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.

Renal Tubular Cell Mitochondrial Dysfunction Occurs Despite Preserved Renal Oxygen Delivery in Experimental Septic Acute Kidney Injury

PubMed Central

Pollen, Sean; Greco, Elisabetta; Courtneidge, Holly; Hall, Andrew M.; Duchen, Michael R.; Tam, Frederick W. K.; Unwin, Robert J.; Singer, Mervyn

2018-01-01

Objective: To explain the paradigm of significant renal functional impairment despite preserved hemodynamics and histology in sepsis-induced acute kidney injury. Design: Prospective observational animal study. Setting: University research laboratory. Subjects: Male Wistar rats. Intervention: Using a fluid-resuscitated sublethal rat model of fecal peritonitis, changes in renal function were characterized in relation to global and renal hemodynamics, and histology at 6 and 24 hours (n = 6–10). Sham-operated animals were used as comparison (n = 8). Tubular cell mitochondrial function was assessed using multiphoton confocal imaging of live kidney slices incubated in septic serum. Measurements and Main Results: By 24 hours, serum creatinine was significantly elevated with a concurrent decrease in renal lactate clearance in septic animals compared with sham-operated and 6-hour septic animals. Renal uncoupling protein-2 was elevated in septic animals at 24 hours although tubular cell injury was minimal and mitochondrial ultrastructure in renal proximal tubular cells preserved. There was no significant change in global or renal hemodynamics and oxygen delivery/consumption between sham-operated and septic animals at both 6- and 24-hour timepoints. In the live kidney slice model, mitochondrial dysfunction was seen in proximal tubular epithelial cells incubated with septic serum with increased production of reactive oxygen species, and decreases in nicotinamide adenine dinucleotide and mitochondrial membrane potential. These effects were prevented by coincubation with the reactive oxygen species scavenger, 4-hydroxy-2,2,6,6-tetramethyl-piperidin-1-oxyl. Conclusions: Renal dysfunction in sepsis occurs independently of hemodynamic instability or structural damage. Mitochondrial dysfunction mediated by circulating mediators that induce local oxidative stress may represent an important pathophysiologic mechanism. PMID:29293148

Renal microvascular disease determines the responses to revascularization in experimental renovascular disease.

PubMed

Chade, Alejandro R; Kelsen, Silvia

2010-08-01

Percutaneous transluminal renal angioplasty (PTRA) is the most frequent therapeutic approach to resolving renal artery stenosis (RAS). However, renal function recovers in only 30% of the cases. The causes of these poor outcomes are still unknown. We hypothesized that preserving the renal microcirculation distal to RAS will improve the responses to PTRA. RAS was induced in 28 pigs. In 14, vascular endothelial growth factor (VEGF)-165 0.05 microg/kg was infused intrarenally (RAS+VEGF). Single-kidney function was assessed in all pigs in vivo using ultrafast CT after 6 weeks. Observation of half of the RAS and RAS+VEGF pigs was completed. The other half underwent PTRA and repeated VEGF, and CT studies were repeated 4 weeks later. Pigs were then euthanized, the stenotic kidney removed, renal microvascular (MV) architecture reconstructed ex vivo using 3D micro-CT, and renal fibrosis quantified. The degree of RAS and hypertension were similar in RAS and RAS+VEGF. Renal function and MV density were decreased in RAS but improved in RAS+VEGF. PTRA largely resolved RAS, but the improvements of hypertension and renal function were greater in RAS+VEGF+PTRA than in RAS+PTRA, accompanied by a 34% increase in MV density and decreased fibrosis. Preservation of the MV architecture and function in the stenotic kidney improved the responses to PTRA, indicating that renal MV integrity plays a role in determining the responses to PTRA. This study indicates that damage and early loss of renal MV is an important determinant of the progression of renal injury in RAS and instigates often irreversible damage.

A Review of Anesthetic Effects on Renal Function: Potential Organ Protection.

PubMed

Motayagheni, Negar; Phan, Sheshanna; Eshraghi, Crystal; Nozari, Ala; Atala, Anthony

2017-01-01

Renal protection is a critical concept for anesthesiologists, nephrologists, and urologists, since anesthesia and renal function are highly interconnected and can potentially interfere with one another. Therefore, a comprehensive understanding of anesthetic drugs and their effects on renal function remains fundamental to the success of renal surgeries, especially transplant procedures. Some experimental studies have shown that some anesthetics provide protection against renal ischemia/reperfusion (IR) injury, but there is limited clinical evidence. The effects of anesthetic drugs on renal failure are particularly important in the context of kidney transplantation, since the conditions of preservation following removal profoundly influence the recovery of organ function. Currently, preservation procedures are typically based on the usage of a cold-storage solution. Some anesthetic drugs induce anti-inflammatory, anti-necrotic, and anti-apoptotic effects. A more thorough understanding of anesthetic effects on renal function can present a novel approach for developing organ-protective strategies. The aim of this review is to discuss the effects of different anesthetic drugs on renal function, with particular focus on IR injury. Many studies have demonstrated the organ-protective effects of some anesthetic drugs, specifically propofol, which indicate the potential of some anesthetics to introduce novel organ protective targets. This is not surprising, since lipid emulsions are major components of propofol, which accumulating data show provide organ protective effects against IR injury. Key Messages: Thorough understanding of the interaction between anesthetic drugs and renal function remains fundamental to the delivery of safe perioperative care and to optimizing outcomes after renal surgeries, particularly transplant procedures. Anesthetics can be repurposed for organ protection with more information about their effects, especially during transplant procedures. Here, we review the effects of different anesthetic drugs - specifically those that contain lipids in their structure, with special reference to IR injury. © 2017 S. Karger AG, Basel.

Endothelin-A receptor blockade slows the progression of renal injury in experimental renovascular disease.

PubMed

Kelsen, Silvia; Hall, John E; Chade, Alejandro R

2011-07-01

Endothelin (ET)-1, a potent renal vasoconstrictor with mitogenic properties, is upregulated by ischemia and has been shown to induce renal injury via the ET-A receptor. The potential role of ET-A blockade in chronic renovascular disease (RVD) has not, to our knowledge, been previously reported. We hypothesized that chronic ET-A receptor blockade would preserve renal hemodynamics and slow the progression of injury of the stenotic kidney in experimental RVD. Renal artery stenosis, a major cause of chronic RVD, was induced in 14 pigs and observed for 6 wk. In half of the pigs, chronic ET-A blockade was initiated (RVD+ET-A, 0.75 mg·kg(-1)·day(-1)) at the onset of RVD. Single-kidney renal blood flow, glomerular filtration rate, and perfusion were quantified in vivo after 6 wk using multidetector computer tomography. Renal microvascular density was quantified ex vivo using three-dimensional microcomputer tomography, and growth factors, inflammation, apoptosis, and fibrosis were determined in renal tissue. The degree of stenosis and increase in blood pressure were similar in RVD and RVD+ET-A pigs. Renal hemodynamics, function, and microvascular density were decreased in the stenotic kidney but preserved by ET-A blockade, accompanied by increased renal expression of vascular endothelial growth factor, hepatocyte growth factor, and downstream mediators such as phosphorilated-Akt, angiopoietins, and endothelial nitric oxide synthase. ET-A blockade also reduced renal apoptosis, inflammation, and glomerulosclerosis. This study shows that ET-A blockade slows the progression of renal injury in experimental RVD and preserves renal hemodynamics, function, and microvascular density in the stenotic kidney. These results support a role for ET-1/ET-A as a potential therapeutic target in chronic RVD.

Endothelin-A receptor blockade slows the progression of renal injury in experimental renovascular disease

PubMed Central

Kelsen, Silvia; Hall, John E.

2011-01-01

Endothelin (ET)-1, a potent renal vasoconstrictor with mitogenic properties, is upregulated by ischemia and has been shown to induce renal injury via the ET-A receptor. The potential role of ET-A blockade in chronic renovascular disease (RVD) has not, to our knowledge, been previously reported. We hypothesized that chronic ET-A receptor blockade would preserve renal hemodynamics and slow the progression of injury of the stenotic kidney in experimental RVD. Renal artery stenosis, a major cause of chronic RVD, was induced in 14 pigs and observed for 6 wk. In half of the pigs, chronic ET-A blockade was initiated (RVD+ET-A, 0.75 mg·kg−1·day−1) at the onset of RVD. Single-kidney renal blood flow, glomerular filtration rate, and perfusion were quantified in vivo after 6 wk using multidetector computer tomography. Renal microvascular density was quantified ex vivo using three-dimensional microcomputer tomography, and growth factors, inflammation, apoptosis, and fibrosis were determined in renal tissue. The degree of stenosis and increase in blood pressure were similar in RVD and RVD+ET-A pigs. Renal hemodynamics, function, and microvascular density were decreased in the stenotic kidney but preserved by ET-A blockade, accompanied by increased renal expression of vascular endothelial growth factor, hepatocyte growth factor, and downstream mediators such as phosphorilated-Akt, angiopoietins, and endothelial nitric oxide synthase. ET-A blockade also reduced renal apoptosis, inflammation, and glomerulosclerosis. This study shows that ET-A blockade slows the progression of renal injury in experimental RVD and preserves renal hemodynamics, function, and microvascular density in the stenotic kidney. These results support a role for ET-1/ET-A as a potential therapeutic target in chronic RVD. PMID:21478482

Renal function decline predicted by left atrial expansion index in non-diabetic cohort with preserved systolic heart function.

PubMed

Hsiao, Shih-Hung; Chiou, Kuan-Rau

2017-05-01

Since natriuretic peptide and troponin are associated with renal prognosis and left atrial (LA) parameters are indicators of subclinical cardiovascular abnormalities, this study investigated whether LA expansion index can predict renal decline. This study analysed 733 (69% male) non-diabetic patients with sinus rhythm, preserved systolic function, and estimated glomerular filtration rate (eGFR) higher than 60 mL/min/1.73 m2. In all patients, echocardiograms were performed and LA expansion index was calculated. Renal function was evaluated annually. The endpoint was a downhill trend in renal function with a final eGFR of <60 mL/min/1.73 m2. Rapid renal decline was defined as an annual decline in eGFR >3 mL/min/1.73 m2. The median follow-up time was 5.2 years, and 57 patients (7.8%) had renal function declines (19 had rapid renal declines, and 38 had incidental renal dysfunction). Events were associated with left ventricular mass index, LA expansion index, and heart failure during the follow-up period. The hazard ratio was 1.426 (95% confidence interval, 1.276-1.671; P < 0.0001) per 10% decrease in LA expansion index and was independently associated with an increased event rate. Compared with the highest quartile for the LA expansion index, the lowest quartile had a 9.7-fold risk of renal function decline in the unadjusted model and a 6.9-fold risk after adjusting for left ventricular mass index and heart failure during the follow-up period. Left atrial expansion index is a useful early indicator of renal function decline and may enable the possibility of early intervention to prevent renal function from worsening. NCT01171040. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Peritoneal dialysis and preservation of residual renal function.

PubMed

Tam, Paul

2009-02-01

Residual renal function (RRF) is now generally recognized as an important factor in the prognosis of patients on dialysis. This review summarizes the differences between peritoneal dialysis (PD) and hemodialysis (HD) with regard to RRF. The literature supports PD as having a more beneficial effect on RRF.

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.

SGLT2 inhibitors and renal outcomes in type 2 diabetes with or without renal impairment: A systematic review and meta-analysis.

PubMed

Seidu, Samuel; Kunutsor, Setor K; Cos, Xavier; Gillani, Syed; Khunti, Kamlesh

2018-06-01

Sodium-glucose co-transporter 2 (SGLT2) inhibitors may have renal protective effects in people with impaired kidney function. We assessed the use of SGLT2 inhibitors in people with type 2 diabetes with or without renal impairment [defined as estimated glomerular filtration rate (eGFR) of ≥30 and <60ml/min/1.73m 2 and/or UACR>300 and ≤5000mg/g] by conducting a systematic review and meta-analysis of available studies. Randomised controlled trials (RCTs) were identified from MEDLINE, EMABASE, Web of Science, the Cochrane Library, and search of bibliographies to March 2017. No relevant observational study was identified. Summary measures were presented as mean differences and narrative synthesis performed for studies that could not be pooled. 42 articles which included 40 RCTs comprising 29,954 patients were included. In populations with renal impairment, SGLT2 inhibition compared with placebo was consistently associated with an initial decrease in eGFR followed by an increase and return to baseline levels. In pooled analysis of 17 studies in populations without renal impairment, there was no significant change in eGFR comparing SGLT2 inhibitors with placebo (mean difference, 0.51ml/min/1.73m 2 ; 95% CI: -0.69, 1.72; p=403). SGLT2 inhibition relative to placebo was associated with preservation in serum creatinine levels or initial increases followed by return to baseline levels in patients with renal impairment, but levels were preserved in patients without renal impairment. In populations with or without renal impairment, SGLT2 inhibitors (particularly canagliflozin and empagliflozin) compared with placebo were associated with decreased urine albumin, improved albuminiuria, slowed progression to macroalbuminuria, and reduced the risk of worsening renal impairment, the initiation of kidney transplant, and death from renal disease. Emerging data suggests that with SGLT2 inhibition, renal function seems to be preserved in people with diabetes with or without renal impairment. Furthermore, SGLT2 inhibition prevents further renal function deterioration and death from kidney disease in these patients. Copyright © 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

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

Residual Renal Function in Children Treated with Chronic Peritoneal Dialysis

PubMed Central

Roszkowska-Blaim, Maria

2013-01-01

Residual renal function (RRF) in patients with end-stage renal disease (ESRD) receiving renal replacement therapy is defined as the ability of native kidneys to eliminate water and uremic toxins. Preserved RRF improves survival and quality of life in adult ESRD patients treated with peritoneal dialysis. In children, RRF was shown not only to help preserve adequacy of renal replacement therapy but also to accelerate growth rate, improve nutrition and blood pressure control, reduce the risk of adverse myocardial changes, facilitate treatment of anemia and calcium-phosphorus balance abnormalities, and result in reduced serum and dialysate fluid levels of advanced glycation end-products. Factors contributing to RRF loss in children treated with peritoneal dialysis include the underlying renal disease such as hemolytic-uremic syndrome and hereditary nephropathy, small urine volume, severe proteinuria at the initiation of renal replacement therapy, and hypertension. Several approaches can be suggested to decrease the rate of RRF loss in pediatric patients treated with chronic peritoneal dialysis: potentially nephrotoxic drugs (e.g., aminoglycosides), episodes of hypotension, and uncontrolled hypertension should be avoided, urinary tract infections should be treated promptly, and loop diuretics may be used to increase salt and water excretion. PMID:24376376

Association between renal function and cardiovascular structure and function in heart failure with preserved ejection fraction.

PubMed

Gori, Mauro; Senni, Michele; Gupta, Deepak K; Charytan, David M; Kraigher-Krainer, Elisabeth; Pieske, Burkert; Claggett, Brian; Shah, Amil M; Santos, Angela B S; Zile, Michael R; Voors, Adriaan A; McMurray, John J V; Packer, Milton; Bransford, Toni; Lefkowitz, Martin; Solomon, Scott D

2014-12-21

Renal dysfunction is a common comorbidity in patients with heart failure and preserved ejection fraction (HFpEF). We sought to determine whether renal dysfunction was associated with measures of cardiovascular structure/function in patients with HFpEF. We studied 217 participants from the PARAMOUNT study with HFpEF who had echocardiography and measures of kidney function. We evaluated the relationships between renal dysfunction [estimated glomerular filtration rate (eGFR) >30 and <60 mL/min/1.73 m(2) and/or albuminuria] and cardiovascular structure/function. The mean age of the study population was 71 years, 55% were women, 94% hypertensive, and 40% diabetic. Impairment of at least one parameter of kidney function was present in 62% of patients (16% only albuminuria, 23% only low eGFR, 23% both). Renal dysfunction was associated with abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) (adjusted P = 0.048), lower midwall fractional shortening (MWFS) (P = 0.009), and higher NT-proBNP (P = 0.006). Compared with patients without renal dysfunction, those with low eGFR and no albuminuria had a higher prevalence of abnormal LV geometry (P = 0.032) and lower MWFS (P < 0.01), as opposed to those with only albuminuria. Conversely, albuminuria alone was associated with greater LV dimensions (P < 0.05). Patients with combined renal impairment had mixed abnormalities (higher LV wall thicknesses, NT-proBNP; lower MWFS). Renal dysfunction, as determined by both eGFR and albuminuria, is highly prevalent in HFpEF, and associated with cardiac remodelling and subtle systolic dysfunction. The observed differences in cardiac structure/function between each type of renal damage suggest that both parameters of kidney function might play a distinct role in HFpEF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

How to manage hypertension with atherosclerotic renal artery stenosis?

PubMed

Ricco, Jean-Baptiste; Belmonte, Romain; Illuminati, Guilio; Barral, Xavier; Schneider, Fabrice; Chavent, Bertrand

2017-04-01

The management of atherosclerotic renal artery stenosis (ARAS) in patients with hypertension has been the topic of great controversy. Major contemporary clinical trials such as the Cardiovascular Outcomes for Renal Artery lesions (CORAL) and Angioplasty and Stenting for Renal Atherosclerotic lesions (ASTRAL) have failed to show significant benefit of revascularization over medical management in controlling blood pressure and preserving renal function. We present here the implications and limitations of these trials and formulate recommendations for management of ARAS.

Intra-renal delivery of mesenchymal stem cells attenuates myocardial injury after reversal of hypertension in porcine renovascular disease.

PubMed

Eirin, Alfonso; Zhu, Xiang-Yang; Ferguson, Christopher M; Riester, Scott M; van Wijnen, Andre J; Lerman, Amir; Lerman, Lilach O

2015-01-19

Percutaneous transluminal renal angioplasty (PTRA) fails to fully improve cardiac injury and dysfunction in patients with renovascular hypertension (RVH). Mesenchymal stem cells (MSCs) restore renal function, but their potential for attenuating cardiac injury after reversal of RVH has not been explored. We hypothesized that replenishment of MSCs during PTRA would improve cardiac function and oxygenation, and decrease myocardial injury in porcine RVH. Pigs were studied after 16 weeks of RVH, RVH treated 4 weeks earlier with PTRA with or without adjunct intra-renal delivery of MSC (10^6 cells), and controls. Cardiac structure, function (fast-computed tomography (CT)), and myocardial oxygenation (Blood-Oxygen-Level-Dependent- magnetic resonance imaging) were assessed in-vivo. Myocardial microvascular density (micro-CT) and myocardial injury were evaluated ex-vivo. Kidney venous and systemic blood levels of inflammatory markers were measured and their renal release calculated. PTRA normalized blood pressure, yet stenotic-kidney glomerular filtration rate, similarly blunted in RVH and RVH + PTRA, normalized only in PTRA + MSC-treated pigs. PTRA attenuated left ventricular remodeling, whereas myocardial oxygenation, subendocardial microvascular density, and diastolic function remained decreased in RVH + PTRA, but normalized in RVH + PTRA-MSC. Circulating isoprostane levels and renal release of inflammatory cytokines increased in RVH and RVH + PTRA, but normalized in RVH + PTRA-MSC, as did myocardial oxidative stress, inflammation, collagen deposition, and fibrosis. Intra-renal MSC delivery during PTRA preserved stenotic-kidney function, reduced systemic oxidative stress and inflammation, and thereby improved cardiac function, oxygenation, and myocardial injury four weeks after revascularization, suggesting a therapeutic potential for adjunctive MSC delivery to preserve cardiac function and structure after reversal of experimental RVH.

Augmented antihypertensive effect of a fixed combination formula of candesartan and hydrochlorothiazide combined with furosemide in a patient on peritoneal dialysis.

PubMed

Kuriyama, Satoru; Otsuka, Yasushi; Ueda, Hiroyuki; Sugano, Naoki; Yoshizawa, Takeo; Yamada, Taku; Hosoya, Tatsuo

2011-02-01

A 38-year-old female patient on peritoneal dialysis (PD) due to type 1 diabetic nephropathy with a well-preserved residual renal function did not respond well to the conventional antihypertensive therapy consisting of candesartan, furosemide, and bunazosin. Switching candesartan for a fixed combination formula of candesartan plus hydrochlorothiazide (HCTZ) while the rest of the other two agents remained unchanged led to the remarkable reduction in both systolic and diastolic blood pressure (BP) without significant changes in the cardiothoracic ratio (CTR), body weight (BW), and residual renal function. This case suggests that when used in combination, diuretics acting on different functional segment of the nephron hold greater potential for enhanced antihypertensive effect, especially in patients on PD whose residual renal function is well preserved. A small dose of HCTZ with an angiotensin II receptor blocker (ARB) may partially explain the therapeutic benefit of this combination therapy in terms of a reliable hypotensive effect, a better adherence, and fewer side effects.

Evaluation of renal function in patients with a main renal stone larger than 1 cm and perioperative renal functional change in minimally invasive renal stone surgery: a prospective, observational study.

PubMed

Piao, Songzhe; Park, Juhyun; Son, Hwancheol; Jeong, Hyeon; Cho, Sung Yong

2016-05-01

To compare the perioperative relative renal function and determine predictors of deterioration and recovery of separate renal function in patients with renal stones >10 mm and who underwent mini-percutaneous nephrolithotomy or retrograde intra-renal surgery. A main stone >10 mm or stones growing, high-risk stone formers and extracorporeal shock-wave lithotripsy-resistant stones were prospectively included in 148 patients. Patients with bilateral renal stones and anatomical deformities were excluded. Renal function was evaluated by estimated glomerular filtration rate, 99m-technetium dimercaptosuccinic acid and 99m-technetium diethylenetriamine pentaacetate prior to intervention and at postoperative 3 months. Logistic regression analyses were performed to find predictors of functional deterioration and recovery. The overall stone-free rate was 85.1 %. A third of patients (53/148, 35.8 %) with renal stones >10 mm showed deterioration of separate renal function. Mean renal function of operative sites showed 58.2 % (36.8 %/63.2 %) of that of contralateral sites in these patients. Abnormal separate renal function showed postoperative recovery in 31 patients (58.5 %). Three cases (5.7 %) showed deterioration of separate renal function despite no presence of remnant stones. Improvement rates of the abnormal separate renal function did not differ according to the type of surgery. The presence of hydronephrosis and three or more stones were significant predictors for renal function deterioration. Female gender and three or more stones were significantly correlated with postoperative recovery. Mini-percutaneous nephrolithotomy or retrograde intra-renal surgery was effective and safe for renal function preservation. Patients with multiple large stones should be considered for candidates of active surgical removal.

The Medical and Endovascular Treatment of Atherosclerotic Renal Artery Stenosis (METRAS) study: rationale and study design.

PubMed

Rossi, G P; Seccia, T M; Miotto, D; Zucchetta, P; Cecchin, D; Calò, L; Puato, M; Motta, R; Caielli, P; Vincenzi, M; Ramondo, G; Taddei, S; Ferri, C; Letizia, C; Borghi, C; Morganti, A; Pessina, A C

2012-08-01

It is unclear whether revascularization of renal artery stenosis (RAS) by means of percutaneous renal angioplasty and stenting (PTRAS) is advantageous over optimal medical therapy. Hence, we designed a randomized clinical trial based on an optimized patient selection strategy and hard experimental endpoints. Primary objective of this study is to determine whether PTRAS is superior or equivalent to optimal medical treatment for preserving glomerular filtration rate (GFR) in the ischemic kidney as assessed by 99mTcDTPA sequential renal scintiscan. Secondary objectives of this study are to establish whether the two treatments are equivalent in lowering blood pressure, preserving overall renal function and regressing target organ damage, preventing cardiovascular events and improving quality of life. The study is designed as a prospective multicentre randomized, un-blinded two-arm study. Eligible patients will have clinical and angio-CT evidence of RAS. Inclusion criteria is RAS affecting the main renal artery or its major branches either >70% or, if <70, with post-stenotic dilatation. Renal function will be assessed with 99mTc-DTPA renal scintigraphy. Patients will be randomized to either arms considering both resistance index value in the ischemic kidney and the presence of unilateral/bilateral stenosis. Primary experimental endpoint will be the GFR of the ischemic kidney, assessed as quantitative variable by 99TcDTPA, and the loss of ischemic kidney defined as a categorical variable.

Rationale and design of the balANZ trial: a randomised controlled trial of low GDP, neutral pH versus standard peritoneal dialysis solution for the preservation of residual renal function.

PubMed

Johnson, David W; Clarke, Margaret; Wilson, Vanessa; Woods, Feidhlim; Brown, Fiona G

2010-09-16

The main hypothesis of this study is that neutral pH, low glucose degradation product (GDP) peritoneal dialysis (PD) fluid better preserves residual renal function in PD patients over time compared with conventional dialysate. Inclusion criteria are adult PD patients (CAPD or APD) aged 18-81 years whose first dialysis was within 90 days prior to or following enrolment and who have a residual GFR ≥ 5 ml/min/1.73 m2, a urine output ≥ 400 ml/day and an ability to understand the nature and requirements of this trial. Pregnant or lactating patients or individuals with an active infection at the time of enrolment, a contra-indication to PD or participation in any other clinical trial where an intervention is designed to moderate rate of change of residual renal function are excluded. Patients will be randomized 1:1 to receive either neutral pH, low GDP dialysis solution (Balance) or conventional dialysis solution (Stay.safe) for a period of 2 years. During this 2 year study period, urinary urea and clearance measurements will be performed at 0, 3, 6, 9, 12, 18 and 24 months. The primary outcome measure will be the slope of residual renal function decline, adjusted for centre and presence of diabetic nephropathy. Secondary outcome measures will include time from initiation of peritoneal dialysis to anuria, peritoneal small solute clearance, peritoneal transport status, peritoneal ultrafiltration, technique survival, patient survival, peritonitis rates and adverse events. A total of 185 patients has been recruited into the trial. This investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysis solution for preserving residual renal function in PD patients. Australian New Zealand Clinical Trials Registry Number: ACTRN12606000044527.

Rationale and design of the balANZ trial: A randomised controlled trial of low GDP, neutral pH versus standard peritoneal dialysis solution for the preservation of residual renal function

PubMed Central

2010-01-01

Background The main hypothesis of this study is that neutral pH, low glucose degradation product (GDP) peritoneal dialysis (PD) fluid better preserves residual renal function in PD patients over time compared with conventional dialysate. Methods/Design Inclusion criteria are adult PD patients (CAPD or APD) aged 18-81 years whose first dialysis was within 90 days prior to or following enrolment and who have a residual GFR ≥ 5 ml/min/1.73 m2, a urine output ≥ 400 ml/day and an ability to understand the nature and requirements of this trial. Pregnant or lactating patients or individuals with an active infection at the time of enrolment, a contra-indication to PD or participation in any other clinical trial where an intervention is designed to moderate rate of change of residual renal function are excluded. Patients will be randomized 1:1 to receive either neutral pH, low GDP dialysis solution (Balance®) or conventional dialysis solution (Stay.safe®) for a period of 2 years. During this 2 year study period, urinary urea and clearance measurements will be performed at 0, 3, 6, 9, 12, 18 and 24 months. The primary outcome measure will be the slope of residual renal function decline, adjusted for centre and presence of diabetic nephropathy. Secondary outcome measures will include time from initiation of peritoneal dialysis to anuria, peritoneal small solute clearance, peritoneal transport status, peritoneal ultrafiltration, technique survival, patient survival, peritonitis rates and adverse events. A total of 185 patients has been recruited into the trial. Discussion This investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysis solution for preserving residual renal function in PD patients. Trial Registration Australian New Zealand Clinical Trials Registry Number: ACTRN12606000044527 PMID:20843375

The Prognostic Importance of Changes in Renal Function during Treatment for Acute Heart Failure Depends on Admission Renal Function

PubMed Central

Reid, Ryan; Ezekowitz, Justin A.; Brown, Paul M.; McAlister, Finlay A.; Rowe, Brian H.; Braam, Branko

2015-01-01

Background Worsening and improving renal function during acute heart failure have been associated with adverse outcomes but few studies have considered the admission level of renal function upon which these changes are superimposed. Objectives The objective of this study was to evaluate definitions that incorporate both admission renal function and change in renal function. Methods 696 patients with acute heart failure with calculable eGFR were classified by admission renal function (Reduced [R, eGFR<45 ml/min] or Preserved [P, eGFR≥45 ml/min]) and change over hospital admission (worsening [WRF]: eGFR ≥20% decline; stable [SRF]; and improving [IRF]: eGFR ≥20% increase). The primary outcome was all-cause mortality. The prevalence of Pres and Red renal function was 47.8% and 52.2%. The frequency of R-WRF, R-SRF, and R-IRF was 11.4%, 28.7%, and 12.1%, respectively; the incidence of P-WRF, P-SRF, and P-IRF was 5.7%, 35.3%, and 6.8%, respectively. Survival was shorter for patients with R-WRF compared to R-IRF (median survival times 13.9 months (95%CI 7.7–24.9) and 32.5 months (95%CI 18.8–56.1), respectively), resulting in an acceleration factor of 2.3 (p = 0.016). Thus, an increase compared with a decrease in renal function was associated with greater than two times longer survival among patients with Reduced renal function. PMID:26380982

[Should morphology of the upper pole in renal duplication with preserved function and associated ureterocele be taken into account during treatment planning?].

PubMed

Materny, Jacek; Chojnacka, Hanna; Urasińska, Elzbieta; Gawrych, Elzbieta

2011-01-01

The aim of this study was to assess structural changes of the upper pole in renal duplication with coexisting ureterocele with regard to primary and/or secondary lesions. These changes might be of importance in treatment planning. The material of this study consisted of clinical documentation and results of histopathology of 23 upper poles removed due to renal duplication with coexisting ureterocele. The qualification criterion was preserved function of the upper pole seen with 99mTc-DTPA (99mTechnetium diethylenetriaminepentaacetic acid)/99mTc-DMSA (99mTechnetium dimercaptosuccinic acid). Resection of the upper pole was indicated in patients with recurrent urinary tract infections and/or persistent vesicoureteral reflux to the lower pole following endoscopic surgery of the ureterocele and/or low function of the upper pole. Morphological lesions were classified as primary (dysplasia) or secondary lesions. The patients were operated at the Department of Pediatric and Oncologic Surgery, PMU, in 1990-2008. The study group consisted of 17 girls and 6 boys aged from 4 months to 9 years (mean 40 months). Recurrent urinary tract infections noted in 16 (70%) children were the most frequent indication for surgery. The preoperative mean function of the renal poles assessed with DTPA/DMSA represented 6% of the differential renal function. Dysplasia was identified in eight resected renal poles (34%) with coexisting secondary lesions in three of them. Secondary lesions only were seen in 15 poles (66%). There was no correlation between age and incidence of dysplasia during follow-up (Pearson's correlation coefficient r = 0.031). Secondary lesions are a quite frequent finding in resected upper poles. As 66% of the renal poles studied with histopathology revealed secondary lesions only, we believe that renal sparing treatment is justified in cases of urinary duplication with coexisting ureterocele.

Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study

PubMed Central

Serra, Andreas L; Kistler, Andreas D; Poster, Diane; Struker, Marian; Wüthrich, Rudolf P; Weishaupt, Dominik; Tschirch, Frank

2007-01-01

Background Currently there is no effective treatment available to retard cyst growth and to prevent the progression to end-stage renal failure in patients with autosomal dominant polycystic kidney disease (ADPKD). Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Based on these promising results in animals we have designed and initiated the first randomized controlled trial (RCT) to examine the effectiveness, safety and tolerability of sirolimus to retard disease progression in ADPKD. Method/design This single center, randomised controlled, open label trial assesses the therapeutic effect, safety and tolerability of the mTOR inhibitor sirolimus (Rapamune®) in patients with autosomal dominant polycystic kidney disease and preserved renal function. The primary outcome will be the inhibition of kidney volume growth measured by magnetic resonance imaging (MRI) volumetry. Secondary outcome parameters will be preservation of renal function, safety and tolerability of sirolimus. Discussion The results from this proof-of-concept RCT will for the first time show whether treatment with sirolimus effectively retards cyst growth in patients with ADPKD. Trial registration NCT00346918 PMID:17868472

We Avoid RAAS Inhibitors in PD Patients with Residual Renal Function.

PubMed

Turner, Jeffrey M

2016-07-01

Preserving residual renal function in patients on peritoneal dialysis (PD) positively impacts mortality. While it is important to avoid nephrotoxic agents in this setting, clinicians should appreciate that inhibitors of the renin-angiotensin-aldosterone system (RAAS), including angiotensin converting enzyme inhibitors, and angiotensin receptor blockers are likely to preserve glomerular filtration rate and prolong the time until patients on PD reach anuria, and this may improve mortality in these patients. In addition, RAAS blockade favorably affects the peritoneal membrane by reducing morphologic changes that can lead to ultrafiltration failure. This in turn may delay or prevent modality failure in patients on PD. Thus, clinicians should avoid the impulse to stop RAAS inhibitors in the PD population. © 2016 Wiley Periodicals, Inc.

Effectiveness of N-acetylcysteine for preserving residual renal function in patients undergoing maintenance hemodialysis: multicenter randomized clinical trial.

PubMed

Ahmadi, Farrokhlaga; Abbaszadeh, Mahsa; Razeghi, Effat; Maziar, Sima; Khoidaki, Simin Dashti; Najafi, Mohammad Taghi; Lessan-Pezeshki, Mahboob

2017-04-01

To investigate the efficacy and safety of oral N-acetylcysteine (NAC) for preserving residual renal function in patients undergoing hemodialysis. Randomized, multi-center, parallel-group, open-label clinical trial (Registration No. IRCT 2014071418482N1). 54 patients who have been undergoing hemodialysis for at least 3 months and had residual urine volume >100 ml/24 h were randomly allocated to NAC or no medication. Residual renal function evaluated by (1) estimated glomerular filtration rate (GFR), (2) 24 h urine volume, and (3) renal Kt/V. GFR and Kt/V was determined at baseline and after 3 months. 24 h urine volume was measured at baseline, after 1, 2, and 3 months. Intention-to-treat analysis was performed on 47 patients (NAC = 26, control = 21). GFR in patients receiving NAC improved, whereas in the control arm a decline of 1.0 ml/min/1.73 m 2 was recorded (3.59 vs. 2.11 ml/min/1.73 m 2 , effect size = 17.0 %, p = 0.004). For 24 h urine volume, the between-group difference after 1 month was significant (669 vs. 533 ml/24 h, effect size = 15.4 %, p = 0.004). After 3 months, 24 h urine volume in the NAC arm was on average 137 ml higher than in the control group, and the difference reached near significance (673 vs. 536 ml/24 h, p = 0.072). In the follow-up visit, Kt/V was higher in the NAC arm but the difference did not reach statistical significance (0.81 vs. 0.54, p = 0.152). Three months treatment with NAC appears to be effective in preserving renal function in patients undergoing hemodialysis and the medication is generally well-tolerated.

Cadaveric renal preservation with hyperosmolar, intracellular hypothermic washout solution and cold storage.

PubMed

Diethelm, A G; Blackstone, E H

1978-07-01

All 54 kidneys obtained from heart-beating cadavers functioned when preserved by a brief washout using a hypothermic, hyperosmolar, hyperkalemic perfusate, followed by cold storage. The duration of preservation ranged from two hours and 57 minutes to 39 hours and 47 minutes. Two other kidneys retrieved from a nonheart-beating cadaver and preserved by the same technique failed to function because of irreversible acute tubular necrosis. Fifty-six consecutive transplant patients were divided into four groups according to the period of preservation. There was no correlation between graft rejection, frequency of post-transplant dialysis, long term graft function and survival time, when the duration of preservation was less than 24 hours. The advantages of this technique included technical simplicity, low cost, minimal risk of graft infection and easy transportation. The two primary disadvantages were an apparent 24 to 30 hour limit of organ preservation with prompt function and the inability to determine intrarenal perfusion pressure during preservation, thereby missing an important parameter of graft viability.

Aortoiliac aneurysm with congenital right pelvic kidney.

PubMed

Date, Kazuma; Okada, Shuuichi; Ezure, Masahiko; Takihara, Hitomi; Okonogi, Shuuichi; Hasegawa, Yutaka; Sato, Yasushi; Kaneko, Tatsuo

2015-05-01

The association of congenital pelvic kidney with abdominal aortoiliac aneurysm is an extremely rare clinical finding. Previous reports have described various methods of aneurysm repair with successful preservation of the function of pelvic kidney. However, to our knowledge, reconstruction of more than two renal arteries has not been established. We report a case of abdominal aortic aneurysm complicated by congenital right pelvic kidney in a 72-year-old man. Computed tomography (CT) revealed an abdominal aortic aneurysm with a maximum diameter of 54 mm and a right common iliac aneurysm of 45 mm. In addition, he had a congenital right pelvic kidney and CT angiography identified three right pelvic renal arteries. The upper artery originated from the bifurcation of the terminal aorta and the lower two originated from the right common iliac artery. Three-dimensional CT was helpful for the accurate planning of the operation. Open surgical repair of the aortoiliac aneurysm with a Dacron bifurcated graft replacement was decided and reimplantation of all three right pelvic kidney arteries to the right limb of the graft was also performed. For renal preservation, the right pelvic kidney arteries were perfused with cold Ringer's lactate using a rapid infusion pump and coronary perfusion cannula. The patient's postoperative course was uneventful, and worsening of renal function was not observed. The perfusion of renal arteries with cold Ringer's solution was thought to be a simple and appropriate procedure for renal protection.

Renal cell carcinoma: new insights and challenges for a clinician scientist.

PubMed

Shingarev, Roman; Jaimes, Edgar A

2017-08-01

There is a growing recognition of the complex interplay between renal cell cancer (RCC), kidney function, mechanical reduction of nephron mass, and systemic agents targeting the cancer. Earlier detection of RCC and rising life expectancy of cancer survivors places a greater emphasis on preservation of renal function after cancer resection and during systemic therapy. Unique adverse effects associated with RCC drugs not only help reveal cancer pathophysiology but also expand our knowledge of normal cell signaling and metabolism. In this review, we outline our current understanding of RCC biology and treatment, their bidirectional relationship with kidney function, and unmet research needs in this field. Copyright © 2017 the American Physiological Society.

Everolimus immunosuppression for renal protection, reduction of allograft vasculopathy and prevention of allograft rejection in de-novo heart transplant recipients: could we have it all?

PubMed

Gude, Einar; Gullestad, Lars; Andreassen, Arne K

2017-06-01

De-novo introduction of everolimus (Eve) in heart transplant recipients opens for early reduction of calcineurin inhibitors (CNI) and potential of preserving renal function, attenuate progression of coronary allograft vasculopathy (CAV) and maintain rejection efficacy. The first trials demonstrated adequate rejection prophylaxis and favorable outcomes on CAV, but observed enhanced nephrotoxicity because of insufficient CNI reduction. The SCHEDULE trial compared de-novo Eve with significantly reduced CNI exposure and conversion to CNI-free treatment week 7-11 postheart transplant, with standard CNI immunosuppression. Improved renal function and attenuation of CAV was found among Eve patients, with higher numbers of treated acute rejections observed. With sustained superior renal and CAV related data also after 36 months with the Eve protocol, cardiac function was equally well preserved in both groups. According to the International Society of Heart and Lunge Transplantation registry, mammalian target of rapamycin inhibitor treatment is uncommon during the first postoperative year, with a prevalence of 20% in patients after 5 years. Current evidence suggests a greater benefit from these immunosuppressives if introduced at an earlier timepoint. Immunosuppressive protocols based on Eve treatment in de-novo patients should be further investigated and developed, enabling CNI avoidance before accelerating side-effects lead to irreversible damage.

Proregenerative Microenvironment Triggered by Donor Mesenchymal Stem Cells Preserves Renal Function and Structure in Mice with Severe Diabetes Mellitus.

PubMed

Ezquer, Fernando; Giraud-Billoud, Maximiliano; Carpio, Daniel; Cabezas, Fabián; Conget, Paulette; Ezquer, Marcelo

2015-01-01

The aim of our work was to evaluate, in an animal model of severe diabetes mellitus, the effect of mesenchymal stem cells (MSCs) administration on diabetic nephropathy (DN) progression. After diabetes induction, one group of mice received the vehicle (DM) and other group received a single dose of MSCs (DM + MSCs). DM + MSCs mice showed a significant improvement in functional parameters of the kidney compared with untreated mice. While DM mice presented marked histopathological changes characteristics of advanced stages of DN (fibrosis, glomerulosclerosis, glomerular basement membrane thickening, capillary occlusion, decreased podocyte density, and effacement of foot processes), DM + MSCs mice showed only slight tubular dilatation. The renoprotection was not associated with an improvement in diabetic condition and very low number of donor cells was found in the kidney of DM + MSCs mice, suggesting that renoprotection could be mediated by paracrine effects. Indeed, DM + MSC mice presented increased renal proliferation index, decreased renal apoptotic index and the restoration of proregenerative factors, and anti-inflammatory cytokines levels. Moreover, macrophage infiltration and oxidative stress damage were also reduced in DM + MSCs mice. Our data demonstrate that MSC administration triggers a proregenerative microenvironment in DN kidney, which allows the preservation of the renal function even if diabetes was uncorrected.

Proregenerative Microenvironment Triggered by Donor Mesenchymal Stem Cells Preserves Renal Function and Structure in Mice with Severe Diabetes Mellitus

PubMed Central

Ezquer, Fernando; Giraud-Billoud, Maximiliano; Carpio, Daniel; Cabezas, Fabián; Conget, Paulette

2015-01-01

The aim of our work was to evaluate, in an animal model of severe diabetes mellitus, the effect of mesenchymal stem cells (MSCs) administration on diabetic nephropathy (DN) progression. After diabetes induction, one group of mice received the vehicle (DM) and other group received a single dose of MSCs (DM + MSCs). DM + MSCs mice showed a significant improvement in functional parameters of the kidney compared with untreated mice. While DM mice presented marked histopathological changes characteristics of advanced stages of DN (fibrosis, glomerulosclerosis, glomerular basement membrane thickening, capillary occlusion, decreased podocyte density, and effacement of foot processes), DM + MSCs mice showed only slight tubular dilatation. The renoprotection was not associated with an improvement in diabetic condition and very low number of donor cells was found in the kidney of DM + MSCs mice, suggesting that renoprotection could be mediated by paracrine effects. Indeed, DM + MSC mice presented increased renal proliferation index, decreased renal apoptotic index and the restoration of proregenerative factors, and anti-inflammatory cytokines levels. Moreover, macrophage infiltration and oxidative stress damage were also reduced in DM + MSCs mice. Our data demonstrate that MSC administration triggers a proregenerative microenvironment in DN kidney, which allows the preservation of the renal function even if diabetes was uncorrected. PMID:26167475

Computed Tomography Volumetry in Preoperative Living Kidney Donor Assessment for Prediction of Split Renal Function.

PubMed

Wahba, Roger; Franke, Mareike; Hellmich, Martin; Kleinert, Robert; Cingöz, Tülay; Schmidt, Matthias C; Stippel, Dirk L; Bangard, Christopher

2016-06-01

Transplant centers commonly evaluate split renal function (SRF) with Tc-99m-mercapto-acetyltriglycin (MAG3) scintigraphy in living kidney donation. Alternatively, the kidney volume can be measured based on predonation CT scans. The aim of this study was to identify the most accurate CT volumetry technique for SRF and the prediction of postdonation kidney function (PDKF). Three CT volumetry techniques (modified ellipsoid volume [MELV], smart region of interest [ROI] volume, renal cortex volume [RCV]) were performed in 101 living kidney donors. Preoperation CT volumetric SRF was determined and compared with MAG3-SRF, postoperation donor kidney function, and graft function. The correlation between donors predonation total kidney volume and predonation kidney function was the highest for RCV (0.58 with creatine clearance, 0.54 with estimated glomerular filtration rate-Cockcroft-Gault). The predonation volume of the preserved kidney was (ROI, MELV, RCV) 148.0 ± 29.1 cm, 151.2 ± 35.4 and 93.9 ± 25.2 (P < 0.005 MELV vs RCV and ROI vs RCV). Bland-Altman analysis showed agreement between CT volumetry SRF and MAG3-SRF (bias, 95% limits of agreement: ROI vs MAG3 0.4%, -7.7% to 8.6%; MELV vs MAG3 0.4%, -8.9% to 9.7%; RCV vs MAG3 0.8%, -9.1% to 10.7%). The correlation between predonation CT volumetric SRF of the preserved kidney and PDKF at day 3 was r = 0.85 to 0.88, between MAG3-SRF and PDKF (r = 0.84). The difference of predonation SRF between preserved and donated kidney was the lowest for ROI and RCV (median, 3% and 4%; 95th percentile, 9% and 13%). Overall renal cortex volumetry seems to be the most accurate technique for the evaluation of predonation SRF and allows a reliable prediction of donor's PDKF.

Renal Denervation to Modify Hypertension and the Heart Failure State.

PubMed

Zhong, Ming; Kim, Luke K; Swaminathan, Rajesh V; Feldman, Dmitriy N

2017-07-01

Sympathetic overactivation of renal afferent and efferent nerves have been implicated in the development and maintenance of several cardiovascular disease states, including resistant hypertension and heart failure with both reduced and preserved systolic function. With the development of minimally invasive catheter-based techniques, percutaneous renal denervation has become a safe and effective method of attenuating sympathetic overactivation. Percutaneous renal denervation, therefore, has the potential to modify and treat hypertension and congestive heart failure. Although future randomized controlled studies are needed to definitively prove its efficacy, renal denervation has the potential to change the way we view and treat cardiovascular disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Three new renal simulators for use in nuclear medicine

NASA Astrophysics Data System (ADS)

Dullius, Marcos; Fonseca, Mateus; Botelho, Marcelo; Cunha, Clêdison; Souza, Divanízia

2014-03-01

Renal scintigraphy is useful to provide both functional and anatomic information of renal flow of cortical functions and evaluation of pathological collecting system. The objective of this study was develop and evaluate the performance of three renal phantoms: Two anthropomorphic static and another dynamic. The static images of the anthropomorphic phantoms were used for comparison with static renal scintigraphy with 99mTc-DMSA in different concentrations. These static phantoms were manufactured in two ways: one was made of acrylic using as mold a human kidney preserved in formaldehyde and the second was built with ABS (acrylonitrile butadiene styrene) in a 3D printer. The dynamic renal phantom was constructed of acrylic to simulate renal dynamics in scintigraphy with 99mTc-DTPA. These phantoms were scanned with static and dynamic protocols and compared with clinical data. Using these phantoms it is possible to acquire similar renal images as in the clinical scintigraphy. Therefore, these new renal phantoms can be very effective for use in the quality control of renal scintigraphy, and image processing systems.

Effect of Neutral-pH, Low–Glucose Degradation Product Peritoneal Dialysis Solutions on Residual Renal Function, Urine Volume, and Ultrafiltration: A Systematic Review and Meta-Analysis

PubMed Central

Yohanna, Seychelle; Alkatheeri, Ali M.A.; Brimble, Scott K.; McCormick, Brendan; Iansavitchous, Arthur; Blake, Peter G.

2015-01-01

Background and objectives Neutral-pH, low–glucose degradation products solutions were developed in an attempt to lessen the adverse effects of conventional peritoneal dialysis solutions. A systematic review was performed evaluating the effect of these solutions on residual renal function, urine volume, peritoneal ultrafiltration, and peritoneal small-solute transport (dialysate to plasma creatinine ratio) over time. Design, setting, participants, & measurements Multiple electronic databases were searched from January of 1995 to January of 2013. Randomized trials reporting on any of four prespecified outcomes were selected by consensus among multiple reviewers. Results Eleven trials of 643 patients were included. Trials were generally of poor quality. The meta-analysis was performed using a random effects model. The use of neutral-pH, low-glucose degradation products solutions resulted in better preserved residual renal function at various study durations, including >1 year (combined analysis: 11 studies; 643 patients; standardized mean difference =0.17 ml/min; 95% confidence interval, 0.01 to 0.32), and greater urine volumes (eight studies; 598 patients; mean difference =128 ml/d; 95% confidence interval, 58 to 198). There was no significant difference in peritoneal ultrafiltration (seven studies; 571 patients; mean difference =−110; 95% confidence interval, −312 to 91) or dialysate to plasma creatinine ratio (six studies; 432 patients; mean difference =0.03; 95% confidence interval, 0.00 to 0.06). Conclusions The use of neutral-pH, low–glucose degradation products solutions results in better preservation of residual renal function and greater urine volumes. The effect on residual renal function occurred early and persisted beyond 12 months. Additional studies are required to evaluate the use of neutral-pH, low–glucose degradation products solutions on hard clinical outcomes. PMID:26048890

Abdominal aortic aneurysm associated with congenital solitary pelvic kidney treated with novel hybrid technique.

PubMed

Malinowski, Michael J; Al-Nouri, Omar; Hershberger, Richard; Halandras, Pegge M; Aulivola, Bernadette; Cho, Jae S

2014-08-01

Renal ectopia in the rare condition of associated abdominal aortic aneurysm presents a difficult clinical challenge with respect to access to the aorto-iliac segment and preservation of renal function because of its anomalous renal arterial anatomy and inevitable renal ischemia at the time of open repair. Multiple operative techniques are described throughout the literature to cope with both problems. We report a case of a 57-year-old male with an aorto-iliac aneurysm and a congenital solitary pelvic kidney successfully treated by hybrid total renal revascularization using iliorenal bypass followed by unilateral internal iliac artery coil embolization and conventional endovascular aortic aneurysm repair without any clinical evidence of renal impairment. Copyright © 2014 Elsevier Inc. All rights reserved.

Inhibition of WISE preserves renal allograft function.

PubMed

Qian, Xueming; Yuan, Xiaodong; Vonderfecht, Steven; Ge, Xupeng; Lee, Jae; Jurisch, Anke; Zhang, Li; You, Andrew; Fitzpatrick, Vincent D; Williams, Alexia; Valente, Eliane G; Pretorius, Jim; Stevens, Jennitte L; Tipton, Barbara; Winters, Aaron G; Graham, Kevin; Harriss, Lindsey; Baker, Daniel M; Damore, Michael; Salimi-Moosavi, Hossein; Gao, Yongming; Elkhal, Abdallah; Paszty, Chris; Simonet, W Scott; Richards, William G; Tullius, Stefan G

2013-01-01

Wnt-modulator in surface ectoderm (WISE) is a secreted modulator of Wnt signaling expressed in the adult kidney. Activation of Wnt signaling has been observed in renal transplants developing interstitial fibrosis and tubular atrophy; however, whether WISE contributes to chronic changes is not well understood. Here, we found moderate to high expression of WISE mRNA in a rat model of renal transplantation and in kidneys from normal rats. Treatment with a neutralizing antibody against WISE improved proteinuria and graft function, which correlated with higher levels of β-catenin protein in kidney allografts. In addition, treatment with the anti-WISE antibody reduced infiltration of CD68(+) macrophages and CD8(+) T cells, attenuated glomerular and interstitial injury, and decreased biomarkers of renal injury. This treatment reduced expression of genes involved in immune responses and in fibrogenic pathways. In summary, WISE contributes to renal dysfunction by promoting tubular atrophy and interstitial fibrosis.

Hemodynamic Measurements for the Selection of Patients With Renal Artery Stenosis: A Systematic Review.

PubMed

van Brussel, Peter M; van de Hoef, Tim P; de Winter, Robbert J; Vogt, Liffert; van den Born, Bert-Jan

2017-05-22

Interventions targeting renal artery stenoses have been shown to lower blood pressure and preserve renal function. In recent studies, the efficacy of catheter-based percutaneous transluminal renal angioplasty with stent placement has been called into question. In the identification of functional coronary lesions, hyperemic measurements have earned a place in daily practice for clinical decision making, allowing discrimination between solitary coronary lesions and diffuse microvascular disease. Next to differences in clinical characteristics, the selection of renal arteries suitable for intervention is currently on the basis of anatomic grading of the stenosis by angiography rather than functional assessment under hyperemia. It is conceivable that, like the coronary circulation, functional measurements may better predict therapeutic efficacy of percutaneous transluminal renal angioplasty with stent placement. In this systematic review, the authors evaluate the available clinical evidence on the optimal hyperemic agents to induce intrarenal hyperemia, their association with anatomic grading, and their predictive value for treatment effects. In addition, the potential value of combined pressure and flow measurements to discriminate macrovascular from microvascular disease is discussed. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

Renal cortical volume: High correlation with pre- and post-operative renal function in living kidney donors.

PubMed

Gardan, Edouard; Jacquemont, Lola; Perret, Christophe; Heudes, Pierre-Marie; Gourraud, Pierre-Antoine; Hourmant, Maryvonne; Frampas, Eric; Limou, Sophie

2018-02-01

CT volumetry has previously been proposed as an alternative to scintigraphy for the evaluation of pre-donation split renal function and the prediction of post-donation renal function in living kidney donors. The aim of our study was to retrospectively assess the relevance of three CT volumetry techniques for estimating pre-donation kidney function and predicting the risk for chronic kidney disease (CKD) at 1-year post-nephrectomy in a French cohort of living donors using isotopic measures of kidney function. Kidney volume was quantified pre-donation for 105 donors using three methods total parenchymal three-dimensional renal volume (3DRV), total parenchymal renal volume contouring (RVCt), and renal cortical volume (RCoV). Subjects also had a 51Cr-EDTA scintigraphy to measure glomerular filtration rate (mGFR) pre-donation and 1-year after donation. For each volume, we tested for association with mGFR using univariate regression models, and computed receiver operating characteristics analyses to assess their predictive potential of post-donation CKD. Our population was composed of healthy subjects, who were predominantly female (69%) with a median age at donation of 51yo. Median mGFR was 102 mL/min/1.73 m 2 at pre-donation and 66 mL/min/1.73 m 2 1-year after nephrectomy. The pre-donation median volume of the preserved kidney was 156 cm 3 , 163 cm 3 and 99 cm 3 for the 3DRV, RVCt and RCoV methods respectively, with a high correlation observed between each technique (R > 0.84). For all methods, total kidney volume was significantly associated with pre-donation mGFR (P < 0.001). Preserved kidney volume was also strongly correlated with post-donation mGFR (P < 0.0001), with the strongest correlation observed for RCoV (R = 0.60 vs. R = 0.39 and R = 0.51 for 3DRV and RVCt, respectively). Finally, the RCoV method yielded the best predictive value of 1-year post-donation CKD (AUC = 0.80 vs. AUC = 0.76 and 0.70 for RVCt and 3DRV, respectively). In our cohort of healthy donors with measured kidney function, cortical volumetry (RCoV) appears as the best volumetric technique to use as a surrogate to scintigraphy for estimating pre-donation split renal function and predicting post-donation renal outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Dichloroacetate Prevents Cisplatin-Induced Nephrotoxicity without Compromising Cisplatin Anticancer Properties

PubMed Central

Galgamuwa, Ramindhu; Hardy, Kristine; Dahlstrom, Jane E.; Blackburn, Anneke C.; Wium, Elize; Rooke, Melissa; Cappello, Jean Y.; Tummala, Padmaja; Patel, Hardip R.; Chuah, Aaron; Tian, Luyang; McMorrow, Linda; Board, Philip G.

2016-01-01

Cisplatin is an effective anticancer drug; however, cisplatin use often leads to nephrotoxicity, which limits its clinical effectiveness. In this study, we determined the effect of dichloroacetate, a novel anticancer agent, in a mouse model of cisplatin-induced AKI. Pretreatment with dichloroacetate significantly attenuated the cisplatin-induced increase in BUN and serum creatinine levels, renal tubular apoptosis, and oxidative stress. Additionally, pretreatment with dichloroacetate accelerated tubular regeneration after cisplatin-induced renal damage. Whole transcriptome sequencing revealed that dichloroacetate prevented mitochondrial dysfunction and preserved the energy-generating capacity of the kidneys by preventing the cisplatin-induced downregulation of fatty acid and glucose oxidation, and of genes involved in the Krebs cycle and oxidative phosphorylation. Notably, dichloroacetate did not interfere with the anticancer activity of cisplatin in vivo. These data provide strong evidence that dichloroacetate preserves renal function when used in conjunction with cisplatin. PMID:26961349

Nephrotic range proteinuria as a strong risk factor for rapid renal function decline during pre-dialysis phase in type 2 diabetic patients with severely impaired renal function.

PubMed

Kitai, Yuichiro; Doi, Yohei; Osaki, Keisuke; Sugioka, Sayaka; Koshikawa, Masao; Sugawara, Akira

2015-12-01

Proteinuria is an established risk factor for progression of renal disease, including diabetic nephropathy. The predictive power of proteinuria, especially nephrotic range proteinuria, for progressive renal deterioration has been well demonstrated in diabetic patients with normal to relatively preserved renal function. However, little is known about the relationship between severity of proteinuria and renal outcome in pre-dialysis diabetic patients with severely impaired renal function. 125 incident dialysis patients with type 2 diabetes were identified. This study was aimed at retrospectively evaluating the impact of nephrotic range proteinuria (urinary protein-creatinine ratio above 3.5 g/gCr) on renal function decline during the 3 months just prior to dialysis initiation. In total, 103 patients (82.4 %) had nephrotic range proteinuria. The median rate of decline in estimated glomerular filtration rate (eGFR) in this study population was 0.98 (interquartile range 0.51-1.46) ml/min/1.73 m(2) per month. Compared to patients without nephrotic range proteinuria, patients with nephrotic range proteinuria showed significantly faster renal function decline (0.46 [0.24-1.25] versus 1.07 [0.64-1.54] ml/min/1.73 m(2) per month; p = 0.007). After adjusting for gender, age, systolic blood pressure, serum albumin, calcium-phosphorus product, hemoglobin A1c, and use of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, patients with nephrotic range proteinuria showed a 3.89-fold (95 % CI 1.08-14.5) increased risk for rapid renal function decline defined as a decline in eGFR ≥0.5 ml/min/1.73 m(2) per month. Nephrotic range proteinuria is the predominant renal risk factor in type 2 diabetic patients with severely impaired renal function receiving pre-dialysis care.

Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD Trial

PubMed Central

Nadkarni, Girish N.; Rao, Veena; Ismail-Beigi, Faramarz; Fonseca, Vivian A.; Shah, Sudhir V.; Simonson, Michael S.; Cantley, Lloyd; Devarajan, Prasad; Parikh, Chirag R.

2016-01-01

Background and objectives Current measures for predicting renal functional decline in patients with type 2 diabetes with preserved renal function are unsatisfactory, and multiple markers assessing various biologic axes may improve prediction. We examined the association of four biomarker-to-creatinine ratio levels (monocyte chemotactic protein-1, IL-18, kidney injury molecule-1, and YKL-40) with renal outcome. Design, setting, participants, & measurements We used a nested case-control design in the Action to Control Cardiovascular Disease Trial by matching 190 participants with ≥40% sustained eGFR decline over the 5-year follow-up period to 190 participants with ≤10% eGFR decline in a 1:1 fashion on key characteristics (age within 5 years, sex, race, baseline albumin-to-creatinine ratio within 20 μg/mg, and baseline eGFR within 10 ml/min per 1.73 m2), with ≤10% decline. We used a Mesoscale Multiplex Platform and measured biomarkers in baseline and 24-month specimens, and we examined biomarker associations with outcome using conditional logistic regression. Results Baseline and 24-month levels of monocyte chemotactic protein-1-to-creatinine ratio levels were higher for cases versus controls. The highest quartile of baseline monocyte chemotactic protein-1-to-creatinine ratio had fivefold greater odds, and each log increment had 2.27-fold higher odds for outcome (odds ratio, 5.27; 95% confidence interval, 2.19 to 12.71 and odds ratio, 2.27; 95% confidence interval, 1.44 to 3.58, respectively). IL-18-to-creatinine ratio, kidney injury molecule-1-to-creatinine ratio, and YKL-40-to-creatinine ratio were not consistently associated with outcome. C statistic for traditional predictors of eGFR decline was 0.70, which improved significantly to 0.74 with monocyte chemotactic protein-1-to-creatinine ratio. Conclusions Urinary monocyte chemotactic protein-1-to-creatinine ratio concentrations were strongly associated with sustained renal decline in patients with type 2 diabetes with preserved renal function. PMID:27189318

Association of Urinary Biomarkers of Inflammation, Injury, and Fibrosis with Renal Function Decline: The ACCORD Trial.

PubMed

Nadkarni, Girish N; Rao, Veena; Ismail-Beigi, Faramarz; Fonseca, Vivian A; Shah, Sudhir V; Simonson, Michael S; Cantley, Lloyd; Devarajan, Prasad; Parikh, Chirag R; Coca, Steven G

2016-08-08

Current measures for predicting renal functional decline in patients with type 2 diabetes with preserved renal function are unsatisfactory, and multiple markers assessing various biologic axes may improve prediction. We examined the association of four biomarker-to-creatinine ratio levels (monocyte chemotactic protein-1, IL-18, kidney injury molecule-1, and YKL-40) with renal outcome. We used a nested case-control design in the Action to Control Cardiovascular Disease Trial by matching 190 participants with ≥40% sustained eGFR decline over the 5-year follow-up period to 190 participants with ≤10% eGFR decline in a 1:1 fashion on key characteristics (age within 5 years, sex, race, baseline albumin-to-creatinine ratio within 20 μg/mg, and baseline eGFR within 10 ml/min per 1.73 m(2)), with ≤10% decline. We used a Mesoscale Multiplex Platform and measured biomarkers in baseline and 24-month specimens, and we examined biomarker associations with outcome using conditional logistic regression. Baseline and 24-month levels of monocyte chemotactic protein-1-to-creatinine ratio levels were higher for cases versus controls. The highest quartile of baseline monocyte chemotactic protein-1-to-creatinine ratio had fivefold greater odds, and each log increment had 2.27-fold higher odds for outcome (odds ratio, 5.27; 95% confidence interval, 2.19 to 12.71 and odds ratio, 2.27; 95% confidence interval, 1.44 to 3.58, respectively). IL-18-to-creatinine ratio, kidney injury molecule-1-to-creatinine ratio, and YKL-40-to-creatinine ratio were not consistently associated with outcome. C statistic for traditional predictors of eGFR decline was 0.70, which improved significantly to 0.74 with monocyte chemotactic protein-1-to-creatinine ratio. Urinary monocyte chemotactic protein-1-to-creatinine ratio concentrations were strongly associated with sustained renal decline in patients with type 2 diabetes with preserved renal function. Copyright © 2016 by the American Society of Nephrology.

Preservation of renal function in atypical hemolytic uremic syndrome by eculizumab: a case report.

PubMed

Giordano, Mario; Castellano, Giuseppe; Messina, Giovanni; Divella, Claretta; Bellantuono, Rosa; Puteo, Flora; Colella, Vincenzo; Depalo, Tommaso; Gesualdo, Loreto

2012-11-01

Genetic mutations in complement components are associated with the development of atypical hemolytic uremic syndrome (aHUS), a rare disease with high morbidity rate triggered by infections or unidentified factors. The uncontrolled activation of the alternative pathway of complement results in systemic endothelial damage leading to progressive development of renal failure. A previously healthy 8-month-old boy was referred to our hospital because of onset of fever, vomiting, and a single episode of nonbloody diarrhea. Acute kidney injury with preserved diuresis, hemolytic anemia, and thrombocytopenia were detected, and common protocols for management of HUS were followed without considerable improvement. The persistent low levels of complement component C3 led us to hypothesize the occurrence of aHUS. In fact, the child carried a specific mutation in complement factor H (Cfh; nonsense mutation in 3514G>T, serum levels of Cfh 138 mg/L, normal range 350-750). Given the lack of response to therapy and the occurrence of kidney failure requiring dialysis, we used eculizumab as rescue therapy, a monoclonal humanized antibody against the complement component C5. One week from the first administration, we observed a significant improvement of all clinical and laboratory parameters with complete recovery from hemodialysis, even in the presence of systemic infections. Our case report shows that complement inhibiting treatment allows the preservation of renal function and avoids disease relapses during systemic infections.

Soy protein preserves basement membrane integrity through a synergistic effect on nephrin, matrix metalloproteinase and vascular endothelial growth factor.

PubMed

Palanisamy, Nallasamy; Anuradha, Carani Venkataraman

2011-01-01

Soy protein improves renal function and prevents albuminuria in diabetic rats. This study investigates whether the renoprotective effect of soy protein is related to sustenance of basement membrane integrity. Adult male albino rats were randomized into four groups and fed one of the following semi-synthetic diets consisting of corn starch (60%) and casein (20%; CCD), fructose (60%) and casein (20%; FCD), fructose (60%) and soy protein (20%; FSD), or corn starch (60%) and soy protein (20%; CSD). Plasma chemistry and renal changes were analyzed after 60 days. FCD rats displayed metabolic derangements and renal ultrastructural changes. FSD rats showed reduction in type IV collagen, tissue inhibitor for matrix metallo-proteinase-2, vascular endothelial growth factor and tumor necrosis factor-α expression and improved matrix metallo-proteinase expression. Renal architecture was preserved in these rats. Soy protein supplementation not only improved insulin sensitivity but also markedly attenuated renal basement membrane changes in fructose diet-fed rats. These findings provide evidence in support of the use of dietary soy protein in patients with diabetic kidney disease. Copyright © 2011 S. Karger AG, Basel.

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.

Medical therapy is best for atherosclerotic renal artery stenosis: Arguments for.

PubMed

Annigeri, R A

2012-01-01

Atherosclerotic renal artery stenosis (ARAS) is a common condition that causes hypertension and reduction in the glomerular filtration rate and is an independent risk factor for death. Despite high technical success, the clinical benefit of renal artery (RA) angioplasty with stenting in ARAS remains doubtful. The published randomized clinical trials provide no support for the notion that renal angioplasty with stenting significantly improves blood pressure, preserves renal function, or reduces episodes of congestive heart failure in patients with ARAS. RA stenting is associated with procedure-related morbidity and mortality. Agents to block the renin-angiotensin-aldosterone system improve outcome and should be a part of a multifaceted medical regimen in ARAS. Medical therapy effectively controls atherosclerotic renovascular disease at all levels of vasculature and hence is the best therapy for ARAS.

Renal artery embolization in a child with delayed hemodynamic instability from penetrating knife wound.

PubMed

Barras, M; Pearson, E; Cousin, I; Le Rouzic, C; Thepaut, M; Gentric, J-C; Roue, J-M; Yevich, S; de Vries, P

2018-06-14

Penetrating laceration injury in the pediatric population may present as an acute or delayed life-threatening injury. Although emergent intra-arterial embolization is commonly utilized in adults, few cases have been reported for children. Surgical treatment for severe renal laceration injuries may require complete nephrectomy; an unfortunate outcome for a pediatric patient if a renal-preserving alternative is feasible. We present a case of penetrating renal laceration in a 10-year-old boy treated with intra-arterial embolization of the lacerated dominant renal artery and subsequent renal perfusion by an uninjured accessory renal artery allowing for renal preservation. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Primary hyperoxaluria type 1 with a novel mutation.

PubMed

Sethi, Sidharth Kumar; Waterham, Hans R; Sharma, Sonika; Sharma, Alok; Hari, Pankaj; Bagga, Arvind

2009-02-01

Primary hyperoxaluria type 1 [PH1] is an autosomal recessive disorder caused by a deficiency of alanine-glyoxylate aminotransferase AGT, which is encoded by the AGXT gene. We report an Indian family with two affected siblings having a novel mutation in the AGXT gene inherited from the parents. The index case progressed to end stage renal disease at 5 months of age. His 4 month old sibling is presently under follow up with preserved renal function.

Case Report-Inguinoscrotal ureteral hernia diagnosed on micturating cystourethrography.

PubMed

Sripathi, Smiti; Rajagopal, Kv; Kakkar, Chandan; Polnaya, Ashwin

2011-07-01

The presence of a ureter within an inguinal hernia is an extremely rare entity, usually discovered incidentally during herniorrhaphy and may pose a surgical risk. Early preoperative diagnosis is crucial to guide proper surgical approach and to preserve renal function.

Hypothermic machine perfusion in kidney transplantation.

PubMed

De Deken, Julie; Kocabayoglu, Peri; Moers, Cyril

2016-06-01

This article summarizes novel developments in hypothermic machine perfusion (HMP) as an organ preservation modality for kidneys recovered from deceased donors. HMP has undergone a renaissance in recent years. This renewed interest has arisen parallel to a shift in paradigms; not only optimal preservation of an often marginal quality graft is required, but also improved graft function and tools to predict the latter are expected from HMP. The focus of attention in this field is currently drawn to the protection of endothelial integrity by means of additives to the perfusion solution, improvement of the HMP solution, choice of temperature, duration of perfusion, and machine settings. HMP may offer the opportunity to assess aspects of graft viability before transplantation, which can potentially aid preselection of grafts based on characteristics such as perfusate biomarkers, as well as measurement of machine perfusion dynamics parameters. HMP has proven to be beneficial as a kidney preservation method for all types of renal grafts, most notably those retrieved from extended criteria donors. Large numbers of variables during HMP, such as duration, machine settings and additives to the perfusion solution are currently being investigated to improve renal function and graft survival. In addition, the search for biomarkers has become a focus of attention to predict graft function posttransplant.

The effect of prolonged of warm ischaemic injury on renal function in an experimental ex vivo normothermic perfusion system.

PubMed

Hosgood, Sarah A; Shah, K; Patel, M; Nicholson, M L

2015-06-30

Donation after circulatory death (DCD) kidney transplants inevitably sustain a degree of warm ischaemic injury, which is manifested clinically as delayed graft function. The aim of this study was to define the effects of prolonged periods of warm ischaemic injury on renal function in a normothermic haemoperfused kidney model. Porcine kidneys were subjected to 15, 60, 90 (n = 6 per group) and 120 min (n = 4) of in situ warm ischaemia (WI) and then retrieved, flushed with cold preservation fluid and stored in ice for 2 h. Kidneys then underwent 3 h of normothermic reperfusion with a whole blood-based perfusate using an ex vivo circuit developed from clinical grade cardiopulmonary bypass technology. Creatinine clearance, urine output and fractional excretion of sodium deteriorated sequentially with increasing warm time. Renal function was severely compromised after 90 or 120 min of WI but haemodynamic, metabolic and histological parameters demonstrated the viability of kidneys subjected to prolonged warm ischaemia. Isolated kidney perfusion using a warm, oxygenated, red cell-based perfusate allows an accurate ex vivo assessment of the potential for recovery from warm ischaemic injury. Prolonged renal warm ischaemic injury caused a severe decrement in renal function but was not associated with tissue necrosis.

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

Geyskes, G.G.; Oei, H.Y.; Puylaert, C.B.

Radioisotope renography was performed in 21 patients with hypertension and unilateral renal artery stenosis with and without premedication with 25 mg of captopril, and the results were compared with the effect of percutaneous transluminal angioplasty on the blood pressure, assessed 6 weeks after angioplasty. Angioplasty caused a considerable decrease in blood pressure in 15 of the 21 patients. In 12 of these 15 patients, captopril induced changes in the time-activity curves of the affected kidney only, suggesting deterioration of the excretory function of that kidney, while the function of the contralateral kidney remained normal. After angioplasty the asymmetry in themore » time-activity curves diminished despite identical pretreatment with captopril. Such captopril-induced unilateral impairment of the renal function was not seen in the six patients with unilateral renal artery stenosis whose blood pressure did not change after percutaneous transluminal angioplasty or in 13 patients with hypertension and normal renal arteries. The functional impairment of the affected kidneys was characterized by a decrease of /sup 99m/Tc-diethylenetriamine pentaacetic acid uptake and a delay of /sup 131/I-hippurate excretion, while the /sup 131/I-hippurate uptake remained unaffected. These data are in agreement with a reduced glomerular filtration rate and diuresis during preservation of the renal blood flow, changes that can be expected after converting enzyme inhibition in a kidney with low perfusion and an active, renin-mediated autoregulation of the glomerular filtration rate. These data suggest that functional captopril-induced unilateral changes, shown by split renal function studies with noninvasive gamma camera scintigraphy, can be used as a diagnostic test for renovascular hypertension caused by unilateral renal artery stenosis.« less

Renal function following xenon anesthesia for partial nephrectomy-An explorative analysis of a randomized controlled study.

PubMed

Stevanovic, Ana; Schaefer, Patrick; Coburn, Mark; Rossaint, Rolf; Stoppe, Christian; Boor, Peter; Pfister, David; Heidenreich, Axel; Christ, Hildegard; Hellmich, Martin; Fahlenkamp, Astrid V

2017-01-01

Perioperative preservation of renal function has a significant impact on morbidity and mortality in kidney surgery. Nephroprotective effects of the anesthetic xenon on ischemia-reperfusion injury were found in several experimental studies. We aimed to explore whether xenon anesthesia can reduce renal damage in humans undergoing partial nephrectomy and to gather pilot data of possible nephroprotection in these patients. A prospective randomized, single-blinded, controlled study. Single-center, University Hospital of Aachen, Germany between July 2013-October 2015. Forty-six patients with regular renal function undergoing partial nephrectomy. Patients were randomly assigned to receive xenon- (n = 23) or isoflurane (n = 23) anesthesia. Primary outcome was the maximum postoperative glomerular filtration rate (GFR) decline within seven days after surgery. Secondary outcomes included intraoperative and tumor-related data, assessment of further kidney injury markers, adverse events and optional determination of renal function after 3-6 months. Unexpected radical nephrectomy was performed in 5 patients, thus they were excluded from the per-protocol analysis, but included in the intention-to-treat analysis. The maximum postoperative GFR decline was attenuated by 45% in the xenon-group (10.9 ml min-1 1.73 cm-2 versus 19.7 ml min-1 1.73 cm-2 in the isoflurane group), but without significance (P = 0.084). Occurrence of adverse events was reduced (P = 0.003) in the xenon group. Renal function was similar among the groups after 3-6 months. Xenon anesthesia was feasible and safe in patients undergoing partial nephrectomy with regard to postoperative renal function. We found no significant effect on early renal function but less adverse events in the xenon group. Larger randomized controlled studies in more heterogeneous collectives are required, to confirm or refute the possible clinical benefit on renal function by xenon. ClinicalTrials.gov NCT01839084 and EudraCT 2012-005698-30.

Uromodulin: a new biomarker of fetal renal function?

PubMed

Botelho, Thais Emanuelle Faria; Pereira, Alamanda Kfoury; Teixeira, Patrícia Gonçalves; Lage, Eura Martins; Osanan, Gabriel Costa; Silva, Ana Cristina Simões E

2016-12-01

Obstructive uropathies are main diseases affecting the fetus. Early diagnosis allows to establish the appropriate therapy to minimize the risk of damage to kidney function at birth. Biochemical markers have been used to predict the prognosis of renal function in fetuses. Uromodulin, also known by Tamm-Horsfall protein (THP) is exclusively produced in the kidneys and in normal conditions is the protein excreted in larger amounts in human urine. It plays important roles in kidneys and urinary tract. Also it participates in ion transport processes, interact with various components of the immune system and has a role in defense against urinary tract infections. Moreover, this protein was proved to be a good marker of renal function in adult patients with several renal diseases. To evaluate if uromodulin is produced and eliminated by the kidneys during fetal life by analyzing fetal urine and amniotic fluid and to establish correlation with biochemical parameter of renal function already used in Fetal Medicine Center at the Clinic Hospital of UFMG (CEMEFE/HC). Between 2013 and 2015, were selected 29 fetuses with indication of invasive tests for fetal diagnosis in monitoring at the CEMEFE/HC. The determination of uromodulin was possible and measurable in all samples and showed statistically significant correlation with the osmolarity. There was a tendency of lower levels of Uromodulin values in fetuses with severe renal impairment prenatally. Thus, high levels of this protein in fetal amniotic fluid or fetal urine dosages possibly mean kidney function preserved.

Case Report-Inguinoscrotal ureteral hernia diagnosed on micturating cystourethrography

PubMed Central

Sripathi, Smiti; Rajagopal, KV; Kakkar, Chandan; Polnaya, Ashwin

2011-01-01

The presence of a ureter within an inguinal hernia is an extremely rare entity, usually discovered incidentally during herniorrhaphy and may pose a surgical risk. Early preoperative diagnosis is crucial to guide proper surgical approach and to preserve renal function. PMID:22013295

Effectiveness of pure argon for renal transplant preservation in a preclinical pig model of heterotopic autotransplantation.

PubMed

Faure, Alice; Bruzzese, Laurie; Steinberg, Jean-Guillaume; Jammes, Yves; Torrents, Julia; Berdah, Stephane V; Garnier, Emmanuelle; Legris, Tristan; Loundou, Anderson; Chalopin, Matthieu; Magalon, Guy; Guieu, Regis; Fenouillet, Emmanuel; Lechevallier, Eric

2016-02-04

In kidney transplantation, the conditions of organ preservation following removal influence function recovery. Current static preservation procedures are generally based on immersion in a cold-storage solution used under atmospheric air (approximately 78 kPa N2, 21 kPa O2, 1 kPa Ar). Research on static cold-preservation solutions has stalled, and modifying the gas composition of the storage medium for improving preservation was considered. Organoprotective strategies successfully used noble gases and we addressed here the effects of argon and xenon on graft preservation in an established preclinical pig model of autotransplantation. The preservation solution Celsior saturated with pure argon (Argon-Celsior) or xenon (Xenon-Celsior) at atmospheric pressure was tested versus Celsior saturated with atmospheric air (Air-Celsior). The left kidney was removed, and Air-Celsior (n = 8 pigs), Argon-Celsior (n = 8) or Xenon-Celsior (n = 6) was used at 4 °C to flush and store the transplant for 30 h, a duration that induced ischemic injury in our model when Air-Celsior was used. Heterotopic autotransplantation and contralateral nephrectomy were performed. Animals were followed for 21 days. The use of Argon-Celsior vs. Air-Celsior: (1) improved function recovery as monitored via creatinine clearance, the fraction of excreted sodium and tubulopathy duration; (2) enabled diuresis recovery 2-3 days earlier; (3) improved survival (7/8 vs. 3/8 pigs survived at postoperative day-21); (4) decreased tubular necrosis, interstitial fibrosis, apoptosis and inflammation, and preserved tissue structures as observed after the natural death/euthanasia; (5) stimulated plasma antioxidant defences during the days following transplantation as shown by monitoring the "reduced ascorbic acid/thiobarbituric acid reactive substances" ratio and Hsp27 expression; (6) limited the inflammatory response as shown by expression of TNF-alpha, IL1-beta and IL6 as observed after the natural death/euthanasia. Conversely, Xenon-Celsior was detrimental, no animal surviving by day-8 in a context where functional recovery, renal tissue properties and the antioxidant and inflammation responses were significantly altered. Thus, the positive effects of argon were not attributable to the noble gases as a group. The saturation of Celsior with argon improved early functional recovery, graft quality and survival. Manipulating the gas composition of a preservation medium constitutes therefore a promising approach to improve preservation.

Recirculation zone length in renal artery is affected by flow spirality and renal-to-aorta flow ratio.

PubMed

Javadzadegan, Ashkan; Fulker, David; Barber, Tracie

2017-07-01

Haemodynamic perturbations such as flow recirculation zones play a key role in progression and development of renal artery stenosis, which typically originate at the aorta-renal bifurcation. The spiral nature of aortic blood flow, division of aortic blood flow in renal artery as well as the exercise conditions have been shown to alter the haemodynamics in both positive and negative ways. This study focuses on the combinative effects of spiral component of blood flow, renal-to-aorta flow ratio and the exercise conditions on the size and distribution of recirculation zones in renal branches using computational fluid dynamics technique. Our findings show that the recirculation length was longest when the renal-to-aorta flow ratio was smallest. Spiral flow and exercise conditions were found to be effective in reducing the recirculation length in particular in small renal-to-aorta flow ratios. These results support the hypothesis that in renal arteries with small flow ratios where a stenosis is already developed an artificially induced spiral flow within the aorta may decelerate the progression of stenosis and thereby help preserve kidney function.

Protection of ischemic preconditioning on renal neural function in rats with acute renal failure.

PubMed

Wu, Ming-Shiou; Chien, Chiang-Ting; Ma, Ming-Chieh; Chen, Chau-Fong

2009-11-30

We tested whether tolerance induced by ischemic preconditioning (IPC) in kidneys was related to renal nerves. Experimental acute renal failure (ARF) in a rat model was induced for 45 min of left renal arterial occlusion (RAO), followed by 6 or 24 h of reperfusion (ischemic reperfusion (I/R) group). The episode of IPC was four cycles of 4 min of RAO at 11 min intervals and then the I/R injury was treated as above (IPC-I/R group). After 6 h of reperfusion, polyuria was found in the I/R group associated with an enhancement of afferent renal nerve activity (ARNA) and a reflexive decrease in efferent renal nerve activity (ERNA). Changes in nerve responses were related with a reduction in neutral endopeptidase (NEP) activity and an increased release of substance P (SP). After 24 h of reperfusion, the I/R group showed oliguria which was associated with a lower ARNA, hyperactivity of ERNA and a nine-fold increase in SP release due to a further 52% loss in NEP activity. Prior IPC treatment did not affect the changed ischemia-induced excretory and nervous activity patterns during the first 6 h of reperfusion, but normalized both responses in the kidneys 24 h after ischemia. The IPC-mediated protection in oliguric ARF was related to the preservation of NEP activity to only 25% loss that caused an increase of SP amounts of only three-fold and a minor change in neurokinin 1 receptor (NK-1R) activities. Finally, both excretory and sensory responses in oliguric ARF after saline loading were significantly ameliorated by IPC. We conclude that IPC results in preservation of the renal sensory response in postischemic kidneys and has a beneficial effect on controlling efferent renal sympathetic nerve activity and excretion of solutes and water.

Zinc deficiency during growth: influence on renal function and morphology.

PubMed

Tomat, Analía Lorena; Costa, María Angeles; Girgulsky, Luciana Carolina; Veiras, Luciana; Weisstaub, Adriana Ruth; Inserra, Felipe; Balaszczuk, Ana María; Arranz, Cristina Teresa

2007-03-13

This study was designed to investigate the effects of moderate zinc deficiency during growth on renal morphology and function in adult life. Weaned male Wistar rats were divided into two groups and fed either a moderately zinc-deficient diet (zinc: 8 mg/kg, n=12) or a control diet (zinc: 30 mg/kg, n=12) for 60 days. We evaluated: renal parameters, NADPH-diaphorase and nitric oxide synthase activity in kidney, renal morphology and apoptotic cells in renal cortex. Zinc-deficient rats showed a decrease in glomerular filtration rate and no changes in sodium and potassium urinary excretion. Zinc deficiency decreased NADPH diaphorase activity in glomeruli and tubular segment of nephrons, and reduced activity of nitric oxide synthase in the renal medulla and cortex, showing that zinc plays an important role in preservation of the renal nitric oxide system. A reduction in nephron number, glomerular capillary area and number of glomerular nuclei in cortical and juxtamedullary areas was observed in zinc deficient kidneys. Sirius red staining and immunostaining for alpha-smooth muscle-actin and collagen III showed no signs of fibrosis in the renal cortex and medulla. An increase in the number of apoptotic cells in distal tubules and cortical collecting ducts neighboring glomeruli and, to a lesser extent, in the glomeruli was observed in zinc deficient rats. The major finding of our study is the emergence of moderate zinc deficiency during growth as a potential nutritional factor related to abnormalities in renal morphology and function that facilitates the development of cardiovascular and renal diseases in adult life.

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

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.

GPER Mediates Functional Endothelial Aging in Renal Arteries.

PubMed

Meyer, Matthias R; Rosemann, Thomas; Barton, Matthias; Prossnitz, Eric R

2017-01-01

Aging is associated with impaired renal artery function, which is partly characterized by arterial stiffening and a reduced vasodilatory capacity due to excessive generation of reactive oxygen species by NADPH oxidases (Nox). The abundance and activity of Nox depends on basal activity of the heptahelical transmembrane receptor GPER; however, whether GPER contributes to age-dependent functional changes in renal arteries is unknown. This study investigated the effect of aging and Nox activity on renal artery tone in wild-type and GPER-deficient (Gper-/-) mice (4 and 24 months old). In wild-type mice, aging markedly impaired endothelium-dependent, nitric oxide (NO)-mediated relaxations to acetylcholine, which were largely preserved in renal arteries of aged Gper-/- mice. The Nox inhibitor gp91ds-tat abolished this difference by greatly enhancing relaxations in wild-type mice, while having no effect in Gper-/- mice. Contractions to angiotensin II and phenylephrine in wild-type mice were partly sensitive to gp91ds-tat but unaffected by aging. Again, deletion of GPER abolished effects of Nox inhibition on contractile responses. In conclusion, basal activity of GPER is required for the age-dependent impairment of endothelium-dependent, NO-mediated relaxation in the renal artery. Restoration of relaxation by a Nox inhibitor in aged wild-type but not Gper-/- mice strongly supports a role for Nox-derived reactive oxygen species as the underlying cause. Pharmacological blockers of GPER signaling may thus be suitable to inhibit functional endothelial aging of renal arteries by reducing Nox-derived oxidative stress and, possibly, the associated age-dependent deterioration of kidney function. © 2017 S. Karger AG, Basel.

Treatment of AA amyloidosis in rheumatoid arthritis.

PubMed

Balakrishnan, C; Sule, A; Mittal, G; Gaitonde, S; Pathan, E; Rajadhyaksha, S; Deshpande, R B; Gurmeet, M; Samant, R; Joshi, V R

2002-07-01

Four patients of rheumatoid arthritis (RA) with biopsy confirmed AA amyloidosis were treated with chlorambucil. All had established but uncontrolled RA with a persistently raised ESR. Moderate (> 1 gm, < 3.5 gm/d) to nephrotic range (> 3.5 gm/d) proteinuria and a relatively well preserved renal function was noted in three patients. One patient had deranged renal function and required dialysis. On chlorambucil, there was complete recovery, partial improvement and no improvement in one patient each. The fourth patient required haemodialysis, did not tolerate chlorambucil and succumbed to the illness. Therapy with chlorambucil can benefit some patients of RA with AA amyloidosis. Leucopenia is the most important dose limiting side effect.

Implications of renal artery anatomy for endovascular repair using fenestrated, branched, or parallel stent graft techniques.

PubMed

Mendes, Bernardo C; Oderich, Gustavo S; Reis de Souza, Leonardo; Banga, Peter; Macedo, Thanila A; DeMartino, Randall R; Misra, Sanjay; Gloviczki, Peter

2016-05-01

This study evaluated renal artery (RA) and accessory renal artery (ARA) anatomy and implications for endovascular repair using fenestrated, branched, or parallel (chimney, snorkel, and periscope) stent graft techniques. We analyzed the digital computed tomography angiograms of 520 consecutive patients treated by open or fenestrated endovascular repair for complex abdominal aortic aneurysms (2000-2012). RA/ARA anatomy was assessed using diameter, length, angles, and kidney perfusion based on analysis of estimated volumetric kidney parenchyma. Endovascular suitability was determined by RA diameter ≥4 mm, length to RA bifurcation ≥13 mm, and preservation of >75% of a single kidney or >60% of two kidneys by volumetric kidney parenchyma analysis. There were 222 juxtarenal (43%), 241 suprarenal (46%), and 57 type IV thoracoabdominal aortic aneurysms (11%), Analysis of 1009 RAs and 177 ARAs showed endovascular incorporation was possible in 884 RAs (88%) and 30 ARAs (17%) using the proposed criteria. One or more factors rendered RA incorporation unsuitable in 97 patients (19%), including early bifurcation in 45 (9%), small diameter in 28 (5%), or inability to preserve kidney parenchyma in 28 (5%). Other anatomic issues were present in 170 patients (33%) that would increase technical difficulty to RA incorporation using transfemoral access, including excessive downward angulation in 125 (24%), high-grade stenosis in 51 (10%), or prior renal stents in 11 (2%). Independent of the endovascular technique that is selected to treat a complex abdominal aortic aneurysm, one of five patients has anatomic limitations to endovascular incorporation. In these patients, open repair may provide the best alterative to maximize RA patency and preserve renal function. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

The possibility of renal function recovery in chronic hemodialysis patients should not be overlooked: Single center experience.

PubMed

Letachowicz, Krzysztof; Madziarska, Katarzyna; Letachowicz, Waldemar; Krajewska, Magdalena; Penar, Józef; Kusztal, Mariusz; Gołębiowski, Tomasz; Weyde, Wacław; Klinger, Marian

2016-04-01

Chronic hemodialysis is implemented when irreversible loss of kidney function occurs. Sometimes renal recovery is overlooked. From January 2005 to December 2014, we identified 28 patients hemodialyzed for more than 3 months who had renal replacement therapy discontinued. The group consisted of 17 (57.7%) males and 11 (42.3%) females. Patients were 18-87 years old. Time of hemodialysis ranged from 3 to 97 months. Of note, 14 (50%) patients were referred from local dialysis units for solution of vascular access problems. In 13 (46.2%) patients dialysis was abandoned within the first 6 months, in 5 (17.8%) patients between 6 and 12 months, and in 10 (35.7%) patients beyond 12 months. Estimated dialysis-free survival was 94.4% (SE 0.054) and 82% (SE 0.095) at 12 and 24 months, respectively. All physicians must be aware of possible kidney function improvement. In patients with preserved diuresis fall in periodical urea or creatinine measurements might be a sign of renal recovery. © 2015 International Society for Hemodialysis.

The kidney in congestive heart failure: 'are natriuresis, sodium, and diuretics really the good, the bad and the ugly?'.

PubMed

Verbrugge, Frederik H; Dupont, Matthias; Steels, Paul; Grieten, Lars; Swennen, Quirine; Tang, W H Wilson; Mullens, Wilfried

2014-02-01

This review discusses renal sodium handling in heart failure. Increased sodium avidity and tendency to extracellular volume overload, i.e. congestion, are hallmark features of the heart failure syndrome. Particularly in the case of concomitant renal dysfunction, the kidneys often fail to elicit potent natriuresis. Yet, assessment of renal function is generally performed by measuring serum creatinine, which has inherent limitations as a biomarker for the glomerular filtration rate (GFR). Moreover, glomerular filtration only represents part of the nephron's function. Alterations in the fractional reabsorptive rate of sodium are at least equally important in emerging therapy-refractory congestion. Indeed, renal blood flow decreases before the GFR is affected in congestive heart failure. The resulting increased filtration fraction changes Starling forces in peritubular capillaries, which drive sodium reabsorption in the proximal tubules. Congestion further stimulates this process by augmenting renal lymph flow. Consequently, fractional sodium reabsorption in the proximal tubules is significantly increased, limiting sodium delivery to the distal nephron. Orthosympathetic activation probably plays a pivotal role in those deranged intrarenal haemodynamics, which ultimately enhance diuretic resistance, stimulate neurohumoral activation with aldosterone breakthrough, and compromise the counter-regulatory function of natriuretic peptides. Recent evidence even suggests that intrinsic renal derangements might impair natriuresis early on, before clinical congestion or neurohumoral activation are evident. This represents a paradigm shift in heart failure pathophysiology, as it suggests that renal dysfunction-although not by conventional GFR measurements-is driving disease progression. In this respect, a better understanding of renal sodium handling in congestive heart failure is crucial to achieve more tailored decongestive therapy, while preserving renal function. © 2013 The Authors. European Journal of Heart Failure © 2013 European Society of Cardiology.

Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial.

PubMed

Chen, Horng H; Anstrom, Kevin J; Givertz, Michael M; Stevenson, Lynne W; Semigran, Marc J; Goldsmith, Steven R; Bart, Bradley A; Bull, David A; Stehlik, Josef; LeWinter, Martin M; Konstam, Marvin A; Huggins, Gordon S; Rouleau, Jean L; O'Meara, Eileen; Tang, W H Wilson; Starling, Randall C; Butler, Javed; Deswal, Anita; Felker, G Michael; O'Connor, Christopher M; Bonita, Raphael E; Margulies, Kenneth B; Cappola, Thomas P; Ofili, Elizabeth O; Mann, Douglas L; Dávila-Román, Víctor G; McNulty, Steven E; Borlaug, Barry A; Velazquez, Eric J; Lee, Kerry L; Shah, Monica R; Hernandez, Adrian F; Braunwald, Eugene; Redfield, Margaret M

2013-12-18

Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested. To test the 2 independent hypotheses that, compared with placebo, addition of low-dose dopamine (2 μg/kg/min) or low-dose nesiritide (0.005 μg/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction. Multicenter, double-blind, placebo-controlled clinical trial (Renal Optimization Strategies Evaluation [ROSE]) of 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73 m2), randomized within 24 hours of admission. Enrollment occurred from September 2010 to March 2013 across 26 sites in North America. Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategy. Within each strategy, participants were randomized in a double-blind, 2:1 ratio to active treatment or placebo. The dopamine (n = 122) and nesiritide (n = 119) groups were independently compared with the pooled placebo group (n = 119). Coprimary end points included 72-hour cumulative urine volume (decongestion end point) and the change in serum cystatin C from enrollment to 72 hours (renal function end point). Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95% CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830 ; difference, 229 mL; 95% CI, -714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, 0.01; 95% CI, -0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95% CI, 8014-9134 vs placebo, 8296 mL; 95% CI, 7762-8830; difference, 279 mL; 95% CI, -618 to 1176 mL; P = .49) or on the change in cystatin C level (nesiritide, 0.07 mg/L; 95% CI, 0.01-0.13 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, -0.04; 95% CI, -0.13 to 0.05; P = .36). Compared with placebo, there was no effect of low-dose dopamine or nesiritide on secondary end points reflective of decongestion, renal function, or clinical outcomes. In participants with acute heart failure and renal dysfunction, neither low-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy. clinicaltrials.gov Identifier: NCT01132846.

Hemoadsorption in a Case of Severe Septic Shock and Necrotizing Fasciitis Caused by Nontraumatic Renal Rupture due to Pyelonephritis with Obstructive Uropathy.

PubMed

Kousoulas, Lampros; Wittel, Uwe; Fichtner-Feigl, Stefan; Utzolino, Stefan

2018-01-01

Nontraumatic renal rupture due to pyelonephritis with obstructive uropathy is an uncommon but life-threatening situation. A 25-year-old female presented to the emergency department with acute worsening of abdominal pain that began four weeks earlier. She was found to have peritonitis, leukocytosis, severe lactic acidosis, and a pronounced anemia and imaging was consistent with nontraumatic renal rupture with retroperitoneal abscess, perforation of the colon, and severe necrotizing fasciitis of the right lower limb. She underwent a right nephrectomy, a right hemicolectomy, surgical debridement of the retroperitoneum, and an upper thigh amputation. Due to severe septic shock and rhabdomyolysis with acute renal failure we performed a combined treatment of hemoadsorption using a Cytosorb hemoadsorber and continuous venovenous hemodialysis (CVVHD). Subsequently the patient recovered and was discharged home with no signs of infections and with normal renal function. We present a case of pyelonephritis with nontraumatic renal rupture leading to necrotizing fasciitis with osteomyelitis of the lower limb. The early treatment of the patient with a Cytosorb hemoadsorber led to a rapid hemodynamic and metabolic stabilization and preservation of the renal function, suggesting that hemoadsorption might be a rescue therapy in patients with severe septic shock and traumatic rhabdomyolysis.

Hemoadsorption in a Case of Severe Septic Shock and Necrotizing Fasciitis Caused by Nontraumatic Renal Rupture due to Pyelonephritis with Obstructive Uropathy

PubMed Central

Wittel, Uwe; Fichtner-Feigl, Stefan; Utzolino, Stefan

2018-01-01

Background Nontraumatic renal rupture due to pyelonephritis with obstructive uropathy is an uncommon but life-threatening situation. Case Presentation A 25-year-old female presented to the emergency department with acute worsening of abdominal pain that began four weeks earlier. She was found to have peritonitis, leukocytosis, severe lactic acidosis, and a pronounced anemia and imaging was consistent with nontraumatic renal rupture with retroperitoneal abscess, perforation of the colon, and severe necrotizing fasciitis of the right lower limb. She underwent a right nephrectomy, a right hemicolectomy, surgical debridement of the retroperitoneum, and an upper thigh amputation. Due to severe septic shock and rhabdomyolysis with acute renal failure we performed a combined treatment of hemoadsorption using a Cytosorb hemoadsorber and continuous venovenous hemodialysis (CVVHD). Subsequently the patient recovered and was discharged home with no signs of infections and with normal renal function. Conclusion We present a case of pyelonephritis with nontraumatic renal rupture leading to necrotizing fasciitis with osteomyelitis of the lower limb. The early treatment of the patient with a Cytosorb hemoadsorber led to a rapid hemodynamic and metabolic stabilization and preservation of the renal function, suggesting that hemoadsorption might be a rescue therapy in patients with severe septic shock and traumatic rhabdomyolysis. PMID:29854478

Supplemental arginine vasopressin during the resuscitation of severe hemorrhagic shock preserves renal mitochondrial function

PubMed Central

Yuxia, Guan; Singh, Khushboo; Reilly, Patrick M.

2017-01-01

Arginine vasopressin (AVP), a hormone secreted by the posterior pituitary, plays a vital role in maintaining vasomotor tone during acute blood loss. We hypothesized that decompensated hemorrhagic shock is associated with decreased AVP stores and supplementation during resuscitation would improve both blood pressure and renal function. Using a decompensated hemorrhagic shock model, male Long-Evans rats were bled to mean arterial blood pressure (MAP) of 40mmHg and maintained until the MAP could not be sustained without fluid. Once 40% of the shed volume was returned in lactated Ringer’s (Severe Shock), animals were resuscitated over 60 minutes with 4x the shed volume in lactated Ringer’s (LR) or the same fluids with AVP (0.5 units/kg+ 0.03 units/kg/min). Animals (n = 6-9/group) were sacrificed before hemorrhage (Sham), at Severe Shock, following resuscitation (60R, 60R with AVP) or 18 hours post-resuscitation (18hr, 18hr with AVP). Blood samples were taken to measure AVP levels and renal function. Pituitaries were harvested and assayed for AVP. Kidney samples were taken to assess mitochondrial function, histology, and oxidative damage. Baseline pituitary AVP stores (30,364 ± 5311 pg/mg) decreased with severe shock and were significantly depressed post-resuscitation (13,910 ± 3016 pg/ml. p<0.05) and at 18hr (15,592 ±1169 pg/ml, p<0.05). Resuscitation with LR+AVP led to higher serum AVP levels at 60R (31±8 vs 79±12; p<0.01) with an improved MAP both at 60R (125±3 vs 77±7mmHg; p<0.01) and 18hr (82±6 vs 69±5mmHg;p<0.05). AVP supplementation preserved complex I respiratory capacity at 60R and both complex I and II function at 18hr (p<0.05). AVP was also associated with decreased reactive oxygen species at 60R (856±67 vs 622±48F RFU) and significantly decreased oxidative damage as measured by mitochondrial lipid peroxidation (0.9±0.1 vs 1.7±0.1 fold change, p<0.01) and nitrosylation (0.9±0.1 vs 1.4±0.2 fold change, p<0.05). With AVP, renal damage was mitigated at 60R and histologic architecture was conserved at 18 hours. In conclusion, pituitary and serum AVP levels decrease during severe hemorrhage and may contribute to the development of decompensated hemorrhagic shock. Supplementing exogenous AVP during resuscitation improves blood pressure, preserves renal mitochondrial function, and mitigates acute kidney injury. PMID:29065123

Antiproteinuric effect of pirfenidone in a rat model of anti-glomerular basement membrane glomerulonephritis.

PubMed

Takakura, Koji; Mizukami, Kazuhiko; Mitori, Hikaru; Noto, Takahisa; Tomura, Yuichi

2014-08-15

While pirfenidone has been established as an effective anti-fibrosis remedy, whether or not its antifibrotic effect contributes to a reduction of proteinuria remains unclear. We investigated the renoprotective properties of pirfenidone in an anti-glomerular basement membrane (GBM) glomerulonephritis model both prophylactically and therapeutically to determine its profile against proteinuria. In the prophylactic regimen, pirfenidone was treated immediately after anti-serum injection. We observed a significant reduction in the progression of proteinuria (P<0.05) and decline in renal function (P<0.01) and also noted histological improvement in renal injury. These effects appeared to be due to the maintained expression of nephrin and podocin on podocytes as well as the reduced expression of profibrotic factors like transforming growth factor-β (TGF-β). The expression of nephrin mRNA was strongly negatively correlated with the amount of urinary protein excretion (R=-0.84, P<0.001), implicating podocyte damage in the outcome of proteinuria (R(2)=0.70). These results suggest that preservation of podocytes with the pirfenidone treatment may have resulted in the decrease of proteinuria. In contrast, when the therapeutic regimen was initiated 2 weeks after nephritis induction, pirfenidone had little effect on the progression of proteinuria, although the decline of renal function and fibrosis were suppressed. Taken together, present findings suggested that pirfenidone prevented the progression of proteinuria only when administered prophylactically but was still able to ameliorate the decline of renal function independent of proteinuria. In conclusion, pirfenidone as a prophylactic regimen reduces proteinuria in anti-GBM nephritis via preservation of podocytes with markedly reduced efficacy when administered as a therapeutic regimen. Copyright © 2014 Elsevier B.V. All rights reserved.

Retzius Space Preservation Technique for Robotic-Assisted Laparoscopic Radical Prostatectomy in a Kidney Transplant Patient: First Case in Thailand and Our First Experience.

PubMed

Jenjitranant, P; Sangkum, P; Sirisreetreerux, P; Viseshsindh, W; Patcharatrakul, S; Kongcharoensombat, W

2016-11-01

The aim of this work was to report our experience in robotic-assisted laparoscopic radical prostatectomy for the treatment of localized prostate cancer in a kidney transplant recipient. A 73-year-old man with chronic renal failure underwent living-donor kidney transplantation (KT) in 1993. His baseline creatinine after KT was ∼1.2 mg/dL. He developed lower urinary tract symptoms in 1999. He was diagnosed with benign prostatic hyperplasia and treated accordingly. He was followed regularly with the use of digital rectal examination and measurement of serum prostatic-specific antigen (PSA). In 2014, his serum PSA was 11.53 ng/mL. Prostate biopsy was done and revealed localized prostatic adenocarcinoma with a Gleason score of 7 (3+4). We performed robotic-assisted laparoscopic radical prostatectomy with the use of the Retzius space preservation technique. The patient underwent successful robotic-assisted laparoscopic radical prostatectomy without any complications. The operative time was 210 minutes with estimated blood loss of 250 mL. The patient tolerated the procedure well and was discharged on the 6th day after surgery with a retained Foley catheter. A cystogram was done on the 13th day after surgery and showed no urethrovesical anastomosis leakage. After Foley catheter removal, the patient could urinate normally without urinary incontinence. Pathologic analysis revealed positive surgical margin with no extraprostatic extension and no seminal vesical invasion. One month after the operation, PSA was 0.08 ng/mL and renal function remained stable. Robotic-assisted laparoscopic radical prostatectomy is technically feasible and safe for the treatment of localized prostate cancer in the renal transplant patient. The Retzius space preservation technique is helpful in minimizing the manipulation of transplanted kidney and urinary bladder during the operation, resulting in favorable postoperative renal function and continence outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

zVAD-fmk prevents cisplatin-induced cleavage of autophagy proteins but impairs autophagic flux and worsens renal function

PubMed Central

Herzog, Christian; Yang, Cheng; Holmes, Alexandrea

2012-01-01

Cisplatin injury to renal tubular epithelial cells (RTEC) is accompanied by autophagy and caspase activation. However, autophagy gradually decreases during the course of cisplatin injury. The role of autophagy and the mechanism of its decrease during cisplatin injury are not well understood. This study demonstrated that autophagy proteins beclin-1, Atg5, and Atg12 were cleaved and degraded during the course of cisplatin injury in RTEC and the kidney. zVAD-fmk, a widely used pancaspase inhibitor, blocked cleavage of autophagy proteins suggesting that zVAD-fmk would promote the autophagy pathway. Unexpectedly, zVAD-fmk blocked clearance of the autophagosomal cargo, indicating lysosomal dysfunction. zVAD-fmk markedly inhibited cisplatin-induced lysosomal cathepsin B and calpain activities and therefore impaired autophagic flux. In a mouse model of cisplatin nephrotoxicity, zVAD-fmk impaired autophagic flux by blocking autophagosomal clearance as revealed by accumulation of key autophagic substrates p62 and LC3-II. Furthermore, zVAD-fmk worsened cisplatin-induced renal dysfunction. Chloroquine, a lysomotropic agent that is known to impair autophagic flux, also exacerbated cisplatin-induced decline in renal function. These findings demonstrate that impaired autophagic flux induced by zVAD-fmk or a lysomotropic agent worsened renal function in cisplatin acute kidney injury (AKI) and support a protective role of autophagy in AKI. These studies also highlight that the widely used antiapoptotic agent zVAD-fmk may be contraindicated as a therapeutic agent for preserving renal function in AKI. PMID:22896037

Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes.

PubMed

Betz, Boris B; Jenks, Sara J; Cronshaw, Andrew D; Lamont, Douglas J; Cairns, Carolynn; Manning, Jonathan R; Goddard, Jane; Webb, David J; Mullins, John J; Hughes, Jeremy; McLachlan, Stela; Strachan, Mark W J; Price, Jackie F; Conway, Bryan R

2016-05-01

Many diabetic patients suffer from declining renal function without developing albuminuria. To identify alternative biomarkers for diabetic nephropathy (DN) we performed urinary peptidomic analysis in a rodent model in which hyperglycemia and hypertension synergize to promote renal pathologic changes consistent with human DN. We identified 297 increased and 15 decreased peptides in the urine of rats with DN compared with controls, including peptides derived from proteins associated with DN and novel candidate biomarkers. We confirmed by ELISA that one of the parent proteins, urinary epidermal growth factor (uEGF), was more than 2-fold reduced in rats with DN in comparison with controls. To assess the clinical utility of uEGF we examined renal outcomes in 642 participants from the Edinburgh Type 2 Diabetes Study who were normoalbuminuric and had preserved renal function at baseline. After adjustment for established renal risk factors, a lower uEGF to creatinine ratio was associated with new-onset estimated glomerular filtration rate less than 60 ml/min per 1.73m(2) (odds ratio 0.48; 95% confidence interval, 0.26-0.90), rapid (over 5% per annum) decline in renal function (odds ratio 0.44; 95% confidence interval, 0.27-0.72) or the composite of both outcomes (odds ratio 0.38; 95% confidence interval, 0.24-0.62). Thus, the utility of a low uEGF to creatinine ratio as a biomarker of progressive decline in renal function in normoalbuminuric patients should be assessed in additional populations. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Ex-vivo machine perfusion for kidney preservation.

PubMed

Hamar, Matyas; Selzner, Markus

2018-06-01

Machine perfusion is a novel strategy to decrease preservation injury, improve graft assessment, and increase organ acceptance for transplantation. This review summarizes the current advances in ex-vivo machine-based kidney preservation technologies over the last year. Ex-vivo perfusion technologies, such as hypothermic and normothermic machine perfusion and controlled oxygenated rewarming, have gained high interest in the field of organ preservation. Keeping kidney grafts functionally and metabolically active during the preservation period offers a unique chance for viability assessment, reconditioning, and organ repair. Normothermic ex-vivo kidney perfusion has been recently translated into clinical practice. Preclinical results suggest that prolonged warm perfusion appears superior than a brief end-ischemic reconditioning in terms of renal function and injury. An established standardized protocol for continuous warm perfusion is still not available for human grafts. Ex-vivo machine perfusion represents a superior organ preservation method over static cold storage. There is still an urgent need for the optimization of the perfusion fluid and machine technology and to identify the optimal indication in kidney transplantation. Recent research is focusing on graft assessment and therapeutic strategies.

[Clinical study on patients with renal-cell carcinoma accompanied with Von Hippel-Lindau disease treated with radiofrequency ablation].

PubMed

Nao, Tomoya; Shimamoto, Tsutomu; Karashima, Takashi; Kamei, Maiko; Fukuhara, Hideo; Fukata, Satoshi; Satake, Hirofumi; Ashida, Shingo; Yamasaki, Ichiro; Kamata, Masayuki; Inoue, Keiji; Yamanishi, Tomoaki; Ogawa, Yasuhiro; Ito, Satoshi; Shuin, Taro

2014-09-01

We report 12 renal cell carcinomas in 6 patients with Von Hippel-Lindau (VHL) disease treated with radiofrequency ablation (RFA). The mean age of the patients was 46 (range 38-53) years (male : 4, female : 2). Computed tomography (CT)-guided transcutaneous RFA was performed under conscious sedation with local anesthetics. The mean size of the tumors was 2.4 (range 0.7-8.1) cm. Nine of the 12 tumors (75%) were locally well controlled. However, 3 tumors in 2 patients developed visceral metastases after RFA. While minimal flank pain, nausea, perinephritic hematoma and lumbago were observed, there was no major complication during or after the procedure. The therapy with CT-guided transcutaneous RFA is efficient and minimal invasive for renal cell carcinoma in patients with VHL, leading to preservation of renal function.

Remission of proteinuria and preservation of renal function in patients with renal AA amyloidosis secondary to rheumatoid arthritis.

PubMed

Ueno, Toshiharu; Takeda, Kazuhito; Nagata, Michio

2012-02-01

Renal AA amyloidosis presents as a life-threatening disease in patients with rheumatoid arthritis (RA). Although several newly developed immunosuppressive drugs have been tried, patients often progress to end-stage renal failure with unsatisfactory survival rate. A total of nine consecutive cases of severe nephrotic renal AA amyloidosis presented to us. Complete remission of proteinuria was observed in four cases (responders), and the remaining five reached the end point of haemodialysis or death (non-responders); these groups were retrospectively compared. The patients were treated with immunosuppressants, biological drugs and anti-hypertensive drugs. Levels of serum creatinine (S-Cr), urinary protein-creatinine ratio (UP/UCr), blood pressure (BP) and C-reactive protein (CRP) were measured. Histological characteristics of renal amyloid deposition and extent of kidney injury were also scored. Prior to treatment, clinical data (S-Cr, UP/UCr, BP and CRP) and histological severity (glomerular sclerosis, tubulointerstitial injury and extent of amyloid deposition) observed in the renal biopsy specimen were not significantly different between the groups. Following therapeutic intervention, proteinuria disappeared (UP/UCr <0.3) in responders within 12 ± 5.4 months but persisted in non-responders. Consequently, renal function stabilized in responders, but it deteriorated in all non-responders. Strict inflammatory control along with optimal control of hypertension was achieved in responders during the treatment. Regardless of histological severity, intensive therapeutic intervention that includes strict inflammatory control and optimal control of hypertension may change the histology-predicted prognosis of RA-associated renal AA amyloidosis.

Oxidative Stress in Hypertension: Role of the Kidney

PubMed Central

Araujo, Magali

2014-01-01

Abstract Significance: Renal oxidative stress can be a cause, a consequence, or more often a potentiating factor for hypertension. Increased reactive oxygen species (ROS) in the kidney have been reported in multiple models of hypertension and related to renal vasoconstriction and alterations of renal function. Nicotinamide adenine dinucleotide phosphate oxidase is the central source of ROS in the hypertensive kidney, but a defective antioxidant system also can contribute. Recent Advances: Superoxide has been identified as the principal ROS implicated for vascular and tubular dysfunction, but hydrogen peroxide (H2O2) has been implicated in diminishing preglomerular vascular reactivity, and promoting medullary blood flow and pressure natriuresis in hypertensive animals. Critical Issues and Future Directions: Increased renal ROS have been implicated in renal vasoconstriction, renin release, activation of renal afferent nerves, augmented contraction, and myogenic responses of afferent arterioles, enhanced tubuloglomerular feedback, dysfunction of glomerular cells, and proteinuria. Inhibition of ROS with antioxidants, superoxide dismutase mimetics, or blockers of the renin-angiotensin-aldosterone system or genetic deletion of one of the components of the signaling cascade often attenuates or delays the onset of hypertension and preserves the renal structure and function. Novel approaches are required to dampen the renal oxidative stress pathways to reduced O2−• rather than H2O2 selectivity and/or to enhance the endogenous antioxidant pathways to susceptible subjects to prevent the development and renal-damaging effects of hypertension. Antioxid. Redox Signal. 20, 74–101. PMID:23472618

Biolasol: novel perfusion and preservation solution for kidneys.

PubMed

Cierpka, L; Ryszka, F; Dolińska, B; Smorąg, Z; Słomski, R; Wiaderkiewicz, R; Caban, A; Budziński, G; Oczkowicz, G; Wieczorek, J

2014-10-01

Biolasol solution (Pharmaceutical Research and Production Plant "Biochefa," Sosnowiec, Poland) is a novel extracellular perfusion and ex vivo hypothermic kidney preservation solution. It ensures maintenance of homeostasis, reduces tissue edema, has low viscosity, and allows the graft to preserve structural and functional integrity. It minimizes ischemia-reperfusion damage. Perfundates from control and transplanted kidneys flushed with Biolasol or ViaSpan solutions (Arkas, Warszawa, Poland) were analyzed. Parameters of serum and urine collected from 12 pigs after auto-transplantation were also analyzed. Renal medulla was investigated for structural alterations by analyzing hematoxylin and eosin-stained slides. The mean survival time of pigs after the auto-transplantation procedure was the measure for the novel Biolasol solution effectiveness. We observed a statistically significant decrease in marker enzyme levels alanine transaminase, aspartate transaminase, lactic dehydrogenase, and ions (Na and K) in pigs with grafts flushed with Biolasol. Histopathologic examination revealed that the renal cortex structure was not damaged after the use of Biolasol solution. Biolasol solution protects kidneys against ischemia damage and does not differ significantly from the "golden standard" ViaSpan solution.

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.

CDP-choline circumvents mercury-induced mitochondrial damage and renal dysfunction.

PubMed

Buelna-Chontal, Mabel; Franco, Martha; Hernández-Esquivel, Luz; Pavón, Natalia; Rodríguez-Zavala, José S; Correa, Francisco; Jasso, Ricardo; Pichardo-Ramos, Gregorio; Santamaría, José; González-Pacheco, Héctor; Soto, Virgilia; Díaz-Ruíz, Jorge L; Chávez, Edmundo

2017-12-01

Heavy metal ions are known to produce harmful alterations on kidney function. Specifically, the accumulation of Hg 2+ in kidney tissue may induce renal failure. In this work, the protective effect of CDP-choline against the deleterious effects induced by Hg 2+ on renal function was studied. CDP-choline administered ip at a dose of 125 mg/kg body weight prevented the damage induced by Hg 2+ administration at a dose of 3 mg/kg body weight. The findings indicate that CDP-choline guards mitochondria against Hg 2+ -toxicity by preserving their ability to retain matrix content, such as accumulated Ca 2+ . This nucleotide also protected mitochondria from Hg 2+ -induced loss of the transmembrane electric gradient and from the generation of hydrogen peroxide and membrane TBARS. In addition, CDP-choline avoided the oxidative damage of mtDNA and inhibited the release of the interleukins IL-1 and IL6, recognized as markers of acute inflammatory reaction. After the administration of Hg 2+ and CDP, CDP-choline maintained nearly normal levels of renal function and creatinine clearance, as well as blood urea nitrogen (BUN) and serum creatinine. © 2017 International Federation for Cell Biology.

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.

Early superoxide scavenging accelerates renal microvascular rarefaction and damage in the stenotic kidney.

PubMed

Kelsen, Silvia; He, Xiaochen; Chade, Alejandro R

2012-08-15

Renal artery stenosis (RAS), the main cause of chronic renovascular disease (RVD), is associated with significant oxidative stress. Chronic RVD induces renal injury partly by promoting renal microvascular (MV) damage and blunting MV repair in the stenotic kidney. We tested the hypothesis that superoxide anion plays a pivotal role in MV dysfunction, reduction of MV density, and progression of renal injury in the stenotic kidney. RAS was induced in 14 domestic pigs and observed for 6 wk. Seven RAS pigs were chronically treated with the superoxide dismutase mimetic tempol (RAS+T) to reduce oxidative stress. Single-kidney hemodynamics and function were quantified in vivo using multidetector computer tomography (CT) and renal MV density was quantified ex vivo using micro-CT. Expression of angiogenic, inflammatory, and apoptotic factors was measured in renal tissue, and renal apoptosis and fibrosis were quantified in tissue sections. The degree of RAS and blood pressure were similarly increased in RAS and RAS+T. Renal blood flow (RBF) and glomerular filtration rate (GFR) were reduced in the stenotic kidney (280.1 ± 36.8 and 34.2 ± 3.1 ml/min, P < 0.05 vs. control). RAS+T kidneys showed preserved GFR (58.5 ± 6.3 ml/min, P = not significant vs. control) but a similar decreases in RBF (293.6 ± 85.2 ml/min) and further decreases in MV density compared with RAS. These changes were accompanied by blunted angiogenic signaling and increased apoptosis and fibrosis in the stenotic kidney of RAS+T compared with RAS. The current study shows that tempol administration provided limited protection to the stenotic kidney. Despite preserved GFR, renal perfusion was not improved by tempol, and MV density was further reduced compared with untreated RAS, associated with increased renal apoptosis and fibrosis. These results suggest that a tight balance of the renal redox status is necessary for a normal MV repair response to injury, at least at the early stage of RVD, and raise caution regarding antioxidant strategies in RAS.

Early superoxide scavenging accelerates renal microvascular rarefaction and damage in the stenotic kidney

PubMed Central

Kelsen, Silvia; He, Xiaochen

2012-01-01

Renal artery stenosis (RAS), the main cause of chronic renovascular disease (RVD), is associated with significant oxidative stress. Chronic RVD induces renal injury partly by promoting renal microvascular (MV) damage and blunting MV repair in the stenotic kidney. We tested the hypothesis that superoxide anion plays a pivotal role in MV dysfunction, reduction of MV density, and progression of renal injury in the stenotic kidney. RAS was induced in 14 domestic pigs and observed for 6 wk. Seven RAS pigs were chronically treated with the superoxide dismutase mimetic tempol (RAS+T) to reduce oxidative stress. Single-kidney hemodynamics and function were quantified in vivo using multidetector computer tomography (CT) and renal MV density was quantified ex vivo using micro-CT. Expression of angiogenic, inflammatory, and apoptotic factors was measured in renal tissue, and renal apoptosis and fibrosis were quantified in tissue sections. The degree of RAS and blood pressure were similarly increased in RAS and RAS+T. Renal blood flow (RBF) and glomerular filtration rate (GFR) were reduced in the stenotic kidney (280.1 ± 36.8 and 34.2 ± 3.1 ml/min, P < 0.05 vs. control). RAS+T kidneys showed preserved GFR (58.5 ± 6.3 ml/min, P = not significant vs. control) but a similar decreases in RBF (293.6 ± 85.2 ml/min) and further decreases in MV density compared with RAS. These changes were accompanied by blunted angiogenic signaling and increased apoptosis and fibrosis in the stenotic kidney of RAS+T compared with RAS. The current study shows that tempol administration provided limited protection to the stenotic kidney. Despite preserved GFR, renal perfusion was not improved by tempol, and MV density was further reduced compared with untreated RAS, associated with increased renal apoptosis and fibrosis. These results suggest that a tight balance of the renal redox status is necessary for a normal MV repair response to injury, at least at the early stage of RVD, and raise caution regarding antioxidant strategies in RAS. PMID:22622460

Emphysematous pyelonephritis with calculus: Management strategies.

PubMed

Goel, Tanmaya; Reddy, Sreedhar; Thomas, Joseph

2007-07-01

Emphysematous pyelonephritis (EPN) with calculus is well recognized but with very few reports on its treatment. Our aim is to elucidate our experience in its successful management. Over four years, we diagnosed seven cases (eight renal units) of EPN, out of which two patients (three renal units) had EPN with urinary calculi. After the initial conservative management of EPN, the stones were tackled appropriately. EPN was initially managed effectively with antibiotics and supportive care. Once the patient was stable, the stones were cleared in a step-wise fashion. The associated postoperative complications were also tackled efficiently with preservation of renal function. In EPN with stones, nephrectomy is not the sole option available and they can be effectively managed with open / endoscopic measures.

Utility of the RENAL index -Radius; Exophytic/endophytic; Nearness to sinus; Anterior/posterior; Location relative to polar lines- in the management of renal masses.

PubMed

Konstantinidis, C; Trilla, E; Lorente, D; Morote, J

2016-12-01

The growing incidence of renal masses and the wide range of available treatments require predictive tools that support the decision making process. The RENAL index -Radius; Exophytic/endophytic; Nearness to sinus; Anterior/posterior; Location relative to polar lines- helps standardise the anatomy of a renal mass by differentiating 3 groups of complexity. Since the introduction of the index, there have been a growing number of studies, some of which have been conflicting, that have evaluated the clinical utility of its implementation. To analyse the scientific evidence on the relationship between the RENAL index and the main strategies for managing renal masses. A search was conducted in the Medline database, which found 576 references on the RENAL index. In keeping with the PRISM Declaration, we selected 100 abstracts and ultimately reviewed 96 articles. The RENAL index has a high degree of interobserver correlation and has been validated as a predictive nomogram of histological results. In active surveillance, the index has been related to the tumour growth rate and probability of nephrectomy. In ablative therapy, the index has been associated with therapeutic efficacy, complications and tumour recurrence. In partial nephrectomy, the index has been related to the rate of complications, conversion to radical surgery, ischaemia time, function preservation and tumour recurrence, a finding also observed in radical nephrectomy. The RENAL index is an objective, reproducible and useful system as a predictive tool of highly relevant clinical parameters such as the rate of complications, ischaemia time, renal function and oncological results in the various currently accepted treatments for the management of renal masses. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Renal cortical involvement in children with first UTI: does it differ in the presence of primary VUR?

PubMed

Aktaş, Gül Ege; Inanir, Sabahat; Turoğlu, Halil Turgut

2008-12-01

The aim of this study was to investigate the influence of vesicoureteral reflux (VUR) on dimercaptosuccinic acid (DMSA) scintigraphic patterns in children with first symptomatic urinary tract infection (UTI). A total of 45 children with the diagnosis of first symptomatic UTI (28 girls, 17 boys, mean age 18 months, range 1 month-11 years) were reviewed. All DMSA scans were obtained within 2 months of bacteriologically proven UTI (median 21 days, mean 26 +/- 21, 14). After the exclusion of the patients with bilateral cortical lesions, 82 renal units were analyzed. The scintigraphic patterns included regional and global description of renal cortical abnormality (normal or decreased differential renal function, regional renal function (RRF), and the number and severity of cortical lesions). Vesicoureteral reflux was detected in 26 (32%) renal units (15 with grade 1-2, 11 with grade 3-4). Renal cortical abnormality was observed in 10 renal units without VUR (10/56, 17%) and 13 renal units with VUR (13/26: 50%). Of the 15 renal units, 5 with grade 1-2 VUR (5/15) and 8 of the 11 renal units with grade 3-4 VUR (8/11) had renal cortical involvement. The most common scintigraphic pattern in the patients without VUR was the preserved RRF (>or=45%) and two or fewer photon-deficient areas. On the other hand, a decreased RRF (<45) associated with cortical lesions was the most frequent finding in patients with refluxing kidneys (8/26, 30%), especially in those with grade 3-4 disease. This investigation showed that the presence of VUR affects DMSA patterns in children with first symptomatic UTI.

Comparative study of enalapril vs. losartan on residual renal function preservation in automated peritoneal dialysis. A randomized controlled study.

PubMed

Reyes-Marín, Fernando Arturo; Calzada, Claudia; Ballesteros, Araceli; Amato, Dante

2012-01-01

Residual renal function (RRF) is an important determinant of mortality and morbidity in patients receiving peritoneal dialysis (PD). Recent studies have shown a positive effect of angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) on RRF in PD patients. To compare enalapril and losartan for RRF preservation in automated peritoneal dialysis (APD) patients. An open label randomized controlled trial (RCT) with a 12 month follow-up period was conducted to compare the effect of enalapril vs. losartan on RRF preservation in 60 APD patients. Measurements were done at the start of the study (baseline), 3, 6, 9, and 12 months. A historical control group (HCG) without treatment was included to assess the natural history of RRF loss. RRF in the enalapril group dropped from 3.65 +/- 1.6 (baseline) to 2.36 +/- 0.38 mL/min/1.73 m2 (12 months). In the losartan group RRF was reduced from 4.1+/- 2.01 (baseline) to 2.54 +/- 0.47 mL/min/ 1.73 m2 (12 months). There were not significant differences between the two groups regarding RRF at 12 months. In the HCG, RRF declined from 3.68 +/- 0.48 to 1.4 +/- 0.29 mL/min/ 1.73 m2 (12 months). RRF in the HCG was significantly lower than RRF in the two treated groups at 12 months (P < 0.05). There was not significant difference on RRF preservation between enalapril and losartan groups. Comparing these results to those of the HCG suggests that the treatment with any of the drugs is useful in preserving RRF.

Treatment of Venous Aortorenal Bypass Graft Aneurysm Using a Stent-Graft

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

Novotny, Jiri, E-mail: jino@medicon.cz; Peregrin, Jan H.; Stribrna, Jarmila

2010-02-15

We present the case of a 77-year-old male patient who had undergone a bilateral venous aortorenal bypass graft 30 years previously. Thirteen years previously, the patient was shown to have a decrease in renal function, with mild shrinking of both kidneys; additionally, a stenosis was found in the left proximal anastomosis. At the most recent follow-up visit (1 year previously), ultrasound revealed an aneurysm (42 mm in diameter) of the left renal bypass graft; the finding was confirmed by CT angiography. A significant ostial stenosis of the left renal bypass graft was also confirmed. It was decided to place amore » self-expandable stent-graft into the aneurysm while also attempting to dilate the stenosis. Proximal endoleak after stent-graft placement necessitated the implantation of another, balloon-expandable stent-graft into the bypass graft ostium. Postprocedural angiography and follow-up by CT angiography at 3 months confirmed good patency of the stent-grafts and complete thrombosis of the aneurysmal sac, with preserved kidney perfusion. Renal function remained unaltered, while the hypertension is better controlled.« less

Laparoscopic partial nephrectomy for hilar tumors: oncologic and renal functional outcomes.

PubMed

George, Arvin K; Herati, Amin S; Rais-Bahrami, Soroush; Waingankar, Nikhil; Kavoussi, Louis R

2014-01-01

To present our experience with laparoscopic partial nephrectomy (LPN) for hilar tumors and evaluate intermediate oncologic and renal functional outcomes. A retrospective review of LPN cases performed in 488 patients was performed. Hilar lesions were defined as renal cortical tumors in direct physical contact with the renal artery, vein, or both, as identified on preoperative imaging and confirmed intraoperatively. The clinicopathologic parameters, perioperative course, complications, and oncologic and 6-month renal functional outcomes were analyzed. A total of 488 patients underwent LPN, of which 43 were hilar. The mean tumor size for hilar and nonhilar tumors was 3.6 cm and 3.1 cm, respectively. The mean operative time was shorter for hilar as compared with nonhilar tumors (129.1 minutes vs 141.8 minutes). Mean estimated blood loss was greater in LPN for hilar tumors (311.65 mL vs 298.4 mL). There were no statistically significant differences noted in any of the perioperative parameters investigated despite a higher nephrometry complexity score in the hilar group. Change in estimated glomerular filtration rate at 6 months showed a decrease of 10.9 mL/min and 8.8 mL/min for hilar and nonhilar tumors, respectively (P = NS). There was 1 recurrence detected in the hilar group, with a median follow-up of 41.6 months. In the hands of an experienced laparoscopist, LPN can safely be performed for hilar tumors, with preservation of perioperative outcomes and durable renal functional and oncologic outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Chronic kidney disease and worsening renal function in acute heart failure: different phenotypes with similar prognostic impact?

PubMed

Palazzuoli, Alberto; Lombardi, Carlo; Ruocco, Gaetano; Padeletti, Margherita; Nuti, Ranuccio; Metra, Marco; Ronco, Claudio

2016-12-01

Nearly a third of patients with acute heart failure experience concomitant renal dysfunction. This condition is often associated with increased costs of care, length of hospitalisation and high mortality. Although the clinical impact of chronic kidney disease (CKD) has been well established, the exact clinical significance of worsening renal function (WRF) during the acute and post-hospitalisation phases is not completely understood. Therefore, it is still unclear which of the common laboratory markers are able to identify WRF at an early stage. Recent studies comparing CKD with WRF showed contradictory results; this could depend on a different WRF definition, clinical characteristics, haemodynamic disorders and the presence of prior renal dysfunction in the population enrolled. The current definition of acute cardiorenal syndrome focuses on both the heart and kidney but it lacks precise laboratory marker cut-offs and a specific diagnostic approach. WRF and CKD could represent different pathophysiological mechanisms in the setting of acute heart failure; the traditional view includes reduced cardiac output with systemic and renal vasoconstriction. Nevertheless, it has become a mixed model that encompasses both forward and backward haemodynamic dysfunction. Increased central venous pressure, renal congestion with tubular obliteration, tubulo-glomerular feedback and increased abdominal pressure are all potential additional contributors. The impact of WRF on patients who experience preserved renal function and individuals affected with CKD is currently unknown. Therefore it is extremely important to understand the origins, the clinical significance and the prognostic impact of WRF on CKD. © The European Society of Cardiology 2015.

Physiology in perspective: The Wisdom of the Body. Neural control of the kidney.

PubMed

DiBona, Gerald F

2005-09-01

Cannon equated the fluid matrix of the body with Bernard's concept of the internal environment and emphasized the importance of "the safe-guarding of an effective fluid matrix." He further emphasized the important role of the autonomic nervous system in the establishment and maintenance of homeostasis in the internal environment. This year's Cannon Lecture discusses the important role of the renal sympathetic nerves to regulate various aspects of overall renal function and to serve as one of the major "self-regulatory agencies which operate to preserve the constancy of the fluid matrix."

Renal functional and perioperative outcomes of off-clamp versus clamped robot-assisted partial nephrectomy: matched cohort study.

PubMed

Tanagho, Youssef S; Bhayani, Sam B; Sandhu, Gurdarshan S; Vaughn, Nicholas P; Nepple, Kenneth G; Figenshau, R Sherburne

2012-10-01

To evaluate the potential benefit of performing off-clamp robot-assisted partial nephrectomy as it relates to renal functional outcomes, while assessing the safety profile of this unconventional surgical approach. Twenty-nine patients who underwent off-clamp robot-assisted partial nephrectomy for suspected renal cell carcinoma at Washington University between March 2008 and September 2011 (group 1) were matched to 29 patients with identical nephrometry scores and comparable baseline renal function who underwent robot-assisted partial nephrectomy with hilar clamping during the same period (group 2). The matched cohorts' perioperative and renal functional outcomes were compared at a mean 9-month follow-up. Mean estimated blood loss was 146.4 mL in group 1, versus 103.9 mL in group 2 (P = .039). Mean hilar clamp time was 0 minutes in group 1 and 14.7 minutes in group 2. No perioperative complications were encountered in group 1; 1 Clavien-2 complication (3.4%) occurred in group 2 (P = 1.000). At 9-month follow-up, mean estimated glomerular filtration rate in group 1 was 79.9 versus 84.8 mL/min/1.73 m(2) preoperatively (P = .013); mean estimated glomerular filtration rate in group 2 was 74.1 versus 85.8 mL/min/1.73 m(2) preoperatively (P < .001). Hence, estimated glomerular filtration rate declined by a mean of 4.9 mL/min/1.73 m(2) in group 1 versus 11.7 mL/min/1.73 m(2) in group 2 (P = .033). Off-clamp robot-assisted partial nephrectomy is associated with a favorable morbidity profile and relatively greater renal functional preservation compared to clamped robot-assisted partial nephrectomy. Nevertheless, the benefit is small in renal functional terms and may have very limited clinical relevance. Copyright © 2012 Elsevier Inc. All rights reserved.

Impact of a quality improvement project on deceased organ donor management

PubMed Central

Olmos, Andrea; Feiner, John; Hirose, Ryutaro; Swain, Sharon; Blasi, Annabel; Roberts, John P.; Niemann, Claus U.

2017-01-01

Context Donors showed poor glucose control in the period between declaration of brain death and organ recovery. The level of hyperglycemia in the donors was associated with a decline in terminal renal function. Objective To determine whether implementation of a quality improvement project improved glucose control and preserved renal function in deceased organ donors. Methods Data collected retrospectively included demographics, medical history, mechanism of death, laboratory values, and data from the United Network for Organ Sharing. Results After implementation of the quality improvement project, deceased donors had significantly lower mean glucose concentrations (mean [SD], 162 [44] vs 212 [42] mg/dL; P < .001) and prerecovery glucose concentration (143 [66] vs 241 [69] mg/dL; P < .001). When the donor cohorts from before and after the quality improvement project were analyzed together, mean glucose concentration remained a significant predictor of terminal creatinine level (P < .001). Multivariate analysis of delayed graft function in kidney recipients matched to donors indicated that higher terminal creatinine level was associated with delayed graft function in recipients (P < .001). Conclusion The quality improvement project improved donor glucose homeostasis, and the data confirm that poor glucose homeostasis is associated with worsening terminal renal function. PMID:26645930

Improved split renal function after percutaneous nephrostomy in young adults with severe hydronephrosis due to ureteropelvic junction obstruction.

PubMed

Zhang, Shiwei; Zhang, Qing; Ji, Changwei; Zhao, Xiaozhi; Liu, Guangxiang; Zhang, Shun; Li, Xiaogong; Lian, Huibo; Zhang, Gutian; Guo, Hongqian

2015-01-01

We evaluated percutaneous nephrostomy for adult kidneys with severe hydronephrosis due to ureteropelvic junction obstruction and less than 10% split renal function. In this retrospective analysis we included patients who underwent percutaneous nephrostomy for unilateral ureteropelvic junction obstruction of the kidneys with hydronephrosis and less than 10% split renal function at our hospital between May 2009 and January 2012. Adults (age 18 years or greater) were divided into those 35 years or younger (young adults) and older than 35 years (older adults). The percutaneous nephrostomy remained in situ a mean ± SD of 6.62 ± 2.55 weeks and patients underwent repeat renography before pyeloplasty. When there was no significant improvement in split renal function (10% or greater) and drainage (greater than 400 ml per day), nephrectomy was performed. Otherwise pyeloplasty was performed. Patients were followed by renography, ultrasound and contrast computerized tomography at 3 and 6 months, at 1 year and annually thereafter. Of 53 patients 30 (56.6%) showed improvement after percutaneous nephrostomy drainage and urine output greater than 400 ml per day with percutaneous nephrostomy. Pyeloplasty was then performed. Of 29 young adults 24 (82.8%) showed improved split renal function vs 6 of 24 older adults (25%). Nephrectomy of the other 23 kidneys was performed. At a mean followup of 19.27 ± 7.82 months (range 12 to 36), no patient showed hypertension or urinary tract infection. Split renal function detected by renography may not accurately predict recovered, poorly functioning kidneys, especially in young adults. First observing the recoverability of hydronephrotic kidneys by percutaneous nephrostomy drainage and then preserving select kidneys may be an effective method to manage poorly functioning kidneys due to ureteropelvic junction obstruction. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Development of a living membrane comprising a functional human renal proximal tubule cell monolayer on polyethersulfone polymeric membrane.

PubMed

Schophuizen, Carolien M S; De Napoli, Ilaria E; Jansen, Jitske; Teixeira, Sandra; Wilmer, Martijn J; Hoenderop, Joost G J; Van den Heuvel, Lambert P W; Masereeuw, Rosalinde; Stamatialis, Dimitrios

2015-03-01

The need for improved renal replacement therapies has stimulated innovative research for the development of a cell-based renal assist device. A key requirement for such a device is the formation of a "living membrane", consisting of a tight kidney cell monolayer with preserved functional organic ion transporters on a suitable artificial membrane surface. In this work, we applied a unique conditionally immortalized proximal tubule epithelial cell (ciPTEC) line with an optimized coating strategy on polyethersulfone (PES) membranes to develop a living membrane with a functional proximal tubule epithelial cell layer. PES membranes were coated with combinations of 3,4-dihydroxy-l-phenylalanine and human collagen IV (Coll IV). The optimal coating time and concentrations were determined to achieve retention of vital blood components while preserving high water transport and optimal ciPTEC adhesion. The ciPTEC monolayers obtained were examined through immunocytochemistry to detect zona occludens 1 tight junction proteins. Reproducible monolayers were formed when using a combination of 2 mg ml(-1) 3,4-dihydroxy-l-phenylalanine (4 min coating, 1h dissolution) and 25 μg ml(-1) Coll IV (4 min coating). The successful transport of (14)C-creatinine through the developed living membrane system was used as an indication for organic cation transporter functionality. The addition of metformin or cimetidine significantly reduced the creatinine transepithelial flux, indicating active creatinine uptake in ciPTECs, most likely mediated by the organic cation transporter, OCT2 (SLC22A2). In conclusion, this study shows the successful development of a living membrane consisting of a reproducible ciPTEC monolayer on PES membranes, an important step towards the development of a bioartificial kidney. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The 6-hydroxychromanol derivative SUL-109 ameliorates renal injury after deep hypothermia and rewarming in rats.

PubMed

Vogelaar, Pieter C; Roorda, Maurits; de Vrij, Edwin L; Houwertjes, Martin C; Goris, Maaike; Bouma, Hjalmar; van der Graaf, Adrianus C; Krenning, Guido; Henning, Robert H

2018-04-11

Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats. Human proximal tubule cell viability was assessed following exposure to H/R for 48/4 h in the presence of various 6-hydroxychromanols. Selected compounds (SUL-109, SUL-121) or vehicle were administered to ketamine-anaesthetized male Wistar rats (IV 135 µg/kg/h) undergoing H/R at 15°C for 3 h followed by rewarming and normothermia for 1 h. Metabolic parameters and body temperature were measured throughout. In addition, renal function, renal injury, histopathology and mitochondrial fitness were assessed. H/R injury in vitro lowered cell viability by 94 ± 1%, which was counteracted dose-dependently by multiple 6-hydroxychomanols derivatives. In vivo, H/R in rats showed kidney injury molecule 1 expression in the kidney and tubular dilation, accompanied by double-strand DNA breaks and protein nitrosylation. SUL-109 and SUL-121 ameliorated tubular kidney damage, preserved mitochondrial mass and maintained cortical adenosine 5'-triphosphate (ATP) levels, although SUL-121 did not reduce protein nitrosylation. The substituted 6-hydroxychromanols SUL-109 and SUL-121 ameliorate kidney injury during in vivo H/R by preserving mitochondrial mass, function and ATP levels. In addition, both 6-hydroxychromanols limit DNA damage, but only SUL-109 also prevented protein nitrosylation in tubular cells. Therefore SUL-109 offers a promising therapeutic strategy to preserve kidney mitochondrial function.

Emphysematous pyelonephritis with calculus: Management strategies

PubMed Central

Goel, Tanmaya; Reddy, Sreedhar; Thomas, Joseph

2007-01-01

Objective: Emphysematous pyelonephritis (EPN) with calculus is well recognized but with very few reports on its treatment. Our aim is to elucidate our experience in its successful management. Materials and Methods: Over four years, we diagnosed seven cases (eight renal units) of EPN, out of which two patients (three renal units) had EPN with urinary calculi. After the initial conservative management of EPN, the stones were tackled appropriately. Results: EPN was initially managed effectively with antibiotics and supportive care. Once the patient was stable, the stones were cleared in a step-wise fashion. The associated postoperative complications were also tackled efficiently with preservation of renal function. Conclusion: In EPN with stones, nephrectomy is not the sole option available and they can be effectively managed with open / endoscopic measures. PMID:19718324

Association between lower serum bicarbonate and renal hyperfiltration in the general population with preserved renal function: a cross-sectional study.

PubMed

Park, Minseon; So, Rina; Joo, Kwon Wook; Yoon, Hyung-Jin

2016-01-06

Lower serum bicarbonate, mainly due to the modern Western-style diet, and renal hyperfiltration (RHF) are both independently associated with higher mortality in the general population with preserved renal function. The objective of this study was to evaluate the association between serum bicarbonate and RHF. The health data of 41,886 adults with an estimated glomerular filtration rate (eGFR) ≥60 mL/min per 1.73 m(2) were analyzed. The eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation and RHF was defined as eGFR with adjusted residuals > sex-specific 95(th) percentile. The adjusted mean of eGFR was lower in the highest quintile of serum bicarbonate than in other quintiles, after adjusting for confounders. A lower percentile rank of serum bicarbonate was associated with higher odds of RHF. The odds ratio (OR) for RHF in the lowest quintile of serum bicarbonate was 1.39 (95 % confidence interval, 95 % CI, 1.11-1.75) compared to the highest, after adjusting for confounders. With subgroup analysis, the association was prominent in participants with a body mass index >25 kg/m(2) (OR 1.98, 95 % CI 1.32-2.95 in the lowest quintile compared to the highest), compared to those with a body mass index ≤25 kg/m(2) (OR 1.18, 95 % CI 0.89-1.56 in the lowest quintile compared to the highest). This study observed an association between lower serum bicarbonate and higher odds of RHF and the possible differential effect of obesity in this association. It is necessary to confirm the association between lower serum bicarbonate and RHF and its causality.

The evaluation of renal ischaemic damage: the value of CD10 monoclonal antibody staining and of biochemical assessments of tissue viability

PubMed Central

Tagboto, S; Griffiths, A Paul

2007-01-01

Background It is well recognised that there is often a disparity between the structural changes observed in the kidney following renal injury and the function of the organ. For this reason, we carried out studies to explore possible means of studying and quantifying the severity of renal ischaemic damage using a laboratory model. Methods To do this, freshly isolated rabbit kidney tissue was subjected to warm (37°C) or cold (1°C) ischaemia for 20 hours. Following this, the tissue was stained using Haematoxylin and Eosin (H+E), Periodic Schiff reagent (PAS) and the novel monoclonal antibody CD10 stain. Additionally, ischaemic damage to the kidneys was assessed by biochemical tests of tissue viability using formazan-based colorimetry. Results CD 10 antibody intensely stained the brush border of control kidney tissue with mild or no cytoplasmic staining. Cell injury was accompanied by a redistribution of CD10 into the lumen and cell cytoplasm. There was good correlation between a score of histological damage using the CD 10 monoclonal antibody stain and the biochemical assessment of viability. Similarly, a score of histological damage using traditional PAS staining correlated well with that using the CD10 antibody stain. In particular, the biochemical assay and the monoclonal antibody staining techniques were able to demonstrate the efficacy of Soltran (this solution is used cold to preserve freshly isolated human kidneys prior to transplantation) in preserving renal tissue at cold temperatures compared to other randomly selected solutions. Conclusion We conclude that the techniques described using the CD10 monoclonal antibody stain may be helpful in the diagnosis and assessment of ischaemic renal damage. In addition, biochemical tests of viability may have an important role in routine histopathological work by giving additional information about cellular viability which may have implications on the function of the organ. PMID:17531101

An update on the arsenal for multidrug-resistant Acinetobacter infections: polymyxin antibiotics.

PubMed

Kassamali, Zahra; Jain, Rupali; Danziger, Larry H

2015-01-01

To review recent clinical pharmacokinetic and pharmacodynamic data to optimize dosing regimens for polymyxin B and colistin for treatment of infections due to A. baumannii. A literature search was performed using the search terms Acinetobacter, polymyxin, colistin, polymyxin B on MEDLINE. Additional references were identified from the resulting citations. Increasing the dose of polymyxin B or colistin and using either in combination with other antibiotic agents demonstrates improved antimicrobial activity against Acinetobacter spp. Polymyxin B, unlike colistin, is available as an active drug and appears to be relatively unaffected by renal function. This is advantageous both for patients with renal impairment and for those with intact renal function. Achieving therapeutic serum concentrations of colistin may be difficult for those with intact renal function due to rapid clearance of the prodrug, colistimethate sodium (CMS). Clinical data are still lacking for polymyxin B, and it remains to be seen whether advantages demonstrated in PK/PD analyses will persist in the larger scale of patient care and safety. The use of higher doses of either colistin or polymyxin B, as well as combination with other antibiotics, may prevent emerging resistance and preserve the activity of polymyxins against A. baumannii. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

Selective Arterial Clamping Versus Hilar Clamping for Minimally Invasive Partial Nephrectomy.

PubMed

Yezdani, Mona; Yu, Sue-Jean; Lee, David I

2016-05-01

Partial nephrectomy has become an accepted treatment of cT1 renal masses as it provides improved long-term renal function compared to radical nephrectomy (Campbell et al. J Urol. 182:1271-9, 2009). Hilar clamping is utilized to help reduce bleeding and improve visibility during tumor resection. However, concern over risk of kidney injury with hilar clamping has led to new techniques to reduce length of warm ischemia time (WIT) during partial nephrectomy. These techniques have progressed over the years starting with early hilar unclamping, controlled hypotension during tumor resection, selective arterial clamping, minimal margin techniques, and off-clamp procedures. Selective arterial clamping has progressed significantly over the years. The main question is what are the exact short- and long-term renal effects from increasing clamp time. Moreover, does it make sense to perform these more time-consuming or more complex procedures if there is no long-term preservation of kidney function? More recent studies have shown no difference in renal function 6 months from surgery when selective arterial clamping or even hilar clamping is employed, although there is short-term improved decline in estimated glomerular filtration rate (eGFR) with selective clamping and off-clamp techniques (Komninos et al. BJU Int. 115:921-8, 2015; Shah et al. 117:293-9, 2015; Kallingal et al. BJU Int. doi: 10.1111/bju.13192, 2015). This paper reviews the progression of total hilar clamping to selective arterial clamping (SAC) and the possible difference its use makes on long-term renal function. SAC may be attempted based on surgeon's decision-making, but may be best used for more complex, larger, more central or hilar tumors and in patients who have renal insufficiency at baseline or a solitary kidney.

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

Clinical outcome of patients with heart failure and preserved left ventricular function.

PubMed

Gotsman, Israel; Zwas, Donna; Planer, David; Azaz-Livshits, Tanya; Admon, Dan; Lotan, Chaim; Keren, Andre

2008-11-01

Patients with heart failure have a poor prognosis. However, it has been presumed that patients with heart failure and preserved left ventricular function (LVF) may have a more benign prognosis. We evaluated the clinical outcome of patients with heart failure and preserved LVF compared with patients with reduced function and the factors affecting prognosis. We prospectively evaluated 289 consecutive patients hospitalized with a definite clinical diagnosis of heart failure based on typical symptoms and signs. They were divided into 2 subsets based on echocardiographic LVF. Patients were followed clinically for a period of 1 year. Echocardiography showed that more than one third (36%) of the patients had preserved systolic LVF. These patients were more likely to be older and female and have less ischemic heart disease. The survival at 1 year in this group was poor and not significantly different from patients with reduced LVF (75% vs 71%, respectively). The adjusted survival by Cox regression analysis was not significantly different (P=.25). However, patients with preserved LVF had fewer rehospitalizations for heart failure (25% vs 35%, P<.05). Predictors of mortality in the whole group by multivariate analysis were age, diabetes, chronic renal failure, atrial fibrillation, residence in a nursing home, and serum sodium < or = 135 mEq/L. The prognosis of patients with clinical heart failure with or without preserved LVF is poor. Better treatment modalities are needed in both subsets.

[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.

Nonmalignant Diseases and Treatments Associated with Primary Ovarian Failure: An Expanded Role for Fertility Preservation

PubMed Central

Hirshfeld-Cytron, Jennifer; Gracia, Clarisa

2011-01-01

Abstract Cancer treatments can be detrimental to fertility; recent literature has focused on the efforts of fertility preservation for this patient population. It should be recognized, however, that several nonmalignant medical conditions and therapeutic interventions could be similarly hazardous to fertility. Some of these nonmalignant diseases and their treatments that can adversely impact the reproductive axis are gastrointestinal diseases, rheumatologic disorders, nonmalignant hematologic conditions, neurologic disorders, renal disorders, gynecologic conditions, and metabolic diseases. Their negative effects on reproductive function are only now being appreciated and include impaired ovarian function, endocrine function, or sexual function and inability to carry a pregnancy to term. Complications and comorbidities associated with certain diseases may limit the success of established fertility preservation options. Recent advances in fertility preservation techniques may provide these patients with new options for childbearing. Here, we review several fertility-threatening conditions and treatments, describe current established and experimental fertility preservation options, and present three initiatives that may help minimize the adverse reproductive effects of these medical conditions and treatments by raising awareness of the issues and options: (1) increase awareness among practitioners about the reproductive consequences of specific diseases and treatments, (2) facilitate referral of patients to fertility-sparing or restorative programs, and (3) provide patient education about the risk of infertility at the time of diagnosis before initiation of treatment. PMID:21827325

Nonmalignant diseases and treatments associated with primary ovarian failure: an expanded role for fertility preservation.

PubMed

Hirshfeld-Cytron, Jennifer; Gracia, Clarisa; Woodruff, Teresa K

2011-10-01

Cancer treatments can be detrimental to fertility; recent literature has focused on the efforts of fertility preservation for this patient population. It should be recognized, however, that several nonmalignant medical conditions and therapeutic interventions could be similarly hazardous to fertility. Some of these nonmalignant diseases and their treatments that can adversely impact the reproductive axis are gastrointestinal diseases, rheumatologic disorders, nonmalignant hematologic conditions, neurologic disorders, renal disorders, gynecologic conditions, and metabolic diseases. Their negative effects on reproductive function are only now being appreciated and include impaired ovarian function, endocrine function, or sexual function and inability to carry a pregnancy to term. Complications and comorbidities associated with certain diseases may limit the success of established fertility preservation options. Recent advances in fertility preservation techniques may provide these patients with new options for childbearing. Here, we review several fertility-threatening conditions and treatments, describe current established and experimental fertility preservation options, and present three initiatives that may help minimize the adverse reproductive effects of these medical conditions and treatments by raising awareness of the issues and options: (1) increase awareness among practitioners about the reproductive consequences of specific diseases and treatments, (2) facilitate referral of patients to fertility-sparing or restorative programs, and (3) provide patient education about the risk of infertility at the time of diagnosis before initiation of treatment.

[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.

Evaluating the benefits of home-based peritoneal dialysis

PubMed Central

François, Karlien; Bargman, Joanne M

2014-01-01

Peritoneal dialysis (PD) is an effective renal replacement strategy for patients suffering from end-stage renal disease. PD offers patient survival comparable to or better than in-center hemodialysis while preserving residual kidney function, empowering patient autonomy, and reducing financial burden to payors. The majority of patients suffering from kidney failure are eligible for PD. In patients with cardiorenal syndrome and uncontrolled fluid status, PD is of particular benefit, decreasing hospitalization rates and duration. This review discusses the benefits of chronic PD, performed by the patient or a caregiver at home. Recognition of the benefits of PD is a cornerstone in stimulating the use of this treatment strategy. PMID:25506238

Incidence and aetiology of renal phosphate loss in patients with hypophosphatemia in the intensive care unit.

PubMed

Bech, Anneke; Blans, Michiel; Telting, Darryl; de Boer, Hans

2013-10-01

Hypophosphatemia is a common finding in patients in the intensive care unit (ICU). Its cause is often poorly understood. The aim of this study was to understand the incidence of renal phosphate loss in ICU-related hypophosphatemia, and to examine the role of phosphaturic hormones in its etiology. Plasma phosphate levels were measured on day 1, 3, 5 and 7 in 290 consecutive patients admitted to the ICU. Renal phosphate handling and phosphaturic hormones were studied in a subset of patients with phosphate levels <0.6 mmol/L. Renal phosphate loss was defined as a TmP/gfr < 0.6 mmol/L. Hypophosphatemia developed in 24% of all patients. This mainly occurred within the first 3 days of stay and in patients with serum creatinine levels <150 μmol/L. Renal phosphate loss was present in 80% of patients who developed hypophosphatemia, and was not related to serum levels of parathyroid hormone (PTH), PTH-related protein (PTH-rp), fibroblast growth factor 23 (FGF-23), or calcitonin. Hypophosphatemia in the ICU is commonly associated with renal phosphate loss. It mainly occurs within the first 3 days of admission, in particular in patients with preserved renal function. Renal phosphate loss is not explained by elevated PTH, PTH-rp, FGF-23 or calcitonin levels.

Endoscopic Management of Upper Urinary Tract Urothelial Carcinoma.

PubMed

Samson, Patrick; Smith, Arthur D; Hoenig, David; Okeke, Zeph

2018-05-01

Endoscopic management of upper tract urothelial carcinoma has become more popular over the last few decades as there has been an impetus for renal preservation in these patients. While radical nephroureterectomy has been the gold standard in treatment of this disease, ureteroscopic and percutaneous management has become a viable option for select patients. The literature on endoscopic management of upper urinary tract tumors was explored. Different management methods are discussed, both from published literature and experience of the authors of this chapter. We review the indications, details of the procedure, and troubleshooting methods in the endoscopic management of upper tract urothelial carcinoma. Imperative indications as well as controversial indications are discussed. The role and efficacy of adjuvant intrarenal topical agents are examined as well as the protocol for administering these agents. Follow-up protocols are also reviewed. In select patients, endoscopic management with ureteroscopy and/or percutaneous resection of upper tract urothelial tumors is appropriate and can preserve renal function while obtaining comparable oncologic control compared with radical surgery.

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

Postrenal acute kidney injury in a patient with unilateral ureteral obstruction caused by urolithiasis: A case report.

PubMed

Kazama, Itsuro; Nakajima, Toshiyuki

2017-10-01

In patients with bilateral ureteral obstruction, the serum creatinine levels are often elevated, sometimes causing postrenal acute kidney injury (AKI). In contrast, those with unilateral ureteral obstruction present normal serum creatinine levels, as long as their contralateral kidneys are preserved intact. However, the unilateral obstruction of the ureter could affect the renal function, as it humorally influences the renal hemodynamics. A 66-year-old man with a past medical history of hypertension and diabetes mellitus came to our outpatient clinic because of right abdominal dullness. Unilateral ureteral obstruction caused by a radio-opaque calculus in the right upper ureter and a secondary renal dysfunction. As oral hydration and the use of calcium antagonists failed to allow the spontaneous stone passage, extracorporeal shock wave lithotripsy (ESWL) was performed. Immediately after the passage of the stone, the number of red blood cells in the urine was dramatically decreased and the serum creatinine level almost returned to the normal range with the significant increase in glomerular filtration rate. Unilateral ureteral obstruction by the calculus, which caused reflex vascular constriction and ureteral spasm in the contralateral kidney, was thought to be responsible for the deteriorating renal function.

Practice-Based Recommendations from the American Society of Transplantation Liver and Intestine Community of Practice

PubMed Central

Levitsky, J.; O’Leary, J.G.; Asrani, S.; Sharma, P.; Fung, J.; Wiseman, A.; Niemann, C.U.

2016-01-01

Acute and chronic kidney disease after liver transplantation is common and results in significant morbidity and mortality. The introduction of MELD has directly correlated with an increased prevalence of perioperative renal dysfunction and the number of simultaneous liver-kidney transplants performed. Thus, kidney dysfunction in this population is typically multifactorial and related to pre-existing conditions, pre-transplant renal injury, peri-operative events, and post-transplant nephrotoxic immunosuppressive therapies. The management of kidney disease following liver transplantation is challenging, as by the time the serum creatinine is significantly elevated, few interventions impact the course of progression. Also, immunological factors such as antibody-mediated rejection have become of greater interest given the rising liver-kidney transplant population. Therefore this review, assembled by experts in the field and endorsed by the American Society of Transplantation Liver and Intestinal Community of Practice, provides a critical assessment of measures of renal function and interventions aimed at preserving renal function early and late after liver and simultaneous liver-kidney transplantation. Key points and practice-based recommendations for the prevention and management of kidney injury in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations. PMID:26932352

Extra-anatomic endovascular repair of an abdominal aortic aneurysm with a horseshoe kidney supplied by the aneurysmal aorta.

PubMed

Rey, Jorge; Golpanian, Samuel; Yang, Jane K; Moreno, Enrique; Velazquez, Omaida C; Goldstein, Lee J; Chahwala, Veer

2015-07-01

Abdominal aortic aneurysm complicated by a horseshoe kidney (HSK, fused kidney) represents a unique challenge for repair. Renal arteries arising from the aneurysmal aorta can further complicate intervention. Reports exist describing the repair of these complex anatomies using fenestrated endografts, hybrid open repairs (debranching), and open aneurysmorrhaphy with preservation of renal circulation. We describe an extra-anatomic, fully endovascular repair of an abdominal aortic aneurysm with a HSK partially supplied by a renal artery arising from the aneurysm. We successfully applied aortouni-iliac endografting, femorofemoral bypass, and retrograde renal artery perfusion via the contralateral femoral artery to exclude the abdominal aortic aneurysm and preserve circulation to the HSK. Copyright © 2015 Elsevier Inc. All rights reserved.

Clopidogrel preserves whole kidney autoregulatory behavior in ANG II-induced hypertension

PubMed Central

Osmond, David A.; Zhang, Shali; Pollock, Jennifer S.; Yamamoto, Tatsuo; De Miguel, Carmen

2014-01-01

This study tested the hypothesis that P2Y12 receptor blockade with clopidogrel preserves renal autoregulatory ability during ANG II-induced hypertension. Clopidogrel was administered orally to male Sprague-Dawley rats chronically infused with ANG II. After 14 days of treatment, whole kidney autoregulation of renal blood flow was assessed in vivo in pentobarbital-anesthetized rats using an ultrasonic flow probe placed around the left renal artery. In ANG II-vehicle-treated rats, decreasing arterial pressure over a range from 160 to 100 mmHg resulted in a 25 ± 5% decrease in renal blood flow, demonstrating a significant loss of autoregulation with an autoregulatory index of 0.66 ± 0.15. However, clopidogrel treatment preserved autoregulatory behavior in ANG II-treated rats to levels indistinguishable from normotensive sham-operated (sham) rats (autoregulatory index: 0.04 ± 0.14). Compared with normotensive sham-vehicle-treated rats, ANG II infusion increased renal CD3-positive T cell infiltration by 66 ± 6%, induced significant thickening of the preglomerular vessels and glomerular basement membrane and increased glomerular collagen I deposition, tubulointerstitial fibrosis, damage to the proximal tubular brush border, and protein excretion. Clopidogrel significantly reduced renal infiltration of T cells by 39 ± 9% and prevented interstitial artery thickening, ANG II-induced damage to the glomerular basement membrane, deposition of collagen type I, and tubulointerstitial fibrosis, despite the maintenance of hypertension. These data demonstrate that systemic P2Y12 receptor blockade with clopidogrel protects against impairment of autoregulatory behavior and renal vascular injury in ANG II-induced hypertension, possibly by reducing renal T cell infiltration. PMID:24477682

Renal function preservation with pioglitazone or with basal insulin as an add-on therapy for patients with type 2 diabetes mellitus.

PubMed

Chang, Yu-Hung; Hwu, Der-Wei; Chang, Dao-Ming; An, Ling-Wang; Hsieh, Chang-Hsun; Lee, Yau-Jiunn

2017-06-01

Clinical outcome may differ owing to the distinct pharmacological characteristics of insulin sensitizers and insulin. This study was performed to compare the metabolic and renal function changes with add-on pioglitazone treatment versus basal insulin in patients with type 2 diabetes mellitus (DM) in whom sulfonylurea and metformin regimens failed. Patients who were consecutively managed in the diabetes comprehensive program with add-on pioglitazone or detemir/glargine treatment for at least 2 years following sulfonylurea and metformin treatment failure were included. A total of 1002 patients were enrolled (pioglitazone: 559, detemir: 264, glargine: 179). After propensity score matching, there were 105 patients with matchable baseline characteristics in each group. After a mean of 3.5 years of follow-up, the pioglitazone group showed a greater HbA1c reduction than the detemir group and the glargine group. Despite patients in all three groups exhibiting significant body weight gain, those in the pioglitazone group and the glargine group showed greater body weight increases than the patients in the detemir group (2.1, 1.6 and 0.8 kg, respectively, p < 0.05). Interestingly, Cox regression analysis indicated that patients under detemir or glargine treatment had a higher probability of CKD progression as compared with the pioglitazone group, with hazard ratios of 2.63 (95% CI 1.79-3.88) and 3.13 (95% CI 2.01-4.87), respectively. Our study first showed that treatment with both pioglitazone and basal insulin improved glycemic control, while only pioglitazone treatment was observed to be advantageous in terms of preserving renal function when used as an add-on therapy for patients with type 2 DM in whom sulfonylurea and metformin regimens failed.

Diuretic renography in hydronephrosis: renal tissue tracer transit predicts functional course and thereby need for surgery.

PubMed

Schlotmann, Andreas; Clorius, John H; Clorius, Sandra N

2009-10-01

The recognition of those hydronephrotic kidneys which require therapy to preserve renal function remains difficult. We retrospectively compared the 'tissue tracer transit' (TTT) of (99m)Tc-mercaptoacetyltriglycine ((99m)Tc-MAG(3)) with 'response to furosemide stimulation' (RFS) and with 'single kidney function < 40%' (SKF < 40%) to predict functional course and thereby need for surgery. Fifty patients with suspected unilateral obstruction and normal contralateral kidney had 115 paired (baseline/follow-up) (99m)Tc-MAG(3) scintirenographies. Three predictions of the functional development were derived from each baseline examination: the first based on TTT (visually assessed), the second on RFS and the third on SKF < 40%. Each prediction also considered whether the patient had surgery. Possible predictions were 'better', 'worse' or 'stable' function. A comparison of SKF at baseline and follow-up verified the predictions. The frequency of correct predictions for functional improvement following surgery was 8 of 10 kidneys with delayed TTT, 9 of 22 kidneys with obstructive RFS and 9 of 21 kidneys with SKF < 40%; for functional deterioration without surgery it was 2 of 3 kidneys with delayed TTT, 3 of 20 kidneys with obstructive RFS and 3 of 23 kidneys with SKF < 40%. Without surgery 67 of 70 kidneys with timely TTT maintained function. Without surgery 0 of 9 kidneys with timely TTT but obstructive RFS and only 1 of 16 kidneys with timely TTT but SKF < 40% lost function. Delayed TTT appears to identify the need for therapy to preserve function of hydronephrotic kidneys, while timely TTT may exclude risk even in the presence of an obstructive RFS or SKF < 40%.

Laparoscopic partial nephrectomy for renal tumor: Nagoya experience.

PubMed

Yoshikawa, Yoko; Ono, Yoshinari; Hattori, Ryohei; Gotoh, Momokazu; Yoshino, Yasushi; Katsuno, Satoshi; Katoh, Masashi; Ohshima, Shinichi

2004-08-01

To clarify the indication for a vascular clamp during laparoscopic partial nephrectomy, the clinical results of 17 patients who underwent the procedure for small renal tumors were reviewed. Seventeen patients with renal tumors were enrolled in our laparoscopic partial nephrectomy program between October 1999 and November 2003. During laparoscopy, a vascular clamp was used to remove the tumor mass and suture the incised renal parenchyma and urinary collecting system in 8 patients who had less-than-1-cm-thick renal parenchyma between the mass and the renal sinus or calices. In the remaining 9 patients, who had 1-cm-or-more-thick renal parenchyma between the mass and sinus or calices, renal bleeding was controlled using ultrasonic scissors, gauze tampon, argon beam coagulator, and fibrin glue. Sixteen patients were successfully treated with laparoscopy; one required conversion to open surgery because of uncontrollable bleeding. The average operative time was 4.5 hours, and average estimated bleeding volume was 301 mL. In the 8 patients requiring vascular clamping by forceps, the average ischemic time was 25 minutes. In all patients, the tumor mass was completely removed with negative surgical margins, and renal function was preserved. Three patients had prolonged urinary leakage for a mean of 21 days. Laparoscopic partial nephrectomy offers many advantages, including surgery that is both nephron sparing and minimally invasive. A vascular clamp was indicated for patients with less-than-1-cm-thick renal parenchyma between the tumor mass and renal sinus or calices.

Optimization of SDS exposure on preservation of ECM characteristics in whole organ decellularization of rat kidneys.

PubMed

He, M; Callanan, A; Lagaras, K; Steele, J A M; Stevens, M M

2017-08-01

Renal transplantation is well established as the optimal form of renal replacement therapy but is restricted by the limited pool of organs available for transplantation. The whole organ decellularisation approach is leading the way for a regenerative medicine solution towards bioengineered organ replacements. However, systematic preoptimization of both decellularization and recellularization parameters is essential prior to any potential clinical application and should be the next stage in the evolution of whole organ decellularization as a potential strategy for bioengineered organ replacements. Here we have systematically assessed two fundamental parameters (concentration and duration of perfusion) with regards to the effects of differing exposure to the most commonly used single decellularizing agent (sodium dodecyl sulphate/SDS) in the perfusion decellularization process for whole rat kidney ECM bioscaffolds, with findings showing improved preservation of both structural and functional components of the whole kidney ECM bioscaffold. Whole kidney bioscaffolds based on our enhanced protocol were successfully recellularized with rat primary renal cells and mesenchymal stromal cells. These findings should be widely applicable to decellularized whole organ bioscaffolds and their optimization in the development of regenerated organ replacements for transplantation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1352-1360, 2017. © 2016 Wiley Periodicals, Inc.

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.

Renal dysfunction in patients with heart failure with preserved versus reduced ejection fraction: impact of the new Chronic Kidney Disease-Epidemiology Collaboration Group formula.

PubMed

McAlister, Finlay A; Ezekowitz, Justin; Tarantini, Luigi; Squire, Iain; Komajda, Michel; Bayes-Genis, Antoni; Gotsman, Israel; Whalley, Gillian; Earle, Nikki; Poppe, Katrina K; Doughty, Robert N

2012-05-01

Prior studies in heart failure (HF) have used the Modification of Diet in Renal Disease (MDRD) equation to calculate estimated glomerular filtration rate (eGFR). The Chronic Kidney Disease-Epidemiology Collaboration Group (CKD-EPI) equation provides a more-accurate eGFR than the MDRD when compared against the radionuclide gold standard. The prevalence and prognostic import of renal dysfunction in HF if the CKD-EPI equation is used rather than the MDRD is uncertain. We used individual patient data from 25 prospective studies to stratify patients with HF by eGFR using the CKD-EPI and the MDRD equations and examined survival across eGFR strata. In 20 754 patients (15 962 with HF with reduced ejection fraction [HF-REF] and 4792 with HF with preserved ejection fraction [HF-PEF]; mean age, 68 years; deaths per 1000 patient-years, 151; 95% CI, 146-155), 10 589 (51%) and 11 422 (55%) had an eGFR <60 mL/min using the MDRD and CKD-EPI equations, respectively. Use of the CKD-EPI equation resulted in 3760 (18%) patients being reclassified into different eGFR risk strata; 3089 (82%) were placed in a lower eGFR category and exhibited higher all-cause mortality rates (net reclassification improvement with CKD-EPI, 3.7%; 95% CI, 1.5%-5.9%). Reduced eGFR was a stronger predictor of all-cause mortality in HF-REF than in HF-PEF. Use of the CKD-EPI rather than the MDRD equation to calculate eGFR leads to higher estimates of renal dysfunction in HF and a more-accurate categorization of mortality risk. Renal function is more closely related to outcomes in HF-REF than in HF-PEF.

Atorvastatin prevents the downregulation of aquaporin-2 receptor after bilateral ureteral obstruction and protects renal function in a rat model.

PubMed

Danilovic, Alexandre; Lopes, Roberto Iglesias; Sanches, Talita Rojas; Shimizu, Maria Heloísa Massola; Oshiro, Fabíola M; Andrade, Lúcia; Dénes, Francisco Tibor; Seguro, Antonio Carlos

2012-08-01

To assess the effects of atorvastatin (ATORV) on renal function after bilateral ureteral obstruction (BUO), measuring inulin clearance and its effect on renal hemodynamic, filtration, and inflammatory response, as well as the expression of Aquaporin-2 (AQP2) in response to BUO and after the release of BUO. Adult Munich-Wistar male rats were subjected to BUO for 24 hours and monitored during the following 48 hours. Rats were divided into 5 groups: sham operated (n = 6); sham + ATORV (n = 6); BUO (n = 6); BUO + ATORV (10 mg/kg in drinking water started 2 days before BUO [n = 5]; and BUO + ATORV (10 mg/kg in drinking water started on the day of the release of BUO [n = 5]). We measured blood pressure (BP, mm Hg); inulin clearance (glomerular filtration rate [GFR]; mL/min/100 g); and renal blood flow (RBF, mL/min, by transient-time flowmeter). Inflammatory response was evaluated by histologic analysis of the interstitial area. AQP2 expression was evaluated by electrophoresis and immunoblotting. Renal function was preserved by ATORV treatment, even if initiated on the day of obstruction release, as expressed by GFR, measured by inulin clearance. Relative interstitial area was decreased in both BUO + ATORV groups. Urine osmolality was improved in the ATORV-treated groups. AQP2 protein expression decreased in BUO animals and was reverted by ATORV treatment. ATORV administration significantly prevented and restored impairment in GFR and renal vascular resistance. Furthermore, ATORV also improved urinary concentration by reversing the BUO-induced downregulation of AQP2. These findings have significant clinical implication in treating obstructive nephropathy. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

Renoprotective effect of the antioxidant curcumin: Recent findings☆

PubMed Central

Trujillo, Joyce; Chirino, Yolanda Irasema; Molina-Jijón, Eduardo; Andérica-Romero, Ana Cristina; Tapia, Edilia; Pedraza-Chaverrí, José

2013-01-01

For years, there have been studies based on the use of natural compounds plant-derived as potential therapeutic agents for various diseases in humans. Curcumin is a phenolic compound extracted from Curcuma longa rhizome commonly used in Asia as a spice, pigment and additive. In traditional medicine of India and China, curcumin is considered as a therapeutic agent used in several foods. Numerous studies have shown that curcumin has broad biological functions particularly antioxidant and antiinflammatory. In fact, it has been established that curcumin is a bifunctional antioxidant; it exerts antioxidant activity in a direct and an indirect way by scavenging reactive oxygen species and inducing an antioxidant response, respectively. The renoprotective effect of curcumin has been evaluated in several experimental models including diabetic nephropathy, chronic renal failure, ischemia and reperfusion and nephrotoxicity induced by compounds such as gentamicin, adriamycin, chloroquine, iron nitrilotriacetate, sodium fluoride, hexavalent chromium and cisplatin. It has been shown recently in a model of chronic renal failure that curcumin exerts a therapeutic effect; in fact it reverts not only systemic alterations but also glomerular hemodynamic changes. Another recent finding shows that the renoprotective effect of curcumin is associated to preservation of function and redox balance of mitochondria. Taking together, these studies attribute the protective effect of curcumin in the kidney to the induction of the master regulator of antioxidant response nuclear factor erythroid-derived 2 (Nrf2), inhibition of mitochondrial dysfunction, attenuation of inflammatory response, preservation of antioxidant enzymes and prevention of oxidative stress. The information presented in this paper identifies curcumin as a promising renoprotective molecule against renal injury. PMID:24191240

Renal preservation in children with neurogenic bladder-sphincter dysfunction followed in a national program.

PubMed

Wide, Peter; Glad Mattsson, Gunilla; Mattsson, Sven

2012-04-01

Neurogenic bladder-sphincter dysfunction (NBSD) constitutes the major reason for morbidity in children with spina bifida. The aim of this study was to identify risk factors for renal damage in children with NBSD followed according to the Swedish national guidelines. Records and cystometries from 6 to 16 years (median 11) follow up of 41 consecutive children born 1993-2003 with NBSD were evaluated. The children were divided into a high pressure group (baseline pressure above 30 cmH(2)O at maximal clean intermittent catheterization volume in at least two cystometries) and a low pressure group. Most children (34/41) were followed from birth. Although renal scarring on DMSA-scintigraphy was found in 5/41 children, all but one had normal renal function. Two already had renal scars on entering the follow-up program at age 2.5 and 3 years. Renal scarring was more frequent in the high pressure group (P < 0.01). Most children with renal scars (4/5) had a combination of low compliant bladder and insufficient compliance with treatment and follow up. High baseline pressure is confirmed as a risk factor that, in combination with complex social issues, creates a demanding situation for families and professionals. A structured early follow up with treatment compliance effectively prevents renal damage. Copyright © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Outcomes of Robot-assisted Partial Nephrectomy for Clinical T2 Renal Tumors: A Multicenter Analysis (ROSULA Collaborative Group).

PubMed

Bertolo, Riccardo; Autorino, Riccardo; Simone, Giuseppe; Derweesh, Ithaar; Garisto, Juan D; Minervini, Andrea; Eun, Daniel; Perdona, Sisto; Porter, James; Rha, Koon Ho; Mottrie, Alexander; White, Wesley M; Schips, Luigi; Yang, Bo; Jacobsohn, Kenneth; Uzzo, Robert G; Challacombe, Ben; Ferro, Matteo; Sulek, Jay; Capitanio, Umberto; Anele, Uzoma A; Tuderti, Gabriele; Costantini, Manuela; Ryan, Stephen; Bindayi, Ahmet; Mari, Andrea; Carini, Marco; Keehn, Aryeh; Quarto, Giuseppe; Liao, Michael; Chang, Kidon; Larcher, Alessandro; De Naeyer, Geert; De Cobelli, Ottavio; Berardinelli, Francesco; Zhang, Chao; Langenstroer, Peter; Kutikov, Alexander; Chen, David; De Luyk, Nicolo; Sundaram, Chandru P; Montorsi, Francesco; Stein, Robert J; Haber, Georges Pascal; Hampton, Lance J; Dasgupta, Prokar; Gallucci, Michele; Kaouk, Jihad; Porpiglia, Francesco

2018-05-18

While partial nephrectomy (PN) represents the standard surgical management for cT1 renal masses, its role for cT2 tumors is controversial. Robot-assisted PN (RAPN) is being increasingly implemented worldwide. To analyze perioperative, functional, and oncological outcomes of RAPN for cT2 tumors. Retrospective analysis of a large multicenter, multinational dataset of patients with nonmetastatic cT2 masses treated with robotic surgery (ROSULA: RObotic SUrgery for LArge renal mass). Robotic-assisted PN. Patients' demographics, lesion characteristics, perioperative variables, renal functional data, pathology, and oncological data were analyzed. Univariable and multivariable regression analyses assessed the relationships with the risk of intra-/postoperative complications, recurrence, and survival. A total of 298 patients were analyzed. Median tumor size was 7.6 (7-8.5) cm. Median RENAL score was 9 (8-10). Median ischemia time was 25 (20-32) min. Median estimated blood loss was 150 (100-300) ml. Sixteen patients had intraoperative complications (5.4%), whereas 66 (22%) had postoperative complications (5% were Clavien grade ≥3). Multivariable analysis revealed that a lower RENAL score (odds ratio [OR] 0.46, 95% confidence interval [CI] 0.21-0.65, p=0.02) and pathological pT2 stage (OR 0.51, 95% CI 0.12-0.86, p=0.001) were protective against postoperative complications. A total of 243 lesions (82%) were malignant. Twenty patients (8%) had positive surgical margins. Ten deaths and 25 recurrences/metastases occurred at a median follow-up of 12 (5-35) mo. At univariable analysis, higher pT stage was predictive of a likelihood of recurrences/metastases (p=0.048). While there was a significant deterioration of renal function at discharge, this remained stable over time at 1-yr follow-up. The main limitation of this study is its retrospective design. RAPN in the setting of select cT2 renal masses can safely be performed with acceptable outcomes. Further studies are warranted to corroborate our findings and to better define the role of robotic nephron sparing for this challenging indication. This report shows that robotic surgery can be used for safe removal of a large renal tumor in a minimally invasive fashion, maximizing preservation of renal function, and without compromising cancer control. Published by Elsevier B.V.

Vascular endothelial growth factor and the kidney: something of the marvellous.

PubMed

Advani, Andrew

2014-01-01

The vascular endothelial growth factor (VEGF) system is a multifarious network and an exemplar of an intraglomerular signalling pathway. Here, we review recent advances that highlight the subtle nature of the renal VEGF system and its influencers. The VEGF system is no longer considered as a simple paracrine, ligand-receptor interaction under the regulatory control of a soluble 'decoy', soluble fms-like tyrosine kinase-1 (sFLT1). Rather, the abundantly expressed, podocyte-derived VEGF isoform, VEGF-A, is now recognized to mediate both paracrine effects across the filtration barrier and autocrine actions, functioning to preserve the integrity of the cells from which it arises. Autocrine actions of the podocyte VEGF system extend beyond those of the VEGF-A isoform, however, with sFLT1 itself now appreciated as regulating podocyte morphology by binding to lipid microdomains. These and other functions of the VEGF system are profoundly affected by the presence, nature and abundance of influencers both intrinsic and extrinsic to the pathway, the latter most readily exemplified by the role of the cytokine in the diabetic kidney. The glomerular VEGF system plays a delicate, yet critical, role in preserving renal homeostasis. It may be intricate, but 'in all things of nature there is something of the marvellous'.

Galectin-3 in heart failure with preserved ejection fraction. A RELAX trial substudy (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure).

PubMed

AbouEzzeddine, Omar F; Haines, Phillip; Stevens, Susanna; Nativi-Nicolau, Jose; Felker, G Michael; Borlaug, Barry A; Chen, Horng H; Tracy, Russell P; Braunwald, Eugene; Redfield, Margaret M

2015-03-01

This study hypothesized that elevated galectin-3 (Gal-3) levels would identify patients with more advanced heart failure (HF) with preserved ejection fraction (HFpEF) as assessed by key pathophysiological domains. Gal-3 is implicated in the pathogenesis of cardiac fibrosis but is also increased with normal aging and renal dysfunction. Cardiac fibrosis may contribute to cardiac dysfunction, exercise intolerance, and congestion in HFpEF. Two hundred eight patients from the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial of sildenafil in HFpEF had Gal-3 measured at enrollment. Pathophysiological domains assessed included biomarkers of neurohumoral activation, fibrosis, inflammation and myocardial necrosis, congestion severity and quality of life, cardiac structure and function, and exercise performance. Analysis adjusted for age, sex, and/or cystatin-C levels. Potential interaction between baseline Gal-3 and treatment (sildenafil) effect on the RELAX study primary endpoint (change in peak oxygen consumption) was tested. Gal-3 levels were associated with age and severity of renal dysfunction. Adjusting for age, sex, and/or cystatin-C, Gal-3 was not associated with biomarkers of neurohumoral activation, fibrosis, inflammation or myocardial necrosis, congestion or quality-of-life impairment, cardiac remodeling or dysfunction, or exercise intolerance. Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p = 0.53). In overt HFpEF, Gal-3 was related to severity of renal dysfunction and accounting for this, was not independently associated with severity of pathophysiological derangements or response PDE-5 inhibition. These findings underscore the need to adjust for renal function when interpreting Gal-3 levels, and call into question the value of Gal-3 to quantify disease severity in overt HFpEF. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Effect of Biocompatible Peritoneal Dialysis Solution on Residual Renal Function: A Systematic Review of Randomized Controlled Trials

PubMed Central

Seo, Eun-Young; An, Sook Hee; Cho, Jang-Hee; Suh, Hae Sun; Park, Sun-Hee; Gwak, Hyesun; Kim, Yong-Lim; Ha, Hunjoo

2014-01-01

♦ Introduction: Residual renal function (RRF) plays an important role in outcome of peritoneal dialysis (PD) including mortality. It is, therefore, important to provide a strategy for the preservation of RRF. The objective of this study was to evaluate relative protective effects of new glucose-based multicompartmental PD solution (PDS), which is well known to be more biocompatible than glucose-based conventional PDS, on RRF compared to conventional PDS by performing a systematic review (SR) of randomized controlled trials. ♦ Methods: We searched studies presented up to January 2014 in MEDLINE, EMBASE, the COCHRANE library, and local databases. Three independent reviewers reviewed and extracted prespecified data from each study. The random effects model, a more conservative analysis model, was used to combine trials and to perform stratified analyses based on the duration of follow-up. Study quality was assessed using the Cochrane Handbook for risk of bias. Eleven articles with 1,034 patients were identified for the SR. ♦ Results: The heterogeneity of the studies under 12 months was very high, and the heterogeneity decreased substantially when we stratified studies by the duration of follow-up. The mean difference of the studies after 12 months was 0.46 mL/min/1.73 m2 (95% confidence interval = 0.25 to + 0.67). ♦ Conclusion: New PDS showed the effect to preserve and improve RRF for long-term use compared to conventional PDS, even though it did not show a significant difference to preserve RRF for short-term use. PMID:25185015

Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in healthy volunteers.

PubMed

Pruijm, Menno; Hofmann, Lucie; Charollais-Thoenig, Julie; Forni, Valentina; Maillard, Marc; Coristine, Andrew; Stuber, Matthias; Burnier, Michel; Vogt, Bruno

2013-09-01

Cocoa is rich in flavonoids, has anti-oxidative properties and increases the bioavailability of nitric oxide (NO). Adequate renal tissue oxygenation is crucial for the maintenance of renal function. The goal of this study was to investigate the effect of cocoa-rich dark chocolate (DC) on renal tissue oxygenation in humans, as compared to flavonoid-poor white chocolate (WC). Ten healthy volunteers with preserved kidney function (mean age ± SD 35 ± 12 years, 70% women, BMI 21 ± 3 kg/m2) underwent blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) before and 2 hours after the ingestion of 1 g/kg of DC (70% cocoa). Renal tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* (= 1/T2*) values in the medulla and cortex were calculated, a low R2* indicating high tissue oxygenation. Eight participants also underwent BOLD-MRI at least 1 week later, before and 2 hours after the intake of 1 g/kg WC. The mean medullary R2* was lower after DC intake compared to baseline (28.2 ± 1.3 s-1 vs. 29.6 ± 1.3 s-1, p = 0.04), whereas cortical and medullary R2* values did not change after WC intake. The change in medullary R2* correlated with the level of circulating (epi)catechines, metabolites of flavonoids (r = 0.74, p = 0.037), and was independent of plasma renin activity. This study suggests for the first time an increase of renal medullary oxygenation after intake of dark chocolate. Whether this is linked to flavonoid-induced changes in renal perfusion or oxygen consumption, and whether cocoa has potentially renoprotective properties, merits further study.

Renal Hemodynamics in AKI: In Search of New Treatment Targets

PubMed Central

Matejovic, Martin; Ince, Can; Chawla, Lakhmir S.; Blantz, Roland; Molitoris, Bruce A.; Okusa, Mark D.; Kellum, John A.; Ronco, Claudio

2016-01-01

Novel therapeutic interventions are required to prevent or treat AKI. To expedite progress in this regard, a consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 to develop recommendations for research priorities and future directions. Here, we highlight the concepts related to renal hemodynamics in AKI that are likely to reveal new treatment targets on investigation. Overall, we must better understand the interactions between systemic, total renal, and glomerular hemodynamics, including the role of tubuloglomerular feedback. Furthermore, the net consequences of therapeutic maneuvers aimed at restoring glomerular filtration need to be examined in relation to the nature, magnitude, and duration of the insult. Additionally, microvascular blood flow heterogeneity in AKI is now recognized as a common occurrence; timely interventions to preserve the renal microcirculatory flow may interrupt the downward spiral of injury toward progressive kidney failure and should, therefore, be investigated. Finally, development of techniques that permit an integrative physiologic approach, including direct visualization of renal microvasculature and measurement of oxygen kinetics and mitochondrial function in intact tissue in all nephron segments, may provide new insights into how the kidney responds to various injurious stimuli and allow evaluation of new therapeutic strategies. PMID:26510884

The Kallikrein-Kinin System: A Novel Mediator of IL-17-Driven Anti-Candida Immunity in the Kidney

PubMed Central

Ramani, Kritika; Garg, Abhishek V.; Jawale, Chetan V.; Jackson, Edwin K.; Shiva, Sruti S.; Horne, William; Kolls, Jay K.; Gaffen, Sarah L.; Biswas, Partha S.

2016-01-01

The incidence of life-threatening disseminated Candida albicans infections is increasing in hospitalized patients, with fatalities as high as 60%. Death from disseminated candidiasis in a significant percentage of cases is due to fungal invasion of the kidney, leading to renal failure. Treatment of candidiasis is hampered by drug toxicity, the emergence of antifungal drug resistance and lack of vaccines against fungal pathogens. IL-17 is a key mediator of defense against candidiasis. The underlying mechanisms of IL-17-mediated renal immunity have so far been assumed to occur solely through the regulation of antimicrobial mechanisms, particularly activation of neutrophils. Here, we identify an unexpected role for IL-17 in inducing the Kallikrein (Klk)-Kinin System (KKS) in C. albicans-infected kidney, and we show that the KKS provides significant renal protection in candidiasis. Microarray data indicated that Klk1 was upregulated in infected kidney in an IL-17-dependent manner. Overexpression of Klk1 or treatment with bradykinin rescued IL-17RA-/- mice from candidiasis. Therapeutic manipulation of IL-17-KKS pathways restored renal function and prolonged survival by preventing apoptosis of renal cells following C. albicans infection. Furthermore, combining a minimally effective dose of fluconazole with bradykinin markedly improved survival compared to either drug alone. These results indicate that IL-17 not only limits fungal growth in the kidney, but also prevents renal tissue damage and preserves kidney function during disseminated candidiasis through the KKS. Since drugs targeting the KKS are approved clinically, these findings offer potential avenues for the treatment of this fatal nosocomial infection. PMID:27814401

Radiofrequency ablation of renal cell carcinoma: a follow up of outcomes.

PubMed

Curry, David; Yassin, Musaab; Thwaini, Ali; Pahuja, Ajay; Alanbuki, Ammar H; Rajan, Thiagarajan Nambi; Loan, Willie

2014-02-01

To present the oncological outcomes in a series of patients with cT1a renal cell carcinoma (RCC) treated with radiofrequency ablation (RFA) and its effect on the glomerular filtration rate (GFR). Forty-five patients (48 renal units) treated at the Belfast City Hospital, over 4 years. Average age is 61.5 years (range 41-80). Eighteen patients (22 renal units) were included with American Society of Anesthesiologists (ASA) II and III. The rest were ASA I. Average tumor size was 2.63 cm (range 1.2 cm-6 cm). Renal function before and after RFA was recorded by means of the estimated glomerular filtration rate (eGFR) and the changes are presented. Oncological outcomes were established from follow up imaging. A satisfactory response was defined by disappearance or a persistence of non-enhancing lesion of smaller size at follow up. A partial response was defined by a persistent but non-enhancing similar size lesion. A failed response was defined by enlarging or persistently enhancing lesions. Mean follow up was 30.6 months (4-60 months). A good response was found in 33 (74%) patients. A partial response was found in 3 (8%) patients and failed response was identified in 8 (18%) patients. The average reduction in eGFR was 11 mL/min. Two patients had a 50% reduction in their eGFR. No patient required dialysis following treatment. RFA presents safe treatment choice for patients with RCC, particularly those that are high risk surgical candidates and those who refuse surgery. Short term results suggest good oncological outcomes and preservation of renal function.

Klotho preservation by Rhein promotes toll-like receptor 4 proteolysis and attenuates lipopolysaccharide-induced acute kidney injury.

PubMed

Bi, Fangfang; Chen, Fang; Li, Yanning; Wei, Ai; Cao, Wangsen

2018-05-05

Renal anti-aging protein Klotho exhibits impressive properties of anti-inflammation and renal protection, however is suppressed early after renal injury, making Klotho restoration an attractive strategy of treating renal inflammatory disorders. Here, we reported that Klotho is enriched in macrophages and Klotho preservation by Rhein, an anthraquinone derived from medicinal plant rhubarb, attenuates lipopolysaccharide (LPS)-induced acute inflammation essentially via promoting toll-like receptor 4 (TLR4) degradation. LPS-induced pro-inflammatory NF-κB signaling and cytokine expressions coincided with Klotho repression and toll-like receptor 4 (TLR4) elevation in macrophages, renal epithelial cells, and acutely- inflamed kidney. Intriguingly, Rhein treatment effectively corrected the inverted alterations of Klotho and TLR4 and mitigated the TLR4 downstream inflammatory response in a Klotho restoration and TLR4 repression-dependent manner. Klotho inducibly associated with TLR4 after LPS stimulation and suppressed TLR4 protein abundance mainly via a proteolytic process sensitive to the inhibition of Klotho's putative β-glucuronidase activity. Consistently, Klotho knockdown by RNA interferences largely diminished the anti-inflammatory and renal protective effects of Rhein in a mouse model of acute kidney injury incurred by LPS. Thus, Klotho suppression of TLR4 via deglycosylation negatively controls TLR-associated inflammatory signaling and the endogenous Klotho preservation by Rhein or possibly other natural or synthetic compounds possesses promising potentials in the clinical treatment of renal inflammatory disorders. • Klotho is highly expressed in macrophages and repressed by LPS in vitro and in vivo. • Klotho inhibits LPS-induced TLR4 accumulation and the downstream signaling. • Klotho decreases TLR4 via a deglycosylation-associated proteolytic process. • Rhein effectively prevents acute inflammation-incurred Klotho suppression. • Rhein reversal of Klotho attenuates LPS-induced acute inflammation and kidney injury.

The effect of renin-angiotensin system blockade on renal protection in chronic kidney disease patients with hyperkalemia.

PubMed

Lee, Ju-Hyun; Kwon, Young Eun; Park, Jung Tak; Lee, Mi Jung; Oh, Hyung Jung; Han, Seung Hyeok; Kang, Shin-Wook; Choi, Kyu Hun; Yoo, Tae-Hyun

2014-12-01

The aim of this study was to determine the effects of renin-angiotensin system (RAS) blockade maintenance on renal protection in chronic kidney disease (CKD) patients with hyperkalemia occurring during treatment with RAS blockade. CKD III or IV patients, who were prescribed with RAS blockers and also had hyperkalemia, were included. The study population was divided into two groups based on maintenance or withdrawal of RAS blocker. Renal outcomes (doubling of creatinine or end-stage renal disease) and incidence of hyperkalemia were compared between the two groups. Out of 258 subjects who developed hyperkalemia during treatment with RAS blockers, 150 (58.1%) patients continued on RAS blockades, while RAS blockades were discontinued for more than 3 months in the remaining 108 patients. Renal event-free survival was significantly higher in the maintenance group compared with the withdrawal group. Cox proportional hazard ratio for renal outcomes was 1.35 (95% CI: 1.08-1.92, p=0.04) in the withdrawal group compared with the maintenance group. However, the incidence of hyperkalemia and hyperkalemia-related hospitalization or mortality did not differ between the two groups. This study demonstrated that the maintenance of RAS blockade is beneficial for the preservation of renal function and relatively tolerable in patients with CKD and hyperkalemia occurring during treatment with RAS blockade. © The Author(s) 2014.

Risk factors for loss of residual renal function in children treated with chronic peritoneal dialysis.

PubMed

Ha, Il-Soo; Yap, Hui K; Munarriz, Reyner L; Zambrano, Pedro H; Flynn, Joseph T; Bilge, Ilmay; Szczepanska, Maria; Lai, Wai-Ming; Antonio, Zenaida L; Gulati, Ashima; Hooman, Nakysa; van Hoeck, Koen; Higuita, Lina M S; Verrina, Enrico; Klaus, Günter; Fischbach, Michel; Riyami, Mohammed A; Sahpazova, Emilja; Sander, Anja; Warady, Bradley A; Schaefer, Franz

2015-09-01

In dialyzed patients, preservation of residual renal function is associated with better survival, lower morbidity, and greater quality of life. To analyze the evolution of residual diuresis over time, we prospectively monitored urine output in 401 pediatric patients in the global IPPN registry who commenced peritoneal dialysis (PD) with significant residual renal function. Associations of patient characteristics and time-variant covariates with daily urine output and the risk of developing oligoanuria (under 100 ml/m(2)/day) were analyzed by mixed linear modeling and Cox regression analysis including time-varying covariates. With an average loss of daily urine volume of 130 ml/m(2) per year, median time to oligoanuria was 48 months. Residual diuresis significantly subsided more rapidly in children with glomerulopathies, lower diuresis at start of PD, high ultrafiltration volume, and icodextrin use. Administration of diuretics significantly reduced oligoanuria risk, whereas the prescription of renin-angiotensin system antagonists significantly increased the risk oligoanuria. Urine output on PD was significantly associated in a negative manner with glomerulopathies (-584 ml/m(2)) and marginally with the use of icodextrin (-179 ml/m(2)) but positively associated with the use of biocompatible PD fluid (+111 ml/m(2)). Children in both Asia and North America had consistently lower urine output compared with those in Europe perhaps due to regional variances in therapy. Thus, in children undergoing PD, residual renal function depends strongly on the cause of underlying kidney disease and may be modifiable by diuretic therapy, peritoneal ultrafiltration, and choice of PD fluid.

Risk factors for loss of residual renal function in children treated with chronic peritoneal dialysis

PubMed Central

Ha, Il-Soo; Yap, Hui K; Munarriz, Reyner L; Zambrano, Pedro H; Flynn, Joseph T; Bilge, Ilmay; Szczepanska, Maria; Lai, Wai-Ming; Antonio, Zenaida L; Gulati, Ashima; Hooman, Nakysa; van Hoeck, Koen; Higuita, Lina M S; Verrina, Enrico; Klaus, Günter; Fischbach, Michel; Riyami, Mohammed A; Sahpazova, Emilja; Sander, Anja; Warady, Bradley A; Schaefer, Franz

2015-01-01

In dialyzed patients, preservation of residual renal function is associated with better survival, lower morbidity, and greater quality of life. To analyze the evolution of residual diuresis over time, we prospectively monitored urine output in 401 pediatric patients in the global IPPN registry who commenced peritoneal dialysis (PD) with significant residual renal function. Associations of patient characteristics and time-variant covariates with daily urine output and the risk of developing oligoanuria (under 100 ml/m2/day) were analyzed by mixed linear modeling and Cox regression analysis including time-varying covariates. With an average loss of daily urine volume of 130 ml/m2 per year, median time to oligoanuria was 48 months. Residual diuresis significantly subsided more rapidly in children with glomerulopathies, lower diuresis at start of PD, high ultrafiltration volume, and icodextrin use. Administration of diuretics significantly reduced oligoanuria risk, whereas the prescription of renin–angiotensin system antagonists significantly increased the risk oligoanuria. Urine output on PD was significantly associated in a negative manner with glomerulopathies (−584 ml/m2) and marginally with the use of icodextrin (−179 ml/m2) but positively associated with the use of biocompatible PD fluid (+111 ml/m2). Children in both Asia and North America had consistently lower urine output compared with those in Europe perhaps due to regional variances in therapy. Thus, in children undergoing PD, residual renal function depends strongly on the cause of underlying kidney disease and may be modifiable by diuretic therapy, peritoneal ultrafiltration, and choice of PD fluid. PMID:25874598

Analysis of factors causing hyperkalemia.

PubMed

Takaichi, Kenmei; Takemoto, Fumi; Ubara, Yoshifumi; Mori, Yasumichi

2007-01-01

Patients with impaired renal function or diabetes are considered to be prone to hyperkalemia. Furthermore, hyperkalemia is an adverse drug reaction of inhibitors of the renin-angiotensin system (RAS) that are established to be efficacious in these patients. However, the current status of hyperkalemia in the clinical setting remains obscure. A total of 9,117 patients treated at Toranomon Hospital between January and October 2005, who had serum creatinine levels below 5 mg/dL were studied. Patients on dialysis and patients using cation exchange resin or diuretics that lower serum potassium were excluded. Serum potassium increased significantly accompanying the increase in serum creatinine, and was significantly elevated in diabetic patients compared to non-diabetic patients. Serum potassium also increased significantly with the administration of angiotensin-II receptor blockers (ARB), angiotensin-converting-enzyme inhibitors (ACEI) or beta-blockers. A combination of diabetes and RAS inhibitor administration significantly increased serum potassium compared to each factor alone in patients with a serum creatinine level below 1.5 mg/dL but not in those with a higher serum creatinine level. According to step-wise multiple regression analyses, an elevated serum creatinine level had the strongest positive correlation with the serum potassium level, followed by diabetes, ACEI use, ARB use, and age. Lowered renal function, diabetes, use of RAS inhibitors and old age are independent factors that increase the serum potassium level. Caution should be exercised when using RAS inhibitors in diabetic patients even if their renal function is relatively preserved. In selected patients with diabetes or impaired renal function, however, RAS inhibitors can be used without hyperkalemia.

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.

Do Alloreactivity and Prolonged Cold Ischemia Cause Different Elementary Lesions in Chronic Allograft Nephropathy?

PubMed Central

Herrero-Fresneda, Immaculada; Torras, Joan; Cruzado, Josep M.; Condom, Enric; Vidal, August; Riera, Marta; Lloberas, Nuria; Alsina, Jeroni; Grinyo, Josep M.

2003-01-01

This study assesses the individual contributions of the nonalloreactive factor, cold ischemia (CI), and alloreactivity to late functional and structural renal graft changes, and examines the effect of the association of both factors on the progression of chronic allograft nephropathy. Lewis rats acted as receptors of kidneys from either Lewis or Fischer rats. For CI, kidneys were preserved for 5 hours. The rats were divided into four groups: Syn, syngeneic graft; SynI, syngeneic graft and CI; Allo, allogeneic graft; AlloI, allogeneic graft and CI. Renal function was assessed every 4 weeks for 24 weeks. Grafts were evaluated for acute inflammatory response at 1 week and for chronic histological damage at 24 weeks. Only when CI and allogenicity were combined did immediate posttransplant mortality occur, while survivors showed accelerated renal insufficiency that induced further mortality at 12 weeks after transplant. Solely ischemic rats developed renal insufficiency. Renal structural damage in ischemic rats was clearly tubulointerstitial, while significant vasculopathy and glomerulosclerosis appeared only in the allogeneic groups. There was increased infiltration of macrophages and expression of mRNA-transforming growth factor-β1 in the ischemic groups, irrespective of the allogeneic background. The joint association of CI plus allogenicity significantly increased cellular infiltration at both early and late stages, aggravating tubulointerstitial and vascular damage considerably. In summary, CI is mainly responsible for tubulointerstitial damage, whereas allogenicity leads to vascular lesion. The association of both factors accelerates and aggravates the progression of experimental chronic allograft nephropathy. PMID:12507896

Peritoneal Dialysis in Diabetics: There Is Room for More

PubMed Central

Cotovio, P.; Rocha, A.; Rodrigues, A.

2011-01-01

End stage renal disease diabetic patients suffer from worse clinical outcomes under dialysis-independently of modality. Peritoneal dialysis offers them the advantages of home therapy while sparing their frail vascular capital and preserving residual renal function. Other benefits and potential risks deserve discussion. Predialysis intervention with early nephrology referral, patient education, and multidisciplinary support are recommended. Skilled and updated peritoneal dialysis protocols must be prescribed to assure better survival. Optimized volume control, glucose-sparing peritoneal dialysis regimens, and elective use of icodextrin are key therapy strategies. Nutritional evaluation and support, preferential use of low-glucose degradation products solutions, and prescription of renin-angiotensin-aldosterone system acting drugs should also be part of the panel to improve diabetic care under peritoneal dialysis. PMID:22013524

Partial Resuscitative Endovascular Balloon Occlusion of the Aorta (P-REBOA) in a Pig Model (Sus scrofa) with ongoing Resuscitation

DTIC Science & Technology

2016-01-08

occlusion, regulated flow provided perfusion to capillary beds. Following 70 minutes of partial aortic occlusion, damage control surgery and whole blood ... renal function, and were weaned from aortic occlusion more rapidly. CONCLUSIONS: P-REBOA is capable of limiting exsanguination while providing blood ...resuscitation was performed and all animals were survived to 360 minutes. Animals that tolerated distal flow had decreased levels of lactate, preserved

FTY720 and everolimus in de novo renal transplant patients at risk for delayed graft function: results of an exploratory one-yr multicenter study.

PubMed

Tedesco-Silva, H; Lorber, M I; Foster, C E; Sollinger, H W; Mendez, R; Carvalho, D B; Shapiro, R; Rajagopalan, P R; Mayer, H; Slade, J; Kahan, B D

2009-01-01

This exploratory, multicenter, open-label study evaluated the efficacy and safety of FTY720, as a part of an immunosuppressive regimen, in combination with everolimus and steroids in de novo renal transplant recipients at increased risk of delayed graft function (DGF). Patients received FTY720 (5 mg) and everolimus (4 mg) 2-12 h pre-transplantation, followed by 2.5 mg/d FTY720 and concentration-controlled everolimus (4-8 ng/mL) post-transplant for 12 months. Induction therapy was prohibited. After enrollment of 56 of the planned 200 patients between 2000 and 2002, the recruitment was terminated. The primary endpoint, rate of graft loss, or death at three months was 15.4% and the biopsy-confirmed acute rejection was 42.3%. Death or graft loss at 12 months in the DGF and non-DGF arms was 36.0% and 25.9%, respectively. The mean estimated creatinine clearance at three months was 63 and 55 mL/min in the non-DGF and DGF groups, respectively, while at 12 months it was 56 mL/min in both the groups. Although there was no comparator arm, the results from this exploratory study (compared with data from other phases II and III trials) indicated no apparent benefits of FTY720-based regimens for prevention of acute rejection and preservation of renal function in renal transplant recipients at high risk of DGF.

Transient Ureteral Obstruction Prevents against Kidney Ischemia/Reperfusion Injury via Hypoxia-Inducible Factor (HIF)-2α Activation

PubMed Central

Chen, Xiao-Song; Zhang, Ming; Xu, Long-Mei; Zhang, Jian-Jun; Xia, Qiang

2012-01-01

Although the protective effect of transient ureteral obstruction (UO) prior to ischemia on subsequent renal ischemia/reperfusion (I/R) injury has been documented, the underlying molecular mechanism remains to be understood. We showed in the current study that 24 h of UO led to renal tubular hypoxia in the ipsilateral kidney in mice, with the accumulation of hypoxia-inducible factor (HIF)-2α, which lasted for a week after the release of UO. To address the functions of HIF-2α in UO-mediated protection of renal IRI, we utilized the Mx-Cre/loxP recombination system to knock out target genes. Inactivation of HIF-2α, but not HIF-1α blunted the renal protective effects of UO, as demonstrated by much higher serum creatinine level and severer histological damage. UO failed to prevent postischemic neutrophil infiltration and apoptosis induction in HIF-2α knockout mice, which also diminished the postobstructive up-regulation of the protective molecule, heat shock protein (HSP)-27. The renal protective effects of UO were associated with the improvement of the postischemic recovery of intra-renal microvascular blood flow, which was also dependent on the activation of HIF-2α. Our results demonstrated that UO protected the kidney via activation of HIF-2α, which reduced tubular damages via preservation of adequate renal microvascular perfusion after ischemia. Thus, preconditional HIF-2α activation might serve as a novel therapeutic strategy for the treatment of ischemic acute renal failure. PMID:22295069

Metabolic Changes in Summer Active and Anuric Hibernating Free-Ranging Brown Bears (Ursus arctos)

PubMed Central

Stenvinkel, Peter; Fröbert, Ole; Anderstam, Björn; Palm, Fredrik; Eriksson, Monica; Bragfors-Helin, Ann-Christin; Qureshi, Abdul Rashid; Larsson, Tobias; Friebe, Andrea; Zedrosser, Andreas; Josefsson, Johan; Svensson, My; Sahdo, Berolla; Bankir, Lise; Johnson, Richard J.

2013-01-01

The brown bear (Ursus arctos) hibernates for 5 to 6 months each winter and during this time ingests no food or water and remains anuric and inactive. Despite these extreme conditions, bears do not develop azotemia and preserve their muscle and bone strength. To date most renal studies have been limited to small numbers of bears, often in captive environments. Sixteen free-ranging bears were darted and had blood drawn both during hibernation in winter and summer. Samples were collected for measurement of creatinine and urea, markers of inflammation, the calcium-phosphate axis, and nutritional parameters including amino acids. In winter the bear serum creatinine increased 2.5 fold despite a 2-fold decrease in urea, indicating a remarkable ability to recycle urea nitrogen during hibernation. During hibernation serum calcium remained constant despite a decrease in serum phosphate and a rise in FGF23 levels. Despite prolonged inactivity and reduced renal function, inflammation does not ensue and bears seem to have enhanced antioxidant defense mechanisms during hibernation. Nutrition parameters showed high fat stores, preserved amino acids and mild hyperglycemia during hibernation. While total, essential, non-essential and branched chain amino acids concentrations do not change during hibernation anorexia, changes in individual amino acids ornithine, citrulline and arginine indicate an active, although reduced urea cycle and nitrogen recycling to proteins. Serum uric acid and serum fructose levels were elevated in summer and changes between seasons were positively correlated. Further studies to understand how bears can prevent the development of uremia despite minimal renal function during hibernation could provide new therapeutic avenues for the treatment of human kidney disease. PMID:24039826

Biocompatibility and hemocompatibility of efficiently decellularized whole porcine kidney for tissue engineering.

PubMed

Hussein, Kamal Hany; Saleh, Tarek; Ahmed, Ebtehal; Kwak, Ho-Hyun; Park, Kyung-Mee; Yang, Se-Ran; Kang, Byung-Jae; Choi, Ki-Young; Kang, Kyung-Sun; Woo, Heung-Myong

2018-07-01

Whole kidney decellularization is a promising approach in regenerative medicine for engineering a functional organ. The reaction of the potential host depends on the biocompatibility of these decellularized constructs. Despite the proven ability of decellularized kidney scaffolds to guide cell attachment and growth, little is known about biocompatibility and hemocompatibility of these scaffolds. Our aim is to prepare decellularized kidneys of a clinically relevant size and evaluate its biocompatibility and hemocompatibility. Porcine kidneys were cannulated via the renal artery, and then perfused with 0.1% sodium dodecyl sulfate solution. Hematoxylin and eosin as well as DAPI staining confirmed cellular clearance from native kidneys in addition to preservation of the microstructure. SEM confirmed the absence of any cellular content within the scaffold, which is maintained in a well-organized 3D architecture. Decellularized kidneys retained the intact renal vasculature upon examination with contrast radiography. The essential structural extracellular matrix molecules were well-preserved. Scaffolds were susceptible to enzymatic degradation upon collagenase treatment. Scaffolds showed a good hemocompatibility when exposed to porcine blood. Decellularization was efficient to remove 97.7% of DNA from native kidneys in addition to the immunogenic and pathogenic antigens. Scaffolds did not induce the human immune response in vitro. Decellularized kidneys were non-cytotoxic to pig kidney cells (PKs). PKs were able to grow and proliferate within the decellularized renal scaffolds with maintaining a higher function than cells grown as monolayers. Thus, we have developed a rapid decellularization technique for generating biocompatible kidney scaffolds that represents a step toward development of a transplantable organ. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2034-2047, 2018. © 2018 Wiley Periodicals, Inc.

Metabolic changes in summer active and anuric hibernating free-ranging brown bears (Ursus arctos).

PubMed

Stenvinkel, Peter; Fröbert, Ole; Anderstam, Björn; Palm, Fredrik; Eriksson, Monica; Bragfors-Helin, Ann-Christin; Qureshi, Abdul Rashid; Larsson, Tobias; Friebe, Andrea; Zedrosser, Andreas; Josefsson, Johan; Svensson, My; Sahdo, Berolla; Bankir, Lise; Johnson, Richard J

2013-01-01

The brown bear (Ursus arctos) hibernates for 5 to 6 months each winter and during this time ingests no food or water and remains anuric and inactive. Despite these extreme conditions, bears do not develop azotemia and preserve their muscle and bone strength. To date most renal studies have been limited to small numbers of bears, often in captive environments. Sixteen free-ranging bears were darted and had blood drawn both during hibernation in winter and summer. Samples were collected for measurement of creatinine and urea, markers of inflammation, the calcium-phosphate axis, and nutritional parameters including amino acids. In winter the bear serum creatinine increased 2.5 fold despite a 2-fold decrease in urea, indicating a remarkable ability to recycle urea nitrogen during hibernation. During hibernation serum calcium remained constant despite a decrease in serum phosphate and a rise in FGF23 levels. Despite prolonged inactivity and reduced renal function, inflammation does not ensue and bears seem to have enhanced antioxidant defense mechanisms during hibernation. Nutrition parameters showed high fat stores, preserved amino acids and mild hyperglycemia during hibernation. While total, essential, non-essential and branched chain amino acids concentrations do not change during hibernation anorexia, changes in individual amino acids ornithine, citrulline and arginine indicate an active, although reduced urea cycle and nitrogen recycling to proteins. Serum uric acid and serum fructose levels were elevated in summer and changes between seasons were positively correlated. Further studies to understand how bears can prevent the development of uremia despite minimal renal function during hibernation could provide new therapeutic avenues for the treatment of human kidney disease.

Successful Dual Kidney Transplantation After Hypothermic Oxygenated Perfusion of Discarded Human Kidneys

PubMed Central

Ravaioli, Matteo; De Pace, Vanessa; Comai, Giorgia; Busutti, Marco; Gaudio, Massimo Del; Amaduzzi, Annalisa; Cucchetti, Alessandro; Siniscalchi, Antonio; La Manna, Gaetano; D’Errico, Antonietta A.D.; Pinna, Antonio Daniele

2017-01-01

Patient: Female, 58 Final Diagnosis: Nephroangiosclerosis Symptoms: Renal failure Medication: — Clinical Procedure: Resuscitation of grafts by hypothermic oxygenated perfusion Specialty: Transplantology Objective: Challenging differential diagnosis Background: The recovery of discarded human kidneys has increased in recent years and impels to use of unconventional organ preservation strategies that improve graft function. We report the first case of human kidneys histologically discarded and transplanted after hypothermic oxygenated perfusion (HOPE). Case Report: Marginal kidneys from a 78-year-old woman with brain death were declined by Italian transplant centers due to biopsy score (right kidney: 6; left kidney: 7). We recovered and preserved both kidneys through HOPE and we revaluated their use for transplantation by means of perfusion parameters. The right kidney was perfused for 1 h 20 min and the left kidney for 2 h 30 min. During organ perfusion, the renal flow increased progressively. We observed an increase of 34% for the left kidney (median flow 52 ml/min) and 50% for the right kidney (median flow 24 ml/min). Both kidneys had low perfusate’s lactate levels. We used perfusion parameters as important determinants of the organ discard. Based on our previous organ perfusion experience, the increase of renal flow and the low level of lactate following 1 h of HOPE lead us to declare both kidneys as appropriate for dual kidney transplantation (DKT). No complications were reported during the transplant and in the post-transplant hospital stay. The recipient had immediate graft function and serum creatinine value of 0.95 mg/dL at 3 months post-transplant. Conclusions: HOPE provides added information in the organ selection process and may improve graft quality of marginal kidneys. PMID:28928357

Benefits of a Continuous Ambulatory Peritoneal Dialysis (CAPD) Technique with One Icodextrin-Containing and Two Biocompatible Glucose-Containing Dialysates for Preservation of Residual Renal Function and Biocompatibility in Incident CAPD Patients

PubMed Central

2014-01-01

In a prospective randomized controlled study, the efficacy and safety of a continuous ambulatory peritoneal dialysis (CAPD) technique has been evaluated using one icodextrin-containing and two glucose-containing dialysates a day. Eighty incident CAPD patients were randomized to two groups; GLU group continuously using four glucose-containing dialysates (n=39) and ICO group using one icodextrin-containing and two glucose-containing dialysates (n=41). Variables related to residual renal function (RRF), metabolic and fluid control, dialysis adequacy, and dialysate effluent cancer antigen 125 (CA125) and interleukin 6 (IL-6) levels were measured. The GLU group showed a significant decrease in mean renal urea and creatinine clearance (-Δ1.2±2.9 mL/min/1.73 m2, P=0.027) and urine volume (-Δ363.6±543.0 mL/day, P=0.001) during 12 months, but the ICO group did not (-Δ0.5±2.7 mL/min/1.73 m2, P=0.266; -Δ108.6±543.3 mL/day, P=0.246). Peritoneal glucose absorption and dialysate calorie load were significantly lower in the ICO group than the GLU group. The dialysate CA125 and IL-6 levels were significantly higher in the ICO group than the GLU group. Dialysis adequacy, β2-microglobulin clearance and blood pressure did not differ between the two groups. The CAPD technique using one icodextrin-containing and two glucose-containing dialysates tends to better preserve RRF and is more biocompatible, with similar dialysis adequacy compared to that using four glucose-containing dialysates in incident CAPD patients. [Clincal Trial Registry, ISRCTN23727549] Graphical Abstract PMID:25246739

A Case of Left Renal Vein Ligation in a Patient with Solitary Left Kidney Undergoing Liver Transplantation to Control Splenorenal Shunt and Improve Portal Venous Flow.

PubMed

Martino, Rodrigo B; Júnior, Eserval Rocha; Manuel, Valdano; Rocha-Santos, Vinicius; D'Albuquerque, Luis Augusto C; Andraus, Wellington

2017-10-11

BACKGROUND Adequate portal venous flow is required for successful liver transplantation. Reduced venous flow and blood flow 'steal' by collateral vessels are a concern, and when there is a prominent splenorenal shunt present, ligation of the left renal vein has been recommended to improve portal venous blood flow. CASE REPORT A 51-year-old man who had undergone right nephrectomy in childhood required liver transplantation for liver cirrhosis and hepatocellular carcinoma due to hepatitis C virus (HCV) infection. The patient had no other comorbidity and no history of hepatorenal syndrome. At transplantation surgery, portal venous flow was poor and did not improve with ligation of shunt veins, but ligation of the left renal vein improved portal venous flow. On the first and fifth postoperative days, the patient was treated with basiliximab, a chimeric monoclonal antibody to the IL-2 receptor, and methylprednisolone. The calcineurin inhibitor, tacrolimus, was introduced on the fifth postoperative day. On the sixteenth postoperative day, renal color Doppler ultrasound showed normal left renal parenchyma; hepatic Doppler ultrasound showed good portal vein flow and preserved hepatic parenchyma in the liver transplant. CONCLUSIONS This case report has shown that in a patient with a single left kidney, left renal vein ligation is feasible and safe in a patient with no other risk factors for renal impairment following liver transplantation. Modification of postoperative immunosuppression to avoid calcineurin inhibitors in the very early postoperative phase may be important in promoting good recovery of renal function and to avoid the need for postoperative renal dialysis.

Worsening renal function and outcome in heart failure patients with preserved ejection fraction and the impact of angiotensin receptor blocker treatment.

PubMed

Damman, Kevin; Perez, Ana C; Anand, Inder S; Komajda, Michel; McKelvie, Robert S; Zile, Michael R; Massie, Barrie; Carson, Peter E; McMurray, John J V

2014-09-16

Worsening renal function (WRF) associated with renin-angiotensin-aldosterone system (RAAS) inhibition does not confer excess risk in heart failure patients with reduced ejection fraction (HFrEF). The goal of this study was to investigate the relationship between WRF and outcomes in heart failure patients with preserved ejection fraction (HFpEF) and the interaction with RAAS blockade. In 3,595 patients included in the I-PRESERVE (Irbesartan in Heart Failure With Preserved Ejection Fraction) trial, change in estimated glomerular filtration rate (eGFR) and development of WRF after initiation of irbesartan or placebo were examined. We examined the association between WRF and the first occurrence of cardiovascular death or heart failure hospitalization (primary outcome in this analysis) and the interaction with randomized treatment. Estimated GFR decreased early with irbesartan treatment and remained significantly lower than in the placebo group. WRF developed in 229 (6.4%) patients and occurred more frequently with irbesartan treatment (8% vs. 4%). Overall, WRF was associated with an increased risk of the primary outcome (adjusted hazard ratio [HR]: 1.43; 95% confidence interval [CI]: 1.10 to 1.85; p = 0.008). Although the risk related to WRF was greater in the irbesartan group (HR: 1.66; 95% CI: 1.21 to 2.28; p = 0.002) than with placebo (HR: 1.09; 95% CI: 0.66 to 1.79; p = 0.73), the interaction between treatment and WRF on outcome was not significant in an adjusted analysis. The incidence of WRF in HFpEF was similar to that previously reported in HFrEF but more frequent with irbesartan than with placebo. WRF after initiation of irbesartan treatment in HFpEF was associated with excess risk, in contrast to WRF occurring with RAAS blockade in HFrEF. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Effect of Icodextrin Solution on the Preservation of Residual Renal Function in Peritoneal Dialysis Patients: A Randomized Controlled Study.

PubMed

Chang, Tae Ik; Ryu, Dong-Ryeol; Yoo, Tae-Hyun; Kim, Hyung Jong; Kang, Ea Wha; Kim, Hyunwook; Chang, Jae Hyun; Kim, Dong Ki; Moon, Sung Jin; Yoon, Soo Young; Han, Seung Hyeok

2016-03-01

Although icodextrin solution has been highlighted in the fluid management compared to glucose-based solutions, proof of a beneficial effect of icodextrin solution on residual renal function (RRF) is lacking. We conducted a multicenter prospective randomized controlled open-label trial to investigate whether icodextrin solution can preserve RRF.One hundred patients with urine volume ≥750 mL/day from 8 centers in Korea were randomly assigned to receive 1 exchange of icodextrin solution for a ≥8 hour-dwell time and 2 exchanges of 1.5% glucose-based biocompatible neutral pH solution or 1 exchange of ≥2.5% and 2 exchanges of 1.5% glucose-based biocompatible solutions. Using mixed-effects general linear models, we analyzed changes in residual glomerular filtration rate (GFR) and daily urine volume at 1 year.Forty-nine patients were assigned to the icodextrin group and 51 to the glucose solution group. During follow-up, the slope of the decline in residual GFR was -0.170 mL/min/month/1.73 m² in the icodextrin group, while it was -0.155 mL/min/month/1.73 m² in the glucose solution group (95% confidence interval [CI], -0.06 to 0.10; P = 0.701). Daily urine volume decreased faster in the glucose solution group than in the icodextrin group (-31.02 vs -11.88 mL per month; 95% CI, -35.85 to -2.44; P = 0.025). Results were consistent when we analyzed using intention-to-treat and per protocol principles. There were no differences in fluid status, peritoneal ultrafiltration, and peritoneal transport between groups during follow-up.This study clearly showed that icodextrin solution preserves residual urine volume better than glucose solution.

[Ultrafiltration versus intravenous diuretics in decompensated heart failure: a meta-analysis of randomized controlled trials].

PubMed

Zhao, Yu-liang; Zhang, Ling; Yang, Ying-ying; Tang, Yi; Liu, Fang; Fu, Ping

2013-08-13

To explore whether ultrafiltration is superior to intravenous diuretics in ameliorating fluid overload and preserving renal functions in decompensated heart failure patients. By searching in Pubmed, Cochrane Library, Embase, Springer, WanFang, CQVIP, CNKI and CBM database as well as related Chinese journals, qualified randomized controlled trials (RCTs) were included for meta-analysis by Revman 5.0 and STATA 10.0. Six RCTs were included with 241 patients in ultrafiltration group and 240 patients in intravenous diuretics group. Pooled analyses demonstrated ultrafiltration was superior to intravenous diuretics in the aspects of weight loss (WMD = 1.44 kg, 95%CI:0.33-2.55 kg, P = 0.01) and fluid removal (WMD = 1.23 kg, 95%CI:0.63-1.82 kg, P < 0.01) while no significant difference was observed in serum creatinine level (WMD = -5.70 µmol/L, 95%CI: -35.02-23.61 µmol/L, P = 0.70), serum creatinine change from baseline (WMD = 4.74 µmol/L, 95%CI:-13.72-23.20 µmol/L, P = 0.61), mortality (RR = 1.09, 95%CI: 0.69-1.70, P = 0.72) or rehospitalization (RR = 0.92, 95%CI:0.53-1.61, P = 0.78). For decompensated heart failure patients, ultrafiltration is superior to intravenous diuretics in mitigating fluid overload. No intergroup difference was observed in renal function preservation, mortality or rehospitalization.

Abnormalities of serum potassium concentration in dialysis-associated hyperglycemia and their correction with insulin: review of published reports.

PubMed

Tzamaloukas, Antonios H; Ing, Todd S; Elisaf, Moses S; Raj, Dominic S C; Siamopoulos, Kostas C; Rohrscheib, Mark; Murata, Glen H

2011-06-01

The main difference between dialysis-associated hyperglycemia (DH) and diabetic ketoacidosis (DKA) or nonketotic hyperglycemia (NKH) occurring in patients with preserved renal function is the absence of osmotic diuresis in DH, which eliminates the need for large fluid and solute (including potassium) replacement. We analyzed published reports of serum potassium (K(+)) abnormalities and their treatment in DH. Hyperkalemia was often present at presentation of DH with higher frequency and severity than in hyperglycemic syndromes in patients with preserved renal function. The frequency and severity of hyperkalemia were higher in DH episodes with DKA than those with NKH in both hemodialysis and peritoneal dialysis. For DKA, the frequency and severity of hyperkalemia were similar in hemodialysis and peritoneal dialysis. For NKH, hyperkalemia was more severe and frequent in hemodialysis than in peritoneal dialysis. Insulin infusion corrected the hyperkalemia of DH in most cases. Additional measures for the management of hyperkalemia or modest potassium infusions for hypokalemia were needed in a few DH episodes. The predictors of the decrease in serum K(+) during treatment of DH with insulin included the starting serum K(+) level, the decreases in serum values of glucose concentration and tonicity, and the increase in serum total carbon dioxide level. DH represents a risk factor for hyperkalemia. Insulin infusion is the only treatment for hyperkalemia usually required.

Curcumin prevents mitochondrial dynamics disturbances in early 5/6 nephrectomy: Relation to oxidative stress and mitochondrial bioenergetics.

PubMed

Aparicio-Trejo, Omar Emiliano; Tapia, Edilia; Molina-Jijón, Eduardo; Medina-Campos, Omar Noel; Macías-Ruvalcaba, Norma Angélica; León-Contreras, Juan Carlos; Hernández-Pando, Rogelio; García-Arroyo, Fernando E; Cristóbal, Magdalena; Sánchez-Lozada, Laura Gabriela; Pedraza-Chaverri, José

2017-03-01

Five-sixths nephrectomy (5/6NX) is a widely used model to study the mechanisms leading to renal damage in chronic kidney disease (CKD). However, early alterations on renal function, mitochondrial dynamics, and oxidative stress have not been explored yet. Curcumin is an antioxidant that has shown nephroprotection in 5/6NX-induced renal damage. The aim of this study was to explore the effect of curcumin on early mitochondrial alterations induced by 5/6NX in rats. In isolated mitochondria, 5/6NX-induced hydrogen peroxide production was associated with decreased activity of complexes I and V, decreased activity of antioxidant enzymes, alterations in oxygen consumption and increased MDA-protein adducts. In addition, it was found that 5/6NX shifted mitochondrial dynamics to fusion, which was evidenced by increased optic atrophy 1 and mitofusin 1 (Mfn1) and decreased fission 1 and dynamin-related protein 1 expressions. These data were confirmed by morphological analysis and immunoelectron microscopy of Mfn-1. All the above-described mechanisms were prevented by curcumin. Also, it was found that curcumin prevented renal dysfunction by improving renal blood flow and the total antioxidant capacity induced by 5/6NX. Moreover, in glomeruli and proximal tubules 5/6NX-induced superoxide anion production by uncoupled nitric oxide synthase (NOS) and nicotinamide adenine dinucleotide phosphate oxidase (NOX) dependent way, this latter was associated with increased phosphorylation of serine 304 of p47phox subunit of NOX. In conclusion, this study shows that curcumin pretreatment decreases early 5/6NX-induced altered mitochondrial dynamics, bioenergetics, and oxidative stress, which may be associated with the preservation of renal function. © 2016 BioFactors, 43(2):293-310, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

Application and analysis of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for patients with multiple renal tumor: initial experience.

PubMed

Zhu, Jundong; Jiang, Fan; Li, Pu; Shao, Pengfei; Liang, Chao; Xu, Aiming; Miao, Chenkui; Qin, Chao; Wang, Zengjun; Yin, Changjun

2017-09-11

To explore the feasibility and safety of retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping for the patients with multiple renal tumor of who have solitary kidney or contralateral kidney insufficiency. Nine patients who have undergone retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping between October 2010 and January 2017 were retrospectively analyzed. Clinical materials and parameters during and after the operation were summarized. Nineteen tumors were resected in nine patients and the operations were all successful. The operation time ranged from 100 to 180 min (125 min); clamping time of segmental renal artery was 10 ~ 30 min (23 min); the amount of blood loss during the operation was 120 ~ 330 ml (190 ml); hospital stay after the operation is 3 ~ 6d (5d). There was no complication during the perioperative period, and the pathology diagnosis after the surgery showed that there were 13 renal clear cell carcinomas, two papillary carcinoma and four perivascular epithelioid cell tumors with negative margins from the 19 tumors. All patients were followed up for 3 ~ 60 months, and no local recurrence or metastasis was detected. At 3-month post-operation follow-up, the mean serum creatinine was 148.6 ± 28.1 μmol/L (p = 0.107), an increase of 3.0 μmol/L from preoperative baseline. For the patients with multiple renal tumors and solitary kidney or contralateral kidney insufficiency, retroperitoneal laparoscopic partial nephrectomy with sequential segmental renal artery clamping was feasible and safe, which minimized the warm ischemia injury to the kidney and preserved the renal function effectively.

Progenitor-like cells derived from mouse kidney protect against renal fibrosis in a remnant kidney model via decreased endothelial mesenchymal transition.

PubMed

Chen, C L; Chou, K J; Fang, H C; Hsu, C Y; Huang, W C; Huang, C W; Huang, C K; Chen, H Y; Lee, P T

2015-12-02

Pathophysiological changes associated with chronic kidney disease impair angiogenic processes and increase renal fibrosis. Progenitor-like cells derived from adult kidney have been previously used to promote regeneration in acute kidney injury, even though it remained unclear whether the cells could be beneficial in chronic kidney disease (CKD). In this study, we established a CKD model by five-sixths nephrectomy and mouse kidney progenitor-like cells (MKPCs) were intravenously administered weekly for 5 weeks after establishing CKD. We examined the impact of MKPCs on the progression of renal fibrosis and the potential of MKPCs to preserve the angiogenic process and prevent endothelial mesenchymal transition in vivo and in vitro. Our results demonstrate that the MKPCs delayed interstitial fibrosis and the progression of glomerular sclerosis and ameliorated the decline of kidney function. At 17 weeks, the treated mice exhibited lower blood pressures, higher hematocrit levels, and larger kidney sizes than the control mice. In addition, the MKPC treatment prolonged the survival of the mice with chronic kidney injuries. We observed a decreased recruitment of macrophages and myofibroblasts in the interstitium and the increased tubular proliferation. Notably, MKPC both decreased the level of vascular rarefaction and prevented endothelial mesenchymal transition (EndoMT) in the remnant kidneys. Moreover, the conditioned medium from the MKPCs ameliorated endothelial cell death under hypoxic culture conditions and prevented TGF-β-induced EndoMT through downregulation of phosphorylated Smad 3 in vitro. MKPCs may be a beneficial treatment for kidney diseases characterized by progressive renal fibrosis. The enhanced preservation of angiogenic processes following MKPC injections may be associated with decreased fibrosis in the remnant kidney. These findings provide further understanding of the mechanisms involved in these processes and will help develop new cell-based therapeutic strategies for regenerative medicine in renal fibrosis.

Autosomal dominant polycystic kidney disease and pain - a review of the disease from aetiology, evaluation, past surgical treatment options to current practice.

PubMed

Badani, K K; Hemal, A K; Menon, M

2004-01-01

Autosomal Dominant Polycystic Kidney Disease (ADPKD), often referred to as "adult" polycystic kidney disease, is one of the commonest hereditary disorders. It affects approximately 4 to 6 million individuals worldwide. The disease progresses to end-stage renal disease and it accounts for 10-15% of patients requiring dialysis in the United States. A comprehensive Medline search for aetiology, evaluation, screening, cellular biology, and treatment was utilized to locate, extract, and synthesize relevant data with respect to this topic. Special attention was focused on urologic literature and surgical textbooks regarding operative treatment of pain associated with ADPKD. Now, patients with ADPKD have more treatment options. More specifically, several therapeutic alternatives are now available for the management of pain in these patients. A recent review of literature supports the performance of open or laparoscopic cyst decortication procedures for control of pain and infection without the worry of causing further renal impairment in those with preserved renal function.

NFκB-Induced Periostin Activates Integrin-β3 Signaling to Promote Renal Injury in GN

PubMed Central

Prakoura, Niki; Kavvadas, Panagiotis; Kormann, Raphaёl; Dussaule, Jean-Claude; Chadjichristos, Christos E.

2017-01-01

De novo expression in the kidney of periostin, a protein involved in odontogenesis and osteogenesis, has been suggested as a biomarker of renal disease. In this study, we investigated the mechanism(s) of induction and the role of periostin in renal disease. Using a combination of bioinformatics, reporter assay, and chromatin immunoprecipitation analyses, we found that NFκB and other proinflammatory transcription factors induce periostin expression in vitro and that binding of these factors on the periostin promoter is enriched in glomeruli during experimental GN. Mice lacking expression of periostin displayed preserved renal function and structure during GN. Furthermore, delayed administration of periostin antisense oligonucleotides in wild-type animals with GN reversed already established proteinuria, diminished tissue inflammation, and improved renal structure. Lack of periostin expression also blunted the de novo renal expression of integrin-β3 and phosphorylation of focal adhesion kinase and AKT, known mediators of integrin-β3 signaling that affect cell motility and survival, observed during GN in wild-type animals. In vitro, recombinant periostin increased the expression of integrin-β3 and the concomitant phosphorylation of focal adhesion kinase and AKT in podocytes. Notably, periostin and integrin-β3 were highly colocalized in biopsy specimens from patients with inflammatory GN. These results demonstrate that interplay between periostin and renal inflammation orchestrates inflammatory and fibrotic responses, driving podocyte damage through downstream activation of integrin-β3 signaling. Targeting periostin may be a novel therapeutic strategy for treating CKD. PMID:27920156

The future of partial nephrectomy.

PubMed

Malthouse, Theo; Kasivisvanathan, Veeru; Raison, Nicholas; Lam, Wayne; Challacombe, Ben

2016-12-01

Innovation in recent times has accelerated due to factors such as the globalization of communication; but there are also more barriers/safeguards in place than ever before as we strive to streamline this process. From the first planned partial nephrectomy completed in 1887, it took over a century to become recommended practice for small renal tumours. At present, identified areas for improvement/innovation are 1) to preserve renal parenchyma, 2) to optimise pre-operative eGFR and 3) to reduce global warm ischaemia time. All 3 of these, are statistically significant predictors of post-operative renal function. Urologists, have a proud history of embracing innovation & have experimented with different clamping techniques of the renal vasculature, image guidance in robotics, renal hypothermia, lasers and new robots under development. The DaVinci model may soon no longer have a monopoly on this market, as it loses its stranglehold with novel technology emerging including added features, such as haptic feedback with reduced costs. As ever, our predictions of the future may well fall wide of the mark, but in order to progress, one must open the mind to the possibilities that already exist, as evolution of existing technology often appears to be a revolution in hindsight. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Management of staghorn renal stones

PubMed Central

Diri, Akif; Diri, Banu

2018-01-01

Abstract Staghorn stones are large branching stones that fill part of all of the renal pelvis and renal calyces and they can be complete or partial depending on the level of occupancy of the collecting system. Although kidney stones are commoner in men, staghorn stones are less often reported in men compared to women and they are usually unilateral. Due to the significant morbidity and potential mortality attributed to staghorn stones, prompt assessment and treatment is mandatory. Conversely, conservative treatment has been shown to carry a mortality rate of 28% in 10-year period and 36% risk of developing significant renal impairment. Staghorn stones are, therefore, significant disease entity that should be managed aggressively and effectively. Generally, the gold standard treatment for staghorn stones is surgical with a view to achieve stone-free collecting system and preserve renal function. Percutaneous nephrolithotomy should be the recommended first-line treatment for staghorn stones. Other non-surgical options are usually considered in combination with surgery or as monotherapy only if patients are surgically unfit. The decision for optimal treatment of staghorn stones should be individualized according to the circumstances of the patient involved and in order to do so, a closer look at the advantages and disadvantages of each option is necessary. PMID:29658394

[Ablative treatments in localized renal cancer: literature review for 2014].

PubMed

Chodez, M; Fiard, G; Arnoux, V; Descotes, J-L; Long, J-A

2015-07-01

To focus on indications and results of ablative treatments (cyoablation, radiofrequency) for small renal masses, a bibliographic research was conducted in MedLine database using terms of "ablative treatment", "cryotherapy", "radiofrequency", "kidney cancer", "renal cell carcinoma". Sixty-four articles were selected. Carcinologic outcomes seem to be better with cryoablation than with radiofrequency. Available results have to be balanced according to surgical approach, teams' experience and duration of follow-up. Tumour's size and central localization are the main factors of failure. The size of 3cm is the most generally validated. Hospital stay and complications seem to be better with ablative therapies than with surgical approach, especially with percutaneous approach. The renal function preservation appears to be better with ablative therapies. It could be an interesting alternative to partial nephrectomy for small masses, in particular for fragile patients or in particular indications (multifocal tumors, in case of solitary kidney or transplanted kidney). The indications in elderly people must be proposed with care after the comorbidities have been evaluated. Indications of ablative treatment for small renal masses improve, but the gold standard treatment remains partial nephrectomy and indications must be individually discussed. Other ablative treatments are under-development, needing further studies. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Renal Hemodynamics in AKI: In Search of New Treatment Targets.

PubMed

Matejovic, Martin; Ince, Can; Chawla, Lakhmir S; Blantz, Roland; Molitoris, Bruce A; Rosner, Mitchell H; Okusa, Mark D; Kellum, John A; Ronco, Claudio

2016-01-01

Novel therapeutic interventions are required to prevent or treat AKI. To expedite progress in this regard, a consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 to develop recommendations for research priorities and future directions. Here, we highlight the concepts related to renal hemodynamics in AKI that are likely to reveal new treatment targets on investigation. Overall, we must better understand the interactions between systemic, total renal, and glomerular hemodynamics, including the role of tubuloglomerular feedback. Furthermore, the net consequences of therapeutic maneuvers aimed at restoring glomerular filtration need to be examined in relation to the nature, magnitude, and duration of the insult. Additionally, microvascular blood flow heterogeneity in AKI is now recognized as a common occurrence; timely interventions to preserve the renal microcirculatory flow may interrupt the downward spiral of injury toward progressive kidney failure and should, therefore, be investigated. Finally, development of techniques that permit an integrative physiologic approach, including direct visualization of renal microvasculature and measurement of oxygen kinetics and mitochondrial function in intact tissue in all nephron segments, may provide new insights into how the kidney responds to various injurious stimuli and allow evaluation of new therapeutic strategies. Copyright © 2016 by the American Society of Nephrology.

Histomorphometry of feline chronic kidney disease and correlation with markers of renal dysfunction.

PubMed

Chakrabarti, S; Syme, H M; Brown, C A; Elliott, J

2013-01-01

Chronic kidney disease is common in geriatric cats, but most cases have nonspecific renal lesions, and few studies have correlated these lesions with clinicopathological markers of renal dysfunction. The aim of this study was to identify the lesions best correlated with renal function and likely mediators of disease progression in cats with chronic kidney disease. Cats were recruited through 2 first-opinion practices between 1992 and 2010. When postmortem examinations were authorized, renal tissues were preserved in formalin. Sections were evaluated by a pathologist masked to all clinicopathological data. They were scored semiquantitatively for the severity of glomerulosclerosis, interstitial inflammation, and fibrosis. Glomerular volume was measured using image analysis; the percentage of glomeruli that were obsolescent was recorded. Sections were assessed for hyperplastic arteriolosclerosis and tubular mineralization. Kidneys from 80 cats with plasma biochemical data from the last 2 months of life were included in the study. Multivariable linear regression (P < .05) was used to assess the association of lesions with clinicopathological data obtained close to death. Interstitial fibrosis was the lesion best correlated with the severity of azotemia, hyperphosphatemia, and anemia. Proteinuria was associated with interstitial fibrosis and glomerular hypertrophy, whereas higher time-averaged systolic blood pressure was associated with glomerulosclerosis and hyperplastic arteriolosclerosis.

Reliability of ⁵¹Cr-EDTA plasma and urinary clearance as a measure of residual renal function in dialysis patients.

PubMed

Kjaergaard, Krista D; Jensen, Jens D; Jespersen, Bente; Rehling, Michael

2011-12-01

In dialysis patients, longer survival is associated with a higher residual renal function. Randomized controlled trials are conducted to clarify how residual renal function can be preserved. However, existing methods for measuring residual renal function are uncertain and there is a need for establishing a standard for measurements of glomerular filtration rate (GFR) in dialysis patients. ⁵¹Cr-EDTA clearances in plasma, urine, and dialysate were evaluated in a sample of 12 hemodialysis and 12 peritoneal dialysis patients. The patients' condition was generally stable, and all patients were investigated twice within 4-10 days. Plasma clearances of ⁵¹Cr-EDTA for all patients ranged between 2.1 and 30.8 mL/min/1.73 m², whereas urinary ⁵¹Cr-EDTA clearances ranged from 0.7-20.0 mL/min/1.73 m². This difference was statistically significant (p < 0.001). Week-to-week reproducibility expressed as coefficients of variation were below or equal to 10% for plasma clearances and 13% for urinary clearances in hemodialysis patients and 14% in peritoneal dialysis patients. This study demonstrated a difference between ⁵¹Cr-EDTA plasma and urinary clearances in dialysis patients. Plasma clearance of ⁵¹Cr-EDTA had the best reproducibility. For repeated measurements as in clinical prospective trials, we recommend ⁵¹Cr-EDTA plasma clearance based on blood sampling at 5 + 24 hours with subtraction of ⁵¹Cr-EDTA dialysate clearance in peritoneal dialysis patients. Further studies are needed to corroborate our findings.

A prospective 10-year study of individualized, intensified enzyme replacement therapy in advanced Fabry disease.

PubMed

Schiffmann, Raphael; Swift, Caren; Wang, Xuan; Blankenship, Derek; Ries, Markus

2015-11-01

To test the hypothesis that more frequent enzyme replacement therapy (ERT) slows the decline in kidney function in adult patients with Fabry disease. A single center open label 10-year prospective clinical trial of 12 patients with advanced Fabry disease who, after having experienced an ongoing decline in renal function after 2-4 years of receiving ERT at the approved dose of 0.2 mg/kg agalsidase alfa every other week (EOW), were switched to weekly (EW) ERT at the same dose. We used linear regression to fit each individual patient's longitudinal estimated glomerular filtration rate (eGFR) record in order to compare the deterioration rates between EOW and EW ERT. For the entire group, mean slope on agalsidase alfa every 2 weeks was -7.92 ± 2.88 ml/min/1.73 m(2)/year and 3.84 ± 4.08 ml/min/1.73 m(2)/year on weekly enzyme infusions (p = 0.01, two-tailed paired t test). Three patients (25 %) completed the entire study with relatively preserved renal function while 50 % of patients reached end-stage renal disease (ESRD) during the 10 years of this study. The estimated average delay to ESRD was 13.8 years [n = 11; 95 % CI 0.66, 27]. One patient had a positive eGFR slope on weekly infusions while the patient with the highest antibody titer had a steeper slope after switching. Mean globotriaosylceramide concentrations in urine and plasma as well as urine protein excretion remained unchanged. Weekly enzyme infusions slow the decline of renal function in a subgroup of more severe patients thus showing that existing ERT can be further optimized.

Serum uric acid to creatinine ratio: A predictor of incident chronic kidney disease in type 2 diabetes mellitus patients with preserved kidney function.

PubMed

Gu, Liubao; Huang, Liji; Wu, Haidi; Lou, Qinglin; Bian, Rongwen

2017-05-01

Serum uric acid has shown to be a predictor of renal disease progression in most but not all studies. This study aims to test whether renal function-normalized serum uric acid is superior to serum uric acid as the predictor of incident chronic kidney disease in type 2 diabetes mellitus patients. In this study, 1339 type 2 diabetes mellitus patients with estimated glomerular filtration rate ⩾60 mL/min/1.73 m 2 and normouricemia were included. Renal function-normalized serum uric acid was calculated using serum uric acid/creatinine. Cox regression analysis was used to estimate the association between serum uric acid, renal function-normalized serum uric acid and incident chronic kidney disease. In total, 74 (5.53%) patients developed to chronic kidney disease 3 or greater during a median follow-up of 4 years, with older ages, longer diabetes duration and lower estimated glomerular filtration rate at baseline. The decline rate of estimated glomerular filtration rate was positively correlated with serum uric acid/creatinine ( r = 0.219, p < 0.001), but not serum uric acid ( r = 0.005, p = 0.858). Moreover, multivariate analysis revealed that serum uric acid was not an independent risk factor for incident chronic kidney disease ( p = 0.055), whereas serum uric acid to creatinine ratio was significantly associated with incident chronic kidney disease independently of potential confounders including baseline estimated glomerular filtration rate. serum uric acid to creatinine ratio might be a better predictor of incident chronic kidney disease in type 2 diabetes mellitus patients.

Post-transplantation nephroptosis causing recurrent episodes of acute renal failure and hypertension secondary to intermittent vascular torsion of intraperitoneal renal allograft

PubMed Central

Dosch, Austin R.; Pahl, Madeleine; Reddy, Uttam; Foster, Clarence E.

2017-01-01

Abstract Nephroptosis is a rare complication in renal transplantation, but one with significant associated risk. Due to non-specific clinical features, there may be a substantial delay in diagnosis and loss of the transplanted kidney due to renal pedicle thrombosis. We present a case of post-transplantation nephroptosis after simultaneous pancreas and kidney transplant, which resulted in accelerated hypertension and reversible acute kidney injury >1 year after transplantation. Prompt detection of this rare entity leading to expeditious surgical intervention is necessary to preserve viability of the renal allograft. PMID:28560019

Do sodium-glucose co-transporter-2 inhibitors prevent heart failure with a preserved ejection fraction by counterbalancing the effects of leptin? A novel hypothesis.

PubMed

Packer, Milton

2018-06-01

Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of serious heart failure events in patients with type 2 diabetes, but little is known about mechanisms that might mediate this benefit. The most common heart failure phenotype in type 2 diabetes is obesity-related heart failure with a preserved ejection fraction (HFpEF). It has been hypothesized that the synthesis of leptin in this disorder leads to sodium retention and plasma volume expansion as well as to cardiac and renal inflammation and fibrosis. Interestingly, leptin-mediated neurohormonal activation appears to enhance the expression of SGLT2 in the renal tubules, and SGLT2 inhibitors exert natriuretic actions at multiple renal tubular sites in a manner that can oppose the sodium retention produced by leptin. In addition, SGLT2 inhibitors reduce the accumulation and inflammation of perivisceral adipose tissue, thus minimizing the secretion of leptin and its paracrine actions on the heart and kidneys to promote fibrosis. Such fibrosis probably contributes to the impairment of cardiac distensibility and glomerular function that characterizes obesity-related HFpEF. Ongoing clinical trials with SGLT2 inhibitors in heart failure are positioned to confirm or refute the hypothesis that these drugs may favourably influence the course of obesity-related HFpEF by their ability to attenuate the secretion and actions of leptin. © 2018 John Wiley & Sons Ltd.

Treatment With Human Wharton’s Jelly-Derived Mesenchymal Stem Cells Attenuates Sepsis-Induced Kidney Injury, Liver Injury, and Endothelial Dysfunction

PubMed Central

Cóndor, José M.; Rodrigues, Camila E.; de Sousa Moreira, Roberto; Canale, Daniele; Volpini, Rildo A.; Shimizu, Maria H.M.; Camara, Niels O.S.; Noronha, Irene de L.

2016-01-01

The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks. Downregulation of endothelial nitric oxide synthase contributes to sepsis-induced endothelial dysfunction. Human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) are known to reduce expression of proinflammatory cytokines and markers of apoptosis. We hypothesized that treatment with WJ-MSCs would protect renal, hepatic, and endothelial function in a cecal ligation and puncture (CLP) model of sepsis in rats. Rats were randomly divided into three groups: sham-operated rats; rats submitted to CLP and left untreated; and rats submitted to CLP and intraperitoneally injected, 6 hours later, with 1 × 106 WJ-MSCs. The glomerular filtration rate (GFR) was measured at 6 and 24 hours after CLP or sham surgery. All other studies were conducted at 24 hours after CLP or sham surgery. By 6 hours, GFR had decreased in the CLP rats. At 24 hours, Klotho renal expression significantly decreased. Treatment with WJ-MSCs improved the GFR; improved tubular function; decreased the CD68-positive cell count; decreased the fractional interstitial area; decreased expression of nuclear factor κB and of cytokines; increased expression of eNOS, vascular endothelial growth factor, and Klotho; attenuated renal apoptosis; ameliorated hepatic function; increased glycogen deposition in the liver; and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate. Klotho protein expression was higher in WJ-MSCs than in human adipose-derived MSCs. Because WJ-MSCs preserve renal and hepatic function, they might play a protective role in sepsis. Significance Sepsis is the leading cause of death in intensive care units. Although many different treatments for sepsis have been tested, sepsis-related mortality rates remain high. It was hypothesized in this study that treatment with human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) would protect renal, hepatic, and endothelial function in a model of sepsis in rats. Treatment with WJ-MSCs improved the glomerular filtration rate, improved tubular function, decreased expression of nuclear factor κB and of cytokines, increased expression of eNOS and of Klotho, attenuated renal apoptosis, and improved survival. Sepsis-induced acute kidney injury is a state of Klotho deficiency, which WJ-MSCs can attenuate. PMID:27280799

Related factors for worsening renal function following percutaneous transluminal renal angioplasty (PTRA) in patients with atherosclerotic renal artery stenosis.

PubMed

Yoshihara, Fumiki; Fukuda, Tetsuya; Iwashima, Yoshio; Nakamura, Satoko; Hayashi, Shin-Ichiro; Kishida, Masatsugu; Ishizuka, Azusa; Kusunoki, Hiroshi; Ohta, Yuko; Kawano, Yuhei

2015-01-01

To identify candidates for PTRA in terms of the preservation of renal function, we herein evaluated factors that caused worsening renal function (WRF) after PTRA. We evaluated 92 patients with atherosclerotic renal artery stenosis (mean age 70.7 ± 8.4 years). WRF was defined as a ≥0.3 mg/dL increase in creatinine levels after PTRA compared to before PTRA. A total of 92 patients exhibited non-WRF 83 (90.2%), WRF 9 (9.8%). Significant differences were observed in serum creatinine levels between two groups both before (non-WRF 1.34 ± 0.49 versus WRF 1.70 ± 0.68 mg/dL, p = 0.0462) and after PTRA (non-WRF 1.31 ± 0.43 versus WRF 2.42 ± 1.12 mg/dL, p < 0.0001). Patients with WRF had higher comorbidity rate of diabetes mellitus (DM) (non-WRF 31.3% versus WRF 66.7%, p = 0.0345) and proteinuria (non-WRF 27.7% versus WRF 66.7%, p = 0.0169), and had higher systolic blood pressure (non-WRF 143.6 ± 18.7 versus WRF 157.1 ± 19.9 mmHg, p = 0.0436), higher plasma B-type natriuretic peptide (BNP) levels, and larger left atrial and left ventricular end-diastolic dimensions before PTRA. Patients with WRF had a higher rate of taking diuretics (non-WRF 27.7% versus WRF 66.7%, p = 0.0169) after PTRA. Multiple logistic regression analysis revealed that comorbidity of DM was an independent related factor for WRF (comorbidity of DM, yes: OR 31.0, 95% CI 2.44-1024.62, p = 0.0055). Comorbidity of DM, coexisting of proteinuria, high creatinine level, high blood pressure, high BNP levels, and large left atrial and ventricular dimensions were related to WRF after PTRA in patients with atherosclerotic renal artery stenosis.

Activating Nrf-2 Signaling Depresses Unilateral Ureteral Obstruction-Evoked Mitochondrial Stress-Related Autophagy, Apoptosis and Pyroptosis in Kidney

PubMed Central

Chung, Shue Dong; Lai, Ting Yu; Chien, Chiang Ting; Yu, Hong Jen

2012-01-01

Exacerbated oxidative stress and inflammation may induce three types of programmed cell death, autophagy, apoptosis and pyroptosis in unilateral ureteral obstruction (UUO) kidney. Sulforaphane activating NF-E2-related nuclear factor erythroid-2 (Nrf-2) signaling may ameliorate UUO-induced renal damage. UUO was induced in the left kidney of female Wistar rats. The level of renal blood flow, cortical and medullary oxygen tension and reactive oxygen species (ROS) was evaluated. Fibrosis, ED-1 (macrophage/monocyte) infiltration, oxidative stress, autophagy, apoptosis and pyroptosis were evaluated by immunohistochemistry and Western blot in UUO kidneys. Effects of sulforaphane, an Nrf-2 activator, on Nrf-2- and mitochondrial stress-related proteins and renal injury were examined. UUO decreased renal blood flow and oxygen tension and increased renal ROS, 3-nitrotyrosine stain, ED-1 infiltration and fibrosis. Enhanced renal tubular Beclin-1 expression started at 4 h UUO and further enhanced at 3d UUO, whereas increased Atg-5-Atg12 and LC3-II expression were found at 3d UUO. Increased renal Bax/Bcl-2 ratio, caspase 3 and PARP fragments, apoptosis formation associated with increased caspase 1 and IL-1β expression for pyroptosis formation were started from 3d UUO. UUO reduced nuclear Nrf-2 translocation, increased cytosolic and inhibitory Nrf-2 expression, increased cytosolic Bax translocation to mitochondrial and enhanced mitochondrial Cytochrome c release into cytosol of the UUO kidneys. Sulforaphane significantly increased nuclear Nrf-2 translocation and decreased mitochondrial Bax translocation and Cytochrome c release into cytosol resulting in decreased renal injury. In conclusion, sulforaphane via activating Nrf-2 signaling preserved mitochondrial function and suppressed UUO-induced renal oxidative stress, inflammation, fibrosis, autophagy, apoptosis and pyroptosis. PMID:23071780

Comparison of Aerobic Preservation by Venous Systemic Oxygen Persufflation or Oxygenated Machine Perfusion of Warm-Ischemia-Damaged Porcine Kidneys.

PubMed

Kalenski, Julia; Mancina, Elina; Paschenda, Pascal; Beckers, Christian; Bleilevens, Christian; Tóthová, Ľubomíra; Boor, Peter; Gross, Dominik; Tolba, René H; Doorschodt, Benedict M

2016-01-01

The global shortage of donor organs for transplantation has necessitated the expansion of the organ pool through increased use of organs from less ideal donors. Venous systemic oxygen persufflation (VSOP) and oxygenated machine perfusion (OMP) have previously demonstrated beneficial results compared to cold storage (CS) in the preservation of warm-ischemia-damaged kidney grafts. The aim of this study was to compare the efficacy of VSOP and OMP for the preservation of warm-ischemia-damaged porcine kidneys using the recently introduced Ecosol preservation solution compared to CS using Ecosol or histidine-tryptophan-ketoglutarate solution (HTK). Kidneys from German Landrace pigs (n = 5/group) were retrieved and washed out with either Ecosol or HTK after 45 min of clamping of the renal pedicle. As controls, kidneys without warm ischemia, cold stored for 24 h in HTK, were employed. Following 24 h of preservation by VSOP, OMP, CS-Ecosol, or CS-HTK, renal function and damage were assessed during 1 h using the isolated perfused porcine kidney model. During reperfusion, urine production was significantly higher in the VSOP and OMP groups than in the CS-HTK group; however, only VSOP could demonstrate lower urine protein concentrations and fractional excretion of sodium, which did not differ from the non-warm-ischemia-damaged control group. VSOP, CS-Ecosol, and controls showed better maintenance of the acid-base balance than CS-HTK. Reduced lipid peroxidation, as reflected in postreperfusion tissue thiobarbituric acid-reactive substance levels, was observed in the VSOP group compared to the OMP group, and the VSOP and CS-Ecosol groups had concentrations similar to the controls. The ratio of reduced to oxidized glutathione was higher in the VSOP, OMP, and CS-Ecosol groups than in the CS-HTK group and controls, with a higher ratio in the VSOP than in the OMP group. VSOP was associated with mitigation of oxidative stress in comparison to OMP and CS. Preservation of warm-ischemia-damaged porcine kidneys by VSOP was improved compared to OMP and CS, and was comparable to preservation of non-warm-ischemia-damaged cold-stored kidneys. © 2016 S. Karger AG, Basel.

Heart failure with preserved left ventricular systolic function: a hospital cohort study

PubMed Central

Berry, C; Hogg, K; Norrie, J; Stevenson, K; Brett, M; McMurray, J

2005-01-01

Objective: To investigate how patients with heart failure with preserved left ventricular systolic function (LVSF) compare with patients with reduced LVSF. Design: Cohort study. Setting: Urban university hospital. Patients: 528 index emergency admissions with heart failure during the year 2000. Information on LVSF and follow up was available for 445 (84%) of these patients. Results: 130 (29%) patients had preserved LVSF (defined as an ejection fraction > 40%). The median follow up was 814 days (range 632–978 days). The average (SD) age was 72 (13) years. Women accounted for 62% and 45% of patients with preserved and reduced LVSF, respectively (p  =  0.001). Patients with preserved LVSF (compared with those with reduced LVSF) had a higher prevalence of left ventricular hypertrophy (56% v 29%) and aortic valve disease (mean gradient > 20 mm Hg; 31% v 9%). Fewer patients with preserved LVSF received an angiotensin converting enzyme inhibitor (65% v 78%, p  =  0.008) or spironolactone (12% v 21%, p  =  0.027). Anaemia tended to occur more often in patients with preserved LVSF than in those with reduced LVSF (43% v 33% for women, p  =  0.12; 59% v 49% for men, p  =  0.22). There was a similarly high prevalence of significant renal dysfunction in both groups (estimated glomerular filtration rate < 60 ml/min/1.73 m2 in 68% with preserved and 64% with reduced LVSF, p  =  0.40). Mortality was similar in both groups (preserved versus reduced 51 (39%) v 132 (42%), p  =  0.51). Compared with patients with reduced LVSF, patients with preserved LVSF tended to have a lower risk of death or hospital admission for heart failure (56 (42%) v 165 (53%), p  =  0.072) but a similar rate of death or readmission for any reason. Conclusion: Patients with preserved LVSF had more co-morbid problems than those with reduced LVSF; however, prognosis was similar for both groups. PMID:15958359

Laparoscopic cryoablation of angiomyolipomas in adolescents and young adults: A report of four cases associated with tuberous sclerosis and 1 case of sporadic origin.

PubMed

Trelborg, Karina; Nielsen, Tommy Kjærgaard; Østraat, Ernst Øyvind; Olsen, Lars Henning

2016-12-01

Renal angiomyolipomas (AMLs) can be of sporadic origin or associated with tuberous sclerosis (TS). TS-associated AMLs often present in childhood, tend to be bilateral and multiple, and often exhibit a faster growth rate with an increased risk of hemorrhage. Renal cryoablation is well described in adults, whereas experiences with adolescents and young adults are limited. We present here for the first time a series of renal AMLs within adolescents and young adults treated with laparoscopic assisted cryoablation (LCA). The aim was to evaluate whether LCA of AMLs in adolescents and young adults is a safe and feasible treatment modality. From October 2009 to September 2013 a total of five patients at our institution were diagnosed with AMLs requiring treatment. Four patients had TS and one had AML of sporadic origin, all five patients underwent LCA. Data were retrospectively collected by a systematic review of patient material and reassessment of renal imaging. The median age was 16 years (range 13-27 years). Eight AMLs with a median size of 3.9 cm (range 2.1-7.7 cm) were treated in five patients because of tumor size and rapid growth. Follow-up was a median 37 months (range 20-62 months), and all tumors showed a reduction in tumor size, and no regrowth was recognized (see summary table). The procedure was well tolerated, with only few perioperative complications and no postoperative complications. When considering the indication for treating AMLs, the origin (sporadic or TS associated) and size of the tumor are the decisive factors. To preserve renal function and prevent spontaneous hemorrhage caution should be intensified when tumors reach 4 cm, particularly if TS is present. After the diagnosis is established, patients should be monitored with renal imaging at regular intervals to identify rapid-growing tumors. As an alternative to current treatment modalities such as partial nephrectomy and super selective angioembolization, cryoablation is an emerging approach, although experience with pediatric patients is limited. For patients not requiring immediate surgery, pharmacological treatment with mTOR inhibitors is now being evaluated as an alternative treatment option or as neo-adjuvant therapy to ablative techniques. Prophylactic treatment of large or rapid growing AMLs with LCA appears to be a safe and feasible nephron-sparing approach in adolescents and young adults. The low perioperative complication rate and promising effect on outcome might allow treatment of subclinical AMLs in order to minimize the risk of potentially life-threatening complications and preserve renal function. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

SECRETED KLOTHO AND CHRONIC KIDNEY DISEASE

PubMed Central

Hu, Ming Chang; Kuro-o, Makoto; Moe, Orson W.

2013-01-01

Soluble Klotho (sKl) in the circulation can be generated directly by alterative splicing of the Klotho transcript or the extracellular domain of membrane Klotho can be released from membrane-anchored Klotho on the cell surface. Unlike membrane Klotho which functions as a coreceptor for fibroblast growth factor-23 (FGF23), sKl, acts as hormonal factor and plays important roles in anti-aging, anti-oxidation, modulation of ion transport, and Wnt signaling. Emerging evidence reveals that Klotho deficiency is an early biomarker for chronic kidney diseases as well as a pathogenic factor. Klotho deficiency is associated with progression and chronic complications in chronic kidney disease including vascular calcification, cardiac hypertrophy, and secondary hyperparathyroidism. In multiple experimental models, replacement of sKl, or manipulated up-regulation of endogenous Klotho protect the kidney from renal insults, preserve kidney function, and suppress renal fibrosis, in chronic kidney disease. Klotho is a highly promising candidate on the horizon as an early biomarker, and as a novel therapeutic agent for chronic kidney disease. PMID:22396167

Results from multiple prospective single-center clinical trials of the off-the-shelf p-Branch fenestrated stent graft.

PubMed

Farber, Mark A; Eagleton, Matthew J; Mastracci, Tara M; McKinsey, James F; Vallabhaneni, Raghuveer; Sonesson, Björn; Dias, Nuno; Resch, Timothy

2017-10-01

The purpose of this study was to report prospective data of an off-the-shelf fenestrated endograft (Zenith p-Branch; Cook Medical, Bloomington, Ind) from four centers for the treatment of patients with pararenal abdominal aortic aneurysms. Data were combined from four single-center investigational studies conducted in the United States and Europe. The p-Branch endograft consists of a proximal off-the-shelf component incorporating a scallop for the celiac artery, a superior mesenteric artery fenestration, and two conical pivot fenestrations to preserve flow to the renal vessels. The device is available in two configurations, a left renal fenestration at the same (configuration A) or lower (configuration B) longitudinal position than the right to accommodate varied anatomy of the patients. Between August 2011 and September 2015, 76 patients (82% male; mean age, 72 years; 65 elective and 11 emergent) were enrolled, with 55% implanted with option A and 45% with B. The device was deployed successfully in all patients, and stents were placed in all target vessels except in three cases (one elective, two emergent): a left kidney was sacrificed in one patient, and a right renal artery was left unstented in two patients during the index procedure. There was no 30-day mortality. During follow-up (mean, 25 ± 13 months), 10 late deaths occurred (6 elective, 4 emergent; none related to device or procedure), and there were no ruptures or conversions to open repair. Two patients experienced bowel ischemia; one case resolved with nonoperative treatment and one required superior mesenteric artery and celiac artery angioplasty and stent placement. Renal artery occlusion occurred in eight patients (11%) and was deemed procedure related in 63% (5/8) of these patients. Four of these were successfully intervened on with preservation of renal function. The overall renal insufficiency incidence was 7% (5/76). One patient developed renal failure requiring dialysis. Early results incorporating learning curves for physicians with a new device and delivery system indicate that the use of the Zenith p-Branch device is feasible and safe. Long-term follow-up is needed to assess the effectiveness and durability of this treatment strategy and to refine the indications for use. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Zero-ischaemia robotic partial nephrectomy (RPN) for hilar tumours.

PubMed

Abreu, André L C; Gill, Inderbir S; Desai, Mihir M

2011-09-01

• Robotic partial nephrectomy (RPN) has emerged as an attractive minimally invasive nephron-sparing surgical option. However, on-going concerns about RPN include: (i) prolonged ischaemia time with potential implications on renal functional outcomes, and (ii) questions about the ability of RPN to address technically challenging hilar tumours. • Herein, we detail the technique and present initial perioperative outcomes of our novel technique of zero-ischaemia RPN for complex hilar tumours. • Since May 2010, >100 patients underwent minimally invasive zero-ischaemia PN. Of these, 21 had procedure done robotically. Of these, seven patients had hilar tumours. RPN was offered to all patients irrespective of tumour or reno-vascular anatomy, contralateral kidney characteristics or renal function. • Data were prospectively collected and recorded in an Institutional Review Board-approved database. • We detail our zero-ischaemia RPN technique and present early perioperative outcomes. • Zero-ischaemia RPN was successful in all cases without any hilar clamping. The median (range) tumour size was 4.1 (2.6-6.4) cm and the median RENAL score was 10 (8-10). • The warm ischaemia time was zero in all cases. • The median (range) operative time was 222 (150-330) min, estimated blood loss was 150 (100-500) mL, and the percentage kidney spared was 75 (50-90)%. The median hospital stay was 4 (3-6) days. • There were no intraoperative complications; two patients had postoperative complications (Clavien grade I and II). No patient had a postoperative haemorrhage, urological/renal complication or lost a kidney. All tumour specimens had negative surgical margins on pathology. • The median absolute decrease in serum creatinine and estimated glomerular filtration rate at discharge was 0 (0.2-0.7) mg/dL (P = 0.4) and 5 (-16 to 29) mL/min per 1.73 m(2) (P = 0.8), respectively. • Zero-ischaemia RPN for hilar tumours is safe and feasible and to our knowledge the first report in the literature. • Elimination of warm ischaemia may optimally preserve renal function. Prospective randomized studies are needed to confirm any renal functional advantages of clamp-free RPN. • Global renal ischaemia appears to be unnecessary during RPN for hilar tumours. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Antigen-specific T cell responses to BK polyomavirus antigens identify functional anti-viral immunity and may help to guide immunosuppression following renal transplantation

PubMed Central

Chakera, A; Bennett, S; Lawrence, S; Morteau, O; Mason, P D; O'Callaghan, C A; Cornall, R J

2011-01-01

Infection with the polyoma virus BK (BKV) is a major cause of morbidity following renal transplantation. Limited understanding of the anti-viral immune response has prevented the design of a strategy that balances treatment with the preservation of graft function. The proven utility of interferon-gamma enzyme-linked immunospot (ELISPOT) assays to measure T cell responses in immunocompetent hosts was the basis for trying to develop a rational approach to the management of BKV following renal transplantation. In a sample of transplant recipients and healthy controls, comparisons were made between T cell responses to the complete panel of BKV antigens, the Epstein–Barr virus (EBV) antigens, BZLF1 and EBNA1, and the mitogen phytohaemagglutinin (PHA). Correlations between responses to individual antigens and immunosuppressive regimens were also analysed. Antigen-specific T cell responses were a specific indicator of recent or ongoing recovery from BKV infection (P < 0·05), with responses to different BKV antigens being highly heterogeneous. Significant BKV immunity was undetectable in transplant patients with persistent viral replication or no history of BKV reactivation. Responses to EBV antigens and mitogen were reduced in patients with BKV reactivation, but these differences were not statistically significant. The T cell response to BKV antigens is a useful and specific guide to recovery from BKV reactivation in renal transplant recipients, provided that the full range of antigenic responses is measured. PMID:21671906

Adaptation, allometry, and hypertension.

PubMed

Weder, A B; Schork, N J

1994-08-01

Essential hypertension is a "disease of civilization" but has a clear genetic component. From an evolutionary perspective, persistence in the human genome of elements capable of raising blood pressure presupposes their adaptive significance. Recently, two hypotheses that explicitly appeal to selectionist arguments, the "slavery" and "thrifty gene" theories, have been forwarded. We find neither completely successful, and we advance an alternative explanation of the adaptive importance of genes responsible for hypertension. We propose that blood pressure rises during childhood and adolescence to subserve homeostatic needs of the organism. Specifically, we contend that blood pressure is a flexible element in the repertoire of renal homeostatic mechanisms serving to match renal function to growth. The effect of modern diet and lifestyle on human growth stimulates earlier and more vigorous development, straining biologically necessary relationships between renal and general somatic growth and requiring compensation via homeostatic mechanisms preserved during evolution. Prime among such mechanisms is blood pressure, which rises as a compensation to maintain renal function in the face of greater growth. Since virtually all members of acculturated societies share in the modern lifestyle, the demands imposed by accelerated growth and development result in a populational shift to higher blood pressures, with a consequent increase in the prevalence of hypertension. We propose that hypertension is the product of maladaptation of highly genetically conserved mechanisms subserving important biological homeostatic needs. Elucidation of the mechanisms underlying hypertension will require approaches that examine the developmental processes linking growth to blood pressure.

The contemporary role of ablative treatment approaches in the management of renal cell carcinoma (RCC): focus on radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), and cryoablation.

PubMed

Klatte, Tobias; Kroeger, Nils; Zimmermann, Uwe; Burchardt, Martin; Belldegrun, Arie S; Pantuck, Allan J

2014-06-01

Currently, most of renal tumors are small, low grade, with a slow growth rate, a low metastatic potential, and with up to 30 % of these tumors being benign on the final pathology. Moreover, they are often diagnosed in elderly patients with preexisting medical comorbidities in whom the underlying medical conditions may pose a greater risk of death than the small renal mass. Concerns regarding overdiagnosis and overtreatment of patients with indolent small renal tumors have led to an increasing interest in minimally invasive, ablative as an alternative to extirpative interventions for selected patients. To provide an overview about the state of the art in radiofrequency ablation (RFA), high-intensity focused ultrasound, and cryoablation in the clinical management of renal cell carcinoma. A PubMed wide the literature search of was conducted. International consensus panels recommend ablative techniques in patients who are unfit for surgery, who are not considered candidates for or elect against elective surveillance, and who have small renal masses. The most often used techniques are cryoablation and RFA. These ablative techniques offer potentially curative outcomes while conferring several advantages over extirpative surgery, including improved patient procedural tolerance, faster recovery, preservation of renal function, and reduction in the risk of intraoperative and postsurgical complications. While it is likely that outcomes associated with ablative modalities will improve with further advances in technology, their application will expand to more elective indications as longer-term efficacy data become available. Ablative techniques pose a valid treatment option in selected patients.

Deep infiltrating ureteral endometriosis with catamenial hydroureteronephrosis: a case report.

PubMed

Lee, Hyun Jung; Lee, Yoon Soon

2017-12-13

This aim of this case report is to raise awareness of ureteral endometriosis in women of reproductive age with hydronephrosis in the absence of urolithiasis to enable early diagnosis and prevent loss of renal function. A 44-year-old Asian woman presented with a 4-year history of cyclic right flank pain and right hydronephrosis during menstruation. Despite several evaluations by physicians, including gynecologists, the cause of her symptoms was not diagnosed. On transvaginal ultrasonography, the uterus was observed deviated to the right, with a nodular lesion at the right uterosacral ligament, and the right ovary was attached to the uterus with no apparent cystic lesion. Magnetic resonance imaging showed a mass in the right uterine wall and mild wall thickening with delayed enhancement of the right distal ureter. Right ureteral endometriosis was suspected. Diagnostic laparoscopy revealed narrowing of the distal right ureter between the right uterosacral ligament and the right ovary with adhesions caused by deep infiltrating endometriosis. The adhesion bands and infiltrating endometriosis around the right ureter were dissected. The nonspecific symptoms of ureteral endometriosis can result in incorrect diagnosis, with renal damage as a result of prolonged hydronephrosis. A high index of suspicion and use of imaging modalities enable earlier diagnosis and preservation of renal function.

Febuxostat for the chronic management of hyperuricemia in patients with gout.

PubMed

Chinchilla, Sandra Pamela; Urionaguena, Irati; Perez-Ruiz, Fernando

2016-01-01

Febuxostat is a non-purine, selective inhibitor of both isoforms of xanthine oxido-reductase (XOR), and a major alternative to the scarce number of urate-lowering medications available in the last decades. Its inhibition of XOR is more potent than allopurinol in a mg to mg comparison, what is associated to achievement of serum urate target more frequently than allopurinol at doses tested in clinical trials, especially in patients with the highest baseline serum urate levels. Its pharmacokinetics is not greatly dependent on renal clearance, contrary to allopurinol, what may be an advantage in patients with chronic kidney disease. Several trials are further evaluating both the cardiovascular safety of febuxostat and its possible beneficial effect on renal function preservation. Still scarce, but clinically interesting, evidence on its use in transplant patients has been recently released.

Minimally invasive aortic valve replacement in high risk patient groups

PubMed Central

Lewis, Harriet; Benedetto, Umberto; Caputo, Massimo; Angelini, Gianni; Vohra, Hunaid A.

2017-01-01

Minimally invasive aortic valve replacement (AVR) aims to preserve the sternal integrity and improve postoperative outcomes. In low risk patients, this technique can be achieved with comparable mortality to the conventional approach and there is evidence of possible reduction in intensive care and hospital length of stay, transfusion requirement, renal dysfunction, improved respiratory function and increased patient satisfaction. In this review, we aim to asses if these benefits can be transferred to the high risk patient groups. We therefore, discuss the available evidence for the following high risk groups: elderly patients, re-operative surgery, poor lung function, pulmonary hypertension, obesity, concomitant procedures and high risk score cohorts. PMID:28740685

Retro-peritoneoscopic assisted cryoablation for small renal tumors: the first cases treated in Romania.

PubMed

Ghervan, L; Lucan, V; Elec, F; Suciu, M; Bologa, F; Iacob, Gh; Lucan, M

2007-01-01

Nephron-sparing surgery (NSS), has been demonstrated to be a safe and effective alternative to radical nephrectomy for selected cases. Retro-peritoneoscopic cryoablation (RCA), combine the benefits of minimal invasiveness of the laparoscopy with the advantage of preserving renal function of the nephron sparing surgery. The aim of our study was to assess the initial results with RCA of small renal tumors. Since Jan 2007, twelve consecutive patients, with small renal tumors (mean tumor size 3.89 cm) underwent RCA at our institution. The patients were assessed using: clinical exam, lab exam, ultrasound, contrast enhanced CT scan. For cryoablation, we used the Galil Medical SeedNet with 17 Gauge cryoprobes, under combined retro-peritoneoscopic and ultrasound guidance. Protocol follow-up design includes clinical exam, lab exam and contrast enhanced CT scan at 3,6 and 12 months and annually thereafter. Mean surgical time was 145.42 min. and mean blood loss was 179.17 ml. Two patients presented: bleeding at the extraction of the cryoprobes and urinary fistula which healed with surgical treatment. Histological examination of the core biopsy revealed clear cell carcinoma in 8 patients, papillary carcinoma in 3 patients and angiomyolipoma in 1 patient. Cryosurgical ablation of small renal tumors using multiple ultrathin 17 Gauge cryoprobes is a feasible treatment option. Retro-peritoneoscopic approach allows optimal access to the kidney and endoscopic real-time ultrasound control of the freezing process.

Notch3 orchestrates epithelial and inflammatory responses to promote acute kidney injury.

PubMed

Kavvadas, Panagiotis; Keuylian, Zela; Prakoura, Niki; Placier, Sandrine; Dorison, Aude; Chadjichristos, Christos E; Dussaule, Jean-Claude; Chatziantoniou, Christos

2018-07-01

Acute kidney injury is a major risk factor for subsequent chronic renal and/or cardiovascular complications. Previous studies have shown that Notch3 was de novo expressed in the injured renal epithelium in the early phases of chronic kidney disease. Here we examined whether Notch3 is involved in the inflammatory response and the epithelial cell damage that typifies ischemic kidneys using Notch3 knockout mice and mice with short-term activated Notch3 signaling (N3ICD) in renal epithelial cells. After ischemia/reperfusion, N3ICD mice showed exacerbated infiltration of inflammatory cells and severe tubular damage compared to control mice. Inversely, Notch3 knockout mice were protected against ischemia/reperfusion injury. Renal macrophages derived from Notch3 knockout mice failed to activate proinflammatory cytokines. Chromatin immunoprecipitation analysis of the Notch3 promoter identified NF-κB as the principal inducer of Notch3 in ischemia/reperfusion. Thus, Notch3 induced by NF-κB in the injured epithelium sustains a proinflammatory environment attracting activated macrophages to the site of injury leading to a rapid deterioration of renal function and structure. Hence, targeting Notch3 may provide a novel therapeutic strategy against ischemia/reperfusion and acute kidney injury by preservation of epithelial structure and disruption of proinflammatory signaling. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Renoprotective effects of combined endothelin-converting enzyme/neutral endopeptidase inhibitor SLV338 in acute and chronic experimental renal damage.

PubMed

Sharkovska, Yuliya; Kalk, Philipp; von Websky, Karoline; Relle, Katharina; Pfab, Thiemo; Alter, Markus; Fischer, Yvan; Hocher, Berthold

2011-01-01

Acute kidney injury (AKI) as well as chronic renal failure are associated with a huge mortality/morbidity. However, so far no drugs have been approved for the treatment of acute kidney failure and only a few for the treatment of chronic kidney disease (CKD). We analysed the effect of SLV338, a neutral endopeptidase (NEP)/endothelin converting enzyme (ECE)-inhibitor in animal models of acute kidney failure as well as chronic renal failure. Acute renal failure was induced in male Wistar rats by uninephrectomy and clamping of the remaining kidney for 55 minutes. SLV338 (total dose: 4.9 mg/kg) or vehicle was continuously infused for 2 hours (starting 20 minutes prior to clamping). Sham operated animals served as controls. Plasma creatinine was measured at baseline and day 2 and 8 after renal ischemia-reperfusion. Hypertensive renal damage was induced in male Sprague Dawley rats by nitric oxide deficiency using L-NAME (50 mg/kg per day, added to drinking water for 4 weeks). One group was treated over the same time period with SLV338 (30 mg/kg per day, mixed with food). Systolic blood pressure was monitored weekly. At study end, urine and blood samples were collected and kidneys were harvested. Acute renal ischemia-reperfusion caused a 5-fold plasma creatinine elevation (day 2), which was significantly attenuated by more than 50% in animals treated with SLV338 (p < 0.05). Renal failure was accompanied by a 67% mortality in vehicle-treated rats, but only 20% after SLV338 treatment (p = 0.03 compared to sham controls). Chronic L-NAME administration caused hypertension, urinary albumin excretion, glomerulosclerosis, renal arterial remodelling, and renal interstitial fibrosis. Treatment with SLV338 did not significantly affect blood pressure, but abolished renal tissue damage (interstitial fibrosis, glomerulosclerosis, renal arterial remodelling (p < 0.05 versus L-NAME group in each case). The dual ECE/NEP inhibitor SLV338 preserves kidney function and reduces mortality in severe acute ischemic renal failure. Moreover, combined ECE/NEP inhibition prevents hypertensive renal tissue damage in a blood pressure independent manner in L-NAME-treated rats.

Imipenem in burn patients: pharmacokinetic profile and PK/PD target attainment.

PubMed

Gomez, David S; Sanches-Giraud, Cristina; Silva, Carlindo V; Oliveira, Amanda M Ribas Rosa; da Silva, Joao Manoel; Gemperli, Rolf; Santos, Silvia R C J

2015-03-01

Unpredictable pharmacokinetics (PK) in burn patients may result in plasma concentrations below concentrations that are effective against common pathogens. The present study evaluated the imipenem PK profile and pharmacokinetic/pharmacodynamics (PK/PD) correlation in burn patients. Fifty-one burn patients, 38.7 years of age (mean), 68.0 kg, 36.3% total burn surface area (TBSA), of whom 84% (43/51) exhibited thermal injury, 63% inhalation injury and 16% electrical injury (8/51), all of whom were receiving imipenem treatment were investigated. Drug plasma monitoring, PK study (120 sets of plasma levels) and PK/PD correlation were performed in a series of blood samples. Only 250 μl of plasma samples were required for drug plasma measurements using the ultra filtration technique for the purification of biological matrix and quantification using liquid chromatography. Probability of target attainment (PTA) was calculated using a PD target of 40% free drug concentrations above the minimum inhibitory concentration (40%fT>MIC). Significant differences in PK parameters (medians), such as biological half-life (2.2 vs 5.5 h), plasma clearance (16.2 vs 1.4 l h(-1)) and volume of distribution (0.86 vs 0.19 l kg(-1)), were registered in burn patients via comparisons of set periods with normal renal function against periods of renal failure. Correlations between creatinine clearance and total body plasma clearance were also obtained. In addition, the PK profile did not change according to TBSA during sets when renal function was preserved. PTA was >89% for MIC values up to 4 mg l(-1). In conclusion, imipenem efficacy for the control of hospital infection on the basis of PK/PD correlation was guaranteed for burn in patients at the recommended dose regimens for normal renal function (31.1±9.7 mg kg(-1) daily), but the daily dose must be reduced to 17.2±9.7 mg kg(-1) during renal failure to avoid neurotoxicity.

Renin-Angiotensin System Inhibition, Worsening Renal Function, and Outcome in Heart Failure Patients With Reduced and Preserved Ejection Fraction: A Meta-Analysis of Published Study Data.

PubMed

Beldhuis, Iris E; Streng, Koen W; Ter Maaten, Jozine M; Voors, Adriaan A; van der Meer, Peter; Rossignol, Patrick; McMurray, John J V; Damman, Kevin

2017-02-01

Renin-angiotensin aldosterone system (RAAS) inhibitors significantly improve outcome in heart failure (HF) patients with reduced ejection fraction (HFREF), irrespective of the occurrence of worsening renal function (WRF). However, in HF patients with preserved ejection fraction (HFPEF), RAAS inhibitors have not been shown to improve outcome but are still frequently prescribed. Random effect meta-analysis was performed to investigate the relationship between RAAS inhibitor therapy, WRF in both HF phenotypes, and mortality. Studies were selected based on literature search in MEDLNE and included randomized, placebo controlled trials of RAAS inhibitors in chronic HF. The primary outcome consisted of the interaction analysis for the association between RAAS inhibition-induced WRF, HF phenotype and outcome. A total of 8 studies (6 HFREF and 2 HFPEF, including 28 961 patients) were included in our analysis. WRF was more frequent in the RAAS inhibitor group, compared with the placebo group, in both HFREF and HFPEF. In HFREF, WRF induced by RAAS inhibitor therapy was associated with a less increased relative risk of mortality (relative risk, 1.19 (1.08-1.31); P <0.001), compared with WRF induced by placebo (relative risk, 1.48 (1.35-1.62); P <0.001; P for interaction 0.005). In contrast, WRF induced by RAAS inhibitor therapy was strongly associated with worse outcomes in HFPEF (relative risk, 1.78 (1.43-2.21); P <0.001), whereas placebo-induced WRF was not (relative risk, 1.25 (0.88-1.77); P =0.21; P for interaction 0.002). RAAS inhibitors induce renal dysfunction in both HFREF and HFPEF. However, in contrast to patients with HFREF where mortality increase with WRF is small, HFPEF patients with RAAS inhibitor-induced WRF have an increased mortality risk, without experiencing improved outcome with RAAS inhibition. © 2017 American Heart Association, Inc.

Increased primary non-function in transplanted deceased-donor kidneys flushed with histidine-tryptophan-ketoglutarate solution.

PubMed

Stevens, R B; Skorupa, J Y; Rigley, T H; Yannam, G R; Nielsen, K J; Schriner, M E; Skorupa, A J; Murante, A; Holdaway, E; Wrenshall, L E

2009-05-01

Histidine-Tryptophan-Ketoglutarate (HTK) solution is increasingly used to flush and preserve organ donor kidneys, with efficacy claimed equivalent to University of Wisconsin (UW) solution. We observed and reported increased graft pancreatitis in pancreata flushed with HTK solution, which prompted this review of transplanting HTK-flushed kidneys. We analyzed outcomes of deceased-donor kidneys flushed with HTK and UW solutions with a minimum of 12 months follow-up, excluding pediatric and multi-organ recipients. We evaluated patient and graft survival and rejection rates, variables that might constitute hazards to graft survival and renal function. Two-year patient survival, rejection, renal function and graft survival were not different, but early graft loss (<6 months) was worse in HTK-flushed kidneys (p < 0.03). A Cox analysis of donor grade, cold ischemic time, panel reactive antibodies (PRA), donor race, first vs. repeat transplant, rejection and flush solution showed that only HTK use predicted early graft loss (p < 0.04; relative risk = 3.24), almost exclusively attributable to primary non-function (HTK, n = 5 (6.30%); UW, n = 1 (0.65%); p = 0.02). Delayed graft function and early graft loss with HTK occurred only in lesser grade kidneys, suggesting it should be used with caution in marginal donors.

Correlation between differential renal function estimation using CT-based functional renal parenchymal volume and (99m)Tc - DTPA renal scan.

PubMed

Sarma, Debanga; Barua, Sasanka K; Rajeev, T P; Baruah, Saumar J

2012-10-01

Nuclear renal scan is currently the gold standard imaging study to determine differential renal function. We propose helical CT as single modality for both the anatomical and functional evaluation of kidney with impaired function. In the present study renal parenchymal volume is measured and percent total renal volume is used as a surrogate marker for differential renal function. The objective of this study is to correlate between differential renal function estimation using CT-based renal parenchymal volume measurement with differential renal function estimation using (99m)TC - DTPA renal scan. Twenty-one patients with unilateral obstructive uropathy were enrolled in this prospective comparative study. They were subjected to (99m)Tc - DTPA renal scan and 64 slice helical CT scan which estimates the renal volume depending on the reconstruction of arterial phase images followed by volume rendering and percent renal volume was calculated. Percent renal volume was correlated with percent renal function, as determined by nuclear renal scan using Pearson coefficient. RESULTS AND OBSERVATION: A strong correlation is observed between percent renal volume and percent renal function in obstructed units (r = 0.828, P < 0.001) as well as in nonobstructed units (r = 0.827, P < 0.001). There is a strong correlation between percent renal volume determined by CT scan and percent renal function determined by (99m)TC - DTPA renal scan both in obstructed and in normal units. CT-based percent renal volume can be used as a single radiological tests for both functional and anatomical assessment of impaired renal units.

[Lower urinary tract symptoms and pelvic floor dysfunction in renal transplant candidates and recipients].

PubMed

Thuret, R; Hurel, S; Kleinclauss, F; Timsit, M O

2016-11-01

To describe lower urinary tract symptoms (LUTS) and their management in renal transplant candidates and recipients. Relevant publications were identified through Medline (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) database using the following keywords, alone or in association: "transplantation", "prostate hyperplasia", "transurethral resection of prostate", "urinary incontinence", "LUTS", "pelvic floor dysfunction". Articles were selected according to methods, language of publication and relevance. The reference lists were used to identify additional historical studies of interest. Both prospective and retrospective series, in French and English, as well as review articles and case reports were selected. In addition, French national transplant and health agencies (http://www.agence-biomedecine.fr and http://www.has-sante.fr) databases were screened using identical keywords. A total of 991 articles were analyzed and after careful selection, 47 publications were eligible for our review. Reduction of bladder capacity, due to dialysis and anuria, is correlated with dialysis duration. This reduction is reversible after renal transplantation and does not seem to put renal transplant recipients at risk for medical complications. Transplant procedure generally allows restoration of bladder maximal output, normal bladder capacity and compliance. Medical treatment of LUTS related to prostate hyperplasia (BPH) includes alpha-blockers and finasteride. Silodosin and dutasteride have not been evaluated in that setting. Antimuscarinics may be used with caution, and favor the use of solifenacin at 5mg per day. Surgical treatment of BPH requires a preserved urine output, otherwise must be delayed after transplantation; it may thus be performed safely in the early postoperative course. Botulinum toxin injections and surgical treatment of stress incontinence and prolapse are barely reported in this population. Precise assessment and optimal management of LUTS in renal transplant candidates and recipients are critical to improve quality of life and to preserve allotransplant function. Literature data lack evidence to propose robust recommendations. However, knowledge of reported specificities in this peculiar setting is mandatory for urologists to provide patients with finest options and optimal treatment timing. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Live Cell Imaging of a Fluorescent Gentamicin Conjugate

PubMed Central

Escobedo, Jorge O.; Chu, Yu-Hsuan; Wang, Qi; Steyger, Peter S.; Strongin, Robert M.

2012-01-01

Understanding cellular mechanisms of ototoxic and nephrotoxic drug uptake, intracellular distribution, and molecular trafficking across cellular barrier systems aids the study of potential uptake blockers that preserve sensory and renal function during critical life-saving therapy. Herein we report the design, synthesis characterization and evaluation of a fluorescent conjugate of the aminoglycoside antibiotic gentamicin. Live cell imaging results show the potential utility of this new material. Related gentamicin conjugates studied to date quench in live kindney cells, and have been largely restricted to use in fixed (delipidated) cells. PMID:22545403

Continuous ambulatory peritoneal dialysis is better than automated peritoneal dialysis as first-line treatment in renal replacement therapy.

PubMed

Li, Philip Kam-Tao; Chung, Kwok Yi; Chow, Kai Ming

2007-06-01

This article examines the roles of continuous ambulatory peritoneal dialysis (CAPD) versus automated peritoneal dialysis (APD) as first-line renal replacement therapy. To date, no high-quality large-scale randomized controlled studies have compared CAPD with APD as first-line therapy. However, a discussion on this issue is important so that nephrologists can decide and patients can have a choice of modality on which to start dialysis, especially in the context of health care economics. We review the literature and present Hong Kong as the model of a "CAPD first" policy, an appealing, cost-effective approach for any country. An ideal renal replacement therapy should provide optimal survival, lowest possible risk for comorbidity, highest level of quality of life, and equally important, acceptable cost to society. When we consider this subject in the context that all patients should be started on one first-line modality, the data suggest that a "CAPD first" policy has all these advantages, with APD probably having the edge only with regard to patient preference. The present review highlights preservation of residual renal function, removal and balancing of sodium, incidence of peritonitis, peritoneal membrane transport status, patient rehabilitation, and financial issues in demonstrating that a "CAPD first" policy is the model that should be adopted.

A Qualitative Assessment of Human Cadavers Embalmed by Thiel's Method Used in Laparoscopic Training for Renal Resection

ERIC Educational Resources Information Center

Rai, Bhavan Prasad; Tang, Benjie; Eisma, Roos; Soames, Roger W.; Wen, Haitao; Nabi, Ghulam

2012-01-01

Human cadaveric tissue is the fundamental substrate for basic anatomic and surgical skills training. A qualitative assessment of the use of human cadavers preserved by Thiel's method for a British Association of Urological Surgeons--approved, advanced laparoscopic renal resection skills training course is described in the present study. Four…

Right-Sided Cardiac Dysfunction in Heart Failure With Preserved Ejection Fraction and Worsening Renal Function.

PubMed

Mukherjee, Monica; Sharma, Kavita; Madrazo, Jose A; Tedford, Ryan J; Russell, Stuart D; Hays, Allison G

2017-07-15

In urban populations, worsening renal function (WRF) is well established in patients hospitalized with acute decompensated heart failure with preserved ejection fraction (HFpEF). However, the mechanisms for development of WRF in the setting of acute HF in HFpEF are unclear. In the present study, we sought to characterize conventional echocardiographic measures of right ventricular (RV) chamber size and function to determine whether RV dysfunction and/or adverse RV remodeling is related to WRF in patients with HFpEF. Our study included 104 adult patients with HFpEF (EF ≥ 55%) with technically adequate 2-dimensional echocardiograms performed during their hospitalization for acute decompensated HF to determine echocardiographic predictors of WRF, defined as a serum creatinine (Cr) increase of ≥ 0.3 mg/dl within 72 hours of hospitalization. Thirty-eight of the 104 patients (36%) developed WRF (mean Cr increase = 0.9 ± 0.1 mg/dl) during the hospitalization (mean age ± SD of 64 ± 12 years, 27 women [71%], 29 black [76%]). There were no significant differences in LV medial E/e' ratio and RV systolic pressure by WRF status or in linear dimensions of RV and right atrial size. RV fractional area change, a measure of RV function, however, was significantly decreased in HFpEF patients with WRF compared with the no WRF group (p = 0.003), whereas RV free wall thickness (p = 0.001) was increased. In conclusion, linear and volumetric measures of dimensions of right atrial and RV chamber size did not distinguish HFpEF patients with and without WRF. However, in HFpEF patients with WRF during acute HF hospitalization, there was a significant decrease in RV function and a significant increase in RV free wall thickness compared with matched patients with no WRF. These findings suggest that adverse RV remodeling and RV dysfunction occur in HFpEF patients with WRF. Copyright © 2017 Elsevier Inc. All rights reserved.

End-stage renal disease, dialysis, kidney transplantation and their impact on CD4+ -T-cell differentiation.

PubMed

Schaier, Matthias; Leick, Angele; Uhlmann, Lorenz; Kälble, Florian; Morath, Christian; Eckstein, Volker; Ho, Anthony; Mueller-Tidow, Carsten; Meuer, Stefan; Mahnke, Karsten; Sommerer, Claudia; Zeier, Martin; Steinborn, Andrea

2018-05-02

Premature aging of both CD4 + -regulatory- (Tregs) and CD4 + -responder-T-cells (Tresps) in end-stage renal disease (ESRD) patients is expected to affect the success of later kidney transplantation. Both T-cell populations are released from the thymus as inducible co-stimulatory (ICOS + -) and ICOS - -recent thymic emigrant (RTE)-Tregs/Tresps, which differ primarily in their proliferative capacities. In this study, we analysed the effect of ESRD and subsequent renal replacement therapies on the differentiation of ICOS + - and ICOS - -RTE-Tregs/Tresps into ICOS + - or ICOS - -CD31 - -Memory-Tregs/Tresps and examined whether diverging pathways affected the suppressive activity of ICOS + - and ICOS - -Tregs in co-culture with autologous Tresps. Compared to healthy controls, we found an increased differentiation of ICOS + -RTE-Tregs/Tresps and ICOS - -RTE-Tregs via CD31 + -memory-Tregs/Tresps into CD31 - -memory-Tregs/Tresps in ESRD and dialysis patients. In contrast, ICOS - -RTE-Tresps showed an increased differentiation via ICOS - -mature naïve (MN)-Tresps into CD31 - -memory-Tresps. Thereby, the ratio of ICOS + -Tregs/ICOS + -Tresps was not changed, while that of ICOS - -Tregs/ICOS - -Tresps was significantly increased. This differentiation preserved the suppressive activity of both Treg populations in ESRD and partly in dialysis patients. After transplantation, the increased differentiation of ICOS + - and ICOS - -RTE-Tresps proceeded, while that of ICOS + -RTE-Tregs ceased and that of ICOS - -RTE-Tregs switched to an increased differentiation via ICOS - -MN-Tregs. Consequently, the ratios of ICOS + -Tregs/ICOS + -Tresps and of ICOS - -Tregs/ICOS - -Tresps decreased significantly, reducing the suppressive activity of Tregs markedly. Our data reveal that an increased tolerance-inducing differentiation of ICOS + - and ICOS - -Tregs preserves the functional activity of Tregs in ESRD patients, but this cannot be maintained during long-term renal replacement therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Functions of the Renal Nerves.

ERIC Educational Resources Information Center

Koepke, John P.; DiBona, Gerald F.

1985-01-01

Discusses renal neuroanatomy, renal vasculature, renal tubules, renin secretion, renorenal reflexes, and hypertension as related to renal nerve functions. Indicates that high intensitites of renal nerve stimulation have produced alterations in several renal functions. (A chart with various stimulations and resultant renal functions and 10-item,…

Ozone Therapy on Rats Submitted to Subtotal Nephrectomy: Role of Antioxidant System

PubMed Central

Calunga, José Luis; Zamora, Zullyt B.; Borrego, Aluet; del Río, Sarahí; Barber, Ernesto; Menéndez, Silvia; Hernández, Frank; Montero, Teresita; Taboada, Dunia

2005-01-01

Chronic renal failure (CRF) represents a world health problem. Ozone increases the endogenous antioxidant defense system, preserving the cell redox state. The aim of this study is to evaluate the effect of ozone/oxygen mixture in the renal function, morphology, and biochemical parameters, in an experimental model of CRF (subtotal nephrectomy). Ozone/oxygen mixture was applied daily, by rectal insufflation (0.5 mg/kg) for 15 sessions after the nephrectomy. Renal function was evaluated, as well as different biochemical parameters, at the beginning and at the end of the study (10 weeks). Renal plasmatic flow (RPF), glomerular filtration rate (GFR), the urine excretion index, and the sodium and potassium excretions (as a measurement of tubular function) in the ozone group were similar to those in Sham group. Nevertheless, nephrectomized rats without ozone (positive control group) showed the lowest RPF, GFR, and urine excretion figures, as well as tubular function. Animals treated with ozone showed systolic arterial pressure (SAP) figures lower than those in the positive control group, but higher values compared to Sham group. Serum creatinine values and protein excretion in 24 hours in the ozone group were decreased compared with nephrectomized rats, but were still higher than normal values. Histological study demonstrated that animals treated with ozone showed less number of lesions in comparison with nephrectomized rats. Thiobarbituric acid reactive substances were significantly increased in nephrectomized and ozone-treated nephrectomized rats in comparison with Sham group. In the positive control group, superoxide dismutase (SOD) and catalase (CAT) showed the lowest figures in comparison with the other groups. However, ozone/oxygen mixture induced a significant stimulation in the enzymatic activity of CAT, SOD, and glutathione peroxidase, as well as reduced glutathione in relation with Sham and positive control groups. In this animal model of CRF, ozone rectal administrations produced a delay in the advance of the disease, protecting the kidneys against vascular, hemorheological, and oxidative mechanisms. This behavior suggests ozone therapy has a protective effect on renal tissue by downregulation of the oxidative stress shown in CRF. PMID:16192672

Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function: Data from the CANVAS Program.

PubMed

Neuen, Brendon L; Ohkuma, Toshiaki; Neal, Bruce; Matthews, David R; de Zeeuw, Dick; Mahaffey, Kenneth W; Fulcher, Greg; Desai, Mehul; Li, Qiang; Deng, Hsiaowei; Rosenthal, Norm; Jardine, Meg J; Bakris, George; Perkovic, Vlado

2018-06-25

Background : Canagliflozin is approved for glucose lowering in type 2 diabetes and confers cardiovascular and renal benefits. We sought to assess whether it had benefits in people with chronic kidney disease (CKD), including those with an estimated glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m 2 in whom the drug is not currently approved for use. Methods : The CANagliflozin cardioVascular Assessment Study Program (CANVAS) randomized 10,142 participants with type 2 diabetes and eGFR greater than 30 mL/min/1.73 m 2 to canagliflozin or placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with other cardiovascular, renal, and safety outcomes. This secondary analysis describes outcomes in participants with and without CKD, defined as eGFR <60 and ≥60 mL/min/1.73 m 2 , and according to baseline kidney function (eGFR <45, 45-<60, 60-<90, and ≥90 mL/min/1.73 m 2 ). Results : At baseline, 2039 (20.1%) participants had an eGFR <60 mL/min/1.73 m 2 , of whom 71.6% had a history of cardiovascular disease. The effect of canagliflozin on the primary outcome was similar in people with CKD (HR 0.70, 95% CI 0.55-0.90) and those with preserved kidney function (HR 0.92, 95% CI 0.79-1.07, P heterogeneity = 0.08). Relative effects on most cardiovascular and renal outcomes were similar across eGFR subgroups, with possible heterogeneity suggested only for the outcome of fatal/nonfatal stroke ( P heterogeneity = 0.01), as were results for almost all safety outcomes. Conclusions : The effect of canagliflozin on cardiovascular and renal outcomes was not modified by baseline level of kidney function in people with type 2 diabetes and a history or high risk of cardiovascular disease down to eGFR levels of 30 mL/min/1.73 m 2 Reassessing current limitations on the use of canagliflozin in CKD may allow additional individuals to benefit from this therapy. Clinical Trial Registration : URL: https://clinicaltrials.gov. Unique identifiers: NCT01032629, NCT01989754.

When Partial Nephrectomy is Unsuccessful: Understanding the Reasons for Conversion from Robotic Partial to Radical Nephrectomy at a Tertiary Referral Center.

PubMed

Kara, Önder; Maurice, Matthew J; Mouracade, Pascal; Malkoç, Ercan; Dagenais, Julien; Nelson, Ryan J; Chavali, Jaya Sai S; Stein, Robert J; Fergany, Amr; Kaouk, Jihad H

2017-07-01

We sought to identify the preoperative factors associated with conversion from robotic partial nephrectomy to radical nephrectomy. We report the incidence of this event. Using our institutional review board approved database, we abstracted data on 1,023 robotic partial nephrectomies performed at our center between 2010 and 2015. Standard and converted cases were compared in terms of patients and tumor characteristics, and perioperative, functional and oncologic outcomes. Logistic regression analysis was done to identify predictors of radical conversion. The overall conversion rate was 3.1% (32 of 1,023 cases). The most common reasons for conversion were tumor involvement of hilar structures (8 cases or 25%), failure to achieve negative margins on frozen section (7 or 21.8%), suspicion of advanced disease (5 or 15.6%) and failure to progress (5 or 15.6%). Patients requiring conversion were older and had a higher Charlson score (both p <0.01), including an increased prevalence of chronic kidney disease (p = 0.02). Increasing tumor size (5 vs 3.1 cm, p <0.01) and R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines and hilar location) score (9 vs 8, p <0.01) were also associated with an increased risk of conversion. Worse baseline renal function (OR 0.98, 95% CI 0.96-0.99, p = 0.04), large tumor size (OR 1.44, 95% CI 1.22-1.7, p <0.01) and increasing R.E.N.A.L. score (p = 0.02) were independent predictors of conversion. Compared to converted cases, at latest followup standard robotic partial nephrectomy cases had similar short-term oncologic outcomes but better renal functional preservation (p <0.01). At a high volume center the rate of robotic partial nephrectomy conversion to radical nephrectomy was 3.1%, including 2.2% of preoperatively anticipated nephrectomy cases. Increasing tumor size and complexity, and poor preoperative renal function are the main predictors of conversion. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Percutaneous Radiofrequency Ablation Versus Robotic-Assisted Partial Nephrectomy for the Treatment of Small Renal Cell Carcinoma

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

Pantelidou, Maria; Challacombe, Ben; McGrath, Andrew

IntroductionThe authors compared the oncologic outcomes of radiofrequency ablation (RFA) with robotic-assisted partial nephrectomy (RPN) for the treatment of T1 stage renal cell carcinoma (RCC).Materials and methodsThis was a retrospective data analysis of a high-volume single tertiary centre. Patients were treated with RFA or RPN following multidisciplinary decision making. Only histologically proven RCCs were included. Baseline demographics were collected, and PADUA scores of tumour features were calculated to standardize baseline anatomy. Peri-operative complications, kidney function and oncological outcomes were compared.ResultsSixty-three cases were included in each group. Baseline renal function was poorer in RFA, and 16/63 RFA patients had tumours inmore » single kidneys compared to 1/63 RPN cases (p < 0.001). Length of stay was shorter in RFA (1 vs. 3 days, p < 0.0001). Post-procedure renal function decline at 30 days was significantly less in RFA [(−0.8) ± 9.6 vs. (−16.1) ± 19.5 mls/min/1.73 m{sup 2}; p < 0.0001]. More minor complications were recorded in RPN (10/63 vs. 4/63, p = 0.15), but local recurrence was numerically higher in RFA (6/63 vs. 1/63, p = 0.11). Disease-free survival (DFS) was not significantly different (adjusted HR = 0.6, 95 % Cl 0.1–3.7; p = 0.60). Increasing tumour size was an independent predictor of local recurrence (adjusted HR = 1.7; 95 % Cl 1.1–2.6 per cm; p = 0.02).ConclusionsBoth RPN and RFA offer very good oncological outcomes for the treatment of T1 RCC with low peri-operative morbidity and similar oncologic outcomes. RFA demonstrated fewer peri-operative complications and better preservation of renal function, whereas RPN had an insignificantly lower local recurrence rate. RFA should be offered alongside RPN for selected cases.« less

Lupus nephritis with preserved kidney function associated with poorer cardiovascular risk control: A call for more awareness.

PubMed

Todolí-Parra, J A; Tung-Chen, Y; Micó, L; Gutiérrez, J; Hernández-Jaras, J; Ruiz-Cerda, J L

2018-01-27

Despite the improvement in the prognosis of lupus nephritis (LN), the cardiovascular morbimortality remains high. The early recognition and remission of flares, while trying to avoid the metabolic adverse effects of medication, must be mandatory. The aim of our study was to assess the cardiovascular (CV) risk profile in a cohort of lupus patients with preserved kidney function after a nephritis episode, compared to patients without a nephritis flare. 130 patients diagnosed of SLE (32 with previous nephritis flare and 98 without) were studied in order to evaluate the CV risk profile, despite the preserved kidney function. The most prevalent risk factors were sedentary lifestyle (57.6%), overweight/obesity (38.3%) and dyslipidemia (36%), followed by smoking (32%) and hypertension (16%). Though more than a half (53.1%) was taking CV medication, a high percentage did not reach a therapeutic target value, especially regarding obesity (11.5%) and cholesterol levels (LDL-C of 16%). The prevalence of dyslipidemia (53.1% vs 30.6%), smoking (46.6% vs 27.5%), left ventricular hypertrophy (LVH) (21.4% vs 6.4%) and lower HDL-C (48.6mg/dL vs 55.4mg/dL) were significantly different in the group with previous nephritis flare. Moreover, young patients with lupus nephritis, received more pulses of corticosteroids and cyclophosphamide, had higher prevalence of hypertension, LVH, higher proteinuria, hospital admissions and waist circumference, constituting the subgroup of patients with greater aggregation of CV risk factors. Patients with previous nephritis flare showed a poor control of CV risk factors despite the preserved renal function, these patients would require a closer therapeutic management. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Impaired Urine Dilution Capability in HIV Stable Patients

PubMed Central

Belloso, Waldo H.; de Paz Sierra, Mariana; Navarro, Matilde; Sanchez, Marisa L.; Perelsztein, Ariel G.; Musso, Carlos G.

2014-01-01

Renal disease is a well-recognized complication among patients with HIV infection. Viral infection itself and the use of some antiretroviral drugs contribute to this condition. The thick ascending limb of Henle's loop (TALH) is the tubule segment where free water clearance is generated, determining along with glomerular filtration rate the kidney's ability to dilute urine. Objective. We analyzed the function of the proximal tubule and TALH in patients with HIV infection receiving or not tenofovir-containing antiretroviral treatment in comparison with healthy seronegative controls, by applying a tubular physiological test, hyposaline infusion test (Chaimowitz' test). Material & Methods. Chaimowitz' test was performed on 20 HIV positive volunteers who had normal renal functional parameters. The control group included 10 healthy volunteers. Results. After the test, both HIV groups had a significant reduction of serum sodium and osmolarity compared with the control group. Free water clearance was lower and urine osmolarity was higher in both HIV+ groups. Proximal tubular function was normal in both studied groups. Conclusion. The present study documented that proximal tubule sodium reabsorption was preserved while free water clearance and maximal urine dilution capability were reduced in stable HIV patients treated or not with tenofovir. PMID:24800076

Establishment of a protocol for the gene expression analysis of laser microdissected rat kidney samples with affymetrix genechips

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

Stemmer, Kerstin; Ellinger-Ziegelbauer, Heidrun; Lotz, Kerstin

2006-11-15

Laser microdissection in conjunction with microarray technology allows selective isolation and analysis of specific cell populations, e.g., preneoplastic renal lesions. To date, only limited information is available on sample preparation and preservation techniques that result in both optimal histomorphological preservation of sections and high-quality RNA for microarray analysis. Furthermore, amplification of minute amounts of RNA from microdissected renal samples allowing analysis with genechips has only scantily been addressed to date. The objective of this study was therefore to establish a reliable and reproducible protocol for laser microdissection in conjunction with microarray technology using kidney tissue from Eker rats p.o. treatedmore » for 7 days and 6 months with 10 and 1 mg Aristolochic acid/kg bw, respectively. Kidney tissues were preserved in RNAlater or snap frozen. Cryosections were cut and stained with either H and E or cresyl violet for subsequent morphological and RNA quality assessment and laser microdissection. RNA quality was comparable in snap frozen and RNAlater-preserved samples, however, the histomorphological preservation of renal sections was much better following cryopreservation. Moreover, the different staining techniques in combination with sample processing time at room temperature can have an influence on RNA quality. Different RNA amplification protocols were shown to have an impact on gene expression profiles as demonstrated with Affymetrix Rat Genome 230{sub 2}.0 arrays. Considering all the parameters analyzed in this study, a protocol for RNA isolation from laser microdissected samples with subsequent Affymetrix chip hybridization was established that was also successfully applied to preneoplastic lesions laser microdissected from Aristolochic acid-treated rats.« less

Aging and physiological changes of the kidneys including changes in glomerular filtration rate.

PubMed

Musso, Carlos G; Oreopoulos, Dimitrios G

2011-01-01

In addition to the structural changes in the kidney associated with aging, physiological changes in renal function are also found in older adults, such as decreased glomerular filtration rate, vascular dysautonomia, altered tubular handling of creatinine, reduction in sodium reabsorption and potassium secretion, and diminished renal reserve. These alterations make aged individuals susceptible to the development of clinical conditions in response to usual stimuli that would otherwise be compensated for in younger individuals, including acute kidney injury, volume depletion and overload, disorders of serum sodium and potassium concentration, and toxic reactions to water-soluble drugs excreted by the kidneys. Additionally, the preservation with aging of a normal urinalysis, normal serum urea and creatinine values, erythropoietin synthesis, and normal phosphorus, calcium and magnesium tubular handling distinguishes decreased GFR due to normal aging from that due to chronic kidney disease. Copyright © 2011 S. Karger AG, Basel.

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.

Endovascular repair of abdominal aortic aneurysms in patients with congenital renal vascular anomalies.

PubMed

Kaplan, D B; Kwon, C C; Marin, M L; Hollier, L H

1999-09-01

The endovascular repair of abdominal aortic aneurysms (AAAs) has been suggested as an alternative to conventional aortic reconstruction. The presence of anomalous renal vascular anatomy frequently necessitates special planning during conventional aortic replacement and may also create unique challenges for endovascular repair. We analyzed our experience with 24 patients with variant renal vascular anatomies who underwent treatment with aortic endografts to determine the safety and efficacy of this technique in this population. During a 6-year period, 204 patients underwent aortic endograft procedures, 24 (11.8%) of whom had variations in renal vascular anatomy. There were 19 men and five women. Each of the 24 patients had variant renal vascular anatomy, which was defined by the presence of multiple renal arteries (n = 32), with or without a renal parenchymal anomaly (horseshoe or solitary pelvic kidney). Twenty patients underwent aneurysm repair with balloon expandable polytetrafluoroethylene grafts, and the remaining patients underwent endograft placement with self-expanding attachment systems. Eighteen patients underwent exclusion and presumed thrombosis of anomalous renal branches to effectively attach the aortic endograft. The decision to sacrifice a supernumerary artery was made on the basis of the vessel size (<3 mm), the absence of coexisting renal insufficiency, and the expectation for successful aneurysm exclusion. The successful exclusion of the AAAs was achieved in all the patients, with the loss of a total of 17 renal artery branches in 12 patients. Small segmental renal infarcts (<20%) were detected in only six of the 12 patients with follow-up computed tomographic scan results, despite angiographic evidence of vessel occlusion at the time of endografting. No evidence of new onset hypertension or changes in antihypertensive medication was seen in this group. No retrograde endoleaks were detected through the excluded renal branches on late follow-up computed tomographic scans. Serum creatinine levels before and after endografting were unchanged after the exclusion of the AAA in all but one patient with multiple renal branches. One patient had a transient rise in serum creatinine level presumed to be caused by contrast nephropathy. On the basis of this experience, we recommend the consideration of endovascular grafting for patients with AAAs and anomalous renal vessels when the main renal vascular anatomy can be preserved and when the loss of only small branches (<3 mm) is necessitated in patients with otherwise normal renal functions.

Hypertensive renal disease: susceptibility and resistance in inbred hypertensive rat lines.

PubMed

Braun, Michael C; Herring, Stacy M; Gokul, Nisha; Monita, Monique; Bell, Rebecca; Hicks, M John; Wenderfer, Scott E; Doris, Peter A

2013-10-01

Spontaneously hypertensive rat (SHR) lines differ in their susceptibility to hypertensive end-organ disease and may provide an informative model of genetic risk of disease. Lines derived from the original SHR-B and SHR-C clades are highly resistant to hypertensive end-organ disease, whereas lines derived from the SHR-A clade were selected for stroke susceptibility and experience hypertensive renal disease. Here we characterize the temporal development of progressive renal injury in SHR-A3 animals consuming 0.3% sodium in the diet and drinking water. SHR-A3 rats demonstrate albuminuria, glomerular damage, tubulointerstitial injury, and renal fibrosis that emerge at 18 weeks of age and progress. Mortality of SHR-A3 animals was 50% at 40 weeks of age, and animals surviving to this age had reduced renal function. In contrast SHR-B2, which are 87% genetically identical to SHR-A3, are substantially protected from renal injury and demonstrate only moderate changes in albuminuria and renal histological injury over this time period. At 40 weeks of age, electron microscopy of the renal glomerulus revealed severe podocyte effacement in SHR-A3, but slit diaphragm architecture in SHR-B2 at this age was well preserved. Renal injury traits in the F1 and F2 progeny of an intercross between SHR-A3 and SHR-B2 were measured to determine heritability of renal injury in this model. Heritability of albuminuria, glomerular injury, and tubulointerstitial injury were estimated at 48.9, 66.5 and 58.6%, respectively. We assessed the relationship between blood pressure and renal injury measures in the F2 animals and found some correlation between these variables that explain up to 26% of the trait variation. Quantitative trait locus (QTL) mapping was performed using over 200 single nucleotide polymorphism markers distributed across the 13% of the genome that differs between these two closely related lines. Mapping of albuminuria, tubulointerstitial injury, and renal fibrosis failed to identify loci linked with disease susceptibility, suggesting a complex inheritance of disease risk. We detected a single QTL conferring susceptibility to glomerular injury that was confined to a small haplotype block at chromosome 14:70-76Mb.

Early administration of tolvaptan preserves renal function in elderly patients with acute decompensated heart failure.

PubMed

Kimura, Kazuhiro; Momose, Tomoyasu; Hasegawa, Tomoya; Morita, Takehiro; Misawa, Takuo; Motoki, Hirohiko; Izawa, Atsushi; Ikeda, Uichi

2016-05-01

Loop diuretics used in the treatment of heart failure often induce renal impairment. This study was conducted in order to evaluate the renal protective effect of adding tolvaptan (TLV), compared to increasing the furosemide (FRM) dose, for the treatment of acute decompensated heart failure (ADHF) in a real-world elderly patient population. This randomized controlled trial enrolled 52 consecutive hospitalized patients (age 83.4±9.6 years) with ADHF. The patients were assigned alternately to either the TLV group (TLV plus conventional treatment, n=26) or the FRM group (increasing the dose of FRM, n=26). TLV was administered within 24h from admission. The incidence of worsening renal function (WRF) within 7 days from admission was significantly lower in the TLV group (26.9% vs. 57.7%, p=0.025). Furthermore, the rates of occurrence of persistent and late-onset (≥5 days from admission) WRF were significantly lower in the TLV group. Persistent and late-onset WRF were significantly associated with a higher incidence of cardiac death or readmission for worsening heart failure in the 90 days following discharge, compared to transient and early-onset WRF, respectively. Early administration of TLV, compared to increased FRM dosage, reduces the incidence of WRF in real-world elderly ADHF patients. In addition, it reduces the occurrence of 'worse' WRF-persistent and late-onset WRF-which are associated with increased rates of cardiac death or readmission for worsening heart failure in the 90 days after discharge. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Human Alpha-1-Antitrypsin (hAAT) therapy reduces renal dysfunction and acute tubular necrosis in a murine model of bilateral kidney ischemia-reperfusion injury

PubMed Central

Maicas, Nuria; van der Vlag, Johan; Bublitz, Janin; Florquin, Sandrine; Bakker-van Bebber, Marinka; Dinarello, Charles A.; Verweij, Vivienne; Masereeuw, Roos; Joosten, Leo A.

2017-01-01

Several lines of evidence have demonstrated the anti-inflammatory and cytoprotective effects of alpha-1-antitrypsin (AAT), the major serum serine protease inhibitor. The aim of the present study was to investigate the effects of human AAT (hAAT) monotherapy during the early and recovery phase of ischemia-induced acute kidney injury. Mild renal ischemia-reperfusion (I/R) injury was induced in male C57Bl/6 mice by bilateral clamping of the renal artery and vein for 20 min. hAAT (80 mg/kg, Prolastin®) was administered daily intraperitoneally (i.p.) from day -1 until day 7 after surgery. Control animals received the same amount of human serum albumin (hAlb). Plasma, urine and kidneys were collected at 2h, 1, 2, 3, 8 and 15 days after reperfusion for histological and biochemical analysis. hAAT partially preserved renal function and tubular integrity after induction of bilateral kidney I/R injury, which was accompanied with reduced renal influx of macrophages and a significant decrease of neutrophil gelatinase-associated lipocalin (NGAL) protein levels in urine and plasma. During the recovery phase, hAAT significantly decreased kidney injury molecule-1 (KIM-1) protein levels in urine but showed no significant effect on renal fibrosis. Although the observed effect size of hAAT administration was limited and therefore the clinical relevance of our findings should be evaluated carefully, these data support the potential of this natural protein to ameliorate ischemic and inflammatory conditions. PMID:28235038

Enhancing patient engagement and blood pressure management for renal transplant recipients via home electronic monitoring and web-enabled collaborative care.

PubMed

Aberger, Edward W; Migliozzi, Daniel; Follick, Michael J; Malick, Tom; Ahern, David K

2014-09-01

Effective management of hypertension in chronic kidney disease and renal transplantation is a clinical priority and has societal implications in terms of preserving and optimizing the value of scarce organs. However, hypertension is optimally managed in only 37% of people with chronic kidney disease, and poor control can contribute to premature graft loss in renal transplant recipients. This article describes a telehealth system that incorporates home electronic blood pressure (BP) monitoring and uploading to a patient portal coupled with a Web-based dashboard that enables clinical pharmacist collaborative care in a renal transplant clinic. The telehealth system was developed and implemented as a quality improvement initiative in a renal transplant clinic in a large, 700-bed, urban hospital with the aim of improving BP in posttransplant patients. A convenience sample of 66 posttransplant patients was recruited by the clinical pharmacist from consecutive referrals to the Transplant Clinic. Preliminary results show statistically significant reductions in average systolic and diastolic BP of 6.0 mm Hg and 3.0 mm Hg, respectively, at 30 days after enrollment. Two case reports describe the instrumental role of home BP monitoring in the context of medication therapy management. Optimizing BP control for both pre- and post-renal transplant patients is likely to benefit society in terms of preserving scarce resources and reducing healthcare costs due to premature graft failure. Connected health systems hold great promise for supporting team-based care and improved health outcomes.

Preservation of renal function during maintenance therapy with cyclosporine.

PubMed

Serón, D; Moreso, F

2004-03-01

During the last 20 years the management of cyclosporine (CsA) has improved due to the introduction of microemulsion technology, C2 monitoring, and combination with other new immunosuppressants. All these modifications have reduced the incidence of biopsy-proven acute rejection episodes to approximately 10%. However despite the wide experience, there are unanswered questions regarding CsA monitoring after the first year. Available clinical and histological data suggest that the therapeutic range to avoid nephrotoxicity or underimmunosuppression during the maintenance period is rather narrow. Furthermore, the combination of CsA with new immunosuppressants may modify the target CsA levels. Although the utility of C2 levels during the first year has been well characterized, there are few data on its utility for maintenance therapy, particularly the therapeutic range for C2 levels in patients receiving different immunosuppressive combinations. Since serum creatinine does not precisely reflect the progression of chronic allograft nephropathy, the efficacy of C2 monitoring during the maintenance period must be assessed not only by means of evaluation of renal function, but also histologic assessment using protocol biopsies.

Effects of microgravity on renal stone risk assessment

NASA Technical Reports Server (NTRS)

Pietrzyk, R. A.; Pak, C. Y. C.; Cintron, N. M.; Whitson, P. A.

1992-01-01

Physiologic changes induced during human exposure to the microgravity environment of space may contribute to an increased potential for renal stone formation. Renal stone risk factors obtained 10 days before flight and immediately after return to earth indicated that calcium oxalate and uric acid stone-forming potential was increased after space flights of 4-10 days. These data describe the need for examining renal stone risk during in-flight phases of space missions. Because of limited availability of space and refrigerated storage on spacecraft, effective methods must be developed for collecting urine samples in-flight and for preserving (or storing) them at temperatures and under conditions commensurate with mission constraints.

A case of antenatal Bartter syndrome with sensorineural deafness.

PubMed

Lee, Hyun Seung; Cheong, Hae Il; Ki, Chang-Seok

2010-10-01

Bartter syndrome type IV, also known as Bartter syndrome with sensorineural deafness (BSND), is caused by loss-of-function mutations in the BSND gene, which encodes barttin, an accessory subunit of chloride channels located in the kidney and inner ear. Patients with BS IV have a highly variable clinical phenotype. This report concerns a Korean male patient with antenatal Bartter syndrome due to a homozygous BSND p.G47R mutation, who presented with severe perinatal symptoms followed by a relatively benign course with preserved renal function after early infancy. In addition, the clinical features and the laboratory data of the patient were compared with those of previously reported patients with the same mutation.

Superagonistic CD28 antibody induces donor-specific tolerance in rat renal allografts.

PubMed

Azuma, H; Isaka, Y; Li, X; Hünig, T; Sakamoto, T; Nohmi, H; Takabatake, Y; Mizui, M; Kitazawa, Y; Ichimaru, N; Ibuki, N; Ubai, T; Inamoto, T; Katsuoka, Y; Takahara, S

2008-10-01

The ultimate goal of organ transplantation is to establish graft tolerance where CD4+CD25+FOXP3+ regulatory T (Treg) cells play an important role. We examined whether a superagonistic monoclonal antibody specific for CD28 (CD28 SA), which expands Treg cells in vivo, would prevent acute rejection and induce tolerance using our established rat acute renal allograft model (Wistar to Lewis). In the untreated or mouse IgG-treated recipients, graft function significantly deteriorated with marked destruction of renal tissue, and all rats died by 13 days with severe azotemia. In contrast, 90% of recipients treated with CD28 SA survived over 100 days, and 70% survived with well-preserved graft function until graft recovery at 180 days. Analysis by flow cytometry and immunohistochemistry demonstrated that CD28 SA induced marked infiltration of FOXP3+ Treg cells into the allografts. Furthermore, these long-surviving recipients showed donor-specific tolerance, accepting secondary (donor-matched) Wistar cardiac allografts, but acutely rejecting third-party BN allografts. We further demonstrated that adoptive transfer of CD4+CD25+ Treg cells, purified from CD28 SA-treated Lewis rats, significantly prolonged allograft survival and succeeded in inducing donor-specific tolerance. In conclusion, CD28 SA treatment successfully induces donor-specific tolerance with the involvement of Treg cells, and thus the therapeutic value of this approach warrants further investigation and preclinical studies.

Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation

PubMed Central

McGee-Lawrence, Meghan; Buckendahl, Patricia; Carpenter, Caren; Henriksen, Kim; Vaughan, Michael; Donahue, Seth

2015-01-01

ABSTRACT Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results. However, previous studies used serum markers of bone remodeling that are known to accumulate with decreased renal function, which bears have during hibernation. Therefore, we measured serum bone remodeling markers (BSALP and TRACP) that do not accumulate with decreased renal function, in addition to the concentrations of serum calcium and hormones involved in regulating bone remodeling in hibernating and active bears. Bone resorption and formation markers were decreased during hibernation compared with when bears were physically active, and these findings were supported by histomorphometric analyses of bone biopsies. The serum concentration of cocaine and amphetamine regulated transcript (CART), a hormone known to reduce bone resorption, was 15-fold higher during hibernation. Serum calcium concentration was unchanged between hibernation and non-hibernation seasons. Suppressed and balanced bone resorption and formation in hibernating bears contributes to energy conservation, eucalcemia and the preservation of bone mass and strength, allowing bears to survive prolonged periods of extreme environmental conditions, nutritional deprivation and anuria. PMID:26157160

The impact of preserved Klotho gene expression on anti-oxidative stress activity in healthy kidney.

PubMed

Kimura, Takaaki; Shiizaki, Kazuhiro; Kurosu, Hiroshi; Akimoto, Tetsu; Shinzato, Takahiro; Shimizu, Toshihiro; Kurosawa, Akira; Kubo, Taro; Nanmoku, Koji; Kuro-O, Makoto; Yagisawa, Takashi

2018-04-25

Klotho, which was originally identified as an anti-aging gene, forms a complex with fibroblast growth factor 23 (FGF23) receptor in kidney, with subsequent signaling that regulates mineral metabolism. Other biological activities of Klotho including anti-aging effects such as protection from various cellular stress have been shown, however, the precise mechanism of these effects of Klotho gene in the healthy human kidney is not well understood. In this study, we examined the relationships of Klotho and anti-oxidative stress gene expression levels in zero-hour biopsy specimens from 44 donors in kidney transplantation and verified them in animal models whose Klotho gene expression levels were varied. The nitrotyrosine expression level in kidney was evaluated in these animal models. Expression levels of Klotho gene were positively correlated with p53 gene, and antioxidant enzyme genes such as Catalase, superoxide dismutase 1 (SOD1), SOD2, peroxiredoxin 3 (PRDX3), and glutathione peroxidase 1 (GPX1) but not clinical parameters such as age and renal function, and pathological features such as glomerulosclerosis and interstitial fibrosis tubular atrophy. The expression levels of all genes were significantly higher in mice with Klotho overexpression than in wild-type mice, and those except for PRDX3 and GPX1 were significantly lower in Klotho-deficient mice than in wild-type littermate mice. Nitrotyrosine-positive bands of various sizes were observed in kidney from Klotho-deficient mice only. The preservation of Klotho gene expression might induce the anti-oxidative stress mechanism for homeostasis of healthy human kidney independently of its general condition including age, renal function, and histological findings.

Effects of aqueous extract of Hibiscus sabdariffa on renal Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in Wistar rats.

PubMed

Olatunji, Lawrence A; Usman, Taofeek O; Adebayo, Joseph O; Olatunji, Victoria A

2012-09-01

To investigate the effects of oral administration of aqueous extract of Hibiscus sabdariffa on renal Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in rats. The 25 and 50 mg/(kg·d) of aqueous extracts of H. sabdariffa were respectively given to rats in the experimental groups for 28 d, and rats in the control group received an appropriate volume of distilled water as vehicle. Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in the kidney were assayed by spectrophotometric method. Administrations of 25 and 50 mg/(kg·d) of aqueous extract of H. sabdariffa significantly decreased the Ca(2+)-Mg(2+)-ATPase activity in the kidney of rats (P<0.05). However, the renal Na(+)-K(+)-ATPase activity of the experimental rats was not affected by either dose of the extract. And the plasma Na(+), K(+) and Ca(2+) levels of the experimental rats had no significant changes. Administration of either dose of the extract did not result in any significant changes in body and kidney weights, the concentrations of plasma albumin and total protein, and alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase activities. However, concentrations of creatinine and urea were significantly reduced by 50 mg/kg of the extract (P<0.05). The present study indicates that oral administration of aqueous extract of H. sabdariffa may preserve the renal function despite a decreased renal Ca(2+)-Mg(2+)-ATPase activity.

Increased renal tubular sodium reabsorption during exercise-induced hypervolemia in humans

NASA Technical Reports Server (NTRS)

Nagashima, K.; Wu, J.; Kavouras, S. A.; Mack, G. W.

2001-01-01

We tested the hypothesis that renal tubular Na(+) reabsorption increased during the first 24 h of exercise-induced plasma volume expansion. Renal function was assessed 1 day after no-exercise control (C) or intermittent cycle ergometer exercise (Ex, 85% of peak O(2) uptake) for 2 h before and 3 h after saline loading (12.5 ml/kg over 30 min) in seven subjects. Ex reduced renal blood flow (p-aminohippurate clearance) compared with C (0.83 +/- 0.12 vs. 1.49 +/- 0.24 l/min, P < 0.05) but did not influence glomerular filtration rates (97 +/- 10 ml/min, inulin clearance). Fractional tubular reabsorption of Na(+) in the proximal tubules was higher in Ex than in C (P < 0.05). Saline loading decreased fractional tubular reabsorption of Na(+) from 99.1 +/- 0.1 to 98.7 +/- 0.1% (P < 0.05) in C but not in Ex (99.3 +/- 0.1 to 99.4 +/- 0.1%). Saline loading reduced plasma renin activity and plasma arginine vasopressin levels in C and Ex, although the magnitude of decrease was greater in C (P < 0.05). These results indicate that, during the acute phase of exercise-induced plasma volume expansion, increased tubular Na(+) reabsorption is directed primarily to the proximal tubules and is associated with a decrease in renal blood flow. In addition, saline infusion caused a smaller reduction in fluid-regulating hormones in Ex. The attenuated volume-regulatory response acts to preserve distal tubular Na(+) reabsorption during saline infusion 24 h after exercise.

Influence of CT-based depth correction of renal scintigraphy in evaluation of living kidney donors on side selection and postoperative renal function: is it necessary to know the relative renal function?

PubMed

Weinberger, Sarah; Klarholz-Pevere, Carola; Liefeldt, Lutz; Baeder, Michael; Steckhan, Nico; Friedersdorff, Frank

2018-03-22

To analyse the influence of CT-based depth correction in the assessment of split renal function in potential living kidney donors. In 116 consecutive living kidney donors preoperative split renal function was assessed using the CT-based depth correction. Influence on donor side selection and postoperative renal function of the living kidney donors were analyzed. Linear regression analysis was performed to identify predictors of postoperative renal function. A left versus right kidney depth variation of more than 1 cm was found in 40/114 donors (35%). 11 patients (10%) had a difference of more than 5% in relative renal function after depth correction. Kidney depth variation and changes in relative renal function after depth correction would have had influence on side selection in 30 of 114 living kidney donors. CT depth correction did not improve the predictability of postoperative renal function of the living kidney donor. In general, it was not possible to predict the postoperative renal function from preoperative total and relative renal function. In multivariate linear regression analysis, age and BMI were identified as most important predictors for postoperative renal function of the living kidney donors. Our results clearly indicate that concerning the postoperative renal function of living kidney donors, the relative renal function of the donated kidney seems to be less important than other factors. A multimodal assessment with consideration of all available results including kidney size, location of the kidney and split renal function remains necessary.

Following specific podocyte injury captopril protects against progressive long term renal damage.

PubMed

Zhou, Yu S; Ihmoda, Ihmoda A; Phelps, Richard G; Bellamy, Christopher Os; Turner, A Neil

2015-01-01

Angiotensin converting enzyme inhibitors (ACEi) reduce proteinuria and preserve kidney function in proteinuric renal diseases. Their nephroprotective effect exceeds that attributable to lowering of blood pressure alone. This study examines the potential of ACEi to protect from progression of injury after a highly specific injury to podocytes in a mouse model. We created transgenic (Podo-DTR) mice in which graded specific podocyte injury could be induced by a single injection of diphtheria toxin. Transgenic and wild-type mice were given the ACEi captopril in drinking water, or water alone, commencing 24h after toxin injection. Kidneys were examined histologically at 8 weeks and injury assessed by observers blinded to experimental group. After toxin injection, Podo-DTR mice developed acute proteinuria, and at higher doses transient renal impairment, which subsided within 3 weeks to be followed by a slow glomerular scarring process. Captopril treatment in Podo-DTR line 57 after toxin injection at 5ng/g body weight reduced proteinuria and ameliorated glomerular scarring, matrix accumulation and glomerulosclerosis almost to baseline (toxin: 17%; toxin + ACEi 10%, p<0.04; control 7% glomerular scarring). Podocyte counts were reduced after toxin treatment and showed no recovery irrespective of captopril treatment (7.1 and 7.3 podocytes per glomerular cross section in water and captopril-treated animals compared with 8.2 of wild-type controls, p<0.05). Observations in Podo-DTR mice support the hypothesis that continuing podocyte dysfunction is a key abnormality in proteinuric disease. Our model is ideal for studying strategies to protect the kidney from progressive injury following podocyte depletion. Demonstrable protective effects from captopril occur, despite indiscernible preservation or restoration of podocyte counts, at least after this degree of relatively mild injury.

Controlled circumferential renal sympathetic denervation with preservation of the renal arterial wall using intraluminal ultrasound: a next-generation approach for treating sympathetic overactivity.

PubMed

Sakakura, Kenichi; Roth, Austin; Ladich, Elena; Shen, Kai; Coleman, Leslie; Joner, Michael; Virmani, Renu

2015-02-01

The Paradise Ultrasound Renal Denervation System is a next-generation catheter-based device which was used to investigate whether the target ablation area can be controlled by changing ultrasound energy and duration to optimise nerve injury while preventing damage to the arterial wall. Five ultrasound doses were tested in a thermal gel model. Catheter-based ultrasound denervation was performed in 15 swine (29 renal arteries) to evaluate five different doses in vivo, and animals were euthanised at seven days for histopathologic assessment. In the gel model, the peak temperature was highest in the low power-long duration (LP-LD) dose, followed by the mid-low power-mid duration (MLP-MD) dose and the mid-high power-short duration (MHP-SD) dose, and lowest in the mid power-short duration (MP-SD) dose and the high power-ultra short duration (HP-USD) dose. In the animal study, total ablation area was significantly greater in the LP-LD group, followed by the MLP-MD group, and it was least in the HP-USD, MP-SD and MHP-SD groups (p=0.02). Maximum distance was significantly greater in the LP-LD group, followed by the MLP-MD group, the MHP-SD group, and the HP-USD group, and shortest in the MP-SD group (p=0.007). The short spare distance was not different among the five groups (p=0.38). Renal artery damage was minimal, while preserving significant nerve damage in all groups. The Paradise Ultrasound Renal Denervation System is a controllable system where total ablation area and depth of ablation can be optimised by changing ultrasound power and duration while sparing renal arterial tissue damage but allowing sufficient peri-arterial nerve damage.

Diagnosis and management of urinary incontinence and functional fecal incontinence (encopresis) in children.

PubMed

Nijman, Rien J M

2008-09-01

The ability to maintain normal continence for urine and stools is not achievable in all children by a certain age. Gaining control of urinary and fecal continence is a complex process, and not all steps and factors involved are fully understood. While normal development of anatomy and physiology are prerequisites to becoming fully continent, anatomic abnormalities, such as bladder exstrophy, epispadias, ectopic ureters, and neurogenic disturbances that can usually be recognized at birth and cause incontinence, will require specialist treatment, not only to restore continence but also to preserve renal function. Most forms of urinary incontinence are not caused by an anatomic or physiologic abnormality and, hence, are more difficult to diagnose and their management requires a sound knowledge of bladder and bowel function.

Comorbidity and ventricular and vascular structure and function in heart failure with preserved ejection fraction: a community-based study.

PubMed

Mohammed, Selma F; Borlaug, Barry A; Roger, Véronique L; Mirzoyev, Sultan A; Rodeheffer, Richard J; Chirinos, Julio A; Redfield, Margaret M

2012-11-01

Patients with heart failure and preserved ejection fraction (HFpEF) display increased adiposity and multiple comorbidities, factors that in themselves may influence cardiovascular structure and function. This has sparked debate as to whether HFpEF represents a distinct disease or an amalgamation of comorbidities. We hypothesized that fundamental cardiovascular structural and functional alterations are characteristic of HFpEF, even after accounting for body size and comorbidities. Comorbidity-adjusted cardiovascular structural and functional parameters scaled to independently generated and age-appropriate allometric powers were compared in community-based cohorts of HFpEF patients (n=386) and age/sex-matched healthy n=193 and hypertensive, n=386 controls. Within HFpEF patients, body size and concomitant comorbidity-adjusted cardiovascular structural and functional parameters and survival were compared in those with and without individual comorbidities. Among HFpEF patients, comorbidities (obesity, anemia, diabetes mellitus, and renal dysfunction) were each associated with unique clinical, structural, functional, and prognostic profiles. However, after accounting for age, sex, body size, and comorbidities, greater concentric hypertrophy, atrial enlargement and systolic, diastolic, and vascular dysfunction were consistently observed in HFpEF compared with age/sex-matched normotensive and hypertensive. Comorbidities influence ventricular-vascular properties and outcomes in HFpEF, yet fundamental disease-specific changes in cardiovascular structure and function underlie this disorder. These data support the search for mechanistically targeted therapies in this disease.

[Cooling shell in renal transplantation. Thermometric evaluation of a prototype].

PubMed

Desgrandchamps, F; Eugene, M; Tuchschmid, Y; Muller, F; Teillac, P; Idatte, J M; Le Duc, A

1996-02-01

We have developed a cooling system for renal transplants designed to eliminate the second period of warm ischaemia corresponding to the vascular anastomosis phase of renal transplantation. This is an autonomous and independent system which forms a shell around the transplant. Following application of the system, cooling is achieved by refrigeration of a Multitherm sponge contained in the wall of the shell. The thermometric characteristics of a prototype were evaluated in vitro and in vivo in pigs. This system allows the kidney to be preserved at a temperature of less than 10 degrees C for 1 hour without inducing any risk of lesions of the renal surface. Human applications should be developed in the near future.

Aquaporins in desert rodent physiology.

PubMed

Pannabecker, Thomas L

2015-08-01

Desert rodents face a sizeable challenge in maintaining salt and water homeostasis due to their life in an arid environment. A number of their organ systems exhibit functional characteristics that limit water loss above that which occurs in non-desert species under similar conditions. These systems include renal, pulmonary, gastrointestinal, nasal, and skin epithelia. The desert rodent kidney preserves body water by producing a highly concentrated urine that reaches a maximum osmolality nearly three times that of the common laboratory rat. The precise mechanism by which urine is concentrated in any mammal is unknown. Insights into the process may be more apparent in species that produce highly concentrated urine. Aquaporin water channels play a fundamental role in water transport in several desert rodent organ systems. The role of aquaporins in facilitating highly effective water preservation in desert rodents is only beginning to be explored. The organ systems of desert rodents and their associated AQPs are described. © 2015 Marine Biological Laboratory.

Hysteroscopic Resection of the Vaginal Septum in Uterus Didelphys with Obstructed Hemivagina: A Case Report

PubMed Central

Kim, Tae Eun; Lee, Gyoung Hoon; Jee, Byung Chul; Ku, Seung-Yup; Suh, Chang Suk; Kim, Seok Hyun; Kim, Jung Gu; Moon, Shin Yong

2007-01-01

Uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis is a rare congenital anomaly. Excision of the obstructed vaginal septum is the treatment of choice for symptom relief and the preservation of reproductive capability. A 14-yr-old girl complained of persistent vaginal spotting following each menstruation. Pelvic magnetic resonance imaging revealed a uterus didelphys with left hematocolpos and ipsilateral renal agenesis. Instead of conventional transvaginal excision of the vaginal septum, we used hysteroscopic excision under transabdominal ultrasonographic guidance to preserve the integrity of the hymen. The postoperative course was uneventful, and clinical symptoms were completely resolved after this intervention. Resectoscopic excision of the vaginal septum was found to be easy, safe, effective, and appropriate for young women as it preserved hymen integrity. We believe that this is the first Korean report on the use of a hysteroscopy for vaginal septum resection in a patient with uterus didelphys with obstructed hemivagina. PMID:17728527

Dynamic 99mTc-MAG3 renography: images for quality control obtained by combining pharmacokinetic modelling, an anthropomorphic computer phantom and Monte Carlo simulated scintillation camera imaging

NASA Astrophysics Data System (ADS)

Brolin, Gustav; Sjögreen Gleisner, Katarina; Ljungberg, Michael

2013-05-01

In dynamic renal scintigraphy, the main interest is the radiopharmaceutical redistribution as a function of time. Quality control (QC) of renal procedures often relies on phantom experiments to compare image-based results with the measurement setup. A phantom with a realistic anatomy and time-varying activity distribution is therefore desirable. This work describes a pharmacokinetic (PK) compartment model for 99mTc-MAG3, used for defining a dynamic whole-body activity distribution within a digital phantom (XCAT) for accurate Monte Carlo (MC)-based images for QC. Each phantom structure is assigned a time-activity curve provided by the PK model, employing parameter values consistent with MAG3 pharmacokinetics. This approach ensures that the total amount of tracer in the phantom is preserved between time points, and it allows for modifications of the pharmacokinetics in a controlled fashion. By adjusting parameter values in the PK model, different clinically realistic scenarios can be mimicked, regarding, e.g., the relative renal uptake and renal transit time. Using the MC code SIMIND, a complete set of renography images including effects of photon attenuation, scattering, limited spatial resolution and noise, are simulated. The obtained image data can be used to evaluate quantitative techniques and computer software in clinical renography.

Native ureteropyelostomy in the treatment of obstructive uropathy in adult renal transplant. Experience and technical alternatives.

PubMed

Trilla, E; Lorente, D; Salvador, C; Planas, J; Placer, J; Celma, A; Cantarell, C; Moreso, F; Seron, D; Morote, J

2014-10-01

To analyze and evaluate our experience in surgical treatment with the open approach of the complex ureteral stenosis after adult kidney transplantation in a tertiary level hospital in the last seven years. We have reviewed the different surgical options used. A total of 589 consecutive adult renal transplants were performed from January 2005 to December 2012. Of these, 1.1% showed some degree of symptomatic obstructive uropathy which after initial urinary diversion required open surgical approach using the ipsilateral or contralateral native urinary tract. Characteristics of the patient, clinical examinations performed and surgical technique performed as well as their results are presented. During the period under review, in 5 men and 2 women who had ureteral stenoses after renal transplant, 7 reparative surgeries were performed by open ureteropyelostomy, using ipsilateral native ureter in 6 cases and contralateral ureter in the remaining case. In one case, uretero-calicial anastomosis was performed due to severe pyelic shrinkage. There were no significant complications. Native kidney nephrectomy was not required for further complications. All the patients operated on had optimum plasma creatinine levels with resolution of previous dilatation. The initial percutaneous nephrostomy followed by open surgical repair using native ureter represents a definitive, valid and optimal alternative in terms of safety and preservation of renal function. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

Robotic partial nephrectomy with intracorporeal renal hypothermia using ice slush.

PubMed

Kaouk, Jihad H; Samarasekera, Dinesh; Krishnan, Jayram; Autorino, Riccardo; Acka, Oktay; Brando, Luis Felipe; Laydner, Humberto; Zargar, Homayoun

2014-09-01

To outline our technique for intracorporeal cooling with ice slush during robotic partial nephrectomy (RPN), with real-time parenchymal temperature monitoring. Eleven consecutive patients with enhancing solid renal masses suitable for treatment with RPN between September 2013 and January 2014 were included in the analysis. Institutional review board approval and informed consent were obtained. Preoperative patient characteristics, intraoperative surgical parameters including patient body temperature and ipsilateral kidney temperature with real-time monitoring, and short-term functional outcomes were analyzed. Median age was 55 years (range, 39-75 years) and American Society of Anesthesiologists score was 3 (range, 2-4). Median tumor size was 4 cm (range, 2.3-7.1) and RENAL nephrometry score was 9 (range, 5-11). One patient had a solitary kidney. During cooling, the lowest median renal parenchymal temperature was 17.05°C (range, 11°C-26°C) and cold ischemia time was 27.17 minutes (range, 18-49 minutes). Median time to latest postoperative estimated glomerular filtration rate was 12 days (range, 2-30 days). Median glomerular filtration rate preservation was 81% (range, 47.9%-126%). There was one positive margin. There were no postoperative complications, and no patients experienced a prolonged ileus. The limitations of this study include a small number of patients and short-term follow-up. RPN with renal hypothermia using intracorporeal ice slush is technically feasible. Our simplified method of introducing the ice slush was free of complications and highly reproducible. The use of a needle temperature probe allowed us to monitor in real time cooling of the renal parenchyma. Copyright © 2014 Elsevier Inc. All rights reserved.

Inappropriate Prescription and Renal Function Among Older Patients with Cognitive Impairment.

PubMed

Sönnerstam, Eva; Sjölander, Maria; Gustafsson, Maria

2016-12-01

Older people are more sensitive to drugs and adverse drug reactions than younger people because of age-related physiological changes such as impaired renal function. As people with dementia are particularly vulnerable to the effects of drugs, it is especially important to evaluate the dosages of renally cleared medications in this group. The aim of this study was to estimate the prevalence of impaired renal function and inappropriate prescriptions on the basis of renal function among older patients with dementia or cognitive impairment. The medical records of 428 patients aged ≥65 years who were admitted to two hospitals in northern Sweden were reviewed and renally cleared medications were identified. The Cockcroft-Gault equation was used to evaluate renal function. Doses were evaluated according to the Geriatric Dosage Handbook. Renal function was impaired (estimated glomerular filtration rate <60 ml/min) in 65.4 % of the study population. Impaired renal function was associated with increasing age. Among 547 prescriptions identified as renally cleared medications, 9.1 % were inappropriate based on the patient's renal function; 13.5 % of the 326 patients prescribed renally cleared medications had inappropriate prescriptions. Inappropriate prescriptions were more common among patients living in nursing homes. Impaired renal function is common and inappropriate prescription is prevalent among old people with cognitive impairment in northern Sweden. Continuous consideration of renal function is important when prescribing medications to this group.

Clinical application of calculated split renal volume using computed tomography-based renal volumetry after partial nephrectomy: Correlation with technetium-99m dimercaptosuccinic acid renal scan data.

PubMed

Lee, Chan Ho; Park, Young Joo; Ku, Ja Yoon; Ha, Hong Koo

2017-06-01

To evaluate the clinical application of computed tomography-based measurement of renal cortical volume and split renal volume as a single tool to assess the anatomy and renal function in patients with renal tumors before and after partial nephrectomy, and to compare the findings with technetium-99m dimercaptosuccinic acid renal scan. The data of 51 patients with a unilateral renal tumor managed by partial nephrectomy were retrospectively analyzed. The renal cortical volume of tumor-bearing and contralateral kidneys was measured using ImageJ software. Split estimated glomerular filtration rate and split renal volume calculated using this renal cortical volume were compared with the split renal function measured with technetium-99m dimercaptosuccinic acid renal scan. A strong correlation between split renal function and split renal volume of the tumor-bearing kidney was observed before and after surgery (r = 0.89, P < 0.001 and r = 0.94, P < 0.001). The preoperative and postoperative split estimated glomerular filtration rate of the operated kidney showed a moderate correlation with split renal function (r = 0.39, P = 0.004 and r = 0.49, P < 0.001). The correlation between reductions in split renal function and split renal volume of the operated kidney (r = 0.87, P < 0.001) was stronger than that between split renal function and percent reduction in split estimated glomerular filtration rate (r = 0.64, P < 0.001). The split renal volume calculated using computed tomography-based renal volumetry had a strong correlation with the split renal function measured using technetium-99m dimercaptosuccinic acid renal scan. Computed tomography-based split renal volume measurement before and after partial nephrectomy can be used as a single modality for anatomical and functional assessment of the tumor-bearing kidney. © 2017 The Japanese Urological Association.

Dynamic analysis of patterns of renal sympathetic nerve activity: implications for renal function.

PubMed

DiBona, Gerald F

2005-03-01

Methods of dynamic analysis are used to provide additional understanding of the renal sympathetic neural control of renal function. The concept of functionally specific subgroups of renal sympathetic nerve fibres conveying information encoded in the frequency domain is presented. Analog pulse modulation and pseudorandom binary sequence stimulation patterns are used for the determination of renal vascular frequency response. Transfer function analysis is used to determine the effects of non-renal vasoconstrictor and vasoconstrictor intensities of renal sympathetic nerve activity on dynamic autoregulation of renal blood flow.

Retroperitoneal Laparoscopic Partial Nephrectomy Versus Radical Nephrectomy for Clinical T1 Renal Hilar Tumor: Comparison of Perioperative Characteristics and Short-Term Functional and Oncologic Outcomes.

PubMed

Yang, Chuance; Wang, Zhenlong; Huang, Shanlong; Xue, Li; Fu, Delai; Chong, Tie

2018-04-18

To present our single-center experience with retroperitoneal laparoscopic partial nephrectomy (LPN) and retroperitoneal laparoscopic radical nephrectomy (LRN) for T1 renal hilar tumors and evaluate which one is better. A retrospective review of 63 patients with hilar tumors undergoing retroperitoneal LPN or LRN was performed. The perioperative characteristics, change in estimated glomerular filtration rate (eGFR) from baseline to month 3, and oncologic outcomes were summarized. In total, 25 patients underwent LPN, and 38 patients underwent LRN. The mean tumor size in the LPN and LRN groups was 4.5 and 4.9 cm, respectively. The mean operation time was longer in the LPN group than that in the LRN group (212.5 minutes versus 160.7 minutes, respectively; P < .05). Patients undergoing the LPN had a longer median length of hospital stay after surgery (9 days versus 7 days, P < .05). Four percent of patients in the LPN group experienced postoperative complications compared with 5% of patients in the LRN group, which was not significantly different. Compared with preoperative eGFR, postoperative eGFR at 3 months decreased by 15.2 mL/min/1.73 m 2 and 27.8 mL/min/1.73 m 2 in the LPN and the LRN groups, respectively (P < .05). There was one local recurrence in the LPN group and three local or distant recurrences in the LRN group (P > .05). In experienced hands, although retroperitoneal LRN can result in shorter operation times and shorter lengths of stay, retroperitoneal LPN can preserve renal function better than LRN. Retroperitoneal LPN should be the priority in selected patients with T1 renal hilar tumors, especially for patients with renal insufficiency.

Predictors of Recoverability of Renal Function after Pyeloplasty in Adults with Ureteropelvic Junction Obstruction.

PubMed

Li, Xiao-Dong; Wu, Yu-Peng; Wei, Yong; Chen, Shao-Hao; Zheng, Qing-Shui; Cai, Hai; Xue, Xue-Yi; Xu, Ning

2018-01-01

This study aimed to identify factors predicting the recoverability of renal function after pyeloplasty in adult patients with ureteropelvic junction obstruction. We retrospectively reviewed 138 adults with unilateral renal obstruction-induced hydronephrosis and who underwent Anderson-Hynes dismembered pyeloplasty from January 2013 to January 2016. Hydronephrosis was classified preoperatively according to the Society for Fetal Urology (SFU) grading system. All patients underwent Doppler ultrasonography, excretory urography, computed tomography, and technetium-99m-diethylenetriamine pentaacetic acid radioisotope (99mTc DTPA) renography before and after surgery. Renal resistive index (RRI) and 99mTc DTPA renography were repeated at 1, 3, 6, and 12 months. Multivariate analysis identified age, renal pelvic type, SFU grade, preoperative RRI, decline of RRI, and renal parenchyma to hydronephrosis area ratio (PHAR) as independent predictors of renal function recoverability after pyeloplasty. However, preoperative RRI and RRI decline were not significantly associated with recoverability of renal function in patients aged >35 years. Lower preoperative RRI, greater decline in RRI, higher PHAR, lower SFU grade, and extrarenal pelvis were associated with greater improvements in postoperative renal function. Preoperative differential renal function cannot independently predict the recoverability of postoperative renal function in adult patients with unilateral renal obstruction-induced hydronephrosis. SFU grade, renal pelvic type, PHAR, preoperative RRI, and decline in RRI were significantly associated with the recoverability of renal function in adult patients aged <35 years, while only SFU grade, renal pelvic type, and PHAR were significantly associated with renal function recoverability in patients aged ≥35 years. Renal function recovery was better in patients younger than 35 years when compared with older patients. © 2018 S. Karger AG, Basel.

Renal dopamine containing nerves. What is their functional significance?

PubMed

DiBona, G F

1990-06-01

Biochemical and morphological studies indicate that there are nerves within the kidney that contain dopamine and that various structures within the kidney contain dopamine receptors. However, the functional significance of these renal dopamine containing nerves in relation to renal dopamine receptors is unknown. The functional significance could be defined by demonstrating that an alteration in one or more renal functions occurring in response to reflex or electrical activation of efferent renal nerves is dependent on release of dopamine as the neurotransmitter from the renal nerve terminals acting on renal dopamine receptors. Thus, the hypothesis becomes: reflex or electrical activation of efferent renal nerves causes alterations in renal function (eg, renal blood flow, water and solute handling) that are inhibited by specific and selective dopamine receptor antagonists. As reviewed herein, the published experimental data do not support the hypothesis. Therefore, the view that alterations in one or more renal functions occurring in response to reflex or electrical activation of efferent renal nerves are dependent on release of dopamine as the neurotransmitter from the renal nerve terminals acting on renal dopamine receptors remains unproven.

The incidental renal mass. Management alternatives.

PubMed

Montie, J E

1991-08-01

The problem of the incidental renal mass will confront all urologists with increasing regularity, and no universal strategy can be employed. Complete excision of the mass, including a margin of normal tissue, may be adequate therapy if a cancer is present and will preserve renal parenchyma if the lesion is benign. Care must be taken not to stretch the limits of this approach. Larger lesions (greater than 3-4 cm) are likely to be cancer and are better treated with a nephrectomy. While this management philosophy is logical and appealing, it has not been validated by clinical experience, and caution must still be exercised.

[Effect of noradrenaline and angiotensin II on the brain and kidney blood supply with changes in systemic arterial pressure].

PubMed

Beketov, A I; Korneliuk, I K

1981-01-01

Hydrogen clearance was used in experiments on anesthetized cats to demonstrate that intravenous infusions of noradrenaline induced an increase in cerebral blood supply and reduction of renal blood flow both in anesthetized animals and in the presence of hypotension. In these conditions, angiotensin II lowered the cerebral and renal blood flow. Hypotension enhanced the reactions of the cerebral and renal blood flow to the action of vasopressor agents. The intensity of the reactions was consistent with the degree of vascular autocontrol preservation in the brain and kidneys.

Renal proximal tubule function is preserved in Cftrtm2camΔF508 cystic fibrosis mice

PubMed Central

Kibble, J D; Balloch, K J D; Neal, A M; Hill, C; White, S; Robson, L; Green, R; Taylor, C J

2001-01-01

Changes in proximal tubule function have been reported in cystic fibrosis patients. The aim of this study was to investigate proximal tubule function in the Cftrtm2camΔF508 cystic fibrosis (CF) mouse model. A range of techniques were used including renal clearance studies, in situ microperfusion, RT-PCR and whole-cell patch clamping. Renal Na+ clearance was similar in wild-type (1.4 ± 0.3 μl min−1, number of animals, N= 12) and CF mice (1.6 ± 0.4 μl min−1, N= 7) under control conditions. Acute extracellular volume expansion resulted in significant natriuresis in wild-type (7.0 ± 0.8 μl min−1, N= 8) and CF mice (9.3 ± 1.4 μl min−1, N= 9); no difference between genotypes was observed. In situ microperfusion revealed that fluid absorptive rate (Jv) was similar under control conditions between wild-type (2.2 ± 0.4 nl mm−1 min−1, n= 10) and CF mice (1.9 ± 0.3 nl mm−1 min−1, n= 11). Addition of a forskolin-dibutyryl cAMP (db-cAMP) cocktail to the perfusate caused no significant change in Jv in either wild-type (2.6 ± 0.7 nl mm−1 min−1, n= 10) or Cftrtm2camΔF508 mice (2.0 ± 0.5 nl mm−1 min−1, n= 10). CFTR expression was confirmed in samples of outer cortex using RT-PCR. However, no evidence for functional CFTR was obtained when outer cortical cells were stimulated with protein kinase A or forskolin-db-cAMP using whole-cell patch clamping. In conclusion, no functional deficit in proximal tubule function was found in Cftrtm2camΔF508 mice. This may be a consequence of a lack of whole-cell cAMP-dependent Cl− conductance in mouse proximal tubule cells. PMID:11306663

Age dependent regulation of bone-mass and renal function by the MEPE ASARM-motif

PubMed Central

Zelenchuk, Lesya V; Hedge, Anne-Marie; Rowe, Peter S N

2015-01-01

Context Mice with null mutations in Matrix Extracellular Phosphoglycoprotein (MEPE) have increased bone mass, increased trabecular density and abnormal cancellous bone (MN-mice). These defects worsen with age and MEPE over expression induces opposite effects. Also, Genome Wide Association studies show MEPE plays a major role in bone mass. We hypothesized the conserved C-terminal MEPE ASARM-motif is chiefly responsible for regulating bone mass and trabecular structure. Design To test our theory we over expressed C-terminal ASARM-peptide in MN-mice using the Col1α1 promoter (MNAt-mice). We then compared the bone and renal phenotypes of the MNAt-mouse with the MN-mouse and the X-linked hypophosphatemic rickets mouse (HYP). The HYP mouse over expresses ASARM-peptides and is defective for the PHEX gene. Results The MN-mouse developed increased bone mass, bone strength and trabecular abnormalities that worsened markedly with age. Defects in bone formation were chiefly responsible with suppressed sclerostin and increased active β-catenin. Increased uric acid levels also suggested abnormalities in purine-metabolism and a reduced fractional excretion of uric acid signaled additional renal transport changes. The MN mouse developed a worsening hyperphosphatemia and reduced FGF23 with age. An increase in the fractional excretion of phosphate (FEP) despite the hyperphosphatemia confirms an imbalance in kidney-intestinal phosphate regulation. Also, the MN mice showed an increased creatinine clearance suggesting hyperfiltration. A reversal of the MN bone-renal phenotype changes occurred with the MNAt mice including the apparent hyperfiltration. The MNAt mice also developed localized hypomineralization, hypophosphatemia and increased FGF23. Conclusions The C-terminal ASARM-motif plays a major role in regulating bone–mass and cancellous structure as mice age. In healthy mice, the processing and release of free ASARM-peptide is chiefly responsible for preserving normal bone and renal function. Free ASARM-peptide also effects renal mineral phosphate handling by influencing FGF23 expression. These findings have implications for understanding age-dependent osteoporosis, unraveling drug-targets and developing treatments. PMID:26051469

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

FLORENCE: a randomized, double-blind, phase III pivotal study of febuxostat versus allopurinol for the prevention of tumor lysis syndrome (TLS) in patients with hematologic malignancies at intermediate to high TLS risk.

PubMed

Spina, M; Nagy, Z; Ribera, J M; Federico, M; Aurer, I; Jordan, K; Borsaru, G; Pristupa, A S; Bosi, A; Grosicki, S; Glushko, N L; Ristic, D; Jakucs, J; Montesinos, P; Mayer, J; Rego, E M; Baldini, S; Scartoni, S; Capriati, A; Maggi, C A; Simonelli, C

2015-10-01

Serum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose achieves a better sUA control than allopurinol while preserving renal function in TLS prevention. Patients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7-9 days. Study treatment was blinded, whereas daily dose (low/standard/high containing allopurinol 200/300/600 mg, respectively, or fixed febuxostat 120 mg) depended on the investigator's choice. The co-primary end points, sUA area under curve (AUC sUA1-8) and serum creatinine change, were assessed from baseline to day 8 and analyzed through analysis of covariance with two-sided overall significance level of 5%. Secondary end points included treatment responder rate, laboratory and clinical TLS incidence and safety. A total of 346 patients (82.1% intermediate TLS risk; 82.7% assigned to standard dose) were randomized. Mean AUC sUA1-8 was 514.0 ± 225.71 versus 708.0 ± 234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum creatinine change was -0.83 ± 26.98% and -4.92 ± 16.70% for febuxostat and allopurinol, respectively (P = 0.0903). No differences among secondary efficacy end points were detected. Drug-related adverse events occurred in 6.4% of patients in both arms. In the largest adult trial carried out in TLS prevention, febuxostat achieved a significant superior sUA control with one fixed dose in comparison to allopurinol with comparable renal function preservation and safety profile. NCT01724528. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Association between pulmonary function and renal function: findings from China and Australia.

PubMed

Yu, Dahai; Chen, Tao; Cai, Yamei; Zhao, Zhanzheng; Simmons, David

2017-05-01

The relationship between obstructive lung function and impaired renal function is unclear. This study investigated the dose-response relationship between obstructive lung function and impaired renal function. Two independent cross-sectional studies with representative sampling were applied. 1454 adults from rural Victoria, Australia (1298 with normal renal function, 156 with impaired renal function) and 5824 adults from Nanjing, China (4313 with normal renal function, 1511 with impaired renal function). Pulmonary function measurements included forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Estimated glomerular filtration rate (eGFR), and impaired renal function marked by eGFR <60 mL/min/1.73m 2 were used as outcome. eGFR increased linearly with FEV1 in Chinese participants and with FVC in Australians. A non-linear relationship with peaked eGFR was found for FEV1 at 2.65 L among Australians and for FVC at 2.78 L among Chinese participants, respectively. A non-linear relationship with peaked eGFR was found for the predicted percentage value of forced expiratory volume in 1 s (PFEV1) at 81-82% and for the predicted percentage value of forced vital capacity (PFVC) at 83-84% among both Chinese and Australian participants, respectively. The non-linear dose-response relationships between lung capacity measurements (both for FEV1 and FVC) and risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 3.05 L both for FEV1 and FVC, respectively. The non-linear relationship between PFEV and PVC and the risk of impaired renal function were consistently identified in both Chinese and Australian participants. An increased risk of impaired renal function was found below 76-77% for PFEV1 and 79-80% for PFVC, respectively. In both Australian and Chinese populations, the risk of impaired renal function increased both with FEV1 and FVC below 3.05 L, with PFEV1 below 76-77% or with PFVC below 79-80%, respectively. Obstructive lung function was associated with increased risk of reduced renal function. The screen for impaired renal function in patients with obstructive lung disease might be useful to ensure there was no impaired renal function before the commencement of potentially nephrotoxic medication where indicated (eg diuretics).

Atypical cells in a voided urine cytology specimen in a renal transplant recipient.

PubMed

Lu, Miao; Ho, Julie; Azordegan, Nazila; Perry, Anamarija M; Gibson, Ian W; Baker, Patricia

2017-01-01

Voided urine is routinely collected from renal transplant patients to screen for polyomavirus. In rare cases, atypical lymphoid cells can be detected in voided urine and raise the suspicion of post-transplant lymphoproliferative disorder (PTLD). However, further immunohistochemistry of the cell block and flow cytometry is frequently limited by the low cellularity and poor preservation of voided urine. Therefore, PTLD of the renal allograft is usually diagnosed from tissue biopsy or nephrectomy specimens. Herein, we report a rare case of atypical cells in a voided urine cytology specimen from a kidney transplant recipient. Needle core biopsy of the renal allograft showed monomorphic PTLD. Diagn. Cytopathol. 2017;45:69-72. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Apixaban Pharmacokinetics at Steady State in Hemodialysis Patients.

PubMed

Mavrakanas, Thomas A; Samer, Caroline F; Nessim, Sharon J; Frisch, Gershon; Lipman, Mark L

2017-07-01

It is unclear whether warfarin is protective or harmful in patients with ESRD and atrial fibrillation. This state of equipoise raises the question of whether alternative anticoagulants may have a therapeutic role. We aimed to determine apixaban pharmacokinetics at steady state in patients on hemodialysis. Seven patients received apixaban 2.5 mg twice daily for 8 days. Blood samples were collected before and after apixaban administration on days 1 and 8 (nondialysis days). Significant accumulation of the drug was observed between days 1 and 8 with the 2.5-mg dose. The area under the concentration-time curve from 0 to 24 hours increased from 628 to 2054 ng h/ml ( P <0.001). Trough levels increased from 45 to 132 ng/ml ( P <0.001). On day 9, after a 2.5-mg dose, apixaban levels were monitored hourly during dialysis. Only 4% of the drug was removed. After a 5-day washout period, five patients received 5 mg apixaban twice daily for 8 days. The area under the concentration-time curve further increased to 6045 ng h/ml ( P =0.03), and trough levels increased to 218 ng/ml ( P =0.03), above the 90th percentile for the 5-mg dose in patients with preserved renal function. Apixaban 2.5 mg twice daily in patients on hemodialysis resulted in drug exposure comparable with that of the standard dose (5 mg twice daily) in patients with preserved renal function and might be a reasonable alternative to warfarin for stroke prevention in patients on dialysis. Apixaban 5 mg twice daily led to supratherapeutic levels in patients on hemodialysis and should be avoided. Copyright © 2017 by the American Society of Nephrology.

Could solutions low in glucose degradation products preserve residual renal function in incident peritoneal dialysis patients? A 1-year multicenter prospective randomized controlled trial (Balnet Study).

PubMed

Kim, Sung Gyun; Kim, Sejoong; Hwang, Young-Hwan; Kim, Kiwon; Oh, Ji Eun; Chung, Wookyung; Oh, Kook-Hwan; Kim, Hyung Jik; Ahn, Curie

2008-06-01

In vitro studies of peritoneal dialysis (PD) solutions demonstrated that a lactate-buffered fluid with neutral pH and low glucose degradation products (LF) has better biocompatibility than a conventional acidic lactate-buffered fluid (CF). However, few clinical trials have evaluated the long-term benefit of the biocompatible solution on residual renal function (RRF). To compare LF with CF, we performed a prospective, randomized study with patients starting PD. After 1-month run-in period, 91 new PD patients were randomized for 12 months of treatment with either LF (Balance: Fresenius Medical Care, Bad Homburg, Germany; n = 48) or CF (Stay Safe: Fresenius; n = 43). We measured RRF, acid-base balance, peritoneal equilibration test, and adequacy of dialysis every 6 months after the run-in period. After 12 months of treatment, the residual glomerular filtration rate (GFR) in patients using LF tended to be higher than that of patients on CF (p = 0.057 by repeated-measures analysis of variance). We observed a significant difference in the changes of residual GFR between the two groups (p = 0.009), a difference that was especially marked in the subgroup whose baseline residual GFR was more than 2 mL/min/1.73 m(2). In addition, serum total CO(2) levels were higher (p = 0.001) and serum anion gap was lower (p = 0.019) in the LF group. We observed no differences between groups for Kt/V, C-reactive protein, or normalized protein equivalent of nitrogen appearance. In incident PD patients with significant residual GFR, LF may better preserve RRF over a 12-month treatment period. Additionally, pH-neutral PD fluid may improve acid-base balance as compared with CF.

Selective Deletion of the Brain-Specific Isoform of Renin Causes Neurogenic Hypertension.

PubMed

Shinohara, Keisuke; Liu, Xuebo; Morgan, Donald A; Davis, Deborah R; Sequeira-Lopez, Maria Luisa S; Cassell, Martin D; Grobe, Justin L; Rahmouni, Kamal; Sigmund, Curt D

2016-12-01

The renin-angiotensin system (RAS) in the brain is a critical determinant of blood pressure, but the mechanisms regulating RAS activity in the brain remain unclear. Expression of brain renin (renin-b) occurs from an alternative promoter-first exon. The predicted translation product is a nonsecreted enzymatically active renin whose function is unknown. We generated a unique mouse model by selectively ablating the brain-specific isoform of renin (renin-b) while preserving the expression and function of the classical isoform expressed in the kidney (renin-a). Preservation of renal renin was confirmed by measurements of renin gene expression and immunohistochemistry. Surprisingly, renin-b-deficient mice exhibited hypertension, increased sympathetic nerve activity to the kidney and heart, and impaired baroreflex sensitivity. Whereas these mice displayed decreased circulating RAS activity, there was a paradoxical increase in brain RAS activity. Physiologically, renin-b-deficient mice exhibited an exaggerated depressor response to intracerebroventricular administration of losartan, captopril, or aliskiren. At the molecular level, renin-b-deficient mice exhibited increased expression of angiotensin-II type 1 receptor in the paraventricular nucleus, which correlated with an increased renal sympathetic nerve response to leptin, which was dependent on angiotensin-II type 1 receptor activity. Interestingly, despite an ablation of renin-b expression, expression of renin-a was significantly increased in rostral ventrolateral medulla. These data support a new paradigm for the genetic control of RAS activity in the brain by a coordinated regulation of the renin isoforms, with expression of renin-b tonically inhibiting expression of renin-a under baseline conditions. Impairment of this control mechanism causes neurogenic hypertension. © 2016 American Heart Association, Inc.

Loss of the BMP antagonist USAG-1 ameliorates disease in a mouse model of the progressive hereditary kidney disease Alport syndrome.

PubMed

Tanaka, Mari; Asada, Misako; Higashi, Atsuko Y; Nakamura, Jin; Oguchi, Akiko; Tomita, Mayumi; Yamada, Sachiko; Asada, Nariaki; Takase, Masayuki; Okuda, Tomohiko; Kawachi, Hiroshi; Economides, Aris N; Robertson, Elizabeth; Takahashi, Satoru; Sakurai, Takeshi; Goldschmeding, Roel; Muso, Eri; Fukatsu, Atsushi; Kita, Toru; Yanagita, Motoko

2010-03-01

The glomerular basement membrane (GBM) is a key component of the filtering unit in the kidney. Mutations involving any of the collagen IV genes (COL4A3, COL4A4, and COL4A5) affect GBM assembly and cause Alport syndrome, a progressive hereditary kidney disease with no definitive therapy. Previously, we have demonstrated that the bone morphogenetic protein (BMP) antagonist uterine sensitization-associated gene-1 (USAG-1) negatively regulates the renoprotective action of BMP-7 in a mouse model of tubular injury during acute renal failure. Here, we investigated the role of USAG-1 in renal function in Col4a3-/- mice, which model Alport syndrome. Ablation of Usag1 in Col4a3-/- mice led to substantial attenuation of disease progression, normalization of GBM ultrastructure, preservation of renal function, and extension of life span. Immunohistochemical analysis revealed that USAG-1 and BMP-7 colocalized in the macula densa in the distal tubules, lying in direct contact with glomerular mesangial cells. Furthermore, in cultured mesangial cells, BMP-7 attenuated and USAG-1 enhanced the expression of MMP-12, a protease that may contribute to GBM degradation. These data suggest that the pathogenetic role of USAG-1 in Col4a3-/- mice might involve crosstalk between kidney tubules and the glomerulus and that inhibition of USAG-1 may be a promising therapeutic approach for the treatment of Alport syndrome.

Renal function in type 2 diabetes with rosiglitazone, metformin, and glyburide monotherapy.

PubMed

Lachin, John M; Viberti, Giancarlo; Zinman, Bernard; Haffner, Steven M; Aftring, R Paul; Paul, Gitanjali; Kravitz, Barbara G; Herman, William H; Holman, Rury R; Kahn, Steven E

2011-05-01

In ADOPT (A Diabetes Outcomes Prevention Trial), initial monotherapy with rosiglitazone provided more durable glycemic control than metformin or glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine differences in albumin excretion, renal function (estimated GFR), and BP over 5 years between treatment groups. A total of 4351 recently diagnosed, drug-naïve patients with type 2 diabetes were treated and followed for up to 5 years with rosiglitazone, metformin, or glyburide and were examined with periodic assessments of albumin/creatinine ratio (ACR), modification of diet in renal disease (MDRD)-estimated GFR, and BP. The ACR rose slowly with metformin. It fell with rosiglitazone and less so with glyburide over the first 2 years, and then rose slowly over time. Estimated GFR (eGFR) with all therapies rose into the high normal range over the first 3 to 4 years, more so with rosiglitazone, and then declined, more so with glyburide. Systolic BP was stable over time, values with rosiglitazone being lower, and diastolic BP declined over time, more so with rosiglitazone than with metformin or glyburide. There was no difference among groups in the incidence of emergent albuminuria (ACR ≥30 mg/g), hypertension, or impaired eGFR (<60 ml/min per 1.73 m(2)). Over a 5-year period, initial monotherapy with rosiglitazone retards the rise of ACR compared with metformin, preserves eGFR compared with glyburide, and lowers BP relative to both comparators. Copyright © 2011 by the American Society of Nephrology

Renal Function Descriptors in Neonates: Which Creatinine-Based Formula Best Describes Vancomycin Clearance?

PubMed

Bhongsatiern, Jiraganya; Stockmann, Chris; Yu, Tian; Constance, Jonathan E; Moorthy, Ganesh; Spigarelli, Michael G; Desai, Pankaj B; Sherwin, Catherine M T

2016-05-01

Growth and maturational changes have been identified as significant covariates in describing variability in clearance of renally excreted drugs such as vancomycin. Because of immaturity of clearance mechanisms, quantification of renal function in neonates is of importance. Several serum creatinine (SCr)-based renal function descriptors have been developed in adults and children, but none are selectively derived for neonates. This review summarizes development of the neonatal kidney and discusses assessment of the renal function regarding estimation of glomerular filtration rate using renal function descriptors. Furthermore, identification of the renal function descriptors that best describe the variability of vancomycin clearance was performed in a sample study of a septic neonatal cohort. Population pharmacokinetic models were developed applying a combination of age-weight, renal function descriptors, or SCr alone. In addition to age and weight, SCr or renal function descriptors significantly reduced variability of vancomycin clearance. The population pharmacokinetic models with Léger and modified Schwartz formulas were selected as the optimal final models, although the other renal function descriptors and SCr provided reasonably good fit to the data, suggesting further evaluation of the final models using external data sets and cross validation. The present study supports incorporation of renal function descriptors in the estimation of vancomycin clearance in neonates. © 2015, The American College of Clinical Pharmacology.

The Interplay between inflammation and fibrosis in kidney transplantation.

PubMed

Torres, Irina B; Moreso, Francesc; Sarró, Eduard; Meseguer, Anna; Serón, Daniel

2014-01-01

Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis.

The Interplay between Inflammation and Fibrosis in Kidney Transplantation

PubMed Central

Torres, Irina B.; Moreso, Francesc; Sarró, Eduard; Serón, Daniel

2014-01-01

Serial surveillance renal allograft biopsies have shown that early subclinical inflammation constitutes a risk factor for the development of interstitial fibrosis. More recently, it has been observed that persistent inflammation is also associated with fibrosis progression and chronic humoral rejection, two histological conditions associated with poor allograft survival. Treatment of subclinical inflammation with steroid boluses prevents progression of fibrosis and preserves renal function in patients treated with a cyclosporine-based regimen. Subclinical inflammation has been reduced after the introduction of tacrolimus based regimens, and it has been shown that immunosuppressive schedules that are effective in preventing acute rejection and subclinical inflammation may prevent the progression of fibrosis and chronic humoral rejection. On the other hand, minimization protocols are associated with progression of fibrosis, and noncompliance with the immunosuppressive regime constitutes a major risk factor for chronic humoral rejection. Thus, adequate immunosuppressive treatment, avoiding minimization strategies and reinforcing educational actions to prevent noncompliance, is at present an effective approach to combat the progression of fibrosis. PMID:24991565

Feasibility of three-dimensional magnetic resonance angiography-fluoroscopy image fusion technique in guiding complex endovascular aortic procedures in patients with renal insufficiency.

PubMed

Schwein, Adeline; Chinnadurai, Ponraj; Shah, Dipan J; Lumsden, Alan B; Bechara, Carlos F; Bismuth, Jean

2017-05-01

Three-dimensional image fusion of preoperative computed tomography (CT) angiography with fluoroscopy using intraoperative noncontrast cone-beam CT (CBCT) has been shown to improve endovascular procedures by reducing procedure length, radiation dose, and contrast media volume. However, patients with a contraindication to CT angiography (renal insufficiency, iodinated contrast allergy) may not benefit from this image fusion technique. The primary objective of this study was to evaluate the feasibility of magnetic resonance angiography (MRA) and fluoroscopy image fusion using noncontrast CBCT as a guidance tool during complex endovascular aortic procedures, especially in patients with renal insufficiency. All endovascular aortic procedures done under MRA image fusion guidance at a single-center were retrospectively reviewed. The patients had moderate to severe renal insufficiency and underwent diagnostic contrast-enhanced magnetic resonance imaging after gadolinium or ferumoxytol injection. Relevant vascular landmarks electronically marked in MRA images were overlaid on real-time two-dimensional fluoroscopy for image guidance, after image fusion with noncontrast intraoperative CBCT. Technical success, time for image registration, procedure time, fluoroscopy time, number of digital subtraction angiography (DSA) acquisitions before stent deployment or vessel catheterization, and renal function before and after the procedure were recorded. The image fusion accuracy was qualitatively evaluated on a binary scale by three physicians after review of image data showing virtual landmarks from MRA on fluoroscopy. Between November 2012 and March 2016, 10 patients underwent endovascular procedures for aortoiliac aneurysmal disease or aortic dissection using MRA image fusion guidance. All procedures were technically successful. A paired t-test analysis showed no difference between preimaging and postoperative renal function (P = .6). The mean time required for MRA-CBCT image fusion was 4:09 ± 01:31 min:sec. Total fluoroscopy time was 20.1 ± 6.9 minutes. Five of 10 patients (50%) underwent stent graft deployment without any predeployment DSA acquisition. Three of six vessels (50%) were cannulated under image fusion guidance without any precannulation DSA runs, and the remaining vessels were cannulated after one planning DSA acquisition. Qualitative evaluation showed 14 of 22 virtual landmarks (63.6%) from MRA overlaid on fluoroscopy were completely accurate, without the need for adjustment. Five of eight incorrect virtual landmarks (iliac and visceral arteries) resulted from vessel deformation caused by endovascular devices. Ferumoxytol or gadolinium-enhanced MRA imaging and image fusion with fluoroscopy using noncontrast CBCT is feasible and allows patients with renal insufficiency to benefit from optimal guidance during complex endovascular aortic procedures, while preserving their residual renal function. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

State-of the-art review on the renal and visceral protection during open thoracoabdominal aortic aneurysm repair.

PubMed

Waked, Karl; Schepens, Marc

2018-01-01

During open thoracoabdominal aortic aneurysm repair (OTAAAR), there is an inevitable organ ischemic period that occurs when the abdominal arteries are being reattached to the aortic graft. Despite various protective techniques, the incidence of renal and visceral complications remains substantial. This state-of-the-art review gives an overview of the current and most evidence-based organ protection methods during OTAAAR, based on the most recent publications and personal experience. An electronic search was performed in four medical databases, using the following MeSH terms: thoracoabdominal aneurysm, TAAAR, visceral protection, renal protection, kidney, perfusion, and intestines. Every publication type was considered. The literature search was ended on August 31st, 2017. The left heart bypass (LHB) is currently the most frequent adjunct to provide distal aortic perfusion (DAP) during aortic clamping. Together with systemic hypothermia, it forms the cornerstone in organ protection during aortic clamping. Further renal protection can be obtained by selective renal perfusion (SRP) with cold blood or cold crystalloid solution, the latter enriched with mannitol. The perfusion should be administered in a volume- and pressure-controlled way and, if possible, by use of a pulsatile pump. Selective visceral perfusion (SVP) is not routinely used, as it does not provide adequate blood flow for visceral protection. The best way to protect the intestines is by minimizing the ischemic time. The preservation of renal and visceral function after OTAAAR can only be obtained with specific strategies before, during, and after the operation. This involves a series of measures, including selective digestive decontamination (SDD), avoidance of nephrotoxic drugs, minimizing the renal and intestinal ischemic time, systemic cooling, avoidance of hemodynamic instability, and regional protective perfusion of the kidneys. Future innovations in catheters, cardiac bypass flow types, mechanical components, hybrid vascular grafts, and pharmaceutical protection measures will hopefully further reduce organ complications.

Assessment of the relationship between renal volume and renal function after minimally-invasive partial nephrectomy: the role of computed tomography and nuclear renal scan.

PubMed

Bertolo, Riccardo; Fiori, Cristian; Piramide, Federico; Amparore, Daniele; Barrera, Monica; Sardo, Diego; Veltri, Andrea; Porpiglia, Francesco

2018-05-14

To evaluate the correlation between the loss of renal function as assessed by Tc99MAG-3 renal scan and the loss of renal volume as calculated by volumetric assessment on CT-scan in patients who underwent minimally-invasive partial nephrectomy (PN). PN prospectively-maintained database was retrospectively queried for patients who underwent minimally-invasive PN (2012-2017) for renal mass

Presence of transient hydronephrosis immediately after surgery has a limited influence on renal function 1 year after ileal neobladder construction.

PubMed

Narita, Takuma; Hatakeyama, Shingo; Koie, Takuya; Hosogoe, Shogo; Matsumoto, Teppei; Soma, Osamu; Yamamoto, Hayato; Yoneyama, Tohru; Tobisawa, Yuki; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Ohyama, Chikara

2017-08-31

Urinary tract obstruction and postoperative hydronephrosis are risk factor for renal function deterioration after orthotopic ileal neobladder construction. However, reports of relationship between transient hydronephrosis and renal function are limited. We assess the influence of postoperative transient hydronephrosis on renal function in patients with orthotopic ileal neobladder construction. Between January 2006 and June 2013, we performed radical cystectomy in 164 patients, and 101 received orthotopic ileal neobladder construction. This study included data available from 64 patients with 128 renal units who were enrolled retrospectively. The hydronephrosis grade of each renal unit scored 0-4. The patients were divided into 4 groups according to the grade of hydronephrosis: control, low, intermediate, and high. The grade of postoperative hydronephrosis was compared with renal function 1 month and 1 year after surgery. There were no significant differences in renal function before surgery between groups. One month after surgery, the presence of hydronephrosis was significantly associated with decreased renal function. However, 1 year after urinary diversion hydronephrosis grades were improved significantly, and renal function was comparable between groups. Postoperative hydronephrosis at 1 month had no significant influence on renal function 1 year after ileal neobladder construction. Limitations include retrospective design, short follow-up periods, and a sample composition. The presence of transient hydronephrosis immediately after surgery may have limited influence on renal function 1 year after ileal neobladder construction.

Lean body mass predicts long-term survival in Chinese patients on peritoneal dialysis.

PubMed

Huang, Jenq-Wen; Lien, Yu-Chung; Wu, Hon-Yen; Yen, Chung-Jen; Pan, Chun-Chun; Hung, Tsai-Wei; Su, Chi-Ting; Chiang, Chih-Kang; Cheng, Hui-Teng; Hung, Kuan-Yu

2013-01-01

Reduced lean body mass (LBM) is one of the main indicators in malnutrition inflammation syndrome among patients on dialysis. However, the influence of LBM on peritoneal dialysis (PD) patients' outcomes and the factors related to increasing LBM are seldom reported. We enrolled 103 incident PD patients between 2002 and 2003, and followed them until December 2011. Clinical characteristics, PD-associated parameters, residual renal function, and serum chemistry profiles of each patient were collected at 1 month and 1 year after initiating PD. LBM was estimated using creatinine index corrected with body weight. Multiple linear regression analysis, Kaplan-Meier survival analysis, and Cox regression proportional hazard analysis were used to define independent variables and compare survival between groups. Using the median LBM value (70% for men and 64% for women), patients were divided into group 1 (n = 52; low LBM) and group 2 (n = 51; high LBM). Group 1 patients had higher rates of peritonitis (1.6 vs. 1.1/100 patient months; p<0.05) and hospitalization (14.6 vs. 9.7/100 patient months; p<0.05). Group 1 patients also had shorter overall survival and technique survival (p<0.01). Each percentage point increase in LBM reduced the hazard ratio for mortality by 8% after adjustment for diabetes, age, sex, and body mass index (BMI). Changes in residual renal function and protein catabolic rate were independently associated with changes in LBM in the first year of PD. LBM serves as a good parameter in addition to BMI to predict the survival of patients on PD. Preserving residual renal function and increasing protein intake can increase LBM.

Lean Body Mass Predicts Long-Term Survival in Chinese Patients on Peritoneal Dialysis

PubMed Central

Huang, Jenq-Wen; Lien, Yu-Chung; Wu, Hon-Yen; Yen, Chung-Jen; Pan, Chun-Chun; Hung, Tsai-Wei; Su, Chi-Ting; Chiang, Chih-Kang; Cheng, Hui-Teng; Hung, Kuan-Yu

2013-01-01

Background Reduced lean body mass (LBM) is one of the main indicators in malnutrition inflammation syndrome among patients on dialysis. However, the influence of LBM on peritoneal dialysis (PD) patients’ outcomes and the factors related to increasing LBM are seldom reported. Methods We enrolled 103 incident PD patients between 2002 and 2003, and followed them until December 2011. Clinical characteristics, PD-associated parameters, residual renal function, and serum chemistry profiles of each patient were collected at 1 month and 1 year after initiating PD. LBM was estimated using creatinine index corrected with body weight. Multiple linear regression analysis, Kaplan–Meier survival analysis, and Cox regression proportional hazard analysis were used to define independent variables and compare survival between groups. Results Using the median LBM value (70% for men and 64% for women), patients were divided into group 1 (n = 52; low LBM) and group 2 (n = 51; high LBM). Group 1 patients had higher rates of peritonitis (1.6 vs. 1.1/100 patient months; p<0.05) and hospitalization (14.6 vs. 9.7/100 patient months; p<0.05). Group 1 patients also had shorter overall survival and technique survival (p<0.01). Each percentage point increase in LBM reduced the hazard ratio for mortality by 8% after adjustment for diabetes, age, sex, and body mass index (BMI). Changes in residual renal function and protein catabolic rate were independently associated with changes in LBM in the first year of PD. Conclusions LBM serves as a good parameter in addition to BMI to predict the survival of patients on PD. Preserving residual renal function and increasing protein intake can increase LBM. PMID:23372806

Distinct Endothelial Cell Responses in the Heart and Kidney Microvasculature Characterize the Progression of Heart Failure With Preserved Ejection Fraction in the Obese ZSF1 Rat With Cardiorenal Metabolic Syndrome.

PubMed

van Dijk, Christian G M; Oosterhuis, Nynke R; Xu, Yan Juan; Brandt, Maarten; Paulus, Walter J; van Heerebeek, Loek; Duncker, Dirk J; Verhaar, Marianne C; Fontoura, Dulce; Lourenço, André P; Leite-Moreira, Adelino F; Falcão-Pires, Inês; Joles, Jaap A; Cheng, Caroline

2016-04-01

The combination of cardiac and renal disease driven by metabolic risk factors, referred to as cardiorenal metabolic syndrome (CRMS), is increasingly recognized as a critical pathological entity. The contribution of (micro)vascular injury to CRMS is considered to be substantial. However, mechanistic studies are hampered by lack of in vivo models that mimic the natural onset of the disease. Here, we evaluated the coronary and renal microvasculature during CRMS development in obese diabetic Zucker fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1) rats. Echocardiographic, urine, and blood evaluations were conducted in 3 groups (Wistar-Kyoto, lean ZSF1, and obese ZSF1) at 20 and 25 weeks of age. Immunohistological evaluation of renal and cardiac tissues was conducted at both time points. At 20 and 25 weeks, obese ZSF1 rats showed higher body weight, significant left ventricular hypertrophy, and impaired diastolic function compared with all other groups. Indices of systolic function did not differ between groups. Obese ZSF1 rats developed hyperproliferative vascular foci in the subendocardium, which lacked microvascular organization and were predilection sites of inflammation and fibrosis. In the kidney, obese ZSF1 animals showed regression of the peritubular and glomerular microvasculature, accompanied by tubulointerstitial damage, glomerulosclerosis, and proteinuria. The obese ZSF1 rat strain is a suitable in vivo model for CRMS, sharing characteristics with the human syndrome during the earliest onset of disease. In these rats, CRMS induces microvascular fibrotic responses in heart and kidneys, associated with functional impairment of both organs. © 2016 American Heart Association, Inc.

Fibroepithelial polyp in a child.

PubMed

Mydlo, J; Reda, E; Gill, B; Kogan, S J; Ziprkowski, M N; Weiss, R; Levitt, S B

1988-04-01

Only 15 cases of fibroepithelial polyp in children have been reported in the world medical literature. Clinical differentiation between this tumor and a malignant ureteral tumor is difficult and often results in unnecessary nephrectomy. We report the sixteenth case of a child with fibroepithelial polyp of the ureter. The lesion was resected, and the kidney was preserved. Optimum treatment of this lesion mandates renal preservation in children. The rationale for this recommendation is explored.

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)

Clinical course of dengue fever and its impact on renal function in renal transplant recipients and patients with chronic kidney disease.

PubMed

Arun Thomas, E T; George, Jacob; Sruthi, Devi; Vineetha, N S; Gracious, Noble

2018-04-01

Dengue fever is a mosquito-borne viral disease endemic in many tropical and sub-tropical countries. There is only limited data in the literature about dengue fever in renal transplant recipients and patients with chronic kidney disease. This study compares the clinical course of dengue fever and its impact on renal function in renal transplant recipients, patients with chronic kidney disease and patients with normal base line renal function. An observational study was conducted from 1 st May to 31 st July 2017, at a tertiary care centre of South India. A major epidemic of dengue had occurred during the study period. Twelve renal transplant recipients, 22 patients with CKD and 58 patients with normal baseline renal function (control group) admitted with dengue fever were prospectively studied. Nadir WBC count was lowest in renal transplant recipients (2575 + 1187/mm 3 ), [P<0.001]. Renal transplant recipients took more time for normalisation of platelet count (6 + 4.5 days), [P<0.001]. All 22 patients with CKD and 11 of 12 renal transplant recipients had worsening of renal function where as only 17 of 58 patients in the control group had worsening [P<0.001]. Sixteen patients with CKD, one renal transplant recipient and none among control group required hemodialysis [P<0.001]. Dialysis requiring patients had more hemoconcentration (52.5+ 19.9% increase in haemoglobin), [P<0.001]. Seven patients with CKD were dialysis dependent at the end of 2 weeks. Clinical features of dengue fever were different in renal transplant recipients and patients with CKD. Severe worsening of renal function was common in CKD patients. Worsening of renal function in renal transplant recipients was less severe and transient. This article is protected by copyright. All rights reserved.

Clinical characteristics and SAP scintigraphic findings in 10 patients with AGel amyloidosis.

PubMed

Rowczenio, Dorota; Tennent, Glenys A; Gilbertson, Janet; Lachmann, Helen J; Hutt, David F; Bybee, Alison; Hawkins, Philip N; Gillmore, Julian D

2014-12-01

The clinical features of hereditary gelsolin (AGel) amyloidosis include corneal lattice dystrophy, distal sensorimotor, cranial neuropathy and cutis laxa. To date, four mutations of the gelsolin (GSN) gene encoding the following variants have been identified as the cause of this malady; p.D214N, p.D214Y, p.G194R and p.N211K (this nomenclature includes the 27-residue signal peptide). Interestingly, the latter two variants are associated exclusively with a renal amyloidosis phenotype. Here we report the clinical features in 10 patients with AGel amyloidosis associated with the p.D214N mutation, all of whom underwent whole body (123)I-SAP scintigraphy and were followed up in a single UK Centre for a prolonged period. Two patients, from the same kindred presented with proteinuria; eight subjects had a characteristic AGel amyloidosis phenotype including cranial neuropathy and/or corneal lattice dystrophy. (123)I-SAP scintigraphy revealed substantial renal amyloid deposits in all 10 patients, including those with preserved renal function, and usually without tracer uptake into other visceral organs. (123)I-SAP scintigraphy is a non-invasive technique that aids early diagnosis of patients with this rare disease, especially those who lack a family history and/or present with an unusual clinical phenotype.

Circumferential targeted renal sympathetic nerve denervation with preservation of the renal arterial wall using intra-luminal ultrasound

NASA Astrophysics Data System (ADS)

Roth, Austin; Coleman, Leslie; Sakakura, Kenichi; Ladich, Elena; Virmani, Renu

2015-03-01

An intra-luminal ultrasound catheter system (ReCor Medical's Paradise System) has been developed to provide circumferential denervation of the renal sympathetic nerves, while preserving the renal arterial intimal and medial layers, in order to treat hypertension. The Paradise System features a cylindrical non-focused ultrasound transducer centered within a balloon that circulates cooling fluid and that outputs a uniform circumferential energy pattern designed to ablate tissues located 1-6 mm from the arterial wall and protect tissues within 1 mm. RF power and cooling flow rate are controlled by the Paradise Generator which can energize transducers in the 8.5-9.5 MHz frequency range. Computer simulations and tissue-mimicking phantom models were used to develop the proper power, cooling flow rate and sonication duration settings to provide consistent tissue ablation for renal arteries ranging from 5-8 mm in diameter. The modulation of these three parameters allows for control over the near-field (border of lesion closest to arterial wall) and far-field (border of lesion farthest from arterial wall, consisting of the adventitial and peri-adventitial spaces) depths of the tissue lesion formed by the absorption of ultrasonic energy and conduction of heat. Porcine studies have confirmed the safety (protected intimal and medial layers) and effectiveness (ablation of 1-6 mm region) of the system and provided near-field and far-field depth data to correlate with bench and computer simulation models. The safety and effectiveness of the Paradise System, developed through computer model, bench and in vivo studies, has been demonstrated in human clinical studies.

Endothelin-A Receptor Antagonism after Renal Angioplasty Enhances Renal Recovery in Renovascular Disease

PubMed Central

Tullos, Nathan; Stewart, Nicholas J.; Surles, Bret

2015-01-01

Percutaneous transluminal renal angioplasty/stenting (PTRAS) is frequently used to treat renal artery stenosis and renovascular disease (RVD); however, renal function is restored in less than one half of the cases. This study was designed to test a novel intervention that could refine PTRAS and enhance renal recovery in RVD. Renal function was quantified in pigs after 6 weeks of chronic RVD (induced by unilateral renal artery stenosis), established renal damage, and hypertension. Pigs with RVD then underwent PTRAS and were randomized into three groups: placebo (RVD+PTRAS), chronic endothelin-A receptor (ET-A) blockade (RVD+PTRAS+ET-A), and chronic dual ET-A/B blockade (RVD+PTRAS+ET-A/B) for 4 weeks. Renal function was again evaluated after treatments, and then, ex vivo studies were performed on the stented kidney. PTRAS resolved renal stenosis, attenuated hypertension, and improved renal function but did not resolve renal microvascular rarefaction, remodeling, or renal fibrosis. ET-A blocker therapy after PTRAS significantly improved hypertension, microvascular rarefaction, and renal injury and led to greater recovery of renal function. Conversely, combined ET-A/B blockade therapy blunted the therapeutic effects of PTRAS alone or PTRAS followed by ET-A blockade. These data suggest that ET-A receptor blockade therapy could serve as a coadjuvant intervention to enhance the outcomes of PTRAS in RVD. These results also suggest that ET-B receptors are important for renal function in RVD and may contribute to recovery after PTRAS. Using clinically available compounds and techniques, our results could contribute to both refinement and design of new therapeutic strategies in chronic RVD. PMID:25377076

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.

The additive effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 function in diabetic rats.

PubMed

Thongnak, Laongdao; Pongchaidecha, Anchalee; Jaikumkao, Krit; Chatsudthipong, Varanuj; Chattipakorn, Nipon; Lungkaphin, Anusorn

2017-10-19

Hyperglycemia-induced oxidative stress is usually found in diabetic condition. 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, statins, are widely used as cholesterol-lowering medication with several "pleiotropic" effects in diabetic patients. This study aims to evaluate whether the protective effects of atorvastatin and insulin on renal function and renal organic anion transporter 3 (Oat3) function involve the modulation of oxidative stress and pancreatic function in type 1 diabetic rats. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin (50 mg/kg BW). Atorvastatin and insulin as single or combined treatment were given for 4 weeks after diabetic condition had been confirmed. Diabetic rats demonstrated renal function and renal Oat3 function impairment with an increased MDA level and decreased SOD protein expression concomitant with stimulation of renal Nrf2 and HO-1 protein expression. Insulin plus atorvastatin (combined) treatment effectively restored renal function as well as renal Oat3 function which correlated with the decrease in hyperglycemia and oxidative stress. Moreover, pancreatic inflammation and apoptosis in diabetic rats were ameliorated by the combined drugs treatment. Therefore, atorvastatin plus insulin seems to exert the additive effect in improving renal functionby alleviating hyperglycemiaand the modulation of oxidative stress, inflammation and apoptosis.

Effects of continuous and pulsatile flows generated by ventricular assist devices on renal function and pathology.

PubMed

Miyamoto, Takuma; Karimov, Jamshid H; Fukamachi, Kiyotaka

2018-03-01

Continuous-flow (CF) left ventricular assist devices (LVADs) are widely used to treat end-stage heart failure. Despite substantial improvement in clinical results, numerous complications remain associated with this technology. Worsening renal function is one, associated with morbidity and mortality in patients supported by CF LVADs. The effects of CF LVAD support on renal function have been investigated since the mid-1990s by many research groups. Area covered: We review the current status of LVAD therapy, experimental results regarding the effects of types of flow generated by LVADs on renal function and pathology, changes in renal function after LVAD implant, the influence of renal function on outcomes, and risk factors for renal dysfunction post implant. This information was obtained through online databases and direct extraction of single studies. Expert commentary: Immediately after CF LVAD implantation, renal function improves temporarily as patients recover from the kidneys' previously low perfusion and congestive state. However, many studies have shown that this initially recovered renal function gradually declines during long-term CF LVAD support. Although it is known that CF LVAD support adversely affects renal function over the long term, just how it does has not yet been clearly defined in terms of clinical symptoms or signs.

Pharmacological strategies for kidney function preservation: are there differences by ethnicity?

PubMed

Lakkis, Jay; Weir, Matthew R

2004-01-01

The prevalence of chronic kidney disease (CKD) is on the rise in all ethnic groups. This is because of the increased prevalence of obesity, diabetes mellitus, the metabolic syndrome, and the inadequate control of elevated blood pressure and other cardiovascular-renal risk factors, especially in ethnic minority populations. The implications of the aforementioned trends in risk factor prevalence and control are profound. Moreover, these trends negatively impact patient quality of life and place an enormous financial burden on the health care system for the provision of care to patients with CKD, end-stage renal disease (ESRD), and/or cardiovascular disease (CVD). Thus, it is of utmost importance to devise strategies that prevent kidney disease and delay progressive loss of kidney function in persons with CKD. Proven strategies include pharmacological interventions that lower blood pressure to less than target levels (<130/80 mm Hg), attainment of optimal glycemic control (Hb A1c <7%), and reducing urinary protein excretion. It is also possible, although yet unproven, that correction of anemia and aggressive treatment of dyslipidemia may forestall the loss of kidney function. In general, ethnic minorities are underrepresented in most large trials. Recently, a few outcome clinical trials in blacks have reinforced the lessons of kidney function preservation already learned in nonblack populations. That is, the reversible risk factors for CKD appear to be virtually identical and, at least in nondiabetic CKD, pharmacological targeting of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers preserves kidney function better than non-RAAS blood pressure-lowering regimens, especially when significant proteinuria exists. Although more CKD studies in ethnic minorities are needed, until they become available, the best available evidence from the existing clinical trial database should be applied to minorities with CKD-even when specific data are not available for a specific racial or ethnic group. Why this approach? First, there are no known unique risk factors for kidney disease in any ethnic group. Second, poor control of reversible risk factors for CKD is universal, particularly in blacks and other ethnic minorities. Thus, it is logical to predict that more efficient use of strategies proven to forestall loss of kidney function will reduce the excess of CKD and ESRD in ethnic minorities relative to non-minority populations. However, medical-based strategies alone are probably not enough. The global epidemic of obesity will fuel the growing population of persons, especially among ethnic minorities, with diabetes, the main cause of CKD, ESRD, and CVD. The obesity and diabetes epidemics are unlikely to abate without innovative and ultimately effective public health approaches.

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.

Curcumin reduces the risk of chronic kidney damage in mice with nonalcoholic steatohepatitis by modulating endoplasmic reticulum stress and MAPK signaling.

PubMed

Afrin, Mst Rejina; Arumugam, Somasundaram; Rahman, Md Azizur; Karuppagounder, Vengadeshprabhu; Harima, Meilei; Suzuki, Hiroshi; Miyashita, Shizuka; Suzuki, Kenji; Ueno, Kazuyuki; Yoneyama, Hiroyuki; Watanabe, Kenichi

2017-08-01

Developing confirmation recommends that in patients with dynamic type of NAFLD, particularly nonalcoholic steatohepatitis (NASH) may have the pathogenic parts in the advancement of kidney damage. In this study we have examined the impact of curcumin on NASH instigated chronic kidney damage (CKD) and the putative mechanisms. To prepare this NASH model, neonatal C57BL/6J male mice were exposed to low-dose streptozotocin (STZ) and were fed high-fat diet (HFD) at the age of 4weeks and continued up to 14weeks, curcumin was given at 100mg/kg dose by oral gavage daily after 10weeks of STZ injection and continued for 4weeks along with HFD feeding. NASH incited mice demonstrated nephrotoxicity as proved by declining renal capacity, which was evaluated by measuring blood urea nitrogen and creatinine in serum and histopathological variations from the norm. These progressions were switched by curcumin treatment, which brought about huge change in renal capacity. Furthermore, curcumin markedly decreased NAD(P)H oxidase subunits (p67phox, p47phox, p22phox), nitrotyrosine and CYP2E1 renal protein expression as well as reduced pro-inflammatory cytokine expression (TNFα, IL-1β, IFNγ). Renal protein expression of mitogen activated protein kinases (MAPKs) (p-JNK, p-ERK1/2) and glucose regulated protein 78, CHOP were increased in NASH induced mice and curcumin treatment attenuated these increased expressions. In addition, curcumin treatment also decreased the apoptosis signaling proteins (cleaved caspase-3, cleaved caspase-12) in the NASH kidney. Taken together, our results suggest that curcumin preserves the renal function, probably by attenuating the ER stress mediated MAPK signaling. Copyright © 2017 Elsevier B.V. All rights reserved.

Atherosclerotic renal artery stenosis in the post-CORAL era part 1: the renal penumbra concept and next-generation functional diagnostic imaging.

PubMed

Sag, Alan Alper; Inal, Ibrahim; Okcuoglu, John; Rossignol, Patrick; Ortiz, Alberto; Afsar, Baris; Sos, Thomas A; Kanbay, Mehmet

2016-04-01

After three neutral trials in which renal artery stenting failed to improve renal function or reduce cardiovascular and renal events, the controversy surrounding diagnosis and treatment of atherosclerotic renal artery stenosis and renovascular hypertension has led to paradigm shifts in the diagnostic algorithm. Noninvasive determination of earlier events (cortex hypoxia and renal artery hemodynamic changes) will supersede late sequelae (calcific stenosis, renal cortical thinning). Therefore, this review proposes the concept of renal penumbra in defining at-risk ischemic renal parenchyma. The complex field of functional renal magnetic resonance imaging will be reviewed succinctly in a clinician-directed fashion. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Population pharmacokinetics of pomalidomide in patients with relapsed or refractory multiple myeloma with various degrees of impaired renal function.

PubMed

Li, Yan; Wang, Xiaomin; O'Mara, Edward; Dimopoulos, Meletios A; Sonneveld, Pieter; Weisel, Katja C; Matous, Jeffrey; Siegel, David S; Shah, Jatin J; Kueenburg, Elisabeth; Sternas, Lars; Cavanaugh, Chloe; Zaki, Mohamed; Palmisano, Maria; Zhou, Simon

2017-01-01

Pomalidomide is an immunomodulatory drug for treatment of relapsed or refractory multiple myeloma (rrMM) in patients who often have comorbid renal conditions. To assess the impact of renal impairment on pomalidomide exposure, a population pharmacokinetics (PPK) model of pomalidomide in rrMM patients with various degrees of impaired renal function was developed. Intensive and sparse pomalidomide concentration data collected from two clinical studies in rrMM patients with normal renal function, moderately impaired renal function, severely impaired renal function not requiring dialysis, and with severely impaired renal function requiring dialysis were pooled over the dose range of 2 to 4 mg, to assess specifically the influence of the impaired renal function as a categorical variable and a continuous variable on pomalidomide clearance and plasma exposure. In addition, pomalidomide concentration data collected on dialysis days from both the withdrawal (arterial) side and from the returning (venous) side of the dialyzer, from rrMM patients with severely impaired renal function requiring dialysis, were used to assess the extent to which dialysis contributes to the removal of pomalidomide from blood circulation. PPK analyses demonstrated that moderate to severe renal impairment not requiring dialysis has no influence on pomalidomide clearance or plasma exposure, as compared to those patients with normal renal function, while pomalidomide exposure increased approximately 35% in patients with severe renal impairment requiring dialysis on nondialysis days. In addition, dialysis increased total body pomalidomide clearance from 5 L/h to 12 L/h, indicating that dialysis will significantly remove pomalidomide from the blood circulation. Thus, pomalidomide should be administered post-dialysis on the days of dialysis.

Factors related to outcome in heart failure with a preserved (or normal) left ventricular ejection fraction.

PubMed

Sanderson, John E

2016-07-01

Heart failure with a preserved ejection faction (HFpEF) is a growing and expensive cause of heart failure (HF) affecting particularly the elderly. It differs in substantial ways in addition to the normal left ventricular ejection fraction, from the more easily recognized form of heart failure with a reduced ejection fraction (HFrEF or 'systolic heart failure') and unlike HFrEF there have been little advances in treatment. In part, this relates to the complexity of the pathophysiology and identifying the correct targets. In HFpEF, there appears to be widespread stiffening of the vasculature and the myocardium affecting ventricular function (both systolic and diastolic), impeding ventricular suction, and thus early diastolic filling leading to breathlessness on exertion and later atrial failure and fibrillation. Left ventricular ejection fraction tends to gradually decline and some evolve into HFrEF. Most patients also have a mixture of several co-morbidities including hypertension, diabetes, obesity, poor renal function, lack of fitness, and often poor social conditions. Therefore, many factors may influence outcome in an individual patient. In this review, the epidemiology, possible causation, pathophysiology, the influence of co-morbidities and some of the many potential predictors of outcome will be considered.

Measuring residual renal function for hemodialysis adequacy: Is there an easier option?

PubMed

Davenport, Andrew

2017-10-01

Most patients starting hemodialysis (HD) have residual renal function. As such, there has been increased interest in starting patients with less frequent and shorter dialysis session times. However, for this incremental approach to be successful, patients require regular monitoring of residual renal function, so that as residual renal function declines, the amount of HD is appropriately increased. Currently most dialysis centers rely on interdialytic urine collections. However, many patients find these inconvenient and there may be marked intrapatient variability due to compliance issues. Thus, alternative markers of residual renal function are required for routine clinical practice. Currently three middle sized molecules; cystatin C, β2 microglobulin, and βtrace protein have been investigated as potential endogenous markers of glomerular filtration. Although none is ideal, combinations of these markers have been proposed to provide a more accurate estimation of glomerular clearance, and in particular cut offs for minimal residual renal function. However, in patients with low levels of residual renal function it remains unclear as to whether the benefits of residual renal function equally apply to glomerular filtration or tubular function. © 2017 International Society for Hemodialysis.

Value of Nephrometry Score Constituents on Perioperative Outcomes and Split Renal Function in Patients Undergoing Minimally Invasive Partial Nephrectomy.

PubMed

Watts, Kara L; Ghosh, Propa; Stein, Solomon; Ghavamian, Reza

2017-01-01

To assess the relationship between individual nephrometry score (NS) constituents (RENAL) on perioperative outcomes and renal function of the surgical kidney in patients undergoing laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy. Two hundred forty-five patients who underwent laparoscopic partial nephrectomy or robotic-assisted partial nephrectomy between 2005 and 2014 were retrospectively reviewed. Each renal mass' NS was calculated from preoperative computed tomography imaging. Multivariate regression analysis was used to evaluate the effect of NS variables on perioperative outcomes and change in overall renal function (as estimated by glomerular filtration rate) from preoperative to 1-year postoperative. A cohort analysis assessed the effect of NS variables on change in split renal function of the surgical kidney from pre- to postoperative based on nuclear medicine renal scintigraphy. Tumor radius (R), endophytic nature (E), and nearness to collecting system (N) variables significantly and incrementally predicted a longer operative time and warm ischemia time. Overall renal function based on glomerular filtration rate was not affected by any NS variable. However, percent function of the surgical kidney by renal scintigraphy significantly decreased postoperatively as R and E values increased. R, E, and N were associated with significant changes in warm ischemia time and operative time. R and E were associated with a significant decrease in split renal function of the surgical kidney at 1 year after surgery but not with overall renal function. R, E, and N are the NS constituents most relevant to perioperative outcomes and postoperative differential renal function after partial nephrectomy. Copyright © 2016. Published by Elsevier Inc.

Benefit of early inflow exclusion during living donor liver transplantation for unresectable hepatoblastoma.

PubMed

Uchida, Hajime; Fukuda, Akinari; Sasaki, Kengo; Hirata, Yoshihiro; Shigeta, Takanobu; Kanazawa, Hiroyuki; Nakazawa, Atsuko; Miyazaki, Osamu; Nosaka, Shunsuke; Mali, Vidyadhar Padmakar; Sakamoto, Seisuke; Kasahara, Mureo

2016-11-01

Hepatoblastoma (HB) is a highly malignant primary liver tumor in children. Although liver transplantation (LT) is an effective treatment for unresectable HB with good long-term outcomes, post-transplant survival is mainly affected by recurrence, despite adjuvant chemotherapy. Novel strategies are needed to improve the outcomes in patients undergoing LT for unresectable HB. Twelve children received LT for unresectable HB. In 9 patients, we applied early exclusion of hepatic inflow (hepatic artery and portal vein) and creation of a temporary portocaval shunt during LT. There were differences in the duration of and the blood loss during operation as compared with previously reports. The estimated glomerular filtration rate was well preserved at 3, 6, and 12months and the latest follow-up after LT, and the recurrence-free survival was 88.9%. Early inflow control during LT for unresectable HB may benefit recurrence-free survival by minimizing blood loss and tumor dissemination, preserving renal function and allowing early adjuvant chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Validation of a Functional Pyelocalyceal Renal Model for the Evaluation of Renal Calculi Passage While Riding a Roller Coaster.

PubMed

Mitchell, Marc A; Wartinger, David D

2016-10-01

The identification and evaluation of activities capable of dislodging calyceal renal calculi require a patient surrogate or validated functional pyelocalyceal renal model. To evaluate roller coaster facilitation of calyceal renal calculi passage using a functional pyelocalyceal renal model. A previously described adult ureteroscopy and renoscopy simulator (Ideal Anatomic) was modified and remolded to function as a patient surrogate. Three renal calculi of different sizes from the patient who provided the original computed tomographic urograph on which the simulator was based were used. The renal calculi were suspended in urine in the model and taken for 20 rides on the Big Thunder Mountain Railroad roller coaster at Walt Disney World in Orlando, Florida. The roller coaster rides were analyzed using variables of renal calculi volume, calyceal location, model position on the roller coaster, and renal calculi passage. Sixty renal calculi rides were analyzed. Independent of renal calculi volume and calyceal location, front seating on the roller coaster resulted in a passage rate of 4 of 24. Independent of renal calculi volume and calyceal location, rear seating on the roller coaster resulted in a passage rate of 23 of 36. Independent of renal calculi volume in rear seating, calyceal location differed in passage rates, with an upper calyceal calculi passage rate of 100%; a middle calyceal passage rate of 55.6%; and a lower calyceal passage rate of 40.0%. The functional pyelocalyceal renal model serves as a functional patient surrogate to evaluate activities that facilitate calyceal renal calculi passage. The rear seating position on the roller coaster led to the most renal calculi passages.

Sodium thiosulfate protects brain in rat model of adenine induced vascular calcification.

PubMed

Subhash, N; Sriram, R; Kurian, Gino A

2015-11-01

Vascular bed calcification is a common feature of ends stage renal disease that may lead to a complication in cardiovascular and cerebrovascular beds, which is a promoting cause of myocardial infarction, stroke, dementia and aneurysms. Sodium thiosulfate (STS) due to its multiple properties such as antioxidant and calcium chelation has been reported to prevent vascular calcification in uremic rats, without mentioning its impact on cerebral function. Moreover, the previous studies have not explored the effect of STS on the mitochondrial dysfunction, one of the main pathophysiological features associated with the disease and the main site for STS metabolism. The present study addresses this limitation by using a rat model where 0.75% adenine was administered to induce vascular calcification and 400 mg/kg b wt. of STS was given as preventive and curative agent. The blood and urine chemistries along with histopathology of aorta confirms the renal protective effect of STS in two modes of administration. The brain oxidative stress assessment was made through TBARS level, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, found to be in the near normal level. STS administration not only reduced the mitochondrial oxidative stress (measured by TBARS, SOD, GPx and CAT) but also preserved the mitochondrial respiratory enzyme activities (NADH dehydrogenase, Succinate dehydrogenase and Malate dehydrogenase) and its physiology (measured by P/O ratio and RCR). In fact, the protective effect of STS was prominent, when it was administered as a curative agent, where low H2S and high thiosulfate level was observed along with low cystathionine β synthase activity, confirms thiosulfate mediated renal protection. In conclusion, STS when given after induction of calcification is protective to the brain by preserving its mitochondria, compared to the treatment given concomitantly. Copyright © 2015 Elsevier Ltd. 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

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.

Intermediate-Term Outcomes With Expanded Criteria Deceased Donors in Kidney Transplantation

PubMed Central

Stratta, Robert J.; Rohr, Michael S.; Sundberg, Aimee K.; Farney, Alan C.; Hartmann, Erica L.; Moore, Phillip S.; Rogers, Jeffrey; Iskandar, Samy S.; Gautreaux, Michael D.; Kiger, David F.; Doares, William; Anderson, Teresa K.; Hairston, Gloria; Adams, Patricia L.

2006-01-01

Objective: To compare intermediate-term outcomes in adult recipients of expanded criteria (ECD) versus concurrent standard criteria (SCD) deceased donor kidney transplants at a single center using a standardized approach. Summary Background Data: Expanded criteria donors (ECDs) are a source of kidneys that increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns regarding diminished survival and predicted poorer intermediate-term outcomes. Methods: Over a 47-month period, we performed 244 deceased donor kidney transplants into adult recipients, including 143 from SCDs and 101 from ECDs. Management algorithms were implemented to preserve nephron function, and recipient selection for an ECD kidney transplant was based on low immunologic risk. All patients received depleting antibody induction in combination with tacrolimus and mycophenolate mofetil. A total of 188 patients (77%) had at least a 1-year follow-up. Results: ECDs were older, had a higher BMI, had an increased incidence of cerebrovascular brain death and preexisting donor hypertension, and had a lower estimated creatinine clearance (CrCl, all P < 0.01) compared with SCDs. Cold ischemic times were similar between groups, but more ECD kidneys were preserved with pulsatile perfusion (P < 0.01). ECD kidney recipients were older, less sensitized, had a lower BMI, had fewer 0-antigen mismatches, and had a shorter waiting time (all P < 0.01) compared with SCD kidney recipients. Actual patient (93%) and kidney graft (83%) survival rates were similar between groups with a mean follow-up of 24 months. The rates of delayed graft function (DGF), acute rejection, readmissions, operative complications, major infections, and resource utilization were comparable between groups. Renal function followed longitudinally was consistently better in SCD patients (P < 0.05). Black recipients had higher rates of DGF, acute rejection, and graft loss (P < 0.05), but the effects were less pronounced in the ECD group. Conclusions: By appropriate donor and recipient profiling and the use of management algorithms to project and protect renal function, excellent intermediate-term outcomes can be achieved with ECD kidney transplants that are comparable to SCD kidney transplants. PMID:16632993

Renal Function in Type 2 Diabetes with Rosiglitazone, Metformin, and Glyburide Monotherapy

PubMed Central

Viberti, Giancarlo; Zinman, Bernard; Haffner, Steven M.; Aftring, R. Paul; Paul, Gitanjali; Kravitz, Barbara G.; Herman, William H.; Holman, Rury R.; Kahn, Steven E.

2011-01-01

Summary Background and objectives In ADOPT (A Diabetes Outcomes Prevention Trial), initial monotherapy with rosiglitazone provided more durable glycemic control than metformin or glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine differences in albumin excretion, renal function (estimated GFR), and BP over 5 years between treatment groups. Design, setting, participants, & measurements A total of 4351 recently diagnosed, drug-naïve patients with type 2 diabetes were treated and followed for up to 5 years with rosiglitazone, metformin, or glyburide and were examined with periodic assessments of albumin/creatinine ratio (ACR), modification of diet in renal disease (MDRD)-estimated GFR, and BP. Results The ACR rose slowly with metformin. It fell with rosiglitazone and less so with glyburide over the first 2 years, and then rose slowly over time. Estimated GFR (eGFR) with all therapies rose into the high normal range over the first 3 to 4 years, more so with rosiglitazone, and then declined, more so with glyburide. Systolic BP was stable over time, values with rosiglitazone being lower, and diastolic BP declined over time, more so with rosiglitazone than with metformin or glyburide. There was no difference among groups in the incidence of emergent albuminuria (ACR ≥30 mg/g), hypertension, or impaired eGFR (<60 ml/min per 1.73 m2). Conclusions Over a 5-year period, initial monotherapy with rosiglitazone retards the rise of ACR compared with metformin, preserves eGFR compared with glyburide, and lowers BP relative to both comparators. PMID:21454723

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.

Nephrotoxicity of ibandronate and zoledronate in Wistar rats with normal renal function and after unilateral nephrectomy.

PubMed

Bergner, R; Siegrist, B; Gretz, N; Pohlmeyer-Esch, G; Kränzlin, B

2015-09-01

A previous animal study compared the nephrotoxic effect of ibandronate (IBN) and zoledronate (ZOL), but interpretation of these study results was limited because of the model of minimal nephrotoxic dosage with a dosage ratio of 1:3. The present study investigated the nephrotoxicity of ibandronate and zoledronate in a 1.5:1 dose ratio, as used in clinical practice and compared the nephrotoxicity in rats with normal and with mildly to moderately impaired renal function. We compared rats with normal renal function (SHAM) and with impaired renal function after unilateral nephrectomy (UNX), treated either with ibandronate 1.5mg/kg, zoledronate 1mg/kg or placebo once (1×) or nine (9×) times. Renal function and markers of tubular toxicity were measured over a 27 week period. After last bisphosphonate treatment the rats were sacrificed and kidneys examined histologically. All bisphosphonate treated animals showed a significant tubular toxicity, which was temporary except in the ZOL-UNX-9×-group. Also the renal function was only transiently reduced except in the ZOL-UNX-9×-group. Histologically, bisphosphonate treatment led to cortical tubuloepithelial degeneration/necrosis and medullary tubuloepithelial swelling which were slightly more pronounced in ibandronate treated animals, when compared to zoledronate treated animals, especially with impaired renal function. In contrast to the previous study we found a similar nephrotoxicity of ibandronate and zoledronate in rats with normal renal function. In rats with impaired renal function the peak of toxicity had not even been fully reached until end of experiment in the zoledronate treated animals. The peak of toxicity seems to be more severe and delayed in rats with impaired renal function compared with rats with normal renal function. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impaired renal function modifies the risk of severe hypoglycaemia among users of insulin but not glyburide: a population-based nested case-control study.

PubMed

Weir, Matthew A; Gomes, Tara; Mamdani, Muhammad; Juurlink, David N; Hackam, Daniel G; Mahon, Jeffrey L; Jain, Arsh K; Garg, Amit X

2011-06-01

Little evidence justifies the avoidance of glyburide in patients with impaired renal function. We aimed to determine if renal function modifies the risk of hypoglycaemia among patients using glyburide. We conducted a nested case-control study using administrative records and laboratory data from Ontario, Canada. We included outpatients 66 years of age and older with diabetes mellitus and prescriptions for glyburide, insulin or metformin. We ascertained hypoglycaemic events using administrative records and estimated glomerular filtration rates (eGFR) using serum creatinine concentrations. From a cohort of 19,620 patients, we identified 204 cases whose eGFR was ≥ 60 mL/min/1.73 m(2) (normal renal function) and 354 cases whose eGFR was < 60 mL/min/1.73 m(2) (impaired renal function). Compared to metformin, glyburide is associated with a greater risk of hypoglycaemia in patients with both normal [adjusted odds ratio (OR) 9.0, 95% confidence interval (95% CI) 4.9-16.4] and impaired renal function (adjusted OR 6.0, 95% CI 3.8-9.5). We observed a similar relationship when comparing insulin to metformin; the risk was greater in patients with normal renal function (adjusted OR 18.7, 95% CI 10.5-33.5) compared to those with impaired renal function (adjusted OR 7.9, 95% CI 5.0-12.4). Tests of interaction showed that among glyburide users, renal function did not significantly modify the risk of hypoglycaemia, but among insulin users, impaired renal function is associated with a lower risk. In this population-based study, impaired renal function did not augment the risk of hypoglycaemia associated with glyburide use.

Multimarker assessment for the prediction of renal function improvement after percutaneous revascularization for renal artery stenosis.

PubMed

Staub, Daniel; Partovi, Sasan; Zeller, Thomas; Breidthardt, Tobias; Kaech, Max; Boeddinghaus, Jasper; Puelacher, Christian; Nestelberger, Thomas; Aschwanden, Markus; Mueller, Christian

2016-06-01

Identifying patients likely to have improved renal function after percutaneous transluminal renal angioplasty and stenting (PTRA) for renal artery stenosis (RAS) is challenging. The purpose of this study was to use a comprehensive multimarker assessment to identify those patients who would benefit most from correction of RAS. In 127 patients with RAS and decreased renal function and/or hypertension referred for PTRA, quantification of hemodynamic cardiac stress using B-type natriuretic peptide (BNP), renal function using estimated glomerular filtration rate (eGFR), parenchymal renal damage using resistance index (RI), and systemic inflammation using C-reactive protein (CRP) were performed before intervention. Predefined renal function improvement (increase in eGFR ≥10%) at 6 months occurred in 37% of patients. Prognostic accuracy as quantified by the area under the receiver-operating characteristics curve for the ability of BNP, eGFR, RI and CRP to predict renal function improvement were 0.59 (95% CI, 0.48-0.70), 0.71 (95% CI, 0.61-0.81), 0.52 (95% CI, 0.41-0.65), and 0.56 (95% CI, 0.44-0.68), respectively. None of the possible combinations increased the accuracy provided by eGFR (lower eGFR indicated a higher likelihood for eGFR improvement after PTRA, P=ns for all). In the subgroup of 56 patients with pre-interventional eGFR <60 mL/min/1.73 m(2), similar findings were obtained. Quantification of renal function, but not any other pathophysiologic signal, provides at least moderate accuracy in the identification of patients with RAS in whom PTRA will improve renal function.

Creatinine, urea, uric acid, water and electrolytes renal handling in the healthy oldest old

PubMed Central

Musso, Carlos Guido; Álvarez Gregori, Joaquín; Jauregui, José Ricardo; Macías Núñez, Juan Florencio

2012-01-01

Renal physiology in the healthy oldest old has the following characteristics, in comparison with the renal physiology in the young: a reduced creatinine clearance, tubular pattern of creatinine back-filtration, preserved proximal tubule sodium reabsorption and uric acid secretion, reduced sodium reabsorption in the thick ascending loop of Henle, reduced free water clearance, increased urea excretion, presence of medulla hypotonicity, reduced urinary dilution and concentration capabilities, and finally a reduced collecting tubules response to furosemide which expresses a reduced potassium excretion in this segment due to a sort of aldosterone resistance. All physiological changes of the aged kidney are the same in both genders. PMID:24175249

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 function monitoring in heart failure – what is the optimal frequency? A narrative review

PubMed Central

Wright, David; Devonald, Mark Alexander John; Pirmohamed, Munir

2017-01-01

The second most common cause of hospitalization due to adverse drug reactions in the UK is renal dysfunction due to diuretics, particularly in patients with heart failure, where diuretic therapy is a mainstay of treatment regimens. Therefore, the optimal frequency for monitoring renal function in these patients is an important consideration for preventing renal failure and hospitalization. This review looks at the current evidence for optimal monitoring practices of renal function in patients with heart failure according to national and international guidelines on the management of heart failure (AHA/NICE/ESC/SIGN). Current guidance of renal function monitoring is in large part based on expert opinion, with a lack of clinical studies that have specifically evaluated the optimal frequency of renal function monitoring in patients with heart failure. Furthermore, there is variability between guidelines, and recommendations are typically nonspecific. Safer prescribing of diuretics in combination with other antiheart failure treatments requires better evidence for frequency of renal function monitoring. We suggest developing more personalized monitoring rather than from the current medication‐based guidance. Such flexible clinical guidelines could be implemented using intelligent clinical decision support systems. Personalized renal function monitoring would be more effective in preventing renal decline, rather than reacting to it. PMID:28901643

Cardiorenal Syndrome in Acute Heart Failure: Revisiting Paradigms.

PubMed

Núñez, Julio; Miñana, Gema; Santas, Enrique; Bertomeu-González, Vicente

2015-05-01

Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney. Worsening renal function that occurs in patients with acute heart failure has been classified as cardiorenal syndrome type 1. In this setting, worsening renal function is a common finding and is due to complex, multifactorial, and not fully understood processes involving hemodynamic (renal arterial hypoperfusion and renal venous congestion) and nonhemodynamic factors. Traditionally, worsening renal function has been associated with worse outcomes, but recent findings have revealed mixed and heterogeneous results, perhaps suggesting that the same phenotype represents a diversity of pathophysiological and clinical situations. Interpreting the magnitude and chronology of renal changes together with baseline renal function, fluid overload status, and clinical response to therapy might help clinicians to unravel the clinical meaning of renal function changes that occur during an episode of heart failure decompensation. In this article, we critically review the contemporary evidence on the pathophysiology and clinical aspects of worsening renal function in acute heart failure. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

PubMed

Triebel, Jakob; Moreno-Vega, Aura Ileana; Vázquez-Membrillo, Miguel; Nava, Gabriel; García-Franco, Renata; López-Star, Ellery; Baldivieso-Hurtado, Olivia; Ochoa, Daniel; Macotela, Yazmín; Bertsch, Thomas; Martinez de la Escalera, Gonzalo; Clapp, Carmen

2015-01-01

The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

[Renovascular hypertension in children and adolescents: diagnosis and treatment over 19 years].

PubMed

Alfonzo, J P; Ugarte, C; Banasco, J; Fraxedas, R; Gutiérrez, F; Lahera, J

2006-01-01

SUMMARY Sixty seven hypertensive children age 2-18 with at least one possible clinical sign of renovascular hypertension (RVH) were enrollment into a screening program for diagnose and treatment of RVH over a 19 year period. Patients underwent a variety of biochemical and imaging studies, but in all cases, renal arteriography was used to determine the precise diagnosis and treatment strategy. Of the 67 patients 21 (31.3%) were identified with renal artery stenosis Group 1, 14 (66.6%) unilateral, 5 (23.8%) bilateral and 2 (9.6%) branches. The mean age was 13.9 +/- 3.73 years, with 26.4 +/- 35.2 months of known hypertension, mean systolic blood pressure 191.1 +/- 30.6 mmHg, mean diastolic blood pressure 135.3 +/- 21.2 mmHg and 69% due to fibromuscular dysplasia. Three therapeutic modalities were chosen: percutaneous transluminal angioplasty (PTA), surgery (autotransplant, and nephrectomy), pharmaceutical therapy with antihypertensive drugs and combination of these. The aim of the treatment was blood pressure control, prevention of chronic renal disease and renal function and organ damage preservation. The outcome was categorized as cure, improvement or no change in hypertension. PTA treated eleven patients, 2 combined with surgery (one nephrectomy and 1 autotransplant). Blood pressure was normalized in 9/11 (81.8%) after a mean follow-up of 11.5 years (range 1-18 years). All 6 RVH cases treated by surgery procedure (one after PTA) were cured and 4 cases were managed medically (pharmacological treatment). On december 2004, 19/21 (90%) RVH adolescents blood pressure was normalized with normal serum creatinina, 10 (48%) of these completed cured, 9/21 (43%) improved (normotensión with decrease in medication requirements) and 2 (9%) other cases ware lost of follow-up. The 46 non-RVH adolescents (68.7%) were treated with long term antihypertensive medications; all of these have adequate BP control and normal renal function. We conclude that our work-up used in order to make a proper and timely diagnosis and treatment of renovascular hypertension in adolescent was successful in our population.

Better preservation of residual renal function in peritoneal dialysis patients treated with a low-protein diet supplemented with keto acids: a prospective, randomized trial.

PubMed

Jiang, Na; Qian, Jiaqi; Sun, Weilan; Lin, Aiwu; Cao, Liou; Wang, Qin; Ni, Zhaohui; Wan, Yanping; Linholm, Bengt; Axelsson, Jonas; Yao, Qiang

2009-08-01

While a low-protein diet may preserve residual renal function (RRF) in chronic kidney disease (CKD) patients before the start of dialysis, a high-protein intake is usually recommended in dialysis patients to prevent protein-energy wasting. Keto acids, which were often recommended to pre-dialysis CKD patients treated with a low-protein diet, had also been reported to be associated with both RRF and nutrition maintenance. We conducted a randomized trial to test whether a low-protein diet with or without keto acids would be safe and associated with a preserved RRF during peritoneal dialysis (PD). To assess the safety of low protein, we first conducted a nitrogen balance study in 34 incident PD patients randomized to receive in-centre diets containing 1.2, 0.9 or 0.6 g of protein/kg ideal body weight (IBW)/day for 10 days. Second, 60 stable PD patients [RRF 4.04 +/- 2.30 ml/ min/1.73 m(2), urine output 1226 +/- 449 ml/day, aged 53.6 +/- 12.8 years, PD duration 8.8 (1.5-17.8) months] were randomized to receive either a low- (LP: 0.6-0.8 g/kg IBW/day), keto acid-supplemented low- (sLP: 0.6-0.8 g/kg IBW/day with 0.12 g/kg IBW/day of keto acids) or high-protein (HP: 1.0-1.2 g/kg IBW/day) diet. The groups were followed for 1 year and RRF as well as nutritional status was evaluated serially. A neutral or positive nitrogen balance was achieved in all three groups. RRF remained stable in group sLP (3.84 +/- 2.17 to 3.39 +/- 3.23 ml/min/1.73 m(2), P = ns) while it decreased in group LP (4.02 +/- 2.49 to 2.29 +/- 1.72 ml/min/1.73 m(2), P < 0.05) and HP (4.25 +/- 2.34 to 2.55 +/- 2.29 ml/min/1.73 m(2), P < 0.05). There was no change from baseline on nutritional status in any of the groups during follow-up. A diet containing 0.6-0.8 g of protein/kg IBW/day is safe and, when combined with keto acids, is associated with an improved preservation of RRF in relatively new PD patients without significant malnutrition or inflammation.

Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation in Relation to Renal Function Over Time: Insights From the ARISTOTLE Randomized Clinical Trial.

PubMed

Hijazi, Ziad; Hohnloser, Stefan H; Andersson, Ulrika; Alexander, John H; Hanna, Michael; Keltai, Matyas; Parkhomenko, Alexander; López-Sendón, José L; Lopes, Renato D; Siegbahn, Agneta; Granger, Christopher B; Wallentin, Lars

2016-07-01

Renal impairment confers an increased risk of stroke, bleeding, and death in patients with atrial fibrillation. Little is known about the efficacy and safety of apixaban in relation to renal function changes over time. To evaluate changes of renal function over time and their interactions with outcomes during a median of 1.8 years of follow-up in patients with atrial fibrillation randomized to apixaban vs warfarin treatment. The prospective, randomized, double-blind Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) clinical trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Serial creatinine measurements were available in 16 869 patients. Worsening of renal function was defined as an annual decrease in estimated glomerular filtration more than 20%. The relations between treatment, outcomes, and renal function were investigated using Cox regression models, with renal function as a time-dependent covariate. Stroke or systemic embolism (primary outcome), major bleeding (safety outcome), and mortality were examined in relation to renal function over time estimated with both the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration equations. Among 16 869 patients, the median age was 70 years and 65.2% of patients were men. Worsening in estimated glomerular filtration more than 20% was observed in 2294 patients (13.6%) and was associated with older age and more cardiovascular comorbidities. The risks of stroke or systemic embolism, major bleeding, and mortality were higher in patients with worsening renal function (HR, 1.53; 95% CI, 1.17-2.01 for stroke or systemic embolism; HR, 1.56; 95% CI, 1.27-1.93 for major bleeding; and HR, 2.31; 95% CI, 1.98-2.68 for mortality). The beneficial effects of apixaban vs warfarin on rates of stroke or systemic embolism and major bleeding were consistent in patients with normal or poor renal function over time and also in those with worsening renal function. In patients with atrial fibrillation, declining renal function was more common in elderly patients and those with cardiovascular comorbidities. Worsening renal function was associated with a higher risk of subsequent cardiovascular events and bleeding. The superior efficacy and safety of apixaban as compared with warfarin were similar in patients with normal, poor, and worsening renal function. clinicaltrials.gov Identifier: NCT00412984.

Renal function following three distinct weight loss dietary strategies during 2 years of a randomized controlled trial.

PubMed

Tirosh, Amir; Golan, Rachel; Harman-Boehm, Ilana; Henkin, Yaakov; Schwarzfuchs, Dan; Rudich, Assaf; Kovsan, Julia; Fiedler, Georg M; Blüher, Matthias; Stumvoll, Michael; Thiery, Joachim; Stampfer, Meir J; Shai, Iris

2013-08-01

This study addressed the long-term effect of various diets, particularly low-carbohydrate high-protein, on renal function on participants with or without type 2 diabetes. In the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT), 318 participants (age, 51 years; 86% men; BMI, 31 kg/m(2); mean estimated glomerular filtration rate [eGFR], 70.5 mL/min/1.73 m(2); mean urine microalbumin-to-creatinine ratio, 12:12) with serum creatinine <176 μmol/L (eGFR ≥ 30 mL/min/1.73 m(2)) were randomized to low-fat, Mediterranean, or low-carbohydrate diets. The 2-year compliance was 85%, and the proportion of protein intake significantly increased to 22% of energy only in the low-carbohydrate diet (P < 0.05 vs. low-fat and Mediterranean). We examined changes in urinary microalbumin and eGFR, estimated by Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration formulas. Significant (P < 0.05 within groups) improvements in eGFR were achieved in low-carbohydrate (+5.3% [95% CI 2.1-8.5]), Mediterranean (+5.2% [3.0-7.4]), and low-fat diets (+4.0% [0.9-7.1]) with similar magnitude (P > 0.05) across diet groups. The increased eGFR was at least as prominent in participants with (+6.7%) or without (+4.5%) type 2 diabetes or those with lower baseline renal function of eGFR <60 mL/min/1.73 m(2) (+7.1%) versus eGFR ≥ 60 mL/min/1.73 m(2) (+3.7%). In a multivariable model adjusted for age, sex, diet group, type 2 diabetes, use of ACE inhibitors, 2-year weight loss, and change in protein intake (confounders and univariate predictors), only a decrease in fasting insulin (β = -0.211; P = 0.004) and systolic blood pressure (β = -0.25; P < 0.001) were independently associated with increased eGFR. The urine microalbumin-to-creatinine ratio improved similarly across the diets, particularly among participants with baseline sex-adjusted microalbuminuria, with a mean change of -24.8 (P < 0.05). A low-carbohydrate diet is as safe as Mediterranean or low-fat diets in preserving/improving renal function among moderately obese participants with or without type 2 diabetes, with baseline serum creatinine <176 μmol/L. Potential improvement is likely to be mediated by weight loss-induced improvements in insulin sensitivity and blood pressure.

Renal Function Following Three Distinct Weight Loss Dietary Strategies During 2 Years of a Randomized Controlled Trial

PubMed Central

Tirosh, Amir; Golan, Rachel; Harman-Boehm, Ilana; Henkin, Yaakov; Schwarzfuchs, Dan; Rudich, Assaf; Kovsan, Julia; Fiedler, Georg M.; Blüher, Matthias; Stumvoll, Michael; Thiery, Joachim; Stampfer, Meir J.; Shai, Iris

2013-01-01

OBJECTIVE This study addressed the long-term effect of various diets, particularly low-carbohydrate high-protein, on renal function on participants with or without type 2 diabetes. RESEARCH DESIGN AND METHODS In the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT), 318 participants (age, 51 years; 86% men; BMI, 31 kg/m2; mean estimated glomerular filtration rate [eGFR], 70.5 mL/min/1.73 m2; mean urine microalbumin-to-creatinine ratio, 12:12) with serum creatinine <176 μmol/L (eGFR ≥30 mL/min/1.73 m2) were randomized to low-fat, Mediterranean, or low-carbohydrate diets. The 2-year compliance was 85%, and the proportion of protein intake significantly increased to 22% of energy only in the low-carbohydrate diet (P < 0.05 vs. low-fat and Mediterranean). We examined changes in urinary microalbumin and eGFR, estimated by Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration formulas. RESULTS Significant (P < 0.05 within groups) improvements in eGFR were achieved in low-carbohydrate (+5.3% [95% CI 2.1–8.5]), Mediterranean (+5.2% [3.0–7.4]), and low-fat diets (+4.0% [0.9–7.1]) with similar magnitude (P > 0.05) across diet groups. The increased eGFR was at least as prominent in participants with (+6.7%) or without (+4.5%) type 2 diabetes or those with lower baseline renal function of eGFR <60 mL/min/1.73 m2 (+7.1%) versus eGFR ≥60 mL/min/1.73 m2 (+3.7%). In a multivariable model adjusted for age, sex, diet group, type 2 diabetes, use of ACE inhibitors, 2-year weight loss, and change in protein intake (confounders and univariate predictors), only a decrease in fasting insulin (β = −0.211; P = 0.004) and systolic blood pressure (β = −0.25; P < 0.001) were independently associated with increased eGFR. The urine microalbumin-to-creatinine ratio improved similarly across the diets, particularly among participants with baseline sex-adjusted microalbuminuria, with a mean change of −24.8 (P < 0.05). CONCLUSIONS A low-carbohydrate diet is as safe as Mediterranean or low-fat diets in preserving/improving renal function among moderately obese participants with or without type 2 diabetes, with baseline serum creatinine <176 μmol/L. Potential improvement is likely to be mediated by weight loss–induced improvements in insulin sensitivity and blood pressure. PMID:23690533

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

Renal Function Recovery with Total Artificial Heart Support.

PubMed

Quader, Mohammed A; Goodreau, Adam M; Shah, Keyur B; Katlaps, Gundars; Cooke, Richard; Smallfield, Melissa C; Tchoukina, Inna F; Wolfe, Luke G; Kasirajan, Vigneshwar

2016-01-01

Heart failure patients requiring total artificial heart (TAH) support often have concomitant renal insufficiency (RI). We sought to quantify renal function recovery in patients supported with TAH at our institution. Renal function data at 30, 90, and 180 days after TAH implantation were analyzed for patients with RI, defined as hemodialysis supported or an estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m. Between January 2008 and December 2013, 20 of the 46 (43.5%) TAH recipients (age 51 ± 9 years, 85% men) had RI, mean preoperative eGFR of 48 ± 7 ml/min/1.73 m. Renal function recovery was noted at each follow-up interval: increment in eGFR (ml/min/1.73 m) at 30, 90, and 180 days was 21 ± 35 (p = 0.1), 16.5 ± 18 (p = 0.05), and 10 ± 9 (p = 0.1), respectively. Six patients (30%) required preoperative dialysis. Of these, four recovered renal function, one remained on dialysis, and one died. Six patients (30%) required new-onset dialysis. Of these, three recovered renal function and three died. Overall, 75% (15 of 20) of patients' renal function improved with TAH support. Total artificial heart support improved renal function in 75% of patients with pre-existing significant RI, including those who required preoperative dialysis.

Effect of risedronate on bone in renal transplant recipients.

PubMed

Coco, Maria; Pullman, James; Cohen, Hillel W; Lee, Sally; Shapiro, Craig; Solorzano, Clemencia; Greenstein, Stuart; Glicklich, Daniel

2012-08-01

Bisphosphonates may prevent or treat the bone loss promoted by the immunosuppressive regimens used in renal transplantation. Risedronate is a commonly used third-generation amino-bisphosphonate, but little is known about its effects on the bone health of renal transplant recipients. We randomly assigned 42 new living-donor kidney recipients to either 35 mg of risedronate weekly or placebo for 12 months. We obtained bone biopsies at the time of renal transplant and after 12 months of protocol treatment. Treatment with risedronate did not affect bone mineral density (BMD) in the overall cohort. In subgroup analyses, it tended to preserve BMD in female participants but did not significantly affect the BMD of male participants. Risedronate did associate with increased osteoid volume and trabecular thickness in male participants, however. There was no evidence for the development of adynamic bone disease. In summary, further study is needed before the use of prophylactic bisphosphonates to attenuate bone loss can be recommended in renal transplant recipients.

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.

Renal, efficacy and safety outcomes following late conversion of kidney transplant patients from calcineurin inhibitor therapy to everolimus: the randomized APOLLO study.

PubMed

Budde, Klemens; Rath, Thomas; Sommerer, Claudia; Haller, Hermann; Reinke, Petra; Witzke, Oliver; Suwelack, Barbara; Baeumer, Daniel; May, Christoph; Porstner, Martina; Arns, Wolfgang

2015-01-01

The primary objective of this trial was to demonstrate, based on the estimated glomerular filtration rate (eGFR), superior renal function at month 12 after conversion of maintenance kidney transplant patients from calcineurin inhibitor (CNI) therapy to everolimus, compared to continuing a standard CNI regimen. APOLLO was an open-label, 12-month, prospective, multicenter study in which 93 maintenance kidney transplant patients were randomized to convert from CNI to everolimus (n = 46) or remain on standard CNI-based immunosuppression (n = 47). The primary efficacy variable was eGFR (Nankivell formula) 12 months after randomization. The study was terminated prematurely due to slow recruitment and was thus underpowered. Mean time post-transplant was 83.5 months with everolimus and 70.1 months with CNI. Adjusted values for eGFR (Nankivell) at month 12 were 61.6 (95% CI 58.1, 65.1) mL/ min/1.73 m² with everolimus and 58.8 (95% CI 55.2, 62.3) mL/min/1.73 m² with CNI, a difference of 2.8 (95% CI -1.0, 6.7) mL/ min/1.73 m² (p = 0.145) i.e., the primary objective was not met. Using the modification of diet in renal disease (MDRD) formula, adjusted eGFR at month 12 was significantly higher with everolimus (p = 0.030). In the subpopulation who remained on the study drug (n = 52), the difference in the adjusted change from randomization was 6.6 (95% CI 1.5, 11.6) mL/min/1.73 m² (p = 0.013) in favor of everolimus. There was no biopsyproven acute rejection and no graft losses. Adverse events led to discontinuation of everolimus and CNI in 32.6% and 10.6% of patients, respectively. Conversion from CNI to everolimus to preserve renal function can be considered several years after kidney transplantation and does not compromise immunosuppressive efficacy.

Multimarker assessment for the prediction of renal function improvement after percutaneous revascularization for renal artery stenosis

PubMed Central

Partovi, Sasan; Zeller, Thomas; Breidthardt, Tobias; Kaech, Max; Boeddinghaus, Jasper; Puelacher, Christian; Nestelberger, Thomas; Aschwanden, Markus; Mueller, Christian

2016-01-01

Background Identifying patients likely to have improved renal function after percutaneous transluminal renal angioplasty and stenting (PTRA) for renal artery stenosis (RAS) is challenging. The purpose of this study was to use a comprehensive multimarker assessment to identify those patients who would benefit most from correction of RAS. Methods In 127 patients with RAS and decreased renal function and/or hypertension referred for PTRA, quantification of hemodynamic cardiac stress using B-type natriuretic peptide (BNP), renal function using estimated glomerular filtration rate (eGFR), parenchymal renal damage using resistance index (RI), and systemic inflammation using C-reactive protein (CRP) were performed before intervention. Results Predefined renal function improvement (increase in eGFR ≥10%) at 6 months occurred in 37% of patients. Prognostic accuracy as quantified by the area under the receiver-operating characteristics curve for the ability of BNP, eGFR, RI and CRP to predict renal function improvement were 0.59 (95% CI, 0.48–0.70), 0.71 (95% CI, 0.61–0.81), 0.52 (95% CI, 0.41–0.65), and 0.56 (95% CI, 0.44–0.68), respectively. None of the possible combinations increased the accuracy provided by eGFR (lower eGFR indicated a higher likelihood for eGFR improvement after PTRA, P=ns for all). In the subgroup of 56 patients with pre-interventional eGFR <60 mL/min/1.73 m2, similar findings were obtained. Conclusions Quantification of renal function, but not any other pathophysiologic signal, provides at least moderate accuracy in the identification of patients with RAS in whom PTRA will improve renal function. PMID:27280085

Renal function had an independent relationship with coronary artery calcification in Chinese elderly men.

PubMed

Fu, Shihui; Zhang, Zhao; Luo, Leiming; Ye, Ping

2017-04-07

Although previous studies have analyzed the relationship between renal function and coronary artery calcification (CAC) in pre-dialysis and dialysis patients, limited studies have discussed the relationship between renal function and CAC in Chinese elderly men without obvious damage of renal function. The present study was designed to explore the relationship between renal function and CAC in Chinese elderly men without obvious damage of renal function. This cross-sectional study was carried out in 105 male participants older than 60 years with glomerular filtration rate (GFR) ≥ 45 ml/min/1.73 m 2 . CAC was detected by high-definition computerized tomography (HDCT), which is a highly sensitive technique for detecting the CAC and provides the most accurate CAC scores up to date. Age was 72 ± 8.4 years on average and ranged from 60 to 89 years. Simple correlation analysis indicated that all kinds of CAC scores including the Agatston, volume and mass scores inversely correlated with GFR values (p < 0.05 for all). In multivariate linear regression analysis, GFR values were independently associated with all these CAC scores (p < 0.05 for all). Renal function had an independent relationship with CAC detected by HDCT in Chinese elderly men, demonstrating that the relationship between renal function and CAC started at the early stage of renal function decline.

WWSSF - a worldwide study on radioisotopic renal split function: reproducibility of renal split function assessment in children.

PubMed

Geist, Barbara Katharina; Dobrozemsky, Georg; Samal, Martin; Schaffarich, Michael P; Sinzinger, Helmut; Staudenherz, Anton

2015-12-01

The split or differential renal function is the most widely accepted quantitative parameter derived from radionuclide renography. To examine the intercenter variance of this parameter, we designed a worldwide round robin test. Five selected dynamic renal studies have been distributed all over the world by e-mail. Three of these studies are anonymized patient data acquired using the EANM standardized protocol and two studies are phantom studies. In a simple form, individual participants were asked to measure renal split function as well as to provide additional information such as data analysis software, positioning of background region of interest, or the method of calculation. We received the evaluation forms from 34 centers located in 21 countries. The analysis of the round robin test yielded an overall z-score of 0.3 (a z-score below 1 reflecting a good result). However, the z-scores from several centers were unacceptably high, with values greater than 3. In particular, the studies with impaired renal function showed a wide variance. A wide variance in the split renal function was found in patients with impaired kidney function. This study indicates the ultimate importance of quality control and standardization of the measurement of the split renal function. It is especially important with respect to the commonly accepted threshold for significant change in split renal function by 10%.

A case of laparoscopic high anterior resection of rectosigmoid colon cancer associated with a horseshoe kidney using preoperative 3D-CT angiography.

PubMed

Kubo, Naoki; Furusawa, Norihiko; Imai, Shinichiro; Terada, Masaru

2018-06-27

Horseshoe kidney is a congenital malformation in which the bilateral kidneys are fused. It is frequently complicated by other congenital malformations and is often accompanied by anomalies of the ureteropelvic and vascular systems, which must be evaluated to avoid iatrogenic injury. We report a case of laparoscopic high anterior resection of rectosigmoid colon cancer associated with a horseshoe kidney using preoperative 3D-CT angiography. A 52-year-old Japanese man with lower abdominal pain underwent lower endoscopy, revealing a type 2 lesion in the rectosigmoid colon. He was diagnosed with rectosigmoid colon cancer with multiple lung metastases and a horseshoe kidney on computed tomography (CT) scan. Three-dimensional (3D)-CT angiography showed an aberrant renal artery at the isthmus from 3 cm under the inferior mesenteric artery (IMA) branch of the aorta. Laparoscopic anterior rectal resection was performed. During the operation, the inferior mesenteric artery, left ureter, left gonadal vessels, and hypogastric nerve plexus could be seen passing over the horseshoe kidney isthmus and were preserved. The left branch of aberrant renal artery that was close to IMA was also detected and preserved. To prevent intraoperative misidentification, 3D-CT angiography should be performed preoperatively to ascertain the precise positional relationships between the extra renal arteries and the kidney. We always must consider anomalous locations of renal vessels, ureter, gonadal vessels, and lumbar splanchnic nerve to avoid laparoscopic iatrogenic injury in patients with a horseshoe kidney.

Preserved arterial flow secures hepatic oxygenation during haemorrhage in the pig

PubMed Central

Rasmussen, Allan; Skak, Claus; Kristensen, Michael; Ott, Peter; Kirkegaard, Preben; Secher, Niels H

1999-01-01

This study examined the extent of liver perfusion and its oxygenation during progressive haemorrhage. We examined hepatic arterial flow and hepatic oxygenation following the reduced portal flow during haemorrhage in 18 pigs. The hepatic surface oxygenation was assessed by near-infrared spectroscopy and the hepatic metabolism of oxygen, lactate and catecholamines determined the adequacy of the hepatic flow. Stepwise haemorrhage until circulatory collapse resulted in proportional reductions in cardiac output and in arterial, central venous and pulmonary wedge pressures. While heart rate increased, pulmonary arterial pressure remained stable. In addition, renal blood flow decreased, renal vascular resistance increased and there was elevated noradrenaline spill-over. Further, renal surface oxygenation was lowered from the onset of haemorrhage. Similarly, the portal blood flow was reduced in response to haemorrhage, and, as for the renal flow, the reduced splanchnic blood flow was associated with an elevated noradrenaline spill-over. In contrast, hepatic arterial blood flow was only slightly reduced by haemorrhage, and surface oxygenation did not change. The hepatic oxygen uptake was maintained until the blood loss represented more than 30 % of the estimated blood volume. At 30 % reduced blood volume, hepatic catecholamine uptake was reduced, and the lactate uptake approached zero. Subsequent reduction of cardiac output and portal blood flow elicited a selective dilatation of the hepatic arterial vascular bed. Due to this dilatation liver blood flow and hepatic cell oxygenation and metabolism were preserved prior to circulatory collapse. PMID:10087351

Renal function monitoring in heart failure - what is the optimal frequency? A narrative review.

PubMed

Al-Naher, Ahmed; Wright, David; Devonald, Mark Alexander John; Pirmohamed, Munir

2018-01-01

The second most common cause of hospitalization due to adverse drug reactions in the UK is renal dysfunction due to diuretics, particularly in patients with heart failure, where diuretic therapy is a mainstay of treatment regimens. Therefore, the optimal frequency for monitoring renal function in these patients is an important consideration for preventing renal failure and hospitalization. This review looks at the current evidence for optimal monitoring practices of renal function in patients with heart failure according to national and international guidelines on the management of heart failure (AHA/NICE/ESC/SIGN). Current guidance of renal function monitoring is in large part based on expert opinion, with a lack of clinical studies that have specifically evaluated the optimal frequency of renal function monitoring in patients with heart failure. Furthermore, there is variability between guidelines, and recommendations are typically nonspecific. Safer prescribing of diuretics in combination with other antiheart failure treatments requires better evidence for frequency of renal function monitoring. We suggest developing more personalized monitoring rather than from the current medication-based guidance. Such flexible clinical guidelines could be implemented using intelligent clinical decision support systems. Personalized renal function monitoring would be more effective in preventing renal decline, rather than reacting to it. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Elevated urinary podocyte-derived extracellular microvesicles in renovascular hypertensive patients

PubMed Central

Kwon, Soon Hyo; Woollard, John R.; Saad, Ahmed; Garovic, Vesna D.; Zand, Ladan; Jordan, Kyra L.; Textor, Stephen C.

2017-01-01

ABSTRACT Background: An increased number of podocyte-derived extracellular vesicles (pEVs) may reflect podocyte injury in renal disease. Elevated glomerular pressure and other insults may injure podocytes, yet it remains unclear whether the numbers of pEVs are altered in hypertensive patients. We tested the hypothesis that urinary pEV levels would be elevated in patients with renovascular hypertension (RVH) compared with essential hypertension (EH) or healthy volunteers (HVs). Methods: We prospectively enrolled patients with EH (n = 30) or RVH (n = 31) to study renal blood flow (RBF) and cortical perfusion using multidetector computed tomography under controlled condition (regulated sodium intake and renin—angiotensin blockade). After isolation from urine samples, pEVs (nephrin and podocalyxin positive) were characterized by flow cytometry. Fourteen RVH patients were studied again 3 months after stenting or continued medical therapy. HVs (n = 15) served as controls. Results: The fraction of pEV among urinary EVs was elevated in RVH compared with HVs and EH (11.4 ± 6.4, 6.8 ± 3.4 and 6.3 ± 3.7%, respectively; P < 0.001) and remained unchanged after 3 additional months of therapy and after controlling for clinical parameters. However, eGFR- and age-adjusted pEV levels did not correlate with any clinical or renal parameters. Conclusions: In hypertensive patients under controlled conditions, urinary pEV levels are elevated in patients with RVH and low eGFR compared with patients with EH and relatively preserved renal function. These pEVs may reflect podocyte injury secondary to kidney damage, and their levels might represent a novel therapeutic target. PMID:27190371

Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality.

PubMed

Starke, Astrid; Corsenca, Alf; Kohler, Thomas; Knubben, Johannes; Kraenzlin, Marius; Uebelhart, Daniel; Wüthrich, Rudolf P; von Rechenberg, Brigitte; Müller, Ralph; Ambühl, Patrice M

2012-09-01

Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate. This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] <24 mmol/L) undergoing treatment with either potassium citrate to maintain S-[HCO(3)(-)] >24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X-ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group. Administration of potassium citrate resulted in persisting normalization of S-[HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry. Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage.

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.

Renal volume assessed by magnetic resonance imaging volumetry correlates with renal function in living kidney donors pre- and postdonation: a retrospective cohort study.

PubMed

Lange, Daniel; Helck, Andreas; Rominger, Axel; Crispin, Alexander; Meiser, Bruno; Werner, Jens; Fischereder, Michael; Stangl, Manfred; Habicht, Antje

2018-07-01

Renal function of potential living kidney donors is routinely assessed with scintigraphy. Kidney anatomy is evaluated by imaging techniques such as magnetic resonance imaging (MRI). We evaluated if a MRI-based renal volumetry is a good predictor of kidney function pre- and postdonation. We retrospectively analyzed the renal volume (RV) in a MRI of 100 living kidney donors. RV was correlated with the tubular excretion rate (TER) of MAG3-scintigraphy, a measured creatinine clearance (CrCl), and the estimated glomerular filtration rate (eGFR) by Cockcroft-Gault (CG), CKD-EPI, and modification of diet in renal disease (MDRD) formula pre- and postdonation during a follow-up of 3 years. RV correlated significantly with the TER (total: r = 0.6735, P < 0.0001). Correlation between RV and renal function was the highest for eGFR by CG (r = 0.5595, P < 0.0001), in comparison with CrCl, MDRD-GFR, and CKD-EPI-GFR predonation. RV significantly correlated with CG-GFR postdonation and predicted CG-GFR until 3 years after donation. MRI renal volumetry might be an alternative technique for the evaluation of split renal function and prediction of renal function postdonation in living kidney donors. © 2018 Steunstichting ESOT.

Inhibition of PKCδ reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer

PubMed Central

Pabla, Navjotsingh; Dong, Guie; Jiang, Man; Huang, Shuang; Kumar, M. Vijay; Messing, Robert O.; Dong, Zheng

2011-01-01

Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. Despite intensive research, the mechanism of cisplatin-induced nephrotoxicity remains unclear, and renoprotective approaches during cisplatin-based chemotherapy are lacking. Here we have identified PKCδ as a critical regulator of cisplatin nephrotoxicity, which can be effectively targeted for renoprotection during chemotherapy. We showed that early during cisplatin nephrotoxicity, Src interacted with, phosphorylated, and activated PKCδ in mouse kidney lysates. After activation, PKCδ regulated MAPKs, but not p53, to induce renal cell apoptosis. Thus, inhibition of PKCδ pharmacologically or genetically attenuated kidney cell apoptosis and tissue damage, preserving renal function during cisplatin treatment. Conversely, inhibition of PKCδ enhanced cisplatin-induced cell death in multiple cancer cell lines and, remarkably, enhanced the chemotherapeutic effects of cisplatin in several xenograft and syngeneic mouse tumor models while protecting kidneys from nephrotoxicity. Together these results demonstrate a role of PKCδ in cisplatin nephrotoxicity and support targeting PKCδ as an effective strategy for renoprotection during cisplatin-based cancer therapy. PMID:21633170

[News in peritoneal dialysis].

PubMed

Ryckelynck, Jean-Philippe; Lobbedez, Thierry; Ficheux, Maxence; Bonnamy, Cécile; El Haggan, Waël; Henri, Patrick; Chatelet, Valérie; Levaltier, Béatrice; Hurault de Ligny, Bruno

2007-12-01

Peritoneal dialysis, like hemodialysis, is a first-line therapy for patients with end-stage renal disease. Progress in medical devices and materials has reduced infectious complications such as peritonitis and catheter exit-site infections and thus decreased morbidity. Peritoneal dialysis fluids are increasingly biocompatible, result in fewer glucose degradation products, protect the peritoneal membrane better and thus improve tolerance. The maintenance of residual renal function, together with better comfort and no pain, help control the fluid and sodium balance. Automated peritoneal dialysis can be performed each night, either autonomously or assisted by a visiting nurse twice a day (to prepare, connect, and disconnect the machine). This treatment can thus be provided to most patients, regardless of their age. Peritoneal dialysis is indicated principally for young people waiting for a kidney transplantation (to preserve their vascular network), elderly patients who wish to remain either at home or in an institution, and patients with cardiac insufficiency, because of the better hemodynamic tolerance. Numerous obstacles, mainly nonmedical, still impede the development of peritoneal dialysis. Patients seen in emergencies start hemodialysis without necessarily receiving any information about peritoneal dialysis. Indeed, neither physicians nor patients receive adequate information.

Impact of high doses of 6% hydroxyethyl starch 130/0.42 and 4% gelatin on renal function in a pediatric animal model.

PubMed

Witt, Lars; Glage, Silke; Lichtinghagen, Ralf; Pape, Lars; Boethig, Dietmar; Dennhardt, Nils; Heiderich, Sebastian; Leffler, Andreas; Sümpelmann, Robert

2016-03-01

Despite serious renal side effects in critically ill adult patients, artificial colloids are still fundamental components of perioperative fluid therapy in infants and children, although the impact of 6% hydroxyethyl starch (HES) and 4% gelatin (GEL) on renal function during pediatric surgery has not been identified yet. To determine the impact of high doses of artificial colloids on renal function, we conducted an experimental animal study and hypothesized that neither the infusion of HES nor of GEL would have a serious impact on renal function. Fifteen sedated piglets were randomly assigned to receive an infusion of either 50 ml · kg(-1) HES or GEL, or a balanced electrolyte solution (crystalloid group). Before and 1 week after infusion, serum and urine renal function tests were recorded and renal biopsies were taken. Serum and urine renal function tests revealed no increase after administration of HES and GEL, and only a discrete increase in serum creatinine (median 9.8 μmol · l(-1), 95% CI 4.0-19.1) in the crystalloid group. Histopathological examination indicated a sparsely, multifocal infiltration of mononuclear cells in all groups and an unspecific pyelectasia of one animal in the GEL group. After high doses of HES or GEL in piglets, no relevant impact on renal function could be found. These results confirm that AKI after HES or GEL is very unlikely in hemodynamically stable perioperative patients with normal renal function. © 2015 John Wiley & Sons Ltd.

Stress and sodium intake in neural control of renal function in hypertension.

PubMed

DiBona, G F

1991-04-01

The interaction between genetic and environmental factors is important in the pathophysiology of hypertension. By examining the effects of two environmental factors--acute psychoemotional stress and dietary sodium intake--in rats with genetic hypertension, an important influence on central neural mechanisms governing the renal sympathetic neural control of renal function has been demonstrated. Additional studies of the central opioid systems have demonstrated an important role of opioid peptides in modulating the renal functional responses to acute psychoemotional stress. The observed renal functional alterations--antidiuresis, antinatriuresis, and renal vasoconstriction--are known to be capable of contributing to the initiation, development, and maintenance of the hypertensive process.

Cytochrome P450 and Lipoxygenase Metabolites on Renal Function

PubMed Central

Imig, John D.; Hye Khan, Md. Abdul

2018-01-01

Arachidonic acid metabolites have a myriad of biological actions including effects on the kidney to alter renal hemodynamics and tubular transport processes. Cyclooxygenase metabolites are products of an arachidonic acid enzymatic pathway that has been extensively studied in regards to renal function. Two lesser-known enzymatic pathways of arachidonic acid metabolism are the lipoxygenase (LO) and cytochrome P450 (CYP) pathways. The importance of LO and CYP metabolites to renal hemodynamics and tubular transport processes is now being recognized. LO and CYP metabolites have actions to alter renal blood flow and glomerular filtration rate. Proximal and distal tubular sodium transport and fluid and electrolyte homeostasis are also significantly influenced by renal CYP and LO levels. Metabolites of the LO and CYP pathways also have renal actions that influence renal inflammation, proliferation, and apoptotic processes at vascular and epithelial cells. These renal LO and CYP pathway actions occur through generation of specific metabolites and cell-signaling mechanisms. Even though the renal physiological importance and actions for LO and CYP metabolites are readily apparent, major gaps remain in our understanding of these lipid mediators to renal function. Future studies will be needed to fill these major gaps regarding LO and CYP metabolites on renal function. PMID:26756638

Renal perfusion index reflects cardiac systolic function in chronic cardio-renal syndrome.

PubMed

Lubas, Arkadiusz; Ryczek, Robert; Kade, Grzegorz; Niemczyk, Stanisław

2015-04-17

Cardiac dysfunction can modify renal perfusion, which is crucial to maintain sufficient kidney tissue oxygenation. Renal cortex perfusion assessed by dynamic ultrasound method is related both to renal function and cardiac hemodynamics. The aim of the study was to test the hypothesis that Renal Perfusion Index (RPI) can more closely reflect cardiac hemodynamics and differentiate etiology of chronic cardio-renal syndrome. Twenty-four patients with hypertension and chronic kidney disease (CKD) at 2-4 stage (12 with hypertensive nephropathy and 12 with CKD prior to hypertension) were enrolled in the study. Blood tests, 24-h ABPM, echocardiography, and ultrasonography with estimation of Total renal Cortical Perfusion intensity and Renal Perfusion Index (RPI) were performed. In the group of all patients, RPI correlated with left ventricular stoke volume (LVSV), and cardiac index, but not with markers of renal function. In multiple stepwise regression analysis CKD-EPI(Cys-Cr) (b=-0.360), LVSV (b=0.924) and MAP (b=0.376) together independently influenced RPI (R2=0.74; p<0.0001). RPI<0.567 allowed for the identification of patients with chronic cardio-renal syndrome with sensitivity of 41.7% and specificity of 83.3%. Renal perfusion index relates more strongly to cardiac output than to renal function, and could be helpful in recognizing chronic cardio-renal syndrome. Applicability of RPI in diagnosing early abnormalities in the cardio-renal axis requires further investigation.

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.

Impact of machine perfusion after long static cold storage on delayed graft function incidence and duration and time to hospital discharge.

PubMed

Matos, Ana Cristina C; Requiao Moura, Lúcio Roberto; Borrelli, Milton; Nogueira, Mario; Clarizia, Gabriela; Ongaro, Paula; Durão, Marcelino Souza; Pacheco-Silva, Alvaro

2018-01-01

Delayed graft function (DGF) is very high in our center (70%-80%), and we usually receive a kidney for transplant after more than 22 hours of static cold ischemia time (CIT). Also, there is an inadequate care of the donors, contributing to a high rate of DGF. We decided to test whether machine perfusion (MP) after a CIT improved the outcome of our transplant patients. We analyzed the incidence of DGF, its duration, and the length of hospital stay (LOS) in patients who received a kidney preserved with MP after a CIT (hybrid perfusion-HP). We included 54 deceased donors kidneys preserved with HP transplanted from Feb/13 to Jul/14, and compared them to 101 kidney transplants preserved by static cold storage (CS) from Nov/08 to May/12. The median pumping time was 11 hours. DGF incidence was 61.1% vs 79.2% (P = .02), median DGF duration was 5 vs 11 days (P < .001), and median LOS was 13 vs 18 days (P < .011), for the HP compared to CS group. The observed reduction of DGF with machine perfusion did not occur in donors over 50 years old. In the multivariate analysis, risk factors for DGF, adjusted for CIT, were donor age (OR, 1.04; P = .005) and the absence of use of MP (OR, 1.54; P = .051). In conclusion, the use of HP contributed to faster recovery of renal function and to a shorter length of hospital stay. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nervous kidney. Interaction between renal sympathetic nerves and the renin-angiotensin system in the control of renal function.

PubMed

DiBona, G F

2000-12-01

Increases in renal sympathetic nerve activity regulate the functions of the nephron, the vasculature, and the renin-containing juxtaglomerular granular cells. Because increased activity of the renin-angiotensin system can also influence nephron and vascular function, it is important to understand the interactions between the renal sympathetic nerves and the renin-angiotensin system in the control of renal function. These interactions can be intrarenal, for example, the direct (by specific innervation) and indirect (by angiotensin II) contributions of increased renal sympathetic nerve activity to the regulation of renal function. The effects of increased renal sympathetic nerve activity on renal function are attenuated when the activity of the renin-angiotensin system is suppressed or antagonized with ACE inhibitors or angiotensin II-type AT(1)-receptor antagonists. The effects of intrarenal administration of angiotensin II are attenuated after renal denervation. These interactions can also be extrarenal, for example, in the central nervous system, wherein renal sympathetic nerve activity and its arterial baroreflex control are modulated by changes in activity of the renin-angiotensin system. In addition to the circumventricular organs, whose permeable blood-brain barrier permits interactions with circulating angiotensin II, there are interactions at sites behind the blood-brain barrier that depend on the influence of local angiotensin II. The responses to central administration of angiotensin II-type AT(1)-receptor antagonists into the ventricular system or microinjected into the rostral ventrolateral medulla are modulated by changes in activity of the renin-angiotensin system produced by physiological changes in dietary sodium intake. Similar modulation is observed in pathophysiological models wherein activity of both the renin-angiotensin and sympathetic nervous systems is increased (eg, congestive heart failure). Thus, both renal and extrarenal sites of interaction between the renin-angiotensin system and renal sympathetic nerve activity are involved in influencing the neural control of renal function.

Acetylator Status Impacts Amifampridine Phosphate (Firdapse™) Pharmacokinetics and Exposure to a Greater Extent Than Renal Function.

PubMed

Haroldsen, Peter E; Sisic, Zlatko; Datt, Joe; Musson, Donald G; Ingenito, Gary

2017-07-01

The purpose of this study is to evaluate safety, tolerability, and pharmacokinetic (PK) properties of amifampridine phosphate (Firdapse™) and its major inactive 3-N-acetyl metabolite in renally impaired and healthy individuals with slow acetylator (SA) and rapid acetylator (RA) phenotypes. This was a Phase I, multicenter, open-label study of the PK properties and safety profile of amifampridine phosphate in individuals with normal, mild, moderate, or severely impaired renal function. Amifampridine phosphate was given as a single 10 mg (base equivalent) dose, and the plasma and urine PK properties of amifampridine and its 3-N-acetyl metabolite were determined. The safety profile was evaluated by monitoring adverse events (AEs), clinical laboratory tests, and physical examinations. Amifampridine clearance was predominantly metabolic through N-acetylation, regardless of renal function in both acetylator phenotypes. In individuals with normal renal function, mean renal clearance represented approximately 3% and 18% of the total clearance of amifampridine in RA and SA, respectively. Large differences in amifampridine exposure were observed between acetylation phenotypes across renal function levels. Mean amifampridine exposure values of AUC 0-∞ and C max were up to 8.8-fold higher in the SA group compared with the RA group across renal function levels. By comparison, mean AUC 0-∞ was less affected by renal function within an acetylator group, only 2- to 3-fold higher in individuals with severe renal impairment (RI) compared with those with normal renal function. Exposure to amifampridine in the SA group with normal renal function was higher (AUC 0-∞, approximately 1.8-fold; C max, approximately 4.1-fold) than the RA group with severe RI. Exposure to the inactive 3-N-acetyl metabolite was higher than amifampridine in both acetylator groups, independent of renal function level. The metabolite is cleared by renal excretion, and exposure was clearly dependent on renal function with 4.0- to 6.8-fold increases in AUC 0-∞ from normal to severe RI. No new tolerability findings were observed. A single dose of 10 mg of amifampridine phosphate was well tolerated, independent of renal function and acetylator status. The results indicate that the PK profile of amifampridine is affected by metabolic acetylator phenotype to a greater extent than by renal function level, supporting Firdapse™ administration in individuals with RI in line with current labeling recommendations. Amifampridine should be dosed to effect per the individual patient need, altering administration frequency and dose in normal through severe RI. The therapeutic dose of amifampridine phosphate should be tailored to the individual patient needs by gradual dose titration up to the present maximum recommended dose (60-80 mg/day) or until dose-limiting AEs intervene to avoid overdosing and underdosing. EudraCT identifier: 2013-005349-35. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Relationship between histopathological changes in post partum renal biopsies and renal function tests of African women with early onset pre-eclampsia.

PubMed

Khedun, S M; Naicker, T; Moodley, J

2000-05-01

To improve the diagnostic accuracy of concurrent renal disease in hypertension of pregnancy, biopsy evaluation is essential. In addition, establishing underlying renal disease is important for prognosis on future pregnancies. We therefore designed a study to determine the diagnostic yield of postpartum renal biopsy and the nature and frequency of complications associated with this procedure. Also, to determine relationships, if any, between renal function tests and ultrastructural and histopathological findings. Fifty renal biopsies were performed in the immediate postpartum period in black African women with early onset pre-eclampsia. Each biopsy specimen was placed in a separate container and coded so that sampling was unknown to the electron microscopist. Each biopsy specimen was divided into three parts, and processed and stained for light, fluorescent and transmission electron microscopy using conventional techniques. Renal tissue biopsies were adequate for diagnostic purposes in all cases. There were no complications in any of the 50 patients studied. Ultrastructural examination confirmed the light microscopy findings. In addition the ultrastructural findings showed intramembranous deposits, foot process fusion and mesangial deposits. In 16 patients with normal renal function tests; the biopsies evaluation from these patients showed ultrastructural changes. In the remaining 34 patients with abnormal renal function tests of varying severity; biopsy evaluation from these patients showed both ultrastructural and histopathological changes. Renal biopsy procedure is safe, and ultrastructural and histological findings obtained from postpartum renal biopsies are more informative than the routine renal function tests.

The renin-angiotensin system in thyroid disorders and its role in cardiovascular and renal manifestations.

PubMed

Vargas, Félix; Rodríguez-Gómez, Isabel; Vargas-Tendero, Pablo; Jimenez, Eugenio; Montiel, Mercedes

2012-04-01

Thyroid disorders are among the most common endocrine diseases and affect virtually all physiological systems, with an especially marked impact on cardiovascular and renal systems. This review summarizes the effects of thyroid hormones on the renin-angiotensin system (RAS) and the participation of the RAS in the cardiovascular and renal manifestations of thyroid disorders. Thyroid hormones are important regulators of cardiac and renal mass, vascular function, renal sodium handling, and consequently blood pressure (BP). The RAS acts globally to control cardiovascular and renal functions, while RAS components act systemically and locally in individual organs. Various authors have implicated the systemic and local RAS in the mediation of functional and structural changes in cardiovascular and renal tissues due to abnormal thyroid hormone levels. This review analyzes the influence of thyroid hormones on RAS components and discusses the role of the RAS in BP, cardiac mass, vascular function, and renal abnormalities in thyroid disorders.

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice.

PubMed

Calvo-Rubio, Miguel; Burón, M Isabel; López-Lluch, Guillermo; Navas, Plácido; de Cabo, Rafael; Ramsey, Jon J; Villalba, José M; González-Reyes, José A

2016-06-01

Calorie restriction (CR) has been repeatedly shown to prevent cancer, diabetes, hypertension, and other age-related diseases in a wide range of animals, including non-human primates and humans. In rodents, CR also increases lifespan and is a powerful tool for studying the aging process. Recently, it has been reported in mice that dietary fat plays an important role in determining lifespan extension with 40% CR. In these conditions, animals fed lard as dietary fat showed an increased longevity compared with mice fed soybean or fish oils. In this paper, we study the effect of these dietary fats on structural and physiological parameters of kidney from mice maintained on 40% CR for 6 and 18 months. Analyses were performed using quantitative electron microcopy techniques and protein expression in Western blots. CR mitigated most of the analyzed age-related parameters in kidney, such as glomerular basement membrane thickness, mitochondrial mass in convoluted proximal tubules and autophagic markers in renal homogenates. The lard group showed improved preservation of several renal structures with aging when compared to the other CR diet groups. These results indicate that dietary fat modulates renal structure and function in CR mice and plays an essential role in the determination of health span in rodents. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Unusual clinical outcome of primary Hyperoxaluria type 1 in Tunisian patients carrying 33_34InsC mutation.

PubMed

Mbarek, Ibtihel Benhaj; Mdimeg, Saoussen; Moussa, Amira; Zellama, Dorsaf; Kaarout, Hayat; Abdelmoula, Jaouida; Achour, Abdellatif; Abroug, Saoussen; Omezzine, Asma; Bouslama, Ali

2017-06-15

Primary hyperoxaluria type 1 (PH1), is a rare and heterogeneous disease and one of major causes of renal insufficiency in Tunisia, caused by mutations in the AGXT gene. 33-34InsC mutation, was mainly described in children with a severe clinical feature leading to early death, but it was uncommonly reported in adult patients. Common mutations in AGXT were tested using PCR/RFLP technique in 111 patients (68 adult, 43 children) with suspected PH1. We described 16 cases (eight adult and eight children) with a 33-34InsC mutation with a median age of 24 years [6 months - 73 years]. All children were in end stage renal disease (ESRD) at the median age of 3 years due to lithiasis and/or nephrocalcinosis. Unfortunately, 75% of them died with a median age of 2.5 years. For the majority of adults only spontaneous elimination of urolithiasis were noted, 37.5% preserved until now a normal renal function and 62.5% of them reached ESRD at the median age of 55.8 ± 12.31 years old. In this study 33-34InsC mutation gives a controversial clinical effect in children and adults. The implication of other genetic and/or environmental factors can play a crucial role in determining the ultimate phenotype.

Changes in Renal Function and Blood Pressure in Patients with Stone Disease

NASA Astrophysics Data System (ADS)

Worcester, Elaine M.

2007-04-01

Stone disease is a rare cause of renal failure, but a history of kidney stones is associated with an increased risk for chronic kidney disease, particularly in overweight patients. Loss of renal function seems especially notable for patients with stones associated with cystinuria, hyperoxaluria, and renal tubular acidosis, in whom the renal pathology shows deposits of mineral obstructing inner medullary collecting ducts, often diffusely. However, even idiopathic calcium oxalate stone formers have a mild but significant decrease in renal function, compared to age, sex and weight-matched normals, and appear to lose renal function with age at a slightly faster rate than non-stone formers. There is also an increased incidence of hypertension among stone formers, although women are more likely to be affected than men.

Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in Japanese patients with type 2 diabetes mellitus.

PubMed

Sarashina, Akiko; Ueki, Kohjiro; Sasaki, Tomohiro; Tanaka, Yuko; Koiwai, Kazuki; Sakamoto, Wataru; Woerle, Hans J; Salsali, Afshin; Broedl, Uli C; Macha, Sreeraj

2014-11-01

The purpose of this study was to assess the effect of renal impairment on the pharmacokinetic, pharmacodynamic, and safety profiles of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in Japanese patients with type 2 diabetes mellitus (T2DM). In an open-label, parallel-group study, 32 Japanese patients with T2DM and different degrees of renal function (n = 8 per renal function category: normal renal function, estimated glomerular filtration rate [eGFR; Japanese equation] ≥90 mL/min/1.73 m(2); mild renal impairment, eGFR of 60-<90 mL/min/1.73 m(2); moderate renal impairment, eGFR of 30-<60 mL/min/1.73 m(2); and severe renal impairment, eGFR of 15-<30 mL/min/1.73 m(2)) received a single 25 mg dose of empagliflozin. Empagliflozin exposure increased with increasing renal impairment. Maximum empagliflozin plasma concentrations were similar among all renal function groups. Adjusted geometric mean ratios for extent of exposure (AUC0-∞) to empagliflozin versus normal renal function were 128.8% (95% CI, 106.0-156.6%), 143.8% (95% CI, 118.3-174.8%), and 152.3% (95% CI, 125.3-185.2%) for patients with mild, moderate, and severe renal impairment, respectively. Decreases in renal clearance of empagliflozin correlated with eGFR. Urinary glucose excretion decreased with increasing renal impairment and correlated with eGFR (adjusted mean [SE] change from baseline: 75.0 [4.84] g, 62.6 [5.75] g, 57.9 [4.86] g, and 23.7 [5.24] g for patients with normal renal function and mild, moderate, and severe renal impairment, respectively). Only 2 patients (6%) had adverse events; both were mild. Pharmacokinetic data suggest that no dose adjustment of empagliflozin is necessary in Japanese patients with T2DM and renal impairment because increases in exposure were <2-fold. Urinary glucose excretion decreased with increasing renal impairment. ClinicalTrials.gov identifier: NCT01581658. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

The rebirth of interest in renal tubular function.

PubMed

Lowenstein, Jerome; Grantham, Jared J

2016-06-01

The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate. Copyright © 2016 the American Physiological Society.

Aspects of renal function in patients with colorectal cancer in a gastroenterology clinic of a county hospital in Western Romania.

PubMed

Velciov, Silvia; Hoinoiu, B; Hoinoiu, Teodora; Popescu, Alina; Gluhovschi, Cristina; Grădinaru, Oana; Popescu, Mădalină; Moţiu, Flavia; Timar, R; Gluhovschi, G H; Sporea, I

2013-01-01

Colorectal cancer represents the third cause of cancer. Since its detection in due time is important resolution, appropriate monitoring is mandatory. The present study deals with the relationship between colorectal cancer and renal function, as well as other associated risk factors. Chronic kidney disease (CKD) represents a risk factor of cancer, both in non-dialysed patients and especially in dialysed patients and in patients with renal transplant. It can get aggravated with cancer in general and particularly with colorectal cancer, partly related to the toxins that cannot be appropriately eliminated because of renal functional disturbances. At the same time, immunosuppressive therapy used for treating glomerular or secondary nephropathies represents an important risk factor of cancer. Some patients with colorectal cancer were found to present also impaired renal function, a fact whose significance is still little known. The object of the present paper is an analysis of the case records of a clinic of gastroenterology on the relationship between colorectal cancer and renal functional impairment. We found in the patients with colorectal cancer under study a glomerular filtration rate (GFR calculated with the EPI formula) of < 60 ml/min/1.73m2 in 31/180 patients, respectively 17.22% of the cases, a value that is similar to that in specialised literature. We also analysed associated risk factors that could be related to renal function impairment in these patients: age, gender, anaemia, diabetes mellitus and hypertension. These could represent, together with the colorectal cancer of the investigated patients, risk factors affecting on the one hand renal function, and on the other hand, potentially increasing the risk of cancer. Correction of these risk factors would have beneficial effects on patients. The relationship between renal functional impairment, respectively CKD, and colorectal cancer is to be regarded from the point of view of complex reciprocity: the impairment of the renal function is a factor of risk of colorectal cancer and colorectal cancer can influence renal function of these patients. This report of reciprocity based on important pathogenic mechanisms also interrelates with factors of risk consecutive to both renal function impairment and colorectal cancer.

Selective Insulin Resistance in the Kidney

PubMed Central

Horita, Shoko; Nakamura, Motonobu; Suzuki, Masashi; Satoh, Nobuhiko; Suzuki, Atsushi; Seki, George

2016-01-01

Insulin resistance has been characterized as attenuation of insulin sensitivity at target organs and tissues, such as muscle and fat tissues and the liver. The insulin signaling cascade is divided into major pathways such as the PI3K/Akt pathway and the MAPK/MEK pathway. In insulin resistance, however, these pathways are not equally impaired. For example, in the liver, inhibition of gluconeogenesis by the insulin receptor substrate (IRS) 2 pathway is impaired, while lipogenesis by the IRS1 pathway is preserved, thus causing hyperglycemia and hyperlipidemia. It has been recently suggested that selective impairment of insulin signaling cascades in insulin resistance also occurs in the kidney. In the renal proximal tubule, insulin signaling via IRS1 is inhibited, while insulin signaling via IRS2 is preserved. Insulin signaling via IRS2 continues to stimulate sodium reabsorption in the proximal tubule and causes sodium retention, edema, and hypertension. IRS1 signaling deficiency in the proximal tubule may impair IRS1-mediated inhibition of gluconeogenesis, which could induce hyperglycemia by preserving glucose production. In the glomerulus, the impairment of IRS1 signaling deteriorates the structure and function of podocyte and endothelial cells, possibly causing diabetic nephropathy. This paper mainly describes selective insulin resistance in the kidney, focusing on the proximal tubule. PMID:27247938

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.

Assessment of renal function and electrolytes in patients with thyroid dysfunction in Addis Ababa, Ethiopia: a cross sectional study.

PubMed

Abebe, Nardos; Kebede, Tedla; Wolde, Mistire

2016-01-01

Studies demonstrated that abnormal thyroid functions may result in decreased or increased kidney size, kidney weight, and affect renal functions. In this regard, studies on the association of abnormal thyroid functions and renal function tests are scarcely found in Ethiopia. To assess renal function and electrolytes in patients with thyroid dysfunction, in Addis Ababa, Ethiopia. Cross sectional study was conducted from March 21/2015-May 27/2015 at Arsho Advanced Medical Laboratory. During the study period, 71 patients with thyroid dysfunction were eligible, and socio demographic data collected by structured questionnaire. Then blood sample was collected for thyroid function tests, renal function and blood electrolyte analysis. The collected data was analyzed by SPSS version 20. ANOVA and binary logistic regression were employed to evaluate the mean deference and associations of thyroid hormone with renal function and electrolyte balances. Among the renal function tests, serum uric acid, and creatinine mean values were significantly decreased in hyperthyroid patients; whereas, eGFR mean value was significantly increased in hyperthyroid study patients (P<0.05). Meanwhile, from the electrolyte measurements made, only the mean serum sodium value was significantly increased in hyperthyroid study participants. Binary logistic regression analysis on the association of thyroid dysfunction with electrolyte balance and renal function tests indicated that serum sodium, creatinine, eGFR values and hyperthyroidism have a statistical significant association at AOR 95% CI of 0.141(0.033-0.593, P=0.008); 16.236(3.481-75.739, P=0.001), and 13.797(3.261-58.67, P=0.001) respectively. The current study reveals, thyroid abnormalities may lead to renal function alterations and also may disturb electrolyte balance. Knowledge of this significant association has worthwhile value for clinicians, to manage their patients' optimally.

Worsening renal function and outcome in heart failure patients with reduced and preserved ejection fraction and the impact of angiotensin receptor blocker treatment: data from the CHARM-study programme.

PubMed

Damman, Kevin; Solomon, Scott D; Pfeffer, Marc A; Swedberg, Karl; Yusuf, Salim; Young, James B; Rouleau, Jean L; Granger, Christopher B; McMurray, John J V

2016-12-01

We investigated the association between worsening renal function (WRF) that occurs during renin-angiotensin-aldosterone system inhibition initation and outcome in heart failure (HF) patients with preserved ejection fraction (HFPEF) and compared this with HF patients with reduced ejection fraction (HFREF). We examined changes in estimated glomerular filtration rate (GFR) and the relationship between WRF (defined as ≥26.5 µmol/L and ≥25% increase in serum creatinine from baseline to 6 weeks) and outcome, according to randomized treatment, in patients with HFREF (EF <45%; n = 1569) and HFPEF (EF ≥45%; n = 836) in the CHARM programme. The primary outcome was cardiovascular death or HF hospitalization. Estimated GFR decreased 9.0 ± 21 vs. 4.0 ± 21 mL/min/1.73 m 2 with candesartan and placebo, respectively, and this was similar in HFREF and HFPEF. WRF developed more frequently with candesartan, 16% vs. 7%, P < 0.001, with similar findings in patients with HFREF and HFPEF. WRF was associated with a higher risk of the primary outcome: multivariable hazard ratio (HR) 1.26, 95% confidence interval 1.03-1.54, P = 0.022, in both treatment groups, and in both HFREF and HFPEF (P for interaction 0.98). In HFREF, WRF was mostly related to HF hospitalization, while in HFPEF, WRF seemed more associated with mortality. GFR decreased more and WRF was more common with candesartan compared with placebo, and this was similar in HFREF and HFPEF. WRF was associated with worse outcomes in HFREF and HFPEF. Although no formal interaction was present, the association between candesartan treatment, WRF, and type of clinical outcome was slightly different between HFREF and HFPEF. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Reduction of severe mitral regurgitation with the MitraClip system improves renal function in two patients presenting with acute kidney injury and progressive renal failure due to cardio renal syndrome.

PubMed

Asdonk, T; Nickenig, G; Hammerstingl, C

2014-10-01

Mitral regurgitation (MR) is a frequent valve disorder in elderly patients, often accompanied by multiple comorbidities such as renal impairment. In these patients percutaneous mitral valve (MV) repair has become an established treatment option but the role of MR on renal dysfunction is not yet well defined. We here report on two cases presenting with severe MR and progressive renal failure caused by cardio renal syndrome, in which percutaneous MV treatment with the MitraClip system significantly improved renal function. These findings suggest that interventional MV repair can prevent progression of renal deterioration in patients suffering from combined advanced heart and renal failure. Further clinical studies are necessary to support our finding and to answer the question whether optimizing renal function by implantation of the MitraClip device is also of prognostic relevance in these patients. © 2014 Wiley Periodicals, Inc.

Quantitative analysis of the renal aging in rats. Stereological study.

PubMed

Melchioretto, Eduardo Felippe; Zeni, Marcelo; Veronez, Djanira Aparecida da Luz; Martins, Eduardo Lopes; Fraga, Rogério de

2016-05-01

To evaluate the renal function and the renal histological alterations through the stereology and morphometrics in rats submitted to the natural process of aging. Seventy two Wistar rats, divided in six groups. Each group was sacrificed in a different age: 3, 6, 9, 12, 18 and 24 months. It was performed right nephrectomy, stereological and morphometric analysis of the renal tissue (renal volume and weight, density of volume (Vv[glom]) and numerical density (Nv[glom]) of the renal glomeruli and average glomerular volume (Vol[glom])) and also it was evaluated the renal function for the dosage of serum creatinine and urea. There was significant decrease of the renal function in the oldest rats. The renal volume presented gradual increase during the development of the rats with the biggest values registered in the group of animals at 12 months of age and significant progressive decrease in older animals. Vv[glom] presented statistically significant gradual reduction between the groups and the Nv[glom] also decreased significantly. The renal function proved to be inferior in senile rats when compared to the young rats. The morphometric and stereological analysis evidenced renal atrophy, gradual reduction of the volume density and numerical density of the renal glomeruli associated to the aging process.

Effects of renal function on pharmacokinetics and pharmacodynamics of lesinurad in adult volunteers.

PubMed

Gillen, Michael; Valdez, Shakti; Zhou, Dongmei; Kerr, Bradley; Lee, Caroline A; Shen, Zancong

2016-01-01

Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI) in patients who have not achieved target serum uric acid (sUA) levels with an XOI alone. Most people with gout have chronic kidney disease. The pharmacokinetics, pharmacodynamics, and safety of lesinurad were assessed in subjects with impaired renal function. Two Phase I, multicenter, open-label, single-dose studies enrolled subjects with normal renal function (estimated creatinine clearance [eCrCl] >90 mL/min; N=12) or mild (eCrCl 60-89 mL/min; N=8), moderate (eCrCl 30-59 mL/min; N=16), or severe (eCrCl <30 mL/min; N=6) renal impairment. Subjects were given a single oral lesinurad dose of 200 mg (N=24) or 400 mg (N=18). Blood and urine samples were analyzed for plasma lesinurad concentrations and serum and urine uric acid concentrations. Safety was assessed by adverse events and laboratory data. Mild, moderate, and severe renal impairment increased lesinurad plasma area under the plasma concentration-time curve by 34%, 54%-65%, and 102%, respectively. Lesinurad plasma C max was unaffected by renal function status. Lower renal clearance and urinary excretion of lesinurad were associated with the degree of renal impairment. The sUA-lowering effect of a single dose of lesinurad was similar between mild renal impairment and normal function, reduced in moderate impairment, and greatly diminished in severe impairment. Lesinurad increased urinary urate excretion in normal function and mild renal impairment; the increase was less with moderate or severe renal impairment. Lesinurad was well tolerated by all subjects. Lesinurad exposure increased with decreasing renal function; however, the effects of lesinurad on sUA were attenuated in moderate to severe renal impairment.

Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease.

PubMed

Zhao, Juanjuan; Lupino, Katherine; Wilkins, Benjamin J; Qiu, Chengxiang; Liu, Jian; Omura, Yasuhiro; Allred, Amanda L; McDonald, Caitlin; Susztak, Katalin; Barish, Grant D; Pei, Liming

2018-05-22

Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.

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.

Histamine H4 receptor antagonism prevents the progression of diabetic nephropathy in male DBA2/J mice.

PubMed

Pini, Alessandro; Grange, Cristina; Veglia, Eleonora; Argenziano, Monica; Cavalli, Roberta; Guasti, Daniele; Calosi, Laura; Ghè, Corrado; Solarino, Roberto; Thurmond, Robin L; Camussi, Giovanni; Chazot, Paul L; Rosa, Arianna Carolina

2018-02-01

Due to the incidence of diabetes and the related morbidity of diabetic nephropathy, identification of new therapeutic strategies represents a priority. In the last few decades new and growing evidence on the possible role of histamine in diabetes has been provided. In particular, the histamine receptor H 4 R is emerging as a new promising pharmacological target for diabetic nephropathy. The aim of this study was to evaluate the efficacy of selective H 4 R antagonism by JNJ39758979 on the prevention of diabetic nephropathy progression in a murine model of diabetes induced by streptozotocin injection. JNJ39758979 (25, 50, 100 mg/kg/day p.o.) was administered for 15 weeks starting from the onset of diabetes. Functional parameters were monitored throughout the experimental period. JNJ39758979 did not significantly affect glycaemic status or body weight. The urine analysis indicated a dose-dependent inhibitory effect of JNJ39758979 on Albumin-Creatinine-Ratio, the Creatinine Clearance, the 24 h urine volume, and pH urine acidification (P < 0.05). The beneficial effects of JNJ39758979 on renal function paralleled comparable effects on renal morphological integrity. These effects were sustained by a significant immune infiltration and fibrosis reduction. Notably, megalin and sodium-hydrogen-exchanger 3 expression levels were preserved. Our data suggest that the H 4 R participates in diabetic nephropathy progression through both a direct effect on tubular reabsorption and an indirect action on renal tissue architecture via inflammatory cell recruitment. Therefore, H 4 R antagonism emerges as a possible new multi-mechanism therapeutic approach to counteract development of diabetic nephropathy development. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neural regulation of the kidney function in rats with cisplatin induced renal failure

PubMed Central

Goulding, Niamh E.; Johns, Edward J.

2015-01-01

Aim: Chronic kidney disease (CKD) is often associated with a disturbed cardiovascular homeostasis. This investigation explored the role of the renal innervation in mediating deranged baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory function in cisplatin-induced renal failure. Methods: Rats were either intact or bilaterally renally denervated 4 days prior to receiving cisplatin (5 mg/kg i.p.) and entered a chronic metabolic study for 8 days. At day 8, other groups of rats were prepared for acute measurement of RSNA or renal function with either intact or denervated kidneys. Results: Following the cisplatin challenge, creatinine clearance was 50% lower while fractional sodium excretion and renal cortical and medullary TGF-β1 concentrations were 3–4 fold higher in both intact and renally denervated rats compared to control rats. In cisplatin-treated rats, the maximal gain of the high-pressure baroreflex curve was only 20% that of control rats, but following renal denervation not different from that of renally denervated control rats. Volume expansion reduced RSNA by 50% in control and in cisplatin-treated rats but only following bilateral renal denervation. The volume expansion mediated natriuresis/diuresis was absent in the cisplatin-treated rats but was normalized following renal denervation. Conclusions: Cisplatin-induced renal injury impaired renal function and caused a sympatho-excitation with blunting of high and low pressure baroreflex regulation of RSNA, which was dependent on the renal innervation. It is suggested that in man with CKD there is a dysregulation of the neural control of the kidney mediated by its sensory innervation. PMID:26175693

Availability of information on renal function in Dutch community pharmacies.

PubMed

Koster, Ellen S; Philbert, Daphne; Noordam, Michelle; Winters, Nina A; Blom, Lyda; Bouvy, Marcel L

2016-08-01

Background Early detection and monitoring of impaired renal function may prevent drug related problems. Objective To assess the availability of information on patient's renal function in Dutch community pharmacies, for patients using medication that might need monitoring in case of renal impairment. Methods Per pharmacy, 25 patients aged ≥65 years using at least one drug that requires monitoring, were randomly selected from the pharmacy information system. For these patients, information on renal function [estimated glomerular filtration rate (eGFR)], was obtained from the pharmacy information system. When absent, this information was obtained from the general practitioner (GP). Results Data were collected for 1632 patients. For 1201 patients (74 %) eGFR values were not directly available in the pharmacy, for another 194 patients (12 %) the eGFR value was not up-to-date. For 1082 patients information could be obtained from the GP, resulting in 942 additional recent eGFR values. Finally, recent information on renal function was available for 72 % (n = 1179) of selected patients. Conclusion In patients using drugs that require renal monitoring, information on renal function is often unknown in the pharmacy. For the majority of patients this information can be retrieved from the GP.

HOGA1 Gene Mutations of Primary Hyperoxaluria Type 3 in Tunisian Patients.

PubMed

M'dimegh, Saoussen; Aquaviva-Bourdain, Cécile; Omezzine, Asma; Souche, Geneviéve; M'barek, Ibtihel; Abidi, Kamel; Gargah, Tahar; Abroug, Saoussen; Bouslama, Ali

2017-05-01

Primary hyperoxaluria type 3 (PH3) is due to mutations in the recently identified 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene. PH3 might be the least severe form with a milder phenotype with good preservation of kidney function in most patients. The aim of this study was to report three PH3 cases carrying mutations in HOGA1. Genetic analysis of HOGA1 was performed in patients with a high clinical suspicion of PH after sequencing of AGXT and GRHPR genes, which was negative. Also, a complete AGXT/GRHPR MLPA was performed in these patients in order to detect large deletions/insertions. Two different HOGA1 gene mutations were identified: the p.Pro190Leu in a homozygous state and the p.Gly287Val in two patients in homozygous and heterozygous carriers. The median age at onset of clinical symptoms was 3.93 years. Most of the patients had a positive family history for recurrent urolithiasis. The p.Pro190Leu mutation was reported with impaired renal function at follow-up; however, the p.Gly287Val was presented with normal renal function. All patients were presented with urolithiasis, but only one had a nephrocalcinosis. This study expanded the number of PH3 patients from 63 to 66 cases. The p.Pro190Leu and the p.Gly287Val mutations found in this study can provide a first-line investigation in Tunisian PH1 patients. © 2016 Wiley Periodicals, Inc.

Carotid artery wall shear stress is independently correlated with renal function in the elderly.

PubMed

Guo, Yuqi; Wei, Fang; Wang, Juan; Zhao, Yingxin; Sun, Shangwen; Zhang, Hua; Liu, Zhendong

2018-01-12

Hemodynamic has increasingly been regarded as an important factor of renal function. However, the relationship between carotid artery wall shear stress (WSS) and renal function is not clarified. To investigate the relationship between carotid WSS and renal function, we recruited 761 older subjects aged 60 years and over from community-dwelling in the Shandong area, China. Carotid WSS, endothelial function, and estimated glomerular filtration rate (eGFR) were assessed in all subjects. Subjects were grouped by the interquartile of the carotid artery mean WSS. We found that the eGFRs derived from serum creatinine and/or cystatin C using three CKD-EPI equations were significantly higher and albumin/creatinine ratio was lower in the higher interquartile groups than in the lower interquartile groups ( P <0.05). The mean WSS was independently correlated with eGFRs even after adjustment for confounders. Similar findings were found between carotid artery peak WSS and eGFRs and albumin/creatinine ratio. In addition, we found that endothelial function was strongly related to carotid WSS and renal function after adjustment for confounders. In conclusion, there is an independent correlation of carotid WSS with renal function in the elderly. The local rheologic forces may play an important role in renal function changing. The correlation may be mediated by regulation of endothelial function.

Combination therapy of exendin-4 and allogenic adipose-derived mesenchymal stem cell preserved renal function in a chronic kidney disease and sepsis syndrome setting in rats

PubMed Central

Chen, Chih-Hung; Cheng, Ben-Chung; Chen, Kuan-Hung; Shao, Pei-Lin; Sung, Pei-Hsun; Chiang, Hsin-Ju; Yang, Chih-Chao; Lin, Kun-Chen; Sun, Cheuk-Kwan; Sheu, Jiunn-Jye; Chang, Hsueh-Wen; Lee, Mel S.; Yip, Hon-Kan

2017-01-01

Combined therapy with exendin-4 (Ex4) and allogenic adipose-derived mesenchymal stem cells (ADMSC) was tested against either therapy alone for protecting kidney function against chronic kidney disease (CKD) complicated by sepsis syndrome (SS) [i.e., by intraperitoneal injection of cecal-derived bacteria (1.0 × 104) cells/milliliter/total 5.0 cc].Adult-male-Sprague Dawley rats (n=36) were equally divided into group 1 (sham-control), group 2 (CKD), group 3 (CKD-SS), group 4 (CKD-SS-Ex4), group 5 (CKD-SS-ADMSC) and group 6 (CKD-SS-Ex4-ADMSC). At day 42 after CKD induction SS was induced. Thirty-minutes after SS induction, ADMSCs (2.0 ×106 cells) were intravenously administered to groups 5 and 6. Ex4 (10 μg/kg) was intraperitoneally administered groups 4 and 6 at 30 min and days 1 to 5 after SS induction. Animals were euthanized at day 47 after CKD induction. Kidney-injury score, collagen-deposition area, and creatinine/BUN levels were lowest in group 1, highest in group 3 and significantly higher in group 2 than in groups 4 to 6 in a progressively increasing manner (all P<0.0001). Protein expressions of inflammatory (MMP-9/TNF-α/NF-κB/IL-1ß/ICAM-1), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (mitochondrial-Bax/cleaved-caspase-3/cleaved-PARP) and fibrotic/DNA-damaged (Smad3/TGF-ß/γ-H2AX) biomarkers showed an identical pattern, whereas anti-fibrotic (BMP-2/Smad1/5), anti-apoptotic/endothelial-integrity (Bcl-2/eNOS) and podocyte-integrity (ZO-1/p-cadherin) biomarkers exhibited an opposite pattern of kidney-injury score among the six groups (all P>0.0001). Cellular expressions of inflammatory (CD14/CD68) and glomerulus/tubular-injury (WT-1/KIM-1) biomarkers displayed an identical pattern, whereas glomerulus/podocyte-component (dystroglycan/nephrin/ZO-1/fibronectin/p-cadherin) biomarkers showed an opposite kidney-injury score among the six groups (all P<0.0001). In conclusion, Ex4-ADMSC therapy effectively preserved renal function in the CKD-SS setting. PMID:29245956

Impact of Sofosbuvir-Based Regimens for the Treatment of Hepatitis C After Liver Transplant on Renal Function: Results of a Canadian National Retrospective Study.

PubMed

Faisal, Nabiha; Bilodeau, Marc; Aljudaibi, Bandar; Hirch, Geri; Yoshida, Eric M; Hussaini, Trana; Ghali, Maged P; Congly, Stephen E; Ma, Mang M; Lilly, Leslie B

2018-04-04

We assessed the impact of sofosbuvir-based regimens on renal function in liver transplant recipients with recurrent hepatitis C virus and the role of renal function on the efficacy and safety of these regimens. In an expanded pan-Canadian cohort, 180 liver transplant recipients were treated with sofosbuvir-based regimens for hepatitis C virus recurrence from January 2014 to May 2015. Mean age was 58 ± 6.85 years, and 50% had F3/4 fibrosis. Patients were stratified into 4 groups based on baseline estimated glomerular filtration rate (calculated by the Modification of Diet in Renal Disease formula): < 30, 30 to 45, 46 to 60, and > 60 mL/min/173 m2. The primary outcome was posttreatment changes in renal function from baseline. Secondary outcomes included sustained virologic response at 12 weeks posttreatment and anemia-related and serious adverse events. Posttreatment renal function was improved in most patients (58%). Renal function declined in 22% of patients, which was more marked in those with estimated glomerular filtration rate < 30 mL/min/173 m2, advanced cirrhosis (P = .05), and aggressive hepatitis C virus/fibrosing cholestatic hepatitis (P < .05). High rates (80%-88%) of sustained virologic response at 12 weeks posttreatment were seen across all renal function strata. Cirrhotic patients with glomerular filtration rates < 30 mL/min/173 m2 had sustained virologic response rates at 12 weeks posttreatment comparable to the overall patient group. Rates of anemia-related adverse events and transfusion requirements increased across decreasing estimated glomerular filtration rate groups, with notably more occurrences with ribavirin-based regimens. Sofosbuvir-based regimens improved overall renal function in liver transplant recipients, with sustained virologic response, suggesting an association of subclinical hepatitis C virus-related renal disease. Sustained virologic response rates at 12 weeks posttreatment (80%-88%) were comparable regardless of baseline renal function but lower in cirrhosis.

[Liver transplantation preserving the vena cava and a temporary portocaval shunt].

PubMed

Hesse, U J; Berrevoet, F; Troisi, R; Mortier, E; Decruyenaere, J; Pattyn, P; de Hemptinne, B

1999-02-01

The experience with laterolateral cavocavostomy for hepatovenous reconstruction in liver transplantation is reviewed with and without the use of a temporary portocaval shunt. A total of 65 liver transplantations were analyzed. In 49 transplantations a laterolateral cavocaval anastomosis was performed (group I). In group II (n = 16) the same technique was used after a temporary portal caval shunt was constructed. Mean arterial pressure (mmHg): group I 128 +/- 34; group II 109 +/- 32. Cardiac output (l/min) decrease during the anhepatic phase was 2.3 +/- 1.9 and 1.2 +/- 1.5, respectively (P < 0.05). The peroperative blood loss measured as the number of packed cells transfused was 16.4 +/- 15.8 versus 1.2 +/- 2.3 (P < 0.04) and fresh frozen plasma 19.0 +/- 14.7 versus 3.7 +/- 4.0 (P < 0.02). Course on ICU (days), liver function tests, renal function and the need for reoperation because of bleeding were not statistically significantly different between the groups. One-year patient survival was 82.7 and 85.7%, respectively. In conclusion, we found that despite preservation of the caval flow during hepatectomy, the additional use of a temporary portocaval shunt was advantageous with regard to peroperative hemorrhage and hemodynamic stability and can potentially facilitate implantation of the liver graft.

Association of serum bicarbonate with risk of renal and cardiovascular outcomes in CKD: a report from the Chronic Renal Insufficiency Cohort (CRIC) study.

PubMed

Dobre, Mirela; Yang, Wei; Chen, Jing; Drawz, Paul; Hamm, L Lee; Horwitz, Edward; Hostetter, Thomas; Jaar, Bernard; Lora, Claudia M; Nessel, Lisa; Ojo, Akinlolu; Scialla, Julia; Steigerwalt, Susan; Teal, Valerie; Wolf, Myles; Rahman, Mahboob

2013-10-01

The purpose of this study is to evaluate serum bicarbonate level as a risk factor for renal outcomes, cardiovascular events, and mortality in patients with chronic kidney disease (CKD). Observational cohort study. 3,939 participants with CKD stages 2-4 who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 and December 2008. Serum bicarbonate level. Renal outcomes, defined as end-stage renal disease (either initiation of dialysis therapy or kidney transplantation) or 50% reduction in estimated glomerular filtration rate (eGFR); atherosclerotic events (myocardial infarction, stroke, or peripheral arterial disease); congestive heart failure events; and death. Time to event. Mean eGFR was 44.8 ± 16.8 (SD) mL/min/1.73 m(2), and median serum bicarbonate level was 24 (IQR, 22-26) mEq/L. During a median follow-up of 3.9 years, 374 participants died, 767 had a renal outcome, 332 experienced an atherosclerotic event, and 391 had a congestive heart failure event. In adjusted analyses, the risk of developing a renal end point was 3% lower per 1-mEq/L increase in serum bicarbonate level (HR, 0.97; 95% CI, 0.94-0.99; P = 0.01). The association was stronger for participants with eGFR >45 mL/min/1.73 m(2) (HR, 0.91; 95% CI, 0.85-0.97; P = 0.004). The risk of heart failure increased by 14% (HR, 1.14; 95% CI, 1.03-1.26; P = 0.02) per 1-mEq/L increase in serum bicarbonate level over 24 mEq/L. Serum bicarbonate level was not associated independently with atherosclerotic events (HR, 0.99; 95% CI, 0.95-1.03; P = 0.6) and all-cause mortality (HR, 0.98; 95% CI, 0.95-1.02; P = 0.3). Single measurement of sodium bicarbonate. In a cohort of participants with CKD, low serum bicarbonate level was an independent risk factor for kidney disease progression, particularly for participants with preserved kidney function. The risk of heart failure was higher at the upper extreme of serum bicarbonate levels. There was no association between serum bicarbonate level and all-cause mortality or atherosclerotic events. Copyright © 2013 National Kidney Foundation, Inc. All rights reserved.

Association of Serum Bicarbonate With Risk of Renal and Cardiovascular Outcomes in CKD: A Report From the Chronic Renal Insufficiency Cohort (CRIC) Study

PubMed Central

Dobre, Mirela; Yang, Wei; Chen, Jing; Drawz, Paul; Hamm, L. Lee; Horwitz, Edward; Hostetter, Thomas; Jaar, Bernard; Lora, Claudia M; Nessel, Lisa; Ojo, Akinlolu; Scialla, Julia; Steigerwalt, Susan; Teal, Valerie; Wolf, Myles; Rahman, Mahboob

2013-01-01

Background The purpose of this study is to evaluate serum bicarbonate as a risk factor for renal outcomes, cardiovascular events and mortality in patients with chronic kidney disease (CKD). Study Design Observational cohort study. Setting & Participants 3939 participants with CKD stages 2-4 who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 - December 2008. Predictor Serum bicarbonate. Outcomes Renal outcomes, defined as end-stage renal disease (either initiation of dialysis or kidney transplantation) or 50% reduction in eGFR; atherosclerotic events (myocardial infarction, stroke, peripheral arterial disease); congestive heart failure events; and death. Measurements Time to event. Results The mean eGFR was 44.8 ± 16.8 (SD) mL/min/1.73 m2, and the median serum bicarbonate was 24 (IQR, 22-26) mEq/L. During a median follow-up of 3.9 years, 374 participants died, 767 had a renal outcome, and 332 experienced an atherosclerotic event and 391 had a congestive heart failure event. In adjusted analyses, the risk of developing a renal endpoint was 3% lower per mEq/L increase in serum bicarbonate (HR, 0.97; 95% CI, 0.94-0.99; p=0.01). The association was stronger for participants with eGFR> 45ml/min/1.73m2 (HR, 0.91; 95%CI, 0.85-0.97; p=0.004). The risk of heart failure increased by 14% (HR, 1.14; 95%CI, 1.03-1.26; p=0.02) per mEq/L increase in serum bicarbonate over 24 mEq/L. Serum bicarbonate was not independently associated with atherosclerotic events (HR, 0.99; 95%CI, 0.95-1.03; p=0.6) and all-cause mortality (HR, 0.98; 95%CI, 0.95-1.02; p=0.3). Limitations Single measurement of sodium bicarbonate. Conclusions In a cohort of participants with CKD, low serum bicarbonate was an independent risk factor for kidney disease progression, particularly for participants with preserved kidney function. The risk of heart failure was higher at the upper extreme of serum bicarbonate. There was no association between serum bicarbonate and all-cause mortality or atherosclerotic events. PMID:23489677

Influence of percutaneous mitral valve repair using the MitraClip® system on renal function in patients with severe mitral regurgitation.

PubMed

Rassaf, Tienush; Balzer, Jan; Rammos, Christos; Zeus, Tobias; Hellhammer, Katharina; v Hall, Silke; Wagstaff, Rabea; Kelm, Malte

2015-04-01

In patients with mitral regurgitation (MR), changes in cardiac stroke volume, and thus renal preload and afterload may affect kidney function. Percutaneous mitral valve repair (PMVR) with the MitraClip® system can be a therapeutic alternative to surgical valve repair. The influence of MitraClip® therapy on renal function and clinical outcome parameters is unknown. Sixty patients with severe MR underwent PMVR using the MitraClip® system in an open-label observational study. Patients were stratified according to their renal function. All clips have been implanted successfully. Effective reduction of MR by 2-3 grades acutely improved KDOQI class. Lesser MR reduction (MR reduction of 0-1 grades) led to worsening of renal function in patients with pre-existing normal or mild (KDOQI 1-2) compared to severe (KDOQI 3-4) renal dysfunction. Reduction of MR was associated with improvement in Minnesota Living with Heart Failure Questionnaire (MLHFQ), NYHA-stadium, and 6-minute walk test. Successful PMVR was associated with an improvement in renal function. The improvement in renal function was associated with the extent of MR reduction and pre-existing kidney dysfunction. Our data emphasize the relevance of PVMR to stabilize the cardiorenal axis in patients with severe MR. © 2014 Wiley Periodicals, Inc.

Functional Renal Imaging with 2-Deoxy-2-18F-Fluorosorbitol PET in Rat Models of Renal Disorders.

PubMed

Werner, Rudolf A; Wakabayashi, Hiroshi; Chen, Xinyu; Hirano, Mitsuru; Shinaji, Tetsuya; Lapa, Constantin; Rowe, Steven P; Javadi, Mehrbod S; Higuchi, Takahiro

2018-05-01

Precise regional quantitative assessment of renal function is limited with conventional 99m Tc-labeled renal radiotracers. A recent study reported that the PET radiotracer 2-deoxy-2- 18 F-fluorosorbitol ( 18 F-FDS) has ideal pharmacokinetics for functional renal imaging. Furthermore, 18 F-FDS is available via simple reduction from routinely used 18 F-FDG. We aimed to further investigate the potential of 18 F-FDS PET as a functional renal imaging agent using rat models of kidney disease. Methods: Two different rat models of renal impairment were investigated: induction of acute renal failure by intramuscular administration of glycerol in the hind legs, and induction of unilateral ureteral obstruction by ligation of the left ureter. At 24 h after these procedures, dynamic 30-min 18 F-FDS PET data were acquired using a dedicated small-animal PET system. Urine 18 F-FDS radioactivity 30 min after radiotracer injection was measured together with coinjected 99m Tc-diethylenetriaminepentaacetic acid urine activity. Results: Dynamic PET imaging demonstrated rapid 18 F-FDS accumulation in the renal cortex and rapid radiotracer excretion via the kidneys in healthy control rats. On the other hand, significantly delayed renal radiotracer uptake (continuous slow uptake) was observed in acute renal failure rats and unilateral ureteral obstruction kidneys. Measured urine radiotracer concentrations of 18 F-FDS and 99m Tc-diethylenetriaminepentaacetic acid correlated well with each other ( R = 0.84, P < 0.05). Conclusion: 18 F-FDS PET demonstrated favorable kinetics for functional renal imaging in rat models of kidney diseases. 18 F-FDS PET imaging, with its advantages of high spatiotemporal resolution and simple tracer production, could potentially complement or replace conventional renal scintigraphy in select cases and significantly improve the diagnostic performance of renal functional imaging. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Safety, Tolerability, and Pharmacokinetics of Ribavirin in Hepatitis C Virus-Infected Patients with Various Degrees of Renal Impairment

PubMed Central

Wang, K.; Blotner, S.; Magnusson, M. O.; Wilkins, J. J.; Martin, P.; Solsky, J.; Nieforth, K.; Wat, C.; Grippo, J. F.

2013-01-01

Ribavirin (RBV) is an integral part of standard-of-care hepatitis C virus (HCV) treatments and many future regimens under investigation. The pharmacokinetics (PK), safety, and tolerability of RBV in chronically HCV-infected patients with renal impairment are not well defined and were the focus of an open-label PK study in HCV-infected patients receiving RBV plus pegylated interferon. Serial RBV plasma samples were collected over 12 h on day 1 of weeks 1 and 12 from patients with moderate renal impairment (creatinine clearance [CLCR], 30 to 50 ml/min; RBV, 600 mg daily), severe renal impairment (CLCR, <30 ml/min; RBV, 400 mg daily), end-stage renal disease (ESRD) (RBV, 200 mg daily), or normal renal function (CLCR, >80 ml/min; RBV, 800 to 1,200 mg daily). Of the 44 patients, 9 had moderately impaired renal function, 10 had severely impaired renal function, 13 had ESRD, and 12 had normal renal function. The RBV dose was reduced because of adverse events (AEs) in 71% and 53% of severe and moderate renal impairment groups, respectively. Despite this modification, patients with moderate and severe impairment had 12-hour (area under the concentration-time curve from 0 to 12 h [AUC0–12]) values 36% (38,452 ng · h/ml) and 25% (35,101 ng · h/ml) higher, respectively, than those with normal renal function (28,192 ng · h/ml). Patients with ESRD tolerated a 200-mg daily dose, and AUC0–12 was 20% lower (22,629 ng · h/ml) than in patients with normal renal function. PK modeling and simulation (M&S) indicated that doses of 200 mg or 400 mg alternating daily for patients with moderate renal impairment and 200 mg daily for patients with severe renal impairment were the most appropriate dose regimens in these patients. PMID:24080649

Determination of split renal function using dynamic CT-angiography: preliminary results.

PubMed

Helck, Andreas; Schönermarck, Ulf; Habicht, Antje; Notohamiprodjo, Mike; Stangl, Manfred; Klotz, Ernst; Nikolaou, Konstantin; la Fougère, Christian; Clevert, Dirk Andrè; Reiser, Maximilian; Becker, Christoph

2014-01-01

To determine the feasibility of a dynamic CT angiography-protocol with regard to simultaneous assessment of renal anatomy and function. 7 healthy potential kidney donors (58 ± 7 years) underwent a dynamic computed tomography angiography (CTA) using a 128-slice CT-scanner with continuous bi-directional table movement, allowing the coverage of a scan range of 18 cm within 1.75 sec. Twelve scans of the kidneys (n = 14) were acquired every 3.5 seconds with the aim to simultaneously obtain CTA and renal function data. Image quality was assessed quantitatively (HU-measurements) and qualitatively (grade 1-4, 1 = best). The glomerular filtration rate (GFR) was calculated by a modified Patlak method and compared with the split renal function obtained with renal scintigraphy. Mean maximum attenuation was 464 ± 58 HU, 435 ± 48 HU and 277 ± 29 HU in the aorta, renal arteries, and renal veins, respectively. The abdominal aorta and all renal vessels were depicted excellently (grade 1.0). The image quality score for cortex differentiation was 1.6 ± 0.49, for the renal parenchyma 2.4 ± 0.49. GFR obtained from dynamic CTA correlated well with renal scintigraphy with a correlation coefficient of r = 0.84; P = 0.0002 (n = 14). The average absolute deviation was 1.6 mL/min. The average effective dose was 8.96 mSv. Comprehensive assessment of renal anatomy and function is feasible using a single dynamic CT angiography examination. The proposed protocol may help to improve management in case of asymmetric kidney function as well as to simplify evaluation of potential living kidney donors.

Important risk factors of allograft survival in cadaveric renal transplantation. A study of 426 patients.

PubMed Central

Diethelm, A G; Blackstone, E H; Naftel, D C; Hudson, S L; Barber, W H; Deierhoi, M H; Barger, B O; Curtis, J J; Luke, R G

1988-01-01

Multiple risk factors contribute to the allograft survival of patients who have cadaveric renal transplantation. A retrospective review of 19 such factors in 426 patients identified race, DR match, B + DR match, number of transplants, and preservation time to have a significant influence. The parametric analysis confirmed the effect to be primarily in the early phase, i.e., first 6 months. All patients received cyclosporine with other methods of immunosuppression resulting in an overall 1-year graft survival rate of 66%. The overall 1-year graft survival rate in the white race was 73% and in the black race was 57% (p = 0.002). Allograft survival and DR match showed white recipients with a 1 DR match to have 75% survival at 1 year compared with 57% in the black patient (p = 0.009). If HLA B + DR match was considered, the white recipient allograft survival increased to 76%, 84%, and 88% for 1, 2, and 3 match kidneys by parametric analysis. Patients receiving first grafts had better graft survival (68%) than those undergoing retransplantation (58%) (p = 0.05). Organ preservation less than 12 hours influenced allograft survival with a 78% 1-year survival rate compared with 63% for kidneys with 12-18 hours of preservation. Despite the benefits of B + DR typing, short preservation time, and first transplants to the white recipient, the allograft survival in the black recipient remained uninfluenced by these parameters. PMID:3288138

Why, when and how should immunosuppressive therapy considered in patients with immunoglobulin A nephropathy?

PubMed Central

Rasche, F. M.; Rasche, W. G.; Schiekofer, S.; Boldt, A.; Sack, U.; Fahnert, J.

2016-01-01

Summary IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Lifelong mesangial deposition of IgA1 complexes subsist inflammation and nephron loss, but the complex pathogenesis in detail remains unclear. In regard to the heterogeneous course, classical immunosuppressive and specific therapeutic regimens adapted to the loss of renal function will here be discussed in addition to the essential common renal supportive therapy. Renal supportive therapy alleviates secondary, surrogate effects or sequelae on renal function and proteinuria of high intraglomerular pressure and subsequent nephrosclerosis by inhibition of the renin angiotensin system (RAASB). In patients with physiological (ΔGFR < 1·5 ml/min/year) or mild (ΔGFR 1·5–5 ml/min/year) decrease of renal function and proteinuric forms (> 1 g/day after RAASB), corticosteroids have shown a reduction of proteinuria and might protect further loss of renal function. In patients with progressive loss of renal function (ΔGFR > 3 ml/min within 3 months) or a rapidly progressive course with or without crescents in renal biopsy, cyclophosphamide with high‐dose corticosteroids as induction therapy and azathioprine maintenance has proved effective in one randomized controlled study of a homogeneous cohort in loss of renal function (ΔGFR). Mycophenolic acid provided further maintenance in non‐randomized trials. Differentiated, precise, larger, randomized, placebo‐controlled studies focused on the loss of renal function in the heterogeneous forms of IgAN are still lacking. Prospectively, fewer toxic agents will be necessary in the treatment of IgAN. PMID:27283488

Impaired left ventricular systolic function and increased brachial-ankle pulse-wave velocity are independently associated with rapid renal function progression.

PubMed

Chen, Szu-Chia; Lin, Tsung-Hsien; Hsu, Po-Chao; Chang, Jer-Ming; Lee, Chee-Siong; Tsai, Wei-Chung; Su, Ho-Ming; Voon, Wen-Chol; Chen, Hung-Chun

2011-09-01

Heart failure and increased arterial stiffness are associated with declining renal function. Few studies have evaluated the association between left ventricular ejection fraction (LVEF) and brachial-ankle pulse-wave velocity (baPWV) and renal function progression. The aim of this study was to assess whether LVEF<40% and baPWV are associated with a decline in the estimated glomerular filtration rate (eGFR) and the progression to a renal end point of ≥25% decline in eGFR. This longitudinal study included 167 patients. The baPWV was measured with an ankle-brachial index-form device. The change in renal function was estimated by eGFR slope. The renal end point was defined as ≥25% decline in eGFR. Clinical and echocardiographic parameters were compared and analyzed. After a multivariate analysis, serum hematocrit was positively associated with eGFR slope, and diabetes mellitus, baPWV (P=0.031) and LVEF<40% (P=0.001) were negatively associated with eGFR slope. Forty patients reached the renal end point. Multivariate, forward Cox regression analysis found that lower serum albumin and hematocrit levels, higher triglyceride levels, higher baPWV (P=0.039) and LVEF<40% (P<0.001) were independently associated with progression to the renal end point. Our results show that LVEF<40% and increased baPWV are independently associated with renal function decline and progression to the renal end point.

The role of interventional radiology in abdominopelvic trauma

PubMed Central

Ierardi, Anna Maria; Duka, Ejona; Lucchina, Natalie; Floridi, Chiara; De Martino, Alessandro; Donat, Daniela; Fontana, Federico

2016-01-01

The management of trauma patients has evolved in recent decades owing to increasing availability of advanced imaging modalities such as CT. Nowadays, CT has replaced the diagnostic function of angiography. The latter is considered when a therapeutic option is hypothesized. Arterial embolization is a life-saving procedure in abdominopelvic haemorrhagic patients, reducing relevant mortality rates and ensuring haemodynamic stabilization of the patient. Percutaneous transarterial embolization has been shown to be effective for controlling ongoing bleeding for patients with high-grade abdominopelvic injuries, thereby reducing the failure rate of non-operative management, preserving maximal organ function. Surgery is not always the optimal solution for stabilization of a patient with polytrauma. Mini-invasivity and repeatability may be considered as relevant advantages. We review technical considerations, efficacy and complication rates of hepatic, splenic, renal and pelvic embolization to extrapolate current evidence about transarterial embolization in traumatic patients. PMID:26642310

ACE Over Expression in Myelomonocytic Cells: Effect on a Mouse Model of Alzheimer's Disease

PubMed Central

Koronyo-Hamaoui, Maya; Shah, Kandarp; Koronyo, Yosef; Bernstein, Ellen; Giani, Jorge F.; Janjulia, Tea; Black, Keith L.; Shi, Peng D.; Gonzalez-Villalobos, Romer A.; Fuchs, Sebastien; Shen, Xiao Z.; Bernstein, Kenneth E.

2014-01-01

While it is well known that angiotensin converting enzyme (ACE) plays an important role in blood pressure control, ACE also has effects on renal function, hematopoiesis, reproduction, and aspects of the immune response. ACE 10/10 mice over express ACE in myelomonocytic cells. Macrophages from these mice have an increased polarization towards a pro-inflammatory phenotype that results in a very effective immune response to challenge by tumors or bacterial infection. In a mouse model of Alzheimer's disease (AD), the ACE 10/10 phenotype provides significant protection against AD pathology, including reduced inflammation, reduced burden of the neurotoxic amyloid-β protein and preserved cognitive function. Taken together, these studies show that increased myelomonocytic ACE expression in mice alters the immune response to better defend against many different types of pathologic insult, including the cognitive decline observed in an animal model of AD. PMID:24792094

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

PubMed Central

Chin, Melanie P.; Bakris, George L.; Block, Geoffrey A.; Chertow, Glenn M.; Goldsberry, Angie; Inker, Lesley A.; Heerspink, Hiddo J.L.; O'Grady, Megan; Pergola, Pablo E.; Wanner, Christoph; Warnock, David G.; Meyer, Colin J.

2018-01-01

Background Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Methods Patients in ­BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Results Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36–0.64]; p < 0.0001). Conclusions Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. PMID:29402767

Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study.

PubMed

Chin, Melanie P; Bakris, George L; Block, Geoffrey A; Chertow, Glenn M; Goldsberry, Angie; Inker, Lesley A; Heerspink, Hiddo J L; O'Grady, Megan; Pergola, Pablo E; Wanner, Christoph; Warnock, David G; Meyer, Colin J

2018-01-01

Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl. Patients in -BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation). Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36-0.64]; p < 0.0001). Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD. © 2018 The Author(s) Published by S. Karger AG, Basel.

Serine/threonine kinase, Cot/Tpl2, regulates renal cell apoptosis in ischaemia/reperfusion injury.

PubMed

Yaomura, Takaaki; Tsuboi, Naotake; Urahama, Yoshinori; Hobo, Akinori; Sugimoto, Kenji; Miyoshi, Jun; Matsuguchi, Tetsuya; Reiji, Kannagi; Matsuo, Seiichi; Yuzawa, Yukio

2008-10-01

Cot/Tpl2, a serine/threonine (Ser/Thr) protein kinase, has been classified as a member of the mitogen-activated protein kinase (MAPK) family, and is known to have a pleiotropic role. Many studies have reported the involvement of Cot/Tpl2, mainly as a member of the Toll-like receptor (TLR) 4 signalling pathway in lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) production. At the same time, it is also related to the caspase-dependent apoptotic pathway. Thus, the role of Cot/Tpl2 in ischaemia/reperfusion injury (IRI) in which TNF-alpha and apoptosis are the major pathogenetic factors was studied. IRI was induced in wild type (Cot/Tpl2(+/+)) mice and in Cot/Tpl2-deficient (Cot/Tpl2(-/-)) mice. The extent of tubular injury and renal function were studied. TNF-alpha production, neutrophil infiltration and apoptosis were also compared between the two groups. Cot/Tpl2(-/-) mice had preserved renal function compared with wild type mice in IRI. Although Cot/Tpl2 was phosphorylated in IRI and in the cultured tubular epithelial cells (TEC) after stimulation with LPS and hydrogen peroxide, there were no significant differences in terms of TNF-alpha production, neutrophil infiltration or MAPK activation between Cot/Tpl2(+/+) and Cot/Tpl2(-/-) mice. In contrast, Cot/Tpl2(-/-) mice showed obviously reduced terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling positive cells and cleaved caspase-3 positive cells. Furthermore, Cot/Tpl2-deficient TECs demonstrated significantly less caspase-3 activation after hydrogen peroxide stimulation with comparable caspase-9 activation to wild type TEC. Cot/Tpl2 did not function as a member of MAPK family, but as a promoter of apoptosis in IRI. These results suggest that Cot/Tpl2 could be a possible therapeutic target in IRI.

Therapeutic Potential and Molecular Mechanisms of Emblica officinalis Gaertn in Countering Nephrotoxicity in Rats Induced by the Chemotherapeutic Agent Cisplatin

PubMed Central

Malik, Salma; Suchal, Kapil; Bhatia, Jagriti; Khan, Sana I.; Vasisth, Swati; Tomar, Ameesha; Goyal, Sameer; Kumar, Rajeev; Arya, Dharamvir S.; Ojha, Shreesh K.

2016-01-01

Emblica officinalis Gaertn. belonging to family Euphorbiaceae is commonly known as Indian gooseberry or “Amla” in India. It is used as a ‘rejuvenating herb’ in traditional system of Indian medicine. It has been shown to possess antioxidant, anti-inflammatory and anti-apoptotic effects. Thus, on the basis of its biological effects, the present study was undertaken to evaluate the protective effect of the dried fruit extract of the E. Officinalis (EO) in cisplatin-induced nephrotoxicity in rats and also to evaluate the mechanism of its nephroprotection. The study was done on male albino Wistar rats. They were divided into six groups (n = 6) viz. control, cisplatin-control, cisplatin and EO (150, 300, and 600 mg/kg; p.o. respectively in different groups) and EO only (600 mg/kg; p.o. only). EO was administered orally to the rats for a period of 10 days and on the 7th day, a single injection of cisplatin (8 mg/kg; i.p.) was administered to the cisplatin-control and EO treatment groups. The rats were sacrificed on the 10th day. Cisplatin-control rats had deranged renal function parameters and the kidney histology confirmed the presence of acute tubular necrosis. Furthermore, there were increased oxidative stress, apoptosis and inflammation along with higher expression of MAPK pathway proteins in the rat kidney from the cisplatin-control group. Contrary to this, EO (600 mg/kg) significantly normalized renal function, bolstered antioxidant status and ameliorated histological alterations. The inflammation and apoptosis were markedly lower in comparison to cisplatin-control rats. Furthermore, EO (600 mg/kg) inhibited MAPK phosphorylation which was instrumental in preserving renal function and morphology. In conclusion, the results of our study demonstrated that EO attenuated cisplatin-induced nephrotoxicity in rats through suppression of MAPK induced inflammation and apoptosis. PMID:27752245

Negative impact of prolonged cold storage time before machine perfusion preservation in donation after circulatory death kidney transplantation.

PubMed

Paloyo, Siegfredo; Sageshima, Junichiro; Gaynor, Jeffrey J; Chen, Linda; Ciancio, Gaetano; Burke, George W

2016-10-01

Kidney grafts are often preserved initially in static cold storage (CS) and subsequently on hypothermic machine perfusion (MP). However, the impact of CS/MP time on transplant outcome remains unclear. We evaluated the effect of prolonged CS/MP time in a single-center retrospective cohort of 59 donation after circulatory death (DCD) and 177 matched donation after brain death (DBD) kidney-alone transplant recipients. With mean overall CS/MP times of 6.0 h/30.0 h, overall incidence of delayed graft function (DGF) was higher in DCD transplants (30.5%) than DBD transplants (7.3%, P < 0.0001). In logistic regression, DCD recipient (P < 0.0001), longer CS time (P = 0.0002), male recipient (P = 0.02), and longer MP time (P = 0.08) were associated with higher DGF incidence. In evaluating the joint effects of donor type (DBD vs. DCD), CS time (<6 vs. ≥6 h), and MP time (<36 vs. ≥36 h) on DGF incidence, one clearly sees an unfavorable effect of MP time ≥36 h (P = 0.003) across each donor type and CS time stratum, whereas the unfavorable effect of CS time ≥6 h (P = 0.01) is primarily seen among DCD recipients. Prolonged cold ischemia time had no unfavorable effect on renal function or graft survival at 12mo post-transplant. Long CS/MP time detrimentally affects early DCD/DBD kidney transplant outcome when grafts were mainly preserved by MP; prolonged CS time before MP has a particularly negative impact in DCD kidney transplantation. © 2016 Steunstichting ESOT.

Renal function and acute heart failure outcome.

PubMed

Llauger, Lluís; Jacob, Javier; Miró, Òscar

2018-06-05

The interaction between acute heart failure (AHF) and renal dysfunction is complex. Several studies have evaluated the prognostic value of this syndrome. The aim of this systematic review, which includes non-selected samples, was to investigate the impact of different renal function variables on the AHF prognosis. The categories included in the studies reviewed included: creatinine, blood urea nitrogen (BUN), the BUN/creatinine quotient, chronic kidney disease, the formula to estimate the glomerular filtration rate, criteria of acute renal injury and new biomarkers of renal damage such as neutrophil gelatinase-associated lipocalin (NGAL and cystatin c). The basal alterations of the renal function, as well as the acute alterations, transient or not, are related to a worse prognosis in AHF, it is therefore necessary to always have baseline, acute and evolutive renal function parameters. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Variability in the reporting of renal function endpoints in immunosuppression trials in renal transplantation: time for consensus?

PubMed

Knight, Simon R; Hussain, Samia

2016-12-01

Early measures of graft function are increasingly used to assess efficacy in clinical trials of kidney transplant immunosuppression. This study aimed to assess the variability and quality of reporting of these endpoints in contemporary trials. Data regarding renal function endpoints were extracted from 213 reports from randomized controlled trials comparing immunosuppressive interventions in renal transplant recipients published between 2010 and 2014. A total of 174 (81.7%) reports included a measure of renal function; in 44 (20.7%), this was the primary endpoint. A total of 103 manuscripts (48.4%) reported serum creatinine, 142 (66.6%) reported estimated glomerular filtration rate (eGFR), and 26 (12.2%) reported measured GFR. Formulas used for GFR estimation were modification of diet in renal disease (42.3%), Cockroft-Gault (23.5%), Nankivell (15.0%), and CKD-EPI (0.9%). Six studies (2.8%) did not report the formula used to estimate GFR. A total of 13.9% of endpoints had missing data. In 10 studies, disagreement was found in the significance of findings using different measures of renal function. There is a great deal of variability in the reporting of renal function endpoints, with a significant proportion of studies using underperforming or inappropriate estimates. There is a need for consensus as to the best tool for monitoring and reporting renal function post-transplant, and in particular for use in clinical trials and registries. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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.

Retrospective Review of Pediatric Blunt Renal Trauma: A Single Institution's Five Year Experience

PubMed Central

Clark, Margaret E; Sutherland, Ronald S; Woo, Russell K

2017-01-01

Children are at higher risk of renal injury from blunt trauma than adults due to a variety of anatomic factors such as decreased perirenal fat, weaker abdominal muscles, and a less ossified thoracic cage. Non-operative management is gaining in popularity for even major injuries, although there are no universally accepted guidelines. We present a retrospective review of pediatric major blunt renal injuries (grade 3 or higher) at a children's hospital in Hawai‘i over a 5-year period. Medical records were examined between January 2009 and September 2014 from Kapi‘olani Medical Center for Women and Children in Honolulu, Hawai‘i. Inclusion criteria were a diagnosis of renal trauma, or the diagnosis of blunt abdominal trauma with hematuria. Exclusion criteria were grade I or II renal injury or death due to an additional traumatic injury. Mechanism of injury, clinical characteristics on admission, blood product requirements, surgical interventions performed, and hospital length of stay were retrospectively analyzed. Eleven total patient records were examined, nine of which fit inclusion criteria. Uniquely, 33% of patients sustained their renal injury while surfing. No patients required laparotomy or nephrectomy, though 22% of patients received a blood transfusion and 44% of patients underwent ureteral stent placement. Non-operative management of major renal injuries in children is feasible and allows for preservation of renal tissue. A novel mechanism of surfing as a cause of major renal trauma is seen in the state of Hawai‘i. PMID:28484665

Retrospective Review of Pediatric Blunt Renal Trauma: A Single Institution's Five Year Experience.

PubMed

Richards, Carly R; Clark, Margaret E; Sutherland, Ronald S; Woo, Russell K

2017-05-01

Children are at higher risk of renal injury from blunt trauma than adults due to a variety of anatomic factors such as decreased perirenal fat, weaker abdominal muscles, and a less ossified thoracic cage. Non-operative management is gaining in popularity for even major injuries, although there are no universally accepted guidelines. We present a retrospective review of pediatric major blunt renal injuries (grade 3 or higher) at a children's hospital in Hawai'i over a 5-year period. Medical records were examined between January 2009 and September 2014 from Kapi'olani Medical Center for Women and Children in Honolulu, Hawai'i. Inclusion criteria were a diagnosis of renal trauma, or the diagnosis of blunt abdominal trauma with hematuria. Exclusion criteria were grade I or II renal injury or death due to an additional traumatic injury. Mechanism of injury, clinical characteristics on admission, blood product requirements, surgical interventions performed, and hospital length of stay were retrospectively analyzed. Eleven total patient records were examined, nine of which fit inclusion criteria. Uniquely, 33% of patients sustained their renal injury while surfing. No patients required laparotomy or nephrectomy, though 22% of patients received a blood transfusion and 44% of patients underwent ureteral stent placement. Non-operative management of major renal injuries in children is feasible and allows for preservation of renal tissue. A novel mechanism of surfing as a cause of major renal trauma is seen in the state of Hawai'i.

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.

High sodium intake increases blood pressure and alters renal function in intrauterine growth-retarded rats.

PubMed

Sanders, Marijke W; Fazzi, Gregorio E; Janssen, Ger M J; Blanco, Carlos E; De Mey, Jo G R

2005-07-01

A suboptimal fetal environment increases the risk to develop cardiovascular disease in the adult. We reported previously that intrauterine stress in response to reduced uteroplacental blood flow in the pregnant rat limits fetal growth and compromises renal development, leading to an altered renal function in the adult offspring. Here we tested the hypothesis that high dietary sodium intake in rats with impaired renal development attributable to intrauterine stress, results in increased blood pressure, altered renal function, and organ damage. In rats, intrauterine stress was induced by bilateral ligation of the uterine arteries at day 17 of pregnancy. At the age of 12 weeks, the offspring was given high-sodium drinking water (2% sodium chloride). At the age of 16 weeks, rats were instrumented for monitoring of blood pressure and renal function. After intrauterine stress, litter size and birth weight were reduced, whereas hematocrit at birth was increased. Renal blood flow, glomerular filtration rate, and the glomerular filtration fraction were increased significantly after intrauterine stress. High sodium intake did not change renal function and blood pressure in control animals. However, during high sodium intake in intrauterine stress offspring, renal blood flow, glomerular filtration rate, and the filtration fraction were decreased, and blood pressure was increased. In addition, these animals developed severe albuminuria, an important sign of renal dysfunction. Thus, a suboptimal fetal microenvironment, which impairs renal development, results in sodium-dependent hypertension and albuminuria.

Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury.

PubMed

Garcia-Martinez, Rita; Noiret, Lorette; Sen, Sambit; Mookerjee, Rajeshwar; Jalan, Rajiv

2015-02-01

In cirrhotic patients with renal failure, renal blood flow autoregulation curve is shifted to the right, which is consequent upon sympathetic nervous system activation and endothelial dysfunction. Albumin infusion improves renal function in cirrhosis by mechanisms that are incompletely understood. We aimed to determine the effect of albumin infusion on systemic haemodynamics, renal blood flow, renal function and endothelial function in patients with acute decompensation of cirrhosis and acute kidney injury. Twelve patients with refractory ascites and 10 patients with acute decompensation of cirrhosis and acute kidney injury were studied. Both groups were treated with intravenous albumin infusion, 40-60 g/days over 3-4 days. Cardiac and renal haemodynamics were measured. Endothelial activation/dysfunction was assessed using von Willebrand factor and serum nitrite levels. F2α Isoprostanes, resting neutrophil burst and noradrenaline levels were quantified as markers of oxidative stress, endotoxemia and sympathetic activation respectively. Albumin infusion leads to a shift in the renal blood flow autoregulation curve towards normalization, which resulted in a significant increase in renal blood flow. Accordingly, improvement of renal function was observed. In parallel, a significant decrease in sympathetic activation, inflammation/oxidative stress and endothelial activation/dysfunction was documented. Improvement of renal blood flow correlated with improvement in endothelial activation (r = 0.741, P < 0.001). The data suggest that albumin infusion improves renal function in acutely decompensated cirrhotic patients with acute kidney injury by impacting on renal blood flow autoregulation. This is possibly achieved through endothelial stabilization and a reduction in the sympathetic tone, endotoxemia and oxidative stress. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chronic administration of sildenafil improves erectile function in a rat model of chronic renal failure

PubMed Central

Gurbuz, Nilgun; Kol, Arif; Ipekci, Tumay; Ates, Erhan; Baykal, Asli; Usta, Mustafa F

2015-01-01

The relationship between erectile dysfunction (ED) and chronic renal failure (CRF) has been reported in several studies. This study aimed to investigate whether the chronic use of sildenafil could enhance the erectile capacity in CRF-induced rats. In addition, we assessed the effect of that treatment on certain molecules, which have been suggested to play crucial roles in erectile physiology and CRF-related ED as well. Three groups of animals were utilized: (1) age-matched control rats, (2) CRF-induced rats, (3) CRF-induced rats treated with chronic administration of sildenafil (5 mg kg−1 p.o. for 6 weeks [treatment started after 6 weeks of CRF induction]). At 3 months, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue advanced glycation end products (AGE's)/5-hydroxymethyl-2-furaldehyde, malondialdehyde (MDA), cGMP (ELISA), inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS) (Western blot) analyses were performed in all rat groups. CRF-induced rats had a significant decrease in erectile function when compared to control rats (P < 0.05). The increase in both intracavernosal pressure (ICP) and area under the curve of CRF-induced rats treated with sildenafil (Group 3) was greater than CRF-induced rats (Group 2). Additionally, sildenafil treatment decreased AGE, MDA and iNOS levels, while it preserved nNOS and cGMP contents in CRF-induced penile tissue. Decreased AGE, MDA, iNOS and increased nNOS, cGMP levels at the sildenafil-treated group increased both ICP and Total ICP to CNS, which led to improve erectile function in CRF-induced rats. The results of the present study revealed the therapeutic effect of chronic sildenafil administration on erectile function in CRF-induced rats. PMID:25652632

Aortic calcification burden predicts deterioration of renal function after radical nephrectomy.

PubMed

Fukushi, Ken; Hatakeyama, Shingo; Yamamoto, Hayato; Tobisawa, Yuki; Yoneyama, Tohru; Soma, Osamu; Matsumoto, Teppei; Hamano, Itsuto; Narita, Takuma; Imai, Atsushi; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Koie, Takuya; Terayama, Yuriko; Funyu, Tomihisa; Ohyama, Chikara

2017-02-06

Radical nephrectomy for renal cell carcinoma (RCC) is a risk factor for the development of chronic kidney disease (CKD), and the possibility of postoperative deterioration of renal function must be considered before surgery. We investigated the contribution of the aortic calcification index (ACI) to the prediction of deterioration of renal function in patients undergoing radical nephrectomy. Between January 1995 and December 2012, we performed 511 consecutive radical nephrectomies for patients with RCC. We retrospectively studied data from 109 patients who had regular postoperative follow-up of renal function for at least five years. The patients were divided into non-CKD and pre-CKD based on a preoperative estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m 2 or <60 mL/min/1.73 m 2 , respectively. The ACI was quantitatively measured by abdominal computed tomography before surgery. The patients in each group were stratified between low and high ACIs. Variables such as age, sex, comorbidities, and pre- and postoperative renal function were compared between patients with a low or high ACI in each group. Renal function deterioration-free interval rates were evaluated by Kaplan-Meier analysis. Factors independently associated with deterioration of renal function were determined using multivariate analysis. The median age, preoperative eGFR, and ACI in this cohort were 65 years, 68 mL/min/1.73 m 2 , and 8.3%, respectively. Higher ACI (≥8.3%) was significantly associated with eGFR decline in both non-CKD and pre-CKD groups. Renal function deterioration-free interval rates were significantly lower in the ACI-high than ACI-low strata in both of the non-CKD and pre-CKD groups. Multivariate analysis showed that higher ACI was an independent risk factor for deterioration of renal function at 5 years after radical nephrectomy. Aortic calcification burden is a potential predictor of deterioration of renal function after radical nephrectomy. This study was registered as a clinical trial: UMIN000023577.

Increased curvature of hollow fiber membranes could up-regulate differential functions of renal tubular cell layers.

PubMed

Shen, Chong; Meng, Qin; Zhang, Guoliang

2013-08-01

Tissue engineering devices as in vitro cell culture systems in scaffolds has encountered the bottleneck due to their much lower cell functions than real tissues/organs in vivo. Such situation has been improved in some extent by mimicking the cell microenvironments in vivo from either chemical or physical ways. However, microenvironmental curvature, commonly seen in real tissues/organs, has never been manipulated to regulate the cell performance in vitro. In this regard, this paper fabricated polysulfone membranes with or without polyethylene glycol modification to investigate the impact of curvature on two renal tubular cells. Regardless the varying membrane curvatures among hollow fiber membranes of different diameters and flat membrane of zero curvature, both renal cells could well attach at 4 h of seeding and form similar confluent layers at 6 days on each membrane. Nevertheless, the renal cells on hollow fibers, though showing confluent morphology as those on flat membranes, expressed higher renal functions and, moreover, the renal functions significantly increased with the membrane curvature among hollow fibers. Such upregulation on functions was unassociated with mass transport barrier of hollow fibers, because the cultures on lengthwise cut hollow fibers without mass transfer barrier showed same curvature effect on renal functions as whole hollow fibers. It could be proposed that the curvature of hollow fiber membrane approaching to the large curvature in kidney tubules increased the mechanical stress in the renal cells and thus might up-regulate the renal cell functions. In conclusion, the increase of substrate curvature could up-regulate the cell functions without altering the confluent cell morphology and this finding will facilitate the design of functional tissue engineering devices. Copyright © 2013 Wiley Periodicals, Inc.

Serum osteoprotegerin and renal function in the general population: the Tromsø Study.

PubMed

Vik, Anders; Brodin, Ellen E; Mathiesen, Ellisiv B; Brox, Jan; Jørgensen, Lone; Njølstad, Inger; Brækkan, Sigrid K; Hansen, John-Bjarne

2017-02-01

Serum osteoprotegerin (OPG) is elevated in patients with chronic kidney disease (CKD) and increases with decreasing renal function. However, there are limited data regarding the association between OPG and renal function in the general population. The aim of the present study was to explore the relation between serum OPG and renal function in subjects recruited from the general population. We conducted a cross-sectional study with 6689 participants recruited from the general population in Tromsø, Norway. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equations. OPG was modelled both as a continuous and categorical variable. General linear models and linear regression with adjustment for possible confounders were used to study the association between OPG and eGFR. Analyses were stratified by the median age, as serum OPG and age displayed a significant interaction on eGFR. In participants ≤62.2 years with normal renal function (eGFR ≥90 mL/min/1.73 m 2 ) eGFR increased by 0.35 mL/min/1.73 m 2 (95% CI 0.13-0.56) per 1 standard deviation (SD) increase in serum OPG after multiple adjustment. In participants older than the median age with impaired renal function (eGFR <90 mL/min/1.73 m 2 ), eGFR decreased by 1.54 (95% CI -2.06 to -1.01) per 1 SD increase in serum OPG. OPG was associated with an increased eGFR in younger subjects with normal renal function and with a decreased eGFR in older subjects with reduced renal function. Our findings imply that the association between OPG and eGFR varies with age and renal function.

[Endovascular radiofrequency denervation of renal arteries as an innovation method of treatment of refractory arterial hypertension. First experience in Russia].

PubMed

Danilov, N M; Matchin, Iu G; Chazova, I E

2012-01-01

Excessive activation of the sympathetic nervous system forms the basis of pathogenesis of essential arterial hypertension (AH). The present work was aimed at evaluating efficacy and safety of endovascular radiofrequency denervation of renal arteries in patients with AH refractory AH based on the initial first experience in with using this methodology in the Russian Federation. The interventions were carried out on December 14-15th, 2011 in the first five patients presenting with AH refractory to antihypertensive therapy consisting of three and more drugs in therapeutic doses, one of which was a diuretic. The selection criteria were systolic arterial pressure (SAP) ≥160 mm Hg or ≥150 mm Hg in the presence of type 2 diabetes mellitus. The obligatory conditions for selection were the preserved renal function [glomerular filtration rate (GFR) ≥45 ml/min] and the absence of the secondary form of AH. The procedure of denervation was performed in the conditions of roentgen-operating room using special Medtronic Ardian Simplicity Catheter System™. In all cases we managed to perform bilateral denervation of renal arteries with the radiofrequency effect in not less than 4 zones of each of vessels. Efficacy of each of the effect was registered with due regard for reaching certain temperature and values of impedance. The interventions were not accompanied by the development of any complications either in the area of manipulations or the site of puncture. Neither were there any complications from the side of the cardiovascular or excretory systems of the body. Diurnal monitoring of AP (DMAP) registered a significant decrease in SAP averagely from 174±12 to 145±10 mm Hg three days after the intervention. A persistent antihypertensive effect was confirmed by the DMAP findings one month after denervation - the SAP level averagely amounted to 131±6 mm Hg. Endovascular radiofrequency denervation of renal arteries is a safe and efficient method of treatment of AH resistant to multicomponent antihypertensive therapy.

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction.

PubMed

Iglesias, Jose; Frank, Elliot; Mehandru, Sushil; Davis, John M; Levine, Jerrold S

2013-07-13

Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction.

Toxicological and pharmacokinetic properties of chemically modified siRNAs targeting p53 RNA following intravenous administration.

PubMed

Thompson, James D; Kornbrust, Douglas J; Foy, Jeffrey W-D; Solano, Elisabeth C R; Schneider, David J; Feinstein, Elena; Molitoris, Bruce A; Erlich, Shai

2012-08-01

We report the toxicological and pharmacokinetic properties of the synthetic, small interfering RNA I5NP following intravenous administration in rodents and nonhuman primates. I5NP is designed to act via the RNA interference (RNAi) pathway to temporarily inhibit expression of the pro-apoptotic protein p53 and is being developed to protect cells from acute ischemia/reperfusion injuries such as acute kidney injury that can occur during major cardiac surgery and delayed graft function that can occur following renal transplantation. Following intravenous administration, I5NP was very rapidly cleared from plasma was distributed predominantly to the kidney, with very low levels in liver and other tissues. Doses of 800 mg/kg I5NP in rodents, and 1,000 mg/kg I5NP in nonhuman primates, were required to elicit adverse effects, which in the monkey were isolated to direct effects on the blood that included a sub-clinical activation of complement and slightly increased clotting times. In the rat, no additional adverse effects were observed with a rat analogue of I5NP, indicating that the effects likely represent class effects of synthetic RNA duplexes rather than toxicity related to the intended pharmacologic activity of I5NP. Taken together, these data support clinical testing of intravenous administration of I5NP for the preservation of renal function following acute ischemia/reperfusion injury.

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.

Short-term preconditioning enhances the therapeutic potential of adipose-derived stromal/stem cell-conditioned medium in cisplatin-induced acute kidney injury.

PubMed

Overath, Jürgen M; Gauer, Stefan; Obermüller, Nicholas; Schubert, Ralf; Schäfer, Richard; Geiger, Helmut; Baer, Patrick C

2016-03-15

The development of new strategies to preserve renal function after acute kidney injury (AKI) is necessary due to limited clinical intervention options. The organ-protective effects of mesenchymal stromal/stem cells (MSCs) and their conditioned medium (CM) have been investigated demonstrating that both separately promoted tubular recovery and ameliorated the outcome of AKI. Nevertheless, strategies to optimise the regenerative potential of both are highly needed. Here we investigated the effects of CM from adipose-derived MSCs (ASCs) preincubated in a hypoxic environment (Hyp). Protective factors were investigated by PCR analysis and a protein array in vitro. The expression of 64 of the 308 proteins assayed was found to be more than two-fold increased after Hyp. CM of Hyp-pretreated ASCs (pCM) was used to enhance regeneration in a mouse model of cisplatin-induced AKI (cisAKI). Renal function was assessed by measurements of markers for AKI and serum cytokine levels. The pCM significantly ameliorated serum creatinine and neutrophil gelatinase-associated lipocalin values, and also the levels of inflammatory cytokines IL-1β and IL-6 in the serum of mice with AKI. Our work clearly showed that a Hyp preconditioning significantly increases the release of protective factors in ASCs and enhances the therapeutic effects of CM in cisAKI in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

[Glycation, glycoxidation and diabetes mellitus].

PubMed

Boulanger, Eric; Wautier, Jean-Luc; Dequiedt, Philippe; Schmidt, Anne-Marie

2006-01-01

Advanced glycation end-products (AGEs) result from a reaction between carbohydrates and the free amino groups of proteins, lipids, and DNA. Non enzymatic glycation, glycoxidation with glucose auto-oxidation and the polyol pathway are involved in glycated protein formation. AGEs also named glycotoxins are found in excess in pathological situations such as diabetes mellitus, renal failure, and aging or after absorption of food containing glycated products. Three major pathophysiological mechanisms are described to explain AGE toxicity, first AGEs can accumulate in the vessel wall and in collagen of different tissues; second in situ glycation is possible; third, AGEs bind to cell receptors inducing deleterious consequences. AGE receptor RAGE is a multiligand member of the immunoglobulin superfamily of cell surface molecules. AGE-receptor interaction can alter, macrophage, endothelial cell, mesangial and mesothelial cell functions and can induce inflammation. Oxidant stress, vascular hyperpermeability, vascular cell adhesion molecule-1 (VCAM-1) overexpression and monocytes chemotactic Protein-1 (MCP-1) production have been observed after cell activation by AGEs. AGEs appear to be involved in the genesis of diabetic macro but also microangiopathy such as retinopathy and glomerulosclerosis. New drugs are tested to prevent or break the AGE-protein cross-linkage, or to control the AGE-receptor interaction and their consequences. Dietary treatment, strict glycemic control and preservation of renal function remain the best approach for preventing AGE formation and limiting their deleterious effects.

Membrane Stabilization and Detoxification of Acetaminophen-Mediated Oxidative Onslaughts in the Kidneys of Wistar Rats by Standardized Fraction of Zea mays L. (Poaceae), Stigma maydis.

PubMed

Sabiu, S; O'Neill, F H; Ashafa, A O T

2016-01-01

This study evaluated membrane stabilization and detoxification potential of ethyl acetate fraction of Zea mays L., Stigma maydis in acetaminophen-induced oxidative onslaughts in the kidneys of Wistar rats. Nephrotoxic rats were orally pre- and posttreated with the fraction and vitamin C for 14 days. Kidney function, antioxidative and histological analyses were thereafter evaluated. The acetaminophen-mediated significant elevations in the serum concentrations of creatinine, urea, uric acid, sodium, potassium, and tissue levels of oxidized glutathione, protein-oxidized products, lipid peroxidized products, and fragmented DNA were dose-dependently assuaged in the fraction-treated animals. The fraction also markedly improved creatinine clearance rate, glutathione, and calcium concentrations as well as activities of superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase in the nephrotoxic rats. These improvements may be attributed to the antioxidative and membrane stabilization activities of the fraction. The observed effects compared favorably with that of vitamin C and are informative of the fraction's ability to prevent progression of renal pathological conditions and preserve kidney functions as evidently supported by the histological analysis. Although the effects were prominently exhibited in the fraction-pretreated groups, the overall data from the present findings suggest that the fraction could prevent or extenuate acetaminophen-mediated oxidative renal damage via fortification of antioxidant defense mechanisms.

Membrane Stabilization and Detoxification of Acetaminophen-Mediated Oxidative Onslaughts in the Kidneys of Wistar Rats by Standardized Fraction of Zea mays L. (Poaceae), Stigma maydis

PubMed Central

Sabiu, S.; O'Neill, F. H.

2016-01-01

This study evaluated membrane stabilization and detoxification potential of ethyl acetate fraction of Zea mays L., Stigma maydis in acetaminophen-induced oxidative onslaughts in the kidneys of Wistar rats. Nephrotoxic rats were orally pre- and posttreated with the fraction and vitamin C for 14 days. Kidney function, antioxidative and histological analyses were thereafter evaluated. The acetaminophen-mediated significant elevations in the serum concentrations of creatinine, urea, uric acid, sodium, potassium, and tissue levels of oxidized glutathione, protein-oxidized products, lipid peroxidized products, and fragmented DNA were dose-dependently assuaged in the fraction-treated animals. The fraction also markedly improved creatinine clearance rate, glutathione, and calcium concentrations as well as activities of superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase in the nephrotoxic rats. These improvements may be attributed to the antioxidative and membrane stabilization activities of the fraction. The observed effects compared favorably with that of vitamin C and are informative of the fraction's ability to prevent progression of renal pathological conditions and preserve kidney functions as evidently supported by the histological analysis. Although the effects were prominently exhibited in the fraction-pretreated groups, the overall data from the present findings suggest that the fraction could prevent or extenuate acetaminophen-mediated oxidative renal damage via fortification of antioxidant defense mechanisms. PMID:27579048

Mendelian randomization analysis associates increased serum urate, due to genetic variation in uric acid transporters, with improved renal function.

PubMed

Hughes, Kim; Flynn, Tanya; de Zoysa, Janak; Dalbeth, Nicola; Merriman, Tony R

2014-02-01

Increased serum urate predicts chronic kidney disease independent of other risk factors. The use of xanthine oxidase inhibitors coincides with improved renal function. Whether this is due to reduced serum urate or reduced production of oxidants by xanthine oxidase or another physiological mechanism remains unresolved. Here we applied Mendelian randomization, a statistical genetics approach allowing disentangling of cause and effect in the presence of potential confounding, to determine whether lowering of serum urate by genetic modulation of renal excretion benefits renal function using data from 7979 patients of the Atherosclerosis Risk in Communities and Framingham Heart studies. Mendelian randomization by the two-stage least squares method was done with serum urate as the exposure, a uric acid transporter genetic risk score as instrumental variable, and estimated glomerular filtration rate and serum creatinine as the outcomes. Increased genetic risk score was associated with significantly improved renal function in men but not in women. Analysis of individual genetic variants showed the effect size associated with serum urate did not correlate with that associated with renal function in the Mendelian randomization model. This is consistent with the possibility that the physiological action of these genetic variants in raising serum urate correlates directly with improved renal function. Further studies are required to understand the mechanism of the potential renal function protection mediated by xanthine oxidase inhibitors.

Effect of bariatric surgery-induced weight loss on renal and systemic inflammation and blood pressure: a 12-month prospective study.

PubMed

Fenske, Wiebke K; Dubb, Sukhpreet; Bueter, Marco; Seyfried, Florian; Patel, Karishma; Tam, Frederick W K; Frankel, Andrew H; le Roux, Carel W

2013-01-01

Bariatric surgery improves arterial hypertension and renal function; however, the underlying mechanisms and effect of different surgical procedures are unknown. In the present prospective study, we compared the 12-month follow-up results after Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, and laparoscopic sleeve gastrectomy on weight loss, hypertension, renal function, and inflammatory status. A total of 34 morbidly obese patients were investigated before, one and 12 months after Roux-en-Y gastric bypass (n = 10), laparoscopic adjustable gastric banding (n = 13), and laparoscopic sleeve gastrectomy (n = 11) for hypertension, kidney function, urinary and serum cytokine levels of macrophage migration inhibitory factor, monocyte chemotactic protein-1, and chemokine ligand-18. At 12 months after surgery, the patients in all 3 treatment arms showed a significant decrease in the mean body mass index, mean arterial pressure, and urinary and serum inflammatory markers (all P < .001). The reduction in urinary and serum cytokine levels correlated directly with body weight loss (P < .05). Patients with impaired renal function at baseline (corresponding to serum cystatin C >.8 mg/L) had a marked improvement in renal function 12 months after surgery (P < .05). Surgically induced weight loss is associated with a marked decrease in renal and systemic inflammation and arterial hypertension and improvement in renal function in patients with pre-existing renal impairment. These effects appear to be independent of surgical procedure. The improvement in renal inflammation could be 1 of the mechanisms contributing to the beneficial effects of bariatric surgery on arterial blood pressure, proteinuria, and renal function. Copyright © 2013 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Neural control of renal function: cardiovascular implications.

PubMed

DiBona, G F

1989-06-01

The innervation of the kidney serves to function of its component parts, for example, the blood vessels, the nephron (glomerulus, tubule), and the juxtaglomerular apparatus. Alterations in efferent renal sympathetic nerve activity produce significant changes in renal blood flow, glomerular filtration rate, the reabsorption of water, sodium, and other ions, and the release of renin, prostaglandins, and other vasoactive substances. These functional effects contribute significantly to the renal regulation of total body sodium and fluid volumes with important implications for the control of arterial pressure. The renal nerves, both efferent and afferent, are known to be important contributors to the pathogenesis of hypertension. In addition, the efferent renal nerves participate in the mediation of the excessive renal sodium retention, which characterizes edema-forming states such as congestive heart failure. Thus, the renal nerves play an important role in overall cardiovascular homeostasis in both normal and pathological conditions.

Clinical types and drug therapy of renal impairment in cirrhosis

PubMed Central

Rodés, J.; Bosch, J.; Arroyo, V.

1975-01-01

Four separate types of renal failure in cirrhosis are described: functional renal failure; diuretic induced uraemia; acute tubular necrosis; chronic intrinsic renal disease. Functional renal failure may arise spontaneously or be precipitated by such factors as haemorrhage, surgery, or infection. It carries a poor prognosis but preliminary results of treating this condition with plasma volume expansion in combination with high doses of furosemide are encouraging. PMID:1234328

Intracavitary irradiation of renal pyelocalyceal transitional cell carcinoma with iridium-192

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

Kadish, S.P.; Danford, R.; Felton, L.M.

1981-11-01

A case of multicentric urothelial transitional cell carcinoma is presented, in which the patient underwent a left ureteronephrectomy and in the remaining right kidney recurrent transitional cell carcinoma was found in the inferior calyx. Because this area was accessible via a cutaneous nephrostomy, it is treated with a combination of external beam radiation and intracavitary implantation with iridium-192. The iridium was placed in the vicinity of the tumor using an angiographic procedure. The technique successfully preserved remaining renal parenchyma. The case illustrates how angiography skills and procedures can be applied in a novel brachytherapy application.

Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review

PubMed Central

2014-01-01

Rhabdomyolysis, a clinical syndrome caused by damage to skeletal muscle and release of its breakdown products into the circulation, can be followed by acute kidney injury (AKI) as a severe complication. The belief that the AKI is triggered by myoglobin as the toxin responsible appears to be oversimplified. Better knowledge of the pathophysiology of rhabdomyolysis and following AKI could widen treatment options, leading to preservation of the kidney: the decision to initiate renal replacement therapy in clinical practice should not be made on the basis of the myoglobin or creatine phosphokinase serum concentrations. PMID:25043142

The role of the renal specialist nurse in prevention of renal failure.

PubMed

Hurst, J

2002-01-01

This article will investigate the care required for those with reduced renal function before renal replacement therapy (RRT) commences. Renal nurses are often involved with the technical, monitoring and evaluative aspects of RRT for those with end stage renal failure. However, many patients may experience reduced renal function many years before reaching the stage of needing RRT. Renal nurses are already involved in the preparation of patients for RRT, but are not presently exercising their specialist skills in the period before this time by contributing to the prevention of end stage renal failure (ESRF). Screening programmes carried out in various parts of the world demonstrate that many members of the population have undetected renal insufficiency, and may benefit from intervention from the nephrology team to prevent further renal dysfunction. It is for this group of patients that this article will consider the potential for the renal nurse to expand their scope of practice.

Renal impairment as a surgical indication in primary hyperparathyroidism: do the data support this recommendation?

PubMed

Hendrickson, Chase D; Castro Pereira, Daniel J; Comi, Richard J

2014-08-01

Management of primary hyperparathyroidism has evolved over the past two decades, yet impaired renal function has consistently been a surgical indication. This recommendation has been based upon the historical association between primary hyperparathyroidism and renal impairment, and a review of the literature is needed to determine whether such a recommendation is warranted. PubMed was utilized to identify English-language articles published between January 1990 and February 2014 using keywords related to hyperparathyroidism and renal function. The keywords were "primary hyperparathyroidism," "surgery," "parathyroidectomy," "kidney," "renal," "glomerular filtration rate," and "creatinine." Of the 1926 articles obtained with this search, all articles germane to the topic that quantified the relationship between primary hyperparathyroidism and renal function were included. All references within these articles were investigated for inclusion. When helpful, data tables were constructed to summarize the results succinctly. A secondary elevation of PTH levels has not been consistently shown to occur at the threshold currently indicated for surgical intervention. While renal impairment is seen with more significant disease, mild asymptomatic primary hyperparathyroidism has not been conclusively associated with renal impairment. Furthermore, there is no evidence to suggest that surgically curing primary hyperparathyroidism via a parathyroidectomy has any impact upon renal function.

Effect of renal denervation on dynamic autoregulation of renal blood flow.

PubMed

DiBona, Gerald F; Sawin, Linda L

2004-06-01

Vasoconstrictor intensities of renal sympathetic nerve stimulation elevate the renal arterial pressure threshold for steady-state stepwise autoregulation of renal blood flow. This study examined the tonic effect of basal renal sympathetic nerve activity on dynamic autoregulation of renal blood flow in rats with normal (Sprague-Dawley and Wistar-Kyoto) and increased levels of renal sympathetic nerve activity (congestive heart failure and spontaneously hypertensive rats). Steady-state values of arterial pressure and renal blood flow before and after acute renal denervation were subjected to transfer function analysis. Renal denervation increased basal renal blood flow in congestive heart failure (+35 +/- 3%) and spontaneously hypertensive rats (+21 +/- 3%) but not in Sprague-Dawley and Wistar-Kyoto rats. Renal denervation significantly decreased transfer function gain (i.e., improved autoregulation of renal blood flow) and increased coherence only in spontaneously hypertensive rats. Thus vasoconstrictor intensities of renal sympathetic nerve activity impaired the dynamic autoregulatory adjustments of the renal vasculature to oscillations in arterial pressure. Renal denervation increased renal blood flow variability in spontaneously hypertensive rats and congestive heart failure rats. The contribution of vasoconstrictor intensities of basal renal sympathetic nerve activity to limiting renal blood flow variability may be important in the stabilization of glomerular filtration rate.

Influence of fluid resuscitation on renal microvascular PO2 in a normotensive rat model of endotoxemia

PubMed Central

Johannes, Tanja; Mik, Egbert G; Nohé, Boris; Raat, Nicolaas JH; Unertl, Klaus E; Ince, Can

2006-01-01

Introduction Septic renal failure is often seen in the intensive care unit but its pathogenesis is only partly understood. This study, performed in a normotensive rat model of endotoxemia, tests the hypotheses that endotoxemia impairs renal microvascular PO2 (μPO2) and oxygen consumption (VO2,ren), that endotoxemia is associated with a diminished kidney function, that fluid resuscitation can restore μPO2, VO2,ren and kidney function, and that colloids are more effective than crystalloids. Methods Male Wistar rats received a one-hour intravenous infusion of lipopolysaccharide, followed by resuscitation with HES130/0.4 (Voluven®), HES200/0.5 (HES-STERIL® ® 6%) or Ringer's lactate. The renal μPO2 in the cortex and medulla and the renal venous PO2 were measured by a recently published phosphorescence lifetime technique. Results Endotoxemia induced a reduction in renal blood flow and anuria, while the renal μPO2 and VO2,ren remained relatively unchanged. Resuscitation restored renal blood flow, renal oxygen delivery and kidney function to baseline values, and was associated with oxygen redistribution showing different patterns for the different compounds used. HES200/0.5 and Ringer's lactate increased the VO2,ren, in contrast to HES130/0.4. Conclusion The loss of kidney function during endotoxemia could not be explained by an oxygen deficiency. Renal oxygen redistribution could for the first time be demonstrated during fluid resuscitation. HES130/0.4 had no influence on the VO2,ren and restored renal function with the least increase in the amount of renal work. PMID:16784545

AGXT2 rs37369 polymorphism predicts the renal function in patients with chronic heart failure.

PubMed

Hu, Xiao-Lei; Zeng, Wen-Jing; Li, Mu-Peng; Yang, Yong-Long; Kuang, Da-Bin; Li, He; Zhang, Yan-Jiao; Jiang, Chun; Peng, Li-Ming; Qi, Hong; Zhang, Ke; Chen, Xiao-Ping

2017-12-30

Patients with chronic heart failure (CHF) are often accompanied with varying degrees of renal diseases. The purpose of this study was to identify rs37369 polymorphism of AGXT2 specific to the renal function of CHF patients. A total of 1012 southern Chinese participants, including 487 CHF patients without history of renal diseases and 525 healthy volunteers, were recruited for this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotypes of AGXT2 rs37369 polymorphism. Levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected to indicate the renal function of the participants. BUN level was significantly higher in CHF patients without history of renal diseases compared with healthy volunteers (p=0.000). And the similar result was also obtained for SCr (p=0.000). Besides, our results indicated that the level of BUN correlated significantly with SCr in both the CHF patients without renal diseases (r=0.4533, p<0.0001) and volunteers (r=0.2489, p<0.0001). Furthermore, we found that the AGXT2 rs37369 polymorphism could significantly affect the level of BUN in CHF patients without history of renal diseases (p=0.036, AA+AG vs GG). Patients with rs37369 GG genotype showed a significantly reduced level of BUN compared to those with the AA genotype (p=0.024), and the significant difference was still observed in the smokers of CHF patients without renal diseases (p=0.023). In conclusion, we found that CHF might induce the impairment of kidney and cause deterioration of renal function. AGXT2 rs37369 polymorphism might affect the renal function of CHF patients free from renal diseases, especially in patients with cigarette smoking. Copyright © 2017. Published by Elsevier B.V.

Correlation of Glomerular Filtration Rate Between Renal Scan and Estimation Equation for Patients With Scleroderma.

PubMed

Suebmee, Patcharawan; Foocharoen, Chingching; Mahakkanukrauh, Ajanee; Suwannaroj, Siraphop; Theerakulpisut, Daris; Nanagara, Ratanavadee

2016-08-01

Renal involvement in scleroderma is life-threatening. Early detection of a deterioration of the glomerular filtration rate (GFR) is needed to preserve kidney function. To (A) determine the correlation between (1) estimated GFR (eGFR) using 4 different formulae and (2) measured GFR (mGFR) using isotopic renal scan in Thai patients with scleroderma with normal serum creatinine and (B) to define the factors influencing eGFR. A cross-sectional study was performed in adult Thai patients with scleroderma at Srinagarind Hospital, Khon Kaen University, between December 2013 and April 2015. GFR was measured using the gold standard Tc-99m DTPA (Tc-99m diethylenetriaminepentaacetic acid) renal scan. We compared the latter with the eGFR, calculated using the Cockroft-Gault formula, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and creatinine clearance equation. A total of 76 patients with scleroderma (50 women and 26 men) with median age 54.8 years (interquartile range: 47.4 to 58.9) were enrolled. Mean disease duration was 5.6 ± 4.5 years. Median value of mGFR was 100.1 ± 27.6mL/minute/1.73m². There was a correlation between mGFR from the Tc-99m DTPA renal scan and the eGFR using the Cockroft-Gault formula, MDRD and CKD-EPI equation (P = 0.01, <0.001 and <0.001, respectively), but no correlation with eGFR using the creatinine clearance equation (P = 0.27). Body weight, prednisolone use and systolic blood pressure (SBP) had a negative association with mGFR (P = 0.01, 0.01 and 0.007, respectively). After multivariate analysis, SBP was the only clinical parameter that influenced mGFR (P = 0.03). The Cockroft-Gault formula, MDRD study equation and CKD-EPI were useful formulae for assessing GFR in Thai patients with scleroderma. Higher SBP was associated with a lower GFR. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Plasma biomarkers are associated with renal outcomes in individuals with APOL1 risk variants.

PubMed

Nadkarni, Girish N; Chauhan, Kinsuk; Verghese, Divya A; Parikh, Chirag R; Do, Ron; Horowitz, Carol R; Bottinger, Erwin P; Coca, Steven G

2018-04-20

G1/G2 variants in the Apolipoprotein L1 (APOL1) gene are associated with end-stage renal disease (ESRD) in people with African ancestry. Plasma biomarkers may have utility for risk stratification in APOL1 high-risk individuals of African ancestry. To evaluate this, we measured tumor necrosis factor receptor 1/2 (TNFR1/2) and kidney injury molecule-1 (KIM1) in baseline plasma specimens from individuals of African ancestry with high-risk APOL1 genotype. Biomarker association with a composite renal outcome of ESRD or 40% sustained decline in estimated glomerular filtration rate (eGFR) was then determined and then assessed as improvement in area under curve. Among the 498 participants, the median age was 56 years, 67.7% were female, and the baseline eGFR was 83.3 ml/min/1.73 m 2 with 80 reaching outcome over 5.9 years. TNFR1, TNFR2, and KIM1 at enrollment were independently associated with renal outcome continuously (adjusted hazard ratio 2.0 [95% confidence interval 1.3-3.1]; 1.5 [1.2-1.9]; and 1.6 [1.3-1.9] per doubling in levels, respectively) or by tertiles. The area under the curve significantly improved from 0.75 with the clinical model to 0.79 with the biomarker-enhanced model. The event rate was 40% with all 3 biomarkers elevated (adjusted odds ratio of 5.3 (2.3-12.0) vs. 17% (adjusted odds ratio 1.8 [0.9-3.6] with 1 or 2 elevated and 7% with no biomarkers elevated. Thus, plasma concentrations of TNFR1, TNFR2, and KIM1 are independently associated with renal outcome and improve discrimination or reclassification of African ancestry individuals with a high-risk APOL1 genotype and preserve renal function. Elevation of all markers had higher risk of outcome and can assist with better clinical prediction and improved clinical trial efficiency by enriching event rates. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

A quantitative systems physiology model of renal function and blood pressure regulation: Model description.

PubMed

Hallow, K M; Gebremichael, Y

2017-06-01

Renal function plays a central role in cardiovascular, kidney, and multiple other diseases, and many existing and novel therapies act through renal mechanisms. Even with decades of accumulated knowledge of renal physiology, pathophysiology, and pharmacology, the dynamics of renal function remain difficult to understand and predict, often resulting in unexpected or counterintuitive therapy responses. Quantitative systems pharmacology modeling of renal function integrates this accumulated knowledge into a quantitative framework, allowing evaluation of competing hypotheses, identification of knowledge gaps, and generation of new experimentally testable hypotheses. Here we present a model of renal physiology and control mechanisms involved in maintaining sodium and water homeostasis. This model represents the core renal physiological processes involved in many research questions in drug development. The model runs in R and the code is made available. In a companion article, we present a case study using the model to explore mechanisms and pharmacology of salt-sensitive hypertension. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Repeated daclizumab administration to delay the introduction of calcineurin inhibitors in heart transplant patients with postoperative renal dysfunction.

PubMed

Sánchez Lázaro, Ignacio J; Almenar Bonet, Luis; Martínez Dolz, Luis; Buendía Fuentes, Francisco; Navarro Manchón, Josep; Agüero Ramón-Llin, Jaime; Vicente Sánchez, José Luis; Salvador Sanz, Antonio

2011-03-01

Daclizumab is an interleukin-2 receptor antagonist which is used for induction therapy in heart transplant patients. It has few side effects and is associated with a low infection rate. Postoperative renal failure after heart transplantation is common and potentially fatal. The administration of calcineurin inhibitors in the postoperative period can aggravate the situation. We report the cases of six patients who underwent heart transplantation and developed acute renal failure in the immediate postoperative period. All were administered daclizumab weekly to avoid the introduction of calcineurin inhibitors and to facilitate recovery of renal function. Calcineurin inhibitors were introduced only once renal function had improved. Renal function recovered in all cases and there was a low complication rate. The administration of repeated doses of daclizumab to patients who experience acute postoperative renal failure after heart transplantation may provide an alternative therapeutic approach that enables calcineurin inhibitors to be avoided and, consequently, renal function to recover. Copyright © 2010 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

MRI to assess renal structure and function.

PubMed

Artunc, Ferruh; Rossi, Cristina; Boss, Andreas

2011-11-01

In addition to excellent anatomical depiction, MRI techniques have expanded to study functional aspects of renal physiology, such as renal perfusion, glomerular filtration rate (GFR) or tissue oxygenation. This review will focus on current developments with an emphasis on clinical applicability. The method of GFR determination is largely heterogeneous and still has weaknesses. However, the technique of employing liver disappearance curves has been shown to be accurate in healthy persons and patients with chronic kidney disease. In potential kidney donors, complete evaluation of kidney anatomy and function can be accomplished in a single-stop investigation. Techniques without contrast media can be utilized to measure renal tissue oxygenation (blood oxygen level-dependent MRI) or perfusion (arterial spin labeling) and could aid in the diagnosis and treatment of ischemic renal diseases, such as renal artery stenosis. Diffusion imaging techniques may provide information on spatially restricted water diffusion and tumor cellularity. Functional MRI opens new horizons in studying renal physiology and pathophysiology in vivo. Although extensively utilized in research, labor-intensive postprocessing and lack of standardization currently limit the clinical applicability of functional MRI. Further studies are necessary to evaluate the clinical value of functional magnetic resonance techniques for early discovery and characterization of kidney disease.

Invariant Natural Killer T Cell Agonist Modulates Experimental Focal and Segmental Glomerulosclerosis

PubMed Central

Semedo, Patricia; Buscariollo, Bruna N.; Donizetti-Oliveira, Cassiano; Cenedeze, Marcos A.; Soares, Maria Fernanda; Pacheco-Silva, Alvaro; Savage, Paul B.; Câmara, Niels O. S.; Keller, Alexandre C.

2012-01-01

A growing body of evidence demonstrates a correlation between Th2 cytokines and the development of focal and segmental glomerulosclerosis (FSGS). Therefore, we hypothesized that GSL-1, a monoglycosylceramide from Sphingomonas ssp. with pro-Th1 activity on invariant Natural Killer T (iNKT) lymphocytes, could counterbalance the Th2 profile and modulate glomerulosclerosis. Using an adriamycin(ADM)-based model of FSGS, we found that BALB/c mice presented albuminuria and glomerular degeneration in association with a Th2-like pro-fibrogenic profile; these mice also expressed a combination of inflammatory cytokines, such as IL-4, IL-1α, IL-1β, IL-17, TNF-α, and chemokines, such as RANTES and eotaxin. In addition, we observed a decrease in the mRNA levels of GD3 synthase, the enzyme responsible for GD3 metabolism, a glycolipid associated with podocyte physiology. GSL-1 treatment inhibited ADM-induced renal dysfunction and preserved kidney architecture, a phenomenon associated with the induction of a Th1-like response, increased levels of GD3 synthase transcripts and inhibition of pro-fibrotic transcripts and inflammatory cytokines. TGF-β analysis revealed increased levels of circulating protein and tissue transcripts in both ADM- and GSL-1-treated mice, suggesting that TGF-β could be associated with both FSGS pathology and iNKT-mediated immunosuppression; therefore, we analyzed the kidney expression of phosphorylated SMAD2/3 and SMAD7 proteins, molecules associated with the deleterious and protective effects of TGF-β, respectively. We found high levels of phosphoSMAD2/3 in ADM mice in contrast to the GSL-1 treated group in which SMAD7 expression increased. These data suggest that GSL-1 treatment modulates the downstream signaling of TGF-β through a renoprotective pathway. Finally, GSL-1 treatment at day 4, a period when proteinuria was already established, was still able to improve renal function, preserve renal structure and inhibit fibrogenic transcripts. In conclusion, our work demonstrates that the iNKT agonist GSL-1 modulates the pathogenesis of ADM-induced glomerulosclerosis and may provide an alternative approach to disease management. PMID:22427838

[Impaired renal function: be aware of exogenous factors].

PubMed

van der Meijden, Wilbert A G; Smak Gregoor, Peter J H

2013-01-01

Renal function is currently estimated using the Modification of Diet in Renal Disease (MDRD) formula, which is partly based on the serum creatinine level. Patients with impaired renal function are referred to nephrologists in accordance with the Dutch national transmural agreement for 'Chronic renal impairment'. A 54-year-old woman without significant history was referred to analyse a coincidentally found decline in the estimated glomerular filtration rate (eGFR). The patient had no complaints and used no medication except creatine supplements. Additional diagnostic testing showed no abnormalities. After cessation of creatine supplementation, the calculated renal function normalized. Serum creatinine is a reflection of muscle mass. The use of creatine-containing dietary supplements, such as creatine ethyl ester, can influence serum creatinine levels and therefore the eGFR as calculated with the MDRD formula. The use of supplements deserves attention when taking the history.

Worsening renal function defined as an absolute increase in serum creatinine is a biased metric for the study of cardio-renal interactions.

PubMed

Testani, Jeffrey M; McCauley, Brian D; Chen, Jennifer; Shumski, Michael; Shannon, Richard P

2010-01-01

Worsening renal function (WRF) during the treatment of decompensated heart failure, frequently defined as an absolute increase in serum creatinine >or=0.3 mg/dl, has been reported as a strong adverse prognostic factor in several studies. We hypothesized that this definition of WRF is biased by baseline renal function secondary to the exponential relationship between creatinine and renal function. We reviewed consecutive admissions with a discharge diagnosis of heart failure. An increase in creatinine >or=0.3 mg/dl (WRF(CREAT)) was compared to a decrease in GFR >or=20% (WRF(GFR)). Overall, 993 admissions met eligibility. WRF(CREAT) occurred in 31.5% and WRF(GFR) in 32.7%. WRF(CREAT) and WRF(GFR) had opposing relationships with baseline renal function (OR = 1.9 vs. OR = 0.51, respectively, p < 0.001). Both definitions had similar unadjusted associations with death at 30 days [WRF(GFR) OR = 2.3 (95% CI 1.1-4.8), p = 0.026; WRF(CREAT) OR = 2.1 (95% CI 1.0-4.4), p = 0.047]. Controlling for baseline renal insufficiency, WRF(GFR) added incrementally in the prediction of mortality (p = 0.009); however, WRF(CREAT) did not (p = 0.11). WRF, defined as an absolute change in serum creatinine, is heavily biased by baseline renal function. An alternative definition of WRF should be considered for future studies of cardio-renal interactions. Copyright 2010 S. Karger AG, Basel.

Prenatal hydronephrosis: postnatal evaluation and management.

PubMed

Vemulakonda, Vijaya; Yiee, Jenny; Wilcox, Duncan T

2014-08-01

Congenital hydronephrosis is one of the most common anomalies identified on antenatal ultrasound. The underlying etiology of congenital hydronephrosis is multifold, ranging from transient hydronephrosis in utero to clinically significant congenital anomalies of the kidney and urinary tract. While traditional management of hydronephrosis was aimed at relieving symptoms, the advent of routine prenatal ultrasound has led to a shift in the goal of treatment to prevention of renal injury in the asymptomatic patient. However, despite this focus on renal preservation, the diagnostic criteria for identification of children "at risk" for renal damage that can be alleviated by surgical treatment remain a subject of debate. Both antenatal and postnatal imaging studies have been evaluated as indicators for potential reversible renal damage and have been used as potential indicators of the need for surgical intervention. The aim of this review is to discuss the current literature regarding the role of postnatal clinical and radiographic evaluation to identify children who may benefit from early surgical intervention.

Direct Revascularization with Autotransplant Technique for a True Aneurysm of the Renal Artery 20 Years after Kidney Transplantation.

PubMed

Mezzetto, Luca; Boschiero, Luigino; Fior, Francesca; Nguefouet Momo, Rostand Emmanuel; Nacchia, Francesco; Eccher, Albino; Macrì, Marco; Veraldi, Gian Franco

2016-04-01

True degenerative aneurysm of renal artery represents a very rare evolution in kidney transplantation. The cases presented in the literature are usually perianastomotic or mycotic pseudoaneurysm related to surgical technical defects or local infections. Herewith, we present the case of a voluminous true aneurysm developed in a young patient transplanted at our hospital 20 years before. All follow-up ultrasounds were always normal until the last disclosing a voluminous aneurysm of the transplanted renal artery. The subsequent angio-CT-scan confirmed the presence of a 52-mm saccular dilatation of the renal artery. For the complex anatomy, the endovascular approach was excluded, and a surgical revascularization was staged. We treated this lesion with the autotransplant technique, preserving the transplanted kidney, resecting the aneurysm, and performing a direct anastomosis after cold perfusion of the kidney. The autotransplant technique demonstrated to be a safe and effective approach in this challenging and very unusual situation. Copyright © 2016 Elsevier Inc. All rights reserved.

Tubulointerstitial nephritis and uveitis syndrome in a twelve-year-old girl.

PubMed

Paladini, Alessia; Venturoli, Vittorio; Mosconi, Giovanni; Zambianchi, Loretta; Serra, Luigi; Valletta, Enrico

2013-01-01

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disorder defined by the combination of biochemical abnormalities, tubulointerstitial nephritis, and uveitis. We describe a 12-year-old female, presented with a ten-day history of fever, characterized by sudden onset and rapid spontaneous resolution in few hours, accompanied by shivering, extreme fatigue, and loss of appetite. Laboratory values were consistent with renal failure of tubular origin. Renal biopsy confirmed a tubulointerstitial nephritis, with acute tubulitis, polymorphonuclear infiltration, and microabscesses. The renal interstitium was occupied by a dense inflammatory infiltrate, consisting of lymphocytes, plasma cells, and neutrophils. Glomerular structures were preserved. Ophthalmological examination that suggested a previous asymptomatic bilateral uveitis and HLA typing (HLA-DQA1∗0101/0201 and HLA-DQB1∗0303/0503) further supported the suspect of TINU syndrome. TINU syndrome is probably an underdiagnosed disorder, responsible for many cases of idiopathic anterior uveitis in young patients, especially in those who have asymptomatic renal disease and when proper diagnostic tests are not performed at the time of presentation.

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

External validation of the Revised Cardiac Risk Index and update of its renal variable to predict 30-day risk of major cardiac complications after non-cardiac surgery: rationale and plan for analyses of the VISION study.

PubMed

Roshanov, Pavel S; Walsh, Michael; Devereaux, P J; MacNeil, S Danielle; Lam, Ngan N; Hildebrand, Ainslie M; Acedillo, Rey R; Mrkobrada, Marko; Chow, Clara K; Lee, Vincent W; Thabane, Lehana; Garg, Amit X

2017-01-09

The Revised Cardiac Risk Index (RCRI) is a popular classification system to estimate patients' risk of postoperative cardiac complications based on preoperative risk factors. Renal impairment, defined as serum creatinine >2.0 mg/dL (177 µmol/L), is a component of the RCRI. The estimated glomerular filtration rate has become accepted as a more accurate indicator of renal function. We will externally validate the RCRI in a modern cohort of patients undergoing non-cardiac surgery and update its renal component. The Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) study is an international prospective cohort study. In this prespecified secondary analysis of VISION, we will test the risk estimation performance of the RCRI in ∼34 000 participants who underwent elective non-cardiac surgery between 2007 and 2013 from 29 hospitals in 15 countries. Using data from the first 20 000 eligible participants (the derivation set), we will derive an optimal threshold for dichotomising preoperative renal function quantified using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) glomerular filtration rate estimating equation in a manner that preserves the original structure of the RCRI. We will also develop a continuous risk estimating equation integrating age and CKD-Epi with existing RCRI risk factors. In the remaining (approximately) 14 000 participants, we will compare the risk estimation for cardiac complications of the original RCRI to this modified version. Cardiac complications will include 30-day non-fatal myocardial infarction, non-fatal cardiac arrest and death due to cardiac causes. We have examined an early sample to estimate the number of events and the distribution of predictors and missing data, but have not seen the validation data at the time of writing. The research ethics board at each site approved the VISION protocol prior to recruitment. We will publish our results and make our models available online at http://www.perioperativerisk.com. ClinicalTrials.gov NCT00512109. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Correction of differential renal function for asymmetric renal area ratio in unilateral hydronephrosis.

PubMed

Aktaş, Gul Ege; Sarıkaya, Ali

2015-11-01

Children with unilateral hydronephrosis are followed up with anteroposterior pelvic diameter (APD), hydronephrosis grade, mercaptoacetyltriglycine (MAG-3) drainage pattern and differential renal function (DRF). Indeterminate drainage preserved DRF in higher grades of hydronephrosis, in some situations, complicating the decision-making process. Due to an asymmetric renal area ratio, falsely negative DRF estimations can result in missed optimal surgery times. This study was designed to assess whether correcting the DRF estimation according to kidney area could reflect the clinical situation of a hydronephrotic kidney better than a classical DRF calculation, concurrently with the hydronephrosis grade, APD and MAG-3 drainage pattern. We reviewed the MAG-3, dimercaptosuccinic acid (DMSA) scans and ultrasonography (US) of 23 children (6 girls, 17 boys, mean age: 29 ± 50 months) with unilateral hydronephrosis. MAG-3 and DMSA scans were performed within 3 months (mean 25.4 ± 30.7 days). The closest US findings (mean 41.5 ± 28.2 days) were used. DMSA DRF estimations were obtained using the geometric mean method. Secondary calculations were performed to correct the counts (the total counts divided by the number of pixels in ROI) according to kidney area. The renogram patterns of patients were evaluated and separated into subgroups. The visual assessment of DMSA scans was noted and the hydronephrotic kidney was classified in comparison to the normal contralateral kidney's uptake. The correlations of the DRF values of classical and area-corrected methods with MAG-3 renogram patterns, the visual classification of DMSA scan, the hydronephrosis grade and the APD were assessed. DRF estimations of two methods were statistically different (p: 0.001). The categories of 12 hydronephrotic kidneys were changed. There were no correlations between classical DRF estimations and the hydronephrosis grade, APD, visual classification of the DMSA scan and uptake evaluation. The DRF distributions according to MAG-3 drainage patterns were not different. Area-corrected DRF estimations correlated with all: with an increasing hydronephrosis grade and APD, DRF estimations decreased and MAG-3 drainage patterns worsened. A decrease in DRF (< 45 %) was determined when APD was ≥ 10 mm. When APD was ≥ 26 mm, a reduction of DRF below 40 % was determined. Our results suggest that correcting DRF estimation for asymmetric renal area ratio in unilateral hydronephrosis can be more robust than the classical method, especially for higher grades of hydronephrotic kidneys, under equivocal circumstances.

Impact of Impaired Renal Function on Gadolinium Retention After Administration of Gadolinium-Based Contrast Agents in a Mouse Model.

PubMed

Kartamihardja, A Adhipatria P; Nakajima, Takahito; Kameo, Satomi; Koyama, Hiroshi; Tsushima, Yoshito

2016-10-01

The aim of this study was to investigate the impact of impaired renal function on gadolinium (Gd) retention in various organs after Gd-based contrast agent injection. After local animal care and review committee approval, 23 normal mice and 26 with renal failure were divided into 4 treatment groups (Gd-DTPA-BMA, 5 mmol/kg; Gd-DOTA, 5 mmol/kg; GdCl3, 0.02 mmol/kg; and saline, 250 μL). Each agent was intravenously administered on weekdays for 4 weeks. Samples were collected on days 3 (short-term) and 45 (long-term) after the last injection. Gadolinium concentrations were quantified by inductively coupled plasma-mass spectrometry. Three mice with renal failure and 2 normal mice in the GdCl3 group and 1 mouse with renal failure in the Gd-DTPA-BMA group died. In the Gd-DTPA-BMA group, impaired renal function increased short-term Gd retention in the liver, bone, spleen, skin, and kidney (P < 0.01) but did not affect long-term Gd retention. Gd-DTPA-BMA showed higher Gd retention than Gd-DOTA. Although Gd retention in the Gd-DOTA group was generally low, impaired renal function increased only long-term hepatic Gd retention. Hepatic and splenic Gd retentions were significantly higher than other organs' Gd retention in the GdCl3 group (P < 0.01). Renal function did not affect brain Gd retention, regardless of the Gd compound used. The tendency of Gd retention varied according to the agent, regardless of renal function. Although renal impairment increased short-term Gd retention after Gd-DTPA-BMA administration, long-term Gd retention for Gd-based contrast agents was almost unaffected by renal function, suggesting that the chemical structures of retained Gd may not be consistent and some Gd is slowly eliminated after initially being retained.

Predictors of Renal Function Decline in Chinese Patients with Type 2 Diabetes Mellitus and in a Subgroup of Normoalbuminuria: A Retrospective Cohort Study.

PubMed

Hu, Ping; Zhou, Xiang-Hai; Wen, Xin; Ji, Linong

2016-10-01

Risk factors related to renal function decline in type 2 diabetes mellitus (T2DM) remain uncertain. This study aimed to investigate risk factors in relation to renal function decline in patients with T2DM and in a subgroup of patients with normoalbuminuria. This study was a retrospective cohort study, which included 451 patients with T2DM aged 63 ± 14 years admitted to a tertiary hospital in Beijing, China, between April and December 2010 and followed up for 6-60 months. Endpoint was renal function decline, defined as estimated glomerular filtration rate less than 60 mL/min 1.73 m 2 or at least twofold increase of serum creatinine. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) for candidate risk factors of renal function decline. After a median follow-up of 3.3 years, 94 (20.8%) patients developed renal function decline. Increased age (HR, 1.045; 95% CI, 1.020-1.070), albuminuria (HR, 1.956; 95%CI, 1.271-3.011), mild renal dysfunction (HR, 4.521; 95%CI, 2.734-7.476), hyperfiltration (HR, 3.897; 95%CI, 1.572-9.663), and increased hemoglobin A1c (HR, 1.128; 95%CI, 1.020-1.249) were identified as major risk factors. Among a subgroup of 344 patients with normoalbuminuria at baseline, 53 (15.4%) patients developed renal function decline. Increased age (HR, 1.089; 95%CI, 1.050-1.129), mild renal dysfunction (HR, 4.667; 95%CI, 2.391-9.107), hyperfiltration (HR, 5.677; 95%CI, 1.544-20.872), smoking (HR, 2.886; 95%CI, 1.370-6.082), higher pulse pressure (HR, 1.022; 95%CI, 1.004-1.040), and increased fasting glucose (HR, 1.104; 95%CI, 1.020-1.194) were major risk factors. Risk factors of diabetic renal impairment in T2DM should be screened and evaluated at an early stage of diabetes. Albuminuria, mild renal dysfunction, hyperfiltration, increased blood glucose, increased pulse pressure, and smoking were all predictors for diabetic renal impairment and interventions that focus on these risk factors may reduce further decline in renal function.

Vesicoureteral reflux in the primate IV: does reflux harm the kidney

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

Roberts, J.A.; Fischman, N.H.; Thomas, R.

1982-09-01

It has been said that vesicoureteral reflux causes renal scarring because of intrarenal reflux. We studied reflux in the monkey because of its similarity to man, especially in regard to the incidence of vesicoureteral reflux and chronic pyelonephritis. High pressure moderate grade reflux was produced and renal function followed by means of quantitative renal camera studies using /sup 131/I hippuran. There was no change in renal function from sterile reflux even when intrarenal reflux occurred. When, however, infection was introduced, renal function decreased. We concluded that sterile moderate vesicoureteral or intrarenal reflux does not harm the kidney.

Why and how to measure renal function in patients with liver disease.

PubMed

Piano, Salvatore; Romano, Antonietta; Di Pascoli, Marco; Angeli, Paolo

2017-01-01

Patients with advanced liver disease frequently have impaired renal function. Both acute kidney injury (AKI) and chronic kidney disease (CKD) are quite common in patients with cirrhosis and both are associated with a worse prognosis in these patients. A careful assessment of renal function is highly important in these patients to help physicians determine their diagnosis, prognosis and therapeutic management and to define transplantation strategies (liver transplantation alone vs simultaneous liver and kidney transplantation). Although they are still widely used in clinical practice, conventional biomarkers of renal function such as serum creatinine have several limitations in these patients. Recent progress has been made in the evaluation of renal function and new diagnostic criteria for AKI have been proposed. However, certain issues such as the noninvasive assessment of the glomerular filtration rate and/or improvement in the differential diagnosis between hepatorenal syndrome and acute tubular necrosis must still be addressed. The purposes of this paper are: (i) to highlight the importance of the evaluation of renal function in patients with cirrhosis; (ii) to review the state of the art in the assessment of renal function in these patients as well as advances that we expect will be made to improve the accuracy of available tools. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Peritoneal dialysis: a primary care perspective.

PubMed

Saxena, Ramesh; West, Cheryl

2006-01-01

As the population of chronic kidney disease (CKD) and end-stage renal disease (ESRD) grows at an alarming rate, primary care physicians will increasingly be involved in the management of these patients. Early recognition of CKD and timely referral to a nephrologist when glomerular filtration rate approaches 30 mL/min/1.73 m(2) is extremely important to improve ESRD outcome and appropriate selection of dialysis modality. Peritoneal dialysis (PD) remains a viable treatment option for ESRD patients. PD is less expensive dialysis modality and may provide a survival advantages over hemodialysis in first 2 to 4 years of treatment. Preserving residual renal function (RRF) is of paramount importance to prolong the survival outcomes in PD patients. Thus preservation of RRF is an important goal in the management of PD patients. Every effort should be made to avoid nephrotoxic drugs like aminoglycosides and nonsteroidal anti-inflammatory drugs, and limit the use of radiocontrast agents in PD patients with RRF. Judicious use of prophylactic antibiotics to prevent peritonitis would further help to reduce morbidity from PD. Protecting peritoneal membrane from long-term toxic and metabolic effects of the conventional glucose-based solutions is another objective to further improve PD outcome. Development of new, more biocompatible PD solutions holds promise for the future. One such solution, icodextrin, is now approved for use in the United States. Although extremely safe to use, it is associated with unique metabolic effects that may concern primary care physicians. They include false elevation of blood glucose, a reversible increase in serum alkaline phosphatase and a false decline in serum amylase. Monitoring of glycemia by assays that use glucose dehydrogenase pyrroloquinoline quinone enzymes should be avoided and serum amylase alone should not be relied on in diagnosing pancreatitis in patients on icodextrin.

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction

PubMed Central

2013-01-01

Background Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Methods Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Results Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. Conclusion These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction. PMID:23849513

Dosing of cytotoxic chemotherapy: impact of renal function estimates on dose.

PubMed

Dooley, M J; Poole, S G; Rischin, D

2013-11-01

Oncology clinicians are now routinely provided with an estimated glomerular filtration rate on pathology reports whenever serum creatinine is requested. The utility of using this for the dose determination of renally excreted drugs compared with other existing methods is needed to inform practice. Renal function was determined by [Tc(99m)]DTPA clearance in adult patients presenting for chemotherapy. Renal function was calculated using the 4-variable Modification of Diet in Renal Disease (4v-MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Cockcroft and Gault (CG), Wright and Martin formulae. Doses for renal excreted cytotoxic drugs, including carboplatin, were calculated. The concordance of the renal function estimates according to the CKD classification with measured Tc(99m)DPTA clearance in 455 adults (median age 64.0 years: range 17-87 years) for the 4v-MDRD, CKD-EPI, CG, Martin and Wright formulae was 47.7%, 56.3%, 46.2%, 56.5% and 60.2%, respectively. Concordance for chemotherapy dose for these formulae was 89.0%, 89.5%, 85.1%, 89.9% and 89.9%, respectively. Concordance for carboplatin dose specifically was 66.4%, 71.4%, 64.0%, 73.8% and 73.2%. All bedside formulae provide similar levels of concordance in dosage selection for the renal excreted chemotherapy drugs when compared with the use of a direct measure of renal function.

RGS4 inhibits angiotensin II signaling and macrophage localization during renal reperfusion injury independent of vasospasm

PubMed Central

Pang, Paul; Jin, Xiaohua; Proctor, Brandon M.; Farley, Michelle; Roy, Nilay; Chin, Matthew S.; von Andrian, Ulrich H.; Vollmann, Elisabeth; Perro, Mario; Hoffman, Ryan J.; Chung, Joseph; Chauhan, Nikita; Mistri, Murti; Muslin, Anthony J.; Bonventre, Joseph V.; Siedlecki, Andrew M.

2014-01-01

Vascular inflammation is a major contributor to the severity of acute kidney injury. In the context of vasospasm-independent reperfusion injury we studied the potential anti-inflammatory role of the Gα-related RGS protein, RGS4. Transgenic RGS4 mice were resistant to 25 minute injury, although post-ischemic renal arteriolar diameter was equal to the wild type early after injury. A 10 minute unilateral injury was performed to study reperfusion without vasospasm. Eighteen hours after injury blood flow was decreased in the inner cortex of wild type mice with preservation of tubular architecture. Angiotensin II levels in the kidneys of wild type and transgenic mice were elevated in a sub-vasoconstrictive range 12 and 18 hours after injury. Angiotensin II stimulated pre-glomerular vascular smooth muscle cells (VSMC) to secrete the macrophage chemoattractant, RANTES; a process decreased by angiotensin II R2 (AT2) inhibition. However, RANTES increased when RGS4 expression was suppressed implicating Gα protein activation in an AT2-RGS4-dependent pathway. RGS4 function, specific to VSMC, was tested in a conditional VSMC-specific RGS4 knockout showing high macrophage density by T2 MRI compared to transgenic and non-transgenic mice after the 10 minute injury. Arteriolar diameter of this knockout was unchanged at successive time points after injury. Thus, RGS4 expression, specific to renal VSMC, inhibits angiotensin II-mediated cytokine signaling and macrophage recruitment during reperfusion, distinct from vasomotor regulation. PMID:25469849

Effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on cardiovascular events and residual renal function in dialysis patients: a meta-analysis of randomised controlled trials.

PubMed

Liu, Youxia; Ma, Xinxin; Zheng, Jie; Jia, Junya; Yan, Tiekun

2017-06-30

The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reducing risk of cardiovascular events (CVEs) and preserving kidney function in patients with chronic kidney disease is well-documented. However, the efficacy and safety of these agents in dialysis patients is still a controversial issue. We systematically searched MEDLINE, Embase, Cochrane Library and Wanfang for randomized trials. The relative risk (RR) reductions were calculated with a random-effects model. Major cardiovascular events, changes in GFR and drug-related adverse events were analyzed. Eleven trials included 1856 participants who were receiving dialysis therapy. Compared with placebo or other active agents groups, ARB therapy reduced the risk of heart failure events by 33% (RR 0.67, 95% CI 0.47 to 0.93) with similar decrement in blood pressure in dialysis patients. Indirect comparison suggested that fewer cardiovascular events happened during treatment with ARB (0.77, 0.63 to 0.94). The results indicated no significant differences between the two treatment regimens with regard to frequency of myocardial infarction (1.0, 0.45 to 2.22), stroke (1.16, 0.69 to 1.96), cardiovascular death (0.89, 0.64 to 1.26) and all-cause mortality (0.94, 0.75 to 1.17). Five studies reported the renoprotective effect and revealed that ACEI/ARB therapy significantly slowed the rate of decline in both residual renal function (MD 0.93 mL/min/1.73 m 2 , 0.38 to 1.47 mL/min/1.73 m 2 ) and urine volume (MD 167 ml, 95% CI 21 ml to 357 ml). No difference in drug-related adverse events was observed in both treatment groups. This study demonstrates that ACE-Is/ARBs therapy decreases the loss of residual renal function, mainly for patients with peritoneal dialysis. Overall, ACE-Is and ARBs do not reduce cardiovascular events in dialysis patients, however, treatment with ARB seems to reduce cardiovascular events including heart failure. ACE-Is and ARBs do not induce an extra risk of side effects.

Artificial Gravity: Will it Preserve Bone Health on Long-Duration Missions?

NASA Technical Reports Server (NTRS)

Davis-Street, Janis; Paloski, William H.

2005-01-01

Prolonged microgravity exposure disrupts bone, muscle, and cardiovascular homeostasis, sensory-motor coordination, immune function, and behavioral performance. Bone loss, in particular, remains a serious impediment to the success of exploration-class missions by increasing the risks of bone fracture and renal stone formation for crew members. Current countermeasures, consisting primarily of resistive and aerobic exercise, have not yet proven fully successful for preventing bone loss during long-duration spaceflight. While other bone-specific countermeasures, such as pharmacological therapy and dietary modifications, are under consideration, countermeasure approaches that simultaneously address multiple physiologic systems may be more desirable for exploration-class missions, particularly if they can provide effective protection at reduced mission resource requirements (up-mass, power, crew time, etc). The most robust of the multi-system approaches under consideration, artificial gravity (AG), could prevent all of the microgravity-related physiological changes from occurring. The potential methods for realizing an artificial gravity countermeasure are reviewed, as well as selected animal and human studies evaluating the effects of artificial gravity on bone function. Future plans for the study of the multi-system effects of artificial gravity include a joint, cooperative international effort that will systematically seek an optimal prescription for intermittent AG to preserve bone, muscle, and cardiovascular function in human subjects deconditioned by 6 degree head-down-tilt-bed rest. It is concluded that AG has great promise as a multi-system countermeasure, but that further research is required to determine the appropriate parameters for implementation of such a countermeasure for exploration-class missions.

mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells.

PubMed

Grahammer, Florian; Ramakrishnan, Suresh K; Rinschen, Markus M; Larionov, Alexey A; Syed, Maryam; Khatib, Hazim; Roerden, Malte; Sass, Jörn Oliver; Helmstaedter, Martin; Osenberg, Dorothea; Kühne, Lucas; Kretz, Oliver; Wanner, Nicola; Jouret, Francois; Benzing, Thomas; Artunc, Ferruh; Huber, Tobias B; Theilig, Franziska

2017-01-01

Renal proximal tubular cells constantly recycle nutrients to ensure minimal loss of vital substrates into the urine. Although most of the transport mechanisms have been discovered at the molecular level, little is known about the factors regulating these processes. Here, we show that mTORC1 and mTORC2 specifically and synergistically regulate PTC endocytosis and transport processes. Using a conditional mouse genetic approach to disable nonredundant subunits of mTORC1, mTORC2, or both, we showed that mice lacking mTORC1 or mTORC1/mTORC2 but not mTORC2 alone develop a Fanconi-like syndrome of glucosuria, phosphaturia, aminoaciduria, low molecular weight proteinuria, and albuminuria. Interestingly, proteomics and phosphoproteomics of freshly isolated kidney cortex identified either reduced expression or loss of phosphorylation at critical residues of different classes of specific transport proteins. Functionally, this resulted in reduced nutrient transport and a profound perturbation of the endocytic machinery, despite preserved absolute expression of the main scavenger receptors, MEGALIN and CUBILIN. Our findings highlight a novel mTOR-dependent regulatory network for nutrient transport in renal proximal tubular cells. Copyright © 2016 by the American Society of Nephrology.

Frequency response of the renal vasculature in congestive heart failure.

PubMed

DiBona, Gerald F; Sawin, Linda L

2003-04-29

The renal vasoconstrictor response to renal nerve stimulation is greater in congestive heart failure (CHF) rats than in control rats. This study tested the hypothesis that the enhanced renal vasoconstrictor response to renal nerve stimulation in CHF is a result of an impairment in the low-pass filter function of the renal vasculature. In response to conventional graded-frequency renal nerve stimulation, the reductions in renal blood flow at each stimulation frequency were greater in CHF rats than control rats. A pseudorandom binary sequence pattern of renal nerve stimulation was used to examine the frequency response of the renal vasculature. Although this did not affect the renal blood flow power spectrum in control rats, there was a 10-fold increase in renal blood flow power over the frequency range of 0.01 to 1.0 Hz in CHF rats. On analysis of transfer function gain, attenuation of the renal nerve stimulation input signal was similar in control and CHF rats over the frequency range of 0.001 to 0.1 Hz. However, over the frequency range of 0.1 to 1.0 Hz, although there was progressive attenuation of the input signal (-30 to -70 dB) in control rats, CHF rats exhibited a flat gain response (-20 dB) without progressive attenuation. The enhanced renal vasoconstrictor response to renal nerve stimulation in CHF rats is caused by an alteration in the low-pass filter function of the renal vasculature, resulting in a greater transfer of input signals into renal blood flow in the 0.1 to 1.0 Hz range.

Changes in urine volume and serum albumin in incident hemodialysis patients.

PubMed

Eriguchi, Rieko; Obi, Yoshitsugu; Rhee, Connie M; Chou, Jason A; Tortorici, Amanda R; Mathew, Anna T; Kim, Taehee; Soohoo, Melissa; Streja, Elani; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2017-10-01

Hypoalbuminemia is a predictor of poor outcomes in dialysis patients. Among hemodialysis patients, there has not been prior study of whether residual kidney function or decline over time impacts serum albumin levels. We hypothesized that a decline in residual kidney function is associated with an increase in serum albumin levels among incident hemodialysis patients. In a large national cohort of 38,504 patients who initiated hemodialysis during 1/2007-12/2011, we examined the association of residual kidney function, ascertained by urine volume and renal urea clearance, with changes in serum albumin over five years across strata of baseline residual kidney function, race, and diabetes using case-mix adjusted linear mixed effects models. Serum albumin levels increased over time. At baseline, patients with greater urine volume had higher serum albumin levels: 3.44 ± 0.48, 3.50 ± 0.46, 3.57 ± 0.44, 3.59 ± 0.45, and 3.65 ± 0.46 g/dL for urine volume groups of <300, 300-<600, 600-<900, 900-<1,200, and ≥1,200 mL/day, respectively (P trend  < 0.001). Over time, urine volume and renal urea clearance declined and serum albumin levels rose, while the baseline differences in serum albumin persisted across groups of urinary volume. In addition, the rate of decline in residual kidney function was not associated with the rate of change in albumin. Hypoalbuminemia in hemodialysis patients is associated with lower residual kidney function. Among incident hemodialysis patients, there is a gradual rise in serum albumin that is independent of the rate of decline in residual kidney function, suggesting that preservation of residual kidney function does not have a deleterious impact on serum albumin levels. © 2016 International Society for Hemodialysis.

78 FR 8535 - Medicare Program: Comprehensive End-Stage Renal Disease Care Model Announcement

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-06

... develop and test innovative health care payment and service delivery models that show promise of reducing program expenditures, while preserving or enhancing the quality of care for Medicare, Medicaid, and... disease (ESRD). This population has complex health care needs, typically with comorbid conditions and...

Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban.

PubMed

Chang, Ming; Yu, Zhigang; Shenker, Andrew; Wang, Jessie; Pursley, Janice; Byon, Wonkyung; Boyd, Rebecca A; LaCreta, Frank; Frost, Charles E

2016-05-01

This open-label study evaluated apixaban pharmacokinetics, pharmacodynamics, and safety in subjects with mild, moderate, or severe renal impairment and in healthy subjects following a single 10-mg oral dose. The primary analysis determined the relationship between apixaban AUC∞ and 24-hour creatinine clearance (CLcr ) as a measure of renal function. The relationships between 24-hour CLcr and iohexol clearance, estimated CLcr (Cockcroft-Gault equation), and estimated glomerular filtration rate (modification of diet in renal disease [MDRD] equation) were also assessed. Secondary objectives included assessment of safety and tolerability as well as international normalized ratio (INR) and anti-factor Xa activity as pharmacodynamic endpoints. The regression analysis showed that decreasing renal function resulted in modestly increased apixaban exposure (AUC∞ increased by 44% in severe impairment with a 24-hour CLcr of 15 mL/min, compared with subjects with normal renal function), but it did not affect Cmax or the direct relationship between apixaban plasma concentration and anti-factor Xa activity or INR. The assessment of renal function measured by iohexol clearance, Cockcroft-Gault, and MDRD was consistent with that determined by 24-hour CLcr . Apixaban was well tolerated in this study. These results suggest that dose adjustment of apixaban is not required on the basis of renal function alone. © 2015, The American College of Clinical Pharmacology.

Renal function in atrial fibrillation patients switched from warfarin to a direct oral anticoagulant.

PubMed

Minhas, Anum S; Jiang, Qingmei; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Krol, Gregory D; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

2016-11-01

All available direct oral anticoagulants (DOACs) are at least partially eliminated by the kidneys. These agents are increasingly being used as alternatives to warfarin for stroke prevention in patients with atrial fibrillation. The aim of this study was to identify changes in renal function and associated DOAC dosing implications in a multicenter cohort of atrial fibrillation patients switched from warfarin to DOAC treatment. We included all patients in the Michigan Anticoagulation Quality Improvement Initiative cohort who switched from warfarin to a DOAC with atrial fibrillation as their anticoagulant indication between 2009 and 2014, and who had at least two creatinine values. Compliance with FDA-recommended dosing based on renal function was assessed. Of the 189 patients switched from warfarin to a DOAC, 34 (18.0 %) had a baseline creatinine clearance <50 mL/min and 23 (12.2 %) experienced important fluctuations in renal function. Of these 23 patients, 6 (26.1 %) should have impacted the DOAC dosing, but only 1 patient actually received an appropriate dose adjustment. Additionally, 15 (7.9 %) of patients on DOACs had a dose change performed, but only one patient demonstrated a change in renal function to justify the dose adjustment. Most atrial fibrillation patients who switched from warfarin to a DOAC had stable renal function. However, the majority of patients who had a change in renal function did not receive the indicated dose change. As the use of DOACs expands, monitoring of renal function and appropriate dose adjustments are critical.

The preservation of urine samples for determination of renal stone risk factors

NASA Technical Reports Server (NTRS)

Nicar, M. J.; Hsu, M. C.; Johnson, T.; Pak, C. Y.

1987-01-01

A preservation technique for urine specimens before determination of stone risk factors was evaluated. The purpose of these experiments was to prove the effectiveness of the preservatives used to prevent changes in the concentrations of those constituents measured. Measured concentrations in fresh specimens were compared with those in the same specimens after storage with the preservatives. Refrigeration at 4 degrees C up to five days was appropriate in a laboratory setting, as no significant changes in urinary concentrations occurred. Refrigeration, however, did not offer a convenient method for shipping. Chemical preservation was found to be an effective alternative to refrigeration. Thymol prevented changes in concentration of pH, citrate, uric acid, sulfate, sodium, potassium, and cyclic AMP, while a mixture of hydrochloric (HCl) acid and boric acid prevented changes in calcium, magnesium, phosphorus, oxalate, ammonium, and creatinine. Thus, the addition of thymol or HCl/boric acid to urine specimens will prevent significant changes in the concentrations of stone risk factors.

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

Dubovsky, E.V.; Curtis, J.J.; Luke, R.G.

Impaired function of renal allografts caused by recurrent disease or rejection is often accompanied by hypertension. The etiology of persistent severe hypertension in recipients with good renal function is more difficult to explain. To study this problem, 33 patients with mean arterial pressure (MAP) > 105 mm Hg (at least one year after transplantation) were tested. When compared to a normotensive group, they were found to have increased renal vascular resistance, lower ERPF, and increased renin-angiotensin activity. The effect of Captopril, a converting enzyme inhibitor, was studied to evaluate the role of angiotension. The paper concludes that Captopril test maymore » permit differentiation between native kidney-dependent hypertension (increase in ERPF) and functionally active renal artery stenosis (decline in ERPF) in patients with persistent hypertension and good renal function.« less

Reference values of renal tubular function tests are dependent on age and kidney function.

PubMed

Bech, Anneke P; Wetzels, Jack F M; Nijenhuis, Tom

2017-12-01

Electrolyte disorders due to tubular disorders are rare, and knowledge about validated clinical diagnostic tools such as tubular function tests is sparse. Reference values for tubular function tests are based on studies with small sample size in young healthy volunteers. Patients with tubular disorders, however, frequently are older and can have a compromised renal function. We therefore evaluated four tubular function tests in individuals with different ages and renal function. We performed furosemide, thiazide, furosemide-fludrocortisone, and desmopressin tests in healthy individuals aged 18-50 years, healthy individuals aged more than 50 years and individuals with compromised renal function. For each tubular function test we included 10 individuals per group. The responses in young healthy individuals were in line with previously reported values in literature. The maximal increase in fractional chloride excretion after furosemide was below the lower limit of young healthy individuals in 5/10 older subjects and in 2/10 patients with compromised renal function. The maximal increase in fractional chloride excretion after thiazide was below the lower limit of young healthy individuals in 6/10 older subjects and in 7/10 patients with compromised renal function. Median maximal urine osmolality after desmopressin was 1002 mosmol/kg H 2 O in young healthy individuals, 820 mosmol/kg H 2 O in older subjects and 624 mosmol/kg H 2 O in patients with compromised renal function. Reference values for tubular function tests obtained in young healthy adults thus cannot simply be extrapolated to older patients or patients with compromised kidney function. Larger validation studies are needed to define true reference values in these patient categories. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Stent-Assisted Coil Embolization of a Mycotic Renal Artery Aneurysm by Use of a Self-Expanding Neurointerventional Stent

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

Rabellino, Martin, E-mail: jmrabellino@hotmail.com; Garcia-Nielsen, Luis, E-mail: luisgarcia@hospiten.es; Zander, Tobias, E-mail: tobiaszander@hospiten.es

2011-02-15

Mycotic aneurysms are uncommon, especially those located in visceral arteries. We present a case of a patient with two visceral mycotic aneurysms due to bacterial endocarditis, one located in right upper pole renal artery and the second in the splenic artery. Both aneurysms were treated as endovascular embolization using microcoils. In the aneurysm located at the renal artery, the technique of stent-assisted coils embolization was preferred to avoid coils migration due to its wide neck. The stent used was the Solitaire AB, which was designed for the treatment of intracranial aneurysms and was used recently in acute stroke as amore » mechanical thrombectomy device. Complete embolization of the aneurysm was achieved, preserving all the arterial branches without nephrogram defects in the final angiogram.« less

PAROTID FLUID TOTAL PROTEIN IN PATIENTS WITH UREMIA AND PROTEINURIA.

DTIC Science & Technology

Stimulated parotid fluid samples (238) were collected from 32 patients to determine if altered renal function was associated with deviations in...tubular necrosis, and 15 had normal renal function. There were no significant differences in parotid fluid protein concentration or minute secretion associated with the state of renal function. (Author)

Acute and cumulative effects of carboplatin on renal function.

PubMed Central

Sleijfer, D. T.; Smit, E. F.; Meijer, S.; Mulder, N. H.; Postmus, P. E.

1989-01-01

Carboplatin, a cisplatinum analogue, has no reported nephrotoxicity in phase I/II studies, assessed by creatinine clearance. We prospectively determined renal function in 10 untreated lung cancer patients with normal baseline renal function, treated with carboplatin 400 mg m-2 day 1 and vincristine 2 mg day 1 and 8 every 4 weeks (max. five cycles) by means of clearance studies with 125I-sodium thalamate and 131I-hippurate to determine GFR and ERPF respectively. Tubular damage was monitored by excretion of tubular enzymes and relative beta 2-microglobulin clearance. During the first course no changes in renal function were seen. After the second course a significant fall in GFR and ERPF started, ultimately leading to a median decrease in GFR of 19.0% (range 6.8-38.7%) and in ERPF of 14% (range 0-38.9%). No increases in the excretion of tubular enzymes or changes in the relative beta 2-microglobulin clearances were seen. We conclude from our data that carboplatin causes considerable loss of renal function. Monitoring renal function in patients treated with multiple courses of carboplatin is warranted. PMID:2679841

Short communication: timeline of radiation-induced kidney function loss after stereotactic ablative body radiotherapy of renal cell carcinoma as evaluated by serial (99m)Tc-DMSA SPECT/CT.

PubMed

Jackson, Price; Foroudi, Farshad; Pham, Daniel; Hofman, Michael S; Hardcastle, Nicholas; Callahan, Jason; Kron, Tomas; Siva, Shankar

2014-11-26

Stereotactic ablative body radiotherapy (SABR) has been proposed as a definitive treatment for patients with inoperable primary renal cell carcinoma. However, there is little documentation detailing the radiobiological effects of hypofractionated radiation on healthy renal tissue. In this study we describe a methodology for assessment of regional change in renal function in response to single fraction SABR of 26 Gy. In a patient with a solitary kidney, detailed follow-up of kidney function post-treatment was determined through 3-dimensional SPECT/CT imaging and (51)Cr-EDTA measurements. Based on measurements of glomerular filtration rate, renal function declined rapidly by 34% at 3 months, plateaued at 43% loss at 12 months, with minimal further decrease to 49% of baseline by 18 months. The pattern of renal functional change in (99m)Tc-DMSA uptake on SPECT/CT imaging correlates with dose delivered. This study demonstrates a dose effect relationship of SABR with loss of kidney function.

[Fetal urology].

PubMed

Jakobovits, Akos; Jakobovits, Antal

2009-06-14

Although it becomes vitally important only after birth, renal function already plays significant role in maintaining fetal metabolic equilibrium. The kidneys significantly contribute to production of amniotic fluid. Adequate amount of amniotic fluid is needed to stimulate the intrauterine fetal respiratory activity. Intrauterine breathing is essential for lung development. As a result, oligohydramnion is conducive to pulmonary hypoplasia. The latter may lead to neonatal demise soon after birth. In extrauterine life kidneys eliminate nitrogen containing metabolic byproducts. Inadequate renal function results therefore lethal uremia. Integrity of ureters and the urethra is essential for the maintenance of renal function. Retention of urine causes degeneration of the functional units of the kidneys and ensuing deterioration of renal function. Intrauterine kidney puncture or shunt procedure may delay this process in some cases. On the other hand, once renal function has been damaged, no therapy can restart it. Certain anomalies of renal excretory pathways may also be associated with other congenital abnormalities, making the therapeutic efforts pointless. Presence of these associated intrauterine defects makes early pregnancy termination a management alternative, as well as it affects favorably perinatal mortality rates.

Neural control of renal function: role of renal alpha adrenoceptors.

PubMed

DiBona, G F

1985-01-01

Adrenoceptors of various subtypes mediate the renal functional responses to alterations in efferent renal sympathetic nerve activity, the neural component, and renal arterial plasma catecholamine concentrations, the humoral component, of the sympathoadrenergic nervous system. Under normal physiologic as well as hypertensive conditions, the influence of the renal sympathetic nerves predominates over that of circulating plasma catecholamines. In most mammalian species, increases in efferent renal sympathetic nerve activity elicit renal vasoconstrictor responses mediated predominantly by renal vascular alpha-1 adrenoceptors, increases in renin release mediated largely by renal juxtaglomerular granular cell beta-1 adrenoceptors with involvement of renal vascular alpha-1 adrenoceptors only when renal vasoconstriction occurs, and direct increases in renal tubular sodium and water reabsorption mediated predominantly by renal tubular alpha-1 adrenoceptors. In most mammalian species, alpha-2 adrenoceptors do not play a significant role in the renal vascular or renin release responses to renal sympathoadrenergic stimulation. Although renal tubular alpha-2 adrenoceptors do not mediate the increases in renal tubular sodium and water reabsorption produced by increases in efferent renal sympathetic nerve activity, they may be involved through their inhibitory effect on adenylate cyclase in modulating the response to other hormonal agents that influence renal tubular sodium and water reabsorption via stimulation of adenylate cyclase.

Longer time spent in bed attempting to sleep is associated with rapid renal function decline: the Dongfeng-Tongji cohort study.

PubMed

Li, Yizhun; Yang, Liangle; Wang, Hao; Jiang, Haijing; Qiu, Gaokun; Liu, Yiyi; Xiao, Yang; Yang, Handong; Wu, Tangchun; Zhang, Xiaomin

2018-03-01

Prospective evidence on the relation between time in bed and renal dysfunction remains limited. We aimed to investigate the association of time spent in bed attempting to sleep (TSBS) with renal function decline in a middle-aged and elderly Chinese population. About 16,733 eligible participants with a mean age of 62.3 years at baseline were included. Rapid renal function decline was defined as (baseline eGFR - revisit eGFR)/years of follow-up ≥5 mL/min per 1.73 m 2 /year. A total of 1738 study participants experienced rapid renal function decline after a median 4.6-year follow-up. Logistic regression models were used for multivariate analyses. The adjusted odds ratio (OR) of rapid renal function decline was 1.18 (95% CI: 1.02, 1.37) for TSBS ≥9 h/night compared with TSBS 7 to <8 h/night. This association remained significant (OR = 1.19, 95% CI: 1.03, 1.38) after further adjustment for sleep quality, midday napping and usage of sleeping pills. Particularly, the association appeared to be prominent in individuals with diabetes. Longer TSBS (≥9 h) was independently associated with an increased risk of rapid renal function decline. Our findings emphasized the importance to have optimal TSBS. Key messages Our study firstly investigated the association between time spent in bed attempting to sleep (TSBS) and renal dysfunction in Chinese adults. Compared with individuals TSBS 7 to <8 h, individuals with TSBS ≥9 h had 19% increased risk for rapid renal function decline after adjustment for multivariate confounders. The association appeared to be prominent in individuals with diabetes.

Enhanced renal prostaglandin production in the dog. I. Effects on renal function.

PubMed

Tannenbaum, J; Splawinski, J A; Oates, J A; Nies, A S

1975-01-01

The changes in renal function produced by endogenous synthesis of prostaglandins by the kidney were evaluated by infusing sodium arachidonate, the prescursor of the prostaglandins, into one renal artery of the dog. These changes were compared with those produced by similar infusions on performed prostaglandin (PG) E2 and F2alpha.PGE2given at 0.01-0.3 mug/kg min--1 produced dose-related increases in urine flow, sodium and potassium excretion, free water clearance, and renal blood flow. The glomerular filtration rage increased only at the lowest dose and the calculated filtration fraction fell. Arachidonic acid at 1.0-30.0 mug/kg min--1 similarly produced dose-related increases in electrolyte excretion, but the increase in renal blood flow was much less than that produced by PGE2 and there were no changes in glomerular filtration rate, filtration fraction, or free water clearances. PGF2alpha had essentially no effects at infusion rates of 0.03-1.0 mug/kg min--1. All renal effects of arachidonic acid were inhibited by simultaneous infusions of an inhibitor of prostaglandin synthetase, 5, 8, 11,14-eicosatetraynoic acid (20:4). None of the effects produced by PGE2 were inhibited by 20:4. These results indicate that enhanced endogenous renal prostaglandin synthesis, which can be produced by arachidonate infusion, results in significant alterations of renal function. This finding strengthens the hypothesis that renal prostaglandins formed in vivo have physiological importance as regulators of renal function.

A comparison of toxicities in acute myeloid leukemia patients with and without renal impairment treated with decitabine.

PubMed

Levine, Lauren B; Roddy, Julianna Vf; Kim, Miryoung; Li, Junan; Phillips, Gary; Walker, Alison R

2018-06-01

Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min). Results Notable differences in the incidence of grade ≥3 cardiotoxicity (33% of renal dysfunction patients vs. 16% of normal renal function patients, p = 0.042) and respiratory toxicity (40% of renal dysfunction patients vs. 14% of normal renal function patients, p = 0.0037) were observed. The majority of heart failure, myocardial infarction, and atrial fibrillation cases occurred in the renal dysfunction group. The odds of developing grade ≥3 cardiotoxicity did not differ significantly between patients with and without baseline cardiac comorbidities (OR 1.43, p = 0.43). Conclusions This study noted a higher incidence of grade ≥3 cardiac and respiratory toxicities in decitabine-treated acute myeloid leukemia patients with renal dysfunction compared to normal renal function. This may prompt closer monitoring, regardless of baseline cardiac comorbidities. Further evaluation of decitabine in patients with renal dysfunction is needed.

Safety and efficacy of repaglinide in type 2 diabetic patients with and without impaired renal function.

PubMed

Hasslacher, Christoph

2003-03-01

To evaluate the influence of renal impairment on the safety and efficacy of repaglinide in type 2 diabetic patients. This multinational, open-label study comprised a 6-week run-in period, continuing prestudy antidiabetic medication, followed by a titration period (1-4 weeks) and a 3-month maintenance period. Patients with normal renal function (n = 151) and various degrees of renal impairment (n = 130) were treated with repaglinide (maximal dose of 4 mg, three times daily). Safety and efficacy assessments were performed at baseline (end of run-in) and at the end of study treatment. The type and severity of adverse events during repaglinide treatment were similar to the run-in period. The number of patients with adverse events was not significantly related to renal function during run-in or repaglinide treatment. Percentage of patients with hypoglycemic episodes increased significantly (P = 0.007) with increasing severity of renal impairment during run-in but not during repaglinide treatment (P = 0.074). Metabolic control (HbA(1c) and fasting blood glucose) with repaglinide was unchanged from that on previous antidiabetic medication. Final repaglinide dose tended to be lower for patients with severe and extreme renal impairment than for patients with less severe renal impairment or normal renal function (P = 0.032). Repaglinide has a good safety and efficacy profile in type 2 diabetic patients complicated by renal impairment and is an appropriate treatment choice, even for individuals with more severe degrees of renal impairment.

Early impact of robot-assisted partial nephrectomy on renal function as assessed by renal scintigraphy.

PubMed

Luciani, Lorenzo G; Chiodini, Stefano; Donner, Davide; Cai, Tommaso; Vattovani, Valentino; Tiscione, Daniele; Giusti, Guido; Proietti, Silvia; Chierichetti, Franca; Malossini, Gianni

2016-06-01

To measure the early impact of robot-assisted partial nephrectomy (RAPN) on renal function as assessed by renal scan (Tc 99m-DTPA), addressing the issue of risk factors for ischemic damage to the kidney. All patients undergoing RAPN for cT1 renal masses between June 2013 and May 2014 were included in this prospective study. Renal function as expressed by glomerular filtration rate (GFR) was assessed by Technetium 99m-diethylenetriaminepentaacetic acid (Tc 99m-DTPA) renal scan preoperatively and postoperatively at 1 month in every patient. A multivariable analysis was used for the determination of independent factors predictive of GFR decrease of the operated kidney. Overall, 32 patients underwent RAPN in the time interval. Median tumor size, blood loss, and ischemia time were 4 cm, 200 mL, and 24 min, respectively. Two grade III complications occurred (postoperative bleeding in the renal fossa, urinoma). The GFR of the operated kidney decreased significantly from 51.7 ± 15.1 mL/min per 1.73 m(2) preoperatively to 40, 12 ± 12.4 mL/min per 1.73 m(2) 1 month postoperatively (p = 0.001) with a decrease of 22.4 %. On multivariable analysis, only tumor size (p = 0.05) was a predictor of GFR decrease of the operated kidney. Robotic-assisted partial nephrectomy had a detectable impact on early renal function in a series of relatively large tumors and prevailing intermediate nephrometric risk. A mean decrease of 22 % of GFR as assessed by renal scan in the operated kidney was found at 1 month postoperatively. In multivariable analysis, tumor size only was a significant predictor of renal function loss.

Comparing Zero Ischemia Laparoscopic Radio Frequency Ablation Assisted Tumor Enucleation and Laparoscopic Partial Nephrectomy for Clinical T1a Renal Tumor: A Randomized Clinical Trial.

PubMed

Huang, Jiwei; Zhang, Jin; Wang, Yanqing; Kong, Wen; Xue, Wei; Liu, Dongming; Chen, YongHui; Huang, Yiran

2016-06-01

We evaluated the functional outcome, safety and efficacy of zero ischemia laparoscopic radio frequency ablation assisted tumor enucleation compared with conventional laparoscopic partial nephrectomy. A prospective randomized controlled trial was conducted from April 2013 to March 2015 in patients with cT1a renal tumor scheduled for laparoscopic nephron sparing surgery. All patients were followed for at least 12 months. Patients in the laparoscopic radio frequency ablation assisted tumor enucleation group underwent tumor enucleation after radio frequency ablation without hilar clamping. The primary outcome was the change in glomerular filtration rate of the affected kidney by renal scintigraphy at 12 months. Secondary outcomes included changes in estimated glomerular filtration rate, estimated blood loss, operative time, hospital stay, postoperative complications and oncologic outcomes. The Pearson chi-square or Fisher exact, Student t-test and Wilcoxon rank sum tests were used. The trial ultimately enrolled 89 patients, of whom 44 were randomized to the laparoscopic radio frequency ablation assisted tumor enucleation group and 45 to the laparoscopic partial nephrectomy group. In the laparoscopic partial nephrectomy group 1 case was converted to radical nephrectomy. Compared with the laparoscopic partial nephrectomy group, patients in the laparoscopic radio frequency ablation assisted tumor enucleation group had a smaller decrease in glomerular filtration rate of the affected kidney at 3 months (10.2% vs 20.5%, p=0.001) and 12 months (7.6% vs 16.2%, p=0.002). Patients in the laparoscopic radio frequency ablation assisted tumor enucleation group had a shorter operative time (p=0.002), lower estimated blood loss (p <0.001) and a shorter hospital stay (p=0.029) but similar postoperative complications (p=1.000). There were no positive margins or local recurrence in this study. Zero ischemia laparoscopic radio frequency ablation assisted tumor enucleation enables tumor excision with better renal function preservation compared to conventional laparoscopic partial nephrectomy. Less blood loss and a shorter operative time were achieved with similar postoperative complication rates. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

PubMed Central

Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C.; Khadayate, Sanjay; Mas, Valeria R.; Nitsch, Dorothea D.; Wang, Zhen; Norman, Jill T.; Wilcox, Christopher S.; Wheeler, David C.; Leiper, James

2015-01-01

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule–specific Ddah1 knockout (Ddah1PT−/−) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1PT−/− mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. PMID:25855779

Long-term Effects of Off-Pump Coronary Bypass Versus Conventional Coronary Bypass Grafting on Renal Function.

PubMed

Hynes, Conor F; Colo, Sanchez; Amdur, Richard L; Chawla, Lakhmir S; Greenberg, Michael D; Trachiotis, Gregory D

2016-01-01

This study aimed to evaluate the short- and long-term effects of conventional on-pump coronary bypass grafting (cCABG) compared with off-pump coronary artery bypass (OPCAB) on renal function. A retrospective review of patients undergoing coronary bypass grafting from 2004 through 2013 at a single center was conducted. Preoperative renal function, perioperative acute kidney injury, and long-term glomerular filtration were evaluated. Multivariable analyses were used to determine factors contributing to short- and long-term renal impairment. A total of 234 patients underwent cCABG, and 582 underwent OPCAB. Patients undergoing OPCAB were significantly older, had greater preoperative renal dysfunction, had greater functional dependence, and took more hypertension medications. Multivariable analyses found that 30-day acute kidney injury was an independent risk factor for a 10% decline in glomerular filtration rate at 1 and 5 years (P < 0.0001 and 0.002, respectively). However, the use of cardiopulmonary bypass was not found to influence long-term renal function (P = 0.78 at 1 year, P = 0.76 at 5 years). The percentage of patients experiencing a 10% drop in renal function from baseline at 1 year (33% OPCAB, 35% cCABG; P = 0.73) and 5 years (16% OPCAB, 16% cCABG; P = 0.93) were not significantly different. Independent predictors of acute kidney injury included baseline kidney function (P = 0.04) and age (P < 0.0001), whereas cardiopulmonary bypass did not affect the incidence (P = 0.17). A propensity-matched analysis confirmed these findings. Acute kidney injury is a risk factor for long-term renal dysfunction after either bypass method and was not greater after cCABG compared with OPCAB. Patients undergoing OPCAB did not experience greater decrease in long-term kidney function despite having worse baseline kidney function.

Microvascular disease precedes the decline in renal function in the streptozotocin-induced diabetic rat

PubMed Central

Maric-Bilkan, Christine; Flynn, Elizabeth R.

2012-01-01

Diabetic nephropathy is a progressive and generalized vasculopathic condition associated with abnormal angiogenesis. We aim to determine whether changes in renal microvascular (MV) density correlate with and play a role in the progressive deterioration of renal function in diabetes. We hypothesize that MV changes represent the early steps of renal injury that worsen as diabetes progresses, initiating a vicious circle that leads to irreversible renal injury. Male nondiabetic (ND) or streptozotocin-induced diabetic (D) Sprague-Dawley rats were followed for 4 or 12 wk. Renal blood flow and glomerular filtration rate (GFR) were measured by PAH and 125I-[iothalamate], respectively. Renal MV density was quantified ex vivo using three-dimensional micro computed tomography and JG-12 immunoreactivity. Vascular endothelial growth factor (VEGF) levels (ELISA) and expression of VEGF receptors and factors involved in MV remodeling were quantified in renal tissue by Western blotting. Finally, renal morphology was investigated by histology. Four weeks of diabetes was associated with increased GFR, accompanied by a 34% reduction in renal MV density and augmented renal VEGF levels. However, at 12 wk, while GFR remained similarly elevated, reduction of MV density was more pronounced (75%) and associated with increased MV remodeling, renal fibrosis, but unchanged renal VEGF compared with ND at 12 wk. The damage, loss, and subsequent remodeling of the renal MV architecture in the diabetic kidney may represent the initiating events of progressive renal injury. This study suggests a novel concept of MV disease as an early instigator of diabetic kidney disease that may precede and likely promote the decline in renal function. PMID:22031855

Renal hemodynamics in space.

PubMed

Kramer, H J; Heer, M; Cirillo, M; De Santo, N G

2001-09-01

Renal excretory function and hemodynamics are determined by the effective circulating plasma volume as well as by the interplay of systemic and local vasoconstrictors and vasodilators. Microgravity results in a headward shift of body fluid. Because the control conditions of astronauts were poorly defined in many studies, controversial results have been obtained regarding diuresis and natriuresis as well as renal hemodynamic changes in response to increased central blood volume, especially during the initial phase of space flight. Renal excretory function and renal hemodynamics in microgravity are affected in a complex fashion, because during the initial phase of space flight, variable mechanisms become operative to modulate the effects of increased central blood volume. They include interactions between vasodilators (dopamine, atrial natriuretic peptide, and prostaglandins) and vasoconstrictors (sympathetic nervous system and the renin-angiotensin system). The available data suggest a moderate rise in glomerular filtration rate during the first 2 days after launch without a significant increase in effective renal plasma flow. In contrast, too few data regarding the effects of space flight on renal function during the first 12 hours after launch are available and are, in addition, partly contradictory. Thus, detailed and well-controlled studies are required to shed more light on the role of the various factors besides microgravity that determine systemic and renal hemodynamics and renal excretory function during the different stages of space flight.

Arterially Delivered Mesenchymal Stem Cells Prevent Obstruction-Induced Renal Fibrosis

PubMed Central

Asanuma, Hiroshi; Vanderbrink, Brian A.; Campbell, Matthew T.; Hile, Karen L.; Zhang, Hongji; Meldrum, Daniel R.; Meldrum, Kirstan K.

2010-01-01

Purpose Mesenchymal stem cells (MSCs) hold promise for the treatment of renal disease. While MSCs have been shown to accelerate recovery and prevent acute renal failure in multiple disease models, the effect of MSC therapy on chronic obstruction-induced renal fibrosis has not previously been evaluated. Materials and Methods Male Sprague-Dawley rats underwent renal artery injection of vehicle or fluorescent-labeled human bone marrow-derived MSCs immediately prior to sham operation or induction of left ureteral obstruction (UUO). One or 4 weeks later, the kidneys were harvested and the renal cortex analyzed for evidence of stem cell infiltration, epithelial-mesenchymal transition (EMT) as evidenced by E-cadherin/α-smooth muscle actin (α-SMA) expression and fibroblast specific protein (FSP+) staining, renal fibrosis (collagen content, Masson’s trichrome staining), and cytokine and growth factor activity (ELISA and real time RT-PCR). Results Fluorescent-labeled MSCs were detected in the interstitium of the kidney up to 4 weeks post-obstruction. Arterially delivered MSCs significantly reduced obstruction-induced α-SMA expression, FSP+ cell accumulation, total collagen content, and tubulointerstitial fibrosis, while simultaneously preserving E-cadherin expression, suggesting that MSCs prevent obstruction-induced EMT and renal fibrosis. Exogenous MSCs reduced obstruction-induced tumor necrosis factor-α (TNF-α) levels, but did not alter transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), interleukin-10 (IL-10), fibroblast growth factor (FGF), or hepatocyte growth factor (HGF) expression. Conclusions Human bone marrow-derived MSCs remain viable several weeks after delivery into the kidney and provide protection against obstruction-induced EMT and chronic renal fibrosis. While the mechanism of MSCs-induced renal protection during obstruction remains unclear, our results demonstrate that alterations in TNF-α production may be involved. PMID:20850784

The Piezo Actuator-Driven Pulsed Water Jet System for Minimizing Renal Damage after Off-Clamp Laparoscopic Partial Nephrectomy.

PubMed

Kamiyama, Yoshihiro; Yamashita, Shinichi; Nakagawa, Atsuhiro; Fujii, Shinji; Mitsuzuka, Koji; Kaiho, Yasuhiro; Ito, Akihiro; Abe, Takaaki; Tominaga, Teiji; Arai, Yoichi

2017-09-01

In the setting of partial nephrectomy (PN) for renal cell carcinoma, postoperative renal dysfunction might be caused by surgical procedure. The aim of this study was to clarify the technical safety and renal damage after off-clamp laparoscopic PN (LPN) with a piezo actuator-driven pulsed water jet (ADPJ) system. Eight swine underwent off-clamp LPN with this surgical device, while off-clamp open PN was also performed with radio knife or soft coagulation. The length of the removed kidney was 40 mm, and the renal parenchyma was dissected until the renal calyx became clearly visible. The degree of renal degeneration from the resection surface was compared by Hematoxylin-Eosin staining and immunostaining for 1-methyladenosine, a sensitive marker for the ischemic tissue damage. The mRNA levels of neutrophil gelatinase-associated lipocalin (Ngal), a biomarker for acute kidney injury, were measured by quantitative real-time PCR. Off-clamp LPN with ADPJ system was successfully performed while preserving fine blood vessels and the renal calix with little bleeding. In contrast to other devices, the resection surface obtained with the ADPJ system showed only marginal degree of ischemic changes. Indeed, the expression level of Ngal mRNA was lower in the resection surface obtained with the ADPJ system than that with soft coagulation (p = 0.02). Furthermore, using the excised specimens of renal cell carcinoma, we measured the breaking strength at each site of the human kidney, suggesting the applicability of this ADPJ to clinical trials. In conclusion, off-clamp LPN with the ADPJ system could be safely performed with attenuated renal damage.

Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats.

PubMed

Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

2016-12-20

The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured. Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups. Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.

Points to consider in renal involvement in systemic sclerosis.

PubMed

Galluccio, Felice; Müller-Ladner, Ulf; Furst, Daniel E; Khanna, Dinesh; Matucci-Cerinic, Marco

2017-09-01

This article discusses points to consider when undertaking a clinical trial to test therapy for renal involvement in SSc, not including scleroderma renal crisis. Double-blind, randomized controlled trials vs placebo or standard background therapy should be strongly considered. Inclusion criteria should consider a pre-specified range of renal functions or stratification of renal function. Gender and age limitations are probably not necessary. Concomitant medications including vasodilators, immunosuppressants and endothelin receptor antagonists and confounding illnesses such as diabetes, kidney stones, hypertension and heart failure need to be considered. A measure of renal function should be strongly considered, while time to dialysis, mortality, prevention of scleroderma renal crisis and progression of renal disease can also be considered, although they remain to be validated. Detailed, pre-planned analysis should be strongly considered and should include accounting for missing data. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Adiponectin is not associated with renal function decline in community-dwelling elderly adults.

PubMed

Kobayashi, Hiroki; Otsuka, Hiromasa; Yanai, Mitsuru; Haketa, Akira; Hara, Motohiko; Hishiki, Mikano; Abe, Masanori; Soma, Masayoshi

2018-05-01

Adiponectin secreted by adipocytes plays an important role in the regulation of glucose and fatty acid metabolism. Contrary to findings in patients with chronic kidney disease (CKD), no prospective data about the association of serum adiponectin with renal function decline in the general population have yet appeared. Our objective was to analyze the relationship of total and high molecular weight (HMW) adiponectin with renal function decline as measured by cystatin C in community-dwelling elderly adults without moderate or severe CKD.In a prospective observational analysis, a total of 216 healthy elderly volunteers with eGFRcys ≥60 mL/min/1.73 m underwent anthropometric and laboratory tests at baseline and at follow-up visits. A subgroup with serum samples collected 5 years apart was further analyzed.There were no differences in either total or HMW adiponectin level between subjects subsequently undergoing rapid renal function decline and subjects with normal physiologic renal function decline (P = .71, P = .81). On univariate linear regression, neither total nor HMW adiponectin were associated with annual renal function decline (β = -0.23; P = .71, β = -0.057; P = .90). Multivariate analysis did not show a significant contribution of either total or HMW adiponectin to annual renal function decline (β = -0.50; P = .46, β = 0.01; P = .98). In the logistic regression analysis, we did not observe any statistically significant association of serum adiponectin levels with rapid renal function decline or incidence of CKD.Contrary to findings in populations with CKD, neither total nor HMW adiponectin had a substantial association with renal function decline in an elderly population with eGFRcys ≥60 mL/min/1.73 m. Our results and conclusions should not be extrapolated to subjects with other characteristics.

Influence of impairment in renal function on the accuracy of high-sensitivity cardiac troponin T for the diagnosis of perioperative myocardial infarction after heart valve surgery.

PubMed

Cubero-Gallego, Hector; Heredia-Rodriguez, Maria; Tamayo, Eduardo

2018-03-12

We aimed to assess the influence of impairment in renal function over the high-sensitivity cardiac troponin T (hs-cTnT) accuracy to diagnose perioperative myocardial infarction (MI) after heart valve surgery. Heart valve surgery was performed in 805 patients from June 2012 to January 2016. Patients with enzymatic curves of hs-cTnT suggestive of myocardial necrosis and electrocardiogram and/or transthoracic echocardiogram criteria were identified as patients with perioperative MI. Impairment in renal function was defined as a postoperative creatinine clearance <50 ml/min at 16 h after surgery and for at least 48 h. Patients included were divided into 2 groups at 16 h: (i) patients with normal renal function (creatinine clearance >50 ml/min) and (ii) patients with impairment in renal function (creatinine clearance <50 ml/min). From a total of 805 patients undergoing heart valve surgery, 88 patients developed perioperative MI. When comparing receiver operating characteristic curves in patients with perioperative MI according to renal function, the optimal threshold of hs-cTnT at 16 h differed in patients with impairment in renal function (1303 vs 1095 pg/ml, P < 0.001). The diagnostic accuracy of hs-cTnT at 16 h was 93.4% [95% confidence interval (CI) 89.98-96.86], with an area under receiver operating characteristic curve (0.993, 95% CI 0.988-0.999 vs 0.972, 95% CI 0.952-0.992; P < 0.001). Renal function might influence in hs-cTnT levels. However, a hs-cTnT threshold of 1303 pg/ml at 16 h may be applied according to renal function to diagnose perioperative MI after cardiac surgery.

[Asymptomatic Renal Stones: Do they really Exist?].

PubMed

Seseke, S; Rudolph, R; Rebmann, U

2011-11-01

Asymptomatic renal calculi without any history of colic, hematuria or infection can be found as an incidental finding during preven-tive check-ups. The aim of our study was to eval-uate whether these stones provoke symptoms with the need for further treatment during the follow-up and whether they cause cortical defects which may consecutively affect the renal func-tion. In a prospective study we evaluated 104  patients with renal calculi. The -medical history, radiological findings and functional imaging as well as urine and blood analyses were recorded and evaluated. The influence of stone size and localisation on the development of acute stone-related symptoms, renal function and renal scarring were evaluated. Furthermore, we analysed whether localised pathological findings in radiographic or functional imaging may influence the creatinine level. The follow-up was be-tween 12 and 48  months (median: 25  months). During the study period 27 / 104 of our patients (26 %) developed symptomatic events (renal colic, hematuria, infection) in which patients with middle pole calculi with a mean -cumulative stone diameter of 9.8  mm had the -highest risk. A localised renal scarring could be found in 36.6 %. These patients had a significantly higher risk in presenting an increased creatinine level. Increasing stone size was diagnosed in 39  cases (37.5 %). Asymptomatic renal stones have to be controlled regularly in order to prevent the -patient from loss of renal function and hypertension caused by increasing stones or urinary tract infection. © Georg Thieme Verlag KG Stuttgart ˙ New York.

Soluble Flt-1 links microvascular disease with heart failure in CKD.

PubMed

Di Marco, Giovana S; Kentrup, Dominik; Reuter, Stefan; Mayer, Anna B; Golle, Lina; Tiemann, Klaus; Fobker, Manfred; Engelbertz, Christiane; Breithardt, Günter; Brand, Eva; Reinecke, Holger; Pavenstädt, Hermann; Brand, Marcus

2015-05-01

Chronic kidney disease (CKD) is associated with an increased risk of heart failure (HF). Elevated plasma concentrations of soluble Flt-1 (sFlt-1) have been linked to cardiovascular disease in CKD patients, but whether sFlt-1 contributes to HF in CKD is still unknown. To provide evidence that concludes a pathophysiological role of sFlt-1 in CKD-associated HF, we measured plasma sFlt-1 concentrations in 586 patients with angiographically documented coronary artery disease and renal function classified according to estimated glomerular filtration rate (eGFR). sFlt-1 concentrations correlated negatively with eGFR and were associated with signs of heart failure, based on New York Heart Association functional class and reduced left ventricular ejection fraction (LVEF), and early mortality. Additionally, rats treated with recombinant sFlt-1 showed a 15 % reduction in LVEF and a 29 % reduction in cardiac output compared with control rats. High sFlt-1 concentrations were associated with a 15 % reduction in heart capillary density (number of vessels/cardiomyocyte) and a 24 % reduction in myocardial blood volume. Electron microscopy and histological analysis revealed mitochondrial damage and interstitial fibrosis in the hearts of sFlt-1-treated, but not control rats. In 5/6-nephrectomised rats, an animal model of CKD, sFlt-1 antagonism with recombinant VEGF121 preserved heart microvasculature and significantly improved heart function. Overall, these findings suggest that a component of cardiovascular risk in CKD patients could be directly attributed to sFlt-1. Assessment of patients with CKD confirmed that sFlt-1 concentrations were inversely correlated with renal function, while studies in rats suggested that sFlt-1 may link microvascular disease with HF in CKD.

Renal uptake of radioactive mercury (/sup 197/HgCl/sub 2/): method for testing the functional value of each kidney. Technique--results--and clinical application in urology and nephrology

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

Raynaud, C.

The first three chapters consider measurement of mercury renal uptake by external counting, by quantitative scintigraphy, and by the gamma camera. Some topics discussed in the remaining 14 chapters are as follows: renal depth; phantoms; precautions regarding the liver, spleen, and intestine; stability of /sup 197/HgCl/sub 2/ solutions; use of mercury renal uptake in pediatric and adult urology; indications for mercury renal uptake in renal transplants; and appraisal of the radiological and chemical toxicity of /sup 197/HgCl/sub 2/. It was concluded that mercury renal uptake is an accurate and nontraumatizing method of measuring the functional value of each kidney. Itmore » makes it possible to determine whether a kidney is normal or pathological and to what extent its function is diminished or increased. (HLW)« less

Pilot Analysis of Late Conversion to Belatacept in Kidney Transplant Recipients for Biopsy-Proven Chronic Tacrolimus Toxicity

PubMed Central

Rosales, Ivy

2018-01-01

Background Calcineurin inhibitors are associated with chronic nephrotoxicity, manifesting as interstitial fibrosis/tubular atrophy (IF/TA) and arteriolar hyalinosis. Conversion from tacrolimus to belatacept may be one strategy to preserve renal function. Methods We conducted a retrospective review of renal transplant patients followed at our institution who were converted to belatacept and found to have chronic tacrolimus toxicity on biopsy. The primary outcome was eGFR at conversion as compared to eGFR at 3, 6, 12, and 24 months after conversion. We also assessed incidence of infection and rates of allograft survival at 1 year. Results The average time between transplant and conversion was 11.9 years. There was no decrease in eGFR at any postconversion time point as compared with preconversion. The mean eGFR at time of preconversion was 32.9 mL/min, as compared with 35.6 mL/min at 3 months (p = 0.09), 34.1 mL/min at 6 months (p = 0.63), 34.9 mL/min at 12 months (p = 0.57), and 39.6 mL/min at 24 months after conversion (p = 0.92). Four of 7 patients had increases in their eGFR after conversion. All grafts were functioning at 1 year after conversion. Conclusion While this study was limited by a small number of patients, belatacept conversion stabilized eGFR at all time points in patients with late allograft function due to chronic tacrolimus toxicity, with a trend towards increased eGFR at 3 months. PMID:29854421

In-line filtration minimizes organ dysfunction: new aspects from a prospective, randomized, controlled trial.

PubMed

Boehne, Martin; Jack, Thomas; Köditz, Harald; Seidemann, Kathrin; Schmidt, Florian; Abura, Michaela; Bertram, Harald; Sasse, Michael

2013-02-06

Infused particles induce thrombogenesis, impair microcirculation and modulate immune response. We have previously shown in critically ill children, that particle-retentive in-line filtration reduced the overall complication rate of severe events, length of stay and duration of mechanical ventilation. We now evaluated the influence of in-line filtration on different organ function and thereby elucidated the potential underlying pathophysiological effects of particle infusion. In this single-centre, prospective, randomized controlled trial 807 critically ill children were assigned to either control (n = 406) or filter group (n = 401), the latter receiving in-line filtration for complete infusion therapy. Both groups were compared regarding the differences of incidence rates and its 95% confidence interval (CI) of different organ dysfunction as defined by the International Pediatric Sepsis Consensus Conference 2005. The incidence rates of respiratory (-5.06%; 95% CI, -9.52 to -0.59%), renal (-3.87%; 95% CI, -7.58 to -0.15%) and hematologic (-3.89%; 95% CI, -7.26 to -0.51%) dysfunction were decreased in the filter group. No difference was demonstrated for the occurrence rates of cardiovascular, hepatic, or neurologic dysfunction between both groups. In-line filtration has beneficial effects on the preservation of hematologic, renal and respiratory function in critically ill patients. The presented clinical data further support our hypothesis regarding potential harmful effects of particles. In critically ill patients infused particles may lead to further deterioration of the microcirculation, induce a systemic hypercoagulability and inflammation with consecutive negative effects on organ function. ClinicalTrials.gov number; NCT00209768.

Predictors of post-hospitalization recovery of renal function among patients with acute kidney injury requiring dialysis.

PubMed

Pajewski, Russell; Gipson, Patrick; Heung, Michael

2018-01-01

Acute kidney injury (AKI) requiring dialysis complicates 1% of all hospital admissions, and up to 30% of survivors will still require dialysis at hospital discharge. There is a paucity of data to describe the postdischarge outcomes or to guide evidence-based dialysis management of this vulnerable population. Single-center, retrospective analysis of 100 consecutive patients with AKI who survived to hospital discharge and required outpatient dialysis. Data collection included baseline characteristics, hospitalization characteristics, and outpatient dialysis treatment variables. Primary outcome was dialysis independence 90 days after discharge. Overall, 43% of patients recovered adequate renal function to discontinue dialysis, with the majority recovering within 30 days post discharge. Worse baseline renal function was associated with lower likelihood of renal recovery. In the first week postdischarge, patients with subsequent nonrecovery of renal function had greater net fluid removal (5.3 vs. 4.1 L, P = 0.037), higher ultrafiltration rates (6.0 vs. 4.7 mL/kg/h, P = 0.041) and more frequent intradialytic hypotension (24.6% vs. 9.3% with 3 or more episodes, P = 0.049) compared to patients that later recovered. A significant proportion of AKI survivors will recover renal function following discharge. Outpatient intradialytic factors may influence subsequent renal function recovery. © 2017 International Society for Hemodialysis.

Neural control of renal function.

PubMed

Johns, Edward J; Kopp, Ulla C; DiBona, Gerald F

2011-04-01

The kidney is innervated with efferent sympathetic nerve fibers that directly contact the vasculature, the renal tubules, and the juxtaglomerular granular cells. Via specific adrenoceptors, increased efferent renal sympathetic nerve activity decreases renal blood flow and glomerular filtration rate, increases renal tubular sodium and water reabsorption, and increases renin release. Decreased efferent renal sympathetic nerve activity produces opposite functional responses. This integrated system contributes importantly to homeostatic regulation of sodium and water balance under physiological conditions and to pathological alterations in sodium and water balance in disease. The kidney contains afferent sensory nerve fibers that are located primarily in the renal pelvic wall where they sense stretch. Stretch activation of these afferent sensory nerve fibers elicits an inhibitory renorenal reflex response wherein the contralateral kidney exhibits a compensatory natriuresis and diuresis due to diminished efferent renal sympathetic nerve activity. The renorenal reflex coordinates the excretory function of the two kidneys so as to facilitate homeostatic regulation of sodium and water balance. There is a negative feedback loop in which efferent renal sympathetic nerve activity facilitates increases in afferent renal nerve activity that in turn inhibit efferent renal sympathetic nerve activity so as to avoid excess renal sodium retention. In states of renal disease or injury, there is activation of afferent sensory nerve fibers that are excitatory, leading to increased peripheral sympathetic nerve activity, vasoconstriction, and increased arterial pressure. Proof of principle studies in essential hypertensive patients demonstrate that renal denervation produces sustained decreases in arterial pressure. © 2011 American Physiological Society. Compr Physiol 1:699-729, 2011.

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.

Successful renal transplantation from a brain-dead deceased donor with head injury, disseminated intravascular coagulation and deranged renal functions.

PubMed

Ghuge, P P; Kute, V B; Vanikar, A V; Gumber, M R; Gera, D N; Patel, H V; Shah, P R; Modi, P R; Shah, V R; Trivedi, H L

2013-11-01

Deceased donors (DDs) with the brain death due to head injury are the major source of organs for transplantation. The incidence of post-head injury disseminated intravascular coagulation (DIC) ranges from 24% to 50%. Many centers do not accept organs from donors with DIC due to increased risk of primary graft non-function and/or high chances of morbidity/mortality. We performed two successful renal transplants from a DD with head injury with DIC and deranged renal function. One of the recipients developed transient thrombocytopenia, but there was no evidence of DIC or delayed graft functions in either of the recipients. Over a follow-up of 1 month, both are doing well with stable graft function and hematological profile. Thus, a carefully selected DD with severe DIC even with deranged renal function is not a contraindication for organ donation if other risk factors for primary non-function are excluded. This approach will also help in overcoming organ shortage.

[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.

Partial Nephrectomy Versus Radical Nephrectomy for Clinical T1b and T2 Renal Tumors: A Systematic Review and Meta-analysis of Comparative Studies.

PubMed

Mir, Maria Carmen; Derweesh, Ithaar; Porpiglia, Francesco; Zargar, Homayoun; Mottrie, Alexandre; Autorino, Riccardo

2017-04-01

Partial nephrectomy (PN) is the reference standard of management for a cT1a renal mass. However, its role in the management of larger tumors (cT1b and cT2) is still under scrutiny. To conduct a meta-analysis assessing functional, oncologic, and perioperative outcomes of PN and radical nephrectomy (RN) in the specific case of larger renal tumors (≥cT1b). The primary endpoint was an overall analysis of cT1b and cT2 masses. The secondary endpoint was a sensitivity analysis for cT2 only. A systematic literature review was performed up to December 2015 using multiple search engines to identify eligible comparative studies. A formal meta-analysis was performed for studies comparing PN to RN for both cT1b and cT2 tumors. In addition, a sensitivity analysis including the subgroup of studies comparing PN to RN for cT2 only was conducted. Pooled estimates were calculated using a fixed-effects model if no significant heterogeneity was identified; alternatively, a random-effects model was used when significant heterogeneity was detected. For continuous outcomes, the weighted mean difference (WMD) was used as summary measure. For binary variables, the odds ratio (OR) or risk ratio (RR) was calculated with 95% confidence interval (CI). Statistical analyses were performed using Review Manager 5 (Cochrane Collaboration, Oxford, UK). Overall, 21 case-control studies including 11204 patients (RN 8620; PN 2584) were deemed eligible and included in the analysis. Patients undergoing PN were younger (WMD -2.3 yr; p<0.001) and had smaller masses (WMD -0.65cm; p<0.001). Lower estimated blood loss was found for RN (WMD 102.6ml; p<0.001). There was a higher likelihood of postoperative complications for PN (RR 1.74, 95% CI 1.34-2.2; p<0.001). Pathology revealed a higher rate of malignant histology for the RN group (RR 0.97; p=0.02). PN was associated with better postoperative renal function, as shown by higher postoperative estimated glomerular filtration rate (eGFR; WMD 12.4ml/min; p<0.001), lower likelihood of postoperative onset of chronic kidney disease (RR 0.36; p<0.001), and lower decline in eGFR (WMD -8.6ml/min; p<0.001). The PN group had a lower likelihood of tumor recurrence (OR 0.6; p<0.001), cancer-specific mortality (OR 0.58; p=0.001), and all-cause mortality (OR 0.67; p=0.005). Four studies compared PN (n=212) to RN (n=1792) in the specific case of T2 tumors (>7cm). In this subset of patients, the estimated blood loss was higher for PN (WMD 107.6ml; p<0.001), as was the likelihood of complications (RR 2.0; p<0.001). Both the recurrence rate (RR 0.61; p=0.004) and cancer-specific mortality (RR 0.65; p=0.03) were lower for PN. PN is a viable treatment option for larger renal tumors, as it offers acceptable surgical morbidity, equivalent cancer control, and better preservation of renal function, with potential for better long-term survival. For T2 tumors, PN use should be more selective, and specific patient and tumor factors should be considered. Further investigation, ideally in a prospective randomized fashion, is warranted to better define the role of PN in this challenging clinical scenario. We performed a cumulative analysis of the literature to determine the best treatment option in cases of localized kidney tumor of higher clinical stage (T1b and T2, as based on preoperative imaging). Our findings suggest that removing only the tumor and saving the kidney might be an effective treatment modality in terms of cancer control, with the advantage of preserving the kidney function. However, a higher risk of perioperative complications should be taken into account when facing larger tumors (clinical stage T2) with kidney-sparing surgery. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Renal function preservation in type 2 diabetes mellitus patients with early nephropathy: a comparative prospective cohort study between primary health care doctors and a nephrologist.

PubMed

Martínez-Ramírez, Héctor R; Jalomo-Martínez, Basilio; Cortés-Sanabria, Laura; Rojas-Campos, Enrique; Barragán, Graciela; Alfaro, Gilberto; Cueto-Manzano, Alfonso M

2006-01-01

Early referral of patients with end-stage renal disease to a nephrologist is associated with lower morbidity and mortality after initiating dialysis therapy; earlier referral may have better results. The aim of the study is to prospectively determine the impact of earlier referral to a nephrologist on renal damage progression of patients with type 2 diabetes mellitus (DM2) with early nephropathy. Fifty-two patients (27 patients, early nephropathy [EN]; 25 patients, overt nephropathy [ON]) from a primary health care unit were referred to a nephrologist (study cohort); 65 patients (34 patients, EN; 31 patients, ON) from another health care unit remained treated by only family doctors (control cohort). Both cohorts were followed up for 1 year. Delta (final-baseline) in serum creatinine levels was maintained better by the nephrologist in the EN (study, 0.02 mg/dL versus control, 0.13 mg/dL [2 versus 11 micromol/L]; P = 0.02) than ON group (study, 0.15 mg/dL versus control, 0.25 mg/dL [13 versus 22 micromol/L]). In concordance, glomerular filtration rate was maintained better by the nephrologist in EN (study, 3.2 mL/min/1.73 m2 versus control, -13.3 mL/min/1.73 m2 [0.05 versus -0.22 mL/s/1.73 m2]; P = 0.01) than ON patients (study, -9.8 mL/min/1.73 m2 versus control, -10.9 mL/min/1.73 m2 [-0.16 versus -0.18 mL/s/1.73 m2]). Albuminuria increased more in patients treated by family doctors in the EN (study, 30 mg/d versus control, 116 mg/d; P < 0.05) and ON groups (study, 160 mg/d versus control, 623 mg/d). The nephrologist controlled systolic blood pressure better in both the EN (study, -3 mm Hg versus control, 2 mm Hg; P < 0.05) and ON groups (study, -19 mm Hg versus control, 5 mm Hg; P < 0.05); diastolic blood pressure had a similar pattern. The nephrologist significantly increased (P < 0.05) the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and statins and discontinued nonsteroidal anti-inflammatory drugs more than family doctors (study, 42%, 43%, 39%, and -11% versus control, 17%, 4%, -7%, and 27%, respectively). Glycemic and lipid control and stopping smoking were not attained by either the nephrologist or family doctors. Earlier referral of patients with DM2 to a nephrologist was associated with better renal function preservation, which was significantly more evident in the EN than ON group. The nephrologist obtained better blood pressure control, more frequently used angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and statins; and discontinued nonsteroidal anti-inflammatory drugs more than family doctors. However, metabolic control and stopping smoking were not attained by either the nephrologist or family doctors.

Essentials of equine renal and urinary tract physiology.

PubMed

Toribio, Ramiro E

2007-12-01

Knowledge of urinary tract anatomy and the numerous functions of the kidney in regulating fluids, electrolytes, acid-base balance, and waste products improves the ability of the clinician to diagnose, treat, and make appropriate recommendations for the management of the horse with renal disease. Several conditions can directly or indirectly affect renal function on a temporary or permanent basis. Endogenous and exogenous compounds (eg, drugs, toxins, hemoglobin) alone or in combination with inappropriate renal blood flow can promote or exacerbate renal disease.

A unified pathogenesis for kidney diseases, including genetic diseases and cancers, by the protein-homeostasis-system hypothesis.

PubMed

Lee, Kyung-Yil

2017-06-01

Every cell of an organism is separated and protected by a cell membrane. It is proposed that harmony between intercellular communication and the health of an organism is controlled by a system, designated the protein-homeostasis-system (PHS). Kidneys consist of a variety of types of renal cells, each with its own characteristic cell-receptor interactions and producing characteristic proteins. A functional union of these renal cells can be determined by various renal function tests, and harmonious intercellular communication is essential for the healthy state of the host. Injury to a kind of renal cells can impair renal function and induce an imbalance in total body health. Every acute or chronic renal disease has unknown etiologic substances that are responsible for renal cell injury at the molecular level. The immune/repair system of the host should control the etiologic substances acting against renal cells; if this system fails, the disease progresses to end stage renal disease. Each renal disease has its characteristic pathologic lesions where immune cells and immune proteins, such as immunoglobulins and complements, are infiltrated. These immune cells and immune proteins may control the etiologic substances involved in renal pathologic lesions. Also, genetic renal diseases and cancers may originate from a protein deficiency or malfunctioning protein under the PHS. A unified pathogenesis for renal diseases, including acute glomerulonephritis, idiopathic nephrotic syndrome, immunoglobulin A nephropathy, genetic renal diseases such as Alport syndrome, and malignancies such as Wilms tumor and renal cell carcinoma, is proposed using the PHS hypothesis.

Arterial stiffness and decline of renal function in a primary care population.

PubMed

van Varik, Bernard J; Vossen, Liv M; Rennenberg, Roger J; Stoffers, Henri E; Kessels, Alfons G; de Leeuw, Peter W; Kroon, Abraham A

2017-01-01

Arterial stiffness is an important pathophysiological factor linking cardiovascular disease and kidney disease. Controversy exists as to whether arterial stiffness causes renal function decline, or kidney dysfunction leads to stiffening or whether the association is mutual. We aimed to investigate the longitudinal association between arterial stiffness and annual rate of renal function decline. We prospectively investigated in a primary care population whether carotid-femoral pulse wave velocity (PWV) was associated with estimated glomerular filtration rate (eGFR) and annual decline in eGFR in participants aged ⩾40 years without overt kidney disease. Baseline data on PWV and eGFR were available for 587 participants; follow-up measurements with a mean duration of 5.6 years were available for 222 patients. PWV, female gender and mean arterial pressure were independently associated with eGFR at baseline, although age confounded this association. More importantly, baseline PWV, age and eGFR were independent predictors of renal function decline. Stratification for age showed that the effect of PWV on rate of eGFR decline was amplified with advancing age. On the other hand, baseline eGFR did not determine annual change in PWV, suggesting a unidirectional association between arterial stiffness and eGFR. Arterial stiffness amplifies age-related renal function decline, suggesting that arterial stiffness plays a causal role in the development of renal damage, at least at later stages of age-related renal function decline, possibly through impaired renal autoregulation and increased arterial blood pressure pulsatility.

Compensatory Structural and Functional Adaptation after Radical Nephrectomy for Renal Cell Carcinoma According to Preoperative Stage of Chronic Kidney Disease.

PubMed

Choi, Don Kyoung; Jung, Se Bin; Park, Bong Hee; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Jeon, Hwang Gyun

2015-10-01

We investigated structural hypertrophy and functional hyperfiltration as compensatory adaptations after radical nephrectomy in patients with renal cell carcinoma according to the preoperative chronic kidney disease stage. We retrospectively identified 543 patients who underwent radical nephrectomy for renal cell carcinoma between 1997 and 2012. Patients were classified according to preoperative glomerular filtration rate as no chronic kidney disease--glomerular filtration rate 90 ml/minute/1.73 m(2) or greater (230, 42.4%), chronic kidney disease stage II--glomerular filtration rate 60 to less than 90 ml/minute/1.73 m(2) (227, 41.8%) and chronic kidney disease stage III--glomerular filtration rate 30 to less than 60 ml/minute/1.73 m(2) (86, 15.8%). Computerized tomography performed within 2 months before surgery and 1 year after surgery was used to assess functional renal volume for measuring the degree of hypertrophy of the remnant kidney, and the preoperative and postoperative glomerular filtration rate per unit volume of functional renal volume was used to calculate the degree of hyperfiltration. Among all patients (mean age 56.0 years) mean preoperative glomerular filtration rate, functional renal volume and glomerular filtration rate/functional renal volume were 83.2 ml/minute/1.73 m(2), 340.6 cm(3) and 0.25 ml/minute/1.73 m(2)/cm(3), respectively. The percent reduction in glomerular filtration rate was statistically significant according to chronic kidney disease stage (no chronic kidney disease 31.2% vs stage II 26.5% vs stage III 12.8%, p <0.001). However, the degree of hypertrophic functional renal volume in the remnant kidney was not statistically significant (no chronic kidney disease 18.5% vs stage II 17.3% vs stage III 16.5%, p=0.250). The change in glomerular filtration rate/functional renal volume was statistically significant (no chronic kidney disease 18.5% vs stage II 20.1% vs stage III 45.9%, p <0.001). Factors that increased glomerular filtration rate/functional renal volume above the mean value were body mass index (p=0.012), diabetes mellitus (p=0.023), hypertension (p=0.015) and chronic kidney disease stage (p <0.001). Patients with a lower preoperative glomerular filtration rate had a smaller reduction in postoperative renal function than those with a higher preoperative glomerular filtration rate due to greater degrees of functional hyperfiltration. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The use of fibrous, supramolecular membranes and human tubular cells for renal epithelial tissue engineering: towards a suitable membrane for a bioartificial kidney.

PubMed

Dankers, Patricia Y W; Boomker, Jasper M; Huizinga-van der Vlag, Ali; Smedts, Frank M M; Harmsen, Martin C; van Luyn, Marja J A

2010-11-10

A bioartificial kidney, which is composed of a membrane cartridge with renal epithelial cells, can substitute important kidney functions in patients with renal failure. A particular challenge is the maintenance of monolayer integrity and specialized renal epithelial cell functions ex vivo. We hypothesized that this can be improved by electro-spun, supramolecular polymer membranes which show clear benefits in ease of processability. We found that after 7 d, in comparison to conventional microporous membranes, renal tubular cells cultured on top of our fibrous supramolecular membranes formed polarized monolayers, which is prerequisite for a well-functioning bioartificial kidney. In future, these supramolecular membranes allow for incorporation of peptides that may increase cell function even further.

Monthly plasmapheresis for systemic lupus erythematosus with diffuse proliferative glomerulonephritis: a pilot study

PubMed Central

Clark, William F.; Lindsay, Robert M.; Cattran, Daniel C.; Chodirker, William B.; Barnes, Colin C.; Linton, Adam L.

1981-01-01

Twelve patients with systemic lupus erythematosus and biopsy-proved diffuse proliferative glomerulonephritis were randomly allocated to a control group (to continue receiving conventional therapy only) or to a plasmapheresis group (to receive conventional therapy along with one 4-I plasma exchange a month). The six patients treated with plasmapheresis had better preservation of renal function, reduced disease activity, fewer admissions to hospital and less need for steroid and immunosuppressive therapy than the six control patients. The patients treated with plasmapheresis also showed evidence of reduced immunologic activity and had no side effects attributable to the plasma exchange. These results suggest that monthly plasma exchange should be assessed in a controlled randomized trial as a possible therapeutic adjunct in patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis. PMID:7272867

Pharmacokinetic/Pharmacodynamic Modeling and Simulation of Cefiderocol, a Parenteral Siderophore Cephalosporin, for Dose Adjustment Based on Renal Function.

PubMed

Katsube, Takayuki; Wajima, Toshihiro; Ishibashi, Toru; Arjona Ferreira, Juan Camilo; Echols, Roger

2017-01-01

Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent efficacy against most Gram-negative bacteria, including carbapenem-resistant strains. Since cefiderocol is excreted primarily via the kidneys, this study was conducted to develop a population pharmacokinetics (PK) model to determine dose adjustment based on renal function. Population PK models were developed based on data for cefiderocol concentrations in plasma, urine, and dialysate with a nonlinear mixed-effects model approach. Monte-Carlo simulations were conducted to calculate the probability of target attainment (PTA) of fraction of time during the dosing interval where the free drug concentration in plasma exceeds the MIC (T f >MIC ) for an MIC range of 0.25 to 16 μg/ml. For the simulations, dose regimens were selected to compare cefiderocol exposure among groups with different levels of renal function. The developed models well described the PK of cefiderocol for each renal function group. A dose of 2 g every 8 h with 3-h infusions provided >90% PTA for 75% T f >MIC for an MIC of ≤4 μg/ml for patients with normal renal function, while a more frequent dose (every 6 h) could be used for patients with augmented renal function. A reduced dose and/or extended dosing interval was selected for patients with impaired renal function. A supplemental dose immediately after intermittent hemodialysis was proposed for patients requiring intermittent hemodialysis. The PK of cefiderocol could be adequately modeled, and the modeling-and-simulation approach suggested dose regimens based on renal function, ensuring drug exposure with adequate bactericidal effect. Copyright © 2016 American Society for Microbiology.

Increasing Body Mass Index Predicts Rapid Decline in Renal Function: A 5 Year Retrospective Study.

PubMed

Ma, Xiaojing; Zhang, Chengyin; Su, Hong; Gong, Xiaojie; Kong, Xianglei

2018-05-02

While obesity is a recognized risk factor for chronic kidney disease, it remains unclear whether change in body mass index (ΔBMI ) is independently associated with decline in renal function (evaluated by the change in estimated glomerular filtration rate, ΔeGFR) over time. Accordingly, to help clarify this we conducted a retrospective study to measure the association of ΔBMI with decline in renal function in Chinese adult population. A total of 4007 adults (aged 45.3±13.7 years, 68.6% male) without chronic kidney disease at baseline were enrolled between 2008 and 2013. Logistic regression models were applied to explore the relationships between baseline BMI and ΔBMI, and rapid decline in renal function (defined as the lowest quartile of ΔeGFR ). During 5 years of follow-up, the ΔBMI and ΔeGFR were 0.47±1.6 (kg/m 2 ) and -3.0±8.8 (ml/min/1.73 m 2 ), respectively. After adjusted for potential confounders, ΔBMI (per 1 kg/m 2 increase) was independently associated with the rapid decline in renal function [with a fully adjusted OR of 1.12 (95% CI, 1.05 to 1.20). By contrast, the baseline BMI was not associated with rapid decline in renal function [OR=1.05 (95% CI, 0.98 to 1.13)]. The results were robust among 2948 hypertension-free and diabetes-free participants, the adjusted ORs of ΔBMI and baseline BMI were 1.14 (95% CI, 1.05 to 1.23) and 1.0 (95% CI, 0.96 to 1.04) for rapid decline in renal function, respectively. The study revealed that increasing ΔBMI predicts rapid decline in renal function. © Georg Thieme Verlag KG Stuttgart · New York.

Cigarette smoking reduced renal function deterioration in hypertensive patients may be mediated by elevated homocysteine.

PubMed

Huang, Feifei; Chen, Jie; Liu, Xun; Han, Feng; Cai, Qingqing; Peng, Guicheng; Zhang, Kun; Chen, Weiqing; Wang, Jingfeng; Huang, Hui

2016-12-27

Elevated homocysteine (HCY) and smoking are both important risk factors for hypertensive patients. However, whether they have crossing effect on renal function deterioration of hypertensive patients and what is the underlying mechanism are unclear. In the present study, 3033 participants diagnosed as essential hypertension with estimated glomerular filtration rate (eGFR)> 30 ml/min/1.73 m2 from southern China were enrolled in this cross-sectional study. We collected the demographic and clinical data. In addition, the mediation effects were analyzed. The results showed that, comparing with non-smokers, smokers had significant higher levels of HCY (13.10 (11.20-16.87) vs. 11.00 (8.90-13.40) umol/L, P < 0.001) and lower eGFR (79.71 (66.83-91.05) vs. 82.89 (69.80-95.85) ml/min/1.73m2, P < 0.001). HCY levels and smoking were independently associated with decreased eGFR. Meanwhile, eGFR levels were significantly negatively correlated with HCY (P < 0.001), and this correlation might be stronger in current smokers. Current smoker consuming over 20 cigarettes per day would accelerate early renal function deterioration (OR = 1.859, P = 0.019). The mediation effects analysis further showed that the association between smoking and renal function deterioration was mediated by HCY. And elevated HCY was accounted for 56.94% of the estimated causal effect of smoking on renal function deterioration in hypertensive patients. Our findings indicated that cigarette smoking was associated with renal function deterioration in hypertensive patients, and the association between cigarette smoking and renal function deterioration was probably mediated by elevated HCY. Therefore, HCY-lowering therapy may be beneficial for renal function deterioration in hypertensive smoking patients.

Effect of renal function status on the prognostic value of heart rate in acute ischemic stroke patients.

PubMed

Zhu, Zhengbao; Zhong, Chongke; Xu, Tian; Wang, Aili; Peng, Yanbo; Xu, Tan; Peng, Hao; Chen, Chung-Shiuan; Wang, Jinchao; Ju, Zhong; Li, Qunwei; Geng, Deqin; Sun, Yingxian; Du, Qingjuan; Li, Yongqiu; Chen, Jing; Zhang, Yonghong; He, Jiang

2017-08-01

The association between heart rate and prognosis of ischemic stroke remains debatable, and whether renal function status influences the relationship between them is still not elucidated. A total of 3923 ischemic stroke patients were included in this prospective multicenter study from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke. Secondary outcomes were, separately, death and major disability. The association between heart rate tertiles and primary outcome was appreciably modified by renal function status (p interaction  = 0.037). After multivariate adjustment, high heart rate was associated with increased risk of primary outcome in patients with abnormal renal function (odds ratio, 1.61; 95% confidence interval, 1.02-2.54; p trend  = 0.039) but not in patients with normal renal function (odds ratio, 0.96; 95% confidence interval, 0.75-1.23; p trend  = 0.741), when two extreme tertiles were compared. Each 10 bpm increase of heart rate was associated with 21% (95% CI: 1%-44%) increased risk of primary outcome, and a linear association between heart rate and risk of primary outcome was observed among patients with abnormal renal function (p for linearity = 0.002). High heart rate may be merely a strong predictor of poor prognosis in acute ischemic stroke patients with abnormal renal function, suggesting that heart rate reduction should be applied to ischemic stroke patients with abnormal renal function to improve their prognosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Meta-analysis of safety and efficacy for direct oral anticoagulation treatment of non-valvular atrial fibrillation in relation to renal function.

PubMed

Zou, Rongjun; Tao, Jun; Shi, Wanting; Yang, Minglei; Li, Hongmu; Lin, Xifeng; Yang, Songran; Hua, Ping

2017-12-01

We performed a meta-analysis of the safety and efficacy of anticoagulation treatment for atrial fibrillation (AF) in relation to renal function. We also examined the change in estimated glomerular filtration rate (eGFR) from baseline and compared the outcomes for patients with stable and worsening renal function. We selected studies that used randomized controlled trials in which outcomes for direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban, or edoxaban) were compared with those for warfarin in AF patients with normal, mild or moderate renal function, except the severe one (creatinine clearance<30). We assessed five clinical trials, involving 72,608 patients. Pooled analysis indicated that the risk of stroke was lower for DOACs than for warfarin among patients with mild renal impairment (Risk ratio, 0.79; 95% confidence interval, 0.68-0.91) and moderate renal impairment (0.80, 0.69-0.92). No major differences were found in patients with normal renal function. Additionally, DOACs were associated with fewer major bleeds among patients with normal (0.77, 0.70-0.84), mild (0.86, 0.77-0.95), and moderate renal impairment (0.73, 0.65-0.82). Among those treated with DOACs, a lower dosage was associated with lower risk of major bleeding (0.75, 0.68-0.83) and higher risk of stroke or systemic embolism (1.28, 1.12-1.47). Further, DOACs tended to be associated with a lower estimated glomerular filtration rate (eGFR) than warfarin even after 30months. Finally, we found significant differences in the risk of stroke (2.09, 1.64-2.68) and major bleeding (2.01, 1.66-2.42) between patients with stable and worsening renal function. DOACs have a greater clinical benefit than warfarin with respect to renal function. They are associated with a comparatively lower risk of stroke and major bleeding, as well lower eGFR. This suggests these agents are a better choice in patients with renal disease. Copyright © 2017. Published by Elsevier Ltd.

Biomarkers of Renal Tumor Burden and Progression in TSC

DTIC Science & Technology

2012-09-01

code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Biomarkers of Renal Tumor Burden and Progression in TSC Dr. Elahna Paul 1...appearance and growth rates) and renal function parameters (e.g. blood pressure, serum chemistries, urinalysis and urine chemistries). (2) Measure...and renal function parameters (e.g. blood pressure, serum chemistries, urinalysis and urine chemistries). (2) Measure soluble growth factors