addition, the removal of sodium in the urine output decreases with loss of renal function. The average concentration of glucose increase in the cycler in both groups (DN: baseline 1.44 ± 0.22, 12 months 1.63 ± 0.39, 24 months 1.73 ± 0.47; NDN: baseline 1.59 ± 0.40, 12 months 1.76 ± 0.47, 24 months 1.80 ± 0.46), in order to maintain the net water balance. The daytime dwell contribution, the fraction of day and the renal fraction of studies parameters provide sustained benefit in the follow-up time, above 30%. Conclusions: The wet day and residual renal function are determinants in the achievement of the objective dose of dialysis, as well as in the water and sodium balance. The cause of chronic kidney disease (CKD) does not seem to influence the cleansing effectiveness of the technique. PMID:26239689

[Long-term outcome of monotherapy by Cohen ureterocystoneostomy for vesicoureteral reflux in spina bifida patients].

PubMed

Momose, H; Torimoto, K; Kishino, T; Ono, T; Joko, M

2001-05-01

The conventional surgical treatment for vesioureteral reflux (VUR) is spina bifida patients is ureterocystoneostomy. Various newer therapies, including augmentation enterocystoplasty and minimally invasive subureteral collagen injection, have been introduced. However, all of these procedures have specific advantages and disadvantages, and no guidelines for deciding on the surgical treatment of VUR in spina bifida patients have yet been established. In this study, the long-term outcome of the Cohen procedure, a method of ureterocystoneostomy, was examined. Among spina bifida patients in whom VUR was treated by the Cohen procedure alone from 1984 to 1989, 27 patients who could be followed up for 5 years or longer were enrolled in the study (11 males and 16 females, with a mean age of 13.4 years at surgery). In principle, they were followed up using annual cystography, excretory urography, and blood and urine tests. At the final assessment, they were examined for the presence at VUR and for morphological abnormalities of the urinary tract. Their renal function was also assessed. They were followed for 6 to 13 years (mean: 8.9 years), and the mean age at final assessment was 22.2 years. Among 42 ureters in the 27 patients examined, 38 ureters (90.5%) in 22 patients (81.5%) did not have VUR postoperatively. Four ureters in 4 patients had the recurrence of VUR, and in another patient new occurrence was detected postoperatively. Augmentation ileocystoplasty was performed to treat the postoperative decrease of bladder compliance in 4 patients. Among 22 patients who had hydronephrosis preoperatively, 9 (40.9%) showed improvement and none suffered from aggravation of this condition. None of the patients showed a decline of renal function, except for 1 who had a serum creatinine of 2.5 mg/dl preoperatively and developed end-stage renal failure at 7 years postoperatively. The Cohen procedure has an excellent anti-reflux effect. It is one of the therapeutic options for VUR in patients with good bladder compliance.

Functional vitamin B-6 status and long-term mortality in renal transplant recipients.

PubMed

Minović, Isidor; van der Veen, Anna; van Faassen, Martijn; Riphagen, Ineke J; van den Berg, Else; van der Ley, Claude; Gomes-Neto, António W; Geleijnse, Johanna M; Eggersdorfer, Manfred; Navis, Gerjan J; Kema, Ido P; Bakker, Stephan Jl

2017-12-01

Background: Low plasma concentrations of pyridoxal 5'-phosphate (PLP) are common in renal transplant recipients (RTRs) and confer increased risk of long-term mortality. To our knowledge, it is not known whether low plasma PLP concentrations have functional (i.e., intracellular) consequences and, if so, whether such consequences are associated with increased risk of mortality. Objectives: We assessed the association of plasma PLP with functional vitamin B-6 status and explored the potential association of functional vitamin B-6 status with long-term mortality in RTRs. Design: In a longitudinal cohort of 678 stable RTRs with a median follow-up of 5.3 y (IQR: 4.8-6.1 y) and 297 healthy controls, PLP, plasma 3-hydroxykynurenine (3-HK), and xanthurenic acid (XA) were analyzed via validated assays. PLP was used as direct biomarker for vitamin B-6 status, and the 3-HK:XA ratio was used as functional biomarker of vitamin B-6 status with a higher ratio reflecting worse functional vitamin B-6 status. Results: Median PLP, 3-HK, and XA concentrations were 41 nmol/L (IQR: 29-60 nmol/L), 40.1 nmol/L (IQR: 33.0-48.0 nmol/L), and 19.1 nmol/L (IQR: 14.5-24.9 nmol/L), respectively, in healthy controls compared with 29 nmol/L (IQR: 17-50 nmol/L), 61.5 nmol/L (IQR: 45.6-86.5 nmol/L), and 25.5 nmol/L (IQR: 17.2-40.0 nmol/L), respectively, in RTRs (all P < 0.001). RTRs had a higher median 3-HK:XA ratio (2.38; IQR: 1.68-3.49) than did healthy controls (2.13; IQR: 1.63-2.71) ( P < 0.05). In RTRs, the 3-HK:XA ratio was inversely associated with plasma PLP (β = -0.21, P < 0.001). Moreover, a higher 3-HK:XA ratio was independently associated with increased risk of all-cause mortality (HR per SD increment: 1.30; 95% CI: 1.13, 1.49), cancer mortality (HR per SD increment: 1.47; 95% CI: 1.12, 1.95), and infectious disease mortality (HR per SD increment: 1.50; 95% CI: 1.21, 1.86) in RTRs. Conclusions: Vitamin B-6-deficient RTRs have a worse functional vitamin B-6 status than do healthy controls and vitamin B-6-sufficient RTRs. Worse functional vitamin B-6 status in RTRs is independently associated with an increased risk of mortality particularly because of cancer and infectious disease. This trial was registered at clinicaltrials.gov as NCT02811835. © 2017 American Society for Nutrition.

Asymptomatic CMV infections in long-term renal transplant recipients are associated with the loss of FcRγ from LIR-1+ NK cells.

PubMed

Makwana, Nandini B; Foley, Bree; Lee, Silvia; Fernandez, Sonia; Irish, Ashley B; Price, Patricia

2016-11-01

While it is established that cytomegalovirus (CMV) disease affects NK-cell profiles, the functional consequences of asymptomatic CMV replication are unclear. Here, we characterize NK cells in clinically stable renal transplant recipients (RTRs; n = 48) >2 years after transplantation. RTRs and age-matched controls (n = 32) were stratified by their CMV serostatus and the presence of measurable CMV DNA. CMV antibody or CMV DNA influenced expression of NKG2C, LIR-1, NKp30, NKp46, and FcRγ, a signaling adaptor molecule, on CD56 dim NK cells. Phenotypic changes ascribed to CMV were clearer in RTRs than in control subjects and affected NK-cell function as assessed by TNF-α and CD107a expression. The most active NK cells were FcRγ - LIR-1 + NKG2C - and displayed high antibody-dependent cell cytotoxicity responses in the presence of immobilized CMV glycoprotein B reactive antibody. However, perforin levels in supernatants from RTRs with active CMV replication were low. Overall we demonstrate that CMV can be reactivated in symptom-free renal transplant recipients, affecting the phenotypic, and functional profiles of NK cells. Continuous exposure to CMV may maintain and expand NK cells that lack FcRγ but express LIR-1. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Prediction of cardiovascular outcome by estimated glomerular filtration rate and estimated creatinine clearance in the high-risk hypertension population of the VALUE trial.

PubMed

Ruilope, Luis M; Zanchetti, Alberto; Julius, Stevo; McInnes, Gordon T; Segura, Julian; Stolt, Pelle; Hua, Tsushung A; Weber, Michael A; Jamerson, Ken

2007-07-01

Reduced renal function is predictive of poor cardiovascular outcomes but the predictive value of different measures of renal function is uncertain. We compared the value of estimated creatinine clearance, using the Cockcroft-Gault formula, with that of estimated glomerular filtration rate (GFR), using the Modification of Diet in Renal Disease (MDRD) formula, as predictors of cardiovascular outcome in 15 245 high-risk hypertensive participants in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial. For the primary end-point, the three secondary end-points and for all-cause death, outcomes were compared for individuals with baseline estimated creatinine clearance and estimated GFR < 60 ml/min and > or = 60 ml/min using hazard ratios and 95% confidence intervals. Coronary heart disease, left ventricular hypertrophy, age, sex and treatment effects were included as covariates in the model. For each end-point considered, the risk in individuals with poor renal function at baseline was greater than in those with better renal function. Estimated creatinine clearance (Cockcroft-Gault) was significantly predictive only of all-cause death [hazard ratio = 1.223, 95% confidence interval (CI) = 1.076-1.390; P = 0.0021] whereas estimated GFR was predictive of all outcomes except stroke. Hazard ratios (95% CIs) for estimated GFR were: primary cardiac end-point, 1.497 (1.332-1.682), P < 0.0001; myocardial infarction, 1.501 (1.254-1.796), P < 0.0001; congestive heart failure, 1.699 (1.435-2.013), P < 0.0001; stroke, 1.152 (0.952-1.394) P = 0.1452; and all-cause death, 1.231 (1.098-1.380), P = 0.0004. These results indicate that estimated glomerular filtration rate calculated with the MDRD formula is more informative than estimated creatinine clearance (Cockcroft-Gault) in the prediction of cardiovascular outcomes.

Journey of a cystinuric patient with a long-term follow-up from a medical stone clinic: necessity to be SaFER (stone and fragments entirely removed).

PubMed

Moore, Sacha L; Somani, Bhaskar K; Cook, Paul

2018-04-25

There is a lack of studies looking at the longitudinal follow-up of patients with cystine stones. We wanted to assess the journey of cystinuric patients through our specialist metabolic stone clinic to improve the understanding of episodes, interventions and current outcomes in this patient cohort. After ethical approval, all patients who attended our metabolic stone clinic from 1994 to 2014 with at least one cystine stone episode were included in our study. Data were retrospectively analysed for patient demographics, stone episodes or intervention, clinical parameters and patient compliance. Over a period of 21 years, 16 patients with a median age of 15.5 years underwent a mean follow-up of 8.6 years (1-21 years). The mean number of surgical interventions was 3.1 (1-8/patient), but patients who were stone free after their first treatment had lower recurrences (p = 0.91) and lower number of interventions during their follow-up (2.7/patient, compared to those who were not stone free at 4/patient). During their follow-up period, patients with < 3 interventions had a significantly better renal function than those with ≥ 3 surgical interventions (p = 0.04). Additionally, linear regression analysis showed that eGFR was demonstrated to decline with increasing numbers of stone episodes (r 2  = 0.169). It was also noted that patients who began early medical management remained stone free during follow-up compared to those who had medical management after ≥ 2 stone episodes, of whom all had a recurrent episode. Our long-term longitudinal study of cystine stone formers highlights that patients who are stone free and receive early metabolic stone screening and medical management after their initial presentation have the lowest recurrence rates and tend to preserve their renal function. Hence, prompt referral for metabolic assessment, and the stone and fragments entirely removed (SaFER) principles are key to preventing stone episodes and improving long-term function.

Acute bacterial sternoclavicular osteomyelitis in a long-term renal transplant recipient

PubMed Central

Dounousi, Evangelia; Duni, Anila; Xiromeriti, Sofia; Pappas, Charalambos; Siamopoulos, Kostas C

2016-01-01

Kidney transplantation is the treatment of choice for a significant number of patients with end-stage renal disease. Although immunosuppression therapy improves graft and patient’s survival, it is a major risk factor for infection following kidney transplantation altering clinical manifestations of the infectious diseases and complicating both the diagnosis and management of renal transplant recipients (RTRs). Existing literature is very limited regarding osteomyelitis in RTRs. Sternoclavicular osteomyelitis is rare and has been mainly reported after contiguous spread of infection or direct traumatic seeding of the bacteria. We present an interesting case of acute, bacterial sternoclavicular osteomyelitis in a long-term RTR. Blood cultures were positive for Streptococcus mitis, while the portal entry site was not identified. Magnetic resonance imaging of the sternoclavicluar region and a three-phase bone scan were positive for sternoclavicular osteomyelitis. Eventually, the patient was successfully treated with Daptomycin as monotherapy. In the presence of immunosuppression, the transplant physician should always remain alert for opportunistic pathogens or unusual location of osteomyelitis. PMID:27358791

Acute bacterial sternoclavicular osteomyelitis in a long-term renal transplant recipient.

PubMed

Dounousi, Evangelia; Duni, Anila; Xiromeriti, Sofia; Pappas, Charalambos; Siamopoulos, Kostas C

2016-06-24

Kidney transplantation is the treatment of choice for a significant number of patients with end-stage renal disease. Although immunosuppression therapy improves graft and patient's survival, it is a major risk factor for infection following kidney transplantation altering clinical manifestations of the infectious diseases and complicating both the diagnosis and management of renal transplant recipients (RTRs). Existing literature is very limited regarding osteomyelitis in RTRs. Sternoclavicular osteomyelitis is rare and has been mainly reported after contiguous spread of infection or direct traumatic seeding of the bacteria. We present an interesting case of acute, bacterial sternoclavicular osteomyelitis in a long-term RTR. Blood cultures were positive for Streptococcus mitis, while the portal entry site was not identified. Magnetic resonance imaging of the sternoclavicluar region and a three-phase bone scan were positive for sternoclavicular osteomyelitis. Eventually, the patient was successfully treated with Daptomycin as monotherapy. In the presence of immunosuppression, the transplant physician should always remain alert for opportunistic pathogens or unusual location of osteomyelitis.

Creatinine reduction ratio: a useful marker to identify medium and high-risk renal transplants.

PubMed

Vilar, Enric; Varagunam, Mira; Yaqoob, Muhammad M; Raftery, Martin; Thuraisingham, Raj

2010-01-15

Delayed graft function (DGF) has a major impact on long-term renal transplant survival. However, it is a diagnosis made retrospectively with little opportunity to modify treatment protocols. A classification based on creatinine reduction ratio between days 1 and 2 (CRR2) suggests that patients with CRR2 less than or equal to 30% (nondialysis requiring DGF [ND-DGF]) have similar outcomes to those with dialysis-requiring delayed graft function (D-DGF). We retrospectively applied this definition in our cohort of patients to examine outcomes. We studied the association between CRR2 and graft outcomes in all 367 patients transplanted between 1996 and 2004 at our center. Patients were divided into the following three groups: IGF (immediate graft function; CRR2 >30%), D-DGF, and ND-DGF. Mean follow-up was 4.2 years. IGF accounted for 36% of patients, D-DGF for 22%, and ND-DGF for 42%. CRR2 was inversely correlated with serum creatinine on days 7, 30, 90, and 365 (r ranging from -0.65 to -0.22, P<0.001). Graft survival at 5 years was 98% (IGF), 74% (D-DGF), and 89% (ND-DGF). There was a significant difference in graft survival between IGF and D-DGF (P<0.001) and IGF and ND-DGF (P=0.005). In a multivariate analysis adjusting for recipient age and sex, donor age and sex, and human leukocyte antigen mismatch, graft failure was 2.4 times more likely to occur in patients with D-DGF than those with ND-DGF(P=0.02). Our study shows CRR2 influences long-term graft outcomes. Unlike the original description, patients with ND-DGF carry an intermediate risk and perhaps should be considered on day 2 for alternative treatment protocols.

Renal function changes after fenestrated endovascular aneurysm repair.

PubMed

Tran, Kenneth; Fajardo, Andres; Ullery, Brant W; Goltz, Christopher; Lee, Jason T

2016-08-01

Limited data exist regarding the effect of fenestrated endovascular aneurysm repair (fEVAR) on renal function. We performed a comprehensive analysis of acute and chronic renal function changes in patients after fEVAR. This study included patients undergoing fEVAR at two institutions between September 2012 and March 2015. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease formula with serum creatinine levels obtained during the study period. Acute and chronic renal dysfunction was assessed using the RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) criteria and the chronic kidney disease (CKD) staging system, respectively. fEVAR was performed in 110 patients for juxtarenal or paravisceral aortic aneurysms, with a mean follow-up of 11.7 months. A total of 206 renal stents were placed, with a mean aneurysm size of 62.9 mm (range, 45-105 mm) and a mean neck length of 4.1 mm. Primary renal stent patency was 97.1% at the latest follow-up. Moderate kidney disease (CKD stage ≥ 3) was present in 51% of patients at baseline, with a mean preoperative glomerular filtration rate of 60.0 ± 19.6 mL/min/1.73 m 2 . Acute kidney injury occurred in 25 patients (22.7%), although 15 of these (60%) were classified as having mild dysfunction. During follow-up, 59 patients (73.7%) were found to have no change or improved renal disease by CKD staging, and 19 (23.7%) had a CKD increase of one stage. Two patients were noted to have end-stage renal failure requiring hemodialysis. Clinically significant renal dysfunction was noted in 21 patients (26.2%) at the latest follow-up. Freedom from renal decline at 1 year was 76.1% (95% confidence interval, 63.2%-85.0%). Surrogate markers for higher operative complexity, including operating time (P = .001), fluoroscopy time (P < .001), contrast volume (P = .017), and blood loss (P = .002), served as dependent risk factors for acute kidney injury, although though no independent predictors were identified. Age (P = .008) was an independent risk factor for long-term decline, whereas paradoxically, baseline kidney disease (P = .032) and longer operative times (P = .014) were protective of future renal dysfunction. Acute and chronic renal dysfunction both occur in approximately one-quarter of patients after fEVAR; however, most of these cases are classified as mild according to consensus definitions of renal injury. The presence of mild or moderate baseline kidney disease should not preclude endovascular repair in the juxtarenal population. Routine biochemical analysis and branch vessel surveillance remain important aspects of clinical follow-up for patients undergoing fEVAR. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

C-A4-01: Computerized Clinical Decision Support During Drug Ordering for Long-term Care Residents With Renal Insufficiency

PubMed Central

Field, Terry S; Rochon, Paula; Lee, Monica; Gavendo, Linda; Baril, Joann L; Gurwitz, Jerry H

2010-01-01

Objective: To determine whether a computerized clinical decision support system (CDSS) providing patient specific recommendations in real- time improves the quality of prescribing for long-term care residents with renal insufficiency. Design: A randomized trial within the long-stay units of a large long-term care facility. Randomization was within blocks by unit type. Alerts related to medication prescribing for residents with renal insufficiency were displayed to prescribers in the intervention units and hidden but tracked in control units. Measurement: The proportions of final drug orders that were appropriate were compared between intervention and control units within alert categories: recommended medication doses; recommended administration frequencies; recommendations to avoid the drug; 4) warnings of missing information. Results: The rates of alerts were nearly equal in the intervention and control units: 2.5 per 1000 resident days in the intervention units and 2.4 in the control units. The proportions of dose alerts for which the final drug orders were appropriate were similar between the intervention and control units (relative risk 0.95, 95% confidence interval 0.83, 1.1). For the remaining alert categories significantly higher proportions of final drug orders were appropriate in the intervention units: relative risk 2.4 for maximum frequency (1.4, 4.4); 2.6 for drugs that should be avoided (1.4, 5.0); and 1.8 for alerts to acquire missing information (1.1, 3.4). Overall, final drug orders were appropriate significantly more often than a relative risk 1.2 (1.0, 1.4). By tracking personnel time and expenditures, we estimated the cost of developing the CDSS as $48,668.57. Drug costs saved during the 12 months of the trial are estimated at $2,137. Conclusion: Clinical decision support for physicians prescribing medications for long-term care residents with renal insufficiency can improve the quality of prescribing decisions. However, patient well-being and quality of care rather than the business case related to cost savings are likely to be the key drivers for adoption of this HIT application.

Long-term prognosis of AL and AA renal amyloidosis: a Japanese single-center experience.

PubMed

Ozawa, Masatoyo; Komatsuda, Atsushi; Ohtani, Hiroshi; Nara, Mizuho; Sato, Ryuta; Togashi, Masaru; Takahashi, Naoto; Wakui, Hideki

2017-04-01

Few studies have been conducted on the long-term prognosis of patients with amyloid light chain (AL) and amyloid A (AA) renal amyloidosis in the same cohort. We retrospectively examined 68 patients with biopsy-proven renal amyloidosis (38 AL and 30 AA). Clinicopathological findings at the diagnosis and follow-up data were evaluated in each patient. We analyzed the relationship between clinicopathological parameters and survival data. Significant differences were observed in several clinicopathological features, such as proteinuria levels, between the AL and AA groups. Among all patients, 84.2 % of the AL group and 93.3 % of the AA group received treatments for the underlying diseases of amyloidosis. During the follow-up period (median 18 months in AL and 61 months in AA), 36.8 % of the AL group and 36.7 % of the AA group developed end-stage renal failure requiring dialysis, while 71.1 % of the AL group and 56.7 % of the AA group died. Patient and renal survivals were significantly longer in the AA group than in the AL group. eGFR of >60 mL/min/1.73 m 2 at biopsy and an early histological stage of glomerular amyloid deposition were identified as low-risk factors. A multivariate analysis showed that cardiac amyloidosis and steroid therapy significantly influenced patient and renal survivals. Our results showed that heart involvement was the major predictor of poor outcomes in renal amyloidosis, and that the prognosis of AA renal amyloidosis was markedly better than that in previously reported cohorts. Therapeutic advances in inflammatory diseases are expected to improve the prognosis of AA amyloidosis.

Survival is not enough: reflections of a long-term renal patient.

PubMed

Eady, Robin A J

2008-01-01

A kidney patient recalls his experience of almost 45 years of renal replacement therapy covering nearly 25 years of dialysis and 20 years with a transplant. At the beginning, patient or graft survival was a major goal and symbol of successful treatment. But for the patient, what really matters is the quality of his life, assuming he can survive.

Induction of IL-8(CXCL8) and MCP-1(CCL2) with oxidative stress and its inhibition with N-acetyl cysteine (NAC) in cell culture model using HK-2 cell.

PubMed

Kumar, Avneesh; Shalmanova, Liliana; Hammad, Abdul; Christmas, Stephen E

2016-03-01

Renal transplantation can often be complicated due to delayed graft function, which is a direct sequel of ischaemia reperfusion injury. The adverse outcome of delayed graft function is not only short term but the long-term function of the graft is also affected. Therefore, it is important to understand the mechanisms of ischaemia reperfusion injury. Reactive oxygen species are the key mediators in ischaemia reperfusion injury causing direct cell damage which also initiate inflammation by inducing chemokines. The presence of inflammation is a marker of severe delayed graft function. However, the effect of oxidative stress on the expression of key chemokines has not been fully established yet. Therefore, the aim of this study was to measure the oxidative stress response and the secretion of chemokines in a cell culture model that mimics the effects of ischaemia reperfusion injury in immortalised human renal proximal tubular epithelial cells, HK-2. Cells were treated with varying concentrations of hydrogen peroxide and markers of oxidative stress response and chemokine release were measured. Exposure to hydrogen peroxide induced a significant increase in the activity of the antioxidant enzyme glutathione peroxidase and the levels of the chemokines Interleukin-8 (IL-8; CXCL8) and MCP-1 (CCL2). A dose related increase of chemokine secretion was also observed. The cytokine Interleukin-1β (IL-1β) at 1 ng/ml significantly potentiated the expression of both IL-8 (CXCL8) and MCP-1 (CCL2) which showed synergistic response in the presence of hydrogen peroxide. Pre-incubation of the cells with the anti-oxidant N-acetyl cysteine (NAC) strongly suppressed the induction of both IL-8 and MCP-1 when stimulated with hydrogen peroxide and IL-1β. This study demonstrates the potential of anti-oxidants like N-acetyl cysteine in ameliorating the effects of ischaemia reperfusion injury thus suggesting a new therapeutic approach in renal transplantation. These findings can have potential implications for clinical use to prevent ischaemia reperfusion injury in renal transplantation. Copyright © 2016 Elsevier B.V. All rights reserved.

Chronic kidney disease in congenital heart disease patients: a narrative review of evidence.

PubMed

Morgan, Catherine; Al-Aklabi, Mohammed; Garcia Guerra, Gonzalo

2015-01-01

Patients with congenital heart disease have a number of risk factors for the development of chronic kidney disease (CKD). It is well known that CKD has a large negative impact on health outcomes. It is important therefore to consider that patients with congenital heart disease represent a population in whom long-term primary and secondary prevention strategies to reduce CKD occurrence and progression could be instituted and significantly change outcomes. There are currently no clear guidelines for clinicians in terms of renal assessment in the long-term follow up of patients with congenital heart disease. Consolidation of knowledge is critical for generating such guidelines, and hence is the purpose of this view. This review will summarize current knowledge related to CKD in patients with congenital heart disease, to highlight important work that has been done to date and set the stage for further investigation, development of prevention strategies, and re-evaluation of appropriate renal follow-up in patients with congenital heart disease. The literature search was conducted using PubMed and Google Scholar. Current epidemiological evidence suggests that CKD occurs in patients with congenital heart disease at a higher frequency than the general population and is detectable early in follow-up (i.e. during childhood). Best evidence suggests that approximately 30 to 50 % of adult patients with congenital heart disease have significantly impaired renal function. The risk of CKD is higher with cyanotic congenital heart disease but it is also present with non-cyanotic congenital heart disease. Although significant knowledge gaps exist, the sum of the data suggests that patients with congenital heart disease should be followed from an early age for the development of CKD. There is an opportunity to mitigate CKD progression and negative renal outcomes by instituting interventions such as stringent blood pressure control and reduction of proteinuria. There is a need to invest time, thought and money to fill existing knowledge gaps to improve health outcomes in this population. This review should serve as an impetus for generation of follow-up guidelines of kidney health evaluation in patients with congenital heart disease.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riezzo, Irene; Turillazzi, Emanuela; Bello, Stefania

Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneysmore » of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways. - Highlights: • We analyze abuse of nandrolone decanoate in strength-trained male CD1 mice. • Nandrolone decanoate administration increases oxidative stress. • Increased cytokine expressions were observed. • Renal apoptosis was described. • Long-term administration of nandrolone promotes oxidative injury in mice kidney.« less

Obesity in the Kidney Transplant Process.

PubMed

Ateş, Damla; Cebeci, Fatma

2018-03-01

Obesity, which has become an increasing problem worldwide, poses a risk for kidney transplant recipients both before and after surgery. In this literature review, we studied the effects of obesity before and after kidney transplant. There are numerous studies and different opinions on the effects of obesity on graft function before and after transplant. Obesity prolongs surgery time and the ischemic process. A large cohort study of 11 836 recipients noted a close association between body mass index and delayed renal transplant and delayed graft function. However, another study found that being overweight or obese before transplant did not have any effects over the medium and long term. A 20-year follow-up study indicated that the firstyear body mass index in recipients after renal transplant had a greater effect on graft function and survival than body mass index before transplant. Still, another study found that body mass index had no effects on graft function and survival. In the study, 3-year graft function and mortality rates of morbidly obese people without diabetes, the functional status without dialysis, and living-donor transplant were reported to be much lower than in those with normal weight. In conclusion, there is no consensus on the effects of obesity before and after transplant, and it has been pointed out that more research should be done on this subject.

The impact of serum uric acid reduction on renal function and blood pressure in chronic kidney disease patients with hyperuricemia.

PubMed

Tsuji, Takayuki; Ohishi, Kazuhisa; Takeda, Asumi; Goto, Daiki; Sato, Taichi; Ohashi, Naro; Fujigaki, Yoshihide; Kato, Akihiko; Yasuda, Hideo

2018-04-26

Febuxostat is tolerable in chronic kidney disease (CKD) patients with hyperuricemia. However, the long-term effect of lowering uric acid with febuxostat on renal function and blood pressure has not been elucidated. This was a 2 years retrospective observational study. 86 CKD patients with hyperuricemia who continued with allopurinol (allopurinol group, n = 30), switched from allopurinol to febuxostat (switched group, n = 25), or were newly prescribed febuxostat (febuxostat group, n = 31) were included in this study. Serum uric acid, estimated glomerular filtration rate (eGFR), blood pressure, and urinary protein were analyzed. Moreover, the impact of serum uric acid reduction on renal function and blood pressure was assessed. Serum uric acid in the switched and febuxostat groups was significantly reduced at 6 months (switched group; 8.49 ± 1.32-7.19 ± 1.14 mg/dL, p < 0.0001, febuxostat group; 9.43 ± 1.63-6.31 ± 0.90 mg/dL, p < 0.0001). In the allopurinol group, serum uric acid was increased (6.86 ± 0.87-7.10 ± 0.85 mg/dL, p = 0.0213). eGFR was significantly increased (35.2 ± 12.8-37.3 ± 13.9 mL/min/1.73 m 2 , p = 0.0232), while mean arterial pressure (93.1 ± 10.8-88.2 ± 9.5 mmHg, p = 0.0039) was significantly decreased at 6 months in the febuxostat group, resulting in the retention of eGFR for 2 years. The impact of serum uric acid reduction might have beneficial effects on CKD progression and blood pressure. However, a large prospective study is needed to determine the long-term efficacy of febuxostat therapy in CKD patients with hyperuricemia.

Predictors of long-term mortality following elective endovascular repair of abdominal aortic aneurysms.

PubMed

Marques-Rios, Guilherme; Oliveira-Pinto, José; Mansilha, Armando

2018-05-09

Endovascular aneurysm repair (EVAR) became the preferred modality for abdominal aortic aneurysm (AAA) repair. However, long term survival benefit may sometimes be questionable as many patients would die from other causes rather than aneurysm rupture. It is paramount to identify critical risk factors for late mortality after EVAR to understand its real benefit. The aim of this review is to identify most clinically relevant determinants of late mortality after elective EVAR. English literature was searched to identify publications on long-term predictors of mortality following elective EVAR. A follow-up extending for at least 5 years was the minimum required as inclusion criteria. Primary endpoint was all-cause mortality. We addressed clinical and demographic variables and observe if they had any associations with long-term all-cause mortality following EVAR. Thirteen studies were included describing more than 82306 patients, exploring at least one predictors of long-term mortality. All-cause mortality was associated to age (Hazard Ratio[HR] 1.06-3.34), gender (HR 1.07), aneurysm diameter (HR 1.09-1.64), smoking habits (HR 1.51-1.73), heart failure (HR 1.60-7.34), ischemic heart disease (HR 1.60), peripheral vascular disease (HR 1.30), cerebrovascular disease (HR 1.55), diabetes mellitus (HR 6.35), chronic obstructive pulmonary disease (HR 1.50-2.06) and chronic renal disease (HR 1.90-3.08). Risk factors associated with long-term mortality following elective EVAR remain scarcely published. Several demographic, anatomical, cardiovascular, pulmonary and renal co-morbidities seem to have an association with long-term mortality. Critical scrutiny of clinical patient status remains fundamental for a fair health resources allocation.

Hypomagnesemia and mild rhabdomyolysis in living related donor renal transplant recipient treated with cyclosporine A.

PubMed

Cavdar, C; Sifil, A; Sanli, E; Gülay, H; Camsari, T

1998-12-01

Since cyclosporine A (CsA) had been used in renal transplant recipients, important improvements in short-term and long-term graft survivals have been detected. In spite of these improvements CsA seems to have several adverse effects. First, CsA leads to nephrotoxicity. Moreover, CsA affects the other organs and systems (skin, liver, nervous system, etc.) and causes, increased risks of infections and malignancies. Hypomagnesemia is one of the side effects of CsA therapy, but it is a rare condition in living related donor renal transplant recipients. It may also cause multi-system dysfunction, especially hypocalcemia and hypokalemia, which cannot be corrected without magnesium therapy. In addition, rhabdomyolysis was detected in animals, but it has not been reported in living related donor renal transplant recipients. In this case report, a living related donor renal transplant recipient who suffered from hypomagnesemia and mild rhabdomyolysis due to CsA therapy will be described and discussed.

Effect of suprarenal versus infrarenal aortic endograft fixation on renal function and renal artery patency: a comparative study with intermediate follow-up.

PubMed

Lau, L Louis; Hakaim, Albert G; Oldenburg, W Andrew; Neuhauser, Beate; McKinney, J Mark; Paz-Fumagalli, Ricardo; Stockland, Andrew

2003-06-01

Suprarenal fixation of aortic endografts appears to be a safe option in patients with a short or conical proximal aortic neck. However, concern persists regarding the long-term effect on renal function when renal artery ostia are crossed by the uncovered stent. We investigated the effect of suprarenal versus infrarenal endograft fixation on renal function and renal artery patency after endovascular aortic aneurysm repair. Records of 91 patients who underwent endovascular aortic aneurysm repair with a modular bifurcated stent graft between November 1999 and January 2002 were reviewed retrospectively. Two patients receiving dialysis because of chronic renal failure were excluded. Infrarenal fixation was used in 57 patients (group 1), and suprarenal fixation was used in 32 patients (group 2). In two patients in group 1 a Gianturco Z stent was inserted transrenally because of intraoperative proximal type I endoleak, and data for these patients were excluded from analysis. Follow-up evaluation was performed at 1, 6, and 12 months, and yearly thereafter, and included clinical assessment, measurement of serum creatinine concentration (SCr), and computed tomography angiography, per standard protocol. Median follow-up was 12 months (range, 1-36 months). There was no statistically significant difference in patient demographic data, aneurysm size, or preoperative risk factors. Median SCr was significantly higher in group 2 (suprarenal fixation) than in group 1 (infrarenal fixation) preoperatively (1.2 mg/dL [range, 0.6-2.3 mg/dL] vs 0.9 mg/dL [range, 0.6-1.9 mg/dL], P =.008) and at 1 month postoperatively (1.1 mg/dL [range, 0.8-5.6 mg/dL] vs 1.0 mg/dL [range, 0.6-2.1 mg/dL], P =.045). There was a significant increase in median SCr in both groups at 1 month postoperatively (group 1, 1.0 mg/dL [range, 0.6-2.1 mg/dL], P =.05; group 2, 1.1 mg/dL [range, 0.8-5.6 mg/dL] [mean SCr, 1.35 mg/dL vs 1.15 mg/dL, respectively], P <.05). In group 1 SCr was increased significantly at 6 and 12 months (P <.001), whereas in group 2 SCr also increased at 6 and 12 months, but not significantly. The change in SCr over time was not significantly different between the two groups. In two of 32 patients in group 2, renal artery occlusion developed, associated with perfusion defects in renal parenchyma and persistently elevated SCr. Analysis of renal artery patency did not demonstrate any association between patency and treatment. No patient developed hypertension during follow-up. Suprarenal endograft fixation does not lead to significant renal dysfunction, and renal artery occlusion is uncommon within 12 months. A larger study with longer follow-up is essential to determine overall effects on renal function and renal artery patency.

The effect of antiepileptic drugs on the kidney function and structure.

PubMed

Hamed, Sherifa Ahmed

2017-09-01

Long-term use of antiepileptic drugs (AEDs) is associated with number of somatic conditions. Data from experimental, cross-sectional and prospective studies have evidence for the deleterious effect of some AEDs on the kidney. Areas covered: This review summarized the current knowledge of the effect of AEDs on the kidney including evidence and mechanisms. Fanconi syndrome was reported with valproate (VPA) therapy in severely disabled children with epilepsy. Renal tubular acidosis and urolithiasis were reported with acetazolamide, topirmate and zonisamide, drugs with carbonic anhydrase inhibition properties. Increased levels of urinary N-acetyl-beta-D-glucosaminidase (NAG) to urinary creatinine (U-NAG/UCr), urinary excretion of α1-micrglobulin, β-galactosidase activity; and urinary malondialdehyde to creatinine (MDA/Cr), markers of renal glomerular and tubular injury, were reported with chronic use of some AEDs (VPA, carbamazepine and phenytoin). The mechanism(s) of kidney dysfunction/injury induced by AEDs is unknown. Experimental and clinical studies have shown that VPA induces oxidative stress, mitochondrial deficits, carnitine deficiency and inflammation and fibrosis in renal tissue in mice and in vitro studies. Expert commentary: It seems reasonable to monitor kidney function during treating patients with epilepsy at high risk of kidney injury (e.g. on combined therapy with more than one AED, severely disabled children, etc).

Renal-Clearable Ultrasmall Coordination Polymer Nanodots for Chelator-Free 64Cu-Labeling and Imaging-Guided Enhanced Radiotherapy of Cancer.

PubMed

Shen, Sida; Jiang, Dawei; Cheng, Liang; Chao, Yu; Nie, Kaiqi; Dong, Ziliang; Kutyreff, Christopher J; Engle, Jonathan W; Huang, Peng; Cai, Weibo; Liu, Zhuang

2017-09-26

Developing tumor-homing nanoparticles with integrated diagnostic and therapeutic functions, and meanwhile could be rapidly excreted from the body, would be of great interest to realize imaging-guided precision treatment of cancer. In this study, an ultrasmall coordination polymer nanodot (CPN) based on the coordination between tungsten ions (W VI ) and gallic acid (W-GA) was developed via a simple method. After polyethylene glycol (PEG) modification, PEGylated W-GA (W-GA-PEG) CPNs with an ultrasmall hydrodynamic diameter of 5 nm were rather stable in various physiological solutions. Without the need of chelator molecules, W-GA-PEG CPNs could be efficiently labeled with radioisotope 64 Cu 2+ , enabling positron emission tomography (PET) imaging, which reveals efficient tumor accumulation and rapid renal clearance of W-GA-PEG CPNs upon intravenous injection. Utilizing the radio-sensitizing function of tungsten with strong X-ray absorption, such W-GA-PEG CPNs were able to greatly enhance the efficacy of cancer radiotherapy in inhibiting the tumor growth. With fast clearance and little long-term body retention, those W-GA-PEG CPNs exhibited no appreciable in vivo toxicity. This study presents a type of CPNs with excellent imaging and therapeutic abilities as well as rapid renal clearance behavior, promising for further clinic translation.

Belatacept: a novel biologic for maintenance immunosuppression after renal transplantation.

PubMed

Martin, Spencer T; Tichy, Eric M; Gabardi, Steven

2011-04-01

In the past decade, the availability of new immunosuppressive maintenance therapies for use in solid organ transplantation has remained limited. Patients and clinicians have relied on immunosuppressive drugs that require a significant amount of therapeutic monitoring and are associated with a variety of adverse effects that affect both quality of life and allograft function. Belatacept is an investigational intravenous biologic agent for long-term use in renal transplant recipients. The costimulatory pathway (signal 2) of T-cell activation and proliferation is produced by stimulation of the T-cell surface marker, CD28, and is essential to the immune system's cellular response and ability to recognize an allograft as foreign. Belatacept is a potent antagonist of B7-1 (CD80) and B7-2 (CD86) ligands present on antigen-presenting cells that are responsible for activation of CD28. Recent phase III trials describe various dosing strategies of belatacept versus a standard cyclosporine protocol in recipients of both living- and deceased-donor renal transplants, as well as in patients receiving kidneys transplanted from extended-criteria donors. Compared with cyclosporine, belatacept has been shown to be noninferior in both patient and allograft survival rates. However, the rate of biopsy-proven acute cellular rejection occurred more frequently in the belatacept groups. Also, compared with standard calcineurin-based regimens, the risk of posttransplant lymphoproliferative disorder is increased in patients receiving belatacept, with the greatest risk in transplant recipients who are Epstein-Barr virus seronegative before transplantation. However, this investigational immunosuppressive agent may avert common adverse effects experienced with standard immunosuppressive protocols including renal dysfunction, metabolic disorders, neurotoxicities, glucose abnormalities, and cosmetic effects. More data on the long-term risks of belatacept are needed to better define its role as immunosuppressive maintenance therapy. Aside from an increased risk of malignancy, belatacept's limited adverse-effect profile and convenient dosing strategy may make it an attractive option for immuno-suppressive maintenance for both the patient and clinician.

Changes of renal sinus fat and renal parenchymal fat during an 18-month randomized weight loss trial.

PubMed

Zelicha, Hila; Schwarzfuchs, Dan; Shelef, Ilan; Gepner, Yftach; Tsaban, Gal; Tene, Lilac; Yaskolka Meir, Anat; Bilitzky, Avital; Komy, Oded; Cohen, Noa; Bril, Nitzan; Rein, Michal; Serfaty, Dana; Kenigsbuch, Shira; Chassidim, Yoash; Sarusi, Benjamin; Thiery, Joachim; Ceglarek, Uta; Stumvoll, Michael; Blüher, Matthias; Haviv, Yosef S; Stampfer, Meir J; Rudich, Assaf; Shai, Iris

2018-08-01

Data regarding the role of kidney adiposity, its clinical implications, and its dynamics during weight-loss are sparse. We investigated the effect of long-term weight-loss induced intervention diets on dynamics of renal-sinus-fat, an ectopic fat depot, and %renal-parenchymal-fat, lipid accumulation within the renal parenchyma. We randomized 278 participants with abdominal obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets, with or without exercise. We quantified renal-sinus-fat and %renal-parenchymal-fat by whole body magnetic-resonance-imaging. Participants (age = 48 years; 89% men; body-mass-index = 31 kg/m 2 ) had 86% retention to the trial after 18 months. Both increased renal-sinus-fat and %renal-parenchymal-fat were directly associated with hypertension, and with higher abdominal deep-subcutaneous-adipose-tissue and visceral-adipose-tissue (p of trend < 0.05 for all) after adjustment for body weight. Higher renal-sinus-fat was associated with lower estimated-glomerular-filtration-rate and with higher microalbuminuria and %HbA1C beyond body weight. After 18 months of intervention, overall renal-sinus-fat (-9%; p < 0.05 vs. baseline) but not %renal-parenchymal-fat (-1.7%; p = 0.13 vs. baseline) significantly decreased, and similarly across the intervention groups. Renal-sinus-fat and %renal-parenchymal-fat changes were correlated with weight-loss per-se (p < 0.05). In a model adjusted for age, sex, and visceral-adipose-tissue changes, 18 months reduction in renal-sinus-fat associated with decreased pancreatic, hepatic and cardiac fats (p < 0.05 for all) and with decreased cholesterol/high-density lipoprotein-cholesterol (HDL-c) (β = 0.13; p = 0.05), triglycerides/HDL-c (β = 0.13; p = 0.05), insulin (β = 0.12; p = 0.05) and gamma glutamyl transpeptidase (β = 0.24; p = 0.001), but not with improved renal function parameters or blood pressure. Decreased intake of sodium was associated with a reduction in %renal-parenchymal-fat, after adjustment for 18 months weight-loss (β = 0.15; p = 0.026) and hypertension (β = 0.14; p = 0.04). Renal-sinus-fat and renal-parenchymal-fat are fairly related to weight-loss. Decreased renal-sinus-fat is associated with improved hepatic parameters, independent of changes in weight or hepatic fat, rather than with improved renal function or blood pressure parameters. CLINICALTRIALS. NCT01530724. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Hypermethylations of RASAL1 and KLOTHO is associated with renal dysfunction in a Chinese population environmentally exposed to cadmium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Chen; Liang, Yihuai; Key Laboratory of Public Health Safety, Ministry of Education, 130 DongAn Road, Shanghai 200032

2013-08-15

Exposure to cadmium (Cd) can affect both DNA methylation and renal function, but there are few examples of the association between epigenetic markers and Cd-induced kidney damage. It has been suggested that hypermethylation of the genes RASAL1 and KLOTHO is associated with renal fibrogenesis. To investigate whether hypermethylation of RASAL1 and KLOTHO in peripheral blood DNA can be associated with Cd exposure and/or Cd-induced renal dysfunction, the degrees of methylation of RASAL1 and KLOTHO in peripheral blood DNA from 81 residents in Cd-polluted and non-polluted areas were measured using bisulfate-PCR-pyrosequencing. Changes in blood cadmium (BCd), urinary cadmium (UCd), and kidneymore » parameters were measured, and the glomerular filtration rate (eGFR) was estimated. The levels of BCd and UCd correlated positively with the levels of DNA methylation in RASAL1 and in KLOTHO. The more heavily exposed residents (BCd, 4.23–13.22 μg/L; UCd, 8.65–32.90 μg/g creatinine) exhibited obvious renal dysfunction. Notably, when Cd concentration in blood and urine was adjusted, the increased methylation level in RASAL1 was inversely correlated with eGFR (P < 0.01) but the relationship between hypermethylation of KLOTHO and eGFR was not statistically significant. The methylation of RASAL1 increased along with the increased abnormal prevalence of eGFR. Our findings suggest that Cd exposure can induce the hypermethylation of RASAL1 and KLOTHO. Hypermethylation of RASAL1 may be an indicator of the progress for chronic kidney disease. - Highlights: • A long term heavily Cd exposure induced renal dysfunction. • Cd exposure correlated positively with DNA methylation in RASAL1 and KLOTHO. • Hypermethylation of RASAL1 correlated with adjusted renal function indicators.« less

Long-term cardiovascular changes following creation of arteriovenous fistula in patients with end stage renal disease.

PubMed

Reddy, Yogesh N V; Obokata, Masaru; Dean, Patrick G; Melenovsky, Vojtech; Nath, Karl A; Borlaug, Barry A

2017-06-21

Short-term studies have reported left ventricular (LV) dilatation following surgical creation of arteriovenous fistulas (AVF) or arteriovenous grafts (AVGs), but chronic cardiac structural and functional changes have not been examined or related to clinical outcomes following AVF/AVG. We sought to characterize the long-term changes in cardiac structure and function in patients undergoing shunt creation for haemodialysis. A retrospective analysis was performed of patients undergoing echocardiography before and after surgical AVF/AVG creation for the initiation of haemodialysis. 137 patients underwent echocardiographic examinations prior to AVF and 2.6 years (median) after AVF creation. Following AVF and dialysis initiation, there were reductions in blood pressure, body weight and estimated plasma volume coupled with modest reverse LV remodelling. In contrast, AVF/AVG creation was associated with significant right ventricular (RV) dilatation and deterioration in RV function. Incident heart failure (HF) developed in 43% of patients in tandem with greater RV remodeling. The development of RV dilation following surgical AVF/AVG was independently associated with increased risk of death [HR 3.9, 95% CI (1.7-9.2), P = 0.001]. In long-term follow-up, RV remodelling and dysfunction develop following AVF/AVG creation and dialysis initiation, despite improved control of LV pressure load through dialysis. Deleterious effects on right heart structure and function are coupled with development of incident HF and increased risk of death. Further study is required to identify patients at greatest risk for detrimental AVF/AVG changes who may benefit from alternate forms of dialysis or potentially ligation of existing AVF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Emergency management of renal and genitourinary trauma: best practices update [digest].

PubMed

Bryant, Whitney K; Shewakramani, Sanjay; Zaurova, Milana

2017-08-22

In up to 10% of patients who experience abdominal trauma, renal and urogenital systems will be involved. In polytrauma patients with other potentially life-threatening injuries, renal and genitourinary trauma may be overlooked initially, but a delayed or missed diagnosis of these injuries may result in preventable complications. This review provides a best-practice approach to the diagnosis and management of renal and genitourinary injuries, with an emphasis on the systematic approach needed to identify subtle injuries and avoid long-term urinary sequelae such as hypertension, incontinence, erectile dysfunction, chronic kidney disease, and nephrectomy. [Points & Pearls is a digest of Emergency Medicine Practice.].

[Case of young woman with Graves' disease and incomplete distal renal tubular acidosis with severe progress and cardiac arrest].

PubMed

Klimm, Wojciech; Kade, Grzegorz; Spaleniak, Sebastian; Dubchak, Ivanna; Niemczyk, Stanisław

2014-07-01

Diagnostic of renal tubular disorders can be often difficult. Incomplete form of distal Renal Tubular Acidosis (dRta) in course of Graves' disease was de novo recognized in a young woman hospitalized with a deep deficiency of potassium in blood serum complicated with cardiac arrest. Series of tests assessing the types and severity of water-electrolyte, acid-base and thyroid disorders were performed during a complex diagnosis. During the treatment of acute phase of the disease we intensified efforts to maintain basic life functions and to eliminate deep water-electrolyte disturbances. In the second phase of the treatment we determined an underlying cause of the disease, recognized dRTA, and introduced a specific long-term electrolyte and hormonal therapy. To confirm the diagnosis oral test with ammonium chloride (Wrong-Davies' test) was performed. After completion of the diagnostic and therapeutic process, the patient was included in the nephrological supervision on an outpatient basis. The basic drug for the therapy was sodium citrate. After a year of observation and continuing treatment we evaluated therapeutic results as good and permanent.

Significance of anti-phospholipid antibodies in patients with lupus nephritis.

PubMed

Frampton, G; Hicks, J; Cameron, J S

1991-06-01

Anti-phospholipid antibodies (APA) as markers or mediators of thrombosis in lupus could be of pathogenetic significance in nephritis, since glomerular capillary thrombi are an indicator of subsequent renal dysfunction. Isotype specific APA antibodies were measured, using cardiolipin as the antigen, in 76 patients with lupus nephritis. Twenty-nine percent of the patients had elevated IgG APA. Overall, 43% of patients showed raised levels of at least one isotype. In general, APA had specificity for anionic phospholipids. In vitro lupus anticoagulant activity was associated with all three isotypes of APA, but only the IgM isotype correlated with the biological false positive test for syphilis. APA were not associated with thromboses or neurological involvement, and only the IgA isotype correlated with thrombocytopenia. We confirmed an association between the presence of intraglomerular thrombi and serum IgG APA. However, we found no association between APA and renal histological pattern, or long-term renal function. Our data, therefore, do not support a major pathogenetic role for APA in the nephritis of lupus in treated patients.

Evaluation of advanced glycation end products and carbonyl compounds in patients with different conditions of oxidative stress.

PubMed

Lapolla, Annunziata; Reitano, Rachele; Seraglia, Roberta; Sartore, Giovanni; Ragazzi, Eugenio; Traldi, Pietro

2005-07-01

Advanced glycation end products (AGE) and dicarbonyl compounds accumulate in serum and tissues of patients with diabetes and chronic renal failure. Pentosidine, free pentosidine, glyoxal and methylglyoxal have been evaluated in plasma of diabetic patients with poor metabolic control at baseline and after the improvement of glycemic levels, and in plasma and peritoneal dialysate of patients with renal failure before and after 12 h of peritoneal dialysis. In diabetic patients, acceptable metabolic control was unable to normalize levels of pentosidine (after 2 and 10 months), glyoxal and methylglyoxal (after 2 months). In patients with end-stage renal disease, mean values of pentosidine, free pentosidine, glyoxal and methylglyoxal decreased in plasma after dialysis. No pentosidine or free pentosidine were present in the peritoneal dialysate at time 0, but were found after 12 h of peritoneal dialysis; glyoxal and methylglyoxal decreased after 12 h of dialysis. So, glyoxal and methylglyoxal, already present in the dialysis fluid, can react with the peritoneal matrix protein, giving a reason for the gradual loss of peritoneal membrane function often observed in patients undergoing long-term peritoneal dialysis.

Nephrotoxicity testing in vitro--what we know and what we need to know.

PubMed Central

Pfaller, W; Gstraunthaler, G

1998-01-01

The kidney is affected by many chemicals. Some of the chemicals may even contribute to end-stage renal disease and thus contribute considerably to health care costs. Because of the large functional reserve of the kidney, which masks signs of dysfunction, early diagnosis of renal disease is often difficult. Although numerous studies aimed at understanding the mechanisms underlying chemicals and drugs that target various renal cell types have delivered enough understanding for a reasonable risk assessment, there is still an urgent need to better understand the mechanisms leading to renal cell injury and organ dysfunction. The increasing use of in vitro techniques using isolated renal cells, nephron fragments, or cell cultures derived from specific renal cell types has improved our insight into the molecular mechanisms involved in nephrotoxicity. A short overview is given on the various in vitro systems currently used to clarify mechanistic aspects leading to sublethal or lethal injury of the functionally most important nephron epithelial cells derived from various species. Whereas freshly isolated cells and nephron fragments appear to represent a sufficient basis to study acute effects (hours) of nephrotoxins, e.g., on cell metabolism, primary cultures of these cells are more appropriate to study long-term effects. In contrast to isolated cells and fragments, however, primary cultures tend to first lose several of their in vivo metabolic properties during culture, and second to have only a limited life span (days to weeks). Moreover, establishing such primary cultures is a time-consuming and laborious procedure. For that reason many studies have been carried out on renal cell lines, which are easy to cultivate in large quantities and which have an unlimited life span. Unfortunately, none of the lines display a state of differentiation comparable to that of freshly isolated cells or their primary cultures. Most often they lack expression of key functions (e.g., gluconeogenesis or organic anion transport) of their in vivo correspondents. Therefore, the use of cell lines for assessment of nephrotoxic mechanisms will be limited to those functions the lines express. Upcoming molecular biology approaches such as the transduction of immortalizing genes into primary cultures and the utilization of cells from transgenic animals may in the near future result in the availability of highly differentiated renal cells with markedly extended life spans and near in vivo characteristics that may facilitate the use of renal cell culture for routine screening of nephrotoxins. Images Figure 1 Figure 2 PMID:9599703

Advanced glycation end products in children with chronic renal failure and type 1 diabetes.

PubMed

Misselwitz, Joachim; Franke, Sybille; Kauf, Eberhard; John, Ulrike; Stein, Günter

2002-05-01

Serum levels of advanced glycation end products (AGEs) are markedly elevated in adults with chronic renal failure (CRF) and diabetes mellitus. Accumulation of AGEs in tissues contributes to the development of long-term complications. Up to now little has been known about the formation of AGEs in childhood. We determined serum levels of the well known AGEs pentosidine and Nvarepsilon-carboxymethyllysine (CML) in children with CRF (n=12), end-stage renal disease (ESRD) (n=9), renal transplantation (n=12), and type 1 diabetes mellitus (n=42) and in healthy children (n=20). Pentosidine was measured by high-performance liquid chromatography (HPLC), CML by a competitive enzyme-linked immunosorbent assay (ELISA) system. Serum levels of pentosidine and CML were significantly higher in the children with CRF and ESRD than in controls (P< 0.001), but nearly within the normal range after transplantation. Both AGEs showed a significant negative correlation with creatinine clearance (P< 0.001). During a single session of low-flux hemodialysis, total pentosidine and CML levels did not change. Free pentosidine, however, was reduced by 78% (P=0.04). Diabetic children showed significantly elevated pentosidine levels (P< 0.001) despite normal renal function. We conclude that, similar to adults, increased formation and accumulation of AGEs also exist in children with CRF and type 1 diabetes mellitus. At present the best prevention of AGE-related complications is an early renal transplantation in children with ESRD, as well as a careful metabolic monitoring of diabetics.

Cinacalcet for hypercalcaemic secondary hyperparathyroidism after renal transplantation: a multicentre, retrospective, 3-year study.

PubMed

Torregrosa, Jose-Vicente; Morales, Enrique; Díaz, Juan Manuel; Crespo, Josep; Bravo, Juan; Gómez, Gonzalo; Gentil, Miguel Ángel; Rodríguez Benot, Alberto; García, Minerva Rodríguez; Jiménez, Verónica López; Gutiérrez Dalmau, Alex; Jimeno, Luisa; Sáez, María José Pérez; Romero, Rafael; Gómez Alamillo, Carlos

2014-02-01

Our aim was to evaluate the long-term effect of cinacalcet in patients with hypercalcaemic secondary hyperparathyroidism (SHPT) after renal transplantation (RT) in order to expand real-world data in this population. We performed a multicentre, observational, retrospective study in 17 renal transplant units from Spain. We collected data from renal recipients with hypercalcaemic (calcium >10.2 mg/dL) SHPT (intact parathyroid hormone (iPTH) > 120 pg/mL) who initiated cinacalcet in the clinical practice. We included 193 patients with a mean (standard deviation (SD)) age of 52 (12) years, 58% men. Cinacalcet treatment was initiated at a median of 20 months after RT (median dose 30 mg/day). Mean calcium levels decreased from a mean (SD) of 11.1 (0.6) at baseline to 10.1 (0.8) at 6 months (9.0% reduction, P < 0.0001). Median iPTH was reduced by 23.0% at 6 months (P = 0.0005) and mean phosphorus levels increased by 11.1% (P < 0.0001). The effects were maintained up to 3-years. No changes were observed in renal function or anticalcineurin drug levels. Only 4.1% of patients discontinued cinacalcet due to intolerance and 1.0% due to lack of efficacy. In renal transplant patients with hypercalcaemic SHPT, cinacalcet controlled serum calcium, iPTH and phosphorus levels up to 3 years. Tolerability was good. © 2013 Asian Pacific Society of Nephrology.

Protective effects of hydrogen sulfide on chronic kidney disease by reducing oxidative stress, inflammation and apoptosis

PubMed Central

Askari, Hassan; Seifi, Behjat; Kadkhodaee, Mehri; Sanadgol, Nima; Elshiekh, Mohammed; Ranjbaran, Mina; Ahghari, Parisa

2018-01-01

The current study aimed to examine the renoprotective effects of long-term treatment with sodium hydrosulfide (NaHS), a prominent hydrogen sulfide donor, in 5/6 nephrectomy animal model. Twenty-four rats were randomly divided into 3 groups including sham-operated group (Sham), 5/6-nephrectomized group (5/6 Nx), and NaHS-treated group (5/6Nx+NaHS). NaHS (30 micromol/l) was added twice daily into the drinking water and renal failure was induced by 5/6 nephrectomy. Twelve weeks after surgical procedure, blood pressure, creatinine clearance (CCr), urine concentration of neutrophil gelatinase associated lipocalin (NGAL) and tissue concentration of malondialdehyde (MDA), superoxide dismutase (SOD), as well as renal morphological changes, apoptosis (cleaved caspase-3) and inflammation (p-NF-κB) were measured. Five-sixth nephrectomy induced severe renal damage as indicated by renal dysfunction, hypertension and significant histopathological injury which were associated with increased NGAL and MDA levels, oxidant/antioxidant imbalance, decreased SOD activity and CCr and also overexpression of p-NF-κB and cleaved caspase-3 proteins. Instead, NaHS treatment attenuated renal dysfunction through reduction of NGAL concentration, hypertension, CCr, oxidant/antioxidant imbalance, inflammation and apoptosis. These findings suggest that long term NaHS treatment can be useful in preventing the progression of CKD by improving oxidant/antioxidant balance and reducing inflammation and apoptosis in the kidney. PMID:29383015

[Long term effect of hepatitis B and C virus infection on the survival of kidney transplant patients].

PubMed

Corrêa, José Roberto Missel; Rocha, Fabrício Domingos; Peres, Alessandro Afonso; Gonçalves, Luiz Felipe; Manfro, Roberto Ceratti

2003-01-01

To evaluate the impact of HCV (hepatitis C virus) and HBV (hepatitis B virus) infection on long-term graft and patient survival in renal transplantation. One hundred and nine kidney allograft recipients were evaluated regarding the presence of antibodies against HCV and hepatitis B surface antigen. Patients were divided into four groups according to their serologic status and followed for ten years for survival analysis. Age, gender, renal failure etiology, length of previous dialysis and post transplantation periods were evaluated. Length on dialysis time was significantly longer in the anti-HCV positive group. There was also a higher number of patients with re-transplants in the HBV and HCV groups. There were no significant differences in 10-year patient survival in the anti-HCV positive group (71.0%; relative risk: 1.13; CI: 0.86-1.47) and in the HBV infected group (77.8%; relative risk: 1.03; CI: 0.7-1.5) compared to the not infected group (80%). However, the group of patients infected with both viruses presented a significantly lower 10-year patient survival (37.5%; relative risk: 2.13; CI: 0.86-5.28) compared to the index group. There were no significant differences on graft survival among the groups. In the present study renal transplant patients infected concomitantly with HBV and HCV present a significantly lower long-term patient survival.

Renal Allograft Outcome After Simultaneous Heart and Kidney Transplantation.

PubMed

Grupper, Avishay; Grupper, Ayelet; Daly, Richard C; Pereira, Naveen L; Hathcock, Matthew A; Kremers, Walter K; Cosio, Fernando G; Edwards, Brooks S; Kushwaha, Sudhir S

2017-08-01

Chronic kidney disease frequently accompanies end-stage heart failure and may result in consideration of simultaneous heart and kidney transplantation (SHKT). In recent years, there has been a significant increase in SHKT. This single-center cohort consisted of 35 patients who underwent SHKT during 1996 to 2015. The aim of this study was to review factors that may predict better long-term outcome after SKHT. Thirteen patients (37%) had delayed graft function (DGF) after transplant (defined as the need for dialysis during the first 7 days after transplant), which was significantly associated with mechanical circulatory support device therapy and high right ventricular systolic pressure before transplant. Most of the recipients had glomerular filtration rate (GFR) ≥50 ml/min/1.73 m 2 at 1 and 3 years after transplant (21 of 26 [81%] and 20 of 21 [95%], respectively). Higher donor age was associated with reduced 1-year GFR (p = 0.017), and higher recipient pretransplant body mass index was associated with reduced 3-year GFR (p = 0.008). There was a significant association between DGF and reduced median GFR at 1 and 3 years after transplant (p <0.005). Patient survival rates at 6 months, 1, and 3 years after transplant were 97%, 91%, and 86% respectively. In conclusions, our data support good outcomes after SHKT. Mechanical circulatory support device therapy and pulmonary hypertension before transplant are associated with DGF, which is a risk factor for poor long-term renal allograft function. Copyright © 2017 Elsevier Inc. All rights reserved.

A joint model for longitudinal and time-to-event data to better assess the specific role of donor and recipient factors on long-term kidney transplantation outcomes.

PubMed

Fournier, Marie-Cécile; Foucher, Yohann; Blanche, Paul; Buron, Fanny; Giral, Magali; Dantan, Etienne

2016-05-01

In renal transplantation, serum creatinine (SCr) is the main biomarker routinely measured to assess patient's health, with chronic increases being strongly associated with long-term graft failure risk (death with a functioning graft or return to dialysis). Joint modeling may be useful to identify the specific role of risk factors on chronic evolution of kidney transplant recipients: some can be related to the SCr evolution, finally leading to graft failure, whereas others can be associated with graft failure without any modification of SCr. Sample data for 2749 patients transplanted between 2000 and 2013 with a functioning kidney at 1-year post-transplantation were obtained from the DIVAT cohort. A shared random effect joint model for longitudinal SCr values and time to graft failure was performed. We show that graft failure risk depended on both the current value and slope of the SCr. Deceased donor graft patient seemed to have a higher SCr increase, similar to patient with diabetes history, while no significant association of these two features with graft failure risk was found. Patient with a second graft was at higher risk of graft failure, independent of changes in SCr values. Anti-HLA immunization was associated with both processes simultaneously. Joint models for repeated and time-to-event data bring new opportunities to improve the epidemiological knowledge of chronic diseases. For instance in renal transplantation, several features should receive additional attention as we demonstrated their correlation with graft failure risk was independent of the SCr evolution.

[Robotic assisted laparoscopic living donor nephrectomy: preoperative assessment and results of 100 cases].

PubMed

Laplace, B; Ladrière, M; Claudon, M; Eschwege, P; Kessler, M; Hubert, J

2014-04-01

To assess short term morbidity and renal function after robotic laparoscopic living donor nephrectomy. We performed a retrospective analysis of 100 consecutives patients undergoing a robotic laparoscopic living donors nephrectomy. We analyzed isotopic measure of the renal function before and 4 months after surgery, the side, the number of arteries, the blood loss, the operative time and warm ischemia time. In the outcomes, we collected the complications, the length of stay, and for the receiver, the renal function recovery time, dialysis, survival and renal function at one year. Left kidney nephrectomy was performed in 85 patients and we observed 25 multiples renal arteries. Mean estimated blood loss was 0,8 g/dL. Mean operative time and warm ischemia time were respectively 174 ± 30 and 4.8 ± 1.7 minutes. Seven complications occured, with 2 major (Clavien-Dindo System). Mean length of stay was 5.1 ± 1.9 days. Mean glomerular filtration decrease was 26% and remains stable at one year after surgery. Grafts had an immediate renal function recovery for 99%, and were all functional after one year, with mean MDRD clearance of 57 ± 14mL/min. Robotic procedure in laparoscopic living donor nephrectomy seems to guarantee low morbidity and the stability of the renal function decrease of 26%. Copyright © 2013. Published by Elsevier Masson SAS.

Durability of small-for-size living donor allografts.

PubMed

Au, Kin Pan; Chan, See Ching; Chok, Kenneth Siu Ho; Chan, Albert Chi Yan; Wong, Tiffany Cho Lam; Sharr, William Wei; Lo, Chung Mau

2015-11-01

Our aim was to study the long-term outcomes of living donor liver transplantation using small-for-size (SFS) grafts. From July 2002 to July 2009, 233 patients received a right liver graft with a middle hepatic vein from a living donor in our center. Recipients were stratified according to the graft weight to recipient standard liver volume (GW/SLV) ratio into 4 groups: >50% (n = 89), >40% to 50% (n = 85), >35% to 40% (n = 38), and ≤ 35% (n = 21). They were compared in terms of graft survivals, biliary stricture rates, renal function in terms of estimated glomerular filtration rate (eGFR), platelet counts, and graft function in terms of serum bilirubin and international normalized ratio (INR). The 5-year graft survivals for patients with GW/SLV of >50%, >40% to 50%, >35% to 40% and ≤ 35% were 88.8%, 88.2%, 81.5%, and 81.0%, respectively. Transplantation for hepatocellular carcinoma affected graft survivals (P = 0.02), but graft size did not (P = 0.66). There were no differences in frequency of biliary stricture (21.3% versus 17.1% versus 21.1% versus 28.6%; P = 0.75). At each year after transplant, their platelet counts (P = 0.12-0.65), eGFR (P = 0.49-0.91), bilirubin (P = 0.14-0.51), and INR (P = 0.20-0.98) remained comparable. SFS grafts with GW/SLV ≤ 35% and >35% to 40% had comparable long-term outcomes with larger liver grafts. Graft size did not affect long-term graft survivals. © 2015 American Association for the Study of Liver Diseases.

Urinary ET-1 excretion after exposure to radio-contrast media in diabetic patients and patients with preexisting mild impaired renal function.

PubMed

Heunisch, Fabian; von Einem, Gina; Alter, Markus; Weist, Andreas; Dschietzig, Thomas; Kretschmer, Axel; Hocher, Berthold

2014-11-24

Contrast media-induced nephropathy (CIN) is associated with increased morbidity and mortality. The renal endothelin system has been associated with disease progression of various acute and chronic renal diseases. However, robust data coming from adequately powered prospective clinical studies analyzing the short and long-term impacts of the renal ET system in patients with CIN are missing so far. We thus performed a prospective study addressing this topic. We included 327 patients with diabetes or renal impairment undergoing coronary angiography. Blood and spot urine were collected before and 24 h after contrast media (CM) application. Patients were followed for 90 days for major clinical events like need for dialysis, unplanned rehospitalization or death. The concentration of ET-1 and the urinary ET-1/creatinine ratio decreased in spot urine after CM application (ET-1 concentration: 0.91±1.23 pg/ml versus 0.63±1.03 pg/ml, p<0.001; ET-1/creatinine ratio: 0.14±0.23 versus 0.09±0.19, p<0.001). The urinary ET-1 concentrations in patients with CIN decreased significantly more than in patients without CIN (-0.26±1.42 pg/ml vs. -0.79±1.69 pg/ml, p=0.041), whereas the decrease of the urinary ET-1/creatinine ratio was not significantly different (non-CIN patients: -0.05±0.30; CIN patients: -0.11±0.21, p=0.223). Urinary ET-1 concentrations as well as the urinary ET-1/creatinine ratio were not associated with clinical events (need for dialysis, rehospitalization or death) during the 90 day follow-up after contrast media exposure. However, the urinary ET-1 concentration and the urinary ET-1/creatinine ratio after CM application were higher in those patients who had a decrease of GFR of at least 25% after 90 days of follow-up. In general the ET-1 system in the kidney seems to be down-regulated after contrast media application in patients with moderate CIN risk. Major long-term complications of CIN (need for dialysis, rehospitalization or death) are not associated with the renal ET system. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Allowable exposure limits for carbon dioxide during extravehicular activity

NASA Technical Reports Server (NTRS)

Seter, Andrew J.

1993-01-01

The intent was to review the research pertaining to human exposure to carbon dioxide (CO2) and to recommend allowable exposure limits for extravehicular activity (EVA). Respiratory, renal, and gastrointestinal systems may be adversely affected by chronic low dose CO2 exposure. Ventilation was increased 15 percent with 1 percent CO2 and 50 percent with 2 percent CO2. Chronic exposure to less than 2 percent CO2 led to 20 day cycles of uncompensated and compensated respiratory acidosis. Acid-base changes were small. Histopathologic changes in guinea pig lungs have been noted with long term exposure to 1 percent CO2. No changes were seen with exposure to 0.5 percent CO2. Cycling of bone calcium stores with associated changes in blood and urinary calcium levels occurs with long term CO2 exposure. Histologic changes in bone have been noted in guinea pigs exposed to 1 percent CO2. Renal calcification has been noted in guinea pigs with exposure to as low as 0.5 percent CO2. An increase in gastric acidity was noted in subjects with long term exposure to 1 percent CO2. Cardiovascular and neurologic function were largely unaffected. A decrease in the incidence of respiratory, renal, and gastrointestinal disease was noted in submariners coincident with a decrease in ambient CO2 from 1.2 percent to 0.8-0.9 percent. Oxygen (O2) and CO2 stimulate respiration independently and cumulatively. The addition of CO2 to high dose O2 led to the faster onset of seizure activity in mice. Experiments evaluating the physiologic responses to intermittent, repetitive exposures to low dose CO2 and 100 percent O2 mixtures should be performed. A reduction in the current NASA standard for CO2 exposure during EVA of 1 percent (7.6 mmHg) for nominal and 2 percent (15.2 mmHg) for heavy exertion to 0.5 percent (3.8 mmHg) for nominal and 1 percent (7.6 mmHg) for heavy exertion may be prudent. At a minimum, the current NASA standard should not be liberalized.

Surgical treatment of middle aortic syndrome with Takayasu arteritis or midaortic dysplastic syndrome.

PubMed

Kim, S M; Jung, I M; Han, A; Min, S-I; Lee, T; Ha, J; Kim, S J; Min, S-K

2015-08-01

Middle aortic syndrome (MAS) is a rare condition characterized by severe stenosis of the distal thoracic or abdominal aorta. The aims of this study are to define the anatomic characteristics of MAS and to review the various surgical methods and their outcomes in terms of long-term durability Ten adult patients were diagnosed with MAS caused by Takayasu arteritis (TA) or midaortic dysplastic syndrome and underwent surgical treatment between July 1992 and January 2013. The aortic lesions were mostly suprarenal (n = 7) and stenoses were commonly found in the celiac axis (n = 6), SMA (n = 7), and renal artery (n = 6). Indications for operation were uncontrolled hypertension in six patients and lower extremity claudication in four. Eight aortic bypasses, one supraceliac aortic interposition graft, and one bilateral aorto-renal bypass were performed. Adjunctive renal bypass with saphenous vein graft (n = 4) and IMA reimplantation (n = 2) were performed simultaneously. There was no post-operative mortality, and one complication of iliac dissection at the distal anastomosis site was detected and treated by stenting. Hypertension was cured or improved in five of the six patients, and lower extremity claudication improved in all of them. With a median follow up of 60 months (range, 12-263), all the aortic bypasses were patent and one adjunctive renal artery bypass graft with aortic bypass was occluded 29 months post-operatively. Aortic bypass for MAS is safe and shows excellent long-term durability. Considering the patients are relatively young with a long life expectancy, aggressive surgical treatment could be beneficial. Lifelong follow up to monitor complications and disease progression is necessary. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Kidney injury biomarkers 5 years after AKI due to pediatric cardiac surgery.

PubMed

Greenberg, Jason H; Devarajan, Prasad; Thiessen-Philbrook, Heather R; Krawczeski, Catherine; Parikh, Chirag R; Zappitelli, Michael

2018-06-01

We previously reported that children undergoing cardiac surgery are at high risk for long-term chronic kidney disease (CKD) and hypertension, although postoperative acute kidney injury (AKI) is not a risk factor for worse long-term kidney outcomes. We report here our evaluation of renal injury biomarkers 5 years after cardiac surgery to determine whether they are associated with postoperative AKI or long-term CKD and hypertension. Children aged 1 month to 18 years old undergoing cardiopulmonary bypass were recruited to this prospective cohort study. At 5 years after cardiac surgery, we measured urine interleukin-18, kidney injury molecule-1, monocyte chemoattractant protein-1, YKL-40, and neutrophil gelatinase-associated lipocalin (NGAL). Biomarker levels were compared between patients with AKI and those without. We also performed a cross-sectional analysis of the association between these biomarkers with CKD and hypertension. Of the 305 subjects who survived hospitalization, four (1.3%) died after discharge, and 110 (36%) participated in the 5-year follow-up. Of these 110 patients, 49 (45%) had AKI. Patients with versus those without postoperative AKI did not have significantly different biomarker concentrations at 5 years after cardiac surgery. None of the biomarker concentrations were associated with CKD or hypertension at 5 years of follow-up, although CKD and hypertension were associated with a higher proportion of participants with abnormal NGAL levels. Postoperative pediatric AKI is not associated with urinary kidney injury biomarkers 5 years after surgery. This may represent a lack of chronic renal injury after AKI, imprecise estimation of the glomerular filtration rate, the need for longer follow-up to detect chronic renal damage, or that our studied biomarkers are inadequate for evaluating subclinical chronic renal injury.

Assessment of the knowledge of living unrelated donors of the complications of kidney donation in Iran.

PubMed

Ossareh, Shahrzad; Karbasi, Arsha

2009-12-01

Living unrelated donors (LURDs) constitute the major source of renal allograft in Iran. LURD transplantation (Tx) is performed in a controlled program, supervised by university Tx teams, and assisted by the Dialysis and Transplant Patient's Association (DATPA). This study evaluated the knowledge of donors about possible short- and long-term complications of kidney donation and the need for regular follow-up. We interviewed 100 consecutive living donors/donation candidates (all called donors), 35 in the postoperative period in the renal Tx ward, and 65 after completion of preoperative assessment in the office of the DATPA, to assess their knowledge about complications of nephrectomy and their intention to participate in the postoperative follow-up. Seventy-nine donors were men and 21 women. Mean age was 27 +/- 4.4 years. Ninety-seven donors were unrelated to the recipient and three were related (LRD). The motivation for donation was altruistic in nine (three LRD and six LURD) and financial in 89. Eighty donors were not aware of the possible short- or long-term complications of nephrectomy. Six donors mentioned the possibility of potential intraoperative complications, and 16 mentioned the risk of renal failure. Only 44 donors knew that they should visit doctors regularly after donation, most of them (61%) from the postoperative group. We conclude that most donors do not have enough knowledge about possible in-hospital and long-term complications of kidney donation and may not participate in regular follow-up after operation. Considering the young age of our renal Tx donors, we suggest that they should receive more preoperative orientation (both verbal and written) about possible complications and the need for regular postoperative medical follow-up.

28 CFR 79.61 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... The term includes in situ lung cancers. (m) Readily available documentation means documents in the... injury means structural or functional damage to the kidney tubules that results in renal disease and... resulting in chronic renal dysfunction. (j) Nonmalignant respiratory disease means fibrosis of the lung...

Recurrent Urinary Tract Infection Among Renal Transplant Recipients: Risk Factors and Long-Term Outcome.

PubMed

Tawab, Khaled Abdel; Gheith, Osama; Al Otaibi, Torki; Nampoory, Naryanam; Mansour, Hany; Halim, Medhat A; Nair, Prasad; Said, Tarek; Abdelmonem, Mohamed; El-Sayed, Ayman; Awadain, Waleed

2017-04-01

Urinary tract infection is the most common type of bacterial infection in kidney transplant procedures, with adverse effects on graft and patient survival. We aimed to evaluate the risk factors of recurrent urinary tract infection in renal transplant recipients and its impact on patient and graft survival. In a cohort of 1019 patients who were transplanted between 2000 and 2010 at Hamed Al-Essa Organ Transplant Center in Kuwait, 86% developed at least 1 episode of urinary tract infection, with only 6.2% of patients having recurrent infections. We compared patients with recurrent urinary tract infections (group 1) with those who had no recurrence (group 2) regarding their risk factors. Patients in group 1 were significantly younger than those in group 2 (34.9 ± 23 vs 42.8 ± 16 y; P < .001), with female preponderance (P < .001). The percentage of patients with thymoglobulin induction (21.5%) was significantly higher in group 1. Patients with pretransplant urologic problems experienced significantly more recurrent urinary tract infections (P < .001). Hepatitis C infections were significantly more prevalent among group 1 (10.8% vs 3.8%; P = .008). Long-term graft outcome (functioning and failed) were 78.5% and 21.5% in group 1 versus 85.1% and 13.9% in group 2 (P = .18). Patient outcomes (living and deceased donors) were 98.4% and 1.6% in group 1 versus 95.7% and 4.3% in group 2 (P = .187). Adult females, thymoglobulin induction, pretransplant urologic problems, and hepatitis C infection were the risk factors of recurrent urinary tract infection among our renal transplant patients. However, recurrence did not adversely affect graft or patient survival.

Long-term outcomes of renal transplants from spousal and living-related and other living-unrelated donors: a single center experience.

PubMed

Kute, Vivek B; Shah, Pankaj R; Vanikar, Aruna V; Gumber, Manoj R; Goplani, Kamal R; Patel, Himanshu V; Munjappa, Bipin C; Trivedi, Hargovind L; Modi, Pranjal R; Shah, Veena R

2012-07-01

Deceased donor organ shortage has made living donors (LD) major source for renal transplantation (RTx) in India. Spouses represent an important source of allograft. We carried out a retrospective study of spousal RTx vs. other LDRTx to compare long-term results. This retrospective single-center study was undertaken to evaluate demographic, patient survival, graft survival, function vis-à-vis serum creatinine (SCr) and rejection episodes in 1523 living donor renal allograft recipients from 1998 to 2009. It included spouse donors (n=337) (group 1), living related donors (LRD) (n=969) (group 2), and living unrelated donors (LUD) (n=217) (group 3). Mean recipient age (years +/- SD)) was 41.48 +/- 8.87, 30.49 +/- 10.61, and 37.13 +/- 13.25, respectively for the three groups who were followed for 4.47 +/- 3.03, 4.47 +/- 3.0 and 5.15 +/- 3.28 years respectively. Female donors were 92.6%, 66.4%, and 41%, mean HLA match was 1.15 +/- 0.93, 3 +/- 1.05 and 1.30 +/- 1.08 respectively. One, 5 and 12 year graft survivals among group 1 were 91.39%, 75.49%, and 73.13%; 90.98%, 74.10% and 64.57% in group 2 and 94.92%, 82.86% and 70.31% in group 3. Patient survival for 1, 5 and 12 years were 89.31%, 72.55% and 66.58% in group 1, 93.57%, 82.25% and 72.23% in group 2, and 92.62%, 79.76% and 66.79% in group 3. Acute rejections were noted in 16.6%, 15.8% and 17% respectively. In circumstances of organ shortage andunavailability of well developed ABO incompatible transplants, spousal donation is viable option.

Metastatic Renal Cell Carcinoma to the Pancreas: A Review.

PubMed

Cheng, Shaun Kian Hong; Chuah, Khoon Leong

2016-06-01

The pancreas is an unusual site for tumor metastasis, accounting for only 2% to 5% of all malignancies affecting the pancreas. The more common metastases affecting the pancreas include renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas, and sarcomas. Although pancreatic involvement by nonrenal malignancies indicates widespread systemic disease, metastatic renal cell carcinoma to the pancreas often represents an isolated event and is thus amenable to surgical resection, which is associated with long-term survival. As such, it is important to accurately diagnose pancreatic involvement by metastatic renal cell carcinoma on histology, especially given that renal cell carcinoma metastasis may manifest more than a decade after its initial presentation and diagnosis. In this review, we discuss the clinicopathologic findings of isolated renal cell carcinoma metastases of the pancreas, with special emphasis on separating metastatic renal cell carcinoma and its various differential diagnoses in the pancreas.

Hepatic and renal function with successful long-term support on a continuous flow left ventricular assist device.

PubMed

Deo, Salil V; Sharma, Vikas; Altarabsheh, Salah E; Hasin, Tal; Dillon, John; Shah, Ishan K; Durham, Lucian A; Stulak, John M; Daly, Richard C; Joyce, Lyle D; Park, Soon J

2014-03-01

Data regarding the long-term clinical effects of a continuous flow left ventricular assist device (CF-LVAD) on hepato-renal function is limited. Hence our aim was to assess changes in hepato-renal function over a one-year period in patients supported on a CF-LVAD. During the study period 126 patients underwent CF-LVAD implant. Changes in hepato-renal laboratory parameters were studied in 61/126 patients successfully supported on a CF-LVAD for period of one year. A separate cohort of a high-risk group (HCrB) of patients (56/126) with a serum creat>1.9 mg/dL (168 μmol/L) (75th percentile) or a serum bil>1.5 mg/dL (25.65 μmol/L) (75th percentile) was created. Changes in serum creatinine and bilirubin were analysed at regular intervals for this group along with the need for renal replacement therapy. Baseline creatinine and blood urea nitrogen (BUN) for the entire cohort was 1.4[1.2,1.9 mg/dL] [123.7(106,168) μmol/L) and 27[20,39.5 mg/dL] [9.6(7.1,14.1) mmol/L] respectively. After an initial reduction at the end of one month [1(0.8,1.2) mg/dL; 88(70,105) μmol/L] (p<0.0001), a gradual increase was noted over the study period to reach (1.25[1.1,1.5] mg/dL; 106(97.2,132.6) μmol/L] (p=0.0003). The serum bilirubin normalised from a [1(0.7,1.55) mg/dL] [17(18.8,25.7) μmol/L) to 0.9(0.6,1.2)mg/dL [15.4(10.2,20.5) μmol/L] (p=0.0005) and continued to decline over one year. Improvement in the synthetic function of the liver was demonstrated by a rise in the serum albumin levels to reach 4.3[4.1,4.5] [43(41,45) gm/L] at the end of one year (p<0.0001). The baseline serum creatinine and bilirubin for the high-risk cohort (HCrB) was 1.9(1.3,2.4) mg/dL [168(115,212) μmol/L] and 1.7(1.00,2.4) mg/dL [29(17.1,68.4) μmol/L] respectively. The high-risk cohort (HCrB) demonstrated a trend towards higher 30-day mortality (p=0.06). While the need for temporary renal replacement therapy was higher in this cohort (16% vs. 4%; p=0.03), only 3% need it permanently. A significant reduction in creatinine was apparent at the end of one month [1.1(0.8,1.4) mg/dL; 97(70.7,123.7) μmol/L] (p<0.0001) and then remained stable at [1.3(1.1,1.5) mg/dL; 115(97,132.6) μmol/L]. Bilirubin demonstrated a 30% decline over one month and then remained low at [0.7(0.5,0.8) mg/dL; 62(44,70) μmol/L] p=0.0005 compared to the pre-operative baseline. Hepato-renal function demonstrates early improvement and then remains stable in the majority of patients on continuous flow left ventricular assist device support for one year. High-risk patients demonstrate a higher 30-day mortality and temporary need for renal replacement therapy. Yet even in this cohort, improvement is present over a period of one year on the device, with a minimal need for permanent haemodialysis. Copyright © 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Maternal fructose-intake-induced renal programming in adult male offspring.

PubMed

Tain, You-Lin; Wu, Kay L H; Lee, Wei-Chia; Leu, Steve; Chan, Julie Y H

2015-06-01

Nutrition in pregnancy can elicit long-term effects on the health of offspring. Although fructose consumption has increased globally and is linked to metabolic syndrome, little is known about the long-term effects of maternal high-fructose (HF) exposure during gestation and lactation, especially on renal programming. We examined potential key genes and pathways that are associated with HF-induced renal programming using whole-genome RNA next-generation sequencing (NGS) to quantify the abundance of RNA transcripts in kidneys from 1-day-, 3-week-, and 3-month-old male offspring. Pregnant Sprague-Dawley rats received regular chow or chow supplemented with HF (60% diet by weight) during the entire period of pregnancy and lactation. Male offspring exhibited programmed hypertension at 3 months of age. Maternal HF intake modified over 200 renal transcripts from nephrogenesis stage to adulthood. We observed that 20 differentially expressed genes identified in 1-day-old kidney are related to regulation of blood pressure. Among them, Hmox1, Bdkrb2, Adra2b, Ptgs2, Col1a2 and Tbxa2r are associated with endothelium-derived hyperpolarizing factor (EDHF). NGS also identified genes in arachidonic acid metabolism (Cyp2c23, Hpgds, Ptgds and Ptges) that may be potential key genes/pathways contributing to renal programming and hypertension. Collectively, our NGS data suggest that maternal HF intake elicits a defective adaptation of interrelated EDHFs during nephrogenesis which may lead to renal programming and hypertension in later life. Moreover, our results highlight genes and pathways involved in renal programming as potential targets for therapeutic approaches to prevent metabolic-syndrome-related comorbidities in children with HF exposure in early life. Copyright © 2015 Elsevier Inc. All rights reserved.

Laser ablation of posterior urethral valves by fetal cystoscopy.

PubMed

Martínez, José María; Masoller, Narcis; Devlieger, Roland; Passchyn, Esther; Gómez, Olga; Rodo, Joan; Deprest, Jan A; Gratacós, Eduard

2015-01-01

To report the results of fetal cystoscopic laser ablation of posterior urethral valves (PUV) in a consecutive series in two referral centers. Twenty pregnant women with a presumptive isolated PUV were treated with fetal cystoscopy under local anesthesia. Identification and fulguration of the PUV by one or several firing-contacts with diode laser were attempted. Perinatal and long-term outcomes were prospectively recorded. The median gestational age at procedure was 18.1 weeks (range 15.0-25.6), and median operation time was 24 min (range 15-40). Access to the urethra was achieved in 19/20 (95%) cases, and postoperative, normalization of bladder size and amniotic fluid was observed in 16/20 (80%). Overall, there were 9 (45%) terminations of pregnancy and 11 women (55%) delivered a liveborn baby at a mean gestational age of 37.3 (29.1-40.2) weeks. No infants developed pulmonary hypoplasia and all were alive at 15-110 months. Eight (40% of all fetuses, 72.7% of newborns) had normal renal function and 3 (27.3%) had renal failure awaiting renal transplantation. Fetoscopic laser ablation for PUV can achieve bladder decompression and amniotic fluid normalization with a single procedure in selected cases with anyhydramnios. There is still a significant risk of progression to renal failure pre or postnatally. © 2014 S. Karger AG, Basel.

Lung-Kidney Cross-Talk in the Critically Ill Patient.

PubMed

Husain-Syed, Faeq; Slutsky, Arthur S; Ronco, Claudio

2016-08-15

Discoveries have emerged highlighting the complex nature of the interorgan cross-talk between the kidney and the lung. Vascular rigidity, neurohormonal activation, tissue hypoxia, and abnormal immune cell signaling have been identified as common pathways leading to the development and progression of chronic kidney disease. However, our understanding of the causal relationships between lung injury and kidney injury is not precise. This review discusses a number of features and mechanisms of renal dysfunction in pulmonary disorders in relation to respiratory acidosis, impaired gas exchange, systemic congestion, respiratory support/replacement therapies, and other issues relevant to the clinical care of these patients. Biotrauma due to injurious ventilatory strategies can lead to the release of mediators into the lung, which may then translocate into the systemic circulation and cause end-organ dysfunction, including renal dysfunction. Right ventricular dysfunction and congestive states may contribute to alterations of renal perfusion and oxygenation, leading to diuretic resistance and recurrent hospitalization. In patients with concomitant respiratory failure, noninvasive ventilation represents a promising treatment option for the correction of impaired renal microcirculation and endothelial dysfunction. In patients requiring extracorporeal membrane oxygenation, short- and long-term monitoring of kidney function is warranted, as they are at highest risk of developing acute kidney injury and fluid overload.

Uncemented total hip arthroplasty in chronic hemodialysis patients

PubMed Central

Li, Wei-Chun; Shih, Chun-Hsiung; Ueng, Steve W; Shih, Hsin-Nung; Lee, Mel S

2010-01-01

Background and purpose Whether or not uncemented total hip arthroplasty (THA) can achieve durable fixation of implants to bone in patients on chronic hemodialysis is unknown. We analyzed the 2–13-year clinical outcomes of cementless THA in patients with end-stage renal diseases who were maintained on long-term hemodialysis. Patients and methods We reviewed the outcome of 23 consecutive uncemented THAs undertaken between 1993 and 2004, in patients with chronic renal failure who had been on long-term hemodialysis (2–18 years). 1 patient died and 2 patients were lost to follow-up within 2 years, leaving 20 hips (20 patients, median age 66 (38–81) years at the time of THA, 11 females) that were reviewed at median 7 (2–13) years postoperatively. Results Radiographic bone-ingrowth fixation of the components was found in 19 patients. 1 patient had aseptic loosening requiring revision surgery. The median d'Aubigne and Postel score was 10 (8–14) preoperatively and 15 (12–18) at final review. No prosthetic infections were found in any of the patients. Interpretation Uncemented THA shows promising medium-term results in patients receiving long-term hemodialysis. PMID:20175645

Gadolinium based contrast agents in current practice: Risks of accumulation and toxicity in patients with normal renal function

PubMed Central

Ranga, Anju; Agarwal, Yatish; Garg, Kanika J

2017-01-01

Despite being decked as the most prized compounds in the nugget box of contrast agents for clinical radiologists, and carrying an indisputable tag of safety of the US Food and Drug Administration for close to three decades, all may not be seemingly well with the family of gadolinium compounds. If the first signs of violations of primum non nocere in relation to gadolinium-based contrast agents (GBCAs) appeared in the millennium year with the first published report of skin fibrosis in patients with compromised renal function, the causal relationship between the development of nephrogenic systemic fibrosis (NSF) and GBCAs, first proposed by two European groups in 2006, further precluded their use in renocompromised patients. The toxicity, pharmacokinetics, and pharmacodynamics of GBCAs, however, has come under hawk-eyed scrutiny with recent reports that gadolinium tends to deposit cumulatively in the brain of patients with normal hepatobiliary function and intact blood–brain barrier. While the jury on the long-term hazard significance of this critical scientific finding is still out, the use of GBCAs must be guided by due clinical diligence, avoidance of repeated doses, and preferring GBCAs with the best safety profiles. PMID:28744073

Postoperative elevation in creatine kinase and its impact on renal function in patients undergoing complex partial nephrectomy.

PubMed

Sidana, Abhinav; Walton-Diaz, Annerleim; Truong, Hong; Siddiqui, M Minhaj; Miao, Ning; Shih, Johanna; Mannes, Andrew; Bratslavsky, Gennady; Linehan, W Marston; Metwalli, Adam R

2016-07-01

To identify the risk factors associated with development of postoperative elevation of creatine kinase (CK) and study its effect on renal function in patients who underwent complex multifocal partial nephrectomy (PN). Patients who underwent PN at National Cancer Institute between January 2007 and December 2012 were included in the study. Elevated serum CK was defined as >2000 U/L. Kidney function was assessed using serum creatinine and estimated glomerular filtration rate (eGFR). Changes were reported as percent change from preoperative values and compared using the Wilcoxon test. Regression analysis was performed to identify the predictors of elevation in CK and decline in eGFR. From 407 total cases, 207 had adequate CK data for analysis. Median number of tumors removed was 3 (1-70). Median peak CK was 1458 (82-36,788). Forty-two percent developed CK elevation >2000 U/L. Factors associated with postoperative elevation of CK > 2000 were young age (p = 0.009), high BMI (p = 0.003) and operating room time (p < 0.001). Although CK > 2000 was associated with significantly greater decline in eGFR (37.4 vs. 20.3 %, p < 0.001) in immediate postoperative period, this change largely resolved to a much less clinically relevant (9.2 vs 3.3 %, p = 0.040) change after 3 months. On multivariate analysis, postoperative elevation in CK was not found to be an independent factor determining renal function at 3 months. In our cohort, a significant proportion of patients developed CK elevations >2000 U/L. While patients with elevated CK had more decline in eGFR in immediate postoperative period, postoperative elevations of CK did not appear to impact overall long-term renal function in patients undergoing PN.

Logic programming to infer complex RNA expression patterns from RNA-seq data.

PubMed

Weirick, Tyler; Militello, Giuseppe; Ponomareva, Yuliya; John, David; Döring, Claudia; Dimmeler, Stefanie; Uchida, Shizuka

2018-03-01

To meet the increasing demand in the field, numerous long noncoding RNA (lncRNA) databases are available. Given many lncRNAs are specifically expressed in certain cell types and/or time-dependent manners, most lncRNA databases fall short of providing such profiles. We developed a strategy using logic programming to handle the complex organization of organs, their tissues and cell types as well as gender and developmental time points. To showcase this strategy, we introduce 'RenalDB' (http://renaldb.uni-frankfurt.de), a database providing expression profiles of RNAs in major organs focusing on kidney tissues and cells. RenalDB uses logic programming to describe complex anatomy, sample metadata and logical relationships defining expression, enrichment or specificity. We validated the content of RenalDB with biological experiments and functionally characterized two long intergenic noncoding RNAs: LOC440173 is important for cell growth or cell survival, whereas PAXIP1-AS1 is a regulator of cell death. We anticipate RenalDB will be used as a first step toward functional studies of lncRNAs in the kidney.

Long-term treatment with chaethomellic acid A reduces glomerulosclerosis and arteriolosclerosis in a rat model of chronic kidney disease.

PubMed

Nogueira, António; Vala, Helena; Vasconcelos-Nóbrega, Carmen; Faustino-Rocha, Ana Isabel; Pires, Carlos André; Colaço, Aura; Oliveira, Paula Alexandra; Pires, Maria João

2017-12-01

The high prevalence of end-stage renal disease emphasizes the failure to provide therapies to effectively prevent and/or reverse renal fibrosis. Therefore, the aim of this study was to evaluate the effect of long-term treatment with chaethomellic acid A (CAA), which selectively blocks Ha-Ras farnesylation, on renal mass reduction-induced renal fibrosis. Male Wistar rats were sham-operated (SO) or subjected to 5/6 renal mass reduction (RMR). One week after surgery, rats were placed in four experimental groups: SO:SO rats without treatment (n=13); SO+CAA: SO rats treated with CAA (n=13); RMR:RMR rats without treatment (n=14); and RMR+CAA:RMR rats treated with CAA (n=13). CAA was intraperitoneally administered in a dose of 0.23μg/kg three times a week for six months. Renal fibrosis was evaluated by two-dimensional ultrasonography and histopathological analysis. The kidneys of the RMR animals treated with CAA showed a significantly decrease in the medullary echogenicity (p<0.05) compared with the RMR rats that received no treatment. Glomerulosclerosis and arteriolosclerosis scores were significantly lower (p<0.001) in the RMR+CAA group when compared with the RMR group. There were no significant differences in interstitial fibrosis, interstitial inflammation and tubular dilatation scores between the RMR+CAA and RMR groups. These data suggest that CAA can be a potential future drug to attenuate the progression of chronic kidney disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Adult Henoch-Schönlein purpura: Clinical and histopathological predictors of systemic disease and profound renal disease.

PubMed

Cao, Ruoxi; Lau, Sandra; Tan, Virlynn; Tey, Hong Liang

2017-01-01

A major challenge in the management of adult Henoch-Schönlein purpura is the difficulty in assessing the risk of systemic involvement. There is currently a paucity of data in this area. This study sought to determine specific clinical and histopathological features associated with systemic involvement in adult Henoch-Schönlein purpura. We reviewed the records of 99 adult Henoch-Schönlein purpura patients who presented at the National Skin Centre, Singapore, between January 2008 and May 2015. Renal involvement was found in 56 (56.6%) patients, joint involvement in 21 (21.2%) and gastrointestinal involvement in 13 (13.1%). Age > 30 years was an independent predictor of renal involvement with an adjusted odds ratio of 2.97 (95% confidence interval, 1.08-8.16; P = 0.04). Risk factors for significant renal involvement necessitating nephrology referral were further evaluated: the odds were approximately 60% higher for every 10-year increase in age (95% confidence interval, 1.02-2.57; P = 0.04) and patients with cutaneous bullae and/or necrosis had an almost six times higher risk (95% confidence interval, 1.43-25.00; P = 0.01). This study was limited by its retrospective design. We also lacked long-term data to examine how clinical and histopathological characteristics correlated with long-term disease outcomes. Adult Henoch-Schönlein purpura patients older than 30 years have a threefold increased risk of renal involvement. The risk of profound renal disease necessitating nephrology referral rose significantly with age and the presence of cutaneous bullae and/or necrosis.

Fluid compartment and renal function alterations in the rat during 7 and 14 day head down tilt

NASA Technical Reports Server (NTRS)

Tucker, Bryan J.

1991-01-01

Exposure to conditions of microgravity for any extended duration can modify the distribution of fluid within the vascular and interstitial spaces, and eventually intracellular volume. Whether the redistribution of fluid and resetting of volume homeostasis mechanisms is appropriate for the long term environmental requirements of the body in microgravity remains to be fully defined. The event that initiates the change in fluid volume homeostasis is the cephalad movement of fluid which potentially triggers volume sensors and stretch receptors (atrial stretch with the resulting release of atrial natriuretic peptide) and suppresses adrenergic activity via the carotid and aortic arch baroreceptors. All these events act in concert to reset blood and interstitial volume to new levels, which in turn modify the renin-angiotensin system. All these factors have an influence on the kidney, the end organ for fluid volume control. How the fluid compartment volume changes interrelate with alterations in renal functions under conditions of simulated microgravity is the focus of the present investigation which utilizes 25-30 deg head-down tilt in the rat.

Preliminary study of a traditional Chinese medicine formula in systemic lupus erythematosus patients to taper steroid dose and prevent disease flare-up.

PubMed

Liao, Yen-Nung; Liu, Ching-Shen; Tsai, Tong-Rong; Hung, Yu-Chiang; Chang, Shun-Jen; Lin, Hong-Long; Chen, Ying-Chou; Lai, Han-Ming; Yu, Shan-Fu; Chen, Chung-Jen

2011-07-01

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease. Prolonged complete remission is rare. Most patients with SLE need long-term treatment with glucocorticoid and immunomodulators. However, side effects because of the above medications are common. We evaluated the effect of adding-on Dan-Chi-Liu-Wei combination (DCLWC) on SLE patients with conventional therapy in tapering steroid and preventing disease flare-up. This was a double-blind and randomized controlled trial. Sixty-six SLE patients were recruited into this study and 53 patients who fulfilled the 1997 revised criteria for the classification of SLE with an SLE disease activity index (SLEDAI) score of 2-12 and a steroid (measured with prednisolone) daily dose of less than 20mg/d were enrolled. The patients were randomized into either an experimental or control group. We checked the urine analysis, hemogram, liver function, renal function, C3, C4, erythrocyte sedimentation rate, and anti-dsDNA, evaluated the SLEDAI score, and recorded the steroid dose at 0 months, 3 months, and 6 months, respectively. After 6 months of study, the C4 and blood urea nitrogen level revealed a statistically significant difference in either group. There was a tendency toward a decreased SLEDAI score in the experimental group (p=0.083) but not in the control group (p=0.867). The steroid dose was not statistically significant in either group. Renal function and liver function revealed no statistically significant statistics changes in either group. Adding-on DCLWC to conventional therapy for the treatment of SLE was safe and might have a borderline effect in decreasing disease activity, but it was not possible to taper the dosage of steroid after 6 months of clinical trial. Therefore, a long-term follow-up and a large-scale study are necessary to confirm the effect of DCLWC. Copyright © 2011 Elsevier Taiwan LLC. All rights reserved.

Follow-up of renal and mesenteric artery revascularization with duplex ultrasonography

PubMed Central

Taylor, David C.; Houston, Gordon T.M.; Anderson, Caroline; Jameson, Margot; Popatia, Shelley

1996-01-01

Objective To evaluate the long-term anatomic results of renal revascularization procedures using duplex ultrasonography. Design A case series. Setting A university-affiliated hospital. Patients Twenty-five patients who had undergone renal percutaneous transluminal angioplasty (PTA) (18 arteries), renal bypass (10 arteries) and mesenteric bypass (6 arteries). The mean follow-up was 22 months (range from 3 to 48 months) for those who underwent renal PTA, 23 months (range from 1.5 to 70 months) for those who underwent renal bypass and 34 months (range from 8 to 144 months) for those who underwent mesenteric bypass. Main Outcome Measures Patency rates for the three procedures as assessed by duplex ultrasonography. Results Duplex ultrasonography demonstrated patency without stenosis after renal and mesenteric artery revascularization in 14 arteries subjected to renal PTA, 9 arteries subjected to renal bypass and 6 arteries subjected to mesenteric bypass. Three arteries that had renal PTA had recurrent vessel stenosis and one had occlusion. One artery that had renal bypass showed occlusion. Conclusions Renal PTA, renal bypass and mesenteric bypass are durable procedures at 2 years of follow-up, and duplex ultrasonography is a valuable method for assessing the patency of arteries after renal and mesenteric revascularization. PMID:8599785

Atherosclerotic renal artery stenosis is associated with elevated cell cycle arrest markers related to reduced renal blood flow and postcontrast hypoxia.

PubMed

Saad, Ahmed; Wang, Wei; Herrmann, Sandra M S; Glockner, James F; Mckusick, Michael A; Misra, Sanjay; Bjarnason, Haraldur; Lerman, Lilach O; Textor, Stephen C

2016-11-01

Atherosclerotic renal artery stenosis (ARAS) reduces renal blood flow (RBF), ultimately leading to kidney hypoxia and inflammation. Insulin-like growth factor binding protein-7 (IGFBP-7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) are biomarkers of cell cycle arrest, often increased in ischemic conditions and predictive of acute kidney injury (AKI). This study sought to examine the relationships between renal vein levels of IGFBP-7, TIMP-2, reductions in RBF and postcontrast hypoxia as measured by blood oxygen level-dependent (BOLD) magnetic resonance imaging. Renal vein levels of IGFBP-7 and TIMP-2 were obtained in an ARAS cohort (n= 29) scheduled for renal artery stenting and essential hypertensive (EH) healthy controls (n = 32). Cortical and medullary RBFs were measured by multidetector computed tomography (CT) immediately before renal artery stenting and 3 months later. BOLD imaging was performed before and 3 months after stenting in all patients, and a subgroup (N = 12) underwent repeat BOLD imaging 24 h after CT/stenting to examine postcontrast/procedure levels of hypoxia. Preintervention IGFBP-7 and TIMP-2 levels were elevated in ARAS compared with EH (18.5 ± 2.0 versus 15.7 ± 1.5 and 97.4 ± 23.1 versus 62.7 ± 9.2 ng/mL, respectively; P< 0.0001); baseline IGFBP-7 correlated inversely with hypoxia developing 24 h after contrast injection (r = -0.73, P< 0.0001) and with prestent cortical blood flow (r = -0.59, P= 0.004). These data demonstrate elevated IGFBP-7 and TIMP-2 levels in ARAS as a function of the degree of reduced RBF. Elevated baseline IGFBP-7 levels were associated with protection against postimaging hypoxia, consistent with 'ischemic preconditioning'. Despite contrast injection and stenting, AKI in these high-risk ARAS subjects with elevated IGFBP-7/TIMP-2 was rare and did not affect long-term kidney function. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Systemic lupus erythematosus in Saudi children: long-term outcomes.

PubMed

Al-Mayouf, Sulaiman M

2013-02-01

To report the long-term outcome of Saudi children with systemic lupus erythematosus (SLE). Charts of all children with SLE treated between 1990 and 2010 at King Faisal Specialist Hospital and Research Center Riyadh, were reviewed. The long-term outcome measured by pediatric adaptation of the Systemic Lupus International Collaborating Clinics American College of Rheumatology Damage Index (pSDI) and death related to SLE were determined. The data included: gender, age at disease onset, clinical features and treatment at last follow-up visit. One hundred and fifty-two patients (129 girls and 23 boys) were included. The mean age at onset of SLE was 8.8 ± 2.6 years, while the mean age at diagnosis was 9.5 ± 2.6 years and the mean disease duration was 7.5 ± 4.6 years. All patients were treated with corticosteroid and immunosuppressive drugs. Eighty (52.6%) patients had damage with a mean SDI score of 1.3 ± 1.7. Damage accrual was mostly in the growth (26.8%), renal (17.1%) and neuropsychiatric (15.8%) domains. Due to progressive renal disease, 14 patients required dialysis; five of them underwent renal transplant. There were nine deaths related to SLE, eight of them due to infection. Based on logistic regression, patient disease damage was significantly associated with young age at disease onset and long disease duration. Similarly, death related to SLE was influenced by early-onset disease. In contrast, gender, disease duration and therapy did not affect the suggested outcome measures. Our results are comparable to reports from other tertiary centers. Early-onset disease probably influences the long-term outcome of SLE in children. Infection remains an important cause of death in children with SLE. © 2012 The Author International Journal of Rheumatic Diseases © 2012 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Congenital renal anomalies in cloacal exstrophy: Is there a difference?

PubMed

Suson, K D; Inouye, B; Carl, A; Gearhart, J P

2016-08-01

Cloacal exstrophy (CE) is the most severe manifestation of the epispadias-exstrophy spectrum. Previous studies have indicated an increased rate of renal anomalies in children with classic bladder exstrophy (CBE). Given the increased severity of the CE defect, it was hypothesized that there would be an even greater incidence among these children. The primary objective was to characterize renal anatomy in CE patients. Two secondary objectives were to compare these renal anatomic findings in male and female patients, and female patients with and without Müllerian anomalies. An Institutional Review Board-approved retrospective review of 75 patients from an institutional exstrophy database. Data points included: age at analysis, sex, and renal and Müllerian anatomy. Abnormal renal anatomy was defined as a solitary kidney, malrotation, renal ectopia, congenital cysts, duplication, and/or proven obstruction. Abnormal Müllerian anatomy was defined as uterine or vaginal duplication, obstruction, and/or absence. The Summary Table presents demographic data and renal anomalies. Males were more likely to have renal anomalies. Müllerian anomalies were present in 65.7% of female patients. Girls with abnormal Müllerian anatomy were 10 times more likely to have renal anomalies than those with normal Müllerian anatomy (95% CI 1.1-91.4, P = 0.027). Patients with CE had a much higher rate of renal anomalies than that reported for CBE. Males and females with Müllerian anomalies were at greater risk than females with normal uterine structures. Mesonephric and Müllerian duct interaction is required for uterine structures to develop normally. It has been proposed that women with both Müllerian and renal anomalies be classified separately from other uterine malformations on an embryonic basis. In these patients, an absent or dysfunctional mesonephric duct has been implicated as potentially causal. This provided an embryonic explanation for uterine anomalies in female CE patients. There were also clinical implications. Women with renal agenesis and uterine anomalies were more likely to have endometriosis than those with isolated uterine anomalies, but were also more likely to have successful pregnancies. Males may have had an analogous condition with renal agenesis and seminal vesicle cysts. Future research into long-term kidney function in this population, uterine function, and possible male sexual duct malformation is warranted. Congenital renal anomalies occurred frequently in children with CE. They were more common in boys than in girls. Girls with abnormal Müllerian anatomy were more likely to have anomalous renal development. Mesonephric duct dysfunction may be embyologically responsible for both renal and Müllerian maldevelopment. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Graft function assessment in mouse models of single- and dual- kidney transplantation.

PubMed

Wang, Lei; Wang, Ximing; Jiang, Shan; Wei, Jin; Buggs, Jacentha; Fu, Liying; Zhang, Jie; Liu, Ruisheng

2018-05-23

Animal models of kidney transplantation (KTX) are widely used in studying immune response of hosts to implanted grafts. Additionally, KTX can be used in generating kidney-specific knockout animal models by transplantation of kidneys from donors with global knockout of a gene to wild type recipients or vise verse. Dual kidney transplantation (DKT) provides a more physiological environment for recipients than single kidney transplantation (SKT). However, DKT in mice is rare due to technical challenges. In this study, we successfully performed DKT in mice and compared the hemodynamic response and graft function with SKT. The surgical time, complications and survival rate of DKT were not significantly different from SKT, where survival rates were above 85%. Mice with DKT showed less injury and quicker recovery with lower plasma creatinine (Pcr) and higher GFR than SKT mice (Pcr = 0.34 and 0.17 mg/dl in DKT vs. 0.50 and 0.36 mg/dl in SKT at 1 and 3 days, respectively; GFR = 215 and 131 µl/min for DKT and SKT, respectively). In addition, the DKT exhibited better renal functional reserve and long-term outcome of renal graft function than SKT based on the response to acute volume expansion. In conclusion, we have successfully generated a mouse DKT model. The hemodynamic responses of DKT better mimic physiological situations with less kidney injury and better recovery than SKT because of reduced confounding factors such as single nephron hyperfiltration. We anticipate DKT in mice will provide an additional tool for evaluation of renal significance in physiology and disease.

Improved Pulse Wave Velocity and Renal Function in Individualized Calcineurin Inhibitor Treatment by Immunomonitoring: The Randomized Controlled Calcineurin Inhibitor-Sparing Trial.

PubMed

Sommerer, Claudia; Brocke, Janina; Bruckner, Thomas; Schaier, Matthias; Morath, Christian; Meuer, Stefan; Zeier, Martin; Giese, Thomas

2018-03-01

A new immune monitoring tool which assesses the expression of nuclear factor of activated T cells (NFAT)-regulated genes measures the functional effects of cyclosporine A. This is the first prospective randomized controlled study to compare standard pharmacokinetic monitoring by cyclosporine trough levels to NFAT-regulated gene expression (NFAT-RE). Expression of the NFAT-regulated genes was determined by qRT-PCR at cyclosporine trough and peak level. Cardiovascular risk was assessed by change of pulse wave velocity from baseline to month 6. Clinical follow-up was 12 months. In total, 55 stable kidney allograft recipients were enrolled. Mean baseline residual NFAT-RE was 13.1 ± 9.1%. Patients in the NFAT-RE group showed a significant decline in pulse wave velocity from baseline to month 6 versus the standard group (-1.7 ± 2.0 m/s vs 0.4 ± 1.4 m/s, P < 0.001). Infections occurred more often in the standard group compared with the immune monitoring group. No opportunistic infections occurred with NFAT-RE monitoring. At 12 months of follow-up, renal function was significantly better with NFAT-RE versus standard monitoring (Nankivell glomerular filtration rate: 68.5 ± 17.4 mL/min vs 57.2 ± 19.0 mL/min; P = 0.009). NFAT-RE as translational immune monitoring tool proved efficacious and safe in individualizing cyclosporine therapy, with the opportunity to reduce the cardiovascular risk and improve long-term renal allograft function.

Long-term fundus changes in acquired partial lipodystrophy.

PubMed

Jansen, Joyce; Delaere, Lien; Spielberg, Leigh; Leys, Anita

2013-11-18

We describe long-term fundus changes in a patient with partial lipodystrophy (PL). Retinal pigment alterations, drusen and subretinal neovascularisation were seen without evidence for membranoproliferative glomerulonephritis. Fundus alterations similar to those seen in age-related macular degeneration can occur at an earlier age in patients with PL, even without renal disease. Dysregulation of an alternative complement pathway with low serum levels of C3 has been implicated as a pathogenetic mechanism.

Long-term fundus changes in acquired partial lipodystrophy

PubMed Central

Jansen, Joyce; Delaere, Lien; Spielberg, Leigh; Leys, Anita

2013-01-01

We describe long-term fundus changes in a patient with partial lipodystrophy (PL). Retinal pigment alterations, drusen and subretinal neovascularisation were seen without evidence for membranoproliferative glomerulonephritis. Fundus alterations similar to those seen in age-related macular degeneration can occur at an earlier age in patients with PL, even without renal disease. Dysregulation of an alternative complement pathway with low serum levels of C3 has been implicated as a pathogenetic mechanism. PMID:24248317

Preoperative proteinuria is associated with long-term progression to chronic dialysis and mortality after coronary artery bypass grafting surgery.

PubMed

Wu, Vin-Cent; Huang, Tao-Min; Wu, Pei-Chen; Wang, Wei-Jie; Chao, Chia-Ter; Yang, Shao-Yu; Shiao, Chih-Chung; Hu, Fu-Chang; Lai, Chun-Fu; Lin, Yu-Feng; Han, Yin-Yi; Chen, Yih-Sharng; Hsu, Ron-Bin; Young, Guang-Huar; Wang, Shoei-Shen; Tsai, Pi-Ru; Chen, Yung-Ming; Chao, Ting-Ting; Ko, Wen-Je; Wu, Kwan-Dun

2012-01-01

Preoperative proteinuria is associated with post-operative acute kidney injury (AKI), but whether it is also associated with increased long-term mortality and end-stage renal disease (ESRD) is unknown. We studied 925 consecutive patients undergoing CABG. Demographic and clinical data were collected prospectively, and patients were followed for a median of 4.71 years after surgery. Proteinuria, according to dipstick tests, was defined as mild (trace to 1+) or heavy (2+ to 4+) according to the results of the dipstick test. A total of 276 (29.8%) patients had mild proteinuria before surgery and 119 (12.9%) patients had heavy proteinuria. During the follow-up, the Cox proportional hazards model demonstrated that heavy proteinuria (hazard ratio [HR], 27.17) was an independent predictor of long-term ESRD. There was a progressive increased risk for mild proteinuria ([HR], 1.88) and heavy proteinuria ([HR], 2.28) to predict all-cause mortality compared to no proteinuria. Mild ([HR], 2.57) and heavy proteinuria ([HR], 2.70) exhibited a stepwise increased ratio compared to patients without proteinuria for long-term composite catastrophic outcomes (mortality and ESRD), which were independent of the baseline GFR and postoperative acute kidney injury (AKI). Our study demonstrated that proteinuria is a powerful independent risk factor of long-term all-cause mortality and ESRD after CABG in addition to preoperative GFR and postoperative AKI. Our study demonstrated that proteinuria should be integrated into clinical risk prediction models for long-term outcomes after CABG. These results provide a high priority for future renal protective strategies and methods for post-operative CABG patients.

A huge bladder calculus causing acute renal failure.

PubMed

Komeya, Mitsuru; Sahoda, Tamami; Sugiura, Shinpei; Sawada, Takuto; Kitami, Kazuo

2013-02-01

A 81-year-old male was referred to our emergency outpatient unit due to acute renal failure. The level of serum creatinine was 276 μmol/l. A CT scan showed bilateral hydronephroureter, large bladder stone (7 cm × 6 cm × 6 cm) and bladder wall thickness. He was diagnosed as post renal failure due to bilateral hydronephroureter. Large bladder stone is thought to be the cause of bilateral hydronephroureter and renal failure. To improve renal failure, we performed open cystolithotomy and urethral catheterization. Three days after the surgery, the level of serum creatinine decreased to 224 μmol/l. He was discharged from our hospital with uneventful course. Bladder calculus is thought to be a rare cause of renal failure. We summarize the characteristics of bladder calculus causing renal failure. We should keep that long-term pyuria and urinary symptom, and repeated urinary tract infection can cause huge bladder calculus and renal failure in mind.

Image-guided percutaneous microwave ablation of small renal tumours: short- and mid-term outcomes.

PubMed

Genson, Pierre-Yves; Mourey, Eric; Moulin, Morgan; Favelier, Sylvain; Di Marco, Lucy; Chevallier, Olivier; Cercueil, Jean-Pierre; Krausé, Denis; Cormier, Luc; Loffroy, Romaric

2015-10-01

The purpose is to assess the short- and mid-term outcomes of microwave ablation (MWA) of small renal tumours in selected patients. From August 2012 to February 2015, 29 renal tumours in 23 patients (17 male, 6 female, mean age 75 years) were treated by percutaneous MWA under imaging guidance. The tumours were 1-4.7 cm in diameter (mean size, 2.7 cm). Therapeutic effects were assessed at follow-up with magnetic resonance imaging (MRI). All patients were followed up for 2-25 months (mean, 12.2 months) to observe the therapeutic effects and complications. Changes in renal function at day 1 after treatment were statistically analyzed using the Student paired t-test or the paired Wilcoxon test. Technical success was achieved in all cases. One severe bleeding complication post-procedure occurred leading to death. No other unexpected side effects were observed after the MWA procedures. Clinical effectiveness was 100%. None of the patients showed recurrence on MRI imaging follow-up. No significant changes in renal function were noted after treatment (P=0.57). Our preliminary study demonstrates that the use of MWA for the treatment of small renal tumours can be applied as safely and efficiently as other ablative techniques in selected patients not eligible for surgery.

Rapid improvement of renal function in patients with acute pulmonary embolism indicates favorable short term prognosis.

PubMed

Kostrubiec, Maciej; Łabyk, Andrzej; Pedowska-Włoszek, Justyna; Pacho, Szymon; Dzikowska-Diduch, Olga; Dul, Przemysław; Ciurzyński, Michał; Bienias, Piotr; Pruszczyk, Piotr

2012-09-01

Various clinical and biochemical parameters predict the prognosis of patients with acute pulmonary embolism(APE). Treatment of APE can improve a patient's hemodynamic status, restoring adequate peripheral organ perfusion. Therefore, we hypothesized that improvement of renal function can predict short term prognosis of APE patients. We evaluated 232 consecutive patients (94 men,aged 67 ± 18 years) with APE proven by spiral computer tomography. Blood samples were collected for creatinine assays on admission and 72 hours later, the glomerular filtration rate(eGFR) was estimated using the MDRD formula. During the first 72 hours, 6 subjects died, while during the first 30 days 24(10%) subjects died (APE mortality 8%). On admission eGFR<60 ml/min was present in 113 patients(49%) and after 72 hours in 85 patients(38%). In 26 patients(11%) eGFR on admission was <60 ml/min and renal function did not improve during subsequent 72 hours. In this group the 30-day all-cause and APE-related mortality rates were 27% and 23%, respectively, while serious adverse events occurred in 38% of them. 206 patients with eGFR>60 ml/min showed a more favorable prognosis (8% 30-day all-cause mortality) than subjects with eGFR<60 ml/min and a stable eGFR during the first 72 hours (27% mortality rate, p<0.003). Persistent renal dysfunction predicted all-cause and PE-related 30-day mortality (hazard risk 2.53(CI 95%:0.96-6.68),p=0.06 and 3.04(CI 95%:1.28-7.26),p=0.01, respectively). Approximately 50% of patients with APE have at least a moderately impaired renal function on admission. Renal function improves within 72 hours in patients with a good prognosis, while "persistent" renal dysfunction indicates an increased mortality. Copyright © 2012 Elsevier Ltd. All rights reserved.

Prophylaxis of Contrast-Induced Nephrotoxicity

PubMed Central

2014-01-01

Contrast-induced nephrotoxicity (CIN) is a form of acute kidney injury that follows intravascular contrast media exposure. CIN may be preventable because its risk factors are well established and the timing of renal insult is commonly known in advance. However, contrast-induced nephrotoxicity is still the third leading cause of iatrogenic renal failure. This important complication accounts up to 10% of acute renal failure cases in hospitalized patients and it is associated with increased short- and long-term morbidity and mortality. Prolonged hospitalization follows and overall increases healthcare resource utilization. This paper will discuss the various prophylactic procedures tested in clinical trials. PMID:24812612

Renal Effects of Long Term Administration of Triamcinolone Acetonide in Normal Dogs

PubMed Central

Osbaldiston, G. W.

1971-01-01

Triamcinolone acetonide was administered in excessive dosage to dogs to study the renal mechanism responsible for polyuria which is a clinically undesirable side effect of long term glucocorticoid therapy. Polyuria occurred coincident with a significant increase in urinary solute output. Although continuous administration of triamcinolone acetonide at 0.1 or 0.2 mg/lb/day caused a small but significant increase in creatinine output, the primary mechanism for the polyuria was increased solute excretion. Associated with the polyuria was pronounced hyperphagia and polydipsia. The cause of the hyperphagia was not established. The increase in electrolyte excretion caused by this synthetic steroid was probably compensated for by the hyperphagia. Because all the dogs showed muscle weakness and loss of body condition, it is likely that alteration in protein and amino acid metabolism was responsible for the hyperphagia. PMID:4251411

Renal denervation: unde venis et quo vadis?

PubMed

Nähle, C P; Düsing, R; Schild, H

2015-04-01

Renal denervation is a minimally invasive, catheter-based option for the treatment of refractory hypertension. Indications and contraindications for renal denervation have been defined in an interdisciplinary manner. The efficacy and safety of the procedure were evaluated. Currently, indication for renal denervation is limited to patients with primary hypertension and a systolic blood pressure of ≥ 160 mm Hg (or ≥ 150 mm Hg in diabetes type 2) despite optimal medical therapy with ≥ 3 different antihypertensive drugs. In this specific patient population, an average blood pressure reduction of 32/14 mmHg was observed in non-randomized/-controlled trials after renal denervation. These results were not confirmed in the first randomized controlled trial with a non-significantly superior blood pressure reduction of 14.1 ± 23.9 mm Hg compared to controls (-11.74 ± 25.94 mm Hg, difference -2.39 mm Hg p = 0.26 for superiority with a margin of 5 mm Hg) who underwent a sham procedure. The efficacy and long-term effects of renal denervation need to be re-evaluated in light of the HTN3 study results. To date, renal denervation should not be performed outside of clinical trials. Future trials should also assess if renal denervation can be performed with sufficient safety and efficacy in patients with hypertension-associated diseases. The use of renal denervation as an alternative therapy (e. g. in patients with drug intolerance) can currently not be advocated. The indication for renal denervation should be assessed in an interdisciplinary fashion and according to current guidelines with a special focus on ruling out secondary causes for arterial hypertension. 5 - 10 % of patients with hypertension suffer from refractory hypertension, but only about 1 % of patients meet the criteria for a renal denervation. Renal denervation leads to a significant decrease in office blood pressure; however, the impact on 24-hour blood pressure measurements remains unclear. In the first randomized controlled trial on renal denervation with a control group undergoing a sham procedure, blood pressure reduction failed to reach the anticipated level of superiority over best medical treatment. Periprocedural complications are rare, but long-term safety can currently not be appraised due to the limited data available. © Georg Thieme Verlag KG Stuttgart · New York.

The viability of transplanting organs from donors who underwent cardiopulmonary resuscitation: A systematic review.

PubMed

West, Stephen; Soar, Jasmeet; Callaway, Clifton W

2016-11-01

To identify reports of patients who underwent cardiopulmonary resuscitation (CPR) prior to solid organ donation and compare recipient and organ function outcomes to those that did not undergo CPR. Donation after restoration of circulation then progressing to death and those donating with on-going CPR who would have otherwise have termination of efforts were both included. Systematic review. Clinical studies comparing the outcome of patients and organs retrieved from donors who underwent CPR with those that did not require CPR. Full-text articles were searched on EmBASE, MEDLINE, Cochrane Database of Systematic Reviews and the Cochrane Register of Controlled Trials. Twenty-two observational studies were included. There were 12,206 adult and 2552 paediatric organ transplantation identified. Comparing donation after restoration of circulation there was no difference in immediate, one year, and five-year graft function. Donation with on-going CPR was associated with reduced immediate graft function for both renal and hepatic transplantation, however long term function was not different. CPR does not appear to adversely affect graft function. Patients who have restored circulation after resuscitation and subsequently progress to death should be evaluated for organ donation. Those with on-going CPR should be considered for hepatic and renal transplantation but there may be worse initial graft function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Perioperative Acute Kidney Injury: Prevention, Early Recognition, and Supportive Measures.

PubMed

Romagnoli, Stefano; Ricci, Zaccaria; Ronco, Claudio

2018-06-26

Acute kidney injury (AKI) is a frequent complication of both cardiac and major non-cardiac surgery. AKI is independently associated with morbidity, mortality, and long-term adverse events including chronic kidney disease in postsurgical patients. Since specific treatment options for kidney failure are very limited, early identification, diagnosis, and renal support strategies are key steps to improve patients' outcome. According to current Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, AKI diagnosis is based on 2 functional markers, serum creatinine increase and urine output decrease, that are not renal-specific and have important limitations. However, preoperative risk stratification for postoperative AKI and/or early diagnosis after surgery could be the best way to apply preventive or timely supportive therapeutic measures. Clinical prediction scores, renal functional reserve assessment, and new biomarkers of kidney stress (suppression of tumorigenicity-2, insulin-like growth factor binding protein-7, tissue inhibitor metalloproteinase-2) may help the clinicians to identify patients at risk of AKI and that could benefit from the application of nephroprotective bundles suggested by the KDIGO guidelines. In severe AKI patients with oligoanuria and fluid accumulation, renal replacement therapy is the only supportive measure even if mode and timing remain open to investigation. Key messages: Perioperative AKI is an important and underdiagnosed complication. Identifying patients at high risk of AKI and diagnosing AKI early are major goals. Preventive interventions are mainly based on the KDIGO guidelines and bundles. Furthermore, a personalized multidisciplinary approach should always be considered to minimize the progression of disease and the complications related to kidney damage. © 2018 S. Karger AG, Basel.

Acute renal proximal tubule alterations during induced metabolic crises in a mouse model of glutaric aciduria type 1.

PubMed

Thies, Bastian; Meyer-Schwesinger, Catherine; Lamp, Jessica; Schweizer, Michaela; Koeller, David M; Ullrich, Kurt; Braulke, Thomas; Mühlhausen, Chris

2013-10-01

The metabolic disorder glutaric aciduria type 1 (GA1) is caused by deficiency of the mitochondrial glutaryl-CoA dehydrogenase (GCDH), leading to accumulation of the pathologic metabolites glutaric acid (GA) and 3-hydroxyglutaric acid (3OHGA) in blood, urine and tissues. Affected patients are prone to metabolic crises developing during catabolic conditions, with an irreversible destruction of striatal neurons and a subsequent dystonic-dyskinetic movement disorder. The pathogenetic mechanisms mediated by GA and 3OHGA have not been fully characterized. Recently, we have shown that GA and 3OHGA are translocated through membranes via sodium-dependent dicarboxylate cotransporter (NaC) 3, and organic anion transporters (OATs) 1 and 4. Here, we show that induced metabolic crises in Gcdh(-/-) mice lead to an altered renal expression pattern of NaC3 and OATs, and the subsequent intracellular GA and 3OHGA accumulation. Furthermore, OAT1 transporters are mislocalized to the apical membrane during metabolic crises accompanied by a pronounced thinning of proximal tubule brush border membranes. Moreover, mitochondrial swelling and increased excretion of low molecular weight proteins indicate functional tubulopathy. As the data clearly demonstrate renal proximal tubule alterations in this GA1 mouse model during induced metabolic crises, we propose careful evaluation of renal function in GA1 patients, particularly during acute crises. Further studies are needed to investigate if these findings can be confirmed in humans, especially in the long-term outcome of affected patients. Copyright © 2013 Elsevier B.V. All rights reserved.

Prolonged carotid sinus reflex is a risk factor for contrast-induced nephropathy following carotid artery stenting.

PubMed

Kato, T; Sakai, H; Tsujimoto, M; Nishimura, Y

2011-03-01

Although many studies have demonstrated that CIN is associated with in-hospital and long-term mortality, the incidence of CIN following CAS is unclear. We investigated the incidence of CIN, defined as an increase from a baseline creatinine value of at least 0.5 mg/dL or 25% within 72 hours of contrast administration, and we also examined renal function in the late phase after CAS. We examined 80 patients who underwent CAS between April 2005 and December 2009. Clinical background, laboratory data, contrast volume, and clinical course were collected and analyzed. The incidence of CIN was 8.8% (7/80), and no patients required hemodialysis. In the group that developed CIN, prolonged CSR after CAS was found in 57.1% (4/7) of cases; this incidence differed significantly (P = .001) from that in the group without development of CIN. Neither preoperative renal function, contrast volume, nor history was related to the incidence of CIN, while on multivariate analysis, prolonged CSR was found to be an independent risk factor for CIN. The incidence of elevation in creatinine values at 6 months after CAS was 8.2% (6/73). All patients who developed delayed renal impairment had pre-existing CKD; this finding differed significantly (P = .04) from that in the group without development of delayed renal impairment. Because patients who develop prolonged CSR after CAS are at increased risk of perioperative major adverse clinical events including CIN, patients at high risk for this condition should be carefully managed to prevent increased morbidity and mortality.

Cardio-renal and metabolic adaptations during pregnancy in female rats born small: implications for maternal health and second generation fetal growth.

PubMed

Gallo, Linda A; Tran, Melanie; Moritz, Karen M; Mazzuca, Marc Q; Parry, Laura J; Westcott, Kerryn T; Jefferies, Andrew J; Cullen-McEwen, Luise A; Wlodek, Mary E

2012-02-01

Intrauterine growth restriction caused by uteroplacental insufficiency increases risk of cardiovascular and metabolic disease in offspring. Cardio-renal and metabolic responses to pregnancy are critical determinants of immediate and long-term maternal health. However, no studies to date have investigated the renal and metabolic adaptations in growth restricted offspring when they in turn become pregnant. We hypothesised that the physiological challenge of pregnancy in growth restricted females exacerbates disease outcome and compromises next generation fetal growth. Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on day 18 of gestation in WKY rats and F1 female offspring birth and postnatal body weights were recorded. F1 Control and Restricted females were mated at 4 months and blood pressure, renal and metabolic parameters were measured in late pregnancy and F2 fetal and placental weights recorded. Age-matched non-pregnant Control and Restricted F1 females were also studied. F1 Restricted females were born 10-15% lighter than Controls. Basal insulin secretion and pancreatic β-cell mass were reduced in non-pregnant Restricted females but restored in pregnancy. Pregnant Restricted females, however, showed impaired glucose tolerance and compensatory glomerular hypertrophy, with a nephron deficit but normal renal function and blood pressure. F2 fetuses from Restricted mothers exposed to physiological measures during pregnancy were lighter than Controls highlighting additive adverse effects when mothers born small experience stress during pregnancy. Female rats born small exhibit mostly normal cardio-renal adaptations but altered glucose control during late pregnancy making them vulnerable to lifestyle challenges.

Far infrared radiation promotes rabbit renal proximal tubule cell proliferation and functional characteristics, and protects against cisplatin-induced nephrotoxicity.

PubMed

Chiang, I-Ni; Pu, Yeong-Shiau; Huang, Chao-Yuan; Young, Tai-Horng

2017-01-01

Far infrared radiation, a subdivision of the electromagnetic spectrum, is beneficial for long-term tissue healing, anti-inflammatory effects, growth promotion, sleep modulation, acceleration of microcirculation, and pain relief. We investigated if far infrared radiation is beneficial for renal proximal tubule cell cultivation and renal tissue engineering. We observed the effects of far infrared radiation on renal proximal tubules cells, including its effects on cell proliferation, gene and protein expression, and viability. We also examined the protective effects of far infrared radiation against cisplatin, a nephrotoxic agent, using the human proximal tubule cell line HK-2. We found that daily exposure to far infrared radiation for 30 min significantly increased rabbit renal proximal tubule cell proliferation in vitro, as assessed by MTT assay. Far infrared radiation was not only beneficial to renal proximal tubule cell proliferation, it also increased the expression of ATPase Na+/K+ subunit alpha 1 and glucose transporter 1, as determined by western blotting. Using quantitative polymerase chain reaction, we found that far infrared radiation enhanced CDK5R1, GNAS, NPPB, and TEK expression. In the proximal tubule cell line HK-2, far infrared radiation protected against cisplatin-mediated nephrotoxicity by reducing apoptosis. Renal proximal tubule cell cultivation with far infrared radiation exposure resulted in better cell proliferation, significantly higher ATPase Na+/K+ subunit alpha 1 and glucose transporter 1 expression, and significantly enhanced expression of CDK5R1, GNAS, NPPB, and TEK. These results suggest that far infrared radiation improves cell proliferation and differentiation. In HK-2 cells, far infrared radiation mediated protective effects against cisplatin-induced nephrotoxicity by reducing apoptosis, as indicated by flow cytometry and caspase-3 assay.

The association between renal recovery after acute kidney injury and long-term mortality after transcatheter aortic valve replacement.

PubMed

Thongprayoon, Charat; Cheungpasitporn, Wisit; Srivali, Narat; Kittanamongkolchai, Wonngarm; Sakhuja, Ankit; Greason, Kevin L; Kashani, Kianoush B

2017-01-01

This study aimed to examine the association between renal recovery status at hospital discharge after acute kidney injury (AKI) and long-term mortality following transcatheter aortic valve replacement (TAVR). We screened all adult patients who survived to hospital discharge after TAVR for aortic stenosis at a quaternary referral medical center from January 1, 2008, through June 30, 2014. An AKI was defined as an increase in serum creatinine level of 0.3 mg/dL or a relative increase of 50% from baseline. Renal outcome at the time of discharge was evaluated by comparing the discharge serum creatinine level to the baseline level. Complete renal recovery was defined as no AKI at discharge, whereas partial renal recovery was defined as AKI without a need for renal replacement therapy at discharge. No renal recovery was defined as a need for renal replacement therapy at discharge. The study included 374 patients. Ninty-eight (26%) patients developed AKI during hospitalization: 55 (56%) had complete recovery; 39 (40%), partial recovery; and 4 (4%), no recovery. AKI development was significantly associated with increased risk of 2-year mortality (hazard ratio [HR], 2.20 [95% CI, 1.37-3.49]). For patients with AKI, the 2-year mortality rate for complete recovery was 34%; for partial recovery, 43%; and for no recovery, 75%; compared with 20% for patients without AKI (P < .001). In adjusted analysis, complete recovery (HR, 1.87 [95% CI, 1.03-3.23]); partial recovery (HR, 2.65 [95% CI, 1.40-4.71]) and no recovery (HR, 10.95 [95% CI, 2.59-31.49]) after AKI vs no AKI were significantly associated with increased risk of 2-year mortality. The mortality rate increased for all patients with AKI undergoing TAVR. A reverse correlation existed for progressively higher risk of death and the extent of AKI recovery.

Epidemiology and Outcome of Acute Kidney Injury According to Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes Criteria in Critically Ill Children-A Prospective Study.

PubMed

Volpon, Leila C; Sugo, Edward K; Consulin, Julio C; Tavares, Tabata L G; Aragon, Davi C; Carlotti, Ana P C P

2016-05-01

We aimed to investigate the epidemiology, risk factors, and short- and medium-term outcome of acute kidney injury classified according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease, and Kidney Disease: Improving Global Outcomes criteria in critically ill children. Prospective observational cohort study. Two eight-bed PICUs of a tertiary-care university hospital. A heterogeneous population of critically ill children. None. Demographic, clinical, laboratory, and outcome data were collected on all patients admitted to the PICUs from August 2011 to January 2012, with at least 24 hours of PICU stay. Of the 214 consecutive admissions, 160 were analyzed. The prevalence of acute kidney injury according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes criteria was 49.4% vs. 46.2%, respectively. A larger proportion of acute kidney injury episodes was categorized as Kidney Disease: Improving Global Outcomes stage 3 (50%) compared with pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease F (39.2%). Inotropic score greater than 10 was a risk factor for acute kidney injury severity. About 35% of patients with acute kidney injury who survived were discharged from the PICU with an estimated creatinine clearance less than 75 mL/min/1.73 m and one persisted with altered renal function 6 months after PICU discharge. Age 12 months old or younger was a risk factor for estimated creatinine clearance less than 75 mL/min/1.73 m at PICU discharge. Acute kidney injury and its severity were associated with increased PICU length of stay and longer duration of mechanical ventilation. Eleven patients died; nine had acute kidney injury (p < 0.05). The only risk factor associated with death after multivariate adjustment was Pediatric Risk of Mortality score greater than or equal to 10. Acute kidney injury defined by both pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes criteria was associated with increased morbidity and mortality, and may lead to long-term renal dysfunction.

Metabolic bone disease in chronic renal failure. II. Renal transplant patients.

PubMed Central

Huffer, W. E.; Kuzela, D.; Popovtzer, M. M.; Starzl, T. E.

1975-01-01

Trabecular vertebral bone of renal transplant patients was quantitatively compared with bone from normal individuals and dialyzed and nondialyzed patienets with chronic renal failure reported in detail in an earlier study. Long- and short-term transplant patients have increased bone resorption and mineralization defects similar to renal osteodystrophy in dialyzed and nondialyzed patients. However, in transplant patients the magnitude of resorption is greater, and bone volume tends to decrease rather than increase. Resorptive activity in transplant patients is maximal during the first year after transplantation. Bone volume decreases continuously for at least 96 months after transplantation. Only decreased bone volume correlated with success or failure of the renal transplant. Morphologic findings in this study correlate with other clinical and morphologic data to suggest that reduction in bone volume in transplant patients results from a combination of persistent hyperparathyroidism and suppression of bone formation by steroid therapy. Images Fig 1 PMID:1091152

Long-term experience of steroid-free pediatric renal transplantation: effects on graft function, body mass index, and longitudinal growth.

PubMed

Wittenhagen, Per; Thiesson, Helle C; Baudier, François; Pedersen, Erik B; Neland, Mette

2014-02-01

Increased focus on the potential negative side effects of steroid usage in pediatric transplantation has led to steroid minimization or steroid-free transplantation. In this study, we report results after complete steroid avoidance in renal transplantation in the period 1994-2009. We evaluate the effects of complete steroid avoidance on allograft function, BMI, and linear growth. The majority of transplanted children were induced with antithymocyte globulin and immunosuppressed with a calcineurin inhibitor and mycophenolate mofetil. Steroids were given only when rejection occurred or due to comorbidities. Anthropometric data were collected from 65 transplantations in 60 children. Patient survival was 93%; graft survival was 81% after five yr (N = 42) and 63% after 10 yr (N = 16). Acute rejection within the first year of transplantation was 9%. The distribution of the children's BMI before transplantation was normal; the mean BMI-SDS was 0.21 before transplantation, and this value remained stable during the next five yr. Post-transplantation the children demonstrated significant improved growth as the mean height-SDS increased significantly from -1.7 to -1.1. Catch-up growth was most pronounced in the youngest (< six yr). Steroid-free immunosuppression in pediatric renal transplantation is safe and protects against steroid-induced obesity and short stature. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Association Between Renin-Angiotensin System Blockade and Long-term Outcomes in Renal Transplant Recipients: The Wisconsin Allograft Recipient Database (WisARD).

PubMed

Shin, Jung-Im; Palta, Mari; Djamali, Arjang; Kaufman, Dixon B; Astor, Brad C

2016-07-01

Renin-angiotensin system (RAS) blockade reduces mortality in the general population and among non-dialysis-dependent patients with chronic kidney disease. The RAS blockade also decreases proteinuria and protects renal function in non-transplant patients with chronic kidney disease. It remains controversial, however, whether this translates to improved patient or graft survival among transplant recipients. We analyzed 2684 primary kidney transplant recipients at the University of Wisconsin in 1994 to 2010 who had a functioning graft at 6 months after transplantation. We assessed the association of RAS blockade with patient and graft survival using time-dependent Cox and marginal structural models. Three hundred seventy-seven deaths and 329 graft failures before death (638 total graft losses) occurred during a median of 5.4 years of follow-up. The RAS blockade was associated with an adjusted-hazard ratio of 0.63 (95% confidence interval, 0.53-0.75) for total graft loss, 0.69 (0.55-0.86) for death, and 0.62 (0.49-0.78) for death-censored graft failure. The associations of RAS blockade with a lower risk of total graft loss and mortality were stronger with more severe proteinuria. The RAS blockade was associated with a 2-fold higher risk of hyperkalemia. Our findings suggest RAS blockade is associated with better patient and graft survival in renal transplant recipients.

Effects of spironolactone on residual renal function and peritoneal function in peritoneal dialysis patients.

PubMed

Yelken, Berna; Gorgulu, Numan; Gursu, Meltem; Yazici, Halil; Caliskan, Yasar; Telci, Aysegul; Ozturk, Savas; Kazancioglu, Rumeyza; Ecder, Tevfik; Bozfakioglu, Semra

2014-01-01

There is increasing evidence that long-term peritoneal dialysis (PD) is associated with structural changes in the peritoneal membrane. Inhibition of the renin-angiotensin system has been demonstrated to lessen peritoneal injury and to slow the decline in residual renal function. Whether spironolactone affects residual renal function in addition to the peritoneal membrane is unknown. We evaluated 23 patients (13 women) with a glomerular filtration rate of 2 mL/min/1.73 m2 or more who were receiving PD. Patients with an active infection or peritonitis episode were excluded. Baseline measurements were obtained for serum high-sensitivity C-reactive protein (hs-CRP), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-beta), and connective tissue growth factor (CTGF); for daily ultrafiltration (in milliliters); for end-to-initial dialysate concentration of glucose (4/D0 glucose), Kt/V, and peritoneal transport status; and for dialysate cancer antigen 125 (CA125). Spironolactone therapy (25 mg) was given daily for 6 months, after which all measurements were repeated. Mean age of the patients was 46 +/- 13 years. Duration of PD was 15 +/- 21 months (range: 2-88 months). After spironolactone therapy, mean dialysate CA125 was significantly increased compared with baseline (20.52 +/- 12.06 U/mL vs. 24.44 +/- 13.97 U/mL, p = 0.028). Serum hs-CRP, VEGF, TGF-beta, CTGF, daily ultrafiltration, D/Do glucose, Kt/V and peritoneal transport status were similar at both times. At the end of the study period, residual glomerular filtration rate in the patients was lower. In PD patients, treatment with spironolactone seems to slow the decline of peritoneal function, suppress the elevation of profibrotic markers, and increase mesothelial cell mass.

A 71-Year-Old Female with Myocardial Infarction and Long-Standing Ulcers on the Thigh

PubMed Central

De Flammineis, Eduardo; Mulvaney, Patrick M.; Kraft, Stefan; Mihm Jr., Martin C.; Das, Shinjita; Kroshinsky, Daniela

2017-01-01

Calciphylaxis is most commonly encountered in patients with end-stage renal disease; however, it is increasingly observed in nonuremic patients as well. It is important to consider and diagnose nonuremic calciphylaxis early, as prompt treatment and mitigation of associated risk factors is essential to improve long-term outcomes for these patients. Here, we present the case of a 71-year-old woman with atrial fibrillation on warfarin, but without renal disease, who presented with two long-standing ulcers on her thigh and was diagnosed with the aid of biopsy with calciphylaxis. We review the existing literature on the subject and offer this case as a representative report of a clinicopathologic correlation for this disorder. PMID:29456997

Enzyme replacement therapy in Fabry disease: influence on cardiac manifestations.

PubMed

Caballero, L; Climent, V; Hernández-Romero, D; Quintanilla, M A; de la Morena, G; Marín, F

2010-01-01

Fabry disease (FD) is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide (Gb3) in the lysosomes of different cells and tissues, causing principally ventricular hypertrophy, renal failure and cerebrovascular accidents, reducing lifespan both in hemizygous males and heterozygous females. Residual enzyme activity might lead to slow progression of the disease and result in the so-called cardiac or renal variants with delayed presentation. Two different forms of alpha-galactosidase A enzyme replacement therapies (ERT) are available for the treatment of FD, one genetically engineered in human cell line (agalsidase alfa, Replagal, Shire) and the other produced in a Chinese hamster ovary cell line (agalsidase beta, Fabrazyme, Genzyme). Although both proteins are structurally and functionally very similar, with the same amino acid sequence as the native human enzyme, they differ in the pattern of glycosilation of the protein depending on the originating cell line. Studies with both preparations have described a reduction in plasma, urinary sediment and tissue levels of Gb3, a decrease in the frequency of pain crisis and a reduction in left ventricular mass and improvement or stabilization of renal function. Studies have generally shown the greatest benefit when treatment is started at an early stage of the disease before extensive fibrosis or other irreversible tissue damage takes place. However, more data are needed to document long-term treatment outcomes. The aim of the present review is to provide an update overview of the two different forms of ERT for FD, their clinical effects in cardiac manifestations and their possible differences in terms of efficacy, side effects and safety profiles.

Renal sympathetic denervation in therapy resistant hypertension - pathophysiological aspects and predictors for treatment success

PubMed Central

Fengler, Karl; Rommel, Karl Philipp; Okon, Thomas; Schuler, Gerhard; Lurz, Philipp

2016-01-01

Many forms of human hypertension are associated with an increased systemic sympathetic activity. Especially the renal sympathetic nervous system has been found to play a prominent role in this context. Therefore, catheter-interventional renal sympathetic denervation (RDN) has been established as a treatment for patients suffering from therapy resistant hypertension in the past decade. The initial enthusiasm for this treatment was markedly dampened by the results of the Symplicity-HTN-3 trial, although the transferability of the results into clinical practice to date appears to be questionable. In contrast to the extensive use of RDN in treating hypertensive patients within or without clinical trial settings over the past years, its effects on the complex pathophysiological mechanisms underlying therapy resistant hypertension are only partly understood and are part of ongoing research. Effects of RDN have been described on many levels in human trials: From altered systemic sympathetic activity across cardiac and metabolic alterations down to changes in renal function. Most of these changes could sustainably change long-term morbidity and mortality of the treated patients, even if blood pressure remains unchanged. Furthermore, a number of promising predictors for a successful treatment with RDN have been identified recently and further trials are ongoing. This will certainly help to improve the preselection of potential candidates for RDN and thereby optimize treatment outcomes. This review summarizes important pathophysiologic effects of renal denervation and illustrates the currently known predictors for therapy success. PMID:27621771

Inhibition of soluble epoxide hydrolase does not improve the course of congestive heart failure and the development of renal dysfunction in rats with volume overload induced by aorto-caval fistula

PubMed Central

Červenka, Luděk; Melenovský, Vojtěch; Husková, Zuzana; Sporková, Alexandra; Bürgelová, Marcela; Škaroupková, Petra; Hwang, Sung Hee; Hammock, Bruce D.; Imig, John D.; Sadowski, Janusz

2016-01-01

The detailed mechanisms determining the course of congestive heart failure (CHF) and associated renal dysfunction remain unclear. In a volume overload model of CHF induced by creation of aorto-caval fistula (ACF) in Hannover Sprague-Dawley (HanSD) rats we explored the putative pathogenetic contribution of epoxyeicosatrienoic acids (EETs), active products of CYP-450 dependent epoxygenase pathway of arachidonic acid metabolism, and compared it with the role of the renin-angiotensin system (RAS). Chronic treatment with cis-4-[4-(3-adamantan-1-yl-ureido) cyclohexyloxy]benzoic acid (c-AUCB, 3 mg/L in drinking water), an inhibitor of soluble epoxide hydrolase (sEH) which normally degrades EETs, increased intrarenal and myocardial EETs to levels observed in sham-operated HanSD rats, but did not improve the survival or renal function impairment. In contrast, chronic angiotensin-converting enzyme inhibition (ACEi, trandolapril, 6 mg/L in drinking water) increased renal blood flow, fractional sodium excretion and markedly improved survival, without affecting left ventricular structure and performance. Hence, renal dysfunction rather than cardiac remodeling determines long-term mortality in advanced stage of CHF due to volume overload. Strong protective actions of ACEi were associated with suppression of the vasoconstrictor/sodium retaining axis and activation of vasodilatory/natriuretic axis of the renin-angiotensin system in the circulating blood and kidney tissue. PMID:26047375

Relationship between worsening renal function and long-term cardiovascular mortality in heart failure patients.

PubMed

Okabe, Toshitaka; Yakushiji, Tadayuki; Kido, Takehiko; Oyama, Yuji; Igawa, Wataru; Ono, Morio; Ebara, Seitaro; Yamashita, Kennosuke; Yamamoto, Myong Hwa; Saito, Shigeo; Amemiya, Kisaki; Isomura, Naoei; Araki, Hiroshi; Ochiai, Masahiko

2017-03-01

Recently several studies showed that worsening renal function (WRF) during hospitalization might be a strong independent predictor of poor prognosis in decompensated heart failure (HF) patients. However, these studies had a relatively short follow-up duration and their data were limited to in-hospital outcomes. Our purpose was to assess the relationship between WRF and long-term cardiovascular mortality in HF patients. We enrolled decompensated HF patients who were admitted to our hospital between April 2010 and March 2015. WRF was defined as a relative increase in serum creatinine of at least 25% or an absolute increase in serum creatinine ≥0.3mg/dL from the baseline. We assessed the cardiovascular mortality and all-cause mortality in HF patients with WRF (WRF group) and without WRF (no WRF group). Among 301 patients enrolled, WRF developed in 118 patients (39.2%). During a median follow-up period of 537days [interquartile range, 304.3 to 1025.8days], cardiovascular mortality and all-cause mortality were significantly higher in the WRF group than in the no WRF group (23.2% vs. 6.1%, P<0.001; 30.3% vs. 14.7%, P<0.001, respectively). In the multivariate Cox proportional hazards model, age and serum B-type natriuretic peptide (BNP) level were associated with both cardiovascular death and all-cause death. However, WRF was not the independent predictor of cardiovascular death (P=0.19) nor all-cause death (P=0.57). WRF was associated with cardiovascular death in patients with HF. Although not an independent predictor, WRF might be one of useful markers to identify patients who should be followed carefully after discharge. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prognostic value of the urea:creatinine ratio in decompensated heart failure and its relationship with acute kidney damage.

PubMed

Josa-Laorden, C; Sola, A; Giménez-López, I; Rubio-Gracia, J; Garcés-Horna, V; Pérez-Calvo, J I

Worsening renal function is associated with an adverse prognosis for patients with acute heart failure (AHF). Urea-creatinine ratio (U:C ratio) might be useful for measuring renal function and could help stratify patients with AHF. An observational and prospective study was conducted to analyse the prognostic value of the U:C ratio, measured during the first 24-28 hours of admission, for patients hospitalised for decompensated Heart failure, and its relationship with estimated glomerular filtration rate (eGFR) and acute kidney injury (AKI). The study included 204 patients, with a mean age of 79.3 years, and a median eGFR of 55 mL/min/1.73m 2 . In the multivariate analysis, an U:C ratio above the median (50) was related to the development of AKI (36.5% vs. 21.9%) and to increased mortality, both overall (OR 2.75) and by HF (OR 3.50) in long term. In combination with eGFR, the U:C ratio showed prognostic value in patients with normal eGFR (mortality of 4.4% for an U:C ratio ≤ 50 vs. 22% for U:C ratio > 50; p=0.01), as well as a better predictive capacity for AKI than each of them separately (AUC, 0.718; 95% CI 0.643-0.793; p>.000). An U:C ratio > 50 is a predictor of increased long-term mortality for patients hospitalised for decompensated HF and with normal eGFR. Given the simplicity of this biomarker, its use in clinical practice should be more systematic. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Forecast of the number of patients with end-stage renal disease in the United States to the year 2010.

PubMed

Xue, J L; Ma, J Z; Louis, T A; Collins, A J

2001-12-01

As the United States end-stage renal disease (ESRD) program enters the new millennium, the continued growth of the ESRD population poses a challenge for policy makers, health care providers, and financial planners. To assist in future planning for the ESRD program, the growth of patient numbers and Medicare costs was forecasted to the year 2010 by modeling of historical data from 1982 through 1997. A stepwise autoregressive method and exponential smoothing models were used. The forecasting models for ESRD patient numbers demonstrated mean errors of -0.03 to 1.03%, relative to the observed values. The model for Medicare payments demonstrated -0.12% mean error. The R(2) values for the forecasting models ranged from 99.09 to 99.98%. On the basis of trends in patient numbers, this forecast projects average annual growth of the ESRD populations of approximately 4.1% for new patients, 6.4% for long-term ESRD patients, 7.1% for dialysis patients, 6.1% for patients with functioning transplants, and 8.2% for patients on waiting lists for transplants, as well as 7.7% for Medicare expenditures. The numbers of patients with ESRD in 2010 are forecasted to be 129,200 +/- 7742 (95% confidence limits) new patients, 651,330 +/- 15,874 long-term ESRD patients, 520,240 +/- 25,609 dialysis patients, 178,806 +/- 4349 patients with functioning transplants, and 95,550 +/- 5478 patients on waiting lists. The forecasted Medicare expenditures are projected to increase to $28.3 +/- 1.7 billion by 2010. These projections are subject to many factors that may alter the actual growth, compared with the historical patterns. They do, however, provide a basis for discussing the future growth of the ESRD program and how the ESRD community can meet the challenges ahead.

Retroperitoneoscopic versus open surgical radical nephrectomy for 152 Chinese patients with large renal cell carcinoma in clinical stage cT2 or cT3a: A long-term retrospective comparison.

PubMed

Zhu, Xuhui; Yang, Xiaoyong; Hu, Xiaopeng; Zhang, Xiaodong

2016-01-01

To evaluate the feasibility, safety, and long-term efficacy of retroperitoneal laparoscopic radical nephrectomy for Chinese patients with a mean body mass index (BMI) of ≤24 and large renal cell carcinoma (RCC). A long-term retrospective analysis of clinical data of 152 Chinese patients with a mean BMI of ≤24 and large RCC. Totally, 84 patients who underwent retroperitoneal laparoscopic radical nephrectomy (RPNx) for tumor size >7 cm (group 1) were compared with 68 patients, who underwent open radical nephrectomy (group 2) for tumor with similar size characteristics. Moreover, their 10 years outcomes (or the number of patients) were divided into segments (e.g., the first 5 and last 5 years, the first 30 and last 30 patients, etc.) looking for the differences of learning curve. RPNx patients experienced significantly shorter hospital stay, less blood loss, and had a decreased analgesic requirement and more rapid convalescence. The incidence of intra- and post-operative complications was 6% and 13%, 7.2% and 16.1% in the two groups, respectively. The 5-year survival rates of the two groups were 86% and 82%, respectively. Retroperitoneal laparoscopic radical nephrectomy for patients with a mean BMI of ≤24 and large RCC is safe, feasible, and the efficacious procedure produced good long-term results.

Worsening renal function during renin-angiotensin-aldosterone system inhibitor initiation and long-term outcomes in patients with left ventricular systolic dysfunction.

PubMed

Clark, Hannah; Krum, Henry; Hopper, Ingrid

2014-01-01

Impaired renal function is associated with worse clinical outcomes in patients with LV systolic dysfunction (LVSD) and heart failure. Renin-angiotensin-aldosterone system (RAAS) inhibitors provide clinical benefit in these settings and often worsen renal function. It is not clear whether worsening renal function (WRF) in patients exposed to these agents predicts a worse prognosis or merely reflects the pharmacological action of the drug on the kidney. We performed a meta-analysis of all RAAS inhibitor LVSD trials reporting on outcomes according to WRF (as per individual study definition) in both active intervention and placebo groups. Five major studies (SOLVD, SAVE, RALES, Val-HeFT and EPHESUS) contributed, with 20 573 patients. Compared with placebo, RAAS inhibitors reduced all-cause mortality overall [n = 20 573, relative risk ratio (RR) 0.91, 95% confidence interval (CI) 0.86-0.95, P = 0.0003], in the group with no WRF (n = 18 209, RR 0.91, 95% CI 0.83-0.99, P = 0.04), and in the WRF group (n = 2364, RR 0.72, 95% CI 0.62-0.84, P < 0.0001). Compared with no WRF, WRF was associated with increased all-cause mortality; however, this was less in the RAAS inhibitor group (n = 8905, RR 1.22, 95% CI 1.10-1.36, P = 0.0003) than in the placebo group (n = 9304, RR 1.52, 95% CI 1.37-1.69, P < 0.00001). WRF shortly after randomization is associated with worsened outcomes compared with no WRF; however, the reduction in all-cause mortality associated with the use of RAAS inhibitors was significantly greater in the presence of WRF than in the no WRF group. Clinicians should not be deterred from using RAAS inhibitors in the setting of WRF. © 2013 The Authors. European Journal of Heart Failure © 2013 European Society of Cardiology.

Multifactorial analysis of renal transplants reported to the United Network for Organ Sharing Registry: a 1994 update.

PubMed

Gjertson, D W

1994-01-01

1. From a multivariate log-linear analysis of 57,303 renal transplants between 1988 and 1994, the top 10 factors influencing one-year and 3-year cadaveric graft survival rates were ranked as follows: [table: see text] 2. Center effects accounted for 30% and 28% of all assignable variations in one-year and 3-year outcomes, respectively. Although center variation dominated 32 other variables, most factors were relatively independent of transplant center. 3. Novel to our own multifactorial analyses of the UNOS Kidney Transplant Registry were 6 pretransplant factors (recipient pretransplant dialysis, pregnancy, PRA technique, donor disposition and preservation, and ABO compatibility). Survival rates over the various combinations of these new factors were not significantly different. 4. For the first time in our multivariate analyses, 4 posttransplantation factors (delayed graft function, rejection episodes prior to discharge, induction and maintenance drug therapies) were included in the log-linear model. It is noteworthy that graft survival in both transplant periods was seriously imperiled following delayed graft function or rejection prior to discharge, yet the accounting for these pseudo-outcome variables did not alter the influence of the remaining 31 transplant factors. Finally, maintenance drug therapies strongly influenced short-term outcomes but did not influence long-term results, except for a noteworthy trend toward increased survival rates for FK506 therapy.

A novel antioxidant agent caffeic acid phenethyl ester prevents long-term mobile phone exposure-induced renal impairment in rat. Prognostic value of malondialdehyde, N-acetyl-beta-D-glucosaminidase and nitric oxide determination.

PubMed

Ozguner, Fehmi; Oktem, Faruk; Ayata, Ali; Koyu, Ahmet; Yilmaz, H Ramazan

2005-09-01

Caffeic acid phenethyl ester (CAPE), a flavonoid like compound, is one of the major components of honeybee propolis. It has been used in folk medicine for many years in Middle East countries. It was found to be a potent free radical scavenger and antioxidant recently. The aim of this study was to examine long-term applied 900 MHz emitting mobile phone-induced oxidative stress that promotes production of reactive oxygen species (ROS) and, was to investigate the role of CAPE on kidney tissue against the possible electromagnetic radiation (EMR)-induced renal impairment in rats. In particular, the ROS such as superoxide and nitric oxide (NO) may contribute to the pathophysiology of EMR-induced renal impairment. Malondialdehyde (MDA, an index of lipid peroxidation) levels, urinary N-acetyl-beta-D-glucosaminidase (NAG, a marker of renal tubular injury) and nitric oxide (NO, an oxidant product) levels were used as markers of oxidative stress-induced renal impairment and the success of CAPE treatment. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in renal tissue were determined to evaluate the changes of antioxidant status. The rats used in the study were randomly grouped (10 each) as follows: i) Control group (without stress and EMR), ii) Sham-operated rats stayed without exposure to EMR (exposure device off), iii) Rats exposed to 900 MHz EMR (EMR group), and iv) A 900 MHz EMR exposed + CAPE treated group (EMR + CAPE group). In the EMR exposed group, while tissue MDA, NO levels and urinary NAG levels increased (p < 0.0001), the activities of SOD, CAT, and GSH-Px in renal tissue were reduced (p < 0.001). CAPE treatment reversed these effects as well (p < 0.0001, p < 0.001 respectively). In conclusion, the increase in NO and MDA levels of renal tissue, and in urinary NAG with the decrease in renal SOD, CAT, GSH-Px activities demonstrate the role of oxidative mechanisms in 900 MHz mobile phone-induced renal tissue damage, and CAPE, via its free radical scavenging and antioxidant properties, ameliorates oxidative renal damage. These results strongly suggest that CAPE exhibits a protective effect on mobile phone-induced and free radical mediated oxidative renal impairment in rats.

Presentation and role of transplantation in adult patients with type 1 primary hyperoxaluria and the I244T AGXT mutation: Single-center experience.

PubMed

Lorenzo, V; Alvarez, A; Torres, A; Torregrosa, V; Hernández, D; Salido, E

2006-09-01

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. We aim to describe the presentation and full single-center experience of the management of PH1 patients bearing the mutation described in our community (I244T mutation+polymorphism P11L). Since 1983, 12 patients with recurrent renal lithiasis have been diagnosed with PH1 and renal failure in the Canary Islands, Spain. Diagnostic confirmation was based on the presence of oxalosis in undecalcified bone or kidney allograft biopsy, reduced alanine:glyoxylate aminotransferase activity in liver biopsy, and blood DNA analysis. Patients underwent different treatment modalities depending on individual clinical circumstances and therapeutic possibilities at the time of diagnosis: hemodialysis, isolated kidney, simultaneous liver-kidney, or pre-emptive liver transplantation. In all cases, the presentation of advanced renal disease was relatively late (>13 years) and no cases were reported during lactancy or childhood. The eight patients treated with hemodialysis or isolated kidney transplantation showed unfavorable evolution leading to death over a variable period of time. In contrast, the four patients undergoing liver transplantation (three liver+kidney and one pre-emptive liver alone) showed favorable long-term allograft and patient survival (up to 12 years follow-up). In conclusion, in this PH1 population, all bearing the I244T mutation, the development of end-stage renal disease was distinctive during late adolescence or adulthood. Our long-term results support pre-emptive liver transplantation at early stages of renal failure, and kidney-liver transplantation for those with advanced renal disease.

A test of the hypothesis that oxalate secretion produces proximal tubule crystallization in primary hyperoxaluria type I

PubMed Central

Evan, Andrew P.; Coe, Fredric L.; Lingeman, James E.; Krambeck, Amy; Sommers, Andre; Phillips, Carrie L.; Milliner, Dawn

2013-01-01

The sequence of events by which primary hyperoxaluria type 1 (PH1) causes renal failure is unclear. We hypothesize that proximal tubule (PT) is vulnerable because oxalate secretion raises calcium oxalate (CaOx) supersaturation (SS) there, leading to crystal formation and cellular injury. We studied cortical and papillary biopsies from two PH1 patients with preserved renal function, and seven native kidneys removed from four patients at the time of transplant, after short-term (2) or longer term (2) dialysis. In these patients, and another five PH1 patients without renal failure, we calculated oxalate secretion, and estimated PT CaOx SS. Plasma oxalate was elevated in all PH1 patients and inverse to creatinine clearance. Renal secretion of oxalate was present in all PH1 but rare in controls. PT CaOx SS was >1 in all nonpyridoxine-responsive PH1 before transplant and most marked in patients who developed end stage renal disease (ESRD). PT from PH1 with preserved renal function had birefringent crystals, confirming the presence of CaOx SS, but had no evidence of cortical inflammation or scarring by histopathology or hyaluronan staining. PH1 with short ESRD showed CaOx deposition and hyaluronan staining particularly at the corticomedullary junction in distal PT while cortical collecting ducts were spared. Longer ESRD showed widespread cortical CaOx, and in both groups papillary tissue had marked intratubular CaOx deposits and fibrosis. CaOx SS in PT causes CaOx crystal formation, and CaOx deposition in distal PT appears to be associated with ESRD. Minimizing PT CaOx SS may be important for preserving renal function in PH1. PMID:24089413

Biomarkers for kidney involvement in pediatric lupus

PubMed Central

Goilav, Beatrice; Putterman, Chaim; Rubinstein, Tamar B

2015-01-01

Lupus nephritis (LN), the renal involvement in systemic lupus erythematosus, is currently diagnosed by histopathology obtained by percutaneous renal biopsy and is associated with increased morbidity and mortality in both adults and children. LN is more prevalent and severe in children, requiring aggressive and prolonged immunosuppression. The consequences of the diagnosis and its treatment have devastating long-term effects on the growth, well-being and quality of life of affected children. The paucity of reliable clinical indicators of the presence and severity of renal involvement have contributed to a halt in the reduction of progression to end-stage renal disease in recent years. Here, we discuss the recent development of biomarkers in the management of LN and their role as therapeutic targets. PMID:26079958

Evaluating the efficacy, safety and evolution of renal function with early initiation of everolimus-facilitated tacrolimus reduction in de novo liver transplant recipients: Study protocol for a randomized controlled trial.

PubMed

Nashan, Bjorn; Schemmer, Peter; Braun, Felix; Dworak, Markus; Wimmer, Peter; Schlitt, Hans

2015-03-26

Introduction of calcineurin inhibitors had led to improved survival rates in liver transplant recipients. However, long-term use of calcineurin inhibitors is associated with a higher risk of chronic renal failure, neurotoxicity, de novo malignancies, recurrence of hepatitis C viral (HCV) infection and hepatocellular carcinoma. Several studies have shown that everolimus has the potential to provide protection against viral replication, malignancy, and progression of fibrosis, as well as preventing nephrotoxicity by facilitating calcineurin inhibitor reduction without compromising efficacy. The Hephaistos study evaluates the beneficial effects of early initiation of everolimus in de novo liver transplant recipients. Hephaistos is an ongoing 12-month, multi-center, open-label, controlled study aiming to enroll 330 de novo liver transplant recipients from 15 centers across Germany. Patients are randomized in a 1:1 ratio (7-21 days post-transplantation) to receive everolimus (trough levels 3-8 ng/mL) with reduced tacrolimus (trough levels <5 ng/mL), or standard tacrolimus (trough levels 6-10 ng/mL) after entering a run-in period (3-5 days post-transplantation). In the run-in period, patients are treated with induction therapy, mycophenolate mofetil, tacrolimus, and corticosteroids according to local practice. Randomization is stratified by HCV status and model of end-stage liver disease scores at transplantation. The primary objective of the study is to exhibit superior renal function (estimated glomerular filtration rate assessed by the Modification of Diet in Renal Disease (MDRD)-4 formula) with everolimus plus reduced tacrolimus compared to standard tacrolimus at Month 12. Other objectives are: to assess the incidence of treated biopsy-proven acute rejection, graft loss, or death; the incidences of components of the composite efficacy endpoint; renal function via estimated glomerular filtration rate using various formulae (MDRD-4, Nankivell, Cockcroft-Gault, chronic kidney disease epidemiology collaboration and Hoek formulae); the incidence of proteinuria; the incidence of adverse events and serious adverse events; the incidence and severity of cytomegalovirus and HCV infections and HCV-related fibrosis. This study aims to demonstrate superior renal function, comparable efficacy, and safety in de novo liver transplant recipients receiving everolimus with reduced tacrolimus compared with standard tacrolimus. This study also evaluates the antiviral benefit by early initiation of everolimus. NCT01551212 .

Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in both AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis.

PubMed

Kuroda, Takeshi; Tanabe, Naohito; Hasegawa, Eriko; Wakamatsu, Ayako; Nozawa, Yukiko; Sato, Hiroe; Nakatsue, Takeshi; Wada, Yoko; Ito, Yumi; Imai, Naofumi; Ueno, Mitsuhiro; Nakano, Masaaki; Narita, Ichiei

2017-06-01

The kidney is a major target organ for systemic amyloidosis, which results in proteinuria and an elevated serum creatinine level. The clinical manifestations and precursor proteins of amyloid A (AA) and light-chain (AL) amyloidosis are different, and the renal damage due to amyloid deposition also seems to differ. The purpose of this study was to clarify haw the difference in clinical features between AA and AL amyloidosis are explained by the difference in the amount and distribution of amyloid deposition in the renal tissues. A total of 119 patients participated: 58 patients with an established diagnosis of AA amyloidosis (AA group) and 61 with AL amyloidosis (AL group). We retrospectively investigated the correlation between clinical data, pathological manifestations, and the area occupied by amyloid in renal biopsy specimens. In most of the renal specimens the percentage area occupied by amyloid was less than 10%. For statistical analyses, the percentage area of amyloid deposition was transformed to a common logarithmic value (Log 10 %amyloid). The results of sex-, age-, and Log 10 %amyloid-adjusted analyses showed that systolic blood pressure (SBP) was higher in the AA group. In terms of renal function parameters, serum creatinine, creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) indicated significant renal impairment in the AA group, whereas urinary protein indicated significant renal impairment in the AL group. Pathological examinations revealed amyloid was predominantly deposited at glomerular basement membrane (GBM) and easily transferred to the mesangial area in the AA group, and it was predominantly deposited at in the AL group. The degree of amyloid deposition in the glomerular capillary was significantly more severe in AL group. The frequency of amyloid deposits in extraglomerular mesangium was not significantly different between the two groups, but in AA group, the degree amyloid deposition was significantly more severe, and the deposition pattern in the glomerulus was nodular. Nodular deposition in extraglomerular mesangium leads to renal impairment in AA group. There are significant differences between AA and AL amyloidosis with regard to the renal function, especially in terms of Ccr, eGFR and urinary protein, even after Log10%amyloid was adjusted; showing that these inter-group differences in renal function would not be depend on the amount of renal amyloid deposits. These differences could be explained by the difference in distribution and morphological pattern of amyloid deposition in the renal tissue.

Microcirculation of human pancreatic islets transplanted under the renal capsule of nude mice.

PubMed

Jansson, L; Tyrberg, B; Carlsson, P O; Nordin, A; Andersson, A; Källskog O

2001-08-27

The aim was to measure the capillary blood pressure in transplanted human islets. Human islets were isolated at the Central Unit of the beta-cell Transplant in Brussels, Belgium. After transport to our laboratory, the islets were implanted under the renal capsule of normoglycemic nude mice. Two weeks later the capillary and venous blood pressures in the islet graft and adjacent renal parenchyma were measured with a micropuncture technique. Capillary blood pressure was approximately 5-8 mmHg in both graft and renal capillaries: twice as high as in native islets. Venous blood pressures were similar (4-5 mmHg) in the veins draining the graft and in the renal interlobular veins. All veins leading from the graft emptied into the renal parenchyma, that is, into interlobular veins. The capillary hypertension seen in transplanted human islets is probably necessary to secure adequate drainage through the renal veins. Whether this contributes to the poor results of long-term islet graft survival is unknown.

Comparative analysis of two porcine kidney decellularization methods for maintenance of functional vascular architectures.

PubMed

Zambon, Joao Paulo; Ko, In Kap; Abolbashari, Mehran; Huling, Jennifer; Clouse, Cara; Kim, Tae Hyoung; Smith, Charesa; Atala, Anthony; Yoo, James J

2018-06-05

Kidney transplantation is currently the only definitive solution for the treatment of end-stage renal disease (ESRD), however transplantation is severely limited by the shortage of available donor kidneys. Recent progress in whole organ engineering based on decellularization/recellularization techniques has enabled pre-clinical in vivo studies using small animal models; however, these in vivo studies have been limited to short-term assessments. We previously developed a decellularization system that effectively removes cellular components from porcine kidneys. While functional re-endothelialization on the porcine whole kidney scaffold was able to improve vascular patency, as compared to the kidney scaffold only, the duration of patency lasted only a few hours. In this study, we hypothesized that significant damage in the microvasculatures within the kidney scaffold resulted in the cessation of blood flow, and that thorough investigation is necessary to accurately evaluate the vascular integrity of the kidney scaffolds. Two decellularization protocols [sodium dodecyl sulfate (SDS) with DNase (SDS + DNase) or Triton X-100 with SDS (TRX + SDS)] were used to evaluate and optimize the levels of vascular integrity within the kidney scaffold. Results from vascular analysis studies using vascular corrosion casting and angiograms demonstrated that the TRX + SDS method was able to better maintain intact and functional microvascular architectures such as glomeruli within the acellular matrices than that by the SDS + DNase treatment. Importantly, in vitro blood perfusion of the re-endothelialized kidney construct revealed improved vascular function of the scaffold by TRX + SDS treatment compared with the SDS + DNase. Our results suggest that the optimized TRX + SDS decellularization method preserves kidney-specific microvasculatures and may contribute to long-term vascular patency following implantation. Kidney transplantation is the only curative therapy for patients with end-stage renal disease (ESRD). However, in the United States, the supply of donor kidneys meets less than one-fifth of the demand; and those patients that receive a donor kidney need life-long immunosuppressive therapy to avoid organ rejection. In the last two decades, regenerative medicine and tissue engineering have emerged as an attractive alternative to overcome these limitations. In 2013, Song et al. published the first experimental orthotopic transplantation of a bioengineering kidney in rodents. In this study, they demonstrated evidences of kidney tissue regeneration and partial function restoration. Despite these initial promising results, there are still many challenges to achieve long-term blood perfusion without graft thrombosis. In this paper, we demonstrated that perfusion of detergents through the renal artery of porcine kidneys damages the glomeruli microarchitecture as well as peritubular capillaries. Modifying dynamic parameters such as flow rate, detergent concentration, and decellularization time, we were able to establish an optimized decellularization protocol with no evidences of disruption of glomeruli microarchitecture. As a proof of concept, we recellularized the kidney scaffolds with endothelial cells and in vitro perfused whole porcine blood successfully for 24 h with no evidences of thrombosis. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Impact of Renal Hilar Control on Outcomes of Robotic Partial Nephrectomy: Systematic Review and Cumulative Meta-analysis.

PubMed

Cacciamani, Giovanni E; Medina, Luis G; Gill, Tania S; Mendelsohn, Alec; Husain, Fatima; Bhardwaj, Lokesh; Artibani, Walter; Sotelo, Renè; Gill, Inderbir S

2018-02-05

During robotic partial nephrectomy (RPN), various techniques of hilar control have been described, including on-clamp, early unclamping, selective/super-selective clamping, and completely-unclamped RPN. To evaluate the impact of various hilar control techniques on perioperative, functional, and oncological outcomes of RPN for tumors. We conducted a systematic literature review and meta-analysis of all comparative studies on various hilar control techniques during RPN using PubMed, Scopus, and Web of Science according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement, and Methods and Guide for Effectiveness and Comparative Effectiveness Review of the Agency for Healthcare Research and Quality. Cumulative meta-analysis of comparative studies was conducted using Review Manager 5.3. Of 987 RPN publications in the literature, 19 qualified for this analysis. Comparison of off-clamp versus on-clamp RPN (n=9), selective clamping versus on-clamp RPN (n=3), super selective clamping versus on-clamp RPN (n=5), and early unclamped versus on-clamp (n=3) were reported. Patients undergoing RPN using off-clamp, selective/super selective, or early unclamp techniques had higher estimated blood loss compared with on-clamp RPN (weight mean difference [WMD]: 47.83, p=0.000, WMD: 41.06, p=0.02, and WMD: 37.50, p=0.47); however, this did not seem clinically relevant, since transfusion rates were similar (odds ratio [OR]: 0.98, p=0.95, OR: 0.72, p=0.7, and OR: 1.36, p=0.33, respectively). All groups appeared similar with regards to hospital stay, transfusions, overall and major complications, and positive cancer margin rates. Short- and long-term renal functional outcomes appeared superior in the off-clamp and super selective clamp groups compared with the on-clamp RPN cohort. Off-clamp, selective/super selective clamp, and early unclamp hilar control techniques are safe and feasible approaches for RPN surgery, with similar perioperative and oncological outcomes compared with on-clamp RPN. Minimizing global renal ischemia may provide superior renal function preservation. However, higher quality data are necessary for definitive conclusions in this regard. The objective of partial nephrectomy is to treat the cancer while maximizing renal function preservation. Clamping the main vessels is done primarily to reduce the blood loss during partial nephrectomy; however, vascular clamping can compromise kidney function. In order to avoid clamping, various techniques have been described. Our analysis showed that techniques that avoid main renal artery clamping during RPN are associated with better renal function preservation, yet deliver non-inferior perioperative and oncological outcomes as compared with robotic partial nephrectomy procedures that clamp the main vessels. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Comprehensive outcomes after lung retransplantation: a single center review.

PubMed

Halloran, Kieran; Aversa, Meghan; Tinckam, Kathryn; Martinu, Tereza; Binnie, Matthew; Chaparro, Cecilia; Chow, Chung-Wai; Waddell, Tom; McRae, Karen; Pierre, Andrew; de Perrot, Marc; Yasufuku, Kazuhiro; Cypel, Marcelo; Keshavjee, Shaf; Singer, Lianne G

2018-05-13

Lung retransplantation is an important therapy for a growing population of lung transplant recipients with graft failure, but detailed outcome data are lacking. We conducted a retrospective cohort study of adult lung retransplant in the Toronto Lung Transplant Program from 2001 to 2013 (n=38). We analyzed the post-operative course, graft function, renal function, microbiology, donor specific antibodies (DSA), quality of life and survival compared to a control cohort of primary transplant recipients matched for age and era. Indication for retransplant was chronic lung allograft dysfunction in most retransplant recipients (35/38, 82%). The post-operative course was more complex after retransplant than primary (ventilation time, 8 vs. 2 days, p<0.01; ICU stay 14 vs. 4 days, 0<0.01) and peak lung function was lower (FEV1 2.2L vs. 3L, p<0.01). Quality of life scores were comparable, as were renal function, microbiology and donor specific antibody formation. Median survival was 1988 days after primary and 1475 days after retransplant (p=0.39). Lung retransplantation is associated with a more complex post-operative course and lower peak lung function, but the long term medical profile is similar to primary transplant. Lung retransplantation can be beneficial for carefully selected candidates with allograft failure. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A comparison of the effects of C2-cyclosporine and C0-tacrolimus on renal function and cardiovascular risk factors in kidney transplant recipients.

PubMed

Kim, S Joseph; Prasad, G V Ramesh; Huang, Michael; Nash, Michelle M; Famure, Olusegun; Park, Joseph; Thenganatt, Mary Ann; Chowdhury, Nizamuddin; Cole, Edward H; Fenton, Stanley S A; Cattran, Daniel C; Zaltzman, Jeffrey S; Cardella, Carl J

2006-10-15

There are few data directly comparing the effects of two-hour postingestion monitored cyclosporine (C2-CsA) vs. trough-monitored tacrolimus (C0-Tac) on renal function and cardiovascular risk factors. We studied 378 (202 C2-CsA vs. 176 C0-Tac) incident kidney transplant recipients in Toronto, Canada, from August 1, 2000 and December 31, 2003. Outcomes included changes in estimated glomerular filtration rate (eGFR at 1 and 6 months by modification of diet in renal disease four-variable equation), mean arterial pressure (MAP), total cholesterol (TC), and new-onset diabetes mellitus (NODM) at six months posttransplant. The independent effect of treatment/monitoring strategies on continuous outcomes and time-to-NODM was modeled using linear and Cox regression, respectively. Mean eGFR was 59.5 vs. 62.9 ml/min at one month and 50.6 vs. 61.2 ml/min at six months for C2-CsA vs. C0-Tac, respectively. Multiple linear regression revealed the slope of eGFR to be 0.93 ml/min/month lower in C2-CsA patients. This was equivalent to an adjusted average eGFR difference of 4.64 ml/min between months one and six posttransplant. There was no significant difference in average MAP and TC. In a stepwise multivariable Cox model and a propensity score analysis, there was no significant association between the type of treatment/monitoring strategy and time-to-NODM. There was a greater decline in eGFR for patients on C2-CsA (vs. C0-Tac) between one and six months posttransplant. However, MAP, TC, and the risk of NODM were comparable in both treatment/monitoring groups. The long-term impact of short-term reductions in eGFR as a function of the type of treatment/monitoring strategy requires further study.

Diagnostic value and biological significance of antibody-coated bacteria in urine

PubMed Central

Mengoli, C; Arosio, E; Bonato, D; Spiazzi, G; Pancera, P; Montesi, G; Lechi, A; Scuro, LA

1980-01-01

The incidence of antibody-coated bacteria (ACB) in the urinary sediments as an indication of the site of urinary tract infections (UTI) was investigated in 103 adult subjects with persistent bacteriuria by means of a direct immunofluorescence technique. ACB were found in 49 of 58 (84·5%) subjects with long-standing upper urinary tract obstruction and in 5 of 45 (11·1%) with lower UTI; this difference was statistically significant (X2 = 51·79; P<0·001). The group with upper UTI was further subdivided according to renal function (patients with renal insufficiency had both bilateral obstruction and bilateral renal damage); 21 positive results were obtained in 27 (77·8%) patients with normal renal function, whereas 28 positive cases were observed among 31 (90·3%) patients with chronic renal insufficiency. Thus the degree of renal involvement also seemed to influence the outcome of the test. Within the group of lower UTI, a higher rate of `false-positive' results was obtained in 14 patients with symptomatic long-standing infection (21·4%) than in 31 subjects with asymptomatic bacteriuria (6·4%). The three major immunoglobulin classes and the secretory component were studied in 42 cases. Of these, 29 were found to be positive for ACB. The constant presence of IgA and secretory component on the surface of ACB suggests that the secretory immune system plays an important role in UTI. ImagesFig. 1 PMID:6988464

Study report on interfacing major physiological subsystem models: An approach for developing a whole-body algorithm

NASA Technical Reports Server (NTRS)

Fitzjerrell, D. G.; Grounds, D. J.; Leonard, J. I.

1975-01-01

Using a whole body algorithm simulation model, a wide variety and large number of stresses as well as different stress levels were simulated including environmental disturbances, metabolic changes, and special experimental situations. Simulation of short term stresses resulted in simultaneous and integrated responses from the cardiovascular, respiratory, and thermoregulatory subsystems and the accuracy of a large number of responding variables was verified. The capability of simulating significantly longer responses was demonstrated by validating a four week bed rest study. In this case, the long term subsystem model was found to reproduce many experimentally observed changes in circulatory dynamics, body fluid-electrolyte regulation, and renal function. The value of systems analysis and the selected design approach for developing a whole body algorithm was demonstrated.

[Severe caffeine poisoning with rhabdomyolysis].

PubMed

Wolter, J; Grün, D; Otto, S

2018-04-01

We report the case of a young man who took a large amount of caffeine powder dissolved in water in a suicide attempt. He was found comatose. The initial diagnosis was difficult. In hospital he suffered from rhabdomyolysis with renal failure and sepsis rapidly developed. After renal replacement treatment with hemodialysis, long-term artificial ventilation with tracheotomy and a 3‑week stay in the intensive care unit, the patient could be discharged to a rehabilitation center.

Factors influencing clinical outcome in patients with primary hyperoxaluria type 1.

PubMed

Fargue, Sonia

2014-12-01

The renal outcome in patients with primary hyperoxaluria type 1 is partly determined by AGXT mutations, including but not limited to the p.Gly170Arg mutation. The study by Mandrile et al. reports on the largest cohort of patients genotyped yet, with long-term renal survival and medical treatment by pyridoxine. In addition to the common p.Gly170Arg mutation, three other mutations were shown to be potentially associated with slower evolution.

Long-term outcome on renal replacement therapy in patients who previously received a keto acid-supplemented very-low-protein diet.

PubMed

Chauveau, Philippe; Couzi, Lionel; Vendrely, Benoit; de Précigout, Valérie; Combe, Christian; Fouque, Denis; Aparicio, Michel

2009-10-01

The consequences of a supplemented very-low-protein diet remain a matter of debate with regard to patient outcome before or after the onset of renal replacement therapy. We evaluated the long-term clinical outcome during maintenance dialysis and/or transplantation in patients who previously received a supplemented very-low-protein diet. We assessed the outcome of 203 patients who received a supplemented very-low-protein diet for >3 mo (inclusion period: 1985-2000) and started dialysis after a mean diet duration of 33.1 mo (4-230 mo). The survival rate in the whole cohort was 79% and 63% at 5 and 10 y, respectively. One hundred two patients continued with chronic dialysis during the entire follow-up, and 101 patients were grafted at least once. Patient outcomes were similar to those of the French Dialysis Registry patients for the dialysis group and similar to the 865 patients who were transplanted in Bordeaux during the same period for the transplant group. There was no correlation between death rate and duration of diet. The lack of correlation between death rate and duration of diet and the moderate mortality rate observed during the first 10 y of renal replacement therapy confirm that a supplemented very-low-protein diet has no detrimental effect on the outcome of patients with chronic kidney disease who receive renal replacement therapy.

Assessment of independent predictors for long-term mortality between women and men after coronary artery bypass grafting: are women different from men?

PubMed

Toumpoulis, Ioannis K; Anagnostopoulos, Constantine E; Balaram, Sandhya K; Rokkas, Chris K; Swistel, Daniel G; Ashton, Robert C; DeRose, Joseph J

2006-02-01

The long-term mortality of coronary artery bypass grafting in women in not certain. The purpose of this study was to determine and compare risk factors for long-term mortality in women and men undergoing coronary artery bypass grafting. Between 1992 and 2002, 3760 consecutive patients (2598 men and 1162 women) underwent isolated coronary artery bypass grafting. Long-term survival data were obtained from the National Death Index (mean follow-up, 5.1 +/- 3.2 years). Multivariable Cox regression analysis was performed, including 64 preoperative, intraoperative, and postoperative factors separately in women and men. There were no differences in in-hospital mortality (2.7% in men vs 2.9% in women, P = .639) and 5-year survival (82.0% +/- 0.8% in men vs 81.1% +/- 1.3% in women, P = .293). After adjustment for all independent predictors of long-term mortality, female sex was an independent predictor of improved 5-year survival (hazard ratio, 0.82; 95% confidence interval, 0.71-0.96; P = .014). Twenty-one independent predictors for long-term mortality were determined in men, whereas only 12 were determined in women. There were 9 common risk factors (age, ejection fraction, diabetes mellitus, > or =2 arterial grafts, postoperative myocardial infarction, deep sternal wound infection, sepsis and/or endocarditis, gastrointestinal complications, and respiratory failure); however, their weights were different between women and men. Malignant ventricular arrhythmias, calcified aorta, and preoperative renal failure were independent predictors only in women. Emergency operation, previous cardiac operation, peripheral vascular disease, left ventricular hypertrophy, current and past congestive heart failure, chronic obstructive pulmonary disease, body mass index of greater than 29, preoperative dialysis, thrombolysis within 7 days before coronary artery bypass grafting, intraoperative stroke, and postoperative renal failure were independent predictors only in men. Despite equality between sexes in early outcome and superiority of female sex in long-term survival, there were 3 independent predictors for long-term mortality after coronary artery bypass grafting unique for women compared with 12 for men. Clinical decision making and follow-up should not be influenced by stereotypes but by specific findings.

Recurrent Renal Colic in a Patient with Munchausen Syndrome

PubMed Central

Miconi, Francesco; Rapaccini, Valentina; Savarese, Emanuela; Cabiati, Gabriele; Pasini, Augusto; Miconi, Giovanni; Principi, Nicola

2018-01-01

Background: In most of the cases regarding children, factitious disorders (FDs) are intentionally produced by parents. Less attention is paid to FDs in which a child or adolescent intentionally induces or falsifies the disease to attain a patient’s role. Case presentation: A 13-year-old immigrated and adopted boy previously underwent an operation for renal joint syndrome and was affected by recurrent episodes of renal colic. The boy was admitted reporting acute left flank pain with scars on the mucous face of his prepuce and had a recent previous hospitalization for the same reason. Laboratory tests and radiological findings did not reveal any morphological or functional alterations. Self-induced FD was suspected, and a psychiatric consultation was performed. After psychiatric consultation and remission of the symptoms with a placebo, a diagnosis of Munchausen syndrome was suspected. The patient’s uncle was not initially convinced of the diagnosis. Some videos clearly showed that the boy was handling his prepuce to excrete stones, explaining the scars. A therapeutic plan with psychiatrist support was later accepted with a positive outcome. No further signs and symptoms of renal colic were reported. Conclusions: It is recommended that paediatricians include FD in the differential diagnosis of a persistent and unexplained medical condition. If suspicion arises, confirmation and long-term therapy by a group of qualified specialists, including psychiatrists, should be planned. PMID:29596350

A Rare Reason of Ileus in Renal Transplant Patients With Peritoneal Dialysis History: Encapsulated Peritoneal Sclerosis.

PubMed

Gökçe, Ali Murat; Özel, Leyla; İbişoğlu, Sevinç; Ata, Pınar; Şahin, Gülizar; Gücün, Murat; Kara, V Melih; Özdemir, Ebru; Titiz, M İzzet

2015-12-01

Encapsulating peritoneal sclerosis is a rare complication of long-term peritoneal dialysis ranging from moderate inflammation of peritoneal structures to severe sclerosing peritonitis and encapsulating peritoneal sclerosis. Complicated it, ileus may occur during or after peritoneal dialysis treatment or after kidney transplant. We sought to evaluate 3 posttransplant encapsulating peritoneal sclerosis through clinical presentation, radiologic findings, and outcomes. We analyzed 3 renal transplant patients with symptoms of encapsulating peritoneal sclerosis admitted posttransplant to our hospital with ileus between 2012 and 2013. Conservative treatment was applied to the patients whenever necessary to avoid surgery. One patient improved with medical therapy. Surgical treatment was delayed and we decided it as a last resort, in 2 cases with no response to conservative treatment for a long time. Finally, patients with peritoneal dialysis history should be searched carefully before renal transplant for intermittent bowel obstruction story.

Modelling of long-term and short-term mechanisms of arterial pressure control in the cardiovascular system: an object-oriented approach.

PubMed

Fernandez de Canete, J; Luque, J; Barbancho, J; Munoz, V

2014-04-01

A mathematical model that provides an overall description of both the short- and long-term mechanisms of arterial pressure regulation is presented. Short-term control is exerted through the baroreceptor reflex while renal elimination plays a role in long-term control. Both mechanisms operate in an integrated way over the compartmental model of the cardiovascular system. The whole system was modelled in MODELICA, which uses a hierarchical object-oriented modelling strategy, under the DYMOLA simulation environment. The performance of the controlled system was analysed by simulation in light of the existing hypothesis and validation tests previously performed with physiological data, demonstrating the effectiveness of both regulation mechanisms under physiological and pathological conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Use of Oral Bisphosphonates by Older Adults with Fractures and Impaired Renal Function

PubMed Central

Sadowski, Cheryl A; Spencer, Tara; Yuksel, Nese

2011-01-01

Background: The manufacturers of oral bisphosphonates (alendronate, risedronate) recommend avoiding use of these drugs in patients with renal impairment. However, many patients who have osteoporosis or who are at risk of fracture are elderly and may have renal impairment. This situation poses a quandary for clinicians in deciding how best to manage osteoporosis in this high-risk population. Objective: To synthesize published evidence regarding the use and safety of oral bisphosphonates for patients with impaired renal function. Methods: The following databases were searched up to October 2010: PubMed, MEDLINE, Embase, the Cochrane Library, and International Pharmaceutical Abstracts. The following key words and terms were used for the searches: bisphosphonates, alendronate, risedronate, Fosamax, Actonel, “renal failure”, “renal insufficiency”, “chronic kidney disease”, and “end-stage renal disease”. The manufacturers of Fosamax and Actonel were asked to provide information about use of their products in patients with renal impairment, including unpublished pharmacokinetic studies or reports of adverse drug events. Results: The search yielded 2 post hoc analyses of safety data, 1 case–control study, 1 case series, 4 retrospective chart analyses, and 2 prospective studies. According to these publications, numerous patients with decreased renal function have received bisphosphonates and have experienced improvement in bone mineral density and/or reduction in risk of fractures, with no increase in adverse effects. Increased renal damage occurred in some individuals with underlying renal disorders, as described in case reports. Conclusions: Although the literature is limited, there is evidence that alendronate and risedronate are well tolerated and effective when used by individuals with renal impairment. Further research is required to confirm the benefits and risks of using these medications in patients with renal impairment. PMID:22479027

Relevance of Flow Cytometric Auto-Crossmatch to the Post-transplant Course of Kidney Transplant Recipients.

PubMed

Demir, E; Yeğit, O; Erol, A; Akgül, S U; Çalışkan, B; Bayraktar, A; Çalışkan, Y; Türkmen, A; Savran, F O; Sever, M S

2017-04-01

The crossmatch test is essential prior to kidney transplantation (tx) to confirm compatibility between the donor and the recipient. However, its results can be misleading due to "undetectable antibodies" in the recipient's serum. To establish if undetectable autoantibodies are responsible for a positive result, an auto-crossmatch test can be performed. In this study, we aim to determine the long-term prognostic value of auto-flow cytometric auto-crossmatch (FCXM) test on kidney survival in kidney tx recipients. The primary outcome variable was reduced renal function. Secondary endpoints were incidence of biopsy-confirmed chronic antibody-mediated rejection (CAMR) and recurrent glomerulonephritis (GN). There were no differences regarding initial serum creatinine levels between the study and control groups (P = .441). Patients who had positive auto-B FCXM had a significantly reduced renal function compared with the control group (P = .016). Four patients developed biopsy-confirmed CAMR in the study group and 1 patient in the control group (P = .047). Five patients had biopsy-confirmed recurrent GN in the GN study group, and only 1 patient had recurrent GN in the GN control group (P = .026). Kidney transplant recipients with positive auto-FCXM test had significantly reduced renal function and a higher incidence of recurrent GN and CAMR compared with the control group. The findings of this study suggest a potential role of auto-antibody causing positive auto-FCXM test result, meanwhile increasing the risk of CAMR, recurrent GN, and new-onset diabetes after tx. Copyright © 2017 Elsevier Inc. All rights reserved.

Ambulatory blood pressure profiles in familial dysautonomia.

PubMed

Goldberg, Lior; Bar-Aluma, Bat-El; Krauthammer, Alex; Efrati, Ori; Sharabi, Yehonatan

2018-02-12

Familial dysautonomia (FD) is a rare genetic disease that involves extreme blood pressure fluctuations secondary to afferent baroreflex failure. The diurnal blood pressure profile, including the average, variability, and day-night difference, may have implications for long-term end organ damage. The purpose of this study was to describe the circadian pattern of blood pressure in the FD population and relationships with renal and pulmonary function, use of medications, and overall disability. We analyzed 24-h ambulatory blood pressure monitoring recordings in 22 patients with FD. Information about medications, disease severity, renal function (estimated glomerular filtration, eGFR), pulmonary function (forced expiratory volume in 1 s, FEV1) and an index of blood pressure variability (standard deviation of systolic pressure) were analyzed. The mean (± SEM) 24-h blood pressure was 115 ± 5.6/72 ± 2.0 mmHg. The diurnal blood pressure variability was high (daytime systolic pressure standard deviation 22.4 ± 1.5 mmHg, nighttime 17.2 ± 1.6), with a high frequency of a non-dipping pattern (16 patients, 73%). eGFR, use of medications, FEV1, and disability scores were unrelated to the degree of blood pressure variability or to dipping status. This FD cohort had normal average 24-h blood pressure, fluctuating blood pressure, and a high frequency of non-dippers. Although there was evidence of renal dysfunction based on eGFR and proteinuria, the ABPM profile was unrelated to the measures of end organ dysfunction or to reported disability.

The role and future challenges for recombinant growth hormone therapy to promote growth in children after renal transplantation.

PubMed

Janjua, Halima S; Mahan, John D

2011-01-01

Chronic kidney disease can severely impair linear growth in children. For many children, growth improves after renal transplantation, but for some, growth velocity remains low and for others, catch-up growth is insufficient to compensate for the deficit imparted by renal disease in the preceding years. Inadequate final adult height after renal transplant is multifactorial and can adversely affect the quality of life (QOL), psychosocial development and long term prospects for these children as they grow into adulthood. Growth failure after renal transplant requires thorough evaluation and its management in renal transplant recipients can involve improved nutritional intake, correction of metabolic acidosis, treatment of secondary hyperparathyroidism, steroid-sparing immunosuppression and/or use of recombinant human growth hormone (rGH). Treatment with rGH after renal transplant has been evaluated by a limited number of clinical trials suggesting efficacy and safety for this treatment strategy. Several important clinical questions regarding rGH use in children post-renal transplant remain unanswered. © 2011 John Wiley & Sons A/S.

Renal autotransplantation: current perspectives.

PubMed

Stewart, B H; Banowsky, L H; Hewitt, C B; Straffon, R A

1977-09-01

Autotransplantation, with or without an extracorporeal renal operation, has been done 39 times in 37 patients. Indications for the procedure included several ureteral injury in 4 patients, failed supravesical diversion in 2, renal carcinoma in a solitary kidney in 1, renovascular hypertension in 1 and donor arterial reconstruction before renal transplantation in 29. Success was obtained in all but 2 procedures, both of which involved previously operated kidneys with severe inflammation and adhesions involving the renal pelvis and pedicle. Based on our experience and a review of currently available literature we believe that renal autotransplantation and extracorporeal reconstruction can provide the best solution for patients with severe renovascular and ureteral disease not correctable by conventional operative techniques. The technique can be of particular value in removing centrally located tumors in solitary kidneys and in preparing donor kidneys with abnormal arteries for renal transplantation. The role of autotransplantation in the management of advanced renal trauma and calculus disease is less clear. A long-term comparison of patients treated by extracorporeal nephrolithotomy versus conventional lithotomy techniques will be necessary before a conclusion is reached in these disease categories.

Renal autotransplantation: current perspectives.

PubMed

Stewart, B H; Banowsky, L H; Hewitt, C B; Straffon, R A

1976-01-01

Autotransplantation, with or without an extracorporeal renal operation, has been done 39 times in 37 patients. Indications for the procedure included severe ureteral injury in 4 patients, failed supravesical diversion in 2, renal carcinoma in a solitary kidney in 1, renovascular hypertension in 1 and donor arterial reconstruction before renal transplantation in 29. Success was obtained in all but 2 procedures, both of which involved previously operated kidneys with severe inflammation and adhesions involving the renal pelvis and pedicle. Based on our experience and a review of currently available literature we believe that renal autotransplantation and extracorporeal reconstruction can provide the best solution for patients with severe renovascular and ureteral disease not correctable by conventional operative techniques. The technique can be of particular value in removing centrally located tumors in solitary kidneys and in preparing donor kidneys with abnormal arteries for renal transplantation. The role of autotransplantation in the management of advanced renal trauma and calculus disease is less clear. A long-term comparison of patients treated by extracorporeal nephrolithotomy versus conventional lithotomy techniques will be necessary before a conclusion is reached in these disease categories.

Low but inducible contribution of renal elimination to clearance of propylene glycol in preterm and term neonates.

PubMed

De Cock, Roosmarijn F W; Allegaert, Karel; Vanhaesebrouck, Sophie; de Hoon, Jan; Verbesselt, Rene; Danhof, Meindert; Knibbe, Catherijne A J

2014-06-01

Despite limited information being available on the pharmacokinetics of excipients, propylene glycol (PG) is often used as an excipient in both adults and children. The aim of this study is to characterize the renal and hepatic elimination of PG in preterm and term neonates. The pharmacokinetic analysis of PG was performed in NONMEM 6.2. on the basis of PG concentrations in plasma and/or urine samples for a total of 69 (pre)term neonates (birth weight 630-3980 g, gestational age 24-41 weeks, postnatal age 1-29 days) who received PG coadministered with intravenous paracetamol (5-10 mg/kg per 6 hours), phenobarbital (5 mg·kg(-1)·d(-1)), or both. To capture the time-dependent trend in the renal excretion of PG, different models based on time after the first dose, urine volume, and creatinine amount in urine were tested. A one-compartment model parameterized in terms of renal clearance, hepatic clearance, and volume of distribution was found to adequately describe the observations in both plasma and urine. After the first dose was administered, the renal elimination of PG was 15% of total clearance, which increased over time to 25% at 24 hours after the first dose of PG. This increase was best described using a hyperbolic function based on time after the first dose. Renal elimination of PG in (pre)term neonates is low, particularly compared with the reported percentage of 45% in adults, but it may increase with time after the first dose of PG. To study whether this increase is caused by an autoinduced increase in the renal secretion or a reduction of tubular reabsorption of PG, further research is needed.

Technical and Clinical Results After Percutaneous Angioplasty in Nonmedial Fibromuscular Dysplasia: Outcome After Endovascular Management of Unifocal Renal Artery Stenoses in 30 Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barrier, Pierre, E-mail: p.barrier@gmail.com; Julien, Auriol; Guillaume, Canevet

2010-04-15

Although percutaneous transluminal renal angioplasty (PTRA) is associated with excellent results in medial fibromuscular dysplasia (FMD), the clinical and technical outcome in the less common nonmedial subtype of FMD is not clearly known. Angiographic PTRA results and clinical follow-up were documented, to report technical and clinical results in 30 patients with unifocal, nonmedial dysplastic stenoses. Balloon angioplasty was technically successful in only 65% of the lesions. Additional stenting, performed after PTRA failure in six patients, increased the initial technical success rate to 82%. Stenting was used in another lesion after restenosis, and long-term patency was achieved in only three ofmore » the seven stented lesions. Frequent restenoses and unusual complications were observed during follow-up. Stent fracture occurred in two cases. Overall, long-term clinical and technical successes were sustained in 70 and 76%, respectively. We conclude that nonmedial, unifocal renal artery dysplastic stenoses do not share the excellent prognosis of the medial type and that stenting should be avoided. Therefore, surgery should be considered in lesions remaining unresponsive to balloon dilatation, after a second PTRA attempt.« less

Immunosuppression With CD40 Costimulatory Blockade Plus Rapamycin for Simultaneous Islet-Kidney Transplantation in Nonhuman Primates.

PubMed

Oura, T; Hotta, K; Lei, J; Markmann, J; Rosales, I; Dehnadi, A; Kawai, K; Ndishabandi, D; Smith, R-N; Cosimi, A B; Kawai, T

2017-03-01

The lack of a reliable immunosuppressive regimen that effectively suppresses both renal and islet allograft rejection without islet toxicity hampers a wider clinical application of simultaneous islet-kidney transplantation (SIK). Seven MHC-mismatched SIKs were performed in diabetic cynomolgus monkeys. Two recipients received rabbit antithymocyte globulin (ATG) induction followed by daily tacrolimus and rapamycin (ATG/Tac/Rapa), and five recipients were treated with anti-CD40 monoclonal antibody (mAb) and rapamycin (aCD40/Rapa). Anti-inflammatory therapy, including anti-interleukin-6 receptor mAb and anti-tumor necrosis factor-α mAb, was given in both groups. The ATG/Tac/Rapa recipients failed to achieve long-term islet allograft survival (19 and 26 days) due to poor islet engraftment and cytomegalovirus pneumonia. In contrast, the aCD40/Rapa regimen provided long-term islet and kidney allograft survival (90, 94, >120, >120, and >120 days), with only one recipient developing evidence of allograft rejection. The aCD40/Rapa regimen was also tested in four kidney-alone transplant recipients. All four recipients achieved long-term renal allograft survival (100% at day 120), which was superior to renal allograft survival (62.9% at day 120) with triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and steroids). The combination of anti-CD40 mAb and rapamycin is an effective and nontoxic immunosuppressive regimen that uses only clinically available agents for kidney and islet recipients. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Pancreas Transplantation: Solid Organ and Islet

PubMed Central

Mittal, Shruti; Johnson, Paul; Friend, Peter

2014-01-01

Transplantation of the pancreas, either as a solid organ or as isolated islets of Langerhans, is indicated in a small proportion of patients with insulin-dependent diabetes in whom severe complications develop, particularly severe glycemic instability and progressive secondary complications (usually renal failure). The potential to reverse diabetes has to be balanced against the morbidity of long-term immunosuppression. For a patient with renal failure, the treatment of choice is often a simultaneous transplant of the pancreas and kidney (SPK), whereas for a patient with glycemic instability, specifically hypoglycemic unawareness, the choice between a solid organ and an islet transplant has to be individual to the patient. Results of SPK transplantation are comparable to other solid-organ transplants (kidney, liver, heart) and there is evidence of improved quality of life and life expectancy, but the results of solitary pancreas transplantation and islets are inferior with respect to graft survival. There is some evidence of benefit with respect to the progression of secondary diabetic complications in patients with functioning transplants for several years. PMID:24616200

Management of Chronic Kidney Disease Patients in the Intensive Care Unit: Mixing Acute and Chronic Illness.

PubMed

De Rosa, Silvia; Samoni, Sara; Villa, Gianluca; Ronco, Claudio

2017-01-01

Patients with chronic kidney disease (CKD) are at high risk for developing critical illness and for admission to intensive care units (ICU). 'Critically ill CKD patients' frequently develop an acute worsening of renal function (i.e. acute-on-chronic, AoC) that contributes to long-term kidney dysfunction, potentially leading to end-stage kidney disease (ESKD). An integrated multidisciplinary effort is thus necessary to adequately manage the multi-organ damage of those kidney patients and contemporaneously reduce the progression of kidney dysfunction when they are critically ill. The aim of this review is to describe (1) the pathophysiological mechanisms underlying the development of AoC kidney dysfunction and its role in the progression toward ESKD; (2) the most common clinical presentations of critical illness among CKD/ESKD patients; and (3) the continuum of care for CKD/ESKD patients from maintenance hemodialysis/peritoneal dialysis to acute renal replacement therapy performed in ICU and, vice-versa, for AoC patients who develop ESKD. © 2017 S. Karger AG, Basel.

One Year Clinical Outcomes of Renal Artery Stenting: The Results of ODORI Registry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sapoval, M., E-mail: marc.sapoval2@egp.aphp.f; Tamari, I.; Goffette, P.

2010-06-15

The safety, efficacy and long term clinical benefits of renal artery revascularization by stenting are still a matter of debate. The aim of our study was to define the safety and efficacy of renal artery stenting with the Tsunami peripheral stent (Terumo Corporation, Tokyo, Japan). The ODORI was a prospective, multicentre registry which enrolled 251 consecutive patients, (276 renal arteries) in 36 centres across Europe. The primary endpoint was acute procedural success defined as <30% residual stenosis after stent placement. Secondary endpoints included major adverse events, blood pressure control, serum creatinine level, and target lesion revascularization (TLR) at 6 andmore » 12 months. Patients were 70 {+-} 10 years old, 59% were male, 33% had diabetes, and 96% hypertension. The main indications for renal stent implantation were hypertension in 83% and renal salvage in 39%. Direct stent implantation was performed in 76% of the cases. Acute success rate was 100% with residual stenosis of 2.5 {+-} 5.4%. Systolic/diastolic blood pressure decreased from a mean of 171/89 at baseline to 142/78 mmHg at 6 months (p < 0.0001 vs. baseline), and 141/80 mmHg at 12 months (p < 0.0001 vs. baseline). Mean serum creatinine concentration did not change significantly in the total population. However, there was significant improvement in the highest tercile (from 283 {mu}mol/l at baseline to 205 and 209 {mu}mol/l at 6 and 12 months respectively). At 12-months, rates of restenosis and TLR were 6.6 and 0.8% respectively. The 12 month cumulative rate of all major clinical adverse events was 6.4% while the rate of device or procedure related events was 2.4%. In hypertensive patients with atherosclerotic renal artery stenosis Tsunami peripheral balloon-expandable stent provides a safe revascularization strategy, with a potential beneficial impact on hypertension control and renal function in the highest risk patients.« less

Resistant Hypertension, Time-Updated Blood Pressure Values and Renal Outcome in Type 2 Diabetes Mellitus.

PubMed

Viazzi, Francesca; Piscitelli, Pamela; Ceriello, Antonio; Fioretto, Paola; Giorda, Carlo; Guida, Pietro; Russo, Giuseppina; De Cosmo, Salvatore; Pontremoli, Roberto

2017-09-22

Apparent treatment resistant hypertension (aTRH) is highly prevalent in patients with type 2 diabetes mellitus (T2D) and entails worse cardiovascular prognosis. The impact of aTRH and long-term achievement of recommended blood pressure (BP) values on renal outcome remains largely unknown. We assessed the role of aTRH and BP on the development of chronic kidney disease in patients with T2D and hypertension in real-life clinical practice. Clinical records from a total of 29 923 patients with T2D and hypertension, with normal baseline estimated glomerular filtration rate and regular visits during a 4-year follow-up, were retrieved and analyzed. The association between time-updated BP control (ie, 75% of visits with BP <140/90 mm Hg) and the occurrence of estimated glomerular filtration rate <60 and/or a reduction ≥30% from baseline was assessed. At baseline, 17% of patients had aTRH. Over the 4-year follow-up, 19% developed low estimated glomerular filtration rate and 12% an estimated glomerular filtration rate reduction ≥30% from baseline. Patients with aTRH showed an increased risk of developing both renal outcomes (adjusted odds ratio, 1.31 and 1.43; P <0.001 respectively), as compared with those with non-aTRH. No association was found between BP control and renal outcomes in non-aTRH, whereas in aTRH, BP control was associated with a 30% ( P =0.036) greater risk of developing the renal end points. ATRH entails a worse renal prognosis in T2D with hypertension. BP control is not associated with a more-favorable renal outcome in aTRH. The relationship between time-updated BP and renal function seems to be J-shaped, with optimal systolic BP values between 120 and 140 mm Hg. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Is a Long Term Work in Automotive Industry a Risk Factor for Renal Dysfunction?

PubMed Central

Assadi, Seyedeh Negar

2015-01-01

Background: Disorders of renal system can cause renal failure; therefore screening is necessary especially in workers who are exposed to harmful materials. Hypertension, diabetes mellitus, and hazardous exposures are non-occupational and occupational risk factors for renal diseases. Aim: The objective of this study was to determine the effects of working in automotive industry on renal function in Iran. Subjects and Methods: In a historical cohort study, workers of automotive industry who worked in production and had low exposure to metal fumes were selected and divided to three groups with 5–10, 11–20, and 21–30 years work duration. risk factors for renal diseases were collected and analyzed with SPSS using one-way ANOVA, correlation coefficient and with P < 0.05 and relative risk with a confidence interval (CI). Results: The means of work duration in Groups (A), (B) and (C) were 9.8 (0.6), 13.8 (2.0), 22.3 (1.6) years respectively with ANOVA (F) =187.864 and P < 0.01. Glomerular filtration rate (GFR) was 59.75 (0.70), 59.16 (1.52) and 59.10 (2.23) in Groups (A), (B), and (C) respectfully The relative risk of creatinine clearance, uric acid and mean blood pressure were the highest in Group (B); 1.970 - CI, 0.541–7.169, 1.571 95% CI: 0.198–12.470, and 1.519 95% CI: 0.425–5.426, but the differences were not significant. Conclusion: GFRs were decreased with work duration, but the differences were not significant. Working in automotive Industry with low exposure to toxic metals and solvents has no significant effect on GFR, creatinine clearance, uric acid, and mean blood pressure. PMID:25861528

Severe renal hemorrhage caused by pyelonephritis in 7 horses: clinical and ultrasonographic evaluation.

PubMed Central

Kisthardt, K K; Schumacher, J; Finn-Bodner, S T; Carson-Dunkerley, S; Williams, M A

1999-01-01

Case records of 7 horses diagnosed with pyelonephritis were reviewed to determine common features that might aid in diagnosis, treatment, and prognosis of this disease. All 7 horses had been admitted for evaluation of hematuria. During cystoscopy of 5 horses, hemorrhage was observed from one or both ureters. Renal biopsy of 1 horse, laboratory analysis of ureteral discharge of 2 horses, and renal ultrasonography of all horses indicated that pyelonephritis was the cause of hemorrhage. Sonographic renal changes included decreased length, increased echogenicity, abnormal outline, loss of corticomedullary distinction, pyelectasia, and focal hypoechoic or hyperechoic cortical defects. Renal hemorrhage in all horses eventually resolved but recurred in 4 of 5 horses that were followed long-term. Images Figure 1. Figure 2. Figure 3. Figure 4A. Figure 4B. Figure 4C. Figure 5A. Figure 5B. Figure 5C. Figure 6A. Figure 6B. Figure 7. PMID:12001337

Renal Denervation: Intractable Hypertension and Beyond

PubMed Central

Ariyanon, Wassawon; Mao, Huijuan; Adýbelli, Zelal; Romano, Silvia; Rodighiero, Mariapia; Reimers, Bernhard; La Vecchia, Luigi; Ronco, Claudio

2014-01-01

Background Hypertension continues to be a major burden of public health concern despite the recent advances and proven benefit of pharmacological therapy. A certain subset of patients has hypertension resistant to maximal medical therapy and appropriate lifestyle measures. A novel catheter-based technique for renal denervation (RDN) as a new therapeutic avenue has great promise for the treatment of refractory hypertension. Summary This review included the physiology of the renal sympathetic nervous system and the renal nerve anatomy. Furthermore, the RDN procedure, technology systems, and RDN clinical trials as well as findings besides antihypertensive effects were discussed. Findings on safety and efficacy seem to suggest that renal sympathetic denervation could be of therapeutic benefit in refractory hypertensive patients. Despite the fast pace of development in RDN therapies, only initial and very limited clinical data are available. Large gaps in knowledge concerning the long-term effects and consequences of RDN still exist, and solid, randomized data are warranted. PMID:24847331

Modeling of Kidney Hemodynamics: Probability-Based Topology of an Arterial Network.

PubMed

Postnov, Dmitry D; Marsh, Donald J; Postnov, Dmitry E; Braunstein, Thomas H; Holstein-Rathlou, Niels-Henrik; Martens, Erik A; Sosnovtseva, Olga

2016-07-01

Through regulation of the extracellular fluid volume, the kidneys provide important long-term regulation of blood pressure. At the level of the individual functional unit (the nephron), pressure and flow control involves two different mechanisms that both produce oscillations. The nephrons are arranged in a complex branching structure that delivers blood to each nephron and, at the same time, provides a basis for an interaction between adjacent nephrons. The functional consequences of this interaction are not understood, and at present it is not possible to address this question experimentally. We provide experimental data and a new modeling approach to clarify this problem. To resolve details of microvascular structure, we collected 3D data from more than 150 afferent arterioles in an optically cleared rat kidney. Using these results together with published micro-computed tomography (μCT) data we develop an algorithm for generating the renal arterial network. We then introduce a mathematical model describing blood flow dynamics and nephron to nephron interaction in the network. The model includes an implementation of electrical signal propagation along a vascular wall. Simulation results show that the renal arterial architecture plays an important role in maintaining adequate pressure levels and the self-sustained dynamics of nephrons.

Renal Sympathetic Denervation for Treatment of Hypertension.

PubMed

Pimenta, Eduardo; Oparil, Suzanne

2012-02-01

OPINION STATEMENT: Sympathetic nervous system activation of the heart, kidney and peripheral vasculature increases cardiac output, fluid retention and vascular resistance and plays an important role in acute and chronic BP elevation. Renal sympathetic denervation via a percutaneous radiofrequency catheter based approach is a safe and effective procedure that lowers BP in patients with resistant hypertension. Exploratory studies in patients with resistant hypertension and a variety of comorbidities, including insulin resistance/metabolic syndrome, obstructive sleep apnea and the polycystic ovary syndrome, have shown benefit of renal denervation in attenuating the severity of the comorbid conditions, as well as reducing BP. However, more studies are needed to further address the long term effects of renal denervation and its safety and effectiveness in other disease states such as congestive heart failure.

Nebivolol ameliorated kidney damage in Zucker diabetic fatty rats by regulation of oxidative stress/NO pathway: comparison with captopril.

PubMed

Wang, Yan; An, Wenjing; Zhang, Fei; Niu, Mengzhen; Liu, Yu; Shi, Ruizan

2018-06-23

The aim was to evaluate the effects and mechanisms of nebivolol on renal damage in Zucker diabetic fatty (ZDF) rats, in comparison with those of atenolol and captopril. Animals were divided into: control lean Zucker rats, ZDF rats, ZDF rats orally treated with nebivolol (10 mg/kg), atenolol (100 mg/kg) or captopril (40 mg/kg) for 6 months. Systolic blood pressure (SBP), blood glucose, kidney structure and function, plasma and kidney levels of nitric oxide (NO) and asymmetric dimethylarginine (ADMA), and oxidant status were evaluated. Kidney expressions of AMP-activated protein kinase (AMPK), NADPH oxidase (NOX) isoforms 2 and 4 and subunit p22 phox , nitric oxide synthase (NOS) isoforms, eNOS uncoupling, protein arginine N-methyltransferase (PRMT) 1, and dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 were tested. All drugs induced a similar control of SBP. Nebivolol did not affect the increased plasma glucose. Unlike atenolol, nebivolol prevented the decrease in plasma insulin, and, like captopril, it reduced plasma lipid contents. Nebivolol ameliorated, to a greater extent than captopril, damages to renal structure and function, which were associated with an improvement in interlobular artery dysfunction. Nebivolol elevated kidney phosphorylation of AMPK, attenuated NOX4 and p22 phox expression and oxidative stress marker levels. Nebivolol increased plasma and renal NO, enhanced expressions of eNOS, p-eNOS and nNOS, and suppressed eNOS uncoupling and iNOS expression. High ADMA in plasma and kidney were decreased by nebivolol through increasing DDAH2 and decreasing PRMT1. Long-term treatment of nebivolol ameliorated diabetic nephropathy, at least in part, via regulation of renal oxidative stress/NO pathway. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Aquatic models for the study of renal transport function and pollutant toxicity.

PubMed Central

Miller, D S

1987-01-01

Studies of renal cell transport mechanisms and their impairment by xenobiotics are often limited by technical difficulties related to renal tubule complexity. Problems include the juxtaposition of multiple tubule segments with different transport functions and severely limited access to the tubular lumen. Some limitations can be overcome by the careful selection of an appropriate aquatic experimental system. Two aquatic models for the vertebrate proximal segment are discussed here. The first is the kidney from certain marine flounder, which offers the following advantages: long-term viability, little tissue of nonproximal origin, and easy tubule isolation. Data are presented to demonstrate how studies with flounder kidney can be used to elucidate cellular mechanisms whereby different classes of toxic pollutants may interact. Results from these experiments indicate that the excretion of certain anionic xenobiotics can be delayed by other anionic xenobiotics that compete for secretory transport sites and by compounds that disrupt cellular ion gradients and energy metabolism needed to drive transport. The second system is the crustacean urinary bladder, a simple, flatsheet epithelium. Bladder morphology and transport physiology closely resemble those of vertebrate proximal segment. Electron micrographs show a brush border membrane at the luminal surface, numerous mitochondria, and an infolded serosal membrane, while in vivo and in vitro transport studies show reabsorption of NaCl, nutrients and water and secretion of organic cations; organic anions are secreted in bladders from some species and reabsorbed in others. Moreover, since bladders can be mounted as flat sheets in flux chambers, studies with this tissue avoid the problems of complex renal tubule geometry and tissue heterogeneity that limit transport studies in proximal tubule. Images FIGURE 3. FIGURE 6. PMID:3297665

Early Application of High Cut-Off Haemodialysis for de-Novo Myeloma Nephropathy is Associated with Long-Term Dialysis-Independency and Renal Recovery

PubMed Central

Khalafallah, Alhossain A.; Loi, Sie Wuong; Love, Sarah; Mohamed, Muhajir; Mace, Rose; Khalil, Ramy; Girgs, Miriam; Raj, Rajesh; Mathew, Mathew

2013-01-01

Background Multiple myeloma (MM) is a haematological malignancy associated with kidney injury resulting from cast nephropathy, which can be caused by monoclonal free light chains (FLC). It has been demonstrated that early reduction of FLC can lead to a higher proportion of patients recovering renal function with a better outcome, especially if high cut-off haemodialysis (HCO-HD) combined with chemotherapy is used. Patients and Methods In this study, four cases with MM nephropathy were treated with HCO-HD and chemotherapy at a single institution during the period from August 2009 to August 2011. All of the patients presented with acute renal failure and high serum FLC. All patients underwent a bone marrow biopsy to confirm the diagnosis of MM, according to the WHO criteria. Three patients had de novo MM and one patient had relapsed light chain myeloma disease. All patients underwent HCO-HD concomitantly with specific myeloma therapy once the diagnosis or relapse of MM was established. Results After a medial follow up of 26 months, (range, 13–36) our data showed that all patients had a significant decrease in serum FLC through HCO-HD, proving the effectiveness of HCO-HD in managing MM. De-novo MM patients restored their renal function and achieved low-level FLC early in the treatment and became dialysis-independent. One patient with relapsed myeloma remained dialysis-dependent. Conclusion In summary, our study suggests that in myeloma nephropathy associated with light-chain MM, HCO-HD should be initiated as early as possible. At the same time a specific MM treatment should be initiated to gain control of the disease and salvage the kidneys in order to achieve dialysis-independency. Further randomized trials to confirm our results are warranted. PMID:23350020

Halo naevi and café au lait macule regression in a renal transplant patient on immunosuppression.

PubMed

Lolatgis, Helena; Varigos, George; Braue, Anna; Scardamaglia, Laura; Boyapati, Ann; Winship, Ingrid

2015-11-01

A case of halo naevi and café au lait macule regression in a renal transplant patient receiving long-term immunosuppressive therapy is described. We propose the direct transfer of an auto-reactive antibody, CD8 T-cells or tumour necrosis factor α from the transplant donor to the recipient as a possible cause. We have also considered insufficient immunosuppressive therapy as a possible mechanism. © 2014 The Australasian College of Dermatologists.

Hypovitaminosis D3, Leukopenia, and Human Serotonin Transporter Polymorphism in Anorexia Nervosa and Bulimia Nervosa.

PubMed

Tasegian, Anna; Curcio, Francesco; Dalla Ragione, Laura; Rossetti, Francesca; Cataldi, Samuela; Codini, Michela; Ambesi-Impiombato, Francesco Saverio; Beccari, Tommaso; Albi, Elisabetta

2016-01-01

Vitamin D3 has been described to have different extraskeletal roles by acting as parahormone in obesity, diabetes, cancer, cognitive impairment, and dementia and to have important regulatory functions in innate immunity. There are no studies showing extraskeletal changes associated with hypovitaminosis D3 in eating disorders. Methods. We have analyzed the blood of 18 patients affected by anorexia nervosa and bulimia nervosa collected over a 15-month period. We performed a panel of chemical and clinical analyses: the assay of vitamin D3, the immunoblotting of vitamin D receptor and peroxisome proliferator-activated receptor gamma, and the genotyping of 5-hydroxytryptamine transporter linked polymorphic region. Results. We choose 18 patients with a normal blood test profile such as thyroid hormones, hepatic and renal parameters, triglycerides, proteins, vitamin B12, and folic acid. Among these emerged the case of a woman with long-term anorexia nervosa and the case of a woman with long-term bulimia nervosa both complicated by anxiety and depression, severe hypovitaminosis D3, decrease of vitamin D receptor, leukopenia, and 5-hydroxytryptamine transporter linked polymorphic region short allele. Conclusion. The results induce hypothesising that the severe hypovitaminosis D3 might be responsible for the lack of the inflammatory response and the depressive symptoms in patients with long-term eating disorders.

Long-term renal and cardiovascular outcomes in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants by baseline estimated GFR.

PubMed

Rahman, Mahboob; Ford, Charles E; Cutler, Jeffrey A; Davis, Barry R; Piller, Linda B; Whelton, Paul K; Wright, Jackson T; Barzilay, Joshua I; Brown, Clinton D; Colon, Pedro J; Fine, Lawrence J; Grimm, Richard H; Gupta, Alok K; Baimbridge, Charles; Haywood, L Julian; Henriquez, Mario A; Ilamaythi, Ekambaram; Oparil, Suzanne; Preston, Richard

2012-06-01

CKD is common among older patients. This article assesses long-term renal and cardiovascular outcomes in older high-risk hypertensive patients, stratified by baseline estimated GFR (eGFR), and long-term outcome efficacy of 5-year first-step treatment with amlodipine or lisinopril, each compared with chlorthalidone. This was a long-term post-trial follow-up of hypertensive participants (n=31,350), aged ≥55 years, randomized to receive chlorthalidone, amlodipine, or lisinopril for 4-8 years at 593 centers. Participants were stratified by baseline eGFR (ml/min per 1.73 m(2)) as follows: normal/increased (≥90; n=8027), mild reduction (60-89; n=17,778), and moderate/severe reduction (<60; n=5545). Outcomes were cardiovascular mortality (primary outcome), total mortality, coronary heart disease, cardiovascular disease, stroke, heart failure, and ESRD. After an average 8.8-year follow-up, total mortality was significantly higher in participants with moderate/severe eGFR reduction compared with those with normal and mildly reduced eGFR (P<0.001). In participants with an eGFR <60, there was no significant difference in cardiovascular mortality between chlorthalidone and amlodipine (P=0.64), or chlorthalidone and lisinopril (P=0.56). Likewise, no significant differences were observed for total mortality, coronary heart disease, cardiovascular disease, stroke, or ESRD. CKD is associated with significantly higher long-term risk of cardiovascular events and mortality in older hypertensive patients. By eGFR stratum, 5-year treatment with amlodipine or lisinopril was not superior to chlorthalidone in preventing cardiovascular events, mortality, or ESRD during 9-year follow-up. Because data on proteinuria were not available, these findings may not be extrapolated to proteinuric CKD.

Long-term Effects of Renin-Angiotensin System–Blocking Therapy and a Low Blood Pressure Goal on Progression of Hypertensive Chronic Kidney Disease in African Americans

PubMed Central

Appel, Lawrence J.; Wright, Jackson T.; Greene, Tom; Kusek, John W.; Lewis, Julia B.; Wang, Xuelei; Lipkowitz, Michael S.; Norris, Keith C.; Bakris, George L.; Rahman, Mahboob; Contreras, Gabriel; Rostand, Stephen G.; Kopple, Joel D.; Gabbai, Francis B.; Schulman, Gerald I.; Gassman, Jennifer J.; Charleston, Jeanne; Agodoa, Lawrence Y.

2013-01-01

Background Antihypertensive drugs that block the renin-angiotensin system (angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers) are recommended for patients with chronic kidney disease (CKD). A low blood pressure (BP) goal (BP, <130/80 mm Hg) is also recommended. The objective of this study was to determine the long-term effects of currently recommended BP therapy in 1094 African Americans with hypertensive CKD. Methods Multicenter cohort study following a randomized trial. Participants were 1094 African Americans with hypertensive renal disease (glomerular filtration rate, 20–65 mL/min/1.73 m2). Following a 3×2-factorial trial (1995–2001) that tested 3 drugs used as initial antihypertensive therapy (ACEIs, calcium channel blockers, and β-blockers) and 2 levels of BP control (usual and low), we conducted a cohort study (2002–2007) in which participants were treated with ACEIs to a BP lower than 130/80 mm Hg. The outcome measures were a composite of doubling of the serum creatinine level, end-stage renal disease, or death. Results During each year of the cohort study, the annual use of an ACEI or an angiotensin receptor blocker ranged from 83.7% to 89.0% (vs 38.5% to 49.8% during the trial). The mean BP in the cohort study was 133/78 mm Hg (vs 136/82 mm Hg in the trial). Overall, 567 participants experienced the primary outcome; the 10-year cumulative incidence rate was 53.9%. Of 576 participants with at least 7 years of follow-up, 33.5% experienced a slow decline in kidney function (mean annual decline in the estimated glomerular filtration rate, <1 mL/min/1.73 m2). Conclusion Despite the benefits of renin-angiotensin system–blocking therapy on CKD progression, most African Americans with hypertensive CKD who are treated with currently recommended BP therapy continue to progress during the long term. PMID:18443258

Acute kidney injury associated with endurance events—is it a cause for concern? A systematic review

PubMed Central

Hodgson, LE; Walter, E; Venn, RM; Galloway, R; Pitsiladis, Y; Sardat, F; Forni, LG

2017-01-01

Introduction A growing body of evidence suggests even small rises in serum creatinine (SCr) are of considerable clinical relevance. Given that participants in endurance events are exposed to potential (repeated) renal insults, a systematic review was undertaken to collate current evidence for acute kidney injury (AKI), complicating such events. Methods A systematic review of studies and case reports meeting inclusion criteria on Medline and EMBASE (inception to October 2015). Included: studies with markers of renal function before and after endurance or ultraendurance events; case reports of severe AKI. Two reviewers assessed risk of bias using the Newcastle-Ottawa scale. Results Eleven case report publications (n=27 individuals) of severe AKI, were retrieved, with risk factors including systemic illness or nephrotoxic medications usually identified. From 30 studies of endurance and ultraendurance events, mean rise in SCr was 29 (±12.3) µmol/L after marathon or ultramarathon (17 studies, n=568 participants) events. Where follow-up tests were conducted, SCr returned to baseline within 48 hours. Rises in biomarkers suggest potential parenchymal insult, rather than simply muscle breakdown. However, evidence of long-term deleterious effects is lacking. Conclusions Raised levels of SCr are reported immediately after endurance events. It is not clear whether this is either clinically significant, or if repeated participation predisposes to long-term sequelae. The aetiology of severe exercise-associated AKI is usually multifactorial, with risk factors generally identified in the rare cases reported. On-site biochemistry, urine analysis and biomarkers of AKI may help identify collapsed runners who are at significant short-term risk and allow suitable follow-up. PMID:29259804

Hypertension impairs hippocampus-related adult neurogenesis, CA1 neuron dendritic arborization and long-term memory.

PubMed

Shih, Y-H; Tsai, S-F; Huang, S-H; Chiang, Y-T; Hughes, M W; Wu, S-Y; Lee, C-W; Yang, T-T; Kuo, Y-M

2016-05-13

Hypertension is associated with neurodegenerative diseases and cognitive impairment. Several studies using spontaneous hypertensive rats to study the effect of hypertension on memory performance and adult hippocampal neurogenesis have reached inconsistent conclusions. The contradictory findings may be related to the genetic variability of spontaneous hypertensive rats due to the conventional breeding practices. The objective of this study is to examine the effect of hypertension on hippocampal structure and function in isogenic mice. Hypertension was induced by the '2 kidneys, 1 clip' method (2K1C) which constricted one of the two renal arteries. The blood pressures of 2K1C mice were higher than the sham group on post-operation day 7 and remained high up to day 28. Mice with 2K1C-induced hypertension had impaired long-term, but not short-term, memory. Dendritic complexity of CA1 neurons and hippocampal neurogenesis were reduced by 2K1C-induced hypertension on post-operation day 28. Furthermore, 2K1C decreased the levels of hippocampal brain-derived neurotrophic factor, while blood vessel density and activation status of astrocytes and microglia were not affected. In conclusion, hypertension impairs hippocampus-associated long-term memory, dendritic arborization and neurogenesis, which may be caused by down-regulation of brain-derived neurotrophic factor signaling pathways. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Immediate and late management of iatrogenic ureteric injuries: 28 years of experience.

PubMed

El Abd, Ahmed S; El-Abd, Shawky A; El-Enen, Mohamed Abo; Tawfik, Ahmed M; Soliman, Mohamed G; Abo-Farha, Mohamed; Gamasy, Abd-El Naser El; El-Sharaby, Mahmoud; El-Gamal, Samir

2015-12-01

To evaluate the long-term results after managing intraoperative and late-diagnosed cases of iatrogenic ureteric injury (IUI), treated endoscopically or by open surgery. Patients immediately diagnosed with IUI were managed under the same anaesthetic, while those referred late had a radiological assessment of the site of injury, and endoscopic management. Open surgical procedures were used only for the failed cases with previous diversion. In all, 98 patients who were followed had IUI after gynaecological, abdominopelvic and ureteroscopic procedures in 60.2%, 14.3% and 25.5%, respectively. The 27 patients diagnosed during surgery were managed immediately, while in the late-referred 71 patients ureteroscopic ureteric realignment with stenting was successful in 26 (36.6%). Complex open reconstruction with re-implantation or ureteric substitution, using bladder-tube or intestinal-loop procedures, was used in 27 (60%), 16 (35.5%) and two (4.5%) patients of the late group, respectively. A long-term radiological follow-up with a mean (range) of 46.6 (24.5-144) months showed recurrent obstruction in 16 (16.3%) patients managed endoscopically and reflux in six (8.3%) patients. Three renal units only (3%) were lost in the late-presenting patients. Patients managed immediately had better long-term results. More than a third of the late-diagnosed patients were successfully managed endoscopically with minimal morbidity. Open reconstruction by an experienced urologist who can perform a complex substitutional procedure was mandatory to preserve renal units in the long-term.

The impact of renal artery stenosis on outcomes after open-heart surgery.

PubMed

Philip, Femi; Gornik, Heather L; Rajeswaran, Jeevanantham; Blackstone, Eugene H; Shishehbor, Mehdi H

2014-02-04

The aim of this study was to assess the impact of atherosclerotic renal artery stenosis (ARAS) on outcomes after open-heart surgery (OHS). Acute kidney injury after OHS portends significant morbidity and mortality. Data from all adult patients undergoing OHS from January 2000 to April 2010 who underwent renal duplex ultrasound were prospectively collected. ARAS was severe (60% to 99% stenosis) if peak systolic velocity was >200 cm/s. The associations between ARAS and post-operative reduction in glomerular filtration rate (GFR), need for renal replacement therapy, length of stay, and overall short-term and long-term mortality (up to 8 years) were tested using multivariate time-to-event adjusted analysis. A total of 714 patients were evaluated, with a mean age of 67 ± 12 years (63% men) and a mean GFR of 52 ± 25.9 ml/min/1.73 m(2). A total of 206 (29%) had ARAS; of these, 79% (n = 163) had unilateral and 21% (n = 43) had bilateral ARAS. ARAS was associated with peripheral artery disease (p = 0.004) and lower high-density lipoprotein levels (p = 0.04). Patients with advanced age (p = 0.01) and descending aorta grafting (p = 0.004) had significant post-operative reductions in GFR. Adjusted models showed a nonsignificant trend between ARAS and reduction in GFR (p = 0.09). ARAS was not associated with need for renal replacement therapy (p = 0.4), longer length of stay (p = 0.7), or mortality (p = 0.7), but low pre-operative GFR was a strong predictor of long-term mortality. ARAS does not appear to be associated with post-operative change in GFR, need for hemodialysis, longer length of stay, or mortality in patients undergoing OHS. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Impact of intrapatient variability (IPV) in tacrolimus trough levels on long-term renal transplant function: multicentre collaborative retrospective cohort study protocol

PubMed Central

Goldsmith, Petra M; Bottomley, Matthew J; Okechukwu, Okidi; Ross, Victoria C; Ghita, Ryan; Wandless, David; Falconer, Stuart J; Papachristos, Stavros; Nash, Philip; Androshchuk, Vitaliy; Clancy, Marc

2017-01-01

Introduction High intrapatient variability (IPV) in tacrolimus trough levels has been shown to be associated with higher rates of renal transplant failure. There is no consensus on what level of IPV constitutes a risk of graft loss. The establishment of such a threshold could help to guide clinicians in identifying at-risk patients to receive targeted interventions to improve IPV and thus outcomes. Methods and analysis A multicentre Transplant Audit Collaborative has been established to conduct a retrospective study examining tacrolimus IPV and renal transplant outcomes. Patients in receipt of a renal transplant at participating centres between 2009 and 2014 and fulfilling the inclusion criteria will be included in the study. The aim is to recruit a minimum of 1600 patients with follow-up spanning at least 2 years in order to determine a threshold IPV above which a renal transplant recipient would be considered at increased risk of graft loss. The study also aims to determine any national or regional trends in IPV and any demographic associations. Ethics and dissemination Consent will not be sought from patients whose data are used in this study as no additional procedures or information will be required from participants beyond that which would normally take place as part of clinical care. The study will be registered locally in each participating centre in line with local research and development protocols. It is anticipated that the results of this audit will be disseminated locally, in participating NHS Trusts, through national and international meetings and publications in peer-reviewed journals. PMID:28756385

Economic evaluation of lupus nephritis in the Systemic Lupus International Collaborating Clinics inception cohort using a multistate model approach.

PubMed

Barber, Megan R W; Hanly, John G; Su, Li; Urowitz, Murray B; Pierre, Yvan St; Romero-Diaz, Juanita; Gordon, Caroline; Bae, Sang-Cheol; Bernatsky, Sasha; Wallace, Daniel J; Isenberg, David A; Rahman, Anisur; Ginzler, Ellen M; Petri, Michelle; Bruce, Ian N; Fortin, Paul R; Gladman, Dafna D; Sanchez-Guerrero, Jorge; Ramsey-Goldman, Rosalind; Khamashta, Munther A; Aranow, Cynthia; Mackay, Meggan; Alarcón, Graciela S; Manzi, Susan; Nived, Ola; Jönsen, Andreas; Zoma, Asad A; van Vollenhoven, Ronald F; Ramos-Casals, Manuel; Ruiz-Irastorza, Guillermo; Sam Lim, S; Kalunian, Kenneth C; Inanc, Murat; Kamen, Diane L; Peschken, Christine A; Jacobsen, Soren; Askanase, Anca; Theriault, Chris; Farewell, Vernon; Clarke, Ann E

2017-11-28

Little is known about the long-term costs of lupus nephritis (LN). These were compared between patients with and without LN based on multistate modelling. Patients from 32 centres in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis and provided annual data on renal function, hospitalizations, medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy or the American College of Rheumatology classification criteria. Renal function was assessed annually using estimated glomerular filtration rate (eGFR) or proteinuria (ePrU). A multistate model was used to predict 10-year cumulative costs by multiplying annual costs associated with each renal state by the expected state duration. 1,545 patients participated, 89.3% female, mean age at diagnosis 35.2 years (SD 13.4), 49.0% Caucasian, and mean follow up 6.3 years (SD 3.3). LN developed in 39.4% by the end of follow up. Ten-year cumulative costs were greater in those with LN and an eGFR < 30 ml/min ($310 579 2015 Canadian dollars versus $19 987 if no LN and eGFR > 60 ml/min) or with LN and ePrU > 3 g/d ($84 040 versus $20 499 if no LN and ePrU < 0.25 g/d). Patients with eGFR < 30 ml/min incurred 10-year costs 15-fold higher than those with normal eGFR. By estimating the expected duration in each renal state and incorporating associated annual costs, disease severity at presentation can be used to anticipate future healthcare costs. This is critical knowledge for cost-effectiveness evaluations of novel therapies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Surgical treatment of a rare primary renal carcinoid tumor with liver metastasis

PubMed Central

Gedaly, Roberto; Jeon, Hoonbae; Johnston, Thomas D; McHugh, Patrick P; Rowland, Randall G; Ranjan, Dinesh

2008-01-01

Background Carcinoid tumors are characteristically low grade malignant neoplasms with neuroendocrine differentiation that arise in various body sites, most commonly the lung and gastrointestinal tract, but less frequently the kidneys, breasts, ovaries, testes, prostate and other locations. We report a case of a carcinoid of renal origin with synchronous single liver metastases on radiological studies. Case presentation A 45 year-old patient who presented with abdominal pain was found on CT scan to have lesions in the right ovary, right kidney, and left hepatic lobe. CA-125, CEA, and CA 19-9 were within normal limits, as were preoperative liver function tests and renal function. Biopsy of the liver mass demonstrated metastatic neuroendocrine tumor. At laparotomy, the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, radical right nephrectomy with lymphadenectomy, and left hepatectomy. Pathology evaluation reported a right ovarian borderline serous tumor, well-differentiated neuroendocrine carcinoma of the kidney (carcinoid) with 2 positive retroperitoneal lymph nodes, and a single liver metastasis. Immunohistochemistry revealed that this lesion was positive for synaptophysin and CD56, but negative for chromogranin as well as CD10, CD7, and CD20, consistent with a well-differentiated neuroendocrine tumor. She is doing well one year after her initial surgery, with no evidence of tumor recurrence. Conclusion Early surgical intervention, together with careful surveillance and follow-up, can achieve successful long-term outcomes in patients with this rare malignancy. PMID:18430248