ELABELA Improves Cardio-Renal Outcome in Fatal Experimental Septic Shock.

PubMed

Coquerel, David; Chagnon, Frédéric; Sainsily, Xavier; Dumont, Lauralyne; Murza, Alexandre; Côté, Jérôme; Dumaine, Robert; Sarret, Philippe; Marsault, Éric; Salvail, Dany; Auger-Messier, Mannix; Lesur, Olivier

2017-11-01

Apelin-13 was recently proposed as an alternative to the recommended β-adrenergic drugs for supporting endotoxin-induced myocardial dysfunction. Since Apelin-13 signals through its receptor (Apelin peptide jejunum) to exert singular inotropic/vasotropic actions and to optimize body fluid balance, this candidate pathway might benefit septic shock management. Whether the newly discovered ELABELA (ELA), a second endogenous ligand of the Apelin peptide jejunum receptor highly expressed in the kidney, further improves cardio-renal impairment remains unknown. Interventional study in a rat model of septic shock (128 adult males) to assess the effects of ELA and Apelin-13 on vascular and cardio-renal function. Experiments were performed in a tertiary care University-based research institute. Polymicrobial sepsis-induced cardiac dysfunction was produced by cecal ligation puncture to assess hemodynamic efficacy, cardioprotection, and biomechanics under acute or continuous infusions of the apelinergic agonists ELA or Apelin-13 (39 and 15 µg/kg/hr, respectively) versus normal saline. Apelinergic agonists improved 72-hour survival after sepsis induction, with ELA providing the best clinical outcome after 24 hours. Apelinergic agonist infusion counteracted cecal ligation puncture-induced myocardial dysfunction by improving left ventricular pressure-volume relationship. ELA-treated cecal ligation puncture rats were the only group to 1) display a significant improvement in left ventricular filling as shown by increased E-wave velocity and left ventricular end-diastolic volume, 2) exhibit a higher plasma volume, and 3) limit kidney injury and free-water clearance. These beneficial renal effects were superior to Apelin-13, likely because full-length ELA enabled a distinctive regulation of pituitary vasopressin release. Activation of the apelinergic system by exogenous ELA or Apelin-13 infusion improves cardiovascular function and survival after cecal ligation puncture-induced sepsis. However, ELA proved better than Apelin-13 by improving fluid homeostasis, cardiovascular hemodynamics recovery, and limiting kidney dysfunction in a vasopressinergic-dependent manner.

Cardio-renal syndrome: an entity cardiologists and nephrologists should be dealing with collegially.

PubMed

Palazzuoli, Alberto; Ronco, Claudio

2011-11-01

Heart failure may lead to acute kidney injury and vice versa. Chronic kidney disease may affect the clinical outcome in terms of cardiovascular morbidity and mortality while chronic heart failure may cause CKD. All these disorders contribute to the composite definition of cardio-renal syndromes. Renal impairment in HF patients has been increasingly recognized as an independent risk factor for morbidity and mortality; however, the most important clinical trials in HF tend to exclude patients with significant renal dysfunction. The mechanisms whereby renal insufficiency worsens the outcome in HF are not known, and several pathways could contribute to the "vicious heart/kidney circle." Traditionally, renal impairment has been attributed to the renal hypoperfusion due to reduced cardiac output and decreased systemic pressure. The hypovolemia leads to sympathetic activity, increased renin-angiotensin-aldosterone pathways and arginine-vasopressin release. All these mechanisms cause fluid and sodium retention, peripheral vasoconstriction and an increased congestion as well as cardiac workload. Therapy addressed to improve renal dysfunction, reduce neurohormonal activation and ameliorate renal blood flow could lead to a reduction in mortality and hospitalization in patients with cardio-renal syndrome.

Direct peritoneal resuscitation improves obesity-induced hepatic dysfunction after trauma.

PubMed

Matheson, Paul J; Franklin, Glen A; Hurt, Ryan T; Downard, Cynthia D; Smith, Jason W; Garrison, Richard N

2012-04-01

The metabolic syndrome and associated fatty liver disease are thought to contribute to poor outcomes in trauma patients. Experimentally, obesity compromises liver blood flow. We sought to correlate the effect of obesity, injury severity, and liver dysfunction with trauma outcomes. We hypothesized that obesity-related liver dysfunction could be mitigated with the novel technique of adjunctive direct peritoneal resuscitation (DPR). This study has clinical and experimental arms. The clinical study was a case-controlled retrospective analysis of ICU trauma patients (n = 72 obese, n = 187 nonobese). The experimental study was a hemorrhagic shock model in obese rats to assess the effect of DPR on liver blood flow, liver function, and inflammatory mediators. In trauma patients, univariate and multivariate analyses demonstrated increasing mortality (p < 0.05), septic complications (p < 0.05), liver dysfunction (p < 0.001), and renal impairment (p < 0.05) with increasing body mass index and injury severity score. Obesity in rats impairs liver blood flow, liver function, renal function, and inflammation (interleukin [IL]-1β, IL-6, high mobility group protein B1[HMGB-1]). The addition of DPR to shock resuscitation restores liver blood flow, improves organ function, and reverses the systemic proinflammatory response. Our clinical review substantiates that obesity worsens trauma outcomes regardless of injury severity. Obesity-related liver and renal dysfunction is aggravated by injury severity. In an obese rat model of resuscitated hemorrhagic shock, the addition of DPR abrogates trauma-induced liver, renal, and inflammatory responses. We conclude that the addition of DPR to the clinical resuscitation regimen will benefit the obese trauma patient. Published by Elsevier Inc.

The impact of galectin-3 inhibition on aldosterone-induced cardiac and renal injuries.

PubMed

Calvier, Laurent; Martinez-Martinez, Ernesto; Miana, Maria; Cachofeiro, Victoria; Rousseau, Elodie; Sádaba, J Rafael; Zannad, Faiez; Rossignol, Patrick; López-Andrés, Natalia

2015-01-01

This study investigated whether galectin (Gal)-3 inhibition could block aldosterone-induced cardiac and renal fibrosis and improve cardiorenal dysfunction. Aldosterone is involved in cardiac and renal fibrosis that is associated with the development of cardiorenal injury. However, the mechanisms of these interactions remain unclear. Gal-3, a β-galactoside-binding lectin, is increased in heart failure and kidney injury. Rats were treated with aldosterone-salt combined with spironolactone (a mineralocorticoid receptor antagonist) or modified citrus pectin (a Gal-3 inhibitor), for 3 weeks. Wild-type and Gal-3 knockout mice were treated with aldosterone for 3 weeks. Hemodynamic, cardiac, and renal parameters were analyzed. Hypertensive aldosterone-salt-treated rats presented cardiac and renal hypertrophy (at morphometric, cellular, and molecular levels) and dysfunction. Cardiac and renal expressions of Gal-3 as well as levels of molecular markers attesting fibrosis were also augmented by aldosterone-salt treatment. Spironolactone or modified citrus pectin treatment reversed all of these effects. In wild-type mice, aldosterone did not alter blood pressure levels but increased cardiac and renal Gal-3 expression, fibrosis, and renal epithelial-mesenchymal transition. Gal-3 knockout mice were resistant to aldosterone effects. In experimental hyperaldosteronism, the increase in Gal-3 expression was associated with cardiac and renal fibrosis and dysfunction but was prevented by pharmacological inhibition (modified citrus pectin) or genetic disruption of Gal-3. These data suggest a key role for Gal-3 in cardiorenal remodeling and dysfunction induced by aldosterone. Gal-3 could be used as a new biotarget for specific pharmacological interventions. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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.

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

New Developments in Hepatorenal Syndrome.

PubMed

Mindikoglu, Ayse L; Pappas, Stephen C

2018-02-01

Hepatorenal syndrome (HRS) continues to be one of the major complications of decompensated cirrhosis, leading to death in the absence of liver transplantation. Challenges in precisely evaluating renal function in the patient with cirrhosis remain because of the limitations of serum creatinine (Cr) alone in estimating glomerular filtration rate (GFR); current GFR estimating models appear to underestimate renal dysfunction. Newer models incorporating renal biomarkers, such as the Cr-Cystatin C GFR Equation for Cirrhosis appear to estimate measured GFR more accurately. A major change in the diagnostic criteria for HRS based on dynamic serial changes in serum Cr that regard HRS type 1 as a special form of acute kidney injury promises the possibility of earlier identification of renal dysfunction in patients with cirrhosis. The diagnostic criteria of HRS still include the exclusion of other causes of kidney injury. Renal biomarkers have been disappointing in assisting with the differentiation of HRS from prerenal azotemia and other kidney disorders. Serum metabolomic profiling may be a more powerful tool to assess renal dysfunction, although the practical clinical significance of this remains unclear. As a result of the difficulties of assessing renal function in cirrhosis and the varying HRS diagnostic criteria and the rigor with which they are applied, the precise incidence and prevalence of HRS is unknown, but it is likely that HRS occurs more commonly than expected. The pathophysiology of HRS is rooted firmly in the setting of progressive reduction in renal blood flow as a result of portal hypertension and splanchnic vasodilation. Progressive marked renal cortical ischemia in patients with cirrhosis parallels the evolution of diuretic-sensitive ascites to diuretic-refractory ascites and HRS, a recognized continuum of renal dysfunction in cirrhosis. Alterations in nitrous oxide production, both increased and decreased, may play a major role in the pathophysiology of this evolution. The inflammatory cascade, triggered by bacterial translocation and endotoxemia, increasingly recognized as important in the manifestation of acute-on-chronic liver failure, also may play a significant role in the pathophysiology of HRS. The mainstay of treatment remains vasopressor therapy with albumin in an attempt to reverse splanchnic vasodilation and improve renal blood flow. Several meta-analyses have confirmed the value of vasopressors, chiefly terlipressin and noradrenaline, in improving renal function and reversing HRS type 1. Other interventions such as renal replacement therapy, transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Liver transplantation remains the definitive treatment for HRS. The frequency of simultaneous liver-kidney transplantation has increased dramatically in the Model for End-stage Liver Disease era, with changes in organ allocation policies. This has resulted in a more urgent need to predict native kidney recovery from HRS after liver transplantation alone, to avoid unnecessary simultaneous liver-kidney transplantation. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

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.

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.

Peri-operative kidney injury and long-term chronic kidney disease following orthotopic heart transplantation in children.

PubMed

Hoskote, Aparna; Burch, Michael

2015-06-01

Significant advances in cardiac intensive care including extracorporeal life support have enabled children with complex congenital heart disease and end-stage heart failure to be supported while awaiting transplantation. With an increasing number of survivors after heart transplantation in children, the complications from long-term immunosuppression, including renal insufficiency, are becoming more apparent. Severe renal dysfunction after heart transplant is defined by a serum creatinine level >2.5 mg/dL (221 μmol/L), and/or need for dialysis or renal transplant. The degree of renal dysfunction is variable and is progressive over time. About 3-10 % of heart transplant recipients will go on to develop severe renal dysfunction within the first 10 years post-transplantation. Multiple risk factors for chronic kidney disease post-transplant have been identified, which include pre-transplant worsening renal function, recipient demographics and morbidity, peri-transplant haemodynamics and long-term exposure to calcineurin inhibitors. Renal insufficiency increases the risk of post-transplant morbidity and mortality. Hence, screening for renal dysfunction pre-, peri- and post-transplantation is important. Early and timely detection of renal insufficiency may help minimize renal insults, and allow prompt implementation of renoprotective strategies. Close monitoring and pre-emptive management of renal dysfunction is an integral aspect of peri-transplant and subsequent post-transplant long-term care.

Uric acid is a strong independent predictor of renal dysfunction in patients with rheumatoid arthritis.

PubMed

Daoussis, Dimitrios; Panoulas, Vasileios; Toms, Tracey; John, Holly; Antonopoulos, Ioannis; Nightingale, Peter; Douglas, Karen M J; Klocke, Rainer; Kitas, George D

2009-01-01

Recent evidence suggests that uric acid (UA), regardless of crystal deposition, may play a direct pathogenic role in renal disease. We have shown that UA is an independent predictor of hypertension and cardiovascular disease (CVD), and that CVD risk factors associate with renal dysfunction, in patients with rheumatoid arthritis (RA). In this study we investigated whether UA associates with renal dysfunction in patients with RA and whether such an association is independent or mediated through other comorbidities or risk factors for renal impairment. Renal function was assessed in 350 consecutive RA patients by estimated glomerular filtration rate (GFR) using the six-variable Modification of Diet in Renal Disease equation. Risk factors for renal dysfunction were recorded or measured in all participants. Linear regression was used to test the independence of the association between GFR and UA. Univariable analysis revealed significant associations between GFR and age, systolic blood pressure, total cholesterol, triglycerides, RA duration and UA. UA had the most powerful association with renal dysfunction (r = -0.45, P < 0.001). A basic model was created, incorporating all of the above parameters along with body mass index and gender. UA ranked as the first correlate of GFR (P < 0.001) followed by age. Adjustments for the use of medications (diuretics, low-dose aspirin, cyclooxygenase II inhibitors and nonsteroidal anti-inflammatory drugs) and further adjustment for markers of inflammation and insulin resistance did not change the results. UA is a strong correlate of renal dysfunction in RA patients. Further studies are needed to address the exact causes and clinical implications of this new finding. RA patients with elevated UA may require screening for renal dysfunction and appropriate management.

Drp1-dependent mitophagy protects against cisplatin-induced apoptosis of renal tubular epithelial cells by improving mitochondrial function

PubMed Central

Qi, Jia; Duan, Suyan; Huang, Zhimin; Zhang, Chengning; Wu, Lin; Zeng, Ming; Zhang, Bo; Wang, Ningning; Mao, Huijuan; Zhang, Aihua; Xing, Changying; Yuan, Yanggang

2017-01-01

Cisplatin chemotherapy often causes acute kidney injury (AKI) in cancer patients. There is increasing evidence that mitochondrial dysfunction plays an important role in cisplatin-induced nephrotoxicity. Degradation of damaged mitochondria is carried out by mitophagy. Although mitophagy is considered of particular importance in protecting against AKI, little is known of the precise role of mitophagy and its molecular mechanisms during cisplatin-induced nephrotoxicity. Also, evidence that activation of mitophagy improved mitochondrial function is lacking. Furthermore, several evidences have shown that mitochondrial fission coordinates with mitophagy. The aim of this study was to investigate whether activation of mitophagy protects against mitochondrial dysfunction and renal proximal tubular cells injury during cisplatin treatment. The effect of mitochondrial fission on mitophagy was also investigated. In cultured human renal proximal tubular cells, we observed that 3-methyladenine, a pharmacological inhibitor of autophagy, blocked mitophagy and exacerbated cisplatin-induced mitochondrial dysfunction and cells injury. In contrast, autophagy activator rapamycin enhanced mitophagy and protected against the harmful effects of cisplatin on mitochondrial function and cells viability. Suppression of mitochondrial fission by knockdown of its main regulator dynamin-related protein-1 (Drp1) decreased cisplatin-induced mitophagy. Meanwhile, Drp1 suppression protected against cisplatin-induced cells injury by inhibiting mitochondrial dysfunction. Our results provide evidence that Drp1-depedent mitophagy has potential as renoprotective targets for the treatment of cisplatin-induced AKI. PMID:28423497

Renal function changes after fenestrated endovascular aneurysm repair.

PubMed

Tran, Kenneth; Fajardo, Andres; Ullery, Brant W; Goltz, Christopher; Lee, Jason T

2016-08-01

Limited data exist regarding the effect of fenestrated endovascular aneurysm repair (fEVAR) on renal function. We performed a comprehensive analysis of acute and chronic renal function changes in patients after fEVAR. This study included patients undergoing fEVAR at two institutions between September 2012 and March 2015. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease formula with serum creatinine levels obtained during the study period. Acute and chronic renal dysfunction was assessed using the RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) criteria and the chronic kidney disease (CKD) staging system, respectively. fEVAR was performed in 110 patients for juxtarenal or paravisceral aortic aneurysms, with a mean follow-up of 11.7 months. A total of 206 renal stents were placed, with a mean aneurysm size of 62.9 mm (range, 45-105 mm) and a mean neck length of 4.1 mm. Primary renal stent patency was 97.1% at the latest follow-up. Moderate kidney disease (CKD stage ≥ 3) was present in 51% of patients at baseline, with a mean preoperative glomerular filtration rate of 60.0 ± 19.6 mL/min/1.73 m 2 . Acute kidney injury occurred in 25 patients (22.7%), although 15 of these (60%) were classified as having mild dysfunction. During follow-up, 59 patients (73.7%) were found to have no change or improved renal disease by CKD staging, and 19 (23.7%) had a CKD increase of one stage. Two patients were noted to have end-stage renal failure requiring hemodialysis. Clinically significant renal dysfunction was noted in 21 patients (26.2%) at the latest follow-up. Freedom from renal decline at 1 year was 76.1% (95% confidence interval, 63.2%-85.0%). Surrogate markers for higher operative complexity, including operating time (P = .001), fluoroscopy time (P < .001), contrast volume (P = .017), and blood loss (P = .002), served as dependent risk factors for acute kidney injury, although though no independent predictors were identified. Age (P = .008) was an independent risk factor for long-term decline, whereas paradoxically, baseline kidney disease (P = .032) and longer operative times (P = .014) were protective of future renal dysfunction. Acute and chronic renal dysfunction both occur in approximately one-quarter of patients after fEVAR; however, most of these cases are classified as mild according to consensus definitions of renal injury. The presence of mild or moderate baseline kidney disease should not preclude endovascular repair in the juxtarenal population. Routine biochemical analysis and branch vessel surveillance remain important aspects of clinical follow-up for patients undergoing fEVAR. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Prevalence and Factors Associated with Renal Dysfunction Among HIV-Infected Patients

DTIC Science & Technology

2010-01-01

cross-sectional study at two military clinics with open access to care to determine the impact of HIV factors, including antiretroviral therap¥, on...clinics with open access to care to determine the impact of HIV factors, including antiretroviral therapi, on renal function. Renal dysfunction was...measurement for determination of renal dysfunction rather than measurements over a 3-month or greater period used to establish chronic kidney disease.21

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

PubMed

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

2018-01-02

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

Assessing the effect of preoperative levosimendan on renal function in patients with right ventricular dysfunction.

PubMed

Guerrero Orriach, Jose L; Galán Ortega, M; Ramírez Fernandez, A; Ariza Villanueva, D; Florez Vela, A; Moreno Cortés, I; Rubio Navarro, M; Cruz Mañas, J

2017-02-01

The Acute Kidney Injury Network (AKIN) classification considers SCr values, urea and urine output in order to improve timely diagnose ARF and improve patient prognosis by early treatment. Preoperative levosimendan is a new way for cardiac and kidney protection, we try to evaluate this drug in fifteen patients comparing values of AKIN scale parameters pre and post cardiac surgery in patients with right ventricle dysfunction.

Improved mitochondrial function underlies the protective effect of pirfenidone against tubulointerstitial fibrosis in 5/6 nephrectomized rats.

PubMed

Chen, Jun-Feng; Liu, Hong; Ni, Hai-Feng; Lv, Lin-Li; Zhang, Ming-Hui; Zhang, Ai-Hua; Tang, Ri-Ning; Chen, Ping-Sheng; Liu, Bi-Cheng

2013-01-01

Dysfunctional mitochondria participate in the progression of chronic kidney disease (CKD). Pirfenidone is a newly identified anti-fibrotic drug. However, its mechanism remains unclear. Mitochondrial dysfunction is an early event that occurs prior to the onset of renal fibrosis. In this context, we investigated the protective effect of pirfenidone on mitochondria and its relevance to apoptosis and oxidative stress in renal proximal tubular cells. A remnant kidney rat model was established. Human renal proximal tubular epithelial cells (HK2) using rotenone, a mitochondrial respiratory chain complex Ι inhibitor were further investigated in vitro to examine the mitochondrial protective effect of pirfenidone. Pirfenidone protected mitochondrial structures and functions by stabilizing the mitochondrial membrane potential, maintaining ATP production and improving the mitochondrial DNA (mtDNA) copy number. Pirfenidone decreased tubular cell apoptosis by inhibiting the mitochondrial apoptotic signaling pathway. Pirfenidone also reduced oxidative stress by enhancing manganese superoxide dismutase (Mn-SOD) and inhibiting intracellular reactive oxygen species (ROS) generation, which suggested that the anti-oxidant effects occurred at least partially via the mitochondrial pathway. Pirfenidone may be effective prior to the onset of renal fibrosis because this drug exerts its anti-fibrotic effect by protection of mitochondria in renal proximal tubular cells.

Improved Mitochondrial Function Underlies the Protective Effect of Pirfenidone against Tubulointerstitial Fibrosis in 5/6 Nephrectomized Rats

PubMed Central

Chen, Jun-Feng; Liu, Hong; Ni, Hai-Feng; Lv, Lin-Li; Zhang, Ming-Hui; Zhang, Ai-Hua; Tang, Ri-Ning; Chen, Ping-Sheng; Liu, Bi-Cheng

2013-01-01

Dysfunctional mitochondria participate in the progression of chronic kidney disease (CKD). Pirfenidone is a newly identified anti-fibrotic drug. However, its mechanism remains unclear. Mitochondrial dysfunction is an early event that occurs prior to the onset of renal fibrosis. In this context, we investigated the protective effect of pirfenidone on mitochondria and its relevance to apoptosis and oxidative stress in renal proximal tubular cells. A remnant kidney rat model was established. Human renal proximal tubular epithelial cells (HK2) using rotenone, a mitochondrial respiratory chain complex Ι inhibitor were further investigated in vitro to examine the mitochondrial protective effect of pirfenidone. Pirfenidone protected mitochondrial structures and functions by stabilizing the mitochondrial membrane potential, maintaining ATP production and improving the mitochondrial DNA (mtDNA) copy number. Pirfenidone decreased tubular cell apoptosis by inhibiting the mitochondrial apoptotic signaling pathway. Pirfenidone also reduced oxidative stress by enhancing manganese superoxide dismutase (Mn-SOD) and inhibiting intracellular reactive oxygen species (ROS) generation, which suggested that the anti-oxidant effects occurred at least partially via the mitochondrial pathway. Pirfenidone may be effective prior to the onset of renal fibrosis because this drug exerts its anti-fibrotic effect by protection of mitochondria in renal proximal tubular cells. PMID:24349535

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.

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

PubMed

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

2017-06-01

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

Neutrophil Gelatinase Associated Lipocalin (NGAL) - a biomarker of renal dysfunction in patients with liver cirrhosis: Do we have enough proof?

PubMed

Firu, S G; Streba, C T; Firu, D; Tache, D E; Rogoveanu, I

2015-01-01

Renal dysfunction has a serious impact on the natural evolution of liver cirrhosis. Treatment and prognosis may be improved if an early diagnosis could be established, and specific therapeutic interventions would be applied. Although RIFLE and AKIN classifications have been successfully implemented in the clinical practice of Nephrology and Intensive Care Units, these did not provide major improvements in patients with liver cirrhosis. In the last decade, various biomarkers of kidney injury have been assessed, and Neutrophil Gelatinase-Associated Lipocalin (NGAL) is one of the most promising and most studied novel biomarker. To offer a brief evaluation on current data on the utility of this biomarker in patients with liver cirrhosis. We have searched through current literature and analyzed all significant full text articles on this topic. NGAL and other new kidney injury molecules may be useful in patients with liver cirrhosis, particularly in identifying structural kidney dysfunction, but larger validation studies to confirm this observation are needed.

Rapid improvement of renal function in patients with acute pulmonary embolism indicates favorable short term prognosis.

PubMed

Kostrubiec, Maciej; Łabyk, Andrzej; Pedowska-Włoszek, Justyna; Pacho, Szymon; Dzikowska-Diduch, Olga; Dul, Przemysław; Ciurzyński, Michał; Bienias, Piotr; Pruszczyk, Piotr

2012-09-01

Various clinical and biochemical parameters predict the prognosis of patients with acute pulmonary embolism(APE). Treatment of APE can improve a patient's hemodynamic status, restoring adequate peripheral organ perfusion. Therefore, we hypothesized that improvement of renal function can predict short term prognosis of APE patients. We evaluated 232 consecutive patients (94 men,aged 67 ± 18 years) with APE proven by spiral computer tomography. Blood samples were collected for creatinine assays on admission and 72 hours later, the glomerular filtration rate(eGFR) was estimated using the MDRD formula. During the first 72 hours, 6 subjects died, while during the first 30 days 24(10%) subjects died (APE mortality 8%). On admission eGFR<60 ml/min was present in 113 patients(49%) and after 72 hours in 85 patients(38%). In 26 patients(11%) eGFR on admission was <60 ml/min and renal function did not improve during subsequent 72 hours. In this group the 30-day all-cause and APE-related mortality rates were 27% and 23%, respectively, while serious adverse events occurred in 38% of them. 206 patients with eGFR>60 ml/min showed a more favorable prognosis (8% 30-day all-cause mortality) than subjects with eGFR<60 ml/min and a stable eGFR during the first 72 hours (27% mortality rate, p<0.003). Persistent renal dysfunction predicted all-cause and PE-related 30-day mortality (hazard risk 2.53(CI 95%:0.96-6.68),p=0.06 and 3.04(CI 95%:1.28-7.26),p=0.01, respectively). Approximately 50% of patients with APE have at least a moderately impaired renal function on admission. Renal function improves within 72 hours in patients with a good prognosis, while "persistent" renal dysfunction indicates an increased mortality. Copyright © 2012 Elsevier Ltd. All rights reserved.

Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy.

PubMed

Lee, Dae-Yeol; Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Kang, Kyung Pyo; Lee, Sik; Kim, Won; Park, Sung Kwang

2006-07-01

Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy. The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction. Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure. The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P < 0.01) than in patients with normal renal function (42.0%) or in the diabetes control group (40.6%). The Leu72Met polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05). These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.

Male gender and renal dysfunction are predictors of adverse outcome in nonpostoperative ischemic colitis patients.

PubMed

Lee, Tsung-Chun; Wang, Hsiu-Po; Chiu, Han-Mo; Lien, Wan-Ching; Chen, Mei-Jyh; Yu, Linda C H; Sun, Chia-Tung; Lin, Jaw-Town; Wu, Ming-Shiang

2010-01-01

Ischemic colitis (IC) spans a broad spectrum from self-limiting illness to intestinal gangrene and mortality. Prognostic factors specifically for nonpostoperative IC were not fully characterized. We aim to focus on nonpostoperative IC in patients with renal dysfunction and try to identify prognostic factors for adverse outcomes. We conducted a retrospective analysis at a university-affiliated tertiary medical center in Taiwan. From January 2003 to August 2008, 25 men and 52 women (mean age: 66 y) had colonoscopic biopsy-proven IC without prior culprit surgery. We estimated glomerular filtration rate with simplified Modification of Diet in Renal Disease equation. Nine patients with glomerular filtration rate below 30 mL per minute per 1.73 m were classified as renal dysfunction group (including 7 dialysis patients). Adverse outcomes were defined as need for surgery and mortality. Predictors for adverse outcomes were captured by univariate and multivariate analysis. Research ethical committee approved the study protocol. Patients with renal dysfunction more often had: diabetes mellitus (56% vs. 16%, P=0.02), prolonged symptoms (6.8 d vs. 3.5 d, P=0.01), lower hemoglobin (11.1 g/dL vs. 13.4 g/dL, P=0.01), and more often right colonic involvement (56% vs. 19%, P=0.03). Renal dysfunction patients also had longer hospitalization days (median 15 d vs. 4 d, P=0.045). However, there was no statistical significance in the rate of either surgery or mortality between these 2 groups (P>0.05). Univariate analysis showed that renal dysfunction, sex, emergency department referral, presentation with abdominal pain were significant for adverse outcome (P<0.1). Multivariate analysis revealed that male sex conveyed 9.5-fold risk (P=0.01) and renal dysfunction conveyed 8.5-fold risk (P=0.03) for adverse outcomes. Nonpostoperative IC patients with concurrent renal dysfunction had distinct clinical profiles. Multivariate analysis showed that male patients had 9.5-fold and renal dysfunction patients had 8.5-fold increased risk for adverse outcomes. Although IC is often self-limited, our data warrants special attention and aggressive therapy in treating these patients.

Renal dysfunction in liver cirrhosis and its correlation with Child-Pugh score and MELD score

NASA Astrophysics Data System (ADS)

Siregar, G. A.; Gurning, M.

2018-03-01

Renal dysfunction (RD) is a serious and common complication in a patient with liver cirrhosis. It provides a poor prognosis. The aim of our study was to evaluate the renal function in liver cirrhosis, also to determine the correlation with the graduation of liver disease assessed by Child-Pugh Score (CPS) and MELD score. This was a cross-sectional study included patients with liver cirrhosis admitted to Adam Malik Hospital Medan in June - August 2016. We divided them into two groups as not having renal dysfunction (serum creatinine < 1.5 mg/dL) and having renal dysfunction (serum creatinine ≤ 1.5 mg/dL). For the processing of data, SPSS 22.0 was used. Statistical methods used: Chi-square, Fisher exact, one way ANOVA, Kruskal Wallis test and Pearson coefficient of correlation. The level of significance was p<0.05. 55 patients with presented with renal dysfunction were 16 (29.1 %). There was statistically significant inverse correlation between GFR and CPS (r = -0.308), GFR and MELD score (r = -0.278). There was a statistically significant correlation between creatinine and MELD score (r = 0.359), creatinine and CPS (r = 0.382). The increase of the degree of liver damage is related to the increase of renal dysfunction.

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2011-03-01

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

Renal dysfunction after total body irradiation: Dose-effect relationship

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

Kal, Henk B.; Kempen-Harteveld, M. Loes van

2006-07-15

Purpose: Late complications related to total body irradiation (TBI) as part of the conditioning regimen for hematopoietic stem cell transplantation have been increasingly noted. We reviewed and compared the results of treatments with various TBI regimens and tried to derive a dose-effect relationship for the endpoint of late renal dysfunction. The aim was to find the tolerance dose for the kidney when TBI is performed. Methods and Materials: A literature search was performed using PubMed for articles reporting late renal dysfunction. For intercomparison, the various TBI regimens were normalized using the linear-quadratic model, and biologically effective doses (BEDs) were calculated.more » Results: Eleven reports were found describing the frequency of renal dysfunction after TBI. The frequency of renal dysfunction as a function of the BED was obtained. For BED >16 Gy an increase in the frequency of dysfunction was observed. Conclusions: The tolerance BED for kidney tissue undergoing TBI is about 16 Gy. This BED can be realized with highly fractionated TBI (e.g., 6 x 1.7 Gy or 9 x 1.2 Gy at dose rates >5 cGy/min). To prevent late renal dysfunction, the TBI regimens with BED values >16 Gy (almost all found in published reports) should be applied with appropriate shielding of the kidneys.« less

EET Enhances Renal Function in Obese Mice Resulting in Restoration of Mfn1/2 -HO-1 Signaling, and Decrease in Hypertension through Inhibition of Sodium Chloride Co-Transporter.

PubMed

Schragenheim, Joseph; Bellner, Lars; Cao, Jian; Singh, Shailendra P; Bamshad, David; McClung, John A; Maayan, Omri; Meissner, Aliza; Grant, Ilana; Stier, Charles T; Abraham, Nader G

2018-05-19

We have previously reported that epoxyeicosatrienoic acid (EET) has multiple beneficial effects on renal and adipose tissue function, in addition to its vasodilatory action; it increases insulin sensitivity and inhibits inflammation. In an examination of the signaling mechanisms by which EET reduces renal and peri-renal fat function, we hypothesized that EET ameliorates obesity-induced renal dysfunction by improving sodium excretion, reducing the sodium-chloride cotransporter NCC, lowering blood pressure, and enhancing mitochondrial and thermogenic gene levels in PGC-1α dependent mice. EET-agonist treatment normalized glucose metabolism, renal ENaC and NCC protein expression, urinary sodium excretion and blood pressure in obese (db/db) mice. A marked improvement in mitochondrial integrity, thermogenic genes, and PGC-1α-HO-1-adiponectin signaling occurred. Knockout of PGC-1α in EET-treated mice resulted in a reversal of these beneficial effects including a decrease in sodium excretion, elevation of blood pressure and an increase in the pro-inflammatory adipokine nephroblastoma overexpressed gene (NOV). In the elucidation of the effects of EET on peri-renal adipose tissue, EET increased adiponectin, mitochondrial integrity, thermogenic genes and decreased NOV, i.e. "Browning' peri-renal adipose phenotype that occurs under high fat diets. Taken together, these data demonstrate a critical role of an EET agonist in the restoration of healthy adipose tissue with reduced release of inflammatory molecules, such as AngII and NOV, thereby preventing their detrimental impact on sodium absorption and NCC levels and the development of obesity-induced renal dysfunction. Copyright © 2018. Published by Elsevier Inc.

Risk factors for renal dysfunction after total knee joint replacement.

PubMed

Hassan, Basim K; Sahlström, Arne; Dessau, Ram B

2015-12-01

Renal injury and dysfunction are serious complications after major surgery, which may lead to increased morbidity and mortality. The objective of our study was to identify the possible risk factors for renal dysfunction after total knee joint replacement. A retrospective study was conducted among 702 consecutive primary knee joint replacements performed between January 2009 and December 2012 in our department. Increased postoperative serum creatinine was considered indicative of postoperative renal injury according to RIFLE criteria. Sixty three patients (9.7%) had significant moderate or severe postoperative renal dysfunction in which 8 patients (1.2%) ended with severe and permanent renal impairment. Advanced age, low intraoperative blood pressure, hypertension, general anaesthesia, and prophylactic dicloxacillin were identified as significant risk factors. Male gender and BMI were independent risk factors for postoperative increase in serum creatinine. Smoking, female gender, diabetes mellitus and duration of surgery were not identified as significant risk factors.

Reversible preoperative renal dysfunction does not add to the risk of postoperative acute kidney injury after cardiac valve surgery

PubMed Central

Xu, Jia-Rui; Zhuang, Ya-Min; Liu, Lan; Shen, Bo; Wang, Yi-Mei; Luo, Zhe; Teng, Jie; Wang, Chun-Sheng; Ding, Xiao-Qiang

2017-01-01

Objective To evaluate the impact of the renal dysfunction (RD) type and change of postoperative cardiac function on the risk of developing acute kidney injury (AKI) in patients who underwent cardiac valve surgery. Method Reversible renal dysfunction (RRD) was defined as preoperative RD in patients who had not been initially diagnosed with chronic kidney disease (CKD). Cardiac function improvement (CFI) was defined as postoperative left ventricular ejection function – preoperative left ventricular ejection function (ΔEF) >0%, and cardiac function not improved (CFNI) as ΔEF ≤0%. Results Of the 4,805 (94%) cardiac valve surgery patients, 301 (6%) were RD cases. The AKI incidence in the RRD group (n=252) was significantly lower than in the CKD group (n=49) (36.5% vs 63.3%, P=0.018). The AKI and renal replacement therapy incidences in the CFI group (n=174) were significantly lower than in the CFNI group (n=127) (33.9% vs 50.4%, P=0.004; 6.3% vs 13.4%, P=0.037). After adjustment for age, gender, and other confounding factors, CKD and CKD + CFNI were identified as independent risk factors for AKI in all patients after cardiac valve surgery. Multivariate logistic regression analysis showed that the risk factors for postoperative AKI in preoperative RD patients were age, gender (male), hypertension, diabetes, chronic heart failure, cardiopulmonary bypass time (every 1 min added), and intraoperative hypotension, while CFI after surgery could reduce the risk. Conclusion For cardiac valve surgery patients, preoperative CKD was an independent risk factor for postoperative AKI, but RRD did not add to the risk. Improved postoperative cardiac function can significantly reduce the risk of postoperative AKI. PMID:29184415

Transient renal tubulopathy in a racing Greyhound.

PubMed

Abraham, L A; Tyrrell, D; Charles, J A

2006-11-01

A 2-year-old female Greyhound was presented for inappetence and lethargy. On referral, results of diagnostic tests indicated renal glucosuria, increased excretion of selected amino acids and abnormal fractional excretion of electrolytes consistent with renal tubular dysfunction. Systemic blood pressure was elevated. Renal biopsy revealed mild proximal renal tubular damage consistent with a subacute toxic or hypoxic insult. Systemic hypertension, renal glucosuria and altered fractional excretion of electrolytes resolved during the 7 day period of hospital treatment. The Greyhound resumed training without recurrence of renal dysfunction.

Chronic hydroxychloroquine improves endothelial dysfunction and protects kidney in a mouse model of systemic lupus erythematosus.

PubMed

Gómez-Guzmán, Manuel; Jiménez, Rosario; Romero, Miguel; Sánchez, Manuel; Zarzuelo, María José; Gómez-Morales, Mercedes; O'Valle, Francisco; López-Farré, Antonio José; Algieri, Francesca; Gálvez, Julio; Pérez-Vizcaino, Francisco; Sabio, José Mario; Duarte, Juan

2014-08-01

Hydroxychloroquine has been shown to be efficacious in the treatment of autoimmune diseases, including systemic lupus erythematosus. Hydroxychloroquine-treated lupus patients showed a lower incidence of thromboembolic disease. Endothelial dysfunction, the earliest indicator of the development of cardiovascular disease, is present in lupus. Whether hydroxychloroquine improves endothelial function in lupus is not clear. The aim of this study was to analyze the effects of hydroxychloroquine on hypertension, endothelial dysfunction, and renal injury in a female mouse model of lupus. NZBWF1 (lupus) and NZW/LacJ (control) mice were treated with hydroxychloroquine 10 mg/kg per day by oral gavage, or with tempol and apocynin in the drinking water, for 5 weeks. Hydroxychloroquine treatment did not alter lupus disease activity (assessed by plasma double-stranded DNA autoantibodies) but prevented hypertension, cardiac and renal hypertrophy, proteinuria, and renal injury in lupus mice. Aortae from lupus mice showed reduced endothelium-dependent vasodilator responses to acetylcholine and enhanced contraction to phenylephrine, which were normalized by hydroxychloroquine or antioxidant treatments. No differences among all experimental groups were found in both the relaxant responses to acetylcholine and the contractile responses to phenylephrine in rings incubated with the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester. Vascular reactive oxygen species content and mRNA levels of nicotinamide adenine dinucleotide phosphate oxidase subunits NOX-1 and p47(phox) were increased in lupus mice and reduced by hydroxychloroquine or antioxidants. Chronic hydroxychloroquine treatment reduced hypertension, endothelial dysfunction, and organ damage in severe lupus mice, despite the persistent elevation of anti-double-stranded DNA, suggesting the involvement of new additional mechanisms to improve cardiovascular complications. © 2014 American Heart Association, Inc.

An update on renal involvement in hemophagocytic syndrome (macrophage activation syndrome).

PubMed

Esmaili, Haydarali; Mostafidi, Elmira; Mehramuz, Bahareh; Ardalan, Mohammadreza; Mohajel-Shoja, Mohammadali

2016-01-01

Hemophagocytic syndrome (HPS) is mainly characterized by massive infiltration of bone marrow by activated macrophages and often presents with pancytopenia. Thrombotic microangiopathy (TMA) is also present with thrombocytopenia and renal involvement. Both conditions could coexist with each other and complicate the condition. Directory of Open Access Journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science with keywords relevant to; Hemophagocytic syndrome, macrophage activation syndrome, interferon-gamma and thrombotic microangiopathy, have been searched. Viral infection, rheumatologic disease and malignancies are the main underlying causes for secondary HPS. calcineurin inhibitors and viral infections are also the main underlying causes of TMA in transplant recipients. In this review, we discussed a 39-year-old male who presented with pancytopenia and renal allograft dysfunction. With the diagnosis of HPS induced TMA his renal condition and pancytopenia improved after receiving intravenous immunoglobulin (IVIG) and plasmapheresis therapy. HPS is an increasingly recognized disorder in the realm of different medical specialties. Renal involvement complicates the clinical picture of the disease, and this condition even is more complex in renal transplant recipients. We should consider the possibility of HPS in any renal transplant recipient with pancytopenia and allograft dysfunction. The combination of HPS with TMA future increases the complexity of the situation.

An update on renal involvement in hemophagocytic syndrome (macrophage activation syndrome)

PubMed Central

Esmaili, Haydarali; Mostafidi, Elmira; Mehramuz, Bahareh; Ardalan, Mohammadreza; Mohajel-Shoja, Mohammadali

2016-01-01

Context: Hemophagocytic syndrome (HPS) is mainly characterized by massive infiltration of bone marrow by activated macrophages and often presents with pancytopenia. Thrombotic microangiopathy (TMA) is also present with thrombocytopenia and renal involvement. Both conditions could coexist with each other and complicate the condition. Evidence Acquisition: Directory of Open Access Journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science with keywords relevant to; Hemophagocytic syndrome, macrophage activation syndrome, interferon-gamma and thrombotic microangiopathy, have been searched. Results: Viral infection, rheumatologic disease and malignancies are the main underlying causes for secondary HPS. calcineurin inhibitors and viral infections are also the main underlying causes of TMA in transplant recipients. In this review, we discussed a 39-year-old male who presented with pancytopenia and renal allograft dysfunction. With the diagnosis of HPS induced TMA his renal condition and pancytopenia improved after receiving intravenous immunoglobulin (IVIG) and plasmapheresis therapy. Conclusions: HPS is an increasingly recognized disorder in the realm of different medical specialties. Renal involvement complicates the clinical picture of the disease, and this condition even is more complex in renal transplant recipients. We should consider the possibility of HPS in any renal transplant recipient with pancytopenia and allograft dysfunction. The combination of HPS with TMA future increases the complexity of the situation. PMID:27047804

Impact of Small Body Weight on Tenofovir-Associated Renal Dysfunction in HIV-Infected Patients: A Retrospective Cohort Study of Japanese Patients

PubMed Central

Nishijima, Takeshi; Komatsu, Hirokazu; Gatanaga, Hiroyuki; Aoki, Takahiro; Watanabe, Koji; Kinai, Ei; Honda, Haruhito; Tanuma, Junko; Yazaki, Hirohisa; Tsukada, Kunihisa; Honda, Miwako; Teruya, Katsuji; Kikuchi, Yoshimi; Oka, Shinichi

2011-01-01

Background Treatment with tenofovir is sometimes associated with renal dysfunction. Limited information is available on this side effect in patients with small body weight, although the use of tenofovir will spread rapidly in Asia and Africa, where patients are likely to be of smaller body weight. Methods In a single-center cohort, Japanese patients with HIV infection who started tenofovir-containing antiretroviral therapy were retrospectively analyzed. The incidence of tenofovir-associated renal dysfunction, defined as more than 25% decrement of estimated glomerular filtration rate (eGFR) from the baseline, was determined. The effects of small body weight and body mass index (BMI) on tenofovir-associated renal dysfunction, respectively, were estimated in univariate and multivariate Cox hazards models as the primary exposure. Other possible risk factors were evaluated by univariate analysis and those found significant were entered into the multivariate analysis. Results The median weight of 495 patients was 63 kg. Tenofovir-related renal dysfunction occurred in 97 (19.6%) patients (incidence: 10.5 per 100 person-years). Univariate analysis showed that the incidence of tenofovir-related renal dysfunction was significantly associated with smaller body weight and BMI, respectively (per 5 kg decrement, HR = 1.23; 95% CI, 1.10–1.37; p<0.001)(per 1 kg/m2 decrement, HR = 1.14; 95% CI, 1.05–1.23; p = 0.001). Old age, high baseline eGFR, low serum creatinine, low CD4 count, high HIV viral load, concurrent nephrotoxic drugs, hepatitis C infection, and current smoking were also associated with tenofovir-related renal dysfunction. Multivariate analysis identified small body weight as a significant risk (adjusted HR = 1.13; 95% CI, 1.01–1.27; p = 0.039), while small BMI had marginal significance (adjusted HR = 1.07; 95% CI 1.00–1.16; p = 0.058). Conclusion The incidence of tenofovir-associated renal dysfunction in Japanese patients was high. Small body weight was identified as an independent risk factor for tenofovir-associated renal dysfunction. Close monitoring of renal function is advocated for patients with small body weight treated with tenofovir. PMID:21799928

Deletion of protein kinase C-ε attenuates mitochondrial dysfunction and ameliorates ischemic renal injury.

PubMed

Nowak, Grazyna; Takacsova-Bakajsova, Diana; Megyesi, Judit

2017-01-01

Previously, we documented that activation of protein kinase C-ε (PKC-ε) mediates mitochondrial dysfunction in cultured renal proximal tubule cells (RPTC). This study tested whether deletion of PKC-ε decreases dysfunction of renal cortical mitochondria and improves kidney function after renal ischemia. PKC-ε levels in mitochondria of ischemic kidneys increased 24 h after ischemia. Complex I- and complex II-coupled state 3 respirations were reduced 44 and 27%, respectively, in wild-type (WT) but unchanged and increased in PKC-ε-deficient (KO) mice after ischemia. Respiratory control ratio coupled to glutamate/malate oxidation decreased 50% in WT but not in KO mice. Activities of complexes I, III, and IV were decreased 59, 89, and 61%, respectively, in WT but not in KO ischemic kidneys. Proteomics revealed increases in levels of ATP synthase (α-subunit), complexes I and III, cytochrome oxidase, α-ketoglutarate dehydrogenase, and thioredoxin-dependent peroxide reductase after ischemia in KO but not in WT animals. PKC-ε deletion prevented ischemia-induced increases in oxidant production. Plasma creatinine levels increased 12-fold in WT and 3-fold in KO ischemic mice. PKC-ε deletion reduced tubular necrosis, brush border loss, and distal segment damage in ischemic kidneys. PKC-ε activation in hypoxic RPTC in primary culture exacerbated, whereas PKC-ε inhibition reduced, decreases in: 1) complex I- and complex II-coupled state 3 respirations and 2) activities of complexes I, III, and IV. We conclude that PKC-ε activation mediates 1) dysfunction of complexes I and III of the respiratory chain, 2) oxidant production, 3) morphological damage to the kidney, and 4) decreases in renal functions after ischemia. Copyright © 2017 the American Physiological Society.

Deletion of protein kinase C-ε attenuates mitochondrial dysfunction and ameliorates ischemic renal injury

PubMed Central

Takacsova-Bakajsova, Diana; Megyesi, Judit

2016-01-01

Previously, we documented that activation of protein kinase C-ε (PKC-ε) mediates mitochondrial dysfunction in cultured renal proximal tubule cells (RPTC). This study tested whether deletion of PKC-ε decreases dysfunction of renal cortical mitochondria and improves kidney function after renal ischemia. PKC-ε levels in mitochondria of ischemic kidneys increased 24 h after ischemia. Complex I- and complex II-coupled state 3 respirations were reduced 44 and 27%, respectively, in wild-type (WT) but unchanged and increased in PKC-ε-deficient (KO) mice after ischemia. Respiratory control ratio coupled to glutamate/malate oxidation decreased 50% in WT but not in KO mice. Activities of complexes I, III, and IV were decreased 59, 89, and 61%, respectively, in WT but not in KO ischemic kidneys. Proteomics revealed increases in levels of ATP synthase (α-subunit), complexes I and III, cytochrome oxidase, α-ketoglutarate dehydrogenase, and thioredoxin-dependent peroxide reductase after ischemia in KO but not in WT animals. PKC-ε deletion prevented ischemia-induced increases in oxidant production. Plasma creatinine levels increased 12-fold in WT and 3-fold in KO ischemic mice. PKC-ε deletion reduced tubular necrosis, brush border loss, and distal segment damage in ischemic kidneys. PKC-ε activation in hypoxic RPTC in primary culture exacerbated, whereas PKC-ε inhibition reduced, decreases in: 1) complex I- and complex II-coupled state 3 respirations and 2) activities of complexes I, III, and IV. We conclude that PKC-ε activation mediates 1) dysfunction of complexes I and III of the respiratory chain, 2) oxidant production, 3) morphological damage to the kidney, and 4) decreases in renal functions after ischemia. PMID:27760765

Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase.

PubMed

Guerrero-Orriach, José Luis; Ariza-Villanueva, Daniel; Florez-Vela, Ana; Garrido-Sánchez, Lourdes; Moreno-Cortés, María Isabel; Galán-Ortega, Manuel; Ramírez-Fernández, Alicia; Alcaide Torres, Juan; Fernandez, Concepción Santiago; Navarro Arce, Isabel; Melero-Tejedor, José María; Rubio-Navarro, Manuel; Cruz-Mañas, José

2016-01-01

To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase. This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL), neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng/mL), or mean ± SD creatinine (1.06±0.24 mg/dL vs 1.25±0.37 mg/dL at 48 hours). RV dilatation decreased from 4.23±0.7 mm to 3.45±0.6 mm and pulmonary artery pressure from 58±18 mmHg to 42±19 mmHg at 48 hours. Preoperative administration of levosimendan has shown a protective role against cardiac, renal, and neurological damage in patients with a high risk of multiple organ dysfunctions undergoing cardiac surgery.

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.

Pregnancy in women with renal disease. Yes or no?

PubMed Central

Edipidis, K

2011-01-01

Women with renal disease who conceive and continue pregnancy, are at significant risk for adverse maternal and fetal outcomes. Although advances in antenatal and neonatal care continue to improve these outcomes, the risks remain proportionate to the degree of underlying renal dysfunction. The aim of this article, is to examine the impact of varying degrees of renal insufficiency on pregnancy outcome, in women with chronic renal disease and to provide if possible, useful conclusions whether and when, a woman with Chronic Kidney Disease (CKD), should decide to get pregnant. This article, reviews briefly the normal physiological changes of renal function during pregnancy, and make an attempt to clarify the nature and severity of the risks, in the settings of chronic renal insufficiency and end stage renal disease, including dialysis patients and transplant recipients. PMID:21897751

Changes in renal function after implantation of continuous-flow left ventricular assist devices.

PubMed

Hasin, Tal; Topilsky, Yan; Schirger, John A; Li, Zhuo; Zhao, Yanjun; Boilson, Barry A; Clavell, Alfredo L; Rodeheffer, Richard J; Frantz, Robert P; Edwards, Brooks S; Pereira, Naveen L; Joyce, Lyle; Daly, Richard; Park, Soon J; Kushwaha, Sudhir S

2012-01-03

The aim of this study was to determine renal outcomes after left ventricular assist device (LVAD) implantation. Renal dysfunction before LVAD placement is frequent, and it is unclear whether it is due to primary renal disease or to poor perfusion. A retrospective single-center analysis was conducted in 83 consecutive patients implanted with HeartMate II continuous-flow LVADs (Thoratec Corp., Pleasanton, California). Calculated glomerular filtration rate (GFR) was assessed on admission and 1, 3, and 6 months after implantation. To define predictors for improvement in GFR, clinical variables were examined in patients with decreased renal function (GFR <60 ml/min/1.73 m(2)) before LVAD, surviving and dialysis-free at 1 month (n = 44). GFR significantly increased from admission (53.2 ± 21.4 ml/min/1.73 m(2)) to 1 month after LVAD implantation (87.4 ± 27.9 ml/min/1.73 m(2)) (p < 0.0001). Subsequently, at 3 and 6 months, GFR remained significantly (p < 0.0001) above pre-LVAD values. Of the 51 patients with GFRs <60 ml/min/1.73 m(2) before LVAD surviving at 1 month, 34 (67%) improved to GFRs >60 ml/min/1.73 m(2). Univariate pre-operative predictors for improvement in renal function at 1 month included younger age (p = 0.049), GFR improvement with optimal medical therapy (p < 0.001), intra-aortic balloon pump use (p = 0.004), kidney length above 10 cm (p = 0.023), no treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (p = 0.029), higher bilirubin (p = 0.002), higher Lietz-Miller score (p = 0.019), and atrial fibrillation (p = 0.007). Multivariate analysis indicated pre-operative improved GFR (slope = 0.5 U per unit improved; 95% confidence interval: 0.2 to 0.8; p = 0.003), atrial fibrillation (slope = 27; 95% confidence interval: 8 to 46; p = 0.006), and intra-aortic balloon pump use (slope = 14; 95% confidence interval: 2 to 26; p = 0.02) as independent predictors. In most patients with end-stage heart failure considered for LVAD implantation, renal dysfunction is reversible and likely related to poor renal perfusion. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Elevation of plasma milrinone concentrations in stage D heart failure associated with renal dysfunction.

PubMed

Cox, Zachary L; Calcutt, Marion W; Morrison, Thomas B; Akers, Wendell S; Davis, Mary Beth; Lenihan, Daniel J

2013-09-01

To determine steady state milrinone concentrations in patients with stage D heart failure (HF) with and without renal dysfunction We retrospectively identified patients with stage D HF at a single medical center on continuous milrinonein fusion at the time of plasma collection for entry into a research registry database. Milrinone was prescribed and titrated to improve hemodynamic and clinical status by a cardiologist. Plasma samples were obtained at steady state milrinone concentrations. Patients were stratified by creatinine clearance (CrCl) into 4 groups: group 1 (CrCl >60 mL/min), group 2 (CrCl 60-30 mL/min), group 3 (CrCl <30 mL/min), and group 4 (intermittent hemodialysis). Retrospective chart review was performed to quantify the post milrinone hemodynamic changes by cardiac catheterization and electrophysiologic changes by implantable cardiac defibrillator (ICD) interrogation. A total of 29 patients were identified: group 1 (n=14), group 2 (n=10), group 3(n=3), and group 4 (n = 2). The mean infusion rate (0.391+0.08 mg/kg/min) did not differ between groups (P=0.14). The mean milrinone concentration was 451+243 ng/mL in group 1, 591+293 ng/mL in group 2, 1575+962 ng/mL in group 3, and 6252+4409 ng/mL in group 4 (P<0.05 compared to groups 1). There was no difference in post milrinone hemodynamic improvements between the groups (P=0.41). The ICD interrogation revealed limited comparisons, but 6 of the 8 post milrinone ventricular tachycardia episodes requiring defibrillation occurred in group 4 patients. Patients with stage D HF having severe renal dysfunction have elevated milrinone concentrations. Future studies of milrinone concentrations are warranted to investigate the potential risk of life-threatening arrhythmias and potential dosing regimens in renal dysfunction.

Methoxyflurane revisited: tale of an anesthetic from cradle to grave.

PubMed

Mazze, Richard I

2006-10-01

Methoxyflurane metabolism and renal dysfunction: clinical correlation in man. By Richard I. Mazze, James R. Trudell, and Michael J. Cousins. Anesthesiology 1971; 35:247-52. Reprinted with permission. Serum inorganic fluoride concentration and urinary inorganic fluoride excretion were found to be markedly elevated in ten patients previously shown to have methoxyflurane induced renal dysfunction. Five patients with clinically evident renal dysfunction had a mean peak serum inorganic fluoride level (190 +/- 21 microm) significantly higher (P < 0.02) than that of those with abnormalities in laboratory tests only (106 +/- 17 microm). Similarly, patients with clinically evident renal dysfunction had a mean peak oxalic acid excretion (286 +/- 39 mg/24 h) significantly greater (P < 0.05) than that of those with laboratory abnormalities only (130 +/- 51 mg/24 h). That patients anesthetized with halothane had insignificant changes in serum inorganic fluoride concentration and oxalic acid excretion indicates that these substances are products of methoxyflurane metabolism. A proposed metabolic pathway to support this hypothesis is presented, as well as evidence to suggest that inorganic fluoride is the substance responsible for methoxyflurane renal dysfunction.

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.

Effect of Huanshuai Recipe Oral Liquid ([characters: see text]) on renal dysfunction progression in patients with atherosclerotic renal artery stenosis.

PubMed

Wang, Xiu-juan; Rao, Xiang-rong; Li, Shen; Wang, Li; Liu, Chang; Zhang, Gai-hua; Han, Dong-yan; Zhao, Yu; Zhang, Nan-nan; Li, Xue-xia; Chen, Shuai

2015-11-01

To investigate the effect of Huanshuai Recipe Oral Liquid ([characters: see text], HSR) on retarding the progression of renal dysfunction in patients with atherosclerotic renal artery stenosis (ARAS). A total of 52 ARAS patients with the Chinese medicine (CM) syndrome of qi deficiency and blood stasis, phlegm and dampness retention were recruited and randomly assigned into the treatment group (36 cases) and the control group (16 cases). Both groups received a basic treatment (high-quality low-protein diet, blood pressure control, lipid-lowering, correcting the acidosis, etc.). In addition, the treatment group received 20 mL HSR and the control group received placebo, 3 times a day for 6 months. Renal function (serum creatinine, blood urea nitrogen and uric acid) and blood lipids (cholesterol, triglycerides and low density lipoprotein) were examined monthly. The estimated glomerular filtration rate (eGFR) and CM syndrome score were compared between groups. After treatment, compared with the control group, the serum creatinine level, uric acid level and CM syndrome score of the treatment group were significantly decreased (P<0.05 or P<0.01), and the eGFR in the treatment group were significantly increased (P<0.05). HSR can effectively improve the renal function and clinical symptoms of ARAS patients.

Safety and efficacy of sofosbuvir and ribavirin for genotype 2 hepatitis C Japanese patients with renal dysfunction.

PubMed

Sho, Takuya; Suda, Goki; Nagasaka, Atsushi; Yamamoto, Yoshiya; Furuya, Ken; Kumagai, Kenichi; Uebayashi, Minoru; Terashita, Katsumi; Kobayashi, Tomoe; Tsunematsu, Izumi; Onodera, Manabu; Meguro, Takashi; Kimura, Megumi; Ito, Jun; Umemura, Machiko; Izumi, Takaaki; Kawagishi, Naoki; Ohara, Masatsugu; Ono, Yuji; Nakai, Masato; Natsuizaka, Mitsuteru; Morikawa, Kenichi; Ogawa, Koji; Sakamoto, Naoya

2018-06-01

The safety and efficacy of sofosbuvir (SOF) and ribavirin (RBV) have not been well clarified in patients with renal dysfunction because clinical trials have not included such patients. We evaluated the safety and efficacy of SOF and RBV for genotype 2 hepatitis C virus (HCV)-infected patients with renal dysfunction. The study included genotype 2 HCV-infected patients who received SOF and RBV between July 2014 and May 2017. The sustained virologic response (SVR) after the treatment and safety during the therapy were evaluated according to renal function. A total of 231 patients were included in this study. The median age was 62 years old, and 45.9% (106/231) were men. Of the 231 patients, 191 (82.8%) and 40 (17.2%) were classified as having chronic kidney disease (CKD) stages G1/2 and G3, respectively. The overall SVR rate was 97% (224/231). The SVR rates in patients with CKD stages G1, 2, G3a, and G3b were 98.1%, 98.6%, 87.9%, and 100%, respectively, and this therapy was tolerated. Multivariate analysis indicated that renal dysfunction was significantly associated with a non-SVR (odds ratio, 6.963; 95% confidence interval, 1.494-32.41; P = 0.013). The patients with renal dysfunction were older, had advanced liver fibrosis, lower baseline platelet and hemoglobin levels, and a higher rate of RBV dose reduction. Sofosbuvir and RBV therapy is highly effective and safe for genotype 2 HCV-infected Japanese patients. However, attention should be paid to baseline renal function when SOF- and RBV-containing regimens are used for patients with renal dysfunction. © 2018 The Japan Society of Hepatology.

Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

PubMed Central

Legrand, Matthieu; Mik, Egbert G; Johannes, Tanja; Payen, Didier; Ince, Can

2008-01-01

Ischemia is the most common cause of acute renal failure. Ischemic-induced renal tissue hypoxia is thought to be a major component in the development of acute renal failure in promoting the initial tubular damage. Renal oxygenation originates from a balance between oxygen supply and consumption. Recent investigations have provided new insights into alterations in oxygenation pathways in the ischemic kidney. These findings have identified a central role of microvascular dysfunction related to an imbalance between vasoconstrictors and vasodilators, endothelial damage and endothelium–leukocyte interactions, leading to decreased renal oxygen supply. Reduced microcirculatory oxygen supply may be associated with altered cellular oxygen consumption (dysoxia), because of mitochondrial dysfunction and activity of alternative oxygen-consuming pathways. Alterations in oxygen utilization and/or supply might therefore contribute to the occurrence of organ dysfunction. This view places oxygen pathways’ alterations as a potential central player in the pathogenesis of acute kidney injury. Both in regulation of oxygen supply and consumption, nitric oxide seems to play a pivotal role. Furthermore, recent studies suggest that, following acute ischemic renal injury, persistent tissue hypoxia contributes to the development of chronic renal dysfunction. Adaptative mechanisms to renal hypoxia may be ineffective in more severe cases and lead to the development of chronic renal failure following ischemia-reperfusion. This paper is aimed at reviewing the current insights into oxygen transport pathways, from oxygen supply to oxygen consumption in the kidney and from the adaptation mechanisms to renal hypoxia. Their role in the development of ischemia-induced renal damage and ischemic acute renal failure are discussed. PMID:18488066

Design and Methodological Considerations of the Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida

PubMed Central

Routh, Jonathan C.; Cheng, Earl Y.; Austin, J. Christopher; Baum, Michelle A.; Gargollo, Patricio C.; Grady, Richard W.; Herron, Adrienne R.; Kim, Steven S.; King, Shelly J.; Koh, Chester J.; Paramsothy, Pangaja; Raman, Lisa; Schechter, Michael S.; Smith, Kathryn A.; Tanaka, Stacy T.; Thibadeau, Judy K.; Walker, William O.; Wallis, M. Chad; Wiener, John S.; Joseph, David B.

2016-01-01

Purpose Care of children with spina bifida has significantly advanced in the last half century, resulting in gains in longevity and quality of life for affected children and caregivers. Bladder dysfunction is the norm in patients with spina bifida and may result in infection, renal scarring and chronic kidney disease. However, the optimal urological management for spina bifida related bladder dysfunction is unknown. Materials and Methods In 2012 the Centers for Disease Control and Prevention convened a working group composed of pediatric urologists, nephrologists, epidemiologists, methodologists, community advocates and Centers for Disease Control and Prevention personnel to develop a protocol to optimize urological care of children with spina bifida from the newborn period through age 5 years. Results An iterative quality improvement protocol was selected. In this model participating institutions agree to prospectively treat all newborns with spina bifida using a single consensus based protocol. During the 5-year study period outcomes will be routinely assessed and the protocol adjusted as needed to optimize patient and process outcomes. Primary study outcomes include urinary tract infections, renal scarring, renal function and bladder characteristics. The protocol specifies the timing and use of testing (eg ultrasonography, urodynamics) and interventions (eg intermittent catheterization, prophylactic antibiotics, antimuscarinic medications). Starting in 2014 the Centers for Disease Control and Prevention began funding 9 study sites to implement and evaluate the protocol. Conclusions The Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida began accruing patients in 2015. Assessment in the first 5 years will focus on urinary tract infections, renal function, renal scarring and clinical process improvements. PMID:27475969

Design and Methodological Considerations of the Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida.

PubMed

Routh, Jonathan C; Cheng, Earl Y; Austin, J Christopher; Baum, Michelle A; Gargollo, Patricio C; Grady, Richard W; Herron, Adrienne R; Kim, Steven S; King, Shelly J; Koh, Chester J; Paramsothy, Pangaja; Raman, Lisa; Schechter, Michael S; Smith, Kathryn A; Tanaka, Stacy T; Thibadeau, Judy K; Walker, William O; Wallis, M Chad; Wiener, John S; Joseph, David B

2016-12-01

Care of children with spina bifida has significantly advanced in the last half century, resulting in gains in longevity and quality of life for affected children and caregivers. Bladder dysfunction is the norm in patients with spina bifida and may result in infection, renal scarring and chronic kidney disease. However, the optimal urological management for spina bifida related bladder dysfunction is unknown. In 2012 the Centers for Disease Control and Prevention convened a working group composed of pediatric urologists, nephrologists, epidemiologists, methodologists, community advocates and Centers for Disease Control and Prevention personnel to develop a protocol to optimize urological care of children with spina bifida from the newborn period through age 5 years. An iterative quality improvement protocol was selected. In this model participating institutions agree to prospectively treat all newborns with spina bifida using a single consensus based protocol. During the 5-year study period outcomes will be routinely assessed and the protocol adjusted as needed to optimize patient and process outcomes. Primary study outcomes include urinary tract infections, renal scarring, renal function and bladder characteristics. The protocol specifies the timing and use of testing (eg ultrasonography, urodynamics) and interventions (eg intermittent catheterization, prophylactic antibiotics, antimuscarinic medications). Starting in 2014 the Centers for Disease Control and Prevention began funding 9 study sites to implement and evaluate the protocol. The Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida began accruing patients in 2015. Assessment in the first 5 years will focus on urinary tract infections, renal function, renal scarring and clinical process improvements. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Low-molecular-weight heparin venous thromboprophylaxis in critically ill patients with renal dysfunction: A subgroup analysis of the PROTECT trial

PubMed Central

Adhikari, Neill K. J.; Ostermann, Marlies; Heels-Ansdell, Diane; Douketis, James D.; Skrobik, Yoanna; Qushmaq, Ismael; Meade, Maureen; Guyatt, Gordon; Geerts, William; Walsh, Michael W.; Crowther, Mark A.; Friedrich, Jan O.; Burry, Lisa; Bellomo, Rinaldo; Brandão da Silva, Nilton; Costa Filho, Rubens; Cox, Michael J.; Alves Silva, Suzana; Cook, Deborah J.

2018-01-01

Introduction There is concern about excessive bleeding when low-molecular-weight heparins (LMWHs) are used for venous thromboembolism (VTE) prophylaxis in renal dysfunction. Our objective was to evaluate whether LMWH VTE prophylaxis was safe and effective in critically ill patients with renal dysfunction by conducting a subgroup analysis of PROTECT, a randomized blinded trial. Methods We studied intensive care unit (ICU) patients with pre-ICU dialysis-dependent end-stage renal disease (ESRD; pre-specified subgroup; n = 118), or severe renal dysfunction at ICU admission (defined as ESRD or non-dialysis dependent with creatinine clearance [CrCl] <30 ml/min; post hoc subgroup; n = 590). We compared dalteparin, 5000 IU daily, with unfractionated heparin (UFH), 5000 IU twice daily, and considered outcomes of proximal leg deep vein thrombosis (DVT); pulmonary embolism (PE); any VTE; and major bleeding. Adjusted hazard ratios [HR] were calculated using Cox regression. Results In patients with ESRD, there was no significant difference in DVT (8.3% vs. 5.2%, p = 0.76), any VTE (10.0% vs. 6.9%; p = 0.39) or major bleeding (5.0% vs. 8.6%; p = 0.32) between UFH and dalteparin. In patients with severe renal dysfunction, there was no significant difference in any VTE (10.0% vs. 6.4%; p = 0.07) or major bleeding (8.9% vs. 11.0%; p = 0.66) but an increase in DVT with dalteparin (7.6% vs. 3.7%; p = 0.04). Interaction p-values for comparisons of HRs (ESRD versus not) were non-significant. Conclusions In critically ill patients with ESRD, or severe renal dysfunction, there was no significant difference in any VTE or major bleeding between UFH and dalteparin. Patients with severe renal dysfunction who received dalteparin had more proximal DVTs than those on UFH; this finding did not hold in patients with ESRD alone. PMID:29856817

Spironolactone Treatment and Effect on Survival in Chronic Heart Failure Patients with Reduced Renal Function: A Propensity-Matched Study

PubMed Central

Stubnova, Viera; Os, Ingrid; Grundtvig, Morten; Atar, Dan; Waldum-Grevbo, Bård

2017-01-01

Background/Aims Spironolactone may be hazardous in heart failure (HF) patients with renal dysfunction due to risk of hyperkalemia and worsened renal function. We aimed to evaluate the effect of spironolactone on all-cause mortality in HF outpatients with renal dysfunction in a propensity-score-matched study. Methods A total of 2,077 patients from the Norwegian Heart Failure Registry with renal dysfunction (eGFR <60 mL/min/1.73 m2) not treated with spironolactone at the first visit at the HF clinic were eligible for the study. Patients started on spironolactone at the outpatient HF clinics (n = 206) were propensity-score-matched 1:1 with patients not started on spironolactone, based on 16 measured baseline characteristics. Kaplan-Meier and Cox regression analyses were used to investigate the independent effect of spironolactone on 2-year all-cause mortality. Results Propensity score matching identified 170 pairs of patients, one group receiving spironolactone and the other not. The two groups were well matched (mean age 76.7 ± 8.1 years, 66.4% males, and eGFR 46.2 ± 10.2 mL/min/1.73 m2). Treatment with spironolactone was associated with increased potassium (delta potassium 0.31 ± 0.55 vs. 0.05 ± 0.41 mmol/L, p < 0.001) and decreased eGFR (delta eGFR −4.12 ± 12.2 vs. −0.98 ± 7.88 mL/min/1.73 m2, p = 0.006) compared to the non-spironolactone group. After 2 years, 84% of patients were alive in the spironolactone group and 73% of patients in the non-spironolactone group (HR 0.59, 95% CI 0.37-0.92, p = 0.020). Conclusion In HF outpatients with renal dysfunction, treatment with spironolactone was associated with improved 2-year survival compared to well-matched patients not treated with spironolactone. Favorable survival was observed despite worsened renal function and increased potassium in the spironolactone group. PMID:28611786

Association between in-hospital mortality and renal dysfunction in 186,219 patients hospitalized for acute stroke in the Emilia-Romagna region of Italy.

PubMed

Fabbian, Fabio; Gallerani, Massimo; Pala, Marco; De Giorgi, Alfredo; Salmi, Raffaella; Dentali, Francesco; Ageno, Walter; Manfredini, Roberto

2014-11-01

Using a regional Italian database, we evaluated the relationship between renal dysfunction and in-hospital mortality (IHM) in patients with acute stroke (ischemic/hemorrhagic). Patients were classified on the basis of renal damage: without renal dysfunction, with chronic kidney disease (CKD), and with end-stage renal disease (ESRD). Of a total of 186,219 patients with a first episode of stroke, 1626 (0.9%) had CKD and 819 (0.4%) had ESRD. Stroke-related IHM (total cases) was independently associated with CKD, ESRD, atrial fibrillation (AF), age, and Charlson comorbidity index (CCI). In patients with ischemic stroke (n=154,026), IHM remained independently associated with CKD, ESRD, AF, and CCI. In patients with hemorrhagic stroke (n=32,189), variables that were independently associated with IHM were CKD, ESRD, and AF. Renal dysfunction is associated with IHM related to stroke, both ischemic and hemorrhagic, with even higher odds ratios than those of other established risk factors, such as age, comorbidities, and AF. © The Author(s) 2013.

[Endoscopic nasobiliary and nasopancreatic drainage contributing to healing of duodenal ulcer perforation: a case report].

PubMed

Enokida, Kohei; Kikuyama, Masataka; Kurokami, Takafumi; Shirane, Naofumi; Aoyama, Haruna; Aoyama, Hiroyuki; Sato, Tatsunori; Taki, Yusuke

2015-10-01

A 75-year-old man with vomiting and right abdominal pain was admitted to the Department of Surgery in our hospital. With a diagnosis of perforated duodenal ulcer, he was treated conservatively. On the day 8 of hospitalization, his general condition worsened and he underwent surgery. During operation, the perforated duodenal ulcer and paraduodenal fluid collection was observed, and percutaneous drainage was accordingly established. After this procedure, renal dysfunction was exacerbated and he was transferred to our department for endoscopic treatment. On day 28 of hospitalization, nasobiliary and nasopancreatic drainage was administered. Renal dysfunction gradually improved, and healing of the perforated duodenal ulcer was recognized on day 93. On day 112, the patient was discharged.

Cardio-renal syndromes: from foggy bottoms to sunny hills.

PubMed

Ronco, Claudio

2011-11-01

"Cardio-renal syndromes" (CRS) are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The current definition has been expanded into five subtypes whose etymology reflects the primary and secondary pathology, the time-frame and simultaneous cardiac and renal co-dysfunction secondary to systemic disease: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. These different subtypes may have a different pathophysiological mechanism and they may represent separate entities in terms of prevention and therapy.

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.

Influence of pre-hydration and pharmacogenetics on plasma methotrexate concentration and renal dysfunction following high-dose methotrexate therapy.

PubMed

Yanagimachi, Masakatsu; Goto, Hiroaki; Kaneko, Tetsuji; Naruto, Takuya; Sasaki, Koji; Takeuchi, Masanobu; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Kajiwara, Ryosuke; Fujii, Hisaki; Tanaka, Fumiko; Goto, Shoko; Takahashi, Hiroyuki; Mori, Masaaki; Kai, Sumio; Yokota, Shumpei

2013-12-01

High-dose methotrexate therapy (HD-MTX) has been well established for the treatment of childhood acute lymphoblastic leukemia (ALL). The aims of this study were to investigate whether clinical and pharmacogenetic factors influence plasma MTX concentration and renal dysfunction in patients treated with HD-MTX. In a total of 127 courses of HD-MTX in 51 patients with childhood ALL, influence of clinical and pharmacogenetic factors on plasma MTX concentration and HD-MTX-related renal dysfunction was evaluated. Clinical factors included age, gender, duration of HD-MTX continuous-infusion and duration of pre-hydration before HD-MTX. Pharmacogenetic factors included 5 gene polymorphisms within the MTX pathway genes, namely, SLC19A1, MTHFR, ABCC2 and ABCG2. Short duration of pre-hydration before HD-MTX is the most important risk factor for prolonged high MTX concentration (p < 0.001, OR 6.40, 95 % CI 2.39-17.16) and renal dysfunction (p = 0.013, OR 3.15, 95 % CI 1.27-7.80). The T allele at MTHFR C677T was the risk factor for prolonged high MTX concentration (p = 0.009, OR 5.54, 95 % CI 1.54-19.85), but not for renal dysfunction. We found the influence of MTHFR C677T polymorphism on prolonged high MTX concentration. We reconfirmed the importance of adequate pre-hydration before HD-MTX to prevent prolonged high MTX concentration and MTX-related renal dysfunction.

Expression of GSK-3β in renal allograft tissue and its significance in pathogenesis of chronic allograft dysfunction.

PubMed

Yan, Qiang; Wang, Baoyao; Sui, Weiguo; Zou, Guimian; Chen, Huaizhou; Xie, Shenping; Zou, Hequn

2012-01-13

To explore the expression of Glycogen synthase kinase 3 beta (GSK-3β) in renal allograft tissue and its significance in the pathogenesis of chronic allograft dysfunction. Renal allograft biopsy was performed in all of the renal allograft recipients with proteinuria or increased serum creatinine level who came into our hospital from January 2007 to December 2009. Among them 28 cases was diagnosed as chronic allograft dysfunction based on pahtological observation, including 21 males with a mean age of 45 ± 10 years old and 7 females with a mean age of 42 ± 9 years old. The time from kidney transplantation to biopsy were 1-9 (3.5) years. Their serum creatinine level were 206 ± 122 umol/L. Immunohistochemical assay and computer-assisted genuine color image analysis system (imagepro-plus 6.0) were used to detect the expression of GSK-3β in the renal allografts of 28 cases of recipients with chronic allograft dysfunction. Mean area and mean integrated optical density of GSK-3β expression were calculated. The relationship between expression level of GSK-3β and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed. Five specimens of healthy renal tissue were used as controls. The expression level of the GSK-3β was significantly increased in the renal allograft tissue of recipients with chronic allograft dysfunction, compared to normal renal tissues, and GSK-3β expression became stronger along with the increasing of the grade of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue. There might be a positive correlation between either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy and high GSK-3β expression in renal allograft tissue. The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/9924478946162998.

Two cases of malignant hypertension with reversible diffuse leukoencephalopathy exhibiting a reversible nocturnal blood pressure "riser" pattern.

PubMed

Eguchi, Kazuo; Kasahara, Kentaro; Nagashima, Akinori; Mor, Tadashi; Nii, Takanobu; Ibaraki, Kazuo; Kario, Kazuomi; Shimada, Kazuyuki

2002-05-01

We report two cases of malignant hypertension with reversible diffuse leukoencephalopathy demonstrating a nocturnal blood pressure (BP) rising pattern ("riser" pattern). Case 1 was a 54-year-old man diagnosed with malignant hypertension who presented with diffuse leukoencephalopathy and nocturnal BP rise during the acute phase. These abnormal findings diminished after treatment of hypertension. Case 2 was a 50-year-old woman diagnosed with malignant hypertension in association with leukoencephalopathy, heart failure and acute renal failure. She also presented with a "riser" pattern during the acute phase. In contrast to case 1, the leukoencephalopathy and "riser" pattern in case 2 were not improved even after 1 month of treatment. Following intensive antihypertensive treatment, renal failure was improved in case 1, but renal failure was not improved after 1 month in case 2. In conclusion, a possible explanation of this phenomenon is that a causative volume overload due to renal dysfunction produced the temporal leukoencephalopathy-like brain edema and "riser" pattern in these cases.

Abnormal factor VIII coagulant antigen in patients with renal dysfunction and in those with disseminated intravascular coagulation.

PubMed Central

Weinstein, M J; Chute, L E; Schmitt, G W; Hamburger, R H; Bauer, K A; Troll, J H; Janson, P; Deykin, D

1985-01-01

Factor VIII antigen (VIII:CAg) exhibits molecular weight heterogeneity in normal plasma. We have compared the relative quantities of VIII:CAg forms present in normal individuals (n = 22) with VIII:CAg forms in renal dysfunction patients (n = 19) and in patients with disseminated intravascular coagulation (DIC; n = 7). In normal plasma, the predominant VIII: CAg form, detectable by sodium dodecyl sulfate polyacrylamide gel electrophoresis, was of molecular weight 2.4 X 10(5), with minor forms ranging from 8 X 10(4) to 2.6 X 10(5) D. A high proportion of VIII:CAg in renal dysfunction patients, in contrast, was of 1 X 10(5) mol wt. The patients' high 1 X 10(5) mol wt VIII: CAg level correlated with increased concentrations of serum creatinine, F1+2 (a polypeptide released upon prothrombin activation), and with von Willebrand factor. Despite the high proportion of the 1 X 10(5) mol wt VIII:CAg form, which suggests VIII:CAg proteolysis, the ratio of Factor VIII coagulant activity to total VIII:CAg concentration was normal in renal dysfunction patients. These results could be simulated in vitro by thrombin treatment of normal plasma, which yielded similar VIII:CAg gel patterns and Factor VIII coagulant activity to antigen ratios. DIC patients with high F1+2 levels but no evidence of renal dysfunction had an VIII:CAg gel pattern distinct from renal dysfunction patients. DIC patients had elevated concentrations of both the 1 X 10(5) and 8 X 10(4) mol wt VIII:CAg forms. We conclude that an increase in a particular VIII:CAg form correlates with the severity of renal dysfunction. The antigen abnormality may be the result of VIII:CAg proteolysis by a thrombinlike enzyme and/or prolonged retention of proteolyzed VIII:CAg fragments. Images PMID:3932466

Hypomagnesemia and mild rhabdomyolysis in living related donor renal transplant recipient treated with cyclosporine A.

PubMed

Cavdar, C; Sifil, A; Sanli, E; Gülay, H; Camsari, T

1998-12-01

Since cyclosporine A (CsA) had been used in renal transplant recipients, important improvements in short-term and long-term graft survivals have been detected. In spite of these improvements CsA seems to have several adverse effects. First, CsA leads to nephrotoxicity. Moreover, CsA affects the other organs and systems (skin, liver, nervous system, etc.) and causes, increased risks of infections and malignancies. Hypomagnesemia is one of the side effects of CsA therapy, but it is a rare condition in living related donor renal transplant recipients. It may also cause multi-system dysfunction, especially hypocalcemia and hypokalemia, which cannot be corrected without magnesium therapy. In addition, rhabdomyolysis was detected in animals, but it has not been reported in living related donor renal transplant recipients. In this case report, a living related donor renal transplant recipient who suffered from hypomagnesemia and mild rhabdomyolysis due to CsA therapy will be described and discussed.

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.

Chronic Kidney Disease in Pregnancy.

PubMed

Koratala, Abhilash; Bhattacharya, Deepti; Kazory, Amir

2017-09-01

With the increasing prevalence of chronic kidney disease (CKD) worldwide, the number of pregnant women with various degrees of renal dysfunction is expected to increase. There is a bidirectional relation between CKD and pregnancy in which renal dysfunction negatively affects pregnancy outcomes, and the pregnancy can have a deleterious impact on various aspects of kidney disease. It has been shown that even mild renal dysfunction can increase considerably the risk of adverse maternal and fetal outcomes. Moreover, data suggest that a history of recovery from acute kidney injury is associated with adverse pregnancy outcomes. In addition to kidney dysfunction, maternal hypertension and proteinuria predispose women to negative outcomes and are important factors to consider in preconception counseling and the process of risk stratification. In this review, we provide an overview of the physiologic renal changes during pregnancy as well as available data regarding CKD and pregnancy outcomes. We also highlight the important management strategies in women with certain selected renal conditions that are seen commonly during the childbearing years. We call for future research on underexplored areas such as the concept of renal functional reserve to develop a potential clinical tool for prognostication and risk stratification of women at higher risk for complications during pregnancy.

Evaluation of chronic kidney disease in chronic heart failure: From biomarkers to arterial renal resistances

PubMed Central

Iacoviello, Massimo; Leone, Marta; Antoncecchi, Valeria; Ciccone, Marco Matteo

2015-01-01

Chronic kidney disease and its worsening are recurring conditions in chronic heart failure (CHF) which are independently associated with poor patient outcome. The heart and kidney share many pathophysiological mechanisms which can determine dysfunction in each organ. Cardiorenal syndrome is the condition in which these two organs negatively affect each other, therefore an accurate evaluation of renal function in the clinical setting of CHF is essential. This review aims to revise the parameters currently used to evaluate renal dysfunction in CHF with particular reference to the usefulness and the limitations of biomarkers in evaluating glomerular dysfunction and tubular damage. Moreover, it is reported the possible utility of renal arterial resistance index (a parameter associated with abnormalities in renal vascular bed) for a better assesment of kidney disfunction. PMID:25610846

Treatment of erectile dysfunction with sildenafil citrate in renal allograft recipients: a randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Sharma, Raj K; Prasad, Narayan; Gupta, Amit; Kapoor, Rakesh

2006-07-01

Erectile dysfunction (ED) is observed frequently in patients with end-stage renal disease, hemodialysis patients, and renal allograft recipients. There are few studies of sildenafil use in renal allograft recipients. The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Efficacy was assessed by using the self-administered International Index of Erectile Function (IIEF), a 15-question validated measure of ED, and a global efficacy question (Did the treatment improve your erection?). Thirty-two eligible renal transplant recipients were included in this study. After treatment with sildenafil citrate, patients had significantly better scores in 13 of 15 questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P < 0.001) and 4 (maintenance frequency; P < 0.001) was significantly better after sildenafil therapy. There were no significant differences between baseline and post-placebo treatment scores, except for question 13 (relationship satisfaction). Patients treated with sildenafil had significantly better scores in 4 domains compared with baseline, but a difference was not observed in the sexual desire domain (P = 0.32). There were no significant differences in scores between placebo and baseline in any domain. On the global efficacy question, 81.3% of patients showed improvement compared with 18.7% with placebo. There were no differences in areas under the curve and maximum cyclosporine concentrations before and after sildenafil therapy. No patient discontinued the drug because of side effects except for 1 patient with visual hallucination. Treatment with sildenafil in renal transplant recipients is a valid option with an effective response.

Evaluation of clinical outcomes among nonvalvular atrial fibrillation patients treated with rivaroxaban or warfarin, stratified by renal function
.

PubMed

Weir, Matthew R; Haskell, Lloyd; Berger, Jeffrey S; Ashton, Veronica; Laliberté, François; Crivera, Concetta; Brown, Kip; Lefebvre, Patrick; Schein, Jeffrey

2018-05-01

Renal dysfunction increases the risk of thromboembolic and bleeding events in patients with nonvalvular atrial fibrillation (NVAF). Adult NVAF patients with ≥ 6 months prior to first warfarin or rivaroxaban dispensing were selected from the IMS Health Real-World Data Adjudicated Claims database (05/2011 - 06/2015) with electronic medical records. Ischemic stroke events, thromboembolic events (venous thromboembolism, myocardial infarction, or ischemic stroke), and major bleeding events were compared between patients by renal function identified by 1) relevant ICD-9-CM diagnosis codes and 2) estimated creatinine clearance (eCrCl). Baseline confounders were adjusted using inverse probability of treatment weights. The diagnosis-based analysis included 39,872 rivaroxaban and 48,637 warfarin users (3,572 and 8,230 with renal dysfunction, respectively). The eCrCl-based analysis included 874 rivaroxaban and 1,069 warfarin users (66 and 208 with eCrCl < 60 mL/min, respectively). In the diagnosis-based analysis, rivaroxaban users with renal dysfunction had a significantly lower stroke rate (HR = 0.55, p = 0.0004) compared to warfarin users; rivaroxaban users with and without renal dysfunction had significantly lower thromboembolic event rates (HR = 0.62, p < 0.0001; and HR = 0.64, p < 0.0001, respectively), and similar major bleeding rates to warfarin users. In the eCrCl-based analysis, rivaroxaban users with eCrCl ≥ 60 mL/min had a significantly lower thromboembolic event rate, but other outcomes were not statistically significant. Rivaroxaban-treated NVAF patients with diagnosed renal dysfunction had a significantly lower stroke rate compared to warfarin-treated patients. Regardless of renal dysfunction diagnoses, rivaroxaban users had lower thromboembolic event rates compared to warfarin users, and a similar rate of major bleeding. eCrCl-based analysis was limited by a small sample size.
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Antiangiogenic Treatment Diminishes Renal Injury and Dysfunction via Regulation of Local AKT in Early Experimental Diabetes

PubMed Central

Zhou, Zhanmei

2014-01-01

In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser473-AKT, phosphorylated Thr308-AKT, nephrin, angiotensin II (Ang II), angiotensin type II receptor 1 (ATR1) were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr308-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr308-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr308-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr308-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr308-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the interstitial fibrosis, urine albumin excretion rate (UAER) and albumin to creatinine ratio. We conclude that phosphorylated Thr308-AKT regulates VEGF-A expression by interacting with either nephrin in glomeruli or Ang II in renal tubules. Antiangiogenic treatment improves renal injury and function in early experimental diabetes. PMID:24759991

Perioperative renal outcome in cardiac surgical patients with preoperative renal dysfunction: aprotinin versus epsilon aminocaproic acid.

PubMed

Maslow, Andrew D; Chaudrey, Alyas; Bert, Arthur; Schwartz, Carl; Singh, Arun

2008-02-01

The administration of aprotinin to patients with pre-existing renal dysfunction who are undergoing cardiac surgery is controversial. Therefore, the authors present their experience with the use of aprotinin for patients with preoperative renal dysfunction who underwent elective cardiac surgery requiring cardiopulmonary bypass (CPB). Retrospective analysis. University hospital. Consecutive cardiac surgical patients with preoperative serum creatinine (SCr) > or =1.8 mg/dL undergoing nonemergent cardiac surgery requiring CPB. None. One hundred twenty-three patients either received epsilon aminocaproic acid (EACA, n = 82) or aprotinin (n = 41) as decided by the attending anesthesiologist and surgeon. Data were collected from the Society of Thoracic Surgeons database and from automated intraoperative anesthesia records. Renal function was assessed from measured serum creatinine (SCr) and calculated creatinine clearances (CrCls). Acute perioperative renal dysfunction was defined as a worsening of perioperative renal function by > or =25% and/or the need for hemodialysis (HD). Data were recorded as mean and standard deviation or percentage of population depending on whether the data were continuous or not. Data were compared by using an analysis of variance, chi-square analysis, Student paired and unpaired t tests, Fisher exact test, Wilcoxon rank sum test, and Mann-Whitney U test. A p value <0.05 was considered significant. Overall, 32% and 41% of patients had acute perioperative renal dysfunction measured by CrCl and SCr, respectively. Seven patients required HD (5.7%). Six of these 7 had complicated postoperative courses. Of all the variables measured, only the duration of the aortic crossclamp (AoXCl) and CPB were significantly associated with acute perioperative renal dysfunction. Acute perioperative renal dysfunction was associated with increased intensive care unit and hospital stays, postoperative blood transfusion, dialysis, and major infection. Aprotinin patients were significantly older (75.2 v 70.2 years, p < 0.05), had lower left ventricular ejection fraction (44.4% v 49.2%, p < 0.05), a greater preoperative history of congestive heart failure (63 v 44%, p < 0.05), a greater renal risk score (5.8 v 4.9, p < 0.05), and underwent more nonisolated coronary artery bypass graft surgeries (77% v 29%, p < 0.0001). CPB time (126.0 v 96.5 minutes, p < 0.001) and AoXCl duration (100.9 v 78.0 minutes, p < 0.005) were longer in the aprotinin group. Diabetes (60.5% v 41.5%, p < 0.05) and hypertension (90.1% v 73.2%, p < 0.05) were more prevalent in the EACA group. Baseline renal function and renal outcomes were not significantly different between the aprotinin and EACA groups. Six of the 7 patients who required HD received EACA (p = 0.1). The earliest SCr recorded > or =3 months after surgery was significantly lower in the aprotinin group compared with the EACA group (1.8 v 2.2 mg/dL, p < 0.05). Acute perioperative renal dysfunction was associated with worse patient outcome and longer CPB and AoXCl times. Demographic and surgical variables indicated that the sicker patients undergoing more complex surgeries were more likely to be treated with aprotinin. Although aprotinin patients had a higher renal risk score, the administration of aprotinin did not negatively impact renal outcome.

Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery.

PubMed

Stafford-Smith, Mark; Podgoreanu, Mihai; Swaminathan, Madhav; Phillips-Bute, Barbara; Mathew, Joseph P; Hauser, Elizabeth H; Winn, Michelle P; Milano, Carmelo; Nielsen, Dahlia M; Smith, Mike; Morris, Richard; Newman, Mark F; Schwinn, Debra A

2005-03-01

Post-cardiac surgery renal dysfunction is a common, serious, multifactorial disorder, with interpatient variability predicted poorly by preoperative clinical, procedural, and biological markers. Therefore, we tested the hypothesis that selected gene variants are associated with acute renal injury, reflected by a serum creatinine level increase after cardiac surgery. One thousand six hundred seventy-one patients undergoing aortocoronary surgery were studied. Clinical covariates were recorded. DNA was isolated from preoperative blood; mass spectrometry was used for genotype analysis. A model was developed relating clinical and genetic factors to postoperative acute renal injury. A race effect was found; therefore, Caucasians and African Americans were analyzed separately. Overall, clinical factors alone account poorly for postoperative renal injury, although more so in African Americans than Caucasians. When 12 candidate polymorphisms were assessed, 2 alleles (interleukin 6 -572C and angiotensinogen 842C) showed a strong association with renal injury in Caucasians (P < 0.0001; >50% decrease in renal filtration when they present together). Using less stringent criteria for significance (0.01 > P > 0.001), 4 additional polymorphisms are identified (apolipoproteinE 448C [4], angiotensin receptor1 1166C, and endothelial nitric oxide synthase [eNOS] 894T in Caucasians; eNOS 894T and angiotensin-converting enzyme deletion and insertion in African Americans). Adding genetic to clinical factors resulted in the best model, with overall ability to explain renal injury increasing approximately 4-fold in Caucasians and doubling in African Americans (P < 0.0005). In this study, we identify genetic polymorphisms that collectively provide 2- to 4-fold improvement over preoperative clinical factors alone in explaining post-cardiac surgery renal dysfunction. From a mechanistic perspective, most identified genetic variants are associated with increased renal inflammatory and/or vasoconstrictor responses.

Evaluation of coronary microvascular function in patients with end-stage renal disease, and renal allograft recipients.

PubMed

Bozbas, Huseyin; Pirat, Bahar; Demirtas, Saadet; Simşek, Vahide; Yildirir, Aylin; Sade, Elif; Sayin, Burak; Sezer, Siren; Karakayali, Hamdi; Muderrisoglu, Haldun

2009-02-01

Approximately half of all deaths in patients with end-stage renal disease (ESRD) are due to cardiovascular diseases. Although renal transplant improves survival and quality of life in these patients, cardiovascular events significantly affect survival. We sought to evaluate coronary flow reserve (CFR), an indicator of coronary microvascular function, in patients with ESRD and in patients with a functioning kidney graft. Eighty-six patients (30 with ESRD, 30 with a functioning renal allograft, and 26 controls) free of coronary artery disease or diabetes mellitus were included. Transthoracic Doppler echocardiography was used to measure coronary peak flow velocities at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak flow velocities and was compared among the groups. The mean age of the study population was 36.1+/-7.3 years. No between-group differences were found regarding age, sex, or prevalences of traditional coronary risk factors other than hypertension. Compared with the renal transplant and control groups, the ESRD group had significantly lower mean CFR values. On multivariate regression analysis, serum levels of creatinine, age, and diastolic dysfunction were independent predictors of CFR. CFR is impaired in patients with ESRD suggesting that coronary microvascular dysfunction, an early finding of atherosclerosis, is evident in these patients. Although associated with a decreased CFR compared with controls, renal transplant on the other hand seems to have a favorable effect on coronary microvascular function.

Mitochondrial-targeted antioxidants represent a promising approach for prevention of cisplatin-induced nephropathy

PubMed Central

Mukhopadhyay, Partha; Horváth, Béla; Zsengellér, Zsuzsanna; Zielonka, Jacek; Tanchian, Galin; Holovac, Eileen; Kechrid, Malek; Patel, Vivek; Stillman, Isaac E.; Parikh, Samir M.; Joseph, Joy; Kalyanaraman, Balaraman; Pacher, Pál

2011-01-01

Cisplatin is a widely used anti-neoplastic agent; however, its major limitation is the development of dose-dependent nephrotoxicity whose precise mechanisms are poorly understood. Here we show that mitochondrial dysfunction is not only a feature of cisplatin nephrotoxicity, but that targeted delivery of superoxide dismutase mimetics to mitochondria largely prevents the renal effects of cisplatin. Cisplatin induced renal oxidative stress, deterioration of mitochondrial structure and function, an intense inflammatory response, histopathological injury, and renal dysfunction. A single systemic dose of mitochondrially-targeted antioxidants, MitoQ or Mito-CP, dose-dependently prevented cisplatin-induced renal dysfunction. Mito-CP also prevented mitochondrial injury and dysfunction, renal inflammation, and tubular injury and apoptosis. Despite being broadly renoprotective against cisplatin, Mito-CP did not diminish cisplatin’s anti-neoplastic effect in a human bladder cancer cell line. Our results highlight the central role of mitochondrially generated oxidants in the pathogenesis of cisplatin nephrotoxicity. Since similar compounds appear to be safe in humans, mitochondrially-targeted antioxidants may represent a novel therapeutic approach against cisplatin nephrotoxicity. PMID:22120494

Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options.

PubMed

Iglesias, Pedro; Carrero, Juan J; Díez, Juan J

2012-01-01

Gonadal dysfunction is a frequent finding in men with chronic kidney disease and with end-stage renal disease. Testosterone deficiency, usually accompanied by elevation of serum gonadotropin concentrations, is present in 26-66% of men with different degrees of renal failure. Uremia-associated hypogonadism is multifactorial in its origin, and rarely improves with initiation of dialysis, although it usually normalizes after renal transplantation. Experimental and clinical evidence suggests that testosterone may have important clinical implications with regards to kidney disease progression, derangements in sexual drive, libido and erectile dysfunction, development of anemia, impairment of muscle mass and strength, and also progression of atherosclerosis and cardiovascular disease. Additionally, low testosterone levels in hemodialysis patients have been associated with increased mortality risk in some studies. Currently, we count with available therapeutic options in the management of uremic hypogonadism, from optimal delivery of dialysis and adequate nutritional intake, to hormone replacement therapy with different testosterone preparations. Other potential options for treatment include the use of antiestrogens, dopamine agonists, erythropoiesis-stimulating factors, vitamins, essential trace elements, chorionic gonadotropin and renal transplantation. Potential adverse effects of androgen replacement therapy in patients with kidney disease comprise, however, erythrocytosis, prostate and breast cancer growth, reduced fertility, gynecomastia, obstructive sleep apnea and fluid retention. Androgen preparations should be used with caution with stringent monitoring in uremic men. Although there are encouraging data suggesting plausible benefits from testosterone replacement therapy, further studies are needed with regards to safety and effectiveness of this therapy.

Ischemic acute renal failure and antioxidant therapy in the rat. The relation between glomerular and tubular dysfunction.

PubMed Central

Bird, J E; Milhoan, K; Wilson, C B; Young, S G; Mundy, C A; Parthasarathy, S; Blantz, R C

1988-01-01

The effects of antioxidant therapy with probucol were evaluated in rats subjected to 1 h renal ischemia and to 24 h reperfusion. Probucol exerted significant antioxidant effects in renal cortical tubules in vitro when exposed to a catalase-resistant oxidant. At 24 h probucol treatment (IP) improved single nephron glomerular filtration rate (SNGFR) (28.1 +/- 3.3 nl/min) in comparison to untreated ischemic (I) rats (15.2 +/- 3.0), primarily as a result of improving SNGFR in a population of low SNGFR, low flow and/or obstructed nephrons. However, absolute proximal reabsorption remained abnormally low in IP rats at 24 h (5.9 +/- 0.8 nl/min), and cell necrosis was greater than in I rats. Kidney GFR remained low in IP rats due to extensive tubular backleak of inulin measured by microinjection studies. Evaluations after 2 h of reperfusion revealed a higher SNGFR in IP (36 +/- 3.1 nl/min) than I rats (20.8 +/- 2.7 nl/min). Absolute proximal reabsorption was essentially normal (11.6 +/- 1.3 nl/min) in IP rats, which was higher than IP rats at 24 h and the concurrent I rats. Administration of the lipophilic antioxidant, probucol, increased SNGFR and proximal tubular reabsorption within 2 h after ischemic renal failure. Although SNGFR remained higher than I rats at 24 h, absolute reabsorption fell below normal levels and tubular necrosis was more extensive in IP rats. Early improvement in nephron filtration with antioxidants may increase load dependent metabolic demand upon tubules and increase the extent of damage and transport dysfunction. Images PMID:2835399

Memantine-associated hyperkalaemia in a patient with Alzheimer's disease.

PubMed

Tsukamoto, Tatsuo; Yamada, Hidetaka; Uchimura, Naohisa

2013-09-01

Memantine is an N-methyl-D-aspartate glutamate receptor antagonist that may improve cognitive functions in patients with Alzheimer's disease. It is predominantly excreted unchanged via the kidneys, and patients with decreased creatinine clearance must be treated with lower doses of memantine. However, it is unclear whether memantine itself can lead to renal dysfunction and/or hyperkalaemia. We report a patient with renal impairment and hyperkalaemia possibly associated with memantine administration. © 2013 The Authors. Psychogeriatrics © 2013 Japanese Psychogeriatric Society.

The relationship between inotrope exposure, six-hour postoperative physiological variables, hospital mortality and renal dysfunction in patients undergoing cardiac surgery.

PubMed

Shahin, Jason; DeVarennes, Benoit; Tse, Chun Wing; Amarica, Dan-Alexandru; Dial, Sandra

2011-07-07

Acute haemodynamic complications are common after cardiac surgery and optimal perioperative use of inotropic agents, typically guided by haemodynamic variables, remains controversial. The aim of this study was to examine the relationship of inotrope use to hospital mortality and renal dysfunction. A retrospective cohort study of 1,326 cardiac surgery patients was carried out at two university-affiliated ICUs. Multivariable logistic regression analysis and propensity matching were performed to evaluate whether inotrope exposure was independently associated with mortality and renal dysfunction. Patients exposed to inotropes had a higher mortality rate than those not exposed. After adjusting for differences in Parsonnet score, left ventricular ejection fraction, perioperative intraaortic balloon pump use, bypass time, reoperation and cardiac index, inotrope exposure appeared to be independently associated with increased hospital mortality (adjusted odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.2 to 4.5) and renal dysfunction (adjusted OR 2.7, 95% CI 1.5 to 4.6). A propensity score-matched analysis similarly demonstrated that death and renal dysfunction were significantly more likely to occur in patients exposed to inotropes (P = 0.01). Postoperative inotrope exposure was independently associated with worse outcomes in this cohort study. Further research is needed to better elucidate the appropriate use of inotropes in cardiac surgery.

[Impact of end-stage renal disease and kidney transplantation on the reproductive system].

PubMed

Delesalle, A-S; Robin, G; Provôt, F; Dewailly, D; Leroy-Billiard, M; Peigné, M

2015-01-01

Chronic renal failure leads to many metabolic disorders affecting reproductive function. For men, hypergonadotropic hypogonadism, hyperprolactinemia, spermatic alterations, decreased libido and erectile dysfunction are described. Kidney transplantation improves sperm parameters and hormonal function within 2 years. But sperm alterations may persist with the use of immunosuppressive drugs. In women, hypothalamic-pituitary-ovarian axis dysfunction due to chronic renal failure results in menstrual irregularities, anovulation and infertility. After kidney transplantation, regular menstruations usually start 1 to 12 months after transplantation. Fertility can be restored but luteal insufficiency can persist. Moreover, 4 to 20% of women with renal transplantation suffer from premature ovarian failure syndrome. In some cases, assisted reproductive technologies can be required and imply risks of ovarian hyperstimulation syndrome and must be performed with caution. Pregnancy risks for mother, fetus and transplant are added to assisted reproductive technologies ones. Only 7 authors have described assisted reproductive technologies for patients with kidney transplantation. No cases of haemodialysis patients have been described yet. So, assisted reproductive technologies management requires a multidisciplinary approach with obstetrics, nephrology and reproductive medicine teams' agreement. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Hypothyroidism presenting as reversible renal impairment: an interesting case report.

PubMed

Vikrant, Sanjay; Chander, Subhash; Kumar, Satish; Gupta, Dalip

2013-10-01

We describe an interesting case of reversible renal impairment secondary to hypothyroidism. A 57-years-old man was referred from peripheral institution for evaluation of elevated serum creatinine. He had vague complaints of weakness, lethargy and muscle ache but no urinary symptoms. He was found to have hypothyroidism, and thyroid hormone replacement therapy (THRT) was started which resulted in reversal of the renal dysfunction. There was marked improvement in estimated glomerular filtration rate. 99mTc DTPA renal scans done before and after THRT suggested hypothyroidism responsible for this reversible renal impairment. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown total amelioration of renal impairment as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. We suggest that patients with renal impairment of unknown cause have thyroid function tests undertaken as part of routine investigation.

Alcohol Intoxication Impact on Outcome from Traumatic Injury

DTIC Science & Technology

2011-05-01

in urine output and decreased urine osmolality as compared to dextrose-infused and no infusion controls; however, at the completion of the infusion...levels of alanine amino transferase (ALT) and blood urea nitrogen (BUN), markers of hepatic and renal damage and dysfunction respectively. To examine...hepatic injury and dysfunction, as well as blood urea nitrogen (BUN) and creatinine, makers of renal dysfunction, were elevated following delayed

Protective role of testosterone in ischemia-reperfusion-induced acute kidney injury

PubMed Central

Soljancic, Andrea; Ruiz, Arnaldo Lopez; Chandrashekar, Kiran; Maranon, Rodrigo; Liu, Ruisheng; Juncos, Luis A.

2013-01-01

Men are at greater risk for renal injury and dysfunction after acute ischemia-reperfusion (I/R) than are women. Studies in animals suggest that the reason for the sex difference in renal injury and dysfunction after I/R is the protective effect of estrogens in females. However, a reduction in testosterone in men is thought to play an important role in mediating cardiovascular and renal disease, in general. In the present study, we tested the hypothesis that I/R of the kidney reduces serum testosterone, and that contributes to renal dysfunction and injury. Male rats that were subjected to renal ischemia of 40 min followed by reperfusion had a 90% reduction in serum testosterone by 3 h after reperfusion that remained at 24 h. Acute infusion of testosterone 3 h after reperfusion attenuated the increase in plasma creatinine and urinary kidney injury molecule-1 (KIM-1) at 24 h, prevented the reduction in outer medullary blood flow, and attenuated the increase in intrarenal TNF-α and the decrease in intrarenal VEGF at 48 h. Castration of males caused greater increases in plasma creatinine and KIM-1 at 24 h than in intact males with renal I/R, and treatment with anastrozole, an aromatase inhibitor, plus testosterone almost normalized plasma creatinine and KIM-1 in rats with renal I/R. These data show that renal I/R is associated with sustained reductions in testosterone, that testosterone repletion protects the kidney, whereas castration promotes renal dysfunction and injury, and that the testosterone-mediated protection is not conferred by conversion to estradiol. PMID:23552495

Aripiprazole prevents renal ischemia/reperfusion injury in rats, probably through nitric oxide involvement.

PubMed

Gholampour, Hanieh; Moezi, Leila; Shafaroodi, Hamed

2017-10-15

Renal ischemia/reperfusion (I/R) injury is strongly related to morbidity and mortality. Oxidative stress, inflammation, and apoptosis play key roles in renal dysfunction following renal I/R. Aripiprazole is an atypical antipsychotic which used for the treatment of schizophrenia and bipolar disorder. Recent studies have reported aripiprazole as displaying certain anti-inflammatory effects. Regarding the underlying mechanisms of renal ischemia-reperfusion, therefore, nephroprotective effects might be predicted to be seen with aripiprazole. I/R injury was induced by bilateral clamping of the renal pedicles (45min) followed by reperfusion (24h). The mechanism of aripiprazole-mediated nephroprotection was explored by a combined use of aripiprazole and L-NAME (non-selective nitric oxide synthase inhibitor). Animals were given aripiprazole (2.5, 5, 10 and 20mg/kg) intraperitoneally, 30min before ischemia. L-NAME was administered before the aripiprazole injection. Serum creatinine and blood urea nitrogen were assessed after 24h of reperfusion. Serum levels of malondialdehyde (MDA), TNF-α and IL-1β were measured for rats treated with aripiprazole. The extent of necrosis was measured by the stereology method. Ischemia/reperfusion caused significant renal dysfunction and marked renal injury. Aripiprazole reduced creatinine and blood urea nitrogen. Serum levels of MDA, IL-1β and TNF-α were significantly lower in the aripiprazole group. Aripiprazole treatment also decreased the volume of kidney necrosis. The administration of L-NAME reversed the renoprotective effect of aripiprazole on BUN and creatinine, but enhanced the anti-necrotic effect of aripiprazole. The results show that a single dose of aripiprazole significantly improved renal function following ischemia/reperfusion injury - probably through the involvement of nitric oxide. Copyright © 2017 Elsevier B.V. All rights reserved.

Notoginsenoside R1 attenuates renal ischemia-reperfusion injury in rats.

PubMed

Liu, Wen-Jun; Tang, Hong-Tai; Jia, Yi-Tao; Ma, Bing; Fu, Jin-Feng; Wang, Yu; Lv, Kai-Yang; Xia, Zhao-Fan

2010-09-01

Ischemia-reperfusion (I/R) injury of the kidney is a complex pathophysiological process and a major cause of acute renal failure. It has been shown that I/R injury is related to inflammatory responses and activation of apoptotic pathways. Inhibition of certain elements of inflammatory responses and apoptotic pathway seemed to ameliorate renal I/R injury. As an effective element of Panax notoginseng, NR1 has antioxidant, anti-inflammatory, antiapoptotic, and immune-stimulatory activities. Therefore, we speculate that NR1 can attenuate renal I/R injury. Ischemia-reperfusion injury was induced by renal pedicle ligation followed by reperfusion along with a contralateral nephrectomy. Male Sprague-Dawley rats were randomized to four groups: sham group, I/R control group, NR1-1 group (rats treated with NR1, 20 mg.kg.d) and NR1-2 group (rats treated with NR1, 40 mg.kg.d). All animals were killed 72 h after I/R induction. Blood and renal tissues were collected. Renal dysfunction was observed by the level of serum creatinine and histological evaluation. Apoptosis and inflammatory response in the tissue of kidney were detected mainly with molecular biological methods. NR1 attenuated I/R-induced renal dysfunction as indicated by the level of serum creatinine and histological evaluation. It prevented the I/R-induced increases in the levels of proinflammatory cytokine TNF-alpha, myeloperoxidase activity, phosphorylation of p38, and activation of nuclear factor kappaB with cell apoptosis in the kidney and enhanced expression of antiapoptosis cytokine bcl-2. Treatment with NR1 improves renal function after I/R associated with a significant reduction in cell apoptosis and inflammatory responses, which may be related to p38 and nuclear factor kappaB inhibition.

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.

Sida rhomboidea.Roxb leaf extract ameliorates gentamicin induced nephrotoxicity and renal dysfunction in rats.

PubMed

Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Devkar, Ranjitsinh V; Ramachandran, A V

2010-10-28

Sida rhomboidea.Roxb (SR) known as "Mahabala" in Ayurveda and marketed as "Shahadeyi" is used in ethnomedicine to treat ailments such as dysuria and urinary disorders. To evaluate nephroprotective potential of SR against gentamicin (GM) induced nephrotoxicity and renal dysfunction. Nephrotoxicity was induced in rats with GM (100 mg/kg bodyweight (i.p.) for 8 days) and were treated with SR extract (200 and 400 mg/kg bodyweight (p.o.) for 8 days) or 0.5% carboxymethyl cellulose (vehicle). Plasma and urine urea and creatinine, renal enzymatic and non-enzymatic antioxidants along with lipid peroxidation were evaluated in various experimental groups. GM treatment induced significant elevation (p<0.05) in plasma and urine urea, creatinine, renal lipid peroxidation along with significant decrement (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR treatment to GM treated rats (GM+SR) recorded significant decrement (p<0.05) in plasma and urine urea and creatinine, renal lipid peroxidation along with significant increment (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR leaf extract ameliorates GM induced nephrotoxicity and renal dysfunction and thus validates its ethnomedicinal use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

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

Paraprotein-Related Kidney Disease: Diagnosing and Treating Monoclonal Gammopathy of Renal Significance.

PubMed

Rosner, Mitchell H; Edeani, Amaka; Yanagita, Motoko; Glezerman, Ilya G; Leung, Nelson

2016-12-07

Paraprotein-related kidney disease represents a complex group of diseases caused by an abnormal paraprotein secreted by a clone of B cells. The disease manifestations range from tubulopathies, such as the Fanconi syndrome, to a spectrum of glomerular diseases that can present with varying degrees of proteinuria and renal dysfunction. Diagnosis of these diseases can be challenging because of the wide range of manifestations as well as the relatively common finding of a serum paraprotein, especially in elderly patients. Thus, renal biopsy along with detailed hematologic workup is essential to link the presence of the paraprotein to the associated renal disease. Recent advances in treatment with more effective and targeted chemotherapies, as well as stem cell transplantation, have improved the renal and overall prognosis for many of these disorders. Copyright © 2016 by the American Society of Nephrology.

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

Reversible renal allograft dysfunction and proteinuria from nutcracker-like syndrome: a case report.

PubMed

Krishnan, S G S; Pritsiolas, J; Susin, M; Linden, E; Beil-Levi, E; Gitman, M; Mossey, R; Bhaskaran, M

2007-06-01

A 27-year-old Hispanic man with hypertension and renal failure was on hemodialysis for 4 years prior to receiving a living donor renal transplant from his 19-year-old sister. His serum creatinine decreased to 1.7 mg/dL at 3 weeks posttransplant with a urine protein creatinine ratio (UP) of 0.1 (g/g). Over the next 2 months, he experienced repeated episodes of allograft dysfunction with elevation of creatinine and proteinuria levels, associated with a lymphocele. Doppler studies of the allograft revealed renal vein compression. His symptoms responded to aspiration of the fluid collection, resolving completely with surgical drainage. We believe that the episodes of allograft dysfunction and proteinuria were related to recurrent lymphocele, causing a nutcracker-like syndrome.

PHARMACOLOGIC PROBING OF AMPHOTERICIN B-INDUCED RENAL DYSFUNCTION IN THE NEONATAL RAT

EPA Science Inventory

Pharmacologic Probing of Amphotericin B-Induced Renal Dysfunction in the Neonatal Rat. Gray, J.A., and Kavlock, R.J. (1988). Toxicol. Appl. Pharmacol. 93, 360-368. Acetazolamide, furosemide, chlorothiazide, and amiloride pharmacologic agents that act primarily in the proximal tub...

Low prevalence of renal dysfunction in HIV-infected pregnant women: implications for guidelines for the prevention of mother-to-child transmission of HIV.

PubMed

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

2013-11-01

Emerging international guidelines for the prevention of mother-to-child transmission of HIV infection across sub-Saharan Africa call for the initiation of a triple-drug antiretroviral regimen containing tenofovir, a potentially nephrotoxic agent, in all HIV-infected pregnant women at the first antenatal clinic visit. While there are significant benefits to the rapid initiation of antiretroviral therapy (ART) in pregnancy, there are few data on the prevalence of pre-existing renal disease in HIV-infected pregnant women and in turn, the potential risks of this approach are not well understood. We analysed data on renal function in consecutive patients eligible for ART at a large primary healthcare clinic in Cape Town. All individuals were screened for renal dysfunction via serum creatinine and estimation of creatinine clearance via the Cockroft-Gault equation. Over a 2-year period, 238 pregnant women, 1014 non-pregnant women and 609 men were screened to initiate ART. Pregnant women eligible were significantly younger, in earlier stages of HIV disease, had higher CD4 cell counts and lower HIV viral loads, than non-pregnant adults. The median serum creatinine in pregnant women (46 µmol/L) was significantly lower and the median creatinine clearance (163 ml/min/1.73 m(2) ) was significantly higher than other groups (P < 0.001 and P = 0.004, respectively). Fewer than 1% of pregnant women had moderate renal dysfunction before ART initiation, with no instances of severe dysfunction observed, compared to 7% moderate or severe renal dysfunction in non-pregnant women or men (P < 0.001). Renal dysfunction in HIV-infected pregnant women is significantly less common than in other HIV-infected adults eligible for ART. The risks associated with initiating tenofovir immediately in pregnant women before reviewing serum creatinine results may be limited, and the benefits of rapid ART initiation in pregnancy may outweigh possible risks of nephrotoxicity. © 2013 John Wiley & Sons Ltd.

Application of path analysis to urinary findings of cadmium-induced renal dysfunction.

PubMed

Abe, T; Kobayashi, E; Okubo, Y; Suwazono, Y; Kido, T; Shaikh, Z A; Nogawa, K

2001-01-01

In order to identify some causal relations among various urinary indices of cadmium-induced renal dysfunction, such as glucose, total protein, amino nitrogen, beta 2-microglobulin (beta 2-m), metallothionein (MT), and cadmium (Cd), we applied path analysis method to previous epidemiological studies targeting the residents of the Cd-polluted Kakehashi River basin of Ishikawa Prefecture, Japan. We obtained a diagram-termed path model, representing some causal relations among the above urinary indices. It shows that urinary Cd is located at the beginning point in the diagram, and Cd-induced renal dysfunction develops in the following order: Cd exposure-->increase of beta 2-m and/or MT excretion-->increase of amino-N and/or total protein excretion-->increase of glucose excretion. It was proved mathematically, that in the case of both males and females, increased excretions of beta 2-m and/or MT were the most sensitive urinary indices of the early stage of chronic Cd-induced renal dysfunction.

Right ventricular systolic dysfunction and vena cava dilatation precede alteration of renal function in adult patients undergoing cardiac surgery: An observational study.

PubMed

Guinot, Pierre Grégoire; Abou-Arab, Osama; Longrois, Dan; Dupont, Herve

2015-08-01

Several authors have suggested that right ventricular dysfunction (RVd) may contribute to renal dysfunction in nonsurgical patients. We tested the hypothesis that RVd diagnosed immediately after cardiac surgery may be associated with subsequent development of renal dysfunction and tried to identify the possible mechanisms. A single-centre, prospective observational study. Amiens University Hospital, France. All adult patients undergoing cardiac surgery were considered eligible for participation. Patients who had undergone pulmonary or tricuspid valve surgery, repeat surgery or who underwent immediate postoperative renal replacement therapy were excluded. Data from 74 patients were analysed. Left ventricular and right ventricular function were assessed before surgery and on admission to ICU by transthoracic echocardiography (TTE): left ventricular and right ventricular ejection fractions (LVEF/RVEF), tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (Sr(t)) and right ventricular dilatation. RVd was defined as values in the lowest quartile of at least two echocardiographic variables. Renal dysfunction was defined as an increase in serum creatinine concentration (sCr) on postoperative day 1. All right ventricular TTE variables decreased (P < 0.05) after surgery: RVEF from 50% (49 to 60) to 40% (35 to 50); TAPSE from 22.3 mm (19.4 to 25.3) to 12.2 mm (8.8 to 14.8); and Sr(t) from 15.0 cm s(-1) (12.0 to 18.0) to 8.1 cm s(-1) (6.3 to 9.2). Fourteen (19%) patients had right ventricular dilatation and RVd was present in 23 (31%) patients. Forty patients had a positive variation in sCr. In multivariate analysis, patients with RVd had an odds ratio (OR) of 12.7 [95% confidence interval (95% CI) 2.6 to 63.4, P = 0.02] for development of renal dysfunction. Renal dysfunction was associated with increased central venous pressure but was not associated with cardiac index (CI). These results suggest that early postoperative RVd is associated with a subsequent increase of sCr and that the mechanism involved is congestion (vena cava dilatation/elevated CVP) rather than decreased CI.

The association between chronic kidney disease and cardiovascular disease risk factors in atomic bomb survivors.

PubMed

Sera, Nobuko; Hida, Ayumi; Imaizumi, Misa; Nakashima, Eiji; Akahoshi, Masazumi

2013-01-01

Atomic bomb (A-bomb) radiation is associated with cardiovascular disease (CVD) and metabolic CVD risk factors. Chronic kidney disease (CKD) is also known to be a risk factor for CVD and little is known whether CKD is associated with A-bomb radiation. To examine whether CKD is associated with CVD risk factors or with A-bomb radiation in A-bomb survivors, we classified renal dysfunction in 1,040 A-bomb survivors who were examined in 2004-2007 as normal [n = 121; estimated glomerular filtration rate (eGFR) ≥ 90 ml/min/1.73 m(2)]; mild (n = 686; eGFR 60-89 ml/min/1.73 m(2)); moderate (n = 217; eGFR 30-59 ml/min/1.73 m(2)); or severe (n = 16; eGFR <30 ml/min/1.73 m(2)). Also, we diagnosed subjects in the moderate and severe renal dysfunction groups as having CKD (n = 233; eGFR <59 ml/min/1.73 m(2)). After adjusting for age, gender, and smoking and drinking habits, we looked for an association between renal dysfunction and hypertension, diabetes mellitus (DM), hyperlipidemia, and metabolic syndrome (MetS), and between renal dysfunction and A-bomb radiation. Hypertension [odds ratio (OR), 1.57; 95% confidence interval (CI), 1.12-2.20, P = 0.009]; DM (OR, 1.79; 95% CI, 1.23-2.61, P = 0.002); hyperlipidemia (OR, 1.55; 95% CI, 1.12-2.14, P = 0.008); and MetS (OR, 1.86; 95% CI, 1.32-2.63, P < 0.001) were associated with CKD (moderate/severe renal dysfunction), and hyperlipidemia and MetS were also associated with mild renal dysfunction. CKD (OR/Gy, 1.29; 95% CI, 1.01-1.63, P = 0.038) and severe renal dysfunction (OR/Gy, 3.19; 95% CI, 1.63-6.25, P < 0.001) were significantly associated with radiation dose. CKD associated with radiation may have played a role in the development of CVD among A-bomb survivors.

Different antidiabetic regimens and the development of renal dysfunction in US Veterans with type 2 diabetes mellitus.

PubMed

Gosmanova, Elvira O; Canada, Robert B; Wan, Jim; Mangold, Therese A; Wall, Barry M

2012-10-01

The aim of this study was to evaluate the development of renal dysfunction in veterans with type 2 diabetes mellitus (T2DM) treated with different antidiabetic regimens. A retrospective cohort study involving 1715 patients with T2DM and baseline serum creatinine (SCr) of 1.5 mg/dL or lesser. The development of renal dysfunction, defined as 0.5 mg/dL or greater increase from baseline SCr during 4.8 years of follow-up with monotherapy metformin (M), 2 combination therapy groups: metformin + insulin (MI) and metformin + sulfonylurea (MS) users were compared with changes observed in sulfonylurea monotherapy users (S). Both MI and MS groups had higher mean baseline hemoglobin A1C (HbA1C) (9.0 and 8.6%, respectively) and higher rates of baseline macroalbuminuria (17.3 and 12.1%, respectively) as compared with M and S groups (mean HbA1C7.7% in both groups, and proteinuria M-5.1% and S-7.4%). In unadjusted analysis, the development of renal dysfunction was more frequent in MI and MS but not in M group as compared with sulfonylurea monotherapy (unadjusted HRs and [95% confidence interval (CI), 2.1[1.4-3.0], 1.4[1.1-1.9], and 1.0[0.6-1.7], respectively). However, differences in the development of renal dysfunction were not significant between the 4 groups after adjusting for baseline variables. Baseline macroalbuminuria was a strong predictor of Scr elevation of 0.5 mg/dL or greater during follow-up (adjusted HR, 3.1[1.9-4.7]). Unexpectedly, baseline use of renin-angiotensin-aldosterone system blockers was also associated with the development of renal dysfunction (adjusted HR, 1.9[1.3-2.8]). In this retrospective cohort study involving US predominantly male veterans with T2DM, baseline macroalbuminuria and use of RAAS blockers were associated with increased risk of development of renal dysfunction, whereas different antidiabetic regimens were not.

Acquired Bartter syndrome following gentamicin therapy

PubMed Central

Singh, J.; Patel, M. L.; Gupta, K. K.; Pandey, S.; Dinkar, A.

2016-01-01

Aminoglycoside nephrotoxicity may manifest as nonoliguric renal failure or tubular dysfunction, such as Fanconi-like syndrome, Bartter-like syndrome (BS), or distal renal tubular acidosis. We report a case who developed severe renal tubular dysfunction on the the 7th day of gentamicin therapy, resulting in metabolic alkalosis, refractory hypokalemia, hypocalcemia, hypomagnesemia, and polyuria. The patient was diagnosed as a case of transient BS associated with gentamicin exposure. The patient recovered with conservative management. PMID:27942182

Acquired Bartter syndrome following gentamicin therapy.

PubMed

Singh, J; Patel, M L; Gupta, K K; Pandey, S; Dinkar, A

2016-01-01

Aminoglycoside nephrotoxicity may manifest as nonoliguric renal failure or tubular dysfunction, such as Fanconi-like syndrome, Bartter-like syndrome (BS), or distal renal tubular acidosis. We report a case who developed severe renal tubular dysfunction on the the 7 th day of gentamicin therapy, resulting in metabolic alkalosis, refractory hypokalemia, hypocalcemia, hypomagnesemia, and polyuria. The patient was diagnosed as a case of transient BS associated with gentamicin exposure. The patient recovered with conservative management.

Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection

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

Sahu, Bidya Dhar; Tatireddy, Srujana; Koneru, Meghana

Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrialmore » NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in the kidney. - Highlights: • Naringin ameliorated gentamicin-induced nephrotoxicity in rats. • Naringin treatment attenuated gentamicin-induced renal apoptosis in rats. • Naringin ameliorated gentamicin-induced renal mitochondrial dysfunction in rats. • Naringin decreased NF-κB activation and pro-inflammatory cytokine release. • U-HPLC-MS data revealed that naringin did not alter the renal uptake of gentamicin.« less

The relationship between inotrope exposure, six-hour postoperative physiological variables, hospital mortality and renal dysfunction in patients undergoing cardiac surgery

PubMed Central

2011-01-01

Introduction Acute haemodynamic complications are common after cardiac surgery and optimal perioperative use of inotropic agents, typically guided by haemodynamic variables, remains controversial. The aim of this study was to examine the relationship of inotrope use to hospital mortality and renal dysfunction. Material and methods A retrospective cohort study of 1,326 cardiac surgery patients was carried out at two university-affiliated ICUs. Multivariable logistic regression analysis and propensity matching were performed to evaluate whether inotrope exposure was independently associated with mortality and renal dysfunction. Results Patients exposed to inotropes had a higher mortality rate than those not exposed. After adjusting for differences in Parsonnet score, left ventricular ejection fraction, perioperative intraaortic balloon pump use, bypass time, reoperation and cardiac index, inotrope exposure appeared to be independently associated with increased hospital mortality (adjusted odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.2 to 4.5) and renal dysfunction (adjusted OR 2.7, 95% CI 1.5 to 4.6). A propensity score-matched analysis similarly demonstrated that death and renal dysfunction were significantly more likely to occur in patients exposed to inotropes (P = 0.01). Conclusions Postoperative inotrope exposure was independently associated with worse outcomes in this cohort study. Further research is needed to better elucidate the appropriate use of inotropes in cardiac surgery. PMID:21736726

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.

Protective effects of hydrogen sulfide on chronic kidney disease by reducing oxidative stress, inflammation and apoptosis

PubMed Central

Askari, Hassan; Seifi, Behjat; Kadkhodaee, Mehri; Sanadgol, Nima; Elshiekh, Mohammed; Ranjbaran, Mina; Ahghari, Parisa

2018-01-01

The current study aimed to examine the renoprotective effects of long-term treatment with sodium hydrosulfide (NaHS), a prominent hydrogen sulfide donor, in 5/6 nephrectomy animal model. Twenty-four rats were randomly divided into 3 groups including sham-operated group (Sham), 5/6-nephrectomized group (5/6 Nx), and NaHS-treated group (5/6Nx+NaHS). NaHS (30 micromol/l) was added twice daily into the drinking water and renal failure was induced by 5/6 nephrectomy. Twelve weeks after surgical procedure, blood pressure, creatinine clearance (CCr), urine concentration of neutrophil gelatinase associated lipocalin (NGAL) and tissue concentration of malondialdehyde (MDA), superoxide dismutase (SOD), as well as renal morphological changes, apoptosis (cleaved caspase-3) and inflammation (p-NF-κB) were measured. Five-sixth nephrectomy induced severe renal damage as indicated by renal dysfunction, hypertension and significant histopathological injury which were associated with increased NGAL and MDA levels, oxidant/antioxidant imbalance, decreased SOD activity and CCr and also overexpression of p-NF-κB and cleaved caspase-3 proteins. Instead, NaHS treatment attenuated renal dysfunction through reduction of NGAL concentration, hypertension, CCr, oxidant/antioxidant imbalance, inflammation and apoptosis. These findings suggest that long term NaHS treatment can be useful in preventing the progression of CKD by improving oxidant/antioxidant balance and reducing inflammation and apoptosis in the kidney. PMID:29383015

Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

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

Ahad, Amjid; Ganai, Ajaz Ahmad; Mujeeb, Mohd

Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16more » weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway.« less

ASSOCIATIONS OF MACRO- AND MICROVASCULAR ENDOTHELIAL DYSFUNCTION WITH SUBCLINICAL VENTRICULAR DYSFUNCTION IN END-STAGE RENAL DISEASE

PubMed Central

Dubin, Ruth F; Guajardo, Isabella; Ayer, Amrita; Mills, Claire; Donovan, Catherine; Beussink, Lauren; Scherzer, Rebecca; Ganz, Peter; Shah, Sanjiv J

2016-01-01

Patients with end-stage renal disease (ESRD) suffer high rates of heart failure and cardiovascular mortality, and we lack a thorough understanding of what, if any, modifiable factors contribute to cardiac dysfunction in these high-risk patients. In order to evaluate endothelial function as a potentially modifiable cause of cardiac dysfunction in ESRD, we investigated cross-sectional associations of macro- and microvascular dysfunction with left and right ventricular dysfunction in a well-controlled ESRD cohort. We performed comprehensive echocardiography, including tissue Doppler imaging and speckle tracking echocardiography of the left and right ventricle, in 149 ESRD patients enrolled in an ongoing prospective, observational study. Of these participants, 123 also underwent endothelium-dependent flow-mediated dilation (FMD) of the brachial artery (macrovascular function). Microvascular function was measured as the velocity time integral (VTI) of hyperemic blood flow following cuff deflation. Impaired FMD was associated with higher LV mass, independently of age and blood pressure: per two-fold lower FMD, LV mass was 4.1% higher (95%CI [0.49, 7.7], p=0.03). After adjustment for demographics, blood pressure, comorbidities and medications, a two-fold lower VTI was associated with 9.5% higher E/e’ ratio (95% CI [1.0, 16], p=0.03) and 6.7% lower absolute RV longitudinal strain (95% CI [2.0, 12], p=0.003). Endothelial dysfunction is a major correlate of cardiac dysfunction in ESRD, particularly diastolic and right ventricular dysfunction, in patients whose volume status is well-controlled. Future investigations are needed to determine whether therapies targeting the vascular endothelium could improve cardiac outcomes in ESRD. PMID:27550915

A2B Adenosine Receptor–Mediated Induction of IL-6 Promotes CKD

PubMed Central

Dai, Yingbo; Zhang, Weiru; Wen, Jiaming; Zhang, Yujin; Kellems, Rodney E.

2011-01-01

Chronic elevation of adenosine, which occurs in the setting of repeated or prolonged tissue injury, can exacerbate cellular dysfunction, suggesting that it may contribute to the pathogenesis of CKD. Here, mice with chronically elevated levels of adenosine, resulting from a deficiency in adenosine deaminase (ADA), developed renal dysfunction and fibrosis. Both the administration of polyethylene glycol–modified ADA to reduce adenosine levels and the inhibition of the A2B adenosine receptor (A2BR) attenuated renal fibrosis and dysfunction. Furthermore, activation of A2BR promoted renal fibrosis in both mice infused with angiotensin II (Ang II) and mice subjected to unilateral ureteral obstruction (UUO). These three mouse models shared a similar profile of profibrotic gene expression in kidney tissue, suggesting that they share similar signaling pathways that lead to renal fibrosis. Finally, both genetic and pharmacologic approaches showed that the inflammatory cytokine IL-6 mediates adenosine-induced renal fibrosis downstream of A2BR. Taken together, these data suggest that A2BR-mediated induction of IL-6 contributes to renal fibrogenesis and shows potential therapeutic targets for CKD. PMID:21511827

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.

[Clinical case of acute renal failure revealing an autoimmune hypothyroidism].

PubMed

Montasser, Dina Ibrahim; Hassani, Mohamed; Zajjari, Yassir; Bahadi, Abdelali; Alayoud, Ahmed; Hamzi, Amine; Hassani, Kawtar; Moujoud, Omar; Asseraji, Mohamed; Kadiri, Moncif; Aatif, Taoufik; El Kabbaj, Driss; Benyahia, Mohamed; Allam, Mustapha; Akhmouch, Ismail; Oualim, Zouhir

2010-04-01

Although the clinic picture is often indicative of muscle manifestations in patients with hypothyroidism, signs and symptoms of this condition are variable from simple elevation of serum muscle enzymes with myalgia, muscle weakness, cramps to rhabdomyolysis with acute renal failure which remains a rare event. Thyroid hormones affect the function of almost every body organ, and thyroid dysfunction produces a wide range of metabolic disturbances. Hypothyroidism is associated with significant effects on the kidney which the pathophysiology seems to be multifactorial, but the exact mechanisms remain poorly understood. Hypothyroidism as a cause of renal impairment is usually overlooked, leading to unnecessary diagnostic procedures. The main objective of our observation is to report a case of acute renal failure revealing an autoimmune hypothyroidism in which thyroid hormone substitution led to a significant improvement in muscular, thyroid and renal disorders. Copyright 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

PubMed

Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Zhou, Zhanmei

2014-01-01

In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II), angiotensin type II receptor 1 (ATR1) were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the interstitial fibrosis, urine albumin excretion rate (UAER) and albumin to creatinine ratio. We conclude that phosphorylated Thr³⁰⁸-AKT regulates VEGF-A expression by interacting with either nephrin in glomeruli or Ang II in renal tubules. Antiangiogenic treatment improves renal injury and function in early experimental diabetes.

[Usefulness of FDG-PET/CT for the diagnosis of intravascular large B-cell lymphoma presenting with fever of unknown origin and renal dysfunction].

PubMed

Yago, Kazuhiro; Yanagita, Soshi; Aono, Maki; Matsuo, Ken; Shimada, Hideto

2009-06-01

A 76-year-old man presented with fever of unknown origin and renal dysfunction. Laboratory examination revealed anemia, thrombocytopenia, hypoalbuminemia, proteinuria, and elevations of C-reactive protein, lactic dehydrogenase, creatinine and ferritin. (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging showed FDG accumulation in the renal cortex and spleen. Based on the imaging study, renal biopsy was performed and histological diagnosis of intravascular large B-cell lymphoma (IVLBCL) was made. Renal impairment due to IVLBCL is uncommon and is often difficult to diagnose early. FDG-PET/CT may be a useful tool for the early diagnosis of IVLBCL.

Cardio-renal syndromes: a systematic approach for consensus definition and classification.

PubMed

Ronco, Claudio; Ronco, Federico

2012-03-01

The "Cardio-Renal Syndrome" (CRS) is a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The general definition has been expanded to five subtypes reflecting the primacy of organ dysfunction and the time-frame of the syndrome: CRS type I: acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF-CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease (CKD) leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Different pathophysiological mechanisms are involved in the combined dysfunction of heart and kidney in these five types of the syndrome.

Hemolytic anemia after ingestion of the natural hair dye Lawsonia inermis (henna) in a dog.

PubMed

Jardes, Daniel J; Ross, Linda A; Markovich, Jessica E

2013-01-01

To describe the clinical presentation and case management of a dog that developed hemolytic anemia and evidence of renal tubular dysfunction after ingestion of a natural hair dye containing Lawsonia inermis (henna). To review cases of henna toxicity reported in the human literature. An 8-year-old female spayed Border Collie was presented 5 days after ingestion of a box of natural hair dye. The dog was showing signs of lethargy, vomiting, diarrhea, and weakness. A serum biochemistry profile, complete blood count, and urinalysis demonstrated evidence of renal tubular dysfunction and a regenerative anemia without spherocytosis. The dog was treated with a transfusion of packed RBCs and IV fluids, resulting in significant clinical improvement. Repeat diagnostics showed resolution of the anemia and no lasting evidence of tubular dysfunction. To the authors' knowledge, this is the first reported case in the veterinary literature of toxicity following ingestion of Lawsonia inermis (henna). Henna ingestion was associated with the development of hemolytic anemia and acute kidney injury. © Veterinary Emergency and Critical Care Society 2013.

Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury

PubMed Central

Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Ban, Tae Hyun; Jang, In-Ae; Yoon, Hye Eun; Park, Cheol Whee; Chang, Yoon Sik

2018-01-01

Background. Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling. We examined whether resveratrol could potentially ameliorate the cellular condition, such as renal injury due to cellular oxidative stress and mitochondrial dysfunction caused by aging. Methods. Male 18-month-old C57BL/6 mice were used. Resveratrol (40 mg/kg) was administered to aged mice for 6 months. We compared histological changes, oxidative stress, and aging-related protein expression in the kidney between the resveratrol-treated group (RSV) and the control group (cont). We performed experiments using small-interfering RNAs (siRNAs) for Nrf2 and SIRT1 in cultured HK2 cells. Results. Resveratrol improved renal function, proteinuria, histological changes and inflammation in aging mice. Also, expression of Nrf2-HO-1-NOQ-1 signaling and SIRT1-AMPK-PGC-1α signaling was increased in the RSV group. Transfection with Nrf2 and SIRT1 siRNA prevented resveratrol-induced anti-oxidative effect in HK2 cells in media treated with H2O2. Conclusions. Activation of the Nrf2 and SIRT1 signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Pharmacological targeting of Nrf2 signaling molecules may reduce the pathologic changes of aging in the kidney. PMID:29326403

RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up.

PubMed

Meybohm, Patrick; Kohlhaas, Madeline; Stoppe, Christian; Gruenewald, Matthias; Renner, Jochen; Bein, Berthold; Albrecht, Martin; Cremer, Jochen; Coburn, Mark; Schaelte, Gereon; Boening, Andreas; Niemann, Bernd; Sander, Michael; Roesner, Jan; Kletzin, Frank; Mutlak, Haitham; Westphal, Sabine; Laufenberg-Feldmann, Rita; Ferner, Marion; Brandes, Ivo F; Bauer, Martin; Stehr, Sebastian N; Kortgen, Andreas; Wittmann, Maria; Baumgarten, Georg; Meyer-Treschan, Tanja; Kienbaum, Peter; Heringlake, Matthias; Schoen, Julika; Treskatsch, Sascha; Smul, Thorsten; Wolwender, Ewa; Schilling, Thomas; Fuernau, Georg; Bogatsch, Holger; Brosteanu, Oana; Hasenclever, Dirk; Zacharowski, Kai

2018-03-26

Remote ischemic preconditioning (RIPC) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham-RIPC. In this follow-up paper, we present 1-year follow-up of the composite primary end point and its individual components (all-cause mortality, myocardial infarction, stroke and acute renal failure), in a sub-group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidence of postoperative neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither showed any beneficial effect on the 1-year composite primary end point (RIPC versus sham-RIPC 16.4% versus 16.9%) and its individual components (all-cause mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved intraoperative myocardial dysfunction or incidence of postoperative neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients) and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively. Similar to our main study, RIPC had no effect on intraoperative myocardial dysfunction, neurocognitive function and long-term outcome in cardiac surgery patients undergoing propofol anesthesia. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

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.

Optical monitoring of kidney oxygenation and hemodynamics using a miniaturized near-infrared sensor

NASA Astrophysics Data System (ADS)

Shadgan, Babak; Macnab, Andrew; Nigro, Mark; Nguan, Christopher

2017-02-01

Background: Following human renal allograft transplant primary graft dysfunction can occur early in the postoperative period as a result of acute tubular necrosis, acute rejection, drug toxicity, and vascular complications. Successful treatment of graft dysfunction requires early detection and accurate diagnosis so that disease-specific medical and/or surgical intervention can be provided promptly. However, current diagnostic methods are not sensitive or specific enough, so that identifying the cause of graft dysfunction is problematic and often delayed. Near-infrared spectroscopy (NIRS) is an established optical method that monitors changes in tissue hemodynamics and oxygenation in real time. We report the feasibility of directly monitoring kidney the kidney in an animal model using NIRS to detect renal ischemia and hypoxia. Methods: In an anesthetized pig, a customized continuous wave spatially resolved (SR) NIRS sensor was fixed directly to the surface of the surgically exposed kidney. Changes in the concentration of oxygenated (O2Hb) deoxygenated (HHb) and total hemoglobin (THb) were monitored before, during and after renal artery clamping and reperfusion, and the resulting fluctuations in chromophore concentration from baseline used to measure variations in renal perfusion and oxygenation. Results: On clamping the renal artery THb and O2Hb concentrations declined progressively while HHb rose. With reperfusion after releasing the artery clamp O2Hb and THb rose while HHb fell with all parameters returning to its baseline. This pattern was similar in all three trials. Conclusion: This pilot study indicates that a miniaturized NIRS sensor applied directly to the surface of a kidney in an animal model can detect the onset of renal ischemia and tissue hypoxia. With modification, our NIRS-based method may contribute to early detection of renal vascular complications and graft dysfunction following renal transplant.

Pathologic Femoral Neck Fracture Due to Fanconi Syndrome Induced by Adefovir Dipivoxil Therapy for Hepatitis B

PubMed Central

Lee, Yoon-Suk; Kim, Byung-Kook; Lee, Ho-Jae

2016-01-01

In Fanconi syndrome, hypophosphatemic osteomalacia is caused by proximal renal tubule dysfunction which leads to impaired reabsorption of amino acids, glucose, urate, and phosphate. We present a rare case of a 43-year-old Korean male who was found to have insufficiency stress fracture of the femoral neck secondary to osteomalacia due to Fanconi syndrome. He had been receiving low-dose adefovir dipivoxil (ADV, 10 mg/day) for the treatment of chronic hepatitis B virus infection for 7 years and he subsequently developed severe hypophosphatemia and proximal renal tubule dysfunction. The incomplete femoral neck fracture was fixed with multiple cannulated screws to prevent further displacement of the initial fracture. After cessation of ADV and correction of hypophosphatemia with oral phosphorus supplementation, the patient's clinical symptoms, such as bone pain, muscle weakness, and laboratory findings improved. PMID:27247753

Tricuspid regurgitation contributes to renal dysfunction in patients with heart failure.

PubMed

Maeder, Micha T; Holst, Diane P; Kaye, David M

2008-12-01

In heart failure (HF), renal dysfunction is associated with an adverse prognosis. Impaired renal perfusion from left ventricular dysfunction is thought to be a principal underlying mechanism. Less is known about the influence of venous congestion, including the potential contribution of tricuspid regurgitation (TR). Echocardiograms and a simultaneous (+/-1 day) blood sample from 196 HF patients were analyzed. Patients with at least moderate TR (n = 78) had larger right-sided cardiac cavities, higher right ventricular systolic pressure, lower estimated glomerular filtration rate (eGFR), higher serum urea nitrogen (SUN), and SUN/creatinine ratio than patients with less than moderate TR (n = 118). In multivariate linear regression analysis, TR severity (P = .003), older age (P < .001), and loop diuretic use (P = .008) were independently associated with lower eGFR, and use of inhibitors of the renin-angiotensin-aldosterone system was associated with higher eGFR (P = .001). TR severity (P < .001) and older age (P < .001) were independently associated with higher SUN. TR severity (P = .004) and smaller left ventricular end-diastolic diameter (P = .048) were independent predictors of a higher SUN/creatinine ratio (P = .004). Although a causal relationship cannot be proven, we suggest that significant TR contributes to renal dysfunction in HF patients, probably by elevation of central and renal venous pressure.

Effects of statin therapy on clinical outcomes after acute myocardial infarction in patients with advanced renal dysfunction: A propensity score-matched analysis.

PubMed

Kim, Jin Sug; Kim, Weon; Park, Ji Yoon; Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyun; Moon, Ju-Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

2017-01-01

Lipid lowering therapy is widely used for the prevention of cardiovascular complications after acute myocardial infarction (AMI). However, some studies show that this benefit is uncertain in patients with renal dysfunction, and the role of statins is based on the severity of renal dysfunction. In this study, we investigated the impact of statin therapy on major adverse cardiac events (MACEs) and all-cause mortality in patients with advanced renal dysfunction undergoing percutaneous coronary intervention (PCI) after AMI. This study was based on the Korea Acute Myocardial Infarction Registry database. We included 861 patients with advanced renal dysfunction from among 33,205 patients who underwent PCI after AMI between November 2005 and July 2012. Patients were divided into two groups: a statin group (n = 537) and a no-statin group (n = 324). We investigated the 12-month MACEs (cardiac death, myocardial infarction, repeated PCI or coronary artery bypass grafting) and all-cause mortality of each group. Subsequently, a propensity score-matched analysis was performed. In the total population studied, no significant differences were observed between the two groups with respect to the rate of recurrent MI, repeated PCI, coronary artery bypass grafting (CABG), or all-cause mortality. However, the cardiac death rate was significantly lower in the statin group (p = 0.009). Propensity score-matched analysis yielded 274 pairs demonstrating, results similar to those obtained from the total population. However, there was no significant difference in the cardiac death rate in the propensity score-matched population (p = 0.103). Cox-regression analysis revealed only left ventricular ejection fraction to be an independent predictor of 12-month MACEs (Hazard ratio [HR] of 0.979, 95% confidence interval [CI], 0962-0.996, p = 0.018). Statin therapy was not significantly associated with a reduction in the 12-month MACEs or all-cause mortality in patients with advanced renal dysfunction undergoing PCI after AMI.

COX-2 is involved in vascular oxidative stress and endothelial dysfunction of renal interlobar arteries from obese Zucker rats.

PubMed

Muñoz, Mercedes; Sánchez, Ana; Pilar Martínez, María; Benedito, Sara; López-Oliva, Maria-Elvira; García-Sacristán, Albino; Hernández, Medardo; Prieto, Dolores

2015-07-01

Obesity is related to vascular dysfunction through inflammation and oxidative stress and it has been identified as a risk factor for chronic renal disease. In the present study, we assessed the specific relationships among reactive oxygen species (ROS), cyclooxygenase 2 (COX-2), and endothelial dysfunction in renal interlobar arteries from a genetic model of obesity/insulin resistance, the obese Zucker rats (OZR). Relaxations to acetylcholine (ACh) were significantly reduced in renal arteries from OZR compared to their counterpart, the lean Zucker rat (LZR), suggesting endothelial dysfunction. Blockade of COX with indomethacin and with the selective blocker of COX-2 restored the relaxations to ACh in obese rats. Selective blockade of the TXA2/PGH2 (TP) receptor enhanced ACh relaxations only in OZR, while inhibition of the prostacyclin (PGI2) receptor (IP) enhanced basal tone and inhibited ACh vasodilator responses only in LZR. Basal production of superoxide was increased in arteries of OZR and involved NADPH and xanthine oxidase activation and NOS uncoupling. Under conditions of NOS blockade, ACh induced vasoconstriction and increased ROS generation that were augmented in arteries from OZR and blunted by COX-2 inhibition and by the ROS scavenger tempol. Hydrogen peroxide (H2O2) evoked both endothelium- and vascular smooth muscle (VSM)-dependent contractions, as well as ROS generation that was reduced by COX-2 inhibition. In addition, COX-2 expression was enhanced in both VSM and endothelium of renal arteries from OZR. These results suggest that increased COX-2-dependent vasoconstriction contributes to renal endothelial dysfunction through enhanced (ROS) generation in obesity. COX-2 activity is in turn upregulated by ROS. Copyright © 2015 Elsevier Inc. All rights reserved.

Renal Failure in Sickle Cell Disease: Prevalence, Predictors of Disease, Mortality and Effect on Length of Hospital Stay.

PubMed

Yeruva, Sri L H; Paul, Yonette; Oneal, Patricia; Nouraie, Mehdi

2016-09-01

Renal dysfunction in sickle cell disease is not only a chronic comorbidity but also a mortality risk factor. Though renal dysfunction starts early in life in sickle cell patients, the predictors that can identify sickle cell disease patients at risk of developing renal dysfunction is not known. We used the Truven Health MarketScan ® Medicaid Databases from 2007 to 2012. Incidence of new acute renal failure (ARF) and chronic kidney disease (CKD) was calculated in this cohort. There were 9481 patients with a diagnosis of sickle cell disease accounting for 64,201 hospital admissions, during the study period. Both ARF and CKD were associated with higher risk of inpatient mortality, longer duration of the hospital stay and expensive hospitalizations. The yearly incidence of new ARF in sickle cell disease patients was 1.4% and annual CKD incidence was 1.3%. The annual rate of new ARF and CKD in the control group was 0.4 and 0.6%, respectively. The most important predictors of new CKD were proteinuria, ARF and hypertension. Chronic kidney disease, hypertension and sickle cell crisis were the most important predictors of new ARF. The annual rate of incidences of ARF and CKD were 2- to 3-fold higher in sickle cell disease compared to the non sickle cell disease group. Besides the common risk factors for renal disease in the general population, it is imperative to monitor the sickle cell disease patients with more severe disease to prevent them from developing renal dysfunction.

Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord injury

PubMed Central

Galeiras, Rita; Mourelo, Mónica; Pértega, Sonia; Lista, Amanda; Ferreiro, Mª Elena; Salvador, Sebastián; Montoto, Antonio; Rodríguez, Antonio

2016-01-01

Background: Patients with acute traumatic spinal cord injuries (SCIs) exhibit factors that, in other populations, have been associated with rhabdomyolysis. Purpose: The aim of the study is to determine the incidence of rhabdomyolysis in patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as well as the development of secondary acute kidney injury and associated factors. Study Design and Setting: This was an observational, retrospective study. Patient Sample: All adult patients admitted to the ICU with acute traumatic SCI who presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels >500 IU/L. Outcome Measures: Incidence of rhabdomyolysis and subsequent renal dysfunction was calculated. Materials and Methods: Data about demographic variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI, severity scores, and laboratory parameters were obtained from clinical records. Multivariate logistic regression was used to identify renal injury risk factors. Results: In 2006–2014, 200 patients with acute SCI were admitted to ICU. Of these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]: 44.3%–58.7%). The most typical American Spinal Injury Association classification was A (70.3%). The injury severity score was 30.3 ± 12.1 and sequential organ failure assessment (SOFA) score was 5.6 ± 3.3 points. During their stay, 57 patients (55.3%; 95% CI: 45.2%–65.4%) presented renal dysfunction (creatinine ≥1.2 mg/dL). In the multivariate analysis, variables associated with renal dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024). Creatinine was a better predictor of renal dysfunction than the peak CPK value during the rhabdomyolysis (area under the receiver operating characteristic curve: 0.91 vs. 0.63, respectively). Conclusions: Rhabdomyolysis is a frequent condition in patients with acute traumatic SCI admitted to the ICU, and renal dysfunction occurs in half of the cases. Creatinine values should be requested starting at the admission while neither the peak CPK values nor the hemodynamic SOFA scores could be used to properly discriminate between patients with and without renal dysfunction. PMID:27688625

Lung-Kidney Cross-Talk in the Critically Ill Patient.

PubMed

Husain-Syed, Faeq; Slutsky, Arthur S; Ronco, Claudio

2016-08-15

Discoveries have emerged highlighting the complex nature of the interorgan cross-talk between the kidney and the lung. Vascular rigidity, neurohormonal activation, tissue hypoxia, and abnormal immune cell signaling have been identified as common pathways leading to the development and progression of chronic kidney disease. However, our understanding of the causal relationships between lung injury and kidney injury is not precise. This review discusses a number of features and mechanisms of renal dysfunction in pulmonary disorders in relation to respiratory acidosis, impaired gas exchange, systemic congestion, respiratory support/replacement therapies, and other issues relevant to the clinical care of these patients. Biotrauma due to injurious ventilatory strategies can lead to the release of mediators into the lung, which may then translocate into the systemic circulation and cause end-organ dysfunction, including renal dysfunction. Right ventricular dysfunction and congestive states may contribute to alterations of renal perfusion and oxygenation, leading to diuretic resistance and recurrent hospitalization. In patients with concomitant respiratory failure, noninvasive ventilation represents a promising treatment option for the correction of impaired renal microcirculation and endothelial dysfunction. In patients requiring extracorporeal membrane oxygenation, short- and long-term monitoring of kidney function is warranted, as they are at highest risk of developing acute kidney injury and fluid overload.

[Oliguria and acute renal dysfunction in a six-month-old infant].

PubMed

Cui, Ya-Jie; Song, Chun-Lan; Cheng, Yi-Bing

2017-02-01

The infant (a girl aged 6 months) was admitted to the hospital because of oliguria and acute renal dysfunction. The laboratory examination results showed serious metabolic acidosis and increased blood urea nitrogen and serum creatinine levels. The patient continued to be anuric after 10 days of treatment with continuous renal replacement therapy (CRRT). she died a day later. The family history showed that the patient's sister died of acute renal failure 6 months after birth. The genomic sequencing results showed AGXT mutation in the patient and confirmed the diagnosis of primary hyperoxaluria type 1 (PH1). Her parents were heterozygous carriers. PH1 should be considered when the children have abnormal renal function or recurrent renal calculi or have a family history of these symptoms. AGXT gene analysis is an important method for PH1 diagnosis.

Multiple Low-Dose Radiation Prevents Type 2 Diabetes-Induced Renal Damage through Attenuation of Dyslipidemia and Insulin Resistance and Subsequent Renal Inflammation and Oxidative Stress

PubMed Central

Shao, Minglong; Lu, Xuemian; Cong, Weitao; Xing, Xiao; Tan, Yi; Li, Yunqian; Li, Xiaokun; Jin, Litai; Wang, Xiaojie; Dong, Juancong; Jin, Shunzi; Zhang, Chi; Cai, Lu

2014-01-01

Background Dyslipidemia and lipotoxicity-induced insulin resistance, inflammation and oxidative stress are the key pathogeneses of renal damage in type 2 diabetes. Increasing evidence shows that whole-body low dose radiation (LDR) plays a critical role in attenuating insulin resistance, inflammation and oxidative stress. Objective The aims of the present study were to investigate whether LDR can prevent type 2 diabetes-induced renal damage and the underlying mechanisms. Methods Mice were fed with a high-fat diet (HFD, 40% of calories from fat) for 12 weeks to induce obesity followed by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg) to develop a type 2 diabetic mouse model. The mice were exposed to LDR at different doses (25, 50 and 75 mGy) for 4 or 8 weeks along with HFD treatment. At each time-point, the kidney weight, renal function, blood glucose level and insulin resistance were examined. The pathological changes, renal lipid profiles, inflammation, oxidative stress and fibrosis were also measured. Results HFD/STZ-induced type 2 diabetic mice exhibited severe pathological changes in the kidney and renal dysfunction. Exposure of the mice to LDR for 4 weeks, especially at 50 and 75 mGy, significantly improved lipid profiles, insulin sensitivity and protein kinase B activation, meanwhile, attenuated inflammation and oxidative stress in the diabetic kidney. The LDR-induced anti-oxidative effect was associated with up-regulation of renal nuclear factor E2-related factor-2 (Nrf-2) expression and function. However, the above beneficial effects were weakened once LDR treatment was extended to 8 weeks. Conclusion These results suggest that LDR exposure significantly prevented type 2 diabetes-induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms of LDR are complicated but may be mainly attributed to the attenuation of dyslipidemia and the subsequent lipotoxicity-induced insulin resistance, inflammation and oxidative stress. PMID:24651118

Echocardiographic predictors of change in renal function with intravenous diuresis for decompensated heart failure.

PubMed

Gannon, Stephen A; Mukamal, Kenneth J; Chang, James D

2018-06-14

The aim of this study was to identify echocardiographic predictors of improved or worsening renal function during intravenous diuresis for decompensated heart failure. Secondary aim included defining the incidence and clinical risk factors for acute changes in renal function with decongestion. A retrospective review of 363 patients admitted to a single centre for decompensated heart failure who underwent intravenous diuresis and transthoracic echocardiography was conducted. Clinical, echocardiographic, and renal function data were retrospectively collected. A multinomial logistic regression model was created to determine relative risk ratios for improved renal function (IRF) or worsening renal function (WRF). Within this cohort, 36% of patients experienced WRF, 35% had stable renal function, and 29% had IRF. Patients with WRF were more likely to have a preserved left ventricular ejection fraction compared with those with stable renal function or IRF (P = 0.02). Patients with IRF were more likely to have a dilated, hypokinetic right ventricle compared with those with stable renal function or WRF (P ≤ 0.01), although this was not significant after adjustment for baseline characteristics. Left atrial size, left ventricular linear dimensions, and diastolic function did not significantly predict change in renal function. An acute change in renal function occurred in 65% of patients admitted with decompensated heart failure. WRF was statistically more likely in patients with a preserved left ventricular ejection fraction. A trend towards IRF was noted in patients with global right ventricular dysfunction. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

IgG4-related tubulointerstitial nephritis: A prospective analysis.

PubMed

Nada, Ritambhra; Ramachandran, Raja; Kumar, Ashwani; Rathi, Manish; Rawat, Amit; Joshi, Kusum; Kohli, Harbir Singh; Gupta, Krishan Lal

2016-07-01

Immunoglobulin-G4 (IgG4)-related tubulo-interstitial nephritis (IgG4TIN) could be the first presentation of IgG4-related systemic disease. Most of the data is from the West or Japan and retrospective, with good patient outcome. This study was carried out from April 2011 to July 2013. We report a prospective follow-up of 11 patients who presented with renal dysfunction and had histological diagnosis of IgG4TIN followed for a minimum period of 1 year or until end-stage renal disease. IgG4TIN constituted 0.28% of total renal biopsies and 6.5% of all tubulointerstitial nephritis. Patient ages ranged between 21 and 71 years with a male predominance. All the patients had renal dysfunction at presentation with a mean serum creatinine of 5.12 mg/dL. Proteinuria was subnephrotic except when there was coexisting membranous glomerulonephritis (36.4%). The mean 24-h urine protien excretion was 1.8 g. Serum IgG4 levels were elevated in 10 (90.9%) patients. Ten (90.9%) patients had renomegaly and one (9.1%) had focal renal mass. Extra-renal manifestations were present in seven (63.6%). Renal histology showed pattern A in five (45.5%), pattern B in four (36.3%) and pattern C in two (18.1%) patients. All but one patient (90.9%) received immunosuppressive therapy. Four (36.3%) achieved complete remission and three (27.2%) progressed to end stage renal disease. Two patients died due to infections while on steroid therapy. One patient with a mass had end stage renal disease for 12 months and did not improve with steroid therapy, and one (pattern C) had progressive chronic kidney disease on follow-up. IgG4TIN in an Indian cohort most often presents with rapidly progressive renal failure and less often has extra-renal organ involvement. On follow-up, patients can experience a more aggressive course with progression to end stage renal disease. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Nephrotoxicity of Natural Products.

PubMed

Nauffal, Mary; Gabardi, Steven

2016-01-01

The manufacture and sale of natural products constitute a multi-billion dollar industry. Nearly a third of the American population admit to using some form of complementary or alternative medicine, with many using them in addition to prescription medications. Most patients fail to inform their healthcare providers of their natural product use and physicians rarely inquire. Annually, thousands of natural product-induced adverse events are reported to Poison Control Centers nationwide. Natural product manufacturers are not responsible for proving safety and efficacy, as the FDA does not regulate them. However, concerns exist surrounding the safety of natural products. This review provides details on natural products that have been associated with renal dysfunction. We have focused on products that have been associated with direct renal injury, immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, hepatorenal syndrome, and common adulterants or contaminants that are associated with renal dysfunction. The potential for natural products to cause renal dysfunction is justifiable. It is imperative that natural product use be monitored closely in all patients. Healthcare practitioners must play an active role in identifying patients using natural products and provide appropriate patient education. © 2016 S. Karger AG, Basel.

Meta-analysis of Renal Function Following Infrarenal EVAR using Suprarenal or Infrarenal Fixation Devices.

PubMed

Stather, Philip W; Ferguson, James; Awopetu, Ayoola; Boyle, Jonathan R

2018-03-03

The effect of suprarenal (SR) as opposed to infrarenal (IR) fixation on renal outcomes post-endovascular aneurysm repair (EVAR) remains controversial. This meta-analysis aims to update current understanding of this issue. A prior meta-analysis was updated through a Preferred Reporting Items for Systematic reviews and Meta-Analyses search for additional studies published in the last 3 years reporting on renal dysfunction or related outcomes post-EVAR. Random effects meta-analysis was undertaken using SPSS. A total of 25 non-randomised studies comparing SR with IR fixation were included, totalling 54,832 patients. In total, 16,634 underwent SR and 38,198 IR. Baseline characteristics, including age, baseline estimated glomerular filtration rate, diabetes, cardiac disease, and smoking, were similar between the groups. There was a small but significant difference in outcomes for renal dysfunction at the study end point (SR 5.98% vs. IR 4.83%; odds ratio [OR] 1.29, 95% confidence interval [CI] 1.18-1.40 [p < .001]); however, at 30 days and 12 months there was no significant difference, and this did not hold up to sensitivity analysis. Incidence of renal infarcts (SR 6.6% vs. IR 2.3%; OR 2.78, 95% CI 1.46-5.29 [p = .002]), renal stenosis (SR 2.4% vs. IR 0.8%; OR 2.89, 95% CI 1.00-8.38 [p = .05]), and renal artery occlusion (SR 2.4% vs. IR 1.2%; OR 2.21, 95% CI 1.15-4.25 [p = 0.02]) favoured IR fixation; however, there was no difference in haemodialysis rates. This meta-analysis has identified small but significantly worse renal outcomes in patients having SR fixation devices compared with IR; however, there was no difference in dialysis rates and a small effect on renal dysfunction, which did not stand up to rigorous sensitivity analysis. This should be taken into consideration during graft selection, and further studies must assess renal outcomes in the longer term, and in those with pre-existing renal dysfunction. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Are levels of NT-proBNP and SDMA useful to determine diastolic dysfunction in chronic kidney disease and renal transplant patients?

PubMed

Memon, Lidija; Spasojevic-Kalimanovska, Vesna; Stanojevic, Natasa Bogavac; Kotur-Stevuljevic, Jelena; Simic-Ogrizovic, Sanja; Giga, Vojislav; Dopsaj, Violeta; Jelic-Ivanovic, Zorana; Spasic, Slavica

2013-11-01

The aim of the study was to determine the clinical usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and symmetric dimethylarginine (SDMA) for detection of renal and left ventricular (LV) diastolic dysfunction in chronic kidney disease (CKD) patients and renal transplant (RT) recipients. We included 98 CKD and 44 RT patients. We assessed LV function using pulsed-wave Doppler ultrasound. Diastolic dysfunction was defined when the E:A ratio was <1. Independent predictors of NT-proBNP levels were age, creatinine, and albumin in CKD patients and age and urea in RT patients. Determinants of SDMA in CKD patients were glomerular filtration rate (GFR) and NT-proBNP and creatinine in RT patients. In RT patients with diastolic dysfunction, NT-proBNP and SDMA were significantly higher than in patients without diastolic dysfunction (F = 7.478, P < 0.011; F = 2.631, P < 0.017). After adjustment for GFR, the differences were not seen. In CKD patients adjusted NT-proBNP and SDMA values for GFR were not significantly higher in patients with diastolic dysfunction than in patients without diastolic dysfunction. NT-proBNP is useful for detection of LV diastolic dysfunction in RT recipients. When evaluating both NT-proBNP and SDMA it is necessary to consider GFR as a confounding factor. © 2013 Wiley Periodicals, Inc.

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

PubMed

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

2007-12-01

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

Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: possible mechanism of nephroprotection.

PubMed

Sahu, Bidya Dhar; Tatireddy, Srujana; Koneru, Meghana; Borkar, Roshan M; Kumar, Jerald Mahesh; Kuncha, Madhusudana; Srinivas, R; Shyam Sunder, R; Sistla, Ramakrishna

2014-05-15

Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in the kidney. Copyright © 2014 Elsevier Inc. All rights reserved.

Disparate effects of single endothelin A and B receptor blocker therapy on the progression of renal injury in advanced renovascular disease

PubMed Central

Chade, Alejandro R.; Stewart, Nicholas J.; Peavy, Patrick R.

2013-01-01

We hypothesized that chronic specific endothelin (ET)-A receptor blockade therapy would reverse renal dysfunction and injury in advanced experimental renovascular disease. To test this, unilateral renovascular disease was induced in 19 pigs and after 6 weeks, single-kidney hemodynamics and function was quantified in vivo using computed-tomography. All pigs with renovascular disease were divided such that 7 were untreated, 7 were treated with ET-A blockers, and 5 were treated with ET-B blockers. Four weeks later, all pigs were re-studied in vivo, then euthanized and ex vivo studies performed on the stenotic kidney to quantify microvascular density, remodeling, renal oxidative stress, inflammation, and fibrosis. RBF, GFR, and redox status were significantly improved in the stenotic kidney after ET-A but not ET-B blockade. Furthermore, only ET-A blockade therapy reversed renal microvascular rarefaction and diminished remodeling, which was accompanied by a marked decreased in renal inflammatory and fibrogenic activity. Thus, ET-A but not ET-B blockade ameliorated renal injury in pigs with advanced renovascular disease by stimulating microvascular proliferation and decreasing the progression of microvascular remodeling, renal inflammation and fibrosis in the stenotic kidney. These effects were functionally consequential since ET-A blockade improved single kidney microvascular endothelial function, RBF, and GFR, and decreased albuminuria. PMID:24352153

Neurogenic Bladder

PubMed Central

Dorsher, Peter T.; McIntosh, Peter M.

2012-01-01

Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented. PMID:22400020

Hypophosphatemia in a Malnourished Child: When Renal Fanconi Syndrome Does Not Stand for Refeeding Syndrome.

PubMed

Runde, Joseph; Rivera-Rivera, Edgardo; Pompeii-Wolfe, Cecelia; Clardy, Christopher; Sentongo, Timothy

2018-05-10

Refeeding syndrome is diagnosed based on the onset of multiple laboratory abnormalities (most commonly hypophosphatemia) and clinical signs in the setting of nutrition rehabilitation of malnourished patients. Because definitions are not uniform, a broad differential diagnosis should always include renal tubular dysfunction. Our report details a 3 year-old child with undiagnosed renal tubular dysfunction who presented with the clinical picture of refeeding syndrome with refractory electrolyte abnormalities. A diagnosis of renal Fanconi syndrome was made after urinalysis that revealed glucosuria and urine electrolyte losses. Thus, urinalysis can aid in making a positive diagnosis of refeeding syndrome. © 2018 American Society for Parenteral and Enteral Nutrition.

Protective effect of agmatine on ischemia/reperfusion-induced renal injury in rats.

PubMed

Sugiura, Takahiro; Tsutsui, Hidenobu; Takaoka, Masanori; Kobuchi, Shuhei; Hayashi, Kentaro; Fujii, Toshihide; Matsumura, Yasuo

2008-03-01

Enhanced renal sympathetic nerve activity (RSNA) during ischemic period and the renal venous norepinephrine (NE) overflow after reperfusion play important roles in the development of ischemic/reperfusion (I/R)-induced acute renal failure (ARF) in rats. This study evaluated whether agmatine, which is known to reduce sympathetic nerve activity and NE overflow by electrical stimulation, would prevent the I/R-induced renal dysfunction. Ischemic ARF was induced by clamping the left renal artery and vein for 45 minutes followed by reperfusion 2 weeks after the contralateral nephrectomy. Intravenous (IV) injection of agmatine (100 and 300 micromol/kg) to ischemic ARF rats dose-dependently suppressed the enhanced RSNA and attenuated the I/R-induced renal dysfunction and histological damage. Intracerebroventricular (ICV) injection of agmatine (600 nmol/kg) to ischemic ARF rats suppressed the enhanced RSNA during the ischemic period and attenuated the I/R-induced renal injury. Furthermore, both IV and ICV injection of agmatine significantly suppressed the renal venous NE overflow after the reperfusion. These results indicate that agmatine prevents the development of I/R-induced renal injury, and the effect is accompanied by suppression of the enhanced RSNA during ischemic period and NE overflow from renal sympathetic nerve endings.

A Canola Oil-Supplemented Diet Prevents Type I Diabetes-Caused Lipotoxicity and Renal Dysfunction in a Rat Model.

PubMed

Cano-Europa, Edgar; Ortiz-Butron, Rocio; Camargo, Estela Melendez; Esteves-Carmona, María Miriam; Oliart-Ros, Rosa Maria; Blas-Valdivia, Vanessa; Franco-Colin, Margarita

2016-11-01

We investigated the effect of a canola oil-supplemented diet on the metabolic state and diabetic renal function of a type I diabetes experimental model. Male Sprague-Dawley rats were randomly divided into four groups: (1) normoglycemic+chow diet, (2) normoglycemic+a canola oil-supplemented chow diet, (3) diabetic+chow diet, and (4) diabetic+a canola oil-supplemented chow diet. For 15 weeks, animals were fed a diet of Purina rat chow alone or supplemented with 30% canola oil. Energetic intake, water intake, body weight, and adipose tissue fat pad were measured; renal function, electrolyte balance, glomerular filtration rate, and the plasmatic concentration of free fatty acids, cholesterol, triglycerides, and glucose were evaluated. The mesenteric, retroperitoneal, and epididymal fat pads were dissected and weighed. The kidneys were used for lipid peroxidation (LP) and reactive oxygen species (ROS) quantifications. Diabetic rats fed with a canola oil-supplemented diet had higher body weights, were less hyperphagic, and their mesenteric, retroperitoneal, and epididymal fat pads weighed more than diabetic rats on an unsupplemented diet. The canola oil-supplemented diet decreased plasmatic concentrations of free fatty acids, triglycerides, and cholesterol; showed improved osmolarity, water clearances, and creatinine depuration; and had decreased LP and ROS. A canola oil-supplemented diet decreases hyperphagia and prevents lipotoxicity and renal dysfunction in a type I diabetes mellitus model.

Proximal Tubular Cannabinoid-1 Receptor Regulates Obesity-Induced CKD.

PubMed

Udi, Shiran; Hinden, Liad; Earley, Brian; Drori, Adi; Reuveni, Noa; Hadar, Rivka; Cinar, Resat; Nemirovski, Alina; Tam, Joseph

2017-12-01

Obesity-related structural and functional changes in the kidney develop early in the course of obesity and occur independently of hypertension, diabetes, and dyslipidemia. Activating the renal cannabinoid-1 receptor (CB 1 R) induces nephropathy, whereas CB 1 R blockade improves kidney function. Whether these effects are mediated via a specific cell type within the kidney remains unknown. Here, we show that specific deletion of CB 1 R in the renal proximal tubule cells did not protect the mice from obesity, but markedly attenuated the obesity-induced lipid accumulation in the kidney and renal dysfunction, injury, inflammation, and fibrosis. These effects associated with increased activation of liver kinase B1 and the energy sensor AMP-activated protein kinase, as well as enhanced fatty acid β -oxidation. Collectively, these findings indicate that renal proximal tubule cell CB 1 R contributes to the pathogenesis of obesity-induced renal lipotoxicity and nephropathy by regulating the liver kinase B1/AMP-activated protein kinase signaling pathway. Copyright © 2017 by the American Society of Nephrology.

The renal nerves in chronic heart failure: efferent and afferent mechanisms

PubMed Central

Schiller, Alicia M.; Pellegrino, Peter R.; Zucker, Irving H.

2015-01-01

The function of the renal nerves has been an area of scientific and medical interest for many years. The recent advent of a minimally invasive catheter-based method of renal denervation has renewed excitement in understanding the afferent and efferent actions of the renal nerves in multiple diseases. While hypertension has been the focus of much this work, less attention has been given to the role of the renal nerves in the development of chronic heart failure (CHF). Recent studies from our laboratory and those of others implicate an essential role for the renal nerves in the development and progression of CHF. Using a rabbit tachycardia model of CHF and surgical unilateral renal denervation, we provide evidence for both renal efferent and afferent mechanisms in the pathogenesis of CHF. Renal denervation prevented the decrease in renal blood flow observed in CHF while also preventing increases in Angiotensin-II receptor protein in the microvasculature of the renal cortex. Renal denervation in CHF also reduced physiological markers of autonomic dysfunction including an improvement in arterial baroreflex function, heart rate variability, and decreased resting cardiac sympathetic tone. Taken together, the renal sympathetic nerves are necessary in the pathogenesis of CHF via both efferent and afferent mechanisms. Additional investigation is warranted to fully understand the role of these nerves and their role as a therapeutic target in CHF. PMID:26300788

Sickle cell disease: renal manifestations and mechanisms

PubMed Central

Nath, Karl A.; Hebbel, Robert P.

2015-01-01

Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ+-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16–18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms. PMID:25668001

Renal dysfunction in patients with thalassaemia.

PubMed

Quinn, Charles T; Johnson, Valerie L; Kim, Hae-Young; Trachtenberg, Felicia; Vogiatzi, Maria G; Kwiatkowski, Janet L; Neufeld, Ellis J; Fung, Ellen; Oliveri, Nancy; Kirby, Melanie; Giardina, Patricia J

2011-04-01

Little is known about the effects of thalassaemia on the kidney. Characterization of underlying renal function abnormalities in thalassaemia is timely because the newer iron chelator, deferasirox, can be nephrotoxic. We aimed to determine the prevalence and correlates of renal abnormalities in thalassaemia patients, treated before deferasirox was widely available, using 24-h collections of urine. We calculated creatinine clearance and urine calcium-to-creatinine ratio and measured urinary β(2) -microglobulin, albumin, and protein. We used multivariate modelling to identify clinical, therapeutic, and laboratory predictors of renal dysfunction. One-third of thalassaemia patients who were not regularly transfused had abnormally high creatinine clearance. Regular transfusions were associated with a decrease in clearance (P = 0·004). Almost one-third of patients with thalassaemia had hypercalciuria, and regular transfusions were associated with an increase in the frequency and degree of hypercalciuria (P < 0·0001). Albuminuria was found in over half of patients, but was not consistently associated with transfusion therapy. In summary, renal hyperfiltration, hypercalciuria, and albuminuria are common in thalassaemia. Higher transfusion intensity is associated with lower creatinine clearance but more frequent hypercalciuria. The transfusion effect needs to be better understood. Awareness of underlying renal dysfunction in thalassaemia can inform decisions now about the use and monitoring of iron chelation. © 2011 Blackwell Publishing Ltd.

Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction

PubMed Central

de Matos, Ana Cristina Carvalho; Requião-Moura, Lúcio Roberto; Clarizia, Gabriela; Durão, Marcelino de Souza; Tonato, Eduardo José; Chinen, Rogério; de Arruda, Érika Ferraz; Filiponi, Thiago Corsi; Pires, Luciana Mello de Mello Barros; Bertocchi, Ana Paula Fernandes; Pacheco-Silva, Alvaro

2015-01-01

ABSTRACT Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction. PMID:26154553

Attenuation of the activated mammalian target of rapamycin pathway might be associated with renal function reserve by a low-protein diet in the rat remnant kidney model.

PubMed

Ohkawa, Sakae; Yanagida, Momoko; Uchikawa, Tsuyoshi; Yoshida, Takuya; Ikegaya, Naoki; Kumagai, Hiromichi

2013-09-01

The mammalian target of rapamycin (mTOR), a regulator of cellular protein synthesis and cell growth, plays an important role in the progression of renal hypertrophy and renal dysfunction in experimental chronic kidney disease models. Because the mTOR activity is regulated by nutrients including amino acids, we tested the hypothesis that the renoprotective effect of a low-protein diet (LPD) might be associated with the attenuation of the renal mTOR pathway. In this study, 5/6 nephrectomized rats were fed an LPD or a normal protein diet (NPD), and a number of rats that were fed an NPD received rapamycin (1.0 mg kg⁻¹ d⁻¹), a specific inhibitor of mTOR. After 6 weeks, renal tissue was collected to evaluate the activity of the mTOR pathway and histologic changes. The phosphorylation of p70S6k, a kinase in the downstream of mTOR, was significantly higher in the NPD-fed rats that showed progressive renal dysfunction than in the sham-operated rats (NPD). The LPD attenuated the excessive phosphorylation of p70S6k concomitant with reduced proteinuria and improved renal histologic changes in the 5/6 nephrectomized rats. The effects of the LPD were similar to the effects of rapamycin. The expression of phosphorylated p70S6k was significantly correlated with proteinuria (r² = 0.63, P < .001), the glomerular area (r² = 0.60, P < .001), and the number of phosphorylated Smad2-positive cells in the glomerulus (r² = 0.26, P < .05) of these rats. These results suggest that the preventive effect of an LPD on the progression of renal failure is associated with attenuation of the activated mTOR/p70S6k pathway in the rat remnant kidney model. © 2013.

Epidemiology and outcome of tuberculosis in immunocompromised patients.

PubMed

Metry, Abdul Massiah; Al Salmi, Issa; Al-Abri, Seif; Al Ismaili, Faisal; Al Mahrouqi, Yaqoub; Hola, Alan; Shaheen, Faissal A M

2017-01-01

The United States Renal Data System showed 1.2% and 1.6% incidences of tuberculosis (TB) in patients on peritoneal dialysis and hemodialysis (HD), respectively. Kidney transplant (KTX) patients have higher rates. We studied the epidemiology and outcome of TB in patients with kidney dysfunction in a tertiary care hospital in the past decade. We examined data of patients with TB with and without kidney dysfunction from 2006 to 2015 through an electronic system. Statistical analysis was completed using Stata software, Chicago, IL, USA. We found 581 patients with active TB of whom 37 had renal dysfunction including chronic kidney disease, HD, and KTX. No difference was found in the prevalence, age, or gender predilection. The age ranged from 1 to 95 with a mean (standard deviation) of 38.6 (21.1) years. The incidence of TB is 3 per 100,000. The number of patients per year with active TB ranges from 52 to 128 and 3 to 4 in the general population and kidney dysfunction group, respectively. Sixty-five percent of patients with kidney dysfunction had pulmonary TB, 5% had pleurisy, and 30% had extrapulmonary TB. Eighty-four percent of patients with kidney dysfunction completed the course of treatment with 16% treatment failure and 0.4% developed multidrug-resistant TB; 8% were lost to follow-up and 8% died during the treatment period. This study showed no gender predilection for TB in the general population and immunocompromised. Duration of symptoms before diagnosis of TB was shorter in kidney dysfunction patients in comparison to the general population. TB cultures were the most positive tests whereas bronchoalveolar lavage and skin test were the least positive for detecting TB in the kidney dysfunction group. Improvement in registries and screening is required to enhance the capturing rate and detection among this group, as well as providing accurate data to health authorities and the public about the magnitude, future trends, treatments, and outcomes regarding TB in kidney dysfunction.

Does renal transplantation improve erectile dysfunction in hemodialysed patients? What is the role of associated factors?

PubMed

Pourmand, G; Emamzadeh, A; Moosavi, S; Mehrsai, A; Taherimahmoudi, M; Nikoobakht, M; Saraji, A; Salem, S

2007-05-01

To assess the effect of successful renal transplantation on improvement of erectile function in hemodialysis (HD) patients and the relationship between the degree of patient response and other factors. From September 2002 to November 2005, erectile function of 64 patients on HD for at least 6 months was evaluated pretransplantation and 6 months posttransplantation by International Index of Erectile Function, version 5 (IIEF-5). Sixty four age-matched persons without renal impairment were enrolled as control group to compare erectile dysfunction (ED) prevalence with the HD group. We evaluated duration of HD, age, and site of arterial anastomosis. In an attempt to find predictors of improvement of ED, after kidney transplantation, we performed linear regression analysis with a backward method. The prevalence of ED in HD patients was 87.5%. Although there were some differences in the prevalence of ED between patients older versus younger than 50 years, the difference was not statistically significant. There was no relationship between the duration of dialysis and the severity of ED in HD group. Compared to the pretransplant IIEF-5 score (13.59), there was significant improvement (19.16). In an attempt to find predictors of ED improvement, we used a linear regression analysis with backward method. Pretransplant IIEF-5 score, age at the time of transplant, and anastomosis to the common iliac artery showed significant associations with improvement, but the duration of dialysis and anastomosis to internal iliac or external iliac artery did not. The incidence of ED among hemodialyzed patients is high. Kidney transplantation is the key treatment for this complaint. ED has a major negative impact on the quality of life and family relations. Its treatment is associated with improvement of psychogenic factors. ED is a sensitive topic and many patients will not spontaneously discuss it with their physician, so better to include potency evaluation in posttransplantation list evaluations.

Clinical effectiveness of secondary interventions for restenosis after renal artery stenting

PubMed Central

Simone, Thomas A.; Brooke, Benjamin S.; Goodney, Philip P.; Walsh, Daniel B.; Stone, David H.; Powell, Richard J.; Cronenwett, Jack L.; Nolan, Brian W.

2013-01-01

Objective Secondary interventions for renal artery restenosis (RAS) after renal artery stenting are common, despite limited data about their effectiveness. This study was designed to evaluate the outcomes of endovascular treatment of recurrent RAS. Methods We conducted a retrospective review of patients who underwent renal artery stenting between 2001 and 2011 at Dartmouth-Hitchcock Medical Center. Patients who required secondary interventions were compared with control patients who underwent only primary interventions for RAS. Multivariate regression models were used to identify factors associated with successful outcomes, as measured by changes in blood pressure, estimated glomerular filtration rate, and number of antihypertensive medications required. Results Sixty-five secondary (57 patients) renal interventions were undertaken for recurrent RAS associated with progressive hypertension or renal dysfunction and compared with outcomes after 216 primary (180 patients) renal artery stenting procedures. Patients undergoing primary vs secondary interventions did not differ significantly in the number of preoperative antihypertensive medications used, comorbid conditions, or blood pressure. All primary and secondary interventions were performed with stents and showed no difference in procedural complications. At a mean follow-up of 23 months (range, 1–128 months), similar improvements in renal function and blood pressure were found between patients undergoing primary and secondary interventions, and there was no difference in rates of restenosis or survival between cohorts. Regression models showed that the use of embolic protection devices was associated with improved renal function after primary (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1–3.8; P < .05) and secondary (OR, 4.7; 95% CI, 1.7–12.5; P < .05) interventions, whereas statin therapy was associated with improved renal (OR, 2.0; 95% CI, 1.3–3.2; P < .05) and blood pressure response (OR, 4.1; 95% CI, 1.1–14.9; P < .05) after secondary interventions. Conclusions Patients undergoing secondary interventions for recurrent RAS have outcomes that are comparable with those for primary interventions. These data suggest that repeated endovascular procedures for RAS can be undertaken with similar expectations for clinical improvement and may be further improved by routine use of embolic protection devices and statin therapy. PMID:23688626

γ-Tocotrienol Protects against Mitochondrial Dysfunction and Renal Cell Death

PubMed Central

Bakajsova, Diana; Hayes, Corey; Hauer-Jensen, Martin; Compadre, Cesar M.

2012-01-01

Oxidative stress is a major mechanism of a variety of renal diseases. Tocopherols and tocotrienols are well known antioxidants. This study aimed to determine whether γ-tocotrienol (GT3) protects against mitochondrial dysfunction and renal proximal tubular cell (RPTC) injury caused by oxidants. Primary cultures of RPTCs were injured by using tert-butyl hydroperoxide (TBHP) in the absence and presence of GT3 or α-tocopherol (AT). Reactive oxygen species (ROS) production increased 300% in TBHP-injured RPTCs. State 3 respiration, oligomycin-sensitive respiration, and respiratory control ratio (RCR) decreased 50, 63, and 47%, respectively. The number of RPTCs with polarized mitochondria decreased 54%. F0F1-ATPase activity and ATP content decreased 31 and 65%, respectively. Cell lysis increased from 3% in controls to 26 and 52% at 4 and 24 h, respectively, after TBHP exposure. GT3 blocked ROS production, ameliorated decreases in state 3 and oligomycin-sensitive respirations and F0F1-ATPase activity, and maintained RCR and mitochondrial membrane potential (ΔΨm) in injured RPTCs. GT3 maintained ATP content, blocked RPTC lysis at 4 h, and reduced it to 13% at 24 h after injury. Treatment with equivalent concentrations of AT did not block ROS production and cell lysis and moderately improved mitochondrial respiration and coupling. This is the first report demonstrating the protective effects of GT3 against RPTC injury by: 1) decreasing production of ROS, 2) improving mitochondrial respiration, coupling, ΔΨm, and F0F1-ATPase function, 3) maintaining ATP levels, and 4) preventing RPTC lysis. Our data suggest that GT3 is superior to AT in protecting RPTCs against oxidant injury and may prove therapeutically valuable for preventing renal injury associated with oxidative stress. PMID:22040679

Blood urea nitrogen/creatinine ratio identifies a high-risk but potentially reversible form of renal dysfunction in patients with decompensated heart failure.

PubMed

Brisco, Meredith A; Coca, Steven G; Chen, Jennifer; Owens, Anjali Tiku; McCauley, Brian D; Kimmel, Stephen E; Testani, Jeffrey M

2013-03-01

Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment. Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with in-hospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3-1.8; P<0.001), an association persisting after adjustment for baseline characteristics (odds ratio, 1.4; 95% CI, 1.1-1.8; P=0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1-1.8; P=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate <45) was substantial (hazard ratio, 2.2; 95% CI, 1.6-3.1; P<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (hazard ratio, 1.2; 95% CI, 0.67-2.0; P=0.59; p interaction=0.03). An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients.

Blood Urea Nitrogen/Creatinine Ratio Identifies a High-Risk but Potentially Reversible Form of Renal Dysfunction in Patients With Decompensated Heart Failure

PubMed Central

Brisco, Meredith A.; Coca, Steven G.; Chen, Jennifer; Owens, Anjali Tiku; McCauley, Brian D.; Kimmel, Stephen E.; Testani, Jeffrey M.

2014-01-01

Background Identifying reversible renal dysfunction (RD) in the setting of heart failure is challenging. The goal of this study was to evaluate whether elevated admission blood urea nitrogen/creatinine ratio (BUN/Cr) could identify decompensated heart failure patients likely to experience improvement in renal function (IRF) with treatment. Methods and Results Consecutive hospitalizations with a discharge diagnosis of heart failure were reviewed. IRF was defined as ≥20% increase and worsening renal function as ≥20% decrease in estimated glomerular filtration rate. IRF occurred in 31% of the 896 patients meeting eligibility criteria. Higher admission BUN/Cr was associated with inhospital IRF (odds ratio, 1.5 per 10 increase; 95% confidence interval [CI], 1.3–1.8; P<0.001), an association persisting after adjustment for baseline characteristics (odds ratio, 1.4; 95% CI, 1.1–1.8; P=0.004). However, higher admission BUN/Cr was also associated with post-discharge worsening renal function (odds ratio, 1.4; 95% CI, 1.1–1.8; P=0.011). Notably, in patients with an elevated admission BUN/Cr, the risk of death associated with RD (estimated glomerular filtration rate <45) was substantial (hazard ratio, 2.2; 95% CI, 1.6–3.1; P<0.001). However, in patients with a normal admission BUN/Cr, RD was not associated with increased mortality (hazard ratio, 1.2; 95% CI, 0.67–2.0; P=0.59; p interaction=0.03). Conclusions An elevated admission BUN/Cr identifies decompensated patients with heart failure likely to experience IRF with treatment, providing proof of concept that reversible RD may be a discernible entity. However, this improvement seems to be largely transient, and RD, in the setting of an elevated BUN/Cr, remains strongly associated with death. Further research is warranted to develop strategies for the optimal detection and treatment of these high-risk patients. PMID:23325460

Alterations of Hepatic Metabolism in Chronic Kidney Disease via D-box-binding Protein Aggravate the Renal Dysfunction.

PubMed

Hamamura, Kengo; Matsunaga, Naoya; Ikeda, Eriko; Kondo, Hideaki; Ikeyama, Hisako; Tokushige, Kazutaka; Itcho, Kazufumi; Furuichi, Yoko; Yoshida, Yuya; Matsuda, Masaki; Yasuda, Kaori; Doi, Atsushi; Yokota, Yoshifumi; Amamoto, Toshiaki; Aramaki, Hironori; Irino, Yasuhiro; Koyanagi, Satoru; Ohdo, Shigehiro

2016-03-04

Chronic kidney disease (CKD) is associated with an increase in serum retinol; however, the underlying mechanisms of this disorder are poorly characterized. Here, we found that the alteration of hepatic metabolism induced the accumulation of serum retinol in 5/6 nephrectomy (5/6Nx) mice. The liver is the major organ responsible for retinol metabolism; accordingly, microarray analysis revealed that the hepatic expression of most CYP genes was changed in 5/6Nx mice. In addition, D-box-binding protein (DBP), which controls the expression of several CYP genes, was significantly decreased in these mice. Cyp3a11 and Cyp26a1, encoding key proteins in retinol metabolism, showed the greatest decrease in expression in 5/6Nx mice, a process mediated by the decreased expression of DBP. Furthermore, an increase of plasma transforming growth factor-β1 (TGF-β1) in 5/6Nx mice led to the decreased expression of the Dbp gene. Consistent with these findings, the alterations of retinol metabolism and renal dysfunction in 5/6Nx mice were ameliorated by administration of an anti-TGF-β1 antibody. We also show that the accumulation of serum retinol induced renal apoptosis in 5/6Nx mice fed a normal diet, whereas renal dysfunction was reduced in mice fed a retinol-free diet. These findings indicate that constitutive Dbp expression plays an important role in mediating hepatic dysfunction under CKD. Thus, the aggravation of renal dysfunction in patients with CKD might be prevented by a recovery of hepatic function, potentially through therapies targeting DBP and retinol. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Rhynchophylline Ameliorates Endothelial Dysfunction via Src-PI3K/Akt-eNOS Cascade in the Cultured Intrarenal Arteries of Spontaneous Hypertensive Rats

PubMed Central

Hao, Hui-Feng; Liu, Li-Mei; Pan, Chun-Shui; Wang, Chuan-She; Gao, Yuan-Sheng; Fan, Jing-Yu; Han, Jing-Yan

2017-01-01

Objectives: To examine the protective effect of Rhynchophylline (Rhy) on vascular endothelial function in spontaneous hypertensive rats (SHRs) and the underlying mechanism. Methods: Intrarenal arteries of SHRs and Wistar rats were suspended in myograph for force measurement. Expression and phosphorylation of endothelial nitric oxide (NO) synthase (eNOS), Akt, and Src kinase (Src) were examined by Western blotting. NO production was assayed by ELISA. Results: Rhy time- and concentration-dependently improved endothelium-dependent relaxation in the renal arteries from SHRs, but had no effect on endothelium-independent relaxation in SHR renal arteries. Wortmannin (an inhibitor of phosphatidylinositol 3-kinase) or PP2 (an inhibitor of Src) inhibited the improvement of relaxation in response to acetylcholine by 12 h-incubation with 300 μM Rhy. Western blot analysis revealed that Rhy elevated phosphorylations of eNOS, Akt, and Src in SHR renal arteries. Moreover, wortmannin reversed the increased phosphorylations of Akt and eNOS induced by Rhy, but did not affect the phosphorylation of Src. Furthermore, the enhanced phosphorylations of eNOS, Akt, and Src were blunted by PP2. Importantly, Rhy increased NO production and this effect was blocked by inhibition of Src or PI3K/Akt. Conclusion: The present study provides evidences for the first time that Rhy ameliorates endothelial dysfunction in SHRs through the activation of Src-PI3K/Akt-eNOS signaling pathway. PMID:29187825

Mechanisms of epoxyeicosatrienoic acids to improve cardiac remodeling in chronic renal failure disease.

PubMed

Zhang, Kun; Wang, Ju; Zhang, Huanji; Chen, Jie; Zuo, Zhiyi; Wang, Jingfeng; Huang, Hui

2013-02-15

Both clinical and basic science studies have demonstrated that cardiac remodeling in patients with chronic renal failure (CRF) is very common. It is a key feature during the course of heart failure and an important risk factor for subsequent cardiac mortality. Traditional drugs or therapies rarely have effects on cardiac regression of CRF and cardiovascular events are still the first cause of death. Epoxyeicosatrienoic acids (EETs) are the products of arachidonic acids metabolized by cytochrome P450 epoxygenases. It has been found that EETs have important biological effects including anti-hypertension and anti-inflammation. Recent data suggest that EETs are involved in regulating cardiomyocyte injury, renal dysfunction, chronic kidney disease (CKD)-related risk factors and signaling pathways, all of which play key roles in cardiac remodeling induced by CRF. This review analyzes the literature to identify the possible mechanisms for EETs to improve cardiac remodeling induced by CRF and indicates the therapeutic potential of EETs in it. Copyright © 2012 Elsevier B.V. All rights reserved.

Pathophysiology of Cardiopulmonary Bypass: Current Strategies for the Prevention and Treatment of Anemia, Coagulopathy, and Organ Dysfunction.

PubMed

Esper, Stephen A; Subramaniam, Kathirvel; Tanaka, Kenichi A

2014-06-01

The techniques and equipment of cardiopulmonary bypass (CPB) have evolved over the past 60 years, and numerous numbers of cardiac surgical procedures are conducted around the world using CPB. Despite more widespread applications of percutaneous coronary and valvular interventions, the need for cardiac surgery using CPB remains the standard approach for certain cardiac pathologies because some patients are ineligible for percutaneous procedures, or such procedures are unsuccessful in some. The ageing patient population for cardiac surgery poses a number of clinical challenges, including anemia, decreased cardiopulmonary reserve, chronic antithrombotic therapy, neurocognitive dysfunction, and renal insufficiency. The use of CPB is associated with inductions of systemic inflammatory responses involving both cellular and humoral interactions. Inflammatory pathways are complex and redundant, and thus, the reactions can be profoundly amplified to produce a multiorgan dysfunction that can manifest as capillary leak syndrome, coagulopathy, respiratory failure, myocardial dysfunction, renal insufficiency, and neurocognitive decline. In this review, pathophysiological aspects of CPB are considered from a practical point of view, and preventive strategies for hemodilutional anemia, coagulopathy, inflammation, metabolic derangement, and neurocognitive and renal dysfunction are discussed. © The Author(s) 2014.

Graphene Oxide/Ag Nanoparticles Cooperated with Simvastatin as a High Sensitive X-Ray Computed Tomography Imaging Agent for Diagnosis of Renal Dysfunctions.

PubMed

Li, Zhan; Tian, Longlong; Liu, Jianli; Qi, Wei; Wu, Qiang; Wang, Haijing; Ali, Mohammad Chand; Wu, Wangsuo; Qiu, Hongdeng

2017-09-01

Graphene oxides (GO) are attracting much attention in the diagnosis and therapy of the subcutaneous tumor as a novel biomaterial, but its diagnosis to tissue dysfunction is yet to be found. Here, a novel application of GO for diagnosis of renal dysfunction via contrast-enhanced computed tomography (CT) is proposed. In order to serve as contrast-enhanced agent, Ag nanoparticles (AgNPs) are composited on the surface of GO to promote its X-ray absorption, and then simvastatin is coinjected for eliminating in vivo toxicity induced by AgNPs. It is found that GO/AgNPs can enhance the imaging of CT into the lung, liver, and kidney of mice for a long circulation time (≈24 h) and a safety profile in vivo in the presence of simvastatin. Interestingly, the lower dose of GO/AgNPs (≈0.5 mg per kg bw) shows an excellent performance for CT imaging of renal perfusion, and visually exhibits the right renal dysfunction in model mice. Hence, this work suggests that graphene nanoparticles will play a vital role for the future medical translational development including drug carrier, biosensing, and disease therapy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Application of 80-kVp scan and raw data-based iterative reconstruction for reduced iodine load abdominal-pelvic CT in patients at risk of contrast-induced nephropathy referred for oncological assessment: effects on radiation dose, image quality and renal function.

PubMed

Nagayama, Yasunori; Tanoue, Shota; Tsuji, Akinori; Urata, Joji; Furusawa, Mitsuhiro; Oda, Seitaro; Nakaura, Takeshi; Utsunomiya, Daisuke; Yoshida, Eri; Yoshida, Morikatsu; Kidoh, Masafumi; Tateishi, Machiko; Yamashita, Yasuyuki

2018-05-01

To evaluate the image quality, radiation dose, and renal safety of contrast medium (CM)-reduced abdominal-pelvic CT combining 80-kVp and sinogram-affirmed iterative reconstruction (SAFIRE) in patients with renal dysfunction for oncological assessment. We included 45 patients with renal dysfunction (estimated glomerular filtration rate  <45 ml per min per 1.73 m 2 ) who underwent reduced-CM abdominal-pelvic CT (360 mgI kg -1 , 80-kVp, SAFIRE) for oncological assessment. Another 45 patients without renal dysfunction (estimated glomerular filtration rate >60 ml per lmin per 1.73 m 2 ) who underwent standard oncological abdominal-pelvic CT (600 mgI kg -1 , 120-kVp, filtered-back projection) were included as controls. CT attenuation, image noise, and contrast-to-noise ratio (CNR) were compared. Two observers performed subjective image analysis on a 4-point scale. Size-specific dose estimate and renal function 1-3 months after CT were measured. The size-specific dose estimate and iodine load of 80-kVp protocol were 32 and 41%,, respectively, lower than of 120-kVp protocol (p < 0.01). CT attenuation and contrast-to-noise ratio of parenchymal organs and vessels in 80-kVp images were significantly better than those of 120-kVp images (p < 0.05). There were no significant differences in quantitative or qualitative image noise or subjective overall quality (p > 0.05). No significant kidney injury associated with CM administration was observed. 80-kVp abdominal-pelvic CT with SAFIRE yields diagnostic image quality in oncology patients with renal dysfunction under substantially reduced iodine and radiation dose without renal safety concerns. Advances in knowledge: Using 80-kVp and SAFIRE allows for 40% iodine load and 32% radiation dose reduction for abdominal-pelvic CT without compromising image quality and renal function in oncology patients at risk of contrast-induced nephropathy.

Analysis of the Sensitivity and Specificity of Noninvasive Imaging Tests for the Diagnosis of Renal Artery Stenosis

PubMed Central

Borelli, Flavio Antonio de Oliveira; Pinto, Ibraim M. F.; Amodeo, Celso; Smanio, Paola E. P.; Kambara, Antonio M.; Petisco, Ana Claudia G.; Moreira, Samuel M.; Paiva, Ricardo Calil; Lopes, Hugo Belotti; Sousa, Amanda G. M. R.

2013-01-01

Background Aging and atherosclerosis are related to renovascular hypertension in elderly individuals. Regardless of comorbidities, renal artery stenosis is itself an important cause of cardiovascular morbidity and mortality. Objective To define the sensitivity, specificity, positive predictive value, and negative predictive value of noninvasive imaging tests used in the diagnosis of renal artery stenosis. Methods In a group of 61 patients recruited, 122 arteries were analized, thus permitting the definition of sensitivity, specificity, and the relative contribution of each imaging study performed (Doppler, scintigraphy and computed tomographic angiography in comparison to renal arteriography). Results The mean age was 65.43 years (standard deviation: 8.7). Of the variables related to the study population that were compared to arteriography, two correlated with renal artery stenosis, renal dysfunction and triglycerides. The median glomerular filtration rate was 52.8 mL/min/m2. Doppler showed sensitivity of 82.90%, specificity of 70%, a positive predictive value of 85% and negative predictive value of 66.70%. For tomography, sensitivity was 66.70%, specificity 80%, positive predictive value 87.50% and negative predictive value 55.20%. With these findings, we could identify the imaging tests that best detected stenosis. Conclusion Tomography and Doppler showed good quality and efficacy in the diagnosis of renal artery stenosis, with Doppler having the advantage of not requiring the use of contrast medium for the assessment of a disease that is common in diabetics and is associated with renal dysfunction and severe left ventricular dysfunction. PMID:24061685

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.

Extracorporeal Life Support Bridge to Ventricular Assist Device: The Double Bridge Strategy.

PubMed

Marasco, Silvana F; Lo, Casey; Murphy, Deirdre; Summerhayes, Robyn; Quayle, Margaret; Zimmet, Adam; Bailey, Michael

2016-01-01

In patients requiring left ventricular assist device (LVAD) support, it can be difficult to ascertain suitability for long-term mechanical support with LVAD and eventual transplantation. LVAD implantation in a shocked patient is associated with increased morbidity and mortality. Interest is growing in the utilization of extracorporeal life support (ECLS) as a bridge-to-bridge support for these critically unwell patients. Here, we reviewed our experience with ECLS double bridging. We hypothesized that ECLS double bridging would stabilize end-organ dysfunction and reduce ventricular assist device (VAD) implant perioperative mortality. We conducted a retrospective review of prospectively collected data for 58 consecutive patients implanted with a continuous-flow LVAD between January 2010 and December 2013 at The Alfred Hospital, Melbourne, Victoria, Australia. Twenty-three patients required ECLS support pre-LVAD while 35 patients underwent LVAD implantation without an ECLS bridge. Preoperative morbidity in the ECLS bridge group was reflected by increased postoperative intensive care duration, blood loss, blood product use, and postoperative renal failure, but without negative impact upon survival when compared with the no ECLS group. ECLS stabilization improved end-organ function pre-VAD implant with significant improvements in hepatic and renal dysfunction. This series demonstrates that the use of ECLS bridge to VAD stabilizes end-organ dysfunction and reduces VAD implant perioperative mortality from that traditionally reported in these "crash and burn" patients. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Association of N-Terminal Pro-B-Type Natriuretic Peptide with Left Ventricular Structure and Function in Chronic Kidney Disease (From the Chronic Renal Insufficiency Cohort [CRIC])

PubMed Central

Mishra, Rakesh K.; Li, Yongmei; Ricardo, Ana C.; Yang, Wei; Keane, Martin; Cuevas, Magdalena; Christenson, Robert; DeFilippi, Christopher; Chen, Jing; He, Jiang; Kallem, Radhakrishna R.; Raj, Dominic S.; Schelling, Jeffrey R.; Wright, Jackson; Go, Alan S.; Shlipak, Michael G.

2017-01-01

We evaluated the cross-sectional associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with cardiac structural and functional abnormalities in a cohort of chronic kidney disease (CKD) patients without clinical heart failure (HF), the Chronic Renal Insufficiency Cohort (n=3,232). Associations of NT-proBNP with echocardiographically determined left ventricular (LV) mass and LV systolic and diastolic function were evaluated by multivariable logistic and linear regression models. Reclassification of participants’ predicted risk of LV hypertrophy (LVH), systolic and diastolic dysfunction was performed using a category-free net reclassification improvement (NRI) index that compared a clinical model with and without NT-proBNP. The median (interquartile range) NT-proBNP was 126.6 pg/ml (55.5–303.7). The highest quartile of NT-proBNP was associated with nearly three-fold odds of LVH (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.8–4.0) and LV systolic dysfunction (2.7, 1.7–4.5) and two-fold odds of diastolic dysfunction (2.0, 1.3–2.9) in the fully adjusted models. When evaluated alone as a screening test, NT-proBNP functioned modestly for the detection of LVH (area under the curve, AUC 0.66) and LV systolic dysfunction (AUC 0.62), and poorly for the detection of diastolic dysfunction (AUC 0.51). However, when added to the clinical model, NT-proBNP significantly reclassified participants’ likelihood of having LVH (NRI 0.14, 95% CI 0.13–0.15; p<0.001) and LV systolic dysfunction (0.28, 0.27–0.30; p<0.001), but not diastolic dysfunction (0.10, 0.10–0.11; p=0.07). In conclusion, in this large CKD cohort without HF, NT-proBNP had strong associations with prevalent LVH and LV systolic dysfunction. PMID:23178053

Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats.

PubMed

Quesada, Andrés; Vargas, Félix; Montoro-Molina, Sebastián; O'Valle, Francisco; Rodríguez-Martínez, María Dolores; Osuna, Antonio; Prieto, Isabel; Ramírez, Manuel; Wangensteen, Rosemary

2012-01-01

This study analyzes the fluorimetric determination of alanyl- (Ala), glutamyl- (Glu), leucyl-cystinyl- (Cys) and aspartyl-aminopeptidase (AspAp) urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group) received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG), albumin, and neutrophil gelatinase-associated lipocalin (NGAL). Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p<0.011; r(2)>0.259) with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.

Pretransplantation Cystatin C, but not Creatinine, Predicts 30-day Cardiovascular Events and Mortality in Liver Transplant Recipients With Normal Serum Creatinine Levels.

PubMed

Kwon, H-M; Moon, Y-J; Jung, K-W; Jun, I-G; Song, J-G; Hwang, G-S

2018-05-01

The connection between renal dysfunction and cardiovascular dysfunction has been consistently shown. In patients with liver cirrhosis, renal dysfunction shows a tight correlation with prognosis after liver transplantation (LT); therefore, precise renal assessment is mandatory. Cystatin C, a sensitive biomarker for assessing renal function, has shown superiority in detecting mild renal dysfunction compared to classical biomarker creatinine. In this study, we aimed to compare cystatin C and creatinine in predicting 30-day major cardiovascular events (MACE) and all-cause mortality in LT recipients with normal serum creatinine levels. Between May 2010 and October 2015, 1181 LT recipients (mean Model for End-stage Liver Disease score 12.1) with pretransplantation creatinine level ≤1.4 mg/dL were divided into tertiles according to each renal biomarker. The 30-day MACE was a composite of troponin I >0.2 ng/mL, arrhythmia, congestive heart failure, death, and cerebrovascular events. The highest tertile of cystatin C (≥0.95 mg/L) was associated with a higher risk for a 30-day MACE event (odds ratio: 1.62; 95% confidence interval: 1.07 to 2.48) and higher risk of death (hazard ratio: 1.96; 95% confidence interval: 1.04 to 3.67) than the lowest tertile (<0.74 mg/L) after multivariate adjustments. However, the highest tertile of creatinine level showed neither increasing MACE event rate nor worse survival rate compared with the lowest tertile (both insignificant after multivariate adjustment). Pretransplantation cystatin C is superior in risk prediction of MACE and all-cause mortality in LT recipients with normal creatinine, compared to creatinine. It would assist further risk stratification which may not be detected with creatinine. Copyright © 2018 Elsevier Inc. All rights reserved.

Low molecular weight fucoidan protects renal tubular cells from injury induced by albumin overload.

PubMed

Jia, Yingli; Sun, Yi; Weng, Lin; Li, Yingjie; Zhang, Quanbin; Zhou, Hong; Yang, Baoxue

2016-08-22

Albuminuria is a causative and aggravating factor for progressive renal damage in chronic kidney disease (CKD). The aim of this study was to determine if low molecular weight fucoidan (LMWF) could protect renal function and tubular cells from albumin overload caused injury. Treatment with 10 mg/g bovine serum albumin caused renal dysfunction, morphological changes, and overexpression of inflammation and fibrosis associated proteins in 129S2/Sv mice. LMWF (100 mg/kg) protected against kidney injury and renal dysfunction with decreased blood creatinine by 34% and urea nitrogen by 25%, increased creatinine clearance by 48%, and decreased significantly urinary albumin concentration. In vitro proximal tubule epithelial cell (NRK-52E) model showed that LMWF dose-dependently inhibited overexpression of proinflammatory and profibrotic factors, oxidative stress and apoptosis caused by albumin overload. These experimental results indicate that LMWF protects against albumin overload caused renal injury by inhibiting inflammation, fibrosis, oxidative stress and apoptosis, which suggests that LMWF could be a promising candidate drug for preventing CKD.

Glutaric Aciduria Type 1 and Acute Renal Failure: Case Report and Suggested Pathomechanisms.

PubMed

du Moulin, Marcel; Thies, Bastian; Blohm, Martin; Oh, Jun; Kemper, Markus J; Santer, René; Mühlhausen, Chris

2018-01-01

Glutaric aciduria type 1 (GA1) is caused by deficiency of the mitochondrial matrix enzyme glutaryl-CoA dehydrogenase (GCDH), leading to accumulation of glutaric acid (GA) and 3-hydroxyglutaric acid (3OHGA) in tissues and body fluids. During catabolic crises, GA1 patients are prone to the development of striatal necrosis and a subsequent irreversible movement disorder during a time window of vulnerability in early infancy. Thus, GA1 had been considered a pure "cerebral organic aciduria" in the past. Single case reports have indicated the occurrence of acute renal dysfunction in children affected by GA1. In addition, growing evidence arises that GA1 patients may develop chronic renal failure during adulthood independent of the previous occurrence of encephalopathic crises. The underlying mechanisms are yet unknown. Here we report on a 3-year-old GA1 patient who died following the development of acute renal failure most likely due to haemolytic uraemic syndrome associated with a pneumococcal infection. We hypothesise that known GA1 pathomechanisms, namely the endothelial dysfunction mediated by 3OHGA, as well as the transporter mechanisms for the urinary excretion of GA and 3OHGA, are involved in the development of glomerular and tubular dysfunction, respectively, and may contribute to a pre-disposition of GA1 patients to renal disease. We recommend careful differential monitoring of glomerular and tubular renal function in GA1 patients.

Early renal dysfunction after contrast media administration despite prophylactic hydration.

PubMed

Burchardt, Pawel; Guzik, Przemyslaw; Tabaczewski, Piotr; Synowiec, Tomasz; Bogdan, Monika; Faner, Paula; Chmielarz-Sobocińska, Anna; Palasz, Anna

2013-06-01

The actual incidence of renal dysfunction after contrast media administration seems to be underestimated, especially in the context of epidemiological data. There are only few data concerning the monitoring of impaired kidney function within a few hours after iodine contrast medium application. Hence, the purpose of this study is to observe the incidence of early renal function deterioration within 12-18 h after administration of iodine contrast media in patients scheduled for elective coronary angiography, who were intravenously and orally hydrated. In addition, the project aims to reclassify the contrast induced nephropathy phenomenon, by identification of early markers of renal dysfunction. Morphology, electrolytes, blood urea nitrogen (BUN), creatinine, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein, and total cholesterol levels were assessed with the use of typical laboratory techniques in 319 patients referred for coronary angiography. We demonstrated that early deterioration of renal function in patients 12-18 h after administration of contrast during imaging tests (even when appropriate prophylactic hydration was used), may occurred just as an increase (or no change) of serum creatinine level and BUN level and a decrease of creatinine clearance and glomerular filtration rate. Depending on the parameter, the phenomenon can be found in 13-28 % of all respondents. Early renal function impairment defined as above was almost 2 and 2.22 × 10(3) times (respectively) more frequently observed in our study than contrast induced nephropathy defined by current definitions.

Protection against renal ischemia-reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ.

PubMed

Dare, Anna J; Bolton, Eleanor A; Pettigrew, Gavin J; Bradley, J Andrew; Saeb-Parsy, Kourosh; Murphy, Michael P

2015-08-01

Ischemia-reperfusion (IR) injury to the kidney occurs in a range of clinically important scenarios including hypotension, sepsis and in surgical procedures such as cardiac bypass surgery and kidney transplantation, leading to acute kidney injury (AKI). Mitochondrial oxidative damage is a significant contributor to the early phases of IR injury and may initiate a damaging inflammatory response. Here we assessed whether the mitochondria targeted antioxidant MitoQ could decrease oxidative damage during IR injury and thereby protect kidney function. To do this we exposed kidneys in mice to in vivo ischemia by bilaterally occluding the renal vessels followed by reperfusion for up to 24h. This caused renal dysfunction, measured by decreased creatinine clearance, and increased markers of oxidative damage. Administering MitoQ to the mice intravenously 15 min prior to ischemia protected the kidney from damage and dysfunction. These data indicate that mitochondrial oxidative damage contributes to kidney IR injury and that mitochondria targeted antioxidants such as MitoQ are potential therapies for renal dysfunction due to IR injury. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Protection against renal ischemia–reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ

PubMed Central

Dare, Anna J.; Bolton, Eleanor A.; Pettigrew, Gavin J.; Bradley, J. Andrew; Saeb-Parsy, Kourosh; Murphy, Michael P.

2015-01-01

Ischemia–reperfusion (IR) injury to the kidney occurs in a range of clinically important scenarios including hypotension, sepsis and in surgical procedures such as cardiac bypass surgery and kidney transplantation, leading to acute kidney injury (AKI). Mitochondrial oxidative damage is a significant contributor to the early phases of IR injury and may initiate a damaging inflammatory response. Here we assessed whether the mitochondria targeted antioxidant MitoQ could decrease oxidative damage during IR injury and thereby protect kidney function. To do this we exposed kidneys in mice to in vivo ischemia by bilaterally occluding the renal vessels followed by reperfusion for up to 24 h. This caused renal dysfunction, measured by decreased creatinine clearance, and increased markers of oxidative damage. Administering MitoQ to the mice intravenously 15 min prior to ischemia protected the kidney from damage and dysfunction. These data indicate that mitochondrial oxidative damage contributes to kidney IR injury and that mitochondria targeted antioxidants such as MitoQ are potential therapies for renal dysfunction due to IR injury. PMID:25965144

Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model.

PubMed

Shao, Minglong; Yu, Lechu; Zhang, Fangfang; Lu, Xuemian; Li, Xiaokun; Cheng, Peng; Lin, Xiufei; He, Luqing; Jin, Shunzi; Tan, Yi; Yang, Hong; Zhang, Chi; Cai, Lu

2015-07-01

The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways. Copyright © 2015 the American Physiological Society.

Additive protection by LDR and FGF21 treatment against diabetic nephropathy in type 2 diabetes model

PubMed Central

Shao, Minglong; Yu, Lechu; Zhang, Fangfang; Lu, Xuemian; Li, Xiaokun; Cheng, Peng; Lin, Xiufei; He, Luqing; Jin, Shunzi; Tan, Yi; Yang, Hong; Cai, Lu

2015-01-01

The onset of diabetic nephropathy (DN) is associated with both systemic and renal changes. Fibroblast growth factor (FGF)-21 prevents diabetic complications mainly by improving systemic metabolism. In addition, low-dose radiation (LDR) protects mice from DN directly by preventing renal oxidative stress and inflammation. In the present study, we tried to define whether the combination of FGF21 and LDR could further prevent DN by blocking its systemic and renal pathogeneses. To this end, type 2 diabetes was induced by feeding a high-fat diet for 12 wk followed by a single dose injection of streptozotocin. Diabetic mice were exposed to 50 mGy LDR every other day for 4 wk with and without 1.5 mg/kg FGF21 daily for 8 wk. The changes in systemic parameters, including blood glucose levels, lipid profiles, and insulin resistance, as well as renal pathology, were examined. Diabetic mice exhibited renal dysfunction and pathological abnormalities, all of which were prevented significantly by LDR and/or FGF21; the best effects were observed in the group that received the combination treatment. Our studies revealed that the additive renal protection conferred by the combined treatment against diabetes-induced renal fibrosis, inflammation, and oxidative damage was associated with the systemic improvement of hyperglycemia, hyperlipidemia, and insulin resistance. These results suggest that the combination treatment with LDR and FGF21 prevented DN more efficiently than did either treatment alone. The mechanism behind these protective effects could be attributed to the suppression of both systemic and renal pathways. PMID:25968574

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.

Hypermethylations of RASAL1 and KLOTHO is associated with renal dysfunction in a Chinese population environmentally exposed to cadmium

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

Zhang, Chen; Liang, Yihuai; Key Laboratory of Public Health Safety, Ministry of Education, 130 DongAn Road, Shanghai 200032

2013-08-15

Exposure to cadmium (Cd) can affect both DNA methylation and renal function, but there are few examples of the association between epigenetic markers and Cd-induced kidney damage. It has been suggested that hypermethylation of the genes RASAL1 and KLOTHO is associated with renal fibrogenesis. To investigate whether hypermethylation of RASAL1 and KLOTHO in peripheral blood DNA can be associated with Cd exposure and/or Cd-induced renal dysfunction, the degrees of methylation of RASAL1 and KLOTHO in peripheral blood DNA from 81 residents in Cd-polluted and non-polluted areas were measured using bisulfate-PCR-pyrosequencing. Changes in blood cadmium (BCd), urinary cadmium (UCd), and kidneymore » parameters were measured, and the glomerular filtration rate (eGFR) was estimated. The levels of BCd and UCd correlated positively with the levels of DNA methylation in RASAL1 and in KLOTHO. The more heavily exposed residents (BCd, 4.23–13.22 μg/L; UCd, 8.65–32.90 μg/g creatinine) exhibited obvious renal dysfunction. Notably, when Cd concentration in blood and urine was adjusted, the increased methylation level in RASAL1 was inversely correlated with eGFR (P < 0.01) but the relationship between hypermethylation of KLOTHO and eGFR was not statistically significant. The methylation of RASAL1 increased along with the increased abnormal prevalence of eGFR. Our findings suggest that Cd exposure can induce the hypermethylation of RASAL1 and KLOTHO. Hypermethylation of RASAL1 may be an indicator of the progress for chronic kidney disease. - Highlights: • A long term heavily Cd exposure induced renal dysfunction. • Cd exposure correlated positively with DNA methylation in RASAL1 and KLOTHO. • Hypermethylation of RASAL1 correlated with adjusted renal function indicators.« less

The effects of heart failure on renal function.

PubMed

Udani, Suneel M; Koyner, Jay L

2010-08-01

Heart-kidney interactions have been increasingly recognized by clinicians and researchers who study and treat heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of concomitant cardiac and renal dysfunction remains unclear; however, evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation. 2010 Elsevier Inc. All rights reserved.

The Effects of Heart Failure on Renal Function

PubMed Central

Udani, Suneel M; Koyner, Jay L

2010-01-01

Summary Heart-kidney interactions have been increasingly recognized by clinicians and researchers involved in the study and treatment of heart failure and kidney disease. A classification system has been developed to categorize the different manifestations of cardiac and renal dysfunction. Recent work has highlighted the significant negative prognostic effect of worsening renal function on outcomes for individuals with heart failure. The etiology of the concomitant cardiac and renal dysfunction remains unclear; however, increasing evidence supports alternatives to the established theory of underfilling, including effects of venous congestion and changes in intra-abdominal pressure. Conventional therapy focuses on blockade of the renin-angiotensin-aldosterone system with expanding use of direct renin and aldosterone antagonists. Novel therapeutic interventions using extracorporeal therapy and antagonists of the adenosine pathway show promise and require further investigation. PMID:20621250

Alamandine reduces leptin expression through the c-Src/p38 MAP kinase pathway in adipose tissue.

PubMed

Uchiyama, Tsuyoshi; Okajima, Fumikazu; Mogi, Chihiro; Tobo, Ayaka; Tomono, Shoichi; Sato, Koichi

2017-01-01

Obesity is associated with an increased risk of diabetes mellitus, hypertension, and renal dysfunction. Angiotensin 1-7 and alamandine are heptameric renin angiotensin system peptide hormones. Further, alamandine levels increase with renal dysfunction. In the cardiovascular system, angiotensin 1-7 and alamandine produce similar improvements and counterbalance angiotensin II in regulating vascular function. We aimed to determine whether the effect of alamandine on leptin expression and secretion in adipocytes was similar to that of angiotensin 1-7. We studied isolated peri-renal visceral adipose tissue and peri-renal isolated visceral adipocytes from male Wistar rats. Angiotensin II from 0.01 to 10nM had no effect on leptin expression. Angiotensin 1-7 (1 nM) increased leptin secretion and expression, whereas alamandine (1 nM) decreased leptin secretion and expression in adipose tissue and isolated adipocytes and reduced blood leptin levels in vivo. These effects were mediated by Gq, c-Src, p38 mitogen-activated protein, and IκB activation. Additionally, alamandine induced nitric oxide expression via inducible nitric oxidase synthase and plasminogen activator inhibitor 1 expression in adipose tissue and isolated adipocytes. Angiotensin 1-7 and alamandine produced opposing effects on leptin expression and secretion in adipose tissue. This result suggests that the action of Mas (angiotensin 1-7 receptor) and Mas-related G-protein coupled receptor D in adipocytes exhibited opposing actions similar to angiotensin II type 1 and type 2 receptors.

Pink1/Parkin-mediated mitophagy play a protective role in cisplatin induced renal tubular epithelial cells injury.

PubMed

Zhao, Chuanyan; Chen, Zhuyun; Xu, Xueqiang; An, Xiaofei; Duan, Suyan; Huang, Zhimin; Zhang, Chengning; Wu, Lin; Zhang, Bo; Zhang, Aihua; Xing, Changying; Yuan, Yanggang

2017-01-15

Cisplatin often causes acute kidney injury (AKI) in the treatment of a wide variety of malignancies. Mitochondrial dysfunction is one of the main reasons for cisplatin nephrotoxicity. Previous study showed that Pink1 and Parkin play central roles in regulating the mitophagy, which is a key protective mechanism by specifically eliminating dysfunctional or damaged mitochondria. However, the mechanisms that modulate mitophagy in cisplatin induced nephrotoxicity remain to be elucidated. The purpose of this study was to investigate the effects of Pink1/Parkin pathway in mitophagy, mitochondrial dysfunction and renal proximal tubular cells injury during cisplatin treatment. In cultured human renal proximal tubular cells, we found that knockdown of Pink1/Parkin induced the aggravation of mitochondrial function, leading to the increase of cell injury through inhibition of mitophagy. Additionally, the overexpression of Pink1/Parkin protected against cisplatin-induced mitochondrial dysfunction and cell injury by promoting mitophagy. Our results provide clear evidence that Pink1/Parkin-dependent mitophagy has identified potential targets for the treatment of cisplatin-induced AKI. Copyright © 2016 Elsevier Inc. All rights reserved.

Endothelial sirtuin 1 deficiency perpetrates nephrosclerosis through downregulation of matrix metalloproteinase-14: relevance to fibrosis of vascular senescence.

PubMed

Vasko, Radovan; Xavier, Sandhya; Chen, Jun; Lin, Chi Hua Sarah; Ratliff, Brian; Rabadi, May; Maizel, Julien; Tanokuchi, Rina; Zhang, Frank; Cao, Jian; Goligorsky, Michael S

2014-02-01

Sirtuin 1 (SIRT1) depletion in vascular endothelial cells mediates endothelial dysfunction and premature senescence in diverse cardiovascular and renal diseases. However, the molecular mechanisms underlying these pathologic effects remain unclear. Here, we examined the phenotype of a mouse model of vascular senescence created by genetically ablating exon 4 of Sirt1 in endothelial cells (Sirt1(endo-/-)). Under basal conditions, Sirt1(endo-/-) mice showed impaired endothelium-dependent vasorelaxation and angiogenesis, and fibrosis occurred spontaneously at low levels at an early age. In contrast, induction of nephrotoxic stress (acute and chronic folic acid-induced nephropathy) in Sirt1(endo-/-) mice resulted in robust acute renal functional deterioration followed by an exaggerated fibrotic response compared with control animals. Additional studies identified matrix metalloproteinase-14 (MMP-14) as a target of SIRT1. In the kidneys of Sirt1(endo-/-) mice, impaired angiogenesis, reduced matrilytic activity, and retention of the profibrotic cleavage substrates tissue transglutaminase and endoglin accompanied MMP-14 suppression. Furthermore, restoration of MMP-14 expression in SIRT1-depeleted mice improved angiogenic and matrilytic functions of the endothelium, prevented renal dysfunction, and attenuated nephrosclerosis. Our findings establish a novel mechanistic molecular link between endothelial SIRT1 depletion, downregulation of MMP-14, and the development of nephrosclerosis.

Acute kidney injury in acute liver failure: a review.

PubMed

Moore, Joanna K; Love, Eleanor; Craig, Darren G; Hayes, Peter C; Simpson, Kenneth J

2013-11-01

Acute liver failure is a rare and often devastating condition consequent on massive liver cell necrosis that frequently affects young, previously healthy individuals resulting in altered cognitive function, coagulopathy and peripheral vasodilation. These patients frequently develop concurrent acute kidney injury (AKI). This abrupt and sustained decline in renal function, through a number of pathogenic mechanisms such as renal hypoperfusion, direct drug-induced nephrotoxicity or sepsis/systemic inflammatory response contributes to increased morbidity and is strongly associated with a worse prognosis. Improved understanding of the pathophysiology AKI in the context of acute liver failure may be beneficial in a number of areas; the development of new and sensitive biomarkers of renal dysfunction, refining prognosis and organ allocation, and ultimately leading to the development of novel treatment strategies, these issues are discussed in more detail in this expert review.

Therapeutic Effects of Human Amniotic Fluid-Derived Stem Cells on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

PubMed Central

Yin, Zhongcheng; Zhou, Xudong; Li, Xiaoju; Xiao, Aiguo

2013-01-01

Interstitial fibrosis is regarded as the main pathway for the progression of chronic kidney disease (CKD) and is often associated with severe renal dysfunction. Stem cell-based therapies may provide alternative approaches for the treatment of CKD. Human amniotic fluid-derived stem cells (hAFSCs) are a novel stem cell population, which exhibit both embryonic and mesenchymal stem cell characteristics. Herein, the present study investigated whether the transplantation of hAFSCs into renal tissues could improve renal interstitial fibrosis in a murine model of unilateral ureteral obstruction (UUO). We showed that hAFSCs provided a protective effect and alleviated interstitial fibrosis as reflected by an increase in microvascular density; additionally, hAFSCs treatment beneficially modulated protein levels of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α (HIF-1α) and transforming growth factor-β1 (TGF-β1). Therefore, we hypothesize that hAFSCs could represent an alternative, readily available source of stem cells that can be applied for the treatment of renal interstitial fibrosis. PMID:23724119

Sinomenine alleviates high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the activation of RhoA/ROCK signaling pathway.

PubMed

Yin, Qingqiao; Xia, Yuanyu; Wang, Guan

2016-09-02

As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression in HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

RenalGuard system to prevent contrast-induced acute kidney injury in Japanese patients with renal dysfunction; RESPECT KIDNEY study.

PubMed

Katoh, Hiromasa; Nozue, Tsuyoshi; Horie, Kazuki; Sozu, Takashi; Inoue, Naoto; Michishita, Ichiro

2018-05-05

Increasing the urine flow rate (UFR) reduces the toxic effect of contrast media. Use of the RenalGuard system enables the achievement of a high UFR by maintaining intravascular volume and prevents the development of contrast-induced acute kidney injury (CI-AKI). However, the efficacy and safety of RenalGuard system have not yet been evaluated in Japan. This multicenter prospective study evaluated the efficacy and safety of the RenalGuard therapy in preventing CI-AKI development in 60 Japanese patients with renal dysfunction [estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m 2 ] undergoing catheter procedures. Baseline eGFR and Mehran's CIN (contrast-induced nephropathy) risk score were 35.1 ± 8.5 mL/min/1.73 m 2 and 11.7 ± 4.3, respectively. Regardless of this high-risk profile, the incidence of CI-AKI was 8.6% (5/58) compared with the 26.1% incidence estimated by the CIN risk score. Moreover, two-sided 95% (Fisher's) exact confidence interval was 2.9-19.0 and its upper limit (i.e., 19.0) was less than the prespecified threshold incidence of 25.0. Univariate logistic regression analysis demonstrated that the UFR during catheter procedure was one of the most important factor associated with CI-AKI (odds ratio 0.99, confidence interval 0.98-1.00, p = 0.03). In conclusion, RenalGuard therapy may prevent CI-AKI development in Japanese patients with renal dysfunction. Further large-scale prospective multicenter studies are necessary to confirm our findings.

Evidence of uncoupling between renal dysfunction and injury in cardiorenal syndrome: insights from the BIONICS study.

PubMed

Legrand, Matthieu; De Berardinis, Benedetta; Gaggin, Hanna K; Magrini, Laura; Belcher, Arianna; Zancla, Benedetta; Femia, Alexandra; Simon, Mandy; Motiwala, Shweta; Sambhare, Rasika; Di Somma, Salvatore; Mebazaa, Alexandre; Vaidya, Vishal S; Januzzi, James L

2014-01-01

The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153).

Evidence of Uncoupling between Renal Dysfunction and Injury in Cardiorenal Syndrome: Insights from the BIONICS Study

PubMed Central

Legrand, Matthieu; De Berardinis, Benedetta; Gaggin, Hanna K.; Magrini, Laura; Belcher, Arianna; Zancla, Benedetta; Femia, Alexandra; Simon, Mandy; Motiwala, Shweta; Sambhare, Rasika; Di Somma, Salvatore; Mebazaa, Alexandre; Vaidya, Vishal S.; Januzzi, James L.; (GREAT), from the Global Research on Acute Conditions Team

2014-01-01

Objective The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). Methods In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. Results 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. Conclusions In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153). PMID:25386851

High serum creatinine nonlinearity: a renal vital sign?

PubMed

Palant, Carlos E; Chawla, Lakhmir S; Faselis, Charles; Li, Ping; Pallone, Thomas L; Kimmel, Paul L; Amdur, Richard L

2016-08-01

Patients with chronic kidney disease (CKD) may have nonlinear serum creatinine concentration (SC) trajectories, especially as CKD progresses. Variability in SC is associated with renal failure and death. However, present methods for measuring SC variability are unsatisfactory because they blend information about SC slope and variance. We propose an improved method for defining and calculating a patient's SC slope and variance so that they are mathematically distinct, and we test these methods in a large sample of US veterans, examining the correlation of SC slope and SC nonlinearity (SCNL) and the association of SCNL with time to stage 4 CKD (CKD4) and death. We found a strong correlation between SCNL and rate of CKD progression, time to CKD4, and time to death, even in patients with normal renal function. We therefore argue that SCNL may be a measure of renal autoregulatory dysfunction that provides an early warning sign for CKD progression. Copyright © 2016 the American Physiological Society.

Hepatitis A complicated with acute renal failure and high hepatocyte growth factor: A case report.

PubMed

Oe, Shinji; Shibata, Michihiko; Miyagawa, Koichiro; Honma, Yuichi; Hiura, Masaaki; Abe, Shintaro; Harada, Masaru

2015-08-28

A 58-year-old man was admitted to our hospital. Laboratory data showed severe liver injury and that the patient was positive for immunoglobulin M anti-hepatitis A virus (HAV) antibodies. He was also complicated with severe renal dysfunction and had an extremely high level of serum hepatocyte growth factor (HGF). Therefore, he was diagnosed with severe acute liver failure with acute renal failure (ARF) caused by HAV infection. Prognosis was expected to be poor because of complications by ARF and high serum HGF. However, liver and renal functions both improved rapidly without intensive treatment, and he was subsequently discharged from our hospital on the 21(st) hospital day. Although complication with ARF and high levels of serum HGF are both important factors predicting poor prognosis in acute liver failure patients, the present case achieved a favorable outcome. Endogenous HGF might play an important role as a regenerative effector in injured livers and kidneys.

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.

Cardiac and renal function in a large cohort of amateur marathon runners.

PubMed

Hewing, Bernd; Schattke, Sebastian; Spethmann, Sebastian; Sanad, Wasiem; Schroeckh, Sabrina; Schimke, Ingolf; Halleck, Fabian; Peters, Harm; Brechtel, Lars; Lock, Jürgen; Baumann, Gert; Dreger, Henryk; Borges, Adrian C; Knebel, Fabian

2015-03-21

Participation of amateur runners in endurance races continues to increase. Previous studies of marathon runners have raised concerns about exercise-induced myocardial and renal dysfunction and damage. In our pooled analysis, we aimed to characterize changes of cardiac and renal function after marathon running in a large cohort of mostly elderly amateur marathon runners. A total of 167 participants of the Berlin-Marathon (female n = 89, male n = 78; age = 50.3 ± 11.4 years) were included and cardiac and renal function was analyzed prior to, immediately after and 2 weeks following the race by echocardiography and blood tests (including cardiac troponin T, NT-proBNP and cystatin C). Among the runners, 58% exhibited a significant increase in cardiac biomarkers after completion of the marathon. Overall, the changes in echocardiographic parameters for systolic or diastolic left and right ventricular function did not indicate relevant myocardial dysfunction. Notably, 30% of all participants showed >25% decrease in cystatin C-estimated glomerular filtration rate (GFR) from baseline directly after the marathon; in 8%, we observed a decline of more than 50%. All cardiac and renal parameters returned to baseline ranges within 2 weeks after the marathon. The increase in cardiac biomarkers after completing a marathon was not accompanied by relevant cardiac dysfunction as assessed by echocardiography. After the race, a high proportion of runners experienced a decrease in cystatin C-estimated GFR, which is suggestive of transient, exercise-related alteration of renal function. However, we did not observe persistent detrimental effects on renal function.

Reduced NO production rapidly aggravates renal function through the NF-κB/ET-1/ETA receptor pathway in DOCA-salt-induced hypertensive rats.

PubMed

Kimura, Kimihiro; Ohkita, Mamoru; Koyama, Maki; Matsumura, Yasuo

2012-10-15

It has been reported that endothelin-1 (ET-1) overproduction and reduced nitric oxide (NO) production are closely related to the progression of renal diseases. In the present study, we examined the interrelation between ET-1 and NO system using rats treated with the combination of deoxycorticosterone acetate (DOCA)-salt and a non selective NO synthase inhibitor N(ω)-nitro-L-arginine (NOARG). Rats were treated with DOCA-salt (15 mg/kg, plus drinking water containing 1% NaCl) for two weeks, and then additional treatment of NOARG (0.6 mg/ml in the drinking water) was performed for three days. Combined treatment of DOCA-salt and NOARG drastically developed the severe renal dysfunction and tissue injury. This treatment additionally enhanced renal ET-1 production compared to the rats treated with DOCA-salt alone, whereas a selective ET(A) receptor antagonist ABT-627 completely prevented renal dysfunction and tissue injury. On the other hand, combined treatment of DOCA-salt and NOARG induced the phosphorylation of inhibitory protein kappa B (IκB), followed by the activation of nuclear factor-kappa B (NF-κB) in the kidney. In addition, pyrrolidine-dithiocarbamate completely suppressed not only NF-κB activation but also renal dysfunction and ET-1 overproduction. These results suggest that NF-κB/ET-1/ET(A) receptor-mediated actions are responsible for the increased susceptibility to DOCA-salt induced renal injuries in the case of reduced NO production. Copyright © 2012 Elsevier Inc. All rights reserved.

THE PATTERN OF LONGITUDINAL CHANGE IN SERUM CREATININE AND NINETY-DAY MORTALITY AFTER MAJOR SURGERY

PubMed Central

Hobson, Charles E; Pardalos, Panos

2016-01-01

Objective Calculate mortality risk that accounts for both severity and recovery of postoperative kidney dysfunction using the pattern of longitudinal change in creatinine. Summary Background Data Although the importance of renal recovery after acute kidney injury (AKI) is increasingly recognized, the complex association that accounts for longitudinal creatinine changes and mortality is not fully described. Methods We used routinely collected clinical information for 46,299 adult patients undergoing major surgery to develop a multivariable probabilistic model optimized for non-linearity of serum creatinine time series that calculates the risk function for ninety-day mortality. We performed a 70/30 cross validation analysis to assess the accuracy of the model. Results All creatinine time series exhibited nonlinear risk function in relation to ninety-day mortality and their addition to other clinical factors improved the model discrimination. For any given severity of AKI, patients with complete renal recovery, as manifested by the return of the discharge creatinine to the baseline value, experienced a significant decrease in the odds of dying within ninety days of admission compared to patients with partial recovery. Yet, for any severity of AKI even complete renal recovery did not entirely mitigate the increased odds of dying as patients with mild AKI and complete renal recovery still had significantly increased odds for dying compared to patients without AKI (odds ratio 1,48 (95% confidence interval 1.30-1.68). Conclusions We demonstrate the nonlinear relationship between both severity and recovery of renal dysfunction and ninety-day mortality after major surgery. We have developed an easily applicable computer algorithm that calculates this complex relationship. PMID:26181482

The safety and tolerability of spironolactone in patients with mild to moderate chronic kidney disease

PubMed Central

Edwards, Nicola C; Steeds, Richard P; Chue, Colin D; Stewart, Paul M; Ferro, Charles J; Townend, Jonathan N

2012-01-01

AIM Mineralocorticoid receptor blockade (MRBs) in combination with angiotensin converting enzyme (ACE) inhibitors and angiotensin-II receptor blockade (ARBs) improve prognostic markers of cardiovascular and renal disease in early stage chronic kidney disease (CKD). Concerns relating to the safety and tolerability of MRBs in CKD may limit their use in a non clinical trial setting. METHODS In the Chronic Renal Impairment in Birmingham II study, 115 patients with non-diabetic early stage CKD (eGFR 30–89 ml/min/1.73m2) received 25 mg daily of spironolactone for 4 weeks before randomization to continuing treatment or placebo for a further 36 weeks. All patients were on ACE inhibitors and/or ARB therapy. Potassium and renal function were checked at weeks 1, 2, 4, 8, 16, 28 and 40. The incidence of hyperkalaemia, significant renal dysfunction (reduction eGFR ≥25%) and adverse effects was assessed. RESULTS After 40 weeks of treatment the incidence of serious hyperkalaemia (K+≥6.0 mmol/L) was <1%. A potassium 5.5–5.9 mmol/L occurred on ≥1 occasion over follow-up in 11 patients (nine on spironolactone) and was predicted by baseline potassium ≥5.0 mmol/L and eGFR ≤45 ml/min/1.73m2. Over follow-up, three patients experienced significant renal dysfunction but no patients withdrew due to intolerance or side effects. Changes in potassium, eGFR and systolic blood pressure were most apparent in the first 4 eeks. CONCLUSION Spironolactone was well tolerated in selected patients with early stage CKD. Strict monitoring over the first month of treatment followed by standard surveillance as for ACE inhibitors and ARBs is suggested. PMID:21950312

The safety and tolerability of spironolactone in patients with mild to moderate chronic kidney disease.

PubMed

Edwards, Nicola C; Steeds, Richard P; Chue, Colin D; Stewart, Paul M; Ferro, Charles J; Townend, Jonathan N

2012-03-01

Mineralocorticoid receptor blockade (MRBs) in combination with angiotensin converting enzyme (ACE) inhibitors and angiotensin-II receptor blockade (ARBs) improve prognostic markers of cardiovascular and renal disease in early stage chronic kidney disease (CKD). Concerns relating to the safety and tolerability of MRBs in CKD may limit their use in a non clinical trial setting. METHODS In the Chronic Renal Impairment in Birmingham II study, 115 patients with non-diabetic early stage CKD (eGFR 30-89ml/min/1.73m(2) ) received 25mg daily of spironolactone for 4 weeks before randomization to continuing treatment or placebo for a further 36 weeks. All patients were on ACE inhibitors and/or ARB therapy. Potassium and renal function were checked at weeks 1, 2, 4, 8, 16, 28 and 40. The incidence of hyperkalaemia, significant renal dysfunction (reduction eGFR ≥25%) and adverse effects was assessed. After 40 weeks of treatment the incidence of serious hyperkalaemia (K(+) ≥6.0mmol/L) was <1%. A potassium 5.5-5.9mmol/L occurred on ≥1 occasion over follow-up in 11 patients (nine on spironolactone) and was predicted by baseline potassium ≥5.0mmol/L and eGFR ≤45 ml/min/1.73m(2) . Over follow-up, three patients experienced significant renal dysfunction but no patients withdrew due to intolerance or side effects. Changes in potassium, eGFR and systolic blood pressure were most apparent in the first 4 eeks. Spironolactone was well tolerated in selected patients with early stage CKD. Strict monitoring over the first month of treatment followed by standard surveillance as for ACE inhibitors and ARBs is suggested. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Bardet-Biedl syndrome: A rare cause of end stage renal disease.

PubMed

Hemachandar, R

2015-01-01

Bardet-Biedl syndrome is a rare autosomal recessive disorder, recently categorized as ciliopathy characterized by dysfunction of primary cilia which results in myriad manifestations in various organ systems. Though renal abnormalities can occur in this syndrome, renal failure is a rare presentation. The author reports a case of 18-year-old female who presented with polydactyly, obesity, retinitis pigmentosa, learning disability and renal failure.

Associations Between Neutrophil Gelatinase Associated Lipocalin, Neutrophil-to-Lymphocyte Ratio, Atrial Fibrillation and Renal Dysfunction in Chronic Heart Failure

PubMed Central

Argan, Onur; Ural, Dilek; Kozdag, Guliz; Sahin, Tayfun; Bozyel, Serdar; Aktas, Mujdat; Karauzum, Kurtulus; Yılmaz, Irem; Dervis, Emir; Agir, Aysen

2016-01-01

Background Atrial fibrillation (AF) and renal dysfunction are two common comorbidities in patients with chronic heart failure with reduced ejection fraction (HFrEF). This study evaluated the effect of permanent AF on renal function in HFrEF and investigated the associations of atrial fibrillation, neutrophil gelatinase-associated lipocalin (NGAL), and neutrophil-to-lymphocyte ratio (NLR) with adverse clinical outcome. Material/Methods Serum NGAL levels measured by ELISA and NLR were compared between patients with sinus rhythm (HFrEF-SR, n=68), with permanent AF (HFrEF-AF, n=62), and a healthy control group (n=50). Results Mean eGFR levels were significantly lower, and NLR and NGAL levels were significantly higher in the HFrEF patients than in the control patients but the difference between HFrEF-SR and HFrEF-AF was not statistically significant (NGAL: 95 ng/mL in HFrEF-SR, 113 ng/mL in HFrEF-AF and 84 ng/mL in the control group; p<0.001). Independent associates of baseline eGFR were age, hemoglobin, NLR, triiodothyronine, and pulmonary artery systolic pressure. In a mean 16 months follow-up, adverse clinical outcome defined as progression of kidney dysfunction and composite of all-cause mortality and re-hospitalization were not different between HFrEF-SR and HFrEF-AF patients. Although NGAL was associated with clinical endpoints in the univariate analysis, Cox regression analysis showed that independent predictors of increased events were the presence of signs right heart failure, C-reactive protein, NLR, triiodothyronine, and hemoglobin. In ROC analysis, a NLR >3 had a 68% sensitivity and 75% specificity to predict progression of kidney disease (AUC=0.72, 95% CI 0.58–0.85, p=0.001). Conclusions Presence of AF in patients with HFrEF was not an independent contributor of adverse clinical outcome (i.e., all-cause death, re-hospitalization) or progression of renal dysfunction. Renal dysfunction in HFrEF was associated with both NLR and NGAL levels, but systemic inflammation reflected by NLR seemed to be a more important determinant of progression of kidney dysfunction. PMID:27918494

Renal function outcomes in pediatric patients with symptomatic reflux into the transplanted kidney treated with redo ureteroneocystostomy.

PubMed

Wang, Mary K; Chuang, Kai-Wen; Li, Yi; Gaither, Thomas; Brakeman, Paul; Gonzalez, Lynette; Brennan, Jessica; Baskin, Laurence S

2018-03-14

Asymptomatic post-renal transplant reflux is common but only 5-10% patients are diagnosed with vesico-ureteral reflux in the setting of post-transplant febrile urinary tract infections, requiring redo ureteroneocystostomy (redo-UNC). Here we report the renal function outcomes of 37 such patients, stratified by lower urinary tract (LUT) status. We hypothesized that those with pre-transplant LUT dysfunction would have lower glomerular filtration rate (GFR) on follow-up. Using procedure codes, 37 patients who underwent renal transplant followed by redo-UNC for transplant reflux at our institution between 1991 and 2014 were identified. Patient characteristics and GFR levels from four different time points were recorded. Comparisons were made between those with and without LUT dysfunction, using Fisher's exact, Wilcoxon rank sum, or signed-rank tests. Generalized estimating equations were constructed to account for the clustered nature of GFR within each LUT group and to assess their change over time. Twelve patients (32%) had pre-transplant LUT dysfunction. The proportion of males in this group was significantly higher (75% vs. 32%, p = 0.032), and there was no statistical difference towards presenting earlier with post-transplant reflux (1.4 vs. 2.3 years, p = 0.087). After an average of 4.9 years, the median GFRs were similar between the two groups (53 mg/dL vs. 58 mg/dL, p = 0.936). There was no significant difference in GFR at this last follow-up time point in patients with and without LUT dysfunction. Vesicoureteral reflux in the setting of renal transplantation is common and doesn't often require repair. In our series, we found that those with LUT dysfunction did not present statistically sooner with symptomatic transplant reflux. Longer-term follow-up did show a decline in GFR but did not reveal a difference in GFR in patients' with and without LUT dysfunction. Pediatric post-transplant GFR after open redo ureteral reimplant decreases over time in similar fashion in patients with symptomatic reflux regardless of whether they have LUT dysfunction or normal anatomy. Vigilance should apply to the recognition, treatment, and follow-up of all symptomatic transplant reflux regardless of LUT status. Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Erectile dysfunction in chronic kidney disease: From pathophysiology to management

PubMed Central

Papadopoulou, Eirini; Varouktsi, Anna; Lazaridis, Antonios; Boutari, Chrysoula; Doumas, Michael

2015-01-01

Chronic kidney disease (CKD) is encountered in millions of people worldwide, with continuously rising incidence during the past decades, affecting their quality of life despite the increase of life expectancy in these patients. Disturbance of sexual function is common among men with CKD, as both conditions share common pathophysiological causes, such as vascular or hormonal abnormalities and are both affected by similar coexisting comorbid conditions such as cardiovascular disease, hypertension and diabetes mellitus. The estimated prevalence of erectile dysfunction reaches 70% in end stage renal disease patients. Nevertheless, sexual dysfunction remains under-recognized and under-treated in a high proportion of these patients, a fact which should raise awareness among clinicians. A multifactorial approach in management and treatment is undoubtedly required in order to improve patients’ quality of life and cardiovascular outcomes. PMID:26167462

Early Focal Segmental Glomerulosclerosis as a Cause of Renal Allograft Primary Nonfunction

PubMed Central

Griffin, Emma J.; Thomson, Peter C.; Kipgen, David; Clancy, Marc; Daly, Conal

2013-01-01

Background. Primary focal segmental glomerulosclerosis (FSGS) is one of the commonest causes of glomerular disease and if left untreated will often progress to established renal failure. In many cases the best treatment option is renal transplantation; however primary FSGS may rapidly recur in renal allografts and may contribute to delayed graft function. We present a case of primary nonfunction in a renal allograft due to biopsy-proven FSGS. Case Report. A 32-year-old man presented with serum albumin of 22 g/L, proteinuria quantified at 12 g/L, and marked peripheral oedema. Renal biopsy demonstrated tip-variant FSGS. Despite treatment, the patient developed progressive renal dysfunction and was commenced on haemodialysis. Cadaveric renal transplantation was undertaken; however this was complicated by primary nonfunction. Renal biopsies failed to demonstrate evidence of acute rejection but did demonstrate clear evidence of FSGS. The patient was treated to no avail. Discussion. Primary renal allograft nonfunction following transplantation is often due to acute kidney injury or acute rejection. Recurrent FSGS is recognised as a phenomenon that drives allograft dysfunction but is not traditionally associated with primary nonfunction. This case highlights FSGS as a potentially aggressive process that, once active in the allograft, may prove refractory to targeted treatment. Preemptive therapies in patients deemed to be at high risk of recurrent disease may be appropriate and should be considered. PMID:23781382

Scleroderma Renal Crisis: A Reversible Cause of Left Ventricular Dysfunction.

PubMed

Martínez-Milla, Juan; Gaebelt, Hans Paul; Sánchez-Pernaute, Olga; Kallmeyer, Andrea; Romero, José; Farré, Jerónimo

2018-05-02

We report a case of acute left ventricular dysfunction due to myocarditis, in the setting of a scleroderma renal crisis. The case is particularly intriguing for the favorable outcome of both symptoms and heart function following immunosuppressive therapy. We also highlight the changes observed over time with image techniques as well as in electrocardiograms. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

[Pulmonary-renal crosstalk in the critically ill patient].

PubMed

Donoso F, Alejandro; Arriagada S, Daniela; Cruces R, Pablo

2015-01-01

Despite advances in the development of renal replacement therapy, mortality of acute renal failure remains high, especially when occurring simultaneously with distant organic failure as it is in the case of the acute respiratory distress syndrome. In this update, birideccional deleterious relationship between lung and kidney on the setting of organ dysfunction is reviewed, which presents important clinical aspects of knowing. Specifically, the renal effects of acute respiratory distress syndrome and the use of positive-pressure mechanical ventilation are discussed, being ventilator induced lung injury one of the most common models for studying the lung-kidney crosstalk. The role of renal failure induced by mechanical ventilation (ventilator-induced kidney injury) in the pathogenesis of acute renal failure is emphasized. We also analyze the impact of the acute renal failure in the lung, recognizing an increase in pulmonary vascular permeability, inflammation, and alteration of sodium and water channels in the alveolar epithelial. This conceptual model can be the basis for the development of new therapeutic strategies to use in patients with multiple organ dysfunction syndrome. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Role of mitochondrial dysfunction in renal fibrosis promoted by hypochlorite-modified albumin in a remnant kidney model and protective effects of antioxidant peptide SS-31.

PubMed

Zhao, Hao; Liu, Yan-Jun; Liu, Zong-Rui; Tang, Dong-Dong; Chen, Xiao-Wen; Chen, Yi-Hua; Zhou, Ru-Ning; Chen, Si-Qi; Niu, Hong-Xin

2017-06-05

Oxidative stress aggravates renal fibrosis, a pathway involved in almost all forms of chronic kidney disease (CKD). However, the underlying mechanism involved in the pathogenesis of renal oxidative stress has not been completely elucidated. In this study, we explored the role and mechanism of hypochlorite-modified albumin (HOCl-alb) in mediating oxidative stress and fibrotic response in a remnant-kidney rat model. Five-sixths nephrectomy (5/6 NX) was performed on the rats and then the animals were randomly assigned to intravenous treatment with either vehicle alone, or HOCl-rat serum albumin (RSA) in the presence or absence of SS-31 (administered intraperitoneally). A sham-operation control group was set up concurrently. Compared with the control group, 5/6 NX animals displayed marked mitochondrial (mt) dysfunction, as evidenced by decrease of mitochondrial membrane potential (MMP), ATP production, mtDNA copy number alterations and manganese superoxide dismutase (MnSOD) activity, release of cytochrome C (Cyto C) from mitochondria to the cytoplasm, and increase of mitochondrial reactive oxygen species in renal tissues. They also displayed increased levels of HOCl-alb in both plasma and renal tissues. These changes were accompanied by accumulation of extracellular matrix, worsened proteinuria, deteriorated renal function, and a marked increase of macrophage infiltration along with up-regulation of monocyte chemoattractant protein (MCP)-1 and transforming growth factor (TGF)-β1 expression. HOCl-alb challenge further exacerbated the above biological effects in 5/6 NX animals, but these adverse effects were prevented by administration of SS-31, a mitochondrial targeted antioxidant peptide. These data suggest that accumulation of HOCl-alb may promote renal inflammation and fibrosis, probably related to mitochondrial oxidative stress and dysfunction and that the mitochondrial targeted peptide SS-31 might be a novel therapy for renal fibrosis and chronic renal failure (CRF). Copyright © 2017 Elsevier B.V. All rights reserved.

Progressive renal insufficiency related to ALK inhibitor, alectinib.

PubMed

Nagai, Kojiro; Ono, Hiroyuki; Matsuura, Motokazu; Hann, Michael; Ueda, Sayo; Yoshimoto, Sakiya; Tamaki, Masanori; Murakami, Taichi; Abe, Hideharu; Ishikura, Hisashi; Doi, Toshio

2018-04-01

Alectinib is a second generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor and is generally effective and tolerated in patients who have demonstrated disease progression or adverse effects while on the first generation inhibitor, crizotinib. ALK inhibitors can cause a reversible chronic increase of serum creatinine concentration; however, they rarely induce progressive renal insufficiency. We herein report a case of a 68-year-old woman diagnosed with ALK-positive advanced non-small cell lung cancer and who received ALK inhibitors. Due to dysgeusia and transaminitis, her medication was switched from crizotinib to alectinib. Rapid progressive glomerulonephritis developed 1 year after the initiation of alectinib treatment. A renal biopsy revealed unique kidney lesions in both tubules and glomeruli. Glucocorticoid therapy partially reversed kidney impairment. However, re-administration of alectinib caused kidney dysfunction, which was improved by the cessation of alectinib. Our case suggests that much attention should be paid to kidney function when using ALK inhibitors.

Rapeseed protein-derived antioxidant peptide RAP alleviates renal fibrosis through MAPK/NF-κB signaling pathways in diabetic nephropathy.

PubMed

Zhang, Mingyan; Yan, Zhibin; Bu, Lili; An, Chunmei; Wang, Dan; Liu, Xin; Zhang, Jianfeng; Yang, Wenle; Deng, Bochuan; Xie, Junqiu; Zhang, Bangzhi

2018-01-01

Kidney fibrosis is the main pathologic change in diabetic nephropathy (DN), which is the major cause of end-stage renal disease. Current therapeutic strategies slow down but cannot reverse the progression of renal dysfunction in DN. Plant-derived bioactive peptides in foodstuffs are widely used in many fields because of their potential pharmaceutical and nutraceutical benefits. However, this type of peptide has not yet been studied in renal fibrosis of DN. Previous studies have indicated that the peptide YWDHNNPQIR (named RAP), a natural peptide derived from rapeseed protein, has an antioxidative stress effect. The oxidative stress is believed to be associated with DN. The aim of this study was to evaluate the pharmacologic effects of RAP against renal fibrosis of DN and high glucose (HG)-induced mesangial dysfunction. Diabetes was induced by streptozotocin and high-fat diet in C57BL/6 mice and these mice were treated by subcutaneous injection of different doses of RAP (0.1 mg/kg and 0.5 mg/kg, every other day) or PBS for 12 weeks. Later, functional and histopathologic analyses were performed. Parallel experiments verifying the molecular mechanism by which RAP alleviates DN were carried out in HG-induced mesangial cells (MCs). RAP improved the renal function indices, including 24-h albuminuria, triglyceride, serum creatinine, and blood urea nitrogen levels, but did not lower blood glucose levels in DN mice. RAP also simultaneously attenuated extracellular matrix accumulation in DN mice and HG-induced MCs. Furthermore, RAP reduced HG-induced cell proliferation, but it showed no toxicity in MCs. Additionally, RAP inhibited the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling pathways. RAP can attenuate fibrosis in vivo and in vitro by antagonizing the MAPK and NF-κB pathways.

RAAS inhibition and cardiorenal syndrome.

PubMed

Onuigbo, Macaulay Amechi C

2014-01-01

The consensus conference on cardio-renal syndromes (2008) defined 'cardio-renal syndromes' as 'disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other' and identified five subtypes of the syndromes. Various pathophysiologic mechanisms underlie cardiorenal syndrome including hemodynamic derangements, reduced cardiac output leading to impaired renal perfusion, reduced stroke volume, raised atrial filling pressures, elevated atrial pressures, sodium and water retention, venous congestion, right ventricular dysfunction and venous hypertension causing increased renal venous pressure, intra-abdominal hypertension, various neurohormonal adaptations including activation of the renin-angiotensin-aldosterone system, adaptive activation of the sympathetic nervous system, cytokine release and oxidative stress. Although there are standardized clinical guidelines for the management of heart failure, and chronic kidney disease, respectively, there are no similar consensus clinical guidelines for the management of the cardiorenal syndromes. RAAS inhibition is advocated in treating systolic heart failure. There is evidence that RAAS inhibition is also useful in cardiorenal syndrome. However, RAAS inhibition, while potentially useful in the management of cardiorenal syndrome, is not the 'magic bullet', is sometimes limited by adverse renal events, is not applicable to all patients, and must be applied by physicians with due diligence and caution. Nevertheless, a more comprehensive multidisciplinary multipronged approach to managing patients with cardiorenal syndrome is even more pragmatic and commonsense given the multiple mechanisms and pathogenetic pathways implicated in the causation and perpetuation of cardiorenal syndrome.

Pharmacological inhibition of Src kinase protects against acute kidney injury in a murine model of renal ischemia/reperfusion

PubMed Central

Zhou, Xiaoxu; Liu, Lirong; Masucci, Monica V.; Tang, Jinhua; Li, Xuezhu; Liu, Na; Bayliss, George; Zhao, Ting C.; Zhuang, Shougang

2017-01-01

Activation of Src kinase has been implicated in the pathogenesis of acute brain, liver, and lung injury. However, the role of Src in acute kidney injury (AKI) remains unestablished. To address this, we evaluated the effects of Src inhibition on renal dysfunction and pathological changes in a murine model of AKI induced by ischemia/reperfusion (I/R). I/R injury to the kidney resulted in increased Src phosphorylation at tyrosine 416 (activation). Administration of PP1, a highly selective Src inhibitor, blocked Src phosphorylation, improved renal function and ameliorated renal pathological damage. PP1 treatment also suppressed renal expression of neutrophil gelatinase-associated lipocalin and reduced apoptosis in the injured kidney. Moreover, Src inhibition prevented downregulation of several adherens and tight junction proteins, including E-cadherin, ZO-1, and claudins-1/−4 in the kidney after I/R injury as well as in cultured renal proximal tubular cells following oxidative stress. Finally, PP1 inhibited I/R–induced renal expression of matrix metalloproteinase-2 and -9, phosphorylation of extracellular signal–regulated kinases1/2, signal transducer and activator of transcription-3, and nuclear factor-κB, and the infiltration of macrophages into the kidney. These data indicate that Src is a pivotal mediator of renal epithelial injury and that its inhibition may have a therapeutic potential to treat AKI. PMID:28415724

Increased renal sympathetic nerve activity leads to hypertension and renal dysfunction in offspring from diabetic mothers.

PubMed

de Almeida Chaves Rodrigues, Aline Fernanda; de Lima, Ingrid Lauren Brites; Bergamaschi, Cássia Toledo; Campos, Ruy Ribeiro; Hirata, Aparecida Emiko; Schoorlemmer, Guus Hermanus Maria; Gomes, Guiomar Nascimento

2013-01-15

The exposure of the fetus to a hyperglycemic environment promotes the development of hypertension and renal dysfunction in the offspring at adult age. We evaluated the role of renal nerves in the hypertension and renal changes seen in offspring of diabetic rats. Diabetes was induced in female Wistar rats (streptozotocin, 60 mg/kg ip) before mating. Male offspring from control and diabetic dams were studied at an age of 3 mo. Systolic blood pressure measured by tail cuff was increased in offspring of diabetic dams (146 ± 1.6 mmHg, n = 19, compared with 117 ± 1.4 mmHg, n = 18, in controls). Renal function, baseline renal sympathetic nerve activity (rSNA), and arterial baroreceptor control of rSNA were analyzed in anesthetized animals. Glomerular filtration rate, fractional sodium excretion, and urine flow were significantly reduced in offspring of diabetic dams. Two weeks after renal denervation, blood pressure and renal function in offspring from diabetic dams were similar to control, suggesting that renal nerves contribute to sodium retention in offspring from diabetic dams. Moreover, basal rSNA was increased in offspring from diabetic dams, and baroreceptor control of rSNA was impaired, with blunted responses to infusion of nitroprusside and phenylephrine. Thus, data from this study indicate that in offspring from diabetic mothers, renal nerves have a clear role in the etiology of hypertension; however, other factors may also contribute to this condition.

Clinical outcomes in overweight heart transplant recipients.

PubMed

Jalowiec, Anne; Grady, Kathleen L; White-Williams, Connie

2016-01-01

Few studies have examined the impact of patient weight on heart transplant (HT) outcomes. Nine outcomes were compared in 2 groups of HT recipients (N = 347) based on their mean body mass index (BMI) during the first 3 years post-HT. Group 1 consisted of 108 non-overweight patients (BMI <25; mean age 52; 29.6% females; 16.7% minorities). Group 2 consisted of 239 overweight patients (BMI ≥25; mean age 52; 15.9% females; 13.8% minorities). Outcomes were: survival, re-hospitalization, rejections, infections, cardiac allograft vasculopathy (CAV), stroke, renal dysfunction, diabetes, and lymphoma. Non-overweight patients had shorter survival, were re-hospitalized more days after the HT discharge, and had more lymphoma and severe renal dysfunction. Overweight patients had more CAV, steroid-induced diabetes, and acute rejections. Overweight HT patients had better survival, but more rejections, CAV, and diabetes. Non-overweight HT patients had worse survival, plus more re-hospitalization time, lymphoma, and renal dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2014-03-01

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

Outcomes of cryptococcosis in renal transplant recipients in a less-resourced health care system.

PubMed

Ponzio, Vinicius; Camargo, Luis F A; Medina-Pestana, José O; Perfect, John R; Colombo, Arnaldo L

2018-04-20

Cryptococcosis is the second most common cause of invasive fungal infections in renal transplant recipients in many countries, and data on graft outcome after treatment for this infection is lacking in less-resourced health care settings. Data from 47 renal transplant recipients were retrospectively collected at a single institution during a period of 13 years. Graft dysfunction, graft loss and mortality rates were evaluated. Predictors of mortality and graft loss were estimated. A total of 38 (97.4%) patients treated with amphotericin B deoxycholate (AMBd) showed graft dysfunction after antifungal initiation and 8 (18.2%) had kidney graft loss. Graft loss within 30 days after cryptococcosis onset was significantly associated with disseminated infection, greater baseline creatinine levels and graft dysfunction concomitant to AMBd therapy and an additional nephrotoxic condition. The 30-day mortality rate was 19.2% and it was significantly associated with disseminated and pulmonary infections, somnolence at admission, high CSF opening pressure, positive CSF India ink, creatinine levels greater than 2.0 mg/dL at admission, graft dysfunction in patients treated with AMBd and an additional nephrotoxic condition and graft loss within 30 days. Graft dysfunction was common in renal transplant recipients with cryptococcosis treated with AMBd. The rate of graft loss rate was high, most frequently in patients with concomitant nephrotoxic conditions. Therefore, the clinical focus should be on the use of less nephrotoxic lipid formulations of amphotericin B in this specific population requiring a polyene induction regimen for treatment of severe cryptococcosis in all health care systems caring for transplantation recipients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

N-Acetyl-Seryl-Aspartyl-Lysyl-Proline: mechanisms of renal protection in mouse model of systemic lupus erythematosus

PubMed Central

Liao, Tang-Dong; Nakagawa, Pablo; Janic, Branislava; D'Ambrosio, Martin; Worou, Morel E.; Peterson, Edward L.; Rhaleb, Nour-Eddine; Yang, Xiao-Ping

2015-01-01

Systemic lupus erythematosus is an autoimmune disease characterized by the development of auto antibodies against a variety of self-antigens and deposition of immune complexes that lead to inflammation, fibrosis, and end-organ damage. Up to 60% of lupus patients develop nephritis and renal dysfunction leading to kidney failure. N-acetyl-seryl-aspartyl-lysyl-proline, i.e., Ac-SDKP, is a natural tetrapeptide that in hypertension prevents inflammation and fibrosis in heart, kidney, and vasculature. In experimental autoimmune myocarditis, Ac-SDKP prevents cardiac dysfunction by decreasing innate and adaptive immunity. It has also been reported that Ac-SDKP ameliorates lupus nephritis in mice. We hypothesize that Ac-SDKP prevents lupus nephritis in mice by decreasing complement C5-9, proinflammatory cytokines, and immune cell infiltration. Lupus mice treated with Ac-SDKP for 20 wk had significantly lower renal levels of macrophage and T cell infiltration and proinflammatory chemokine/cytokines. In addition, our data demonstrate for the first time that in lupus mouse Ac-SDKP prevented the increase in complement C5-9, RANTES, MCP-5, and ICAM-1 kidney expression and it prevented the decline of glomerular filtration rate. Ac-SDKP-treated lupus mice had a significant improvement in renal function and lower levels of glomerular damage. Ac-SDKP had no effect on the production of autoantibodies. The protective Ac-SDKP effect is most likely achieved by targeting the expression of proinflammatory chemokines/cytokines, ICAM-1, and immune cell infiltration in the kidney, either directly or via C5-9 proinflammatory arm of complement system. PMID:25740596

Urinary NGAL, KIM-1 and L-FABP concentrations in antenatal hydronephrosis.

PubMed

Noyan, Aytul; Parmaksiz, Gonul; Dursun, Hasan; Ezer, Semire Serin; Anarat, Ruksan; Cengiz, Nurcan

2015-10-01

The clinical tests currently in use for obstructive nephropathy (such as renal ultrasonography, differential radionuclide renal scans and urinary creatinine concentration data) are not efficient predictors of the subsequent clinical course. Novel and simple biomarkers are required which, if proven, could be clinically beneficial in determining if a patient is eligible for surgery or reno-protective therapy. More recently, the interest of clinicians has focused on the potential of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecule-1 (uKIM-1) and urinary liver-type fatty acid-binding proteins (uL-FABP) as biomarkers for renal function in children with hydronephrosis (HN). The purpose of this study was to investigate possible clinical applications of uNGAL, uKIM-1 and uL-FABP as beneficial non-invasive biomarkers to determine whether or not surgical intervention is required in children with HN. Renal ultrasonography and radionuclide renal scans were used as diagnostic tools to detect HN. Patients were divided into two groups based on the antero-posterior diameter of their renal pelvis and the presence of dysfunction. Group 1 included 26 children with severe HN (with dysfunction), and group 2 consisted of 36 children with mild HN (without dysfunction). Urine samples were collected from 62 children with HN and 20 healthy children. Hydronephrosis was more common in males than in females, with a male to female ratio of 9:1 in the study sample. The incidence of left kidney involvement (32 patients) was slightly higher than right kidney involvement (28 patients). Compared with controls and group 2, the ratio of uNGAL to creatinine was significantly higher in group 1 (p < 0.05). The biomarker uNGAL/Cr exhibited fairly good diagnostic accuracy, with an area under the curve of 0.68 [95% confidence interval 0.6-0.7] and an optimal cut-off value of 0.16 ng/mg Cr (sensitivity 58%, specificity 75%) (p < 0.05). There was a positive correlation between the uNGAL/Cr ratio and the uKIM-1/Cr ratio (r = 0.582, p < 0.05) and uL-FABP/Cr ratio (r = 0675, p < 0.05) in group 1. The results clearly demonstrated that children with hydronephrosis and dysfunction had significantly increased uNGAL, and uNGAL/Cr concentrations. However, uKIM-1, uKIM-1/Cr, uL-FABP and uL-FABP/Cr concentrations were not significantly different when compared with controls. These results support the use of uNGAL concentrations as an early marker for renal dysfunction in HN. The study clearly demonstrated that pediatric patients with hydronephrosis and dysfunction had significantly higher uNGAL to creatinine concentrations as compared with controls. Copyright © 2015 Journal of Pediatric Urology Company. All rights reserved.

[Factors related to the QT prolongation in chronic renal failure].

PubMed

Kurosu, M; Ando, Y; Akimoto, T; Ono, S; Kusano, E; Asano, Y

1999-04-01

QT prolongation, a risk factor for arrhythmia and cardiac death, is observed in uremic patients. Though hypocalcemia, autonomic nerve dysfunction and cardiac hypertrophy are assumed to cause the uremic QT prolongation, the exact mechanism remains unspecified. We therefore examined factors related to the QT interval in chronic renal failure (CRF). Corrected QT interval (QTc) was significantly prolonged in CRF just before the induction of dialysis therapy (group A) compared with nephrotic syndrome with the intact or mildly impaired renal function (group B). QTc was also prolonged in acute renal failure (group C). Cardio-thoracic ratio, serum albumin and Ca correlated with QTc in group A, but not in B or C. A single HD session in group A failed to shorten QTc, despite a significant increase in serum Ca++. Autonomic dysfunction did not appear to be a major determinant of QT prolongation, since QTc was not different between diabetics and non-diabetics in group A and in chronic HD patients (group D). In group D, QTc did not correlate with SV1 + RV5 on ECG or left ventricular wall thickness (LVWT) on echocardiography. In another group of chronic HD patients (group E), there was no significant correlation between QTc and the parameters of left ventricular mass, plasma brain natriuretic peptide (BNP). However, in the patients subjected to repeated echocardiography in group D, QTc and LVWT changed in parallel. In a retrospective analysis of QTc in group D, QTc was maximally prolonged at the time of starting HD therapy, and gradually improved in the following 1-5 years in both diabetics and non-diabetics. In contrast, chronic CAPD patients (group F) revealed no improvement of QTc. Thus, uremic QT prolongation cannot be explained simply by any of the previously assumed factors, but appears to be affected by multiple factors, which are partially correctable by chronic HD therapy.

Inhibition of NA+/H+ Exchanger 1 Attenuates Renal Dysfunction Induced by Advanced Glycation End Products in Rats

PubMed Central

Li, Peng; Chen, Geng-Rong; Wang, Fu; Xu, Ping; Liu, Li-Ying; Yin, Ya-Ling; Wang, Shuang-Xi

2016-01-01

It has been recognized that sodium hydrogen exchanger 1 (NHE1) is involved in the development of diabetic nephropathy. The role of NHE1 in kidney dysfunction induced by advanced glycation end products (AGEs) remains unknown. Renal damage was induced by AGEs via tail vein injections in rats. Function and morphology of kidney were determined. Compared to vehicle- or BSA-treated rats, AGEs caused abnormalities of kidney structures and functions in rats, accompanied with higher MDA level and lower GSH content. Gene expressions of NHE1 gene and TGF-β1 in the renal cortex and urine were also increased in AGEs-injected rats. Importantly, all these detrimental effects induced by AGEs were reversed by inhibition of NHE1 or suppression of oxidative stress. These pieces of data demonstrated that AGEs may activate NHE1 to induce renal damage, which is related to TGF-β1. PMID:26697498

Impact of N-acetylcysteine on endothelial function, B-type natriuretic peptide and renal function in patients with the cardiorenal syndrome: a pilot cross over randomised controlled trial.

PubMed

Camuglia, Anthony C; Maeder, Micha T; Starr, Jennifer; Farrington, Catherine; Kaye, David M

2013-04-01

Both heart and renal failure are characterised by increased systemic oxidative stress and endothelial dysfunction and occur in the cardiorenal syndrome (CRS). The aim of the present study was to assess the impact of N-acetylcysteine (NAC), a potent antioxidant, on endothelial function, B-type natriuretic peptide (BNP) and renal function in patients with CRS. In a double blind, placebo controlled manner, we randomised nine stable outpatients with both heart failure (LVEF<40% and NYHA class II or III) and renal failure (Cockroft Gault clearance of 20-60ml/min) to placebo or NAC (500mg orally twice daily) for 28 days followed by a wash out period (>7 days) and crossover to the other treatment. Eight patients completed the study and all data (N=9) was used in the analysis. Mean forearm blood flow improved significantly with NAC with mean ratio of improvement of 1.99 (SEM: ±0.49) for NAC and 0.73 (SEM: ±0.23) for placebo with a p-value of 0.047. There was no significant difference in BNP (p=0.25), renal function (p=0.71) or NYHA class (p=0.5). No deaths occurred during the trial. In this pilot trial of patients with CRS, NAC therapy was associated with improved forearm blood flow. This may represent a general improvement in endothelial function and warrants further investigation of antioxidant therapy in these patients. Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Anterior urethral valve associated with posterior urethral valves: report of 2 cases and review of the literature.

PubMed

Tran, Christine N; Reichard, Chad A; McMahon, Daniel; Rhee, Audrey

2014-08-01

Anterior urethral valve (AUV) associated with posterior urethral valves (PUVs) is an extremely rare congenital urologic anomaly resulting in lower urinary tract obstruction. We present our experience with 2 children with concomitant AUV and PUV as well as a literature review. The clinical presentation of concomitant AUV and PUV is variable. Successful endoscopic management can result in improvement in renal function, reversal of obstructive changes, and improvement or resolution of voiding dysfunction. Copyright © 2014 Elsevier Inc. All rights reserved.

Improvement in Renal Hemodynamics following Combined Angiotensin II Infusion and AT1R Blockade in Aged Female Sheep following Fetal Unilateral Nephrectomy

PubMed Central

Singh, Reetu R.; Lankadeva, Yugeesh R.

2013-01-01

Renin-angiotensin system (RAS) is a powerful modulator of renal hemodynamic and fluid homeostasis. Up-regulation in components of intra-renal RAS occurs with ageing. Recently we reported that 2 year old uninephrectomised (uni-x) female sheep have low renin hypertension and reduced renal function. By 5 years of age, these uni-x sheep had augmented decrease in renal blood flow (RBF) compared to sham. We hypothesised that this decrease in RBF in 5 year old uni-x sheep was due to an up-regulation in components of the intra-renal RAS. In this study, renal responses to angiotensin II (AngII) infusion and AngII type 1 receptor (AT1R) blockade were examined in the same 5 year old sheep. We also administered AngII in the presence of losartan to increase AngII bioavailability to the AT2R in order to understand AT2R contribution to renal function in this model. Uni-x animals had significantly lower renal cortical content of renin, AngII (∼40%) and Ang 1–7 (∼60%) and reduced cortical expression of AT1R gene than sham animals. In response to both AngII infusion and AT1R blockade via losartan, renal hemodynamic responses and tubular sodium excretion were significantly attenuated in uni-x animals compared to sham. However, AngII infusion in the presence of losartan caused ∼33% increase in RBF in uni-x sheep compared to ∼14% in sham (P<0.05). This was associated with a significant decrease in renal vascular resistance in the uni-x animals (22% vs 15%, P<0.05) without any changes in systemic blood pressure. The present study shows that majority of the intra-renal RAS components are suppressed in this model of low renin hypertension. However, increasing the availability of AngII to AT2R by AT1R blockade improved renal blood flow in uni-x sheep. This suggests that manipulation of the AT2R maybe a potential therapeutic target for treatment of renal dysfunction associated with a congenital nephron deficit. PMID:23840884

Borderline Changes on Dysfunctional Renal Allograft Biopsies: Clinical Relevance in a Living Related Renal Transplant Setting.

PubMed

Mubarak, Muhammed; Shakeel, Shaheera; Abbas, Khawar; Aziz, Tahir; Zafar, Mirza Naqi; Naqvi, Syed Anwer; Rizvi, Syed Adibul Hasan

2017-02-01

Our aim was to determine the clinical significance of borderline lymphocytic infiltrates on indicated renal allograft biopsies in a living related renal transplant setting. The study was conducted at the histopathology department of Sindh Institute of Urology and Transplantation. A retrospective review of 421 renal transplant patients was conducted from October 2007 to September 2008 to identify patients in whom a histologic diagnosis of borderline changes was made on dysfunctional renal allograft biopsies. Demographic, clinical, and laboratory data; biopsy findings; treatments given; and responses to treatment were collected and analyzed. Standard biopsy indications determined the need for graft biopsies. Biopsies were reported according to Banff criteria. Mean age was 26.92 ± 9.14 years (range, 10-45) for recipients and 38.46 ± 9.16 years (range, 19-50) for donors. Males were predominant among recipients (84.6% vs 15.4%), and females were predominant among donors (57.7% vs 42.3%). The best serum creatinine levels were 1.79 ± 1.15 mg/dL (range, 0.83-6.12). These were achieved after a median of 3 days (interquartile range, 2-7.25). Dysfunctional biopsies exhibiting borderline infiltrates were performed at a median duration of 5.5 days (interquartile range, 3-14.25). Mean serum creatinine at the time of biopsy was 2.34 ± 1.43 mg/dL (range, 1.25-8.25). The biopsies showed borderline cellular infiltrates (interstitial inflammation 1 [i1] and tubulitis 1 and [t1] lesions). All recipients except one received antirejection treatment (antithymocyte globulin, n = 5; escalation of mycophenolate mofetil dosage, n = 1; pulse steroids, n = 19); all recipients responded with a decline in serum creatinine toward baseline, with a mean serum creatinine of 1.31 ± 0.42 mg/dL (range, 0.40-2.71). This response was achieved at a median duration of 9.73 ± 5.32 days (range, 1-23) after starting treatment. The borderline cellular infiltrates on dysfunctional renal allograft biopsies signify evolving phases of acute cellular rejection. These infiltrates responded favorably to antirejection treatment in our setting.

Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

PubMed Central

Cristóbal-García, Magdalena; García-Arroyo, Fernando E.; Arellano-Buendía, Abraham S.; Madero, Magdalena; Rodríguez-Iturbe, Bernardo; Pedraza-Chaverrí, José; Zazueta, Cecilia; Johnson, Richard J.; Sánchez Lozada, Laura-Gabriela

2015-01-01

We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks) and short-term (3 weeks) effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW), OA+Allopurinol (AP, 150 mg/L drinking water), OA+Tempol (T, 15 mg/kg BW), or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase) and oxidative stress markers (lipid and protein oxidation) along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident. PMID:25918583

Effect of recombinant human brain natriuretic peptide (rhBNP) versus nitroglycerin in patients with heart failure

PubMed Central

Zhang, Sijie; Wang, Zhiqian

2016-01-01

Abstract Background: This study was the first to evaluate the therapeutic outcomes of recombinant human brain natriuretic peptide (rhBNP) versus nitroglycerin (NIT) in patients with heart failure (HF). Methods: The electronic databases were systematically searched to identify available studies. The pooled odds ratios (ORs) and their 95% confidence intervals (95% CIs) were analyzed to assess the mortality, readmission, hypotension, and renal dysfunction in the comparison of rhBNP and NIT therapies. Results: Final 5 randomized controlled trials (RCTs) involving 782 patients with HF were carried out in our study. The pooled OR of mortality, readmission, and hypotension showed that no significant difference was found in both drugs (P > 0.05), with the absence of heterogeneity. The incidence of renal dysfunction was not significant difference in both groups (P = 0.85). The pooled OR from 2 studies of Asian population using multivariate analysis demonstrated that the use of rhBNP was correlated with a significantly decreased risk of renal dysfunction (I2 = 0.0%, OR = 0.19, P = 0.001). Possible publication bias was not detected using Egger's test (P > 0.05). Conclusions: The results suggested that rhBNP and NIT therapies were not significant difference in mortality, readmission, and hypotension. The use of rhBNP may become a useful predictor of renal dysfunction in Asian patients with HF. Additional studies are needed for Caucasian population with HF. PMID:27858837

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

Yin, Qingqiao; Xia, Yuanyu, E-mail: xiayuanyu.wh@gmail.com; Wang, Guan

As an early sign of diabetic cardiovascular disease, endothelial dysfunction may contribute to progressive diabetic nephropathy (DN). Endothelial hyperpermeability induced by hyperglycemia (HG) is a central pathogenesis for DN. Sinomenine (SIN) has strong anti-inflammatory and renal protective effects, following an unknown protective mechanism against HG-induced hyperpermeability. We herein explored the role of SIN in vitro in an HG-induced barrier dysfunction model in human renal glomerular endothelial cells (HRGECs). The cells were exposed to SIN and/or HG for 24 h, the permeability of which was significantly increased by HG. Moreover, junction protein occludin in the cell-cell junction area and its total expression inmore » HRGECs were significantly decreased by HG. However, the dysfunction of tight junction and hyperpermeability of HRGECs were significantly reversed by SIN. Furthermore, SIN prevented HG-increased reactive oxygen species (ROS) by activating nuclear factor-E2-related factor 2 (Nrf2). Interestingly, activation of RhoA/ROCK induced by HG was reversed by SIN or ROCK inhibitor. HG-induced hyperpermeability was prevented by SIN. High ROS level, tight junction dysfunction and RhoA/ROCK activation were significantly attenuated with knockdown of Nrf2. Mediated by activation of Nrf2, SIN managed to significantly prevent HG-disrupted renal endothelial barrier function by suppressing the RhoA/ROCK signaling pathway through reducing ROS. We successfully identified a novel pathway via which SIN exerted antioxidative and renal protective functions, and provided a molecular basis for potential SIN applications in treating DN vascular disorders.« less

Etiological analysis of graft dysfunction following living kidney transplantation: a report of 366 biopsies.

PubMed

Zhang, Jin; Qiu, Jiang; Chen, Guo-Dong; Wang, Chang-Xi; Wang, Chang; Yu, Shuang-Jin; Chen, Li-Zhong

2018-11-01

The aim of this study is to investigate the clinical features of graft dysfunction following living kidney transplantation and to assess its causes. We retrospectively analyzed a series of 366 living kidney transplantation indication biopsies with a clear etiology and diagnosis from July 2003 to June 2016 at our center. The classifications and diagnoses were performed based on clinical and pathological characteristics. All biopsies were evaluated according to the Banff 2007 schema. Acute rejection (AR) occurred in 85 cases (22.0%), chronic rejection (CR) in 62 cases (16.1%), borderline rejection (BR) in 12 cases (3.1%), calcineurin inhibitor (CNI) toxicity damage in 41 cases (10.6%), BK virus-associated nephropathy (BKVAN) in 43 cases (11.1%), de novo or recurrent renal diseases in 134 cases (34.7%), and other causes in nine cases (2.3%); additionally, 20 cases had two simultaneous causes. The 80 cases with IgA nephropathy (IgAN) had the highest incidence (59.7%) of de novo or recurrent renal diseases. After a mean ± SD follow up of 3.7 ± 2.3 years, the 5-year graft cumulative survival rates of AR, CR, CNI toxicity, BKVAN, and de novo or recurrent renal diseases were 60.1%, 31.2%, 66.6%, 66.9%, and 67.1%, respectively. A biopsy is helpful for the diagnosis of graft dysfunction. De novo or recurrent renal disease, represented by IgAN, is a major cause of graft dysfunction following living kidney transplantation.

Effect of recombinant human brain natriuretic peptide (rhBNP) versus nitroglycerin in patients with heart failure: A systematic review and meta-analysis.

PubMed

Zhang, Sijie; Wang, Zhiqian

2016-11-01

This study was the first to evaluate the therapeutic outcomes of recombinant human brain natriuretic peptide (rhBNP) versus nitroglycerin (NIT) in patients with heart failure (HF). The electronic databases were systematically searched to identify available studies. The pooled odds ratios (ORs) and their 95% confidence intervals (95% CIs) were analyzed to assess the mortality, readmission, hypotension, and renal dysfunction in the comparison of rhBNP and NIT therapies. Final 5 randomized controlled trials (RCTs) involving 782 patients with HF were carried out in our study. The pooled OR of mortality, readmission, and hypotension showed that no significant difference was found in both drugs (P > 0.05), with the absence of heterogeneity. The incidence of renal dysfunction was not significant difference in both groups (P = 0.85). The pooled OR from 2 studies of Asian population using multivariate analysis demonstrated that the use of rhBNP was correlated with a significantly decreased risk of renal dysfunction (I = 0.0%, OR = 0.19, P = 0.001). Possible publication bias was not detected using Egger's test (P > 0.05). The results suggested that rhBNP and NIT therapies were not significant difference in mortality, readmission, and hypotension. The use of rhBNP may become a useful predictor of renal dysfunction in Asian patients with HF. Additional studies are needed for Caucasian population with HF.

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.

Epidemiology and Outcome of Acute Kidney Injury According to Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes Criteria in Critically Ill Children-A Prospective Study.

PubMed

Volpon, Leila C; Sugo, Edward K; Consulin, Julio C; Tavares, Tabata L G; Aragon, Davi C; Carlotti, Ana P C P

2016-05-01

We aimed to investigate the epidemiology, risk factors, and short- and medium-term outcome of acute kidney injury classified according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease, and Kidney Disease: Improving Global Outcomes criteria in critically ill children. Prospective observational cohort study. Two eight-bed PICUs of a tertiary-care university hospital. A heterogeneous population of critically ill children. None. Demographic, clinical, laboratory, and outcome data were collected on all patients admitted to the PICUs from August 2011 to January 2012, with at least 24 hours of PICU stay. Of the 214 consecutive admissions, 160 were analyzed. The prevalence of acute kidney injury according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes criteria was 49.4% vs. 46.2%, respectively. A larger proportion of acute kidney injury episodes was categorized as Kidney Disease: Improving Global Outcomes stage 3 (50%) compared with pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease F (39.2%). Inotropic score greater than 10 was a risk factor for acute kidney injury severity. About 35% of patients with acute kidney injury who survived were discharged from the PICU with an estimated creatinine clearance less than 75 mL/min/1.73 m and one persisted with altered renal function 6 months after PICU discharge. Age 12 months old or younger was a risk factor for estimated creatinine clearance less than 75 mL/min/1.73 m at PICU discharge. Acute kidney injury and its severity were associated with increased PICU length of stay and longer duration of mechanical ventilation. Eleven patients died; nine had acute kidney injury (p < 0.05). The only risk factor associated with death after multivariate adjustment was Pediatric Risk of Mortality score greater than or equal to 10. Acute kidney injury defined by both pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes criteria was associated with increased morbidity and mortality, and may lead to long-term renal dysfunction.

Pharmacological Management of Cardiorenal Syndromes

PubMed Central

House, Andrew A.; Haapio, Mikko; Lassus, Johan; Bellomo, Rinaldo; Ronco, Claudio

2011-01-01

Cardiorenal syndromes are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The pharmacological management of Cardiorenal syndromes may be complicated by unanticipated or unintended effects of agents targeting one organ on the other. Hence, a thorough understanding of the pathophysiology of these disorders is paramount. The treatment of cardiovascular diseases and risk factors may affect renal function and modify the progression of renal injury. Likewise, management of renal disease and associated complications can influence heart function or influence cardiovascular risk. In this paper, an overview of pharmacological management of acute and chronic Cardiorenal Syndromes is presented, and the need for high-quality future studies in this field is highlighted. PMID:21660311

A case of reversible dilated cardiomyopathy after alpha-interferon therapy in a patient with renal cell carcinoma.

PubMed

Kuwata, Akiko; Ohashi, Masuo; Sugiyama, Masaya; Ueda, Ryuzo; Dohi, Yasuaki

2002-12-01

A 47-year-old man with renal cell carcinoma underwent nephrectomy, and postoperative chemotherapy was performed with recombinant alpha-interferon. Five years later, he experienced dyspnea during physical exertion. An echocardiogram revealed dilatation and systolic dysfunction of the left ventricle, and thallium-201 myocardial scintigraphy showed diffuse heterogeneous perfusion. We diagnosed congestive heart failure because of cardiomyopathy induced by alpha-interferon therapy. Withdrawal of interferon therapy and the combination of an angiotensin-converting enzyme inhibitor, diuretics, and digitalis improved left ventricular systolic function. Furthermore, myocardial scintigraphy using [123I] beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) or [123 I]metaiodobenzylguanidine (123I-MIBG) revealed normal perfusion after the improvement of congestive heart failure. This is a rare case of interferon-induced cardiomyopathy that resulted in normal myocardial images in 123I-BMIPP and 123I-MIBG scintigrams after withdrawal of interferon therapy.

Inpatient Coronary Angiography and Revascularisation following Non-ST-Elevation Acute Coronary Syndrome in Patients with Renal Impairment: A Cohort Study Using the Myocardial Ischaemia National Audit Project

PubMed Central

Shaw, Catriona; Nitsch, Dorothea; Steenkamp, Retha; Junghans, Cornelia; Shah, Sapna; O’Donoghue, Donal; Fogarty, Damian; Weston, Clive; Sharpe, Claire C.

2014-01-01

Background International guidelines support an early invasive management strategy (including early coronary angiography and revascularisation) for non-ST-elevation acute coronary syndrome (NSTE-ACS) in patients with renal impairment. However, evidence from outside the UK suggests that this approach is underutilised. We aimed to describe practice within the NHS, and to determine whether the severity of renal dysfunction influenced the provision of angiography and modified the association between early revascularisation and survival. Methods We performed a cohort study, using multivariable logistic regression and propensity score analyses, of data from the Myocardial Ischaemia National Audit Project for patients presenting with NSTE-ACS to English or Welsh hospitals between 2008 and 2010. Findings Of 35 881 patients diagnosed with NSTE-ACS, eGFR of <60 ml/minute/1.73 m2 was present in 15 680 (43.7%). There was a stepwise decline in the odds of undergoing inpatient angiography with worsening renal dysfunction. Compared with an eGFR>90 ml/minute/1.73 m2, patients with an eGFR between 45–59 ml/minute/1.73 m2 were 33% less likely to undergo angiography (adjusted OR 0.67, 95% CI 0.55–0.81); those with an eGFR<30/minute/1.73 m2 had a 64% reduction in odds of undergoing angiography (adjusted OR 0.36, 95%CI 0.29–0.43). Of 16 646 patients who had inpatient coronary angiography, 58.5% underwent inpatient revascularisation. After adjusting for co-variables, inpatient revascularisation was associated with approximately a 30% reduction in death within 1 year compared with those managed medically after coronary angiography (adjusted OR 0.66, 95%CI 0.57–0.77), with no evidence of modification by renal function (p interaction = 0.744). Interpretation Early revascularisation may offer a similar survival benefit in patients with and without renal dysfunction, yet renal impairment is an important determinant of the provision of coronary angiography following NSTE-ACS. A randomised controlled trial is needed to evaluate the efficacy of an early invasive approach in patients with severe renal dysfunction to ensure that all patients who may benefit are offered this treatment option. PMID:24937680

Predictive value of myocardial perfusion single-photon emission computed tomography and the impact of renal function on cardiac death.

PubMed

Hakeem, Abdul; Bhatti, Sabha; Dillie, Kathryn Sullivan; Cook, Jeffrey R; Samad, Zainab; Roth-Cline, Michelle D; Chang, Su Min

2008-12-09

Patients with chronic kidney disease (CKD) have worse cardiovascular outcomes than those without CKD. The prognostic utility of myocardial perfusion single-photon emission CT (MPS) in patients with varying degrees of renal dysfunction and the impact of CKD on cardiac death prediction in patients undergoing MPS have not been investigated. We followed up 1652 consecutive patients who underwent stress MPS (32% exercise, 95% gated) for cardiac death for a mean of 2.15+/-0.8 years. MPS defects were defined with a summed stress score (normal summed stress score <4, abnormal summed stress score>or=4). Ischemia was defined as a summed stress score >or=4 plus a summed difference score >or=2, and scar was defined as a summed difference score <2 plus a summed stress score >or=4. Renal function was calculated with the Modified Diet in Renal Disease equation. CKD (estimated glomerular filtration rate <60 mL . min(-1) . 1.73 m(-2)) was present in 36%. Cardiac death increased with worsening levels of perfusion defects across the entire spectrum of renal function. Presence of ischemia was independently predictive of cardiac death, all-cause mortality, and nonfatal myocardial infarction. Patients with normal MPS and CKD had higher unadjusted cardiac death event rates than those with no CKD and normal MPS (2.7% versus 0.8%, P=0.001). Multivariate Cox proportional hazards models revealed that both perfusion defects (hazard ratio 1.90, 95% CI 1.47 to 2.46) and CKD (hazard ratio 1.96, 95% CI 1.29 to 2.95) were independent predictors of cardiac death after accounting for risk factors, left ventricular dysfunction, pharmacological stress, and symptom status. Both MPS and CKD had incremental power for cardiac death prediction over baseline risk factors and left ventricular dysfunction (global chi(2) 207.5 versus 169.3, P<0.0001). MPS provides effective risk stratification across the entire spectrum of renal function. Renal dysfunction is also an important independent predictor of cardiac death in patients undergoing MPS. Renal function and MPS have additive value in risk stratisfying patients with suspected coronary artery disease. Patients with CKD appear to have a relatively less benign prognosis than those without CKD, even in the presence of a normal scan.

The Predictive Role of Serum Triglyceride to High-Density Lipoprotein Cholesterol Ratio According to Renal Function in Patients with Acute Myocardial Infarction.

PubMed

Kim, Jin Sug; Kim, Weon; Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyoon; Moon, Joo Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

2016-01-01

A high serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been reported as an independent predictor for cardiovascular events in the general population. However, the prognostic value of this ratio in patients with renal dysfunction is unclear. We examined the association of the TG/HDL-C ratio with major adverse cardiovascular events (MACEs) according to renal function in patients with acute myocardial infarction (AMI). This study was based on the Korea Acute Myocardial Infarction Registry database. Of 13,897 patients who were diagnosed with AMI, the study population included the 7,016 patients with available TG/HDL-C ratio data. Patients were stratified into three groups according to their estimated glomerular filtration rate (eGFR), and the TG/HDL-C ratio was categorized into tertiles. We investigated 12-month MACEs, which included cardiac death, myocardial infarction, and repeated percutaneous coronary intervention or coronary artery bypass grafting. During the 12-month follow up period, 593 patients experienced MACEs. There was a significant association between the TG/HDL-C ratio and MACEs (p<0.001) in the entire study cohort. Having a TG/HDL-C ratio value in the highest tertile of TG/HDL-C ratio was an independent factor associated with increased risk of MACEs (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.26-1.93; p<0.001). Then we performed subgroup analyses according to renal function. In patients with normal renal function (eGFR ≥ 90 ml/min/1.73m2) and mild renal dysfunction (eGFR ≥ 60 to < 90ml/min/1.73m2), a higher TG/HDL-C ratio was significantly associated with increased risk of MACEs (HR, 1.64; 95% CI, 1.04-2.60; p = 0.035; and HR, 1.56; 95% CI, 1.14-2.12; p = 0.005, respectively). However, in patients with moderate renal dysfunction (eGFR < 60 ml/min/1.73m2), TG/HDL-C ratio lost its predictive value on the risk of MACEs (HR, 1.23; 95% CI, 0.82-1.83; p = 0.317). In patients with AMI, TG/HDL-C ratio is a useful independent predictor of 12-month MACEs. However, this ratio does not have predictive power in patients with moderate renal dysfunction.

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

PubMed

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

2015-01-01

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

The protective effect of baicalin against renal ischemia-reperfusion injury through inhibition of inflammation and apoptosis

PubMed Central

2014-01-01

Background Renal ischemia-reperfusion injury (IRI) increases the rates of acute kidney failure, delayed graft function, and early mortality after kidney transplantation. The pathophysiology involved includes oxidative stress, mitochondrial dysfunction, and immune-mediated injury. The anti-oxidation, anti-apoptosis, and anti-inflammation properties of baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis, have been verified. This study therefore assessed the effects of baicalin against renal IRI in rats. Methods Baicalin was intraperitoneally injected 30 min before renal ischemia. Serum and kidneys were harvested 24 h after reperfusion. Renal function and histological changes were assessed. Markers of oxidative stress, the Toll-like receptor (TLR)2 and TLR4 signaling pathway, mitochondrial stress, and cell apoptosis were also evaluated. Results Baicalin treatment decreased oxidative stress and histological injury, and improved kidney function, as well as inhibiting proinflammatory responses and tubular apoptosis. Baicalin pretreatment also reduced the expression of TLR2, TLR4, MyD88, p-NF-κB, and p-IκB proteins, as well as decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio. Conclusions Baicalin may attenuate renal ischemia-reperfusion injury by inhibiting proinflammatory responses and mitochondria-mediated apoptosis. These effects are associated with the TLR2/4 signaling pathway and mitochondrial stress. PMID:24417870

The protective effect of baicalin against renal ischemia-reperfusion injury through inhibition of inflammation and apoptosis.

PubMed

Lin, Miao; Li, Long; Li, Liping; Pokhrel, Gaurab; Qi, Guisheng; Rong, Ruiming; Zhu, Tongyu

2014-01-13

Renal ischemia-reperfusion injury (IRI) increases the rates of acute kidney failure, delayed graft function, and early mortality after kidney transplantation. The pathophysiology involved includes oxidative stress, mitochondrial dysfunction, and immune-mediated injury. The anti-oxidation, anti-apoptosis, and anti-inflammation properties of baicalin, a flavonoid glycoside isolated from Scutellaria baicalensis, have been verified. This study therefore assessed the effects of baicalin against renal IRI in rats. Baicalin was intraperitoneally injected 30 min before renal ischemia. Serum and kidneys were harvested 24 h after reperfusion. Renal function and histological changes were assessed. Markers of oxidative stress, the Toll-like receptor (TLR)2 and TLR4 signaling pathway, mitochondrial stress, and cell apoptosis were also evaluated. Baicalin treatment decreased oxidative stress and histological injury, and improved kidney function, as well as inhibiting proinflammatory responses and tubular apoptosis. Baicalin pretreatment also reduced the expression of TLR2, TLR4, MyD88, p-NF-κB, and p-IκB proteins, as well as decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio. Baicalin may attenuate renal ischemia-reperfusion injury by inhibiting proinflammatory responses and mitochondria-mediated apoptosis. These effects are associated with the TLR2/4 signaling pathway and mitochondrial stress.

A bio-artificial renal epithelial cell system conveys survival advantage in a porcine model of septic shock.

PubMed

Westover, Angela J; Buffington, Deborah A; Johnston, Kimberly A; Smith, Peter L; Pino, Christopher J; Humes, H David

2017-03-01

Renal cell therapy using the hollow fiber based renal assist device (RAD) improved survival time in an animal model of septic shock (SS) through the amelioration of cardiac and vascular dysfunction. Safety and ability of the RAD to improve clinical outcomes was demonstrated in a Phase II clinical trial, in which patients had high prevalence of sepsis. Even with these promising results, clinical delivery of cell therapy is hampered by manufacturing hurdles, including cell sourcing, large-scale device manufacture, storage and delivery. To address these limitations, the bioartificial renal epithelial cell system (BRECS) was developed. The BRECS contains human renal tubule epithelial cells derived from adult progenitor cells using enhanced propagation techniques. Cells were seeded onto trabeculated disks of niobium-coated carbon, held within cryopreservable, perfusable, injection-moulded polycarbonate housing. The study objective was to evaluate the BRECS in a porcine model of SS to establish conservation of efficacy after necessary cell sourcing and design modifications; a pre-clinical requirement to move back into clinical trials. SS was incited by peritoneal injection of E. coli simultaneous to insertion of BRECS (n=10) or control (n=15), into the ultrafiltrate biofeedback component of an extracorporeal circuit. Comparable to RAD, prolonged survival of the BRECS cohort was conveyed through stabilization of cardiac output and vascular leak. In conclusion, the demonstration of conserved efficacy with BRECS therapy in a porcine SS model represents a crucial step toward returning renal cell therapy to the clinical setting, initially targeting ICU patients with acute kidney injury requiring continuous renal replacement therapy. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Euterpe oleracea Mart. seed extract protects against renal injury in diabetic and spontaneously hypertensive rats: role of inflammation and oxidative stress.

PubMed

da Silva Cristino Cordeiro, Viviane; de Bem, Graziele Freitas; da Costa, Cristiane Aguiar; Santos, Izabelle Barcellos; de Carvalho, Lenize Costa Reis Marins; Ognibene, Dayane Teixeira; da Rocha, Ana Paula Machado; de Carvalho, Jorge José; de Moura, Roberto Soares; Resende, Angela Castro

2018-03-01

Euterpe oleracea Mart. (açaí) seed extract (ASE), through its anti-hypertensive, antioxidant and anti-inflammatory properties, may be useful to treat or prevent human diseases. Several evidences suggest that oxidative stress and inflammation contribute to the pathogenesis of diabetic nephropathy; therefore, we tested the hypothesis that ASE (200 mg/kg -1 day -1 ) prevents diabetes and hypertension-related oxidative stress and inflammation, attenuating renal injury. Male rats with streptozotocin (STZ)-induced diabetes (D), and spontaneously hypertensive rats with STZ-induced diabetes (DH) were treated daily with tap water or ASE (D + ASE and DH + ASE, respectively) for 45 days. The control (C) and hypertensive (H) animals received water. The elevated serum levels of urea and creatinine in D and DH, and increased albumin excretion in HD were reduced by ASE. Total glomeruli number in D and DH, were increased by ASE that also reduced renal fibrosis in both groups by decreasing collagen IV and TGF-β1 expression. ASE improved biomarkers of renal filtration barrier (podocin and nephrin) in D and DH groups and prevented the increased expression of caspase-3, IL-6, TNF-α and MCP-1 in both groups. ASE reduced oxidative damage markers (TBARS, carbonyl levels and 8-isoprostane) in D and DH associated with a decrease in Nox 4 and p47 subunit expression and increase in antioxidant enzyme activity in both groups (SOD, catalase and GPx). ASE substantially reduced renal injury and prevented renal dysfunction by reducing inflammation, oxidative stress and improving the renal filtration barrier, providing a nutritional resource for prevention of diabetic and hypertensive-related nephropathy.

Potential beneficial effects of sacubitril-valsartan in renal disease: a new field for a new drug.

PubMed

Gervasini, Guillermo; Robles, Nicolas Roberto

2017-05-01

Patients with renal dysfunction are at a higher risk of cardiovascular disease (CVD), which often shares manifestations with heart failure (HF). Last year, the FDA approved the use of sacubitril-valsartan in patients with HF. This dual-acting agent enhances the functions of natriuretic peptides and inhibits the renin-angiotensin system. Areas covered: This review summarizes the existing preclinical and clinical studies carried out with sacubitril-valsartan (and other drugs with similar pharmacological mechanisms) in HF and hypertensive patients. We put the focus on the renal data provided by these studies. Data were obtained from English peer-reviewed articles on PubMed and clinical trials registered in ClinicalTrials.gov. Expert opinion: Overall, sacubitril-valsartan might be a promising therapeutic approach in patients with renal dysfunction. Renal conditions with marked CV risk, such as arterionephrosclerosis, could constitute a particular setting where to evaluate the impact of the drug. Nevertheless, large, randomized trials are needed to confirm the beneficial effects and safety profile of the drug in renal patients, as well as to elucidate some concerns observed in HF trials, such as the slight increase in proteinuria.

Effect of first myocardial ischemic event on renal function.

PubMed

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

2007-07-01

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

Renal hemodynamic effects of the HMG-CoA reductase inhibitors in autosomal dominant polycystic kidney disease

PubMed Central

Zand, Ladan; Torres, Vicente E.; Larson, Timothy S.; King, Bernard F.; Sethi, Sanjeev; Bergstralh, Eric J.; Angioi, Andrea; Fervenza, Fernando C.

2016-01-01

Background To determine the effect of statins on renal hemodynamics in normal volunteers and those with autosomal dominant polycystic kidney disease either with mild or moderate renal dysfunction. Methods Thirty-two study subjects were enrolled in this study: 11 normal volunteers, 11 study subjects with autosomal dominant polycystic kidney disease (ADPKD) and mild kidney disease and 10 study subjects with ADPKD and moderate kidney disease. Subjects in each group received simvastatin 40 mg once daily for a period of 4 weeks. Renal blood flow was measured based on para-amino-hippurate (PAH) clearance and with the use of a magnetic resonance (MR) scanner at the beginning and following 4 weeks of therapy with statins. Results At the end of the study, except for the lipid profile, which was significantly lower in all groups, other laboratory results showed no change. Four weeks of therapy with simvastatin resulted in no change in serum creatinine, 24-h urinary protein, sodium, iothalamate clearance, PAH clearance or renal blood flow as measured by MRI or based on PAH clearance. Conclusions Four weeks of therapy with simvastatin did not change renal blood flow in the study subjects with ADPKD with mild-to-moderate renal dysfunction or in healthy volunteers. Clinical Trial Registration Number NCT02511418. PMID:26614268

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.

Cerebro-renal interactions: impact of uremic toxins on cognitive function.

PubMed

Watanabe, Kimio; Watanabe, Tsuyoshi; Nakayama, Masaaki

2014-09-01

Cognitive impairment (CI) associated with chronic kidney disease (CKD) has received attention as an important problem in recent years. Causes of CI with CKD are multifactorial, and include cerebrovascular disease, renal anemia, secondary hyperparathyroidism, dialysis disequilibrium, and uremic toxins (UTs). Among these causes, little is known about the role of UTs. We therefore selected 21 uremic compounds, and summarized reports of cerebro-renal interactions associated with UTs. Among the compounds, uric acid, indoxyl sulfate, p-cresyl sulfate, interleukin 1-β, interleukin 6, TNF-α, and PTH were most likely to affect the cerebro-renal interaction dysfunction; however, sufficient data have not been obtained for other UTs. Notably, most of the data were not obtained under uremic conditions; therefore, the impact and mechanism of each UT on cognition and central nervous system in uremic state remains unknown. At present, impacts and mechanisms of UT effects on cognition are poorly understood. Clarifying the mechanisms and establishing novel therapeutic strategies for cerebro-renal interaction dysfunction is expected to be subject of future research. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-01-01

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

Thyroid function modifies the association between ratio of triglyceride to high-density lipoprotein cholesterol and renal function: a multicenter cross-sectional study

PubMed Central

Yuan, Zhongshang; Zhao, Meng; Zhang, Bingchang; Zhang, Haiqing; Zhang, Xu; Guan, Qingbo; Ning, Guang; Gao, Ling; Xue, Fuzhong; Zhao, Jiajun

2015-01-01

Hypothyroidism was confirmed to be associated with both dyslipidemia and renal dysfunction. However, the impact of thyroid function on the relationship between serum lipid levels and renal function has never been given sufficient attention. In this large-scale multicenter cross-sectional study, the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) and the prevalence of hypothyroidism in CKD subjects were significantly higher than those in non-CKD ones (P < 0.001). After adjustment for potential confounding factors, TG/HDL was shown to be significantly associated with serum Cr levels (β = 0.551; 95%CI, 0.394–0.708), and eGFR (β = −0.481; 95%CI, −0.731–−0.230). The risk for CKD was significantly increased as TG/HDL ratio was elevated (adjusted odds ratio = 1.20; 95%CI, 1.11–1.27). These significant associations were found among subjects with euthyroidism and hypothyroidism rather than hyperthyroidism. Furthermore, the associations between TG/HDL and Cr or CKD status were significantly greater in hypothyroidism than those in euthyroidism (P < 0.05). These results suggested that elevated TG/HDL ratio was associated with renal dysfunction; it exhibited a significantly stronger association with Cr and CKD in hypothyroidism than in euthyroidism. Therefore, more attention should be paid on lipid profile to prevent or delay the occurrence and progression of renal dysfunction, especially for those with hypothyroidism. PMID:26179571

Thyroid function modifies the association between ratio of triglyceride to high-density lipoprotein cholesterol and renal function: a multicenter cross-sectional study.

PubMed

Yuan, Zhongshang; Zhao, Meng; Zhang, Bingchang; Zhang, Haiqing; Zhang, Xu; Guan, Qingbo; Ning, Guang; Gao, Ling; Xue, Fuzhong; Zhao, Jiajun

2015-07-16

Hypothyroidism was confirmed to be associated with both dyslipidemia and renal dysfunction. However, the impact of thyroid function on the relationship between serum lipid levels and renal function has never been given sufficient attention. In this large-scale multicenter cross-sectional study, the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) and the prevalence of hypothyroidism in CKD subjects were significantly higher than those in non-CKD ones (P < 0.001). After adjustment for potential confounding factors, TG/HDL was shown to be significantly associated with serum Cr levels (β = 0.551; 95%CI, 0.394-0.708), and eGFR (β = -0.481; 95%CI, -0.731--0.230). The risk for CKD was significantly increased as TG/HDL ratio was elevated (adjusted odds ratio = 1.20; 95%CI, 1.11-1.27). These significant associations were found among subjects with euthyroidism and hypothyroidism rather than hyperthyroidism. Furthermore, the associations between TG/HDL and Cr or CKD status were significantly greater in hypothyroidism than those in euthyroidism (P < 0.05). These results suggested that elevated TG/HDL ratio was associated with renal dysfunction; it exhibited a significantly stronger association with Cr and CKD in hypothyroidism than in euthyroidism. Therefore, more attention should be paid on lipid profile to prevent or delay the occurrence and progression of renal dysfunction, especially for those with hypothyroidism.

Impact of initial 24-h urine output on short-term outcomes in patients with ST-segment elevation myocardial infarction admitted without cardiogenic shock and renal dysfunction.

PubMed

Huang, Bi; Yang, Yanmin; Zhu, Jun; Liang, Yan; Tan, Huiqiong; Yu, Litian; Gao, Xin; Li, Jiandong; Zhang, Han; Wang, Juan; Wan, Huaibin

2015-05-01

Our study aims to evaluate the prognostic value of initial 24-h urine output (UO) in patients with ST-segment elevation myocardial infarction (STEMI) admitted without cardiogenic shock and renal dysfunction, and to determine the additional risk stratification offered by adding initial 24-h UO to TIMI risk score (TRS). Data from 7078 consecutive STEMI patients in a multi-center registry were retrospectively analyzed. Patients were divided into 4 groups according to initial 24-h UO quartiles. The primary endpoints were 7- and 30-day all-cause mortality. Patients in the lowest UO quartile (≤1020 mL) had significantly higher 7- and 30-day all-cause mortality rates, cardiogenic shock, and major adverse cardiovascular events (MACE) than those in other groups (all P<0.05). After multivariate adjustment, initial 24-h UO≤1020 mL was independently associated with an increased risk in 7-day all-cause mortality (HR=4.649, 95%CI 3.348-6.455) and 30-day all-cause mortality (HR=3.775, 95%CI 2.891-4.931) as well as 7-day MACE (HR=1.845, 95%CI 1.563-2.179) and 30-day MACE (HR=1.818, 95%CI 1.553-2.127). Initial 24-h UO provided additional risk stratification across all TRS groups and improved the discriminatory ability of TRS with respect to 7-day all-cause mortality (c-statistic from 0.704 to 0.764) and 30-day all-cause mortality (c-statistic from 0.706 to 0.743). Reduced initial 24-h UO (≤1020 mL) was associated with an increased risk in 7- and 30-day all-cause mortality and MACE in STEMI patients admitted without cardiogenic shock and renal dysfunction. The combination of initial 24-h UO and TRS improved short-term outcome prediction when compared to TRS alone, particularly in patients with initial 24-h UO≤1020 mL. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

28 CFR 79.61 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the lung or pulmonary fibrosis means chronic inflammation and scarring of the pulmonary interstitium... Criteria for Claims by Ore Transporters § 79.61 Definitions. (a) Chronic renal disease means the chronic... resulting in chronic renal dysfunction. (j) Nonmalignant respiratory disease means fibrosis of the lung...

28 CFR 79.61 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... The term includes in situ lung cancers. (m) Readily available documentation means documents in the... injury means structural or functional damage to the kidney tubules that results in renal disease and... resulting in chronic renal dysfunction. (j) Nonmalignant respiratory disease means fibrosis of the lung...

Valsartan attenuates cardiac and renal hypertrophy in rats with experimental cardiorenal syndrome possibly through down-regulating galectin-3 signaling.

PubMed

Zhang, M-J; Gu, Y; Wang, H; Zhu, P-F; Liu, X-Y; Wu, J

2016-01-01

Aortocaval fistula (AV) induced chronic volume overload in rats with preexisting mild renal dysfunction (right kidney remove: UNX) could mimic the type 4 cardiorenal syndrome (CRS): chronic renocardiac syndrome. Galectin-3, a β-galactoside binding lectin, is an emerging biomarker in cardiovascular as well as renal diseases. We observed the impact of valsartan on cardiac and renal hypertrophy and galectin-3 changes in this model. Adult male Sprague-Dawley (SD) rats (200-250 g) were divided into S (Sham, n = 7), M (UNX+AV, n = 7) and M+V (UNX+AV+valsartan, n = 7) groups. Eight weeks later, cardiac function was measured by echocardiography. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, renal blood flow and 24 hours albuminuria. Immunohistochemistry and real-time PCR were used to evaluate the expressions of galectin-3 in heart and renal. Cardiac hypertrophy and renal hypertrophy as well as cardiac enlargement were evidenced in this AV shunt induced chronic volume overload rat model with preexisting mild renal dysfunction. Cardiac and renal hypertrophy were significantly attenuated but cardiac enlargement was unaffected by valsartan independent of its blood pressure lowering effect. 24 hours urine albumin was significantly increased, which was significantly reduced by valsartan in this model. Immunohistochemistry and real-time PCR evidenced significantly up-regulated galectin-3 expression in heart and kidney and borderline increased myocardial collagen I expression, which tended to be lower post valsartan treatment. Up-regulated galectin-3 signaling might also be involved in the pathogenesis in this CRS model. The beneficial effects of valsartan in terms of attenuating cardiac and renal hypertrophy and reducing 24 hours albumin in this model might partly be mediated through down-regulating galectin-3 signal pathway.

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis

PubMed Central

Yeh, Huei-Ming; Lin, Ting-Tse; Yeh, Chih-Fan; Huang, Ho-Shiang; Chang, Sheng-Nan; Lin, Jou-Wei; Tsai, Chia-Ti; Lai, Ling-Ping; Huang, Yi-You

2017-01-01

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson’s correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis. PMID:29161313

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis.

PubMed

Yeh, Huei-Ming; Lin, Ting-Tse; Yeh, Chih-Fan; Huang, Ho-Shiang; Chang, Sheng-Nan; Lin, Jou-Wei; Tsai, Chia-Ti; Lai, Ling-Ping; Huang, Yi-You; Chu, Chun-Lin

2017-01-01

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson's correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.

Tolerability of sirolimus: a decade of experience at a single cardiac transplant center.

PubMed

Thibodeau, Jennifer T; Mishkin, Joseph D; Patel, Parag C; Kaiser, Patricia A; Ayers, Colby R; Mammen, Pradeep P A; Markham, David W; Ring, William Steves; Peltz, Matthias; Drazner, Mark H

2013-01-01

Sirolimus is used in cardiac transplant recipients to prevent rejection, progression of cardiac allograft vasculopathy, and renal dysfunction. However, sirolimus has many potential side effects and its tolerability when used outside of clinical trials is not well established. We describe a decade of experience with sirolimus in cardiac transplant recipients at our institution. We retrospectively reviewed records of all adult cardiac transplant recipients living between September 1999 and February 2010 (n = 329) and identified 67 patients (20%) who received sirolimus. The indications for sirolimus were cardiac allograft vasculopathy (67%), renal dysfunction (25%), rejection (4%), and intolerability of tacrolimus (3%). One-third of patients discontinued sirolimus at a median (25th, 75th percentiles) of 0.9 (0.2, 1.6) yr of duration. Over 70% of subjects experienced an adverse event attributed to sirolimus. Adverse events were associated with higher average sirolimus levels (9.1 ng/mL vs. 7.1 ng/mL, p = 0.004). We conclude that sirolimus is frequently used in cardiac transplant recipients (20%) and commonly causes side effects, often necessitating discontinuation. Higher average sirolimus levels were associated with adverse events, suggesting that tolerability may improve if levels are maintained within the lower end of the current therapeutic range; however, the improvement in tolerability would need to be balanced with the potential for decreased efficacy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

PubMed Central

Zheng, Hong; Liu, Xuefei; Sharma, Neeru M.

2016-01-01

Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/dt to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/dt (by 71%) and −dP/dt (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition. PMID:27288440

Serum cystatin C is an independent biomarker associated with the renal resistive index in patients with chronic kidney disease.

PubMed

Ogawa-Akiyama, Ayu; Sugiyama, Hitoshi; Kitagawa, Masashi; Tanaka, Keiko; Onishi, Akifumi; Yamanari, Toshio; Morinaga, Hiroshi; Uchida, Haruhito Adam; Nakamura, Kazufumi; Ito, Hiroshi; Wada, Jun

2018-01-01

Cystatin C is a cysteine protease inhibitor that is produced by nearly all human cells. The serum level of cystatin C is a stronger predictor of the renal outcome and the risk of cardiovascular events than the creatinine level. The resistive index (RI) on renal Doppler ultrasonography is a good indicator of vascular resistance as well as the renal outcomes in patients with chronic kidney disease (CKD). However, it is unclear whether serum cystatin C is associated with signs of vascular dysfunction, such as the renal RI. We measured the serum cystatin C levels in 101 CKD patients and investigated the relationships between cystatin C and markers of vascular dysfunction, including the renal RI, ankle-brachial pulse wave velocity (baPWV), intima-media thickness (IMT), and cardiac function. The renal RI was significantly correlated with the serum cystatin C level (p < 0.0001, r = 0.6920). The serum cystatin C level was found to be a significant determinant of the renal RI (p < 0.0001), but not the baPWV, in a multivariate regression analysis. The multivariate odds ratio of the serum cystatin C level for a renal RI of more than 0.66 was statistically significant (2.92, p = 0.0106). The area under the receiver-operating characteristic curve comparing the sensitivity and specificity of cystatin C for predicting an RI of more than 0.66 was 0.882 (cutoff value: 2.04 mg/L). In conclusion, the serum cystatin C level is an independent biomarker associated with the renal RI in patients with CKD.

[Cyclic vomiting with ketosis as a cause of acute kidney dysfunction: own clinical experience].

PubMed

Ostrowska-Nawarycz, L; Rapacka, E; Baszczyński, J; Górski, P; Czajka, J; Makowski, M; Kudzin, A

2000-04-01

The aim of the study was to evaluate renal activity during cyclic vomiting with ketosis. The clinical material was obtained from 50 cases of children hospitalized in Department of Pediatrics Military Medical University within 1993-1999 what makes about 1% of all patients. The examined group consisted of 26 boys (52%) and 24 girls (48%). Three of the children were repeatedly hospitalized (3 to 8 times) because of acetonemic vomiting. The special attention during the laboratory studies was paid to evaluation of renal activity. Vomiting with ketosis were associated with temporary kidneys acute dysfunction in 46% of cases. In 98% of cases the parenteral hydration was necessary. Ketonemic vomiting with kidneys dysfunction was observed mainly with the children in pre-school age.

Histological analysis on adhesive molecules of renal intravascular large B cell lymphoma treated with CHOP chemotherapy and rituximab.

PubMed

Kusaba, T; Hatta, T; Tanda, S; Kameyama, H; Tamagaki, K; Okigaki, M; Inaba, T; Shimazaki, C; Sasaki, S

2006-03-01

A 48-year-old man was admitted to our hospital for investigation of mild renal dysfunction. A blood examination revealed mild elevation of creatinine level (1.77 mg/dl). Urinary examination revealed mild protein excretion (0.54 g/day) and microhematuria; renal biopsy revealed the focal proliferation of large mononuclear cells with mitosis in glomerular capillaries. According to immunohistochemical analysis, the intravascular lymphomatous cells stained positively with anti-leukocyte common antigen (LCA: CD45) and CD20, indicating a B lymphocyte lineage. In electron microscopy, the glomerular capillary was filled with lymphoma cells and epithelial foot process fusion was noted. Immunohistochemical analysis on adhesive molecules revealed a lack of CD11a expression on lymphoma cells, but positive CD54 expression on endothelial cells. Systemic 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) revealed no abnormal uptake of isotopes. On the basis of these findings, we diagnosed intravascular diffuse large B cell lymphoma localized in the kidney. Despite treatment with rituximab and CHOP (prednisolone, doxorubicin, vincristine, cyclophosphamide) for 3 cycles at 1-month intervals, the renal dysfunction did not change. In histopathological analysis of the second biopsy, lymphoma cells disappeared, but focal segmental glomerulosclerosis and moderate interstitial fibrosis were noted. Electron microscopic findings revealed severe subendothelial edema with mesangial interposition, indicating severe endothelial damage. Epithelial foot process fusion was improved. These pathological analyses let us conclude that a lack of CD11a could be a candidate factor for prevention of the extravasation of lymphoma cells from blood vessels in our patient. We also presumed that the intraglomerular endothelial damage occurred due to chemotherapy-associated cell injury.

Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628.

PubMed

Ma, Frank Y; Han, Yingjie; Nikolic-Paterson, David J; Kolkhof, Peter; Tesch, Greg H

2015-01-01

Steroidal mineralocorticoid receptor antagonists (MRAs) are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis. Accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid) from day 0 until being killed on day 15 of disease. Mice were examined for renal injury. Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ) and profibrotic molecules (collagen I, fibronectin). In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction). The non-steroidal MRA (BR-4628) provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

Effect of Cordyceps sinensis on renal function of patients with chronic allograft nephropathy.

PubMed

Zhang, Zhihong; Wang, Xiangwei; Zhang, Yuanning; Ye, Gang

2011-01-01

To investigate the effect of Cordyceps sinensis (Bailing capsule, fermented agent of C. sinensis) on renal function of patients with chronic allograft nephropathy (CAN). A total of 231 CAN patients who underwent transplantation between 2005 and 2008 and experienced chronic graft dysfunction were randomly divided into 2 groups. Patients in group A (n = 122) were treated with immunosuppressive agents and C. sinensis (2.0 g/day, 3 times a day), while patients in group B (n = 109) were treated with traditional immunosuppressive drugs. Serum creatinine (SCr), blood urea nitrogen (BUN), creatinine clearance rate (C(Cr)) and urinary protein in 24 h (24-hour Upro) of all patients were measured before and after treatment. Urinary concentrations of transforming growth factor (TGF)-β(1), retinol-binding protein (RBP) and β(2)-microglobulin (β(2)-MG) were detected at the same time. After 6-month treatment with C. sinensis, SCr and C(Cr) in group A were significantly improved (p < 0.05), while there was no significant improvement observed for group B. There was no significant change in BUN in groups A and B (p > 0.05). 24-hour Upro, RBP and β(2)-MG were lower in group A after treatment with C. sinensis (p < 0.05 or p < 0.01), and urinary TGF-β(1) in group A was significantly lower than the values before C. sinensis treatment (p < 0.05), but showed no change in patients of group B. In group A, renal function had improved in 72 cases, stabilized in 38 cases, and worsened in 12 cases. In group B, renal function had improved in 14 cases, stabilized in 50 cases, and worsened in 45 cases (p < 0.05). C. sinensis therapy is advantageous in improving renal function of CAN patients by retarding CAN progression. Copyright © 2011 S. Karger AG, Basel.

28 CFR 79.51 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Cor pulmonale means heart disease, including hypertrophy of the right ventricle, due to pulmonary... Criteria for Claims by Uranium Millers § 79.51 Definitions. (a) Chronic renal disease means the chronic... or functional damage to the kidney tubules that results in renal disease and dysfunction. (g) Miller...

28 CFR 79.51 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Cor pulmonale means heart disease, including hypertrophy of the right ventricle, due to pulmonary... Criteria for Claims by Uranium Millers § 79.51 Definitions. (a) Chronic renal disease means the chronic... or functional damage to the kidney tubules that results in renal disease and dysfunction. (g) Miller...

[Chronic renal disease as cardiovascular risk factor].

PubMed

Hermans, M M H; Kooman, J P; Stehouwer, C D A

2008-07-19

A lowering of the glomerular filtration rate (GFR) and/or the presence of albuminuria are signs of chronic renal disease. Both variables are for the most part independently associated with an increased risk of cardiovascular morbidity and mortality. Albuminuria is a marker of endothelial dysfunction. A decrease of the GFR is associated with non-traditional risk factors, e.g. renal anaemia, uraemic toxins due to a decrease of the renal clearance, hyperhomocysteinaemia caused by a diminished homocysteine metabolism, excessive activation of the sympathetic nervous system which is related to sleep apnoea syndrome, oxidative stress and dyslipidaemia associated with the formation of vasotoxic, oxidised LDL cholesterol. These non-traditional risk factors may, alone or in combination with traditional atherogenic risk factors (e.g. age, male gender, smoking, hypercholesterolaemia, hypertension, obesity, positive family history and diabetes mellitus), partially via endothelial dysfunction, result in harmful effects on arterial function, increasing cardiovascular morbidity and mortality. Different stages of chronic kidney disease are associated with specific risk factors, making a specific therapeutic approach essential.

Acute kidney injury by radiographic contrast media: pathogenesis and prevention.

PubMed

Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Sabbatini, Massimo; Michael, Ashour

2014-01-01

It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24-72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both.

Acute Kidney Injury by Radiographic Contrast Media: Pathogenesis and Prevention

PubMed Central

Faga, Teresa; Pisani, Antonio; Michael, Ashour

2014-01-01

It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24–72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both. PMID:25197639

Activation of adenosine receptors improves renal antioxidant status in diabetic Wistar but not SHR rats

PubMed Central

Patinha, Daniela; Afonso, Joana; Sousa, Teresa; Albino-Teixeira, António

2014-01-01

Background Diabetes and hypertension independently contribute to renal injury, and the major mechanisms involved are increased reactive oxygen species (ROS) bioavailability and renin-angiotensin system (RAS) activation. We investigated the role of adenosine in controlling ROS production and RAS activation associated with renal dysfunction in hypertension and diabetes. Methods Fourteen days after induction of diabetes with streptozotocin in 12-week-old male Wistar and spontaneously hypertensive (SHR) rats, animals were treated during 7 days with 2-chloroadenosine (CADO group, 5 mg/kg/d), a stable analogue of adenosine, or underwent a sham operation procedure. At the end of the study (day 21), intra-arterial systolic blood pressure (SBP) was measured, and 24-h urine and plasma samples and renal tissue were collected. Results CADO treatment decreased the plasma glucose concentration and glucose and protein excretion by more than 30% in both strains. CADO treatment decreased SBP in diabetic SHR rats (143 ± 8 versus 114 ± 4 mmHg, p < 0.05), but not in diabetic Wistar rats. The hypotensive effect of CADO was associated to a ∼70% increase in plasma angiotensinogen (AGT) concentration and a ∼50% decrease in urinary AGT excretion. CADO also caused a decrease in medullary and cortical hydrogen peroxide production of about 40%, which was associated with a proportional increase in glutathione peroxidase (GPx) activity in diabetic Wistar but not in diabetic SHR animals. Conclusions These results suggest that activation of adenosine receptors improves renal antioxidant capacity in diabetic Wistar but not SHR rats, although it improves glucose metabolism in both strains. Furthermore, activation of adenosine receptors does not seem to be directly influencing AGT production. PMID:24195577

5-aminoisoquinoline improves renal function and fibrosis during recovery phase of cisplatin-induced acute kidney injury in rats.

PubMed

Quesada, Andrés; O'Valle, Francisco; Montoro-Molina, Sebastián; Gómez-Morales, Mercedes; Caba-Molina, Mercedes; González, Juan Francisco; de Gracia, María C; Osuna, Antonio; Vargas, Félix; Wangensteen, Rosemary

2018-04-27

The aim of the present study is to analyze the effects of 5-aminoisoquinoline (5-AIQ), a poly(ADP-ribose) polymerase-1 (PARP1) inhibitor, over renal dysfunction and fibrosis during recovery phase of cisplatin (CisPt)-induced acute kidney injury (AKI) in rats. Male Wistar rats were distributed in three groups ( n =8 each group): control, CisPt, and CisPt + 5-AIQ. Control and CisPt groups received a subcutaneous injection of either saline or 7 mg/kg CisPt, respectively. CisPt + 5-AIQ group received two intraperitoneal injections of 10 mg/kg 5-AIQ 2 h before and 24 h after CisPt treatment. Thirteen days after the treatment, rats were housed in metabolic cages and 24-h urine collection was made. At day 14, CisPt-treated rats showed increased diuresis, N-acetyl-β-d-glucosaminidase (NAG) excretion, glucosuria and sodium fractional excretion (NaFE), and decreased creatinine clearance (CrCl). 5-AIQ significantly increased CrCl and decreased NAG excretion, glucosuria, and NaFE. In plasma, CisPt increased sodium, urea, and creatinine concentrations, while 5-AIQ treatment decreased these variables to the levels of control group. 5-AIQ completely prevented the body weight loss evoked by CisPt treatment. CisPt also induced an increased renal expression of PAR polymer, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and collagen-IV. These variables were decreased in CisPt + 5-AIQ group. Tubular lesions and renal fibrosis were also decreased by 5-AIQ treatment. We conclude that inhibition of PARP1 with 5-AIQ can attenuate long-term nephrotoxic effects associated with the CisPt treatment, preventing renal dysfunction and body weight decrease and ameliorating tubular lesions and collagen deposition. © 2018 The Author(s).

5-aminoisoquinoline improves renal function and fibrosis during recovery phase of cisplatin-induced acute kidney injury in rats

PubMed Central

Quesada, Andrés; O’Valle, Francisco; Montoro-Molina, Sebastián; Gómez-Morales, Mercedes; Caba-Molina, Mercedes; González, Juan Francisco; de Gracia, María C.; Osuna, Antonio; Vargas, Félix; Wangensteen, Rosemary

2018-01-01

The aim of the present study is to analyze the effects of 5-aminoisoquinoline (5-AIQ), a poly(ADP-ribose) polymerase-1 (PARP1) inhibitor, over renal dysfunction and fibrosis during recovery phase of cisplatin (CisPt)-induced acute kidney injury (AKI) in rats. Male Wistar rats were distributed in three groups (n=8 each group): control, CisPt, and CisPt + 5-AIQ. Control and CisPt groups received a subcutaneous injection of either saline or 7 mg/kg CisPt, respectively. CisPt + 5-AIQ group received two intraperitoneal injections of 10 mg/kg 5-AIQ 2 h before and 24 h after CisPt treatment. Thirteen days after the treatment, rats were housed in metabolic cages and 24-h urine collection was made. At day 14, CisPt-treated rats showed increased diuresis, N-acetyl-β-d-glucosaminidase (NAG) excretion, glucosuria and sodium fractional excretion (NaFE), and decreased creatinine clearance (CrCl). 5-AIQ significantly increased CrCl and decreased NAG excretion, glucosuria, and NaFE. In plasma, CisPt increased sodium, urea, and creatinine concentrations, while 5-AIQ treatment decreased these variables to the levels of control group. 5-AIQ completely prevented the body weight loss evoked by CisPt treatment. CisPt also induced an increased renal expression of PAR polymer, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and collagen-IV. These variables were decreased in CisPt + 5-AIQ group. Tubular lesions and renal fibrosis were also decreased by 5-AIQ treatment. We conclude that inhibition of PARP1 with 5-AIQ can attenuate long-term nephrotoxic effects associated with the CisPt treatment, preventing renal dysfunction and body weight decrease and ameliorating tubular lesions and collagen deposition. PMID:29599129

Endothelial Dysfunction Exacerbates Renal Interstitial Fibrosis through Enhancing Fibroblast Smad3 Linker Phosphorylation in the Mouse Obstructed Kidney

PubMed Central

Sun, Yu Bo Yang; Qu, Xinli; Li, Xueling; Nikolic-Paterson, David J.; Li, Jinhua

2013-01-01

Endothelial dysfunction and enhanced transforming growth factor-β (TGF-β)/Smad3 signalling are common features of progressive renal fibrosis. This study investigated a potential link between these mechanisms. In unilateral ureteric obstruction (UUO) we observed an acute (6 hr) down-regulation of nitric oxide synthase 3 (NOS3/eNOS) levels and increased phosphorylation of the linker region of Smad3 at T179 and S208 in Smad3/JNK complexes. These events preceded Smad3 C-terminal domain phosphorylation and the induction of myofibroblast proliferation at 48 hrs. Mice deficient in NOS3 showed enhanced myofibroblast proliferation and collagen accumulation compared to wild type mice in a 7 day UUO model. This was associated with enhanced phosphorylation of Smad3 T179 and S208 by 92% and 88%, respectively, whereas Smad3-C-terminal phosphorylation was not affected. Resolvin D1 (RvD1) can suppress renal fibrosis in the UUO model, and further analysis herein showed that RvD1 protected against endothelial dysfunction and suppressed Smad3/JNK complex formation with a consequent reduction in phosphorylation of Smad3 T179 and S208 by 78% and 65%, respectively, while Smad3 C-terminal phosphorylation was unaltered. In vitro, conditioned media from mouse microvascular endothelial cells (MMEC) treated with a general inhibitor of nitric oxide synthase (L-NAME) augmented the proliferation and collagen production of renal fibroblasts (NRK49F cells) compared to control MMEC media and this was associated with increased phosphorylation of JNK and Smad3 T179 and S208, whereas Smad3-C-terminal domain phosphorylation was unaffected. The addition of RvD1 to L-NAME treated MMEC abrogated these effects of the conditioned media on renal fibroblasts. Finally, Smad3 T179/V and S208/A mutations significantly inhibit TGF-β1 induced up-regulation collagen I promoter. In conclusion, these data suggest that endothelial dysfunction can exacerbate renal interstitial fibrosis through increased fibroblast proliferation and collagen production via enhanced Smad3 linker phosphorylation. PMID:24391884

Endothelial dysfunction exacerbates renal interstitial fibrosis through enhancing fibroblast Smad3 linker phosphorylation in the mouse obstructed kidney.

PubMed

Sun, Yu Bo Yang; Qu, Xinli; Li, Xueling; Nikolic-Paterson, David J; Li, Jinhua

2013-01-01

Endothelial dysfunction and enhanced transforming growth factor-β (TGF-β)/Smad3 signalling are common features of progressive renal fibrosis. This study investigated a potential link between these mechanisms. In unilateral ureteric obstruction (UUO) we observed an acute (6 hr) down-regulation of nitric oxide synthase 3 (NOS3/eNOS) levels and increased phosphorylation of the linker region of Smad3 at T179 and S208 in Smad3/JNK complexes. These events preceded Smad3 C-terminal domain phosphorylation and the induction of myofibroblast proliferation at 48 hrs. Mice deficient in NOS3 showed enhanced myofibroblast proliferation and collagen accumulation compared to wild type mice in a 7 day UUO model. This was associated with enhanced phosphorylation of Smad3 T179 and S208 by 92% and 88%, respectively, whereas Smad3-C-terminal phosphorylation was not affected. Resolvin D1 (RvD1) can suppress renal fibrosis in the UUO model, and further analysis herein showed that RvD1 protected against endothelial dysfunction and suppressed Smad3/JNK complex formation with a consequent reduction in phosphorylation of Smad3 T179 and S208 by 78% and 65%, respectively, while Smad3 C-terminal phosphorylation was unaltered. In vitro, conditioned media from mouse microvascular endothelial cells (MMEC) treated with a general inhibitor of nitric oxide synthase (L-NAME) augmented the proliferation and collagen production of renal fibroblasts (NRK49F cells) compared to control MMEC media and this was associated with increased phosphorylation of JNK and Smad3 T179 and S208, whereas Smad3-C-terminal domain phosphorylation was unaffected. The addition of RvD1 to L-NAME treated MMEC abrogated these effects of the conditioned media on renal fibroblasts. Finally, Smad3 T179/V and S208/A mutations significantly inhibit TGF-β1 induced up-regulation collagen I promoter. In conclusion, these data suggest that endothelial dysfunction can exacerbate renal interstitial fibrosis through increased fibroblast proliferation and collagen production via enhanced Smad3 linker phosphorylation.

Progressive kidney failure as the sole manifestation of extrapulmonary sarcoidosis.

PubMed

Sethi, Supreet; Relia, Nitin; Syal, Gaurav; Kaushik, Chhavi; Gokden, Neriman; Malik, Ahmad B

2013-09-01

Sarcoidosis is a chronic multisystem disorder characterized by an accumulation of T lymphocytes and mononuclear phagocytes, non-caseating epitheliod granulomas and derangement of normal tissue architecture in affected organs. Sarcoidosis can affect any organ system, however approximately 90% of patients with sarcoidosis have pulmonary, lymph node, cutaneous or ocular manifestations. Renal involvement in sarcoidosis is rare and clinically significant renal dysfunction even less common. We present a case of isolated renal sarcoidosis which manifested with progressively worsening renal function and hypercalcemia. A systematic diagnostic approach with pertinent laboratory studies, imaging and renal biopsy elucidated the diagnosis of renal sarcoidosis without any evidence of systemic involvement.

Continuous Flow Left Ventricular Assist Device Implant Significantly Improves Pulmonary Hypertension, Right Ventricular Contractility, and Tricuspid Valve Competence

PubMed Central

Atluri, Pavan; Fairman, Alexander S.; MacArthur, John W.; Goldstone, Andrew B.; Cohen, Jeffrey E.; Howard, Jessica L.; Zalewski, Christyna M.; Shudo, Yasuhiro; Woo, Y. Joseph

2014-01-01

Background Continuous flow left ventricular assist devices (CF LVAD) are being implanted with increasing frequency for end-stage heart failure. At the time of LVAD implant, a large proportion of patients have pulmonary hypertension, right ventricular (RV) dysfunction, and tricuspid regurgitation (TR). RV dysfunction and TR can exacerbate renal dysfunction, hepatic dysfunction, coagulopathy, edema, and even prohibit isolated LVAD implant. Repairing TR mandates increased cardiopulmonary bypass time and bicaval cannulation, which should be reserved for the time of orthotopic heart transplantation. We hypothesized that CF LVAD implant would improve pulmonary artery pressures, enhance RV function, and minimize TR, obviating need for surgical tricuspid repair. Methods One hundred fourteen continuous flow LVADs implanted from 2005 through 2011 at a single center, with medical management of functional TR, were retrospectively analyzed. Pulmonary artery pressures were measured immediately prior to and following LVAD implant. RV function and TR were graded according to standard echocardiographic criteria, prior to, immediately following, and long-term following LVAD. Results There was a significant improvement in post-VAD mean pulmonary arterial pressures (26.6 ± 4.9 vs. 30.2 ± 7.4 mmHg, p = 0.008) with equivalent loading pressures (CVP = 12.0 ± 4.0 vs. 12.1 ± 5.1 p = NS). RV function significantly improved, as noted by right ventricular stroke work index (7.04 ± 2.60 vs. 6.05 ± 2.54, p = 0.02). There was an immediate improvement in TR grade and RV function following LVAD implant, which was sustained long term. Conclusion Continuous flow LVAD implant improves pulmonary hypertension, RV function, and tricuspid regurgitation. TR may be managed nonoperatively during CF LVAD implant. PMID:24118109

Prognostic Significance of Interleukin-34 (IL-34) in Patients With Chronic Heart Failure With or Without Renal Insufficiency.

PubMed

Tao, Rong; Fan, Qin; Zhang, Hang; Xie, Hongyang; Lu, Lin; Gu, Gang; Wang, Fang; Xi, Rui; Hu, Jian; Chen, Qiujing; Niu, Wenquan; Shen, Weifeng; Zhang, Ruiyan; Yan, Xiaoxiang

2017-04-01

Renal dysfunction, commonly associated with cardiac dysfunction, has predictive value for adverse long-term outcomes in heart failure (HF). We previously identified a novel renal biomarker, interleukin-34 (IL-34), elevated in HF patients and associated with kidney dysfunction and coronary artery disease during HF. However, the prognostic value of IL-34 in HF remains unclear, so that the present study aimed to determine it. This prospective, observational study included 510 consecutive HF patients with their serum IL-34 as well as other variables measured at baseline, and they were followed up for 2 years. The primary end point was a composite of cardiovascular death or a first HF hospitalization, with cardiovascular death, HF hospitalization, and all-cause mortality as secondary outcomes. There was a significant and gradual increase in risk as IL-34 increased, determined by log-rank tests with Kaplan-Meier curves. Serum IL-34 was also a significant prognostic predictor of the primary end point (1.301 [1.115-1.518]; P =0.001), cardiovascular death (1.347 [1.096-1.655]; P =0.005), HF hospitalization (1.234 [1.018-1.494]; P =0.032), and all-cause mortality (1.343 [1.115-1.618]; P =0.002) in HF as per SD increase in the log IL-34 level after adjusting for age, sex, traditional risk factors, and N-terminal pro-brain natriuretic peptide. Especially, IL-34 had a more-significant prognostic value in HF patients with kidney impairment than those without. IL-34 is a significant predictor of cardiovascular death, HF hospitalization, and all-cause mortality in chronic HF, especially when concomitant with renal dysfunction. Serum IL-34 measurement may provide new insights linking kidney impairment to poor HF outcomes beyond other renal markers. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Loss of the Endothelial Glycocalyx Links Albuminuria and Vascular Dysfunction

PubMed Central

Ferguson, Joanne K.; Burford, James L.; Gevorgyan, Haykanush; Nakano, Daisuke; Harper, Steven J.; Bates, David O.; Peti-Peterdi, Janos

2012-01-01

Patients with albuminuria and CKD frequently have vascular dysfunction but the underlying mechanisms remain unclear. Because the endothelial surface layer, a meshwork of surface-bound and loosely adherent glycosaminoglycans and proteoglycans, modulates vascular function, its loss could contribute to both renal and systemic vascular dysfunction in proteinuric CKD. Using Munich-Wistar-Fromter (MWF) rats as a model of spontaneous albuminuric CKD, multiphoton fluorescence imaging and single-vessel physiology measurements revealed that old MWF rats exhibited widespread loss of the endothelial surface layer in parallel with defects in microvascular permeability to both water and albumin, in both continuous mesenteric microvessels and fenestrated glomerular microvessels. In contrast to young MWF rats, enzymatic disruption of the endothelial surface layer in old MWF rats resulted in neither additional loss of the layer nor additional changes in permeability. Intravenous injection of wheat germ agglutinin lectin and its adsorption onto the endothelial surface layer significantly improved glomerular albumin permeability. Taken together, these results suggest that widespread loss of the endothelial surface layer links albuminuric kidney disease with systemic vascular dysfunction, providing a potential therapeutic target for proteinuric kidney disease. PMID:22797190

An in vivo photodynamic therapy with diode laser to cell activation of kidney dysfunction

NASA Astrophysics Data System (ADS)

Dyah Astuti, Suryani; Indra Prasaja, Brahma; Anggono Prijo, Tri

2017-05-01

This study aims to analyze the effect of photodynamic therapy (PDT) low level laser therapy (LLLT) 650 nm in the experimental animals mice (Musmuculus) suffering from kidney organ damage in mice (Musmuculus) in vivo. Exposure laser acupuncture was performed on the kidney BL-23. The conditioning of kidney damage in mice used carbofuraan 35 at a dose of 0.041697 mg/mice. LLLT 650 nm exposure was done on a wide variety of energy (0.5; 1.0; 1.5; 2.0; 4.0; 5.0; 6.0; 7.0) J. The histopathological kidney cells in mice renal impairment showed that exposure to 650 nm laser energy 1 Joule resulted in the reduction of damaged cells (necrosis) and normal cells were increased with the improvement of renal tubular cells (64.14 ± 8:02)%. Therefore, exposure to 650 nm LLLT on acupuncture points Shenshu (BL-23) has the ability to proliferation of renal tubular cells of mice.

A case report of massive acute boric acid poisoning.

PubMed

Corradi, Francesco; Brusasco, Claudia; Palermo, Salvatore; Belvederi, Giulio

2010-02-01

Boric acid comes as colourless, odourless white powder and, if ingested, has potential fatal effects including metabolic acidosis, acute renal failure and shock. An 82-year-old male was brought to the emergency room 3 h after unintentional ingestion of a large amount of boric acid. Clinical course was monitored by collecting data at admittance, 12 h after admission, every 24 h for 5 days and again 1 week after admission. During the first 132 h, serum and urinary concentrations of boric acid were measured. Serum boric acid levels decreased from 1800 to 530 microg/ml after haemodialysis and from 530 to 30 microg/ml during the forced diuresis period. During dialysis, boric acid clearance averaged 235 ml/min with an extraction ratio of 70%. The overall patient's condition steadily improved over 84 h after admission. In conclusion, early treatment with forced diuresis and haemodialysis may be considered for boric acid poisoning, even if signs of renal dysfunction are not apparent, to prevent severe renal damage and its complications.

The effects of low environmental cadmium exposure on bone density

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

Trzcinka-Ochocka, M., E-mail: ochocka@imp.lodz.pl; Jakubowski, M.; Szymczak, W.

2010-04-15

Recent epidemiological data indicate that low environmental exposure to cadmium, as shown by cadmium body burden (Cd-U), is associated with renal dysfunction as well as an increased risk of cadmium-induced bone disorders. The present study was designed to assess the effects of low environmental cadmium exposure, at the level sufficient to induce kidney damage, on bone metabolism and mineral density (BMD). The project was conducted in the area contaminated with cadmium, nearby a zinc smelter located in the region of Poland where heavy industry prevails. The study population comprised 170 women (mean age=39.7; 18-70 years) and 100 men (mean age=31.9;more » 18-76 years). Urinary and blood cadmium and the markers of renal tubular dysfunction ({beta}{sub 2}M-U RBP, NAG), glomerular dysfunction (Alb-U and {beta}{sub 2}M-S) and bone metabolism markers (BAP-S, CTX-S) as well as forearm BMD, were measured. The results of this study based on simple dose-effect analysis showed the relationship between increasing cadmium concentrations and an increased excretion of renal dysfunction markers and decreasing bone density. However, the results of the multivariate analysis did not indicate the association between exposure to cadmium and decrease in bone density. They showed that the most important factors that have impact on bone density are body weight and age in the female subjects and body weight and calcium excretion in males. Our investigation revealed that the excretion of low molecular weight proteins occurred at a lower level of cadmium exposure than the possible loss of bone mass. It seems that renal tubular markers are the most sensitive and significant indicators of early health effects of cadmium intoxication in the general population. The correlation of urinary cadmium concentration with markers of kidney dysfunction was observed in the absence of significant correlations with bone effects. Our findings did not indicate any effects of environmental cadmium exposure on bone density.« less

Renal dysfunction and barttin expression in Bartter syndrome Type IV associated with a G47R mutation in BSND in a family.

PubMed

Park, C W; Lim, J H; Youn, D-Y; Chung, S; Lim, M-H; Kim, Y K; Chang, Y S; Lee, J-H

2011-02-01

Bartter syndrome (BS) Type IV, associated with a G47R mutation in the BSND gene, is known to result in a mild renal phenotype. However, we report here on three brothers with varying degrees of renal dysfunction from mild to end-stage renal disease associated with renal barttin and ClC-K expression. The brothers had histories of polyhydramnios, prematurity, polyuria, deafness, and small body size. Laboratory findings showed hypokalemic metabolic alkalosis, normotensive hyperreninemic hyperaldosteronism, and an increased urinary excretion of sodium, potassium and chloride, consistent with BS Type IV. Microscopic examination of renal tissue showed hyperplasia of cells at the juxtaglomerular apparatus with dilated atrophic tubules and tubulointerstitial fibrosis. A weak barttin signal related to CIC-K expression in the cytoplasm of tubule cells, but not the basement membrane, was noted. A sequence analysis of the BSND gene showed that the affected males were homozygous for a missense G47R mutation in exon 1 of BSND. These findings suggest that the G47R mutation results in a dramatic decrease in barttin expression, which appears to be related to the location of CIC-K being changed from the basement membrane to the cytoplasm in the tubule and might have varying effects on renal function associated with factors other than this gene.

Adrenalectomy prevents renal ischemia-reperfusion injury.

PubMed

Ramírez, Victoria; Trujillo, Joyce; Valdes, Rafael; Uribe, Norma; Cruz, Cristino; Gamba, Gerardo; Bobadilla, Norma A

2009-10-01

Spironolactone treatment prevents renal damage induced by ischemia-reperfusion (I/R), suggesting that renoprotection conferred by spironolactone is mediated by mineralocorticoid receptor (MR) blockade. It is possible, however, that this effect is due to other mechanisms. Therefore, this study evaluated whether adrenalectomy prevented renal damage induced by I/R. Three groups of Wistar rats were studied: 1) a group subjected to a sham surgery, 2) a group subjected to bilateral I/R, and 3) a group of rats in which adrenal glands were removed 3 days before induction of I/R. As expected, I/R resulted in renal dysfunction and severe tubular injury that was associated with a significant increase in tubular damage markers. In contrast, there was no renal dysfunction or tubular injury in rats that were adrenalectomized before I/R. These effects were demonstrated by normalization of glomerular filtration rate, markers of oxidative stress, and tubular injury markers in adrenalectomized rats. The renoprotection observed was associated with the reestablishment of nitric oxide metabolites, increased endothelial nitric oxide synthase expression and its activating phosphorylation, as well as normalization of Rho-kinase expression and ET(A) mRNA levels. Our results show that aldosterone plays a central role in the pathogenesis of renal damage induced by I/R and that MR blockade may be a promising strategy that opens a new therapeutic option for preventing acute renal injury.

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.

The Predictive Role of Serum Triglyceride to High-Density Lipoprotein Cholesterol Ratio According to Renal Function in Patients with Acute Myocardial Infarction

PubMed Central

Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyoon; Moon, Joo Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

2016-01-01

Objective A high serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been reported as an independent predictor for cardiovascular events in the general population. However, the prognostic value of this ratio in patients with renal dysfunction is unclear. We examined the association of the TG/HDL-C ratio with major adverse cardiovascular events (MACEs) according to renal function in patients with acute myocardial infarction (AMI). Method This study was based on the Korea Acute Myocardial Infarction Registry database. Of 13,897 patients who were diagnosed with AMI, the study population included the 7,016 patients with available TG/HDL-C ratio data. Patients were stratified into three groups according to their estimated glomerular filtration rate (eGFR), and the TG/HDL-C ratio was categorized into tertiles. We investigated 12-month MACEs, which included cardiac death, myocardial infarction, and repeated percutaneous coronary intervention or coronary artery bypass grafting. Results During the 12-month follow up period, 593 patients experienced MACEs. There was a significant association between the TG/HDL-C ratio and MACEs (p<0.001) in the entire study cohort. Having a TG/HDL-C ratio value in the highest tertile of TG/HDL-C ratio was an independent factor associated with increased risk of MACEs (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.26–1.93; p<0.001). Then we performed subgroup analyses according to renal function. In patients with normal renal function (eGFR ≥ 90 ml/min/1.73m2) and mild renal dysfunction (eGFR ≥ 60 to < 90ml/min/1.73m2), a higher TG/HDL-C ratio was significantly associated with increased risk of MACEs (HR, 1.64; 95% CI, 1.04–2.60; p = 0.035; and HR, 1.56; 95% CI, 1.14–2.12; p = 0.005, respectively). However, in patients with moderate renal dysfunction (eGFR < 60 ml/min/1.73m2), TG/HDL-C ratio lost its predictive value on the risk of MACEs (HR, 1.23; 95% CI, 0.82–1.83; p = 0.317). Conclusions In patients with AMI, TG/HDL-C ratio is a useful independent predictor of 12-month MACEs. However, this ratio does not have predictive power in patients with moderate renal dysfunction. PMID:27788233

Renal albumin absorption in physiology and pathology.

PubMed

Birn, H; Christensen, E I

2006-02-01

Albumin is the most abundant plasmaprotein serving multiple functions as a carrier of metabolites, hormones, vitamins, and drugs, as an acid/base buffer, as antioxidant and by supporting the oncotic pressure and volume of the blood. The presence of albumin in urine is considered to be the result of the balance between glomerular filtration and tubular reabsorption. Albuminuria has been accepted as an independent risk factor and a marker for renal as well as cardiovascular disease, and during the past decade, evidence has suggested that albumin itself may cause progression of renal disease. Thus, the reduction of proteinuria and, in particular, albuminuria has become a target in itself to prevent deterioration of renal function. Studies have shown albumin and its ligands to induce expression of inflammatory and fibrogenic mediators, and it has been hypothesized that increased filtration of albumin causes excessive tubular reabsorption, resulting in inflammation and fibrosis, resulting in the loss of renal function. In addition, it is known that tubular dysfunction in itself may cause albuminuria owing to decreased reabsorption of filtered albumin, and, recently, it has been suggested that significant amounts of albumin fragments are excreted in the urine as a result of tubular degradation. Thus, although both tubular and glomerular dysfunction influences renal handling of albumin, it appears that tubular reabsorption plays a central role in mediating the effects of albumin on renal function. The present paper will review the mechanisms for tubular albumin uptake and the possible implications for the development of renal disease.

[Organ damage and cardiorenal syndrome in acute heart failure].

PubMed

Casado Cerrada, Jesús; Pérez Calvo, Juan Ignacio

2014-03-01

Heart failure is a complex syndrome that affects almost all organs and systems of the body. Signs and symptoms of organ dysfunction, in particular kidney dysfunction, may be accentuated or become evident for the first time during acute decompensation of heart failure. Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney, regardless of which of the two organs may have suffered the initial damage and regardless also of their previous functional status. Research into the mechanisms regulating the complex relationship between the two organs is prompting the search for new biomarkers to help physicians detect renal damage in subclinical stages. Hence, a preventive approach to renal dysfunction may be adopted in the clinical setting in the near future. This article provides a general overview of cardiorenal syndrome and an update of the physiopathological mechanisms involved. Special emphasis is placed on the role of visceral congestion as an emergent mechanism in this syndrome. Copyright © 2014 Elsevier España, S.L. All rights reserved.

The central role of renal microcirculatory dysfunction in the pathogenesis of acute kidney injury.

PubMed

Ince, Can

2014-01-01

Acute kidney injury (AKI) is a rapidly developing condition often associated with critical illness, with a high degree of morbidity and mortality, whose pathophysiology is ill understood. Recent investigations have identified the dysfunction of the renal microcirculation and its cellular and subcellular constituents as being central to the etiology of AKI. Injury is caused by inflammatory activation involving endothelial leucocyte interactions in combination with dysregulation of the homeostatis between oxygen, nitric oxide, and reactive oxygen species. Effective therapies expected to resolve AKI will have to control inflammation and restore this homeostasis. In order to apply and guide these therapies effectively, diagnostic tools aimed at physiological biomarkers of AKI for monitoring renal microcirculatory function in advance of changes in pharmacological biomarkers associated with structural damage of the kidney will need to be developed. 2014 S. Karger AG, Basel.

ARFI-based tissue elasticity quantification and kidney graft dysfunction: first clinical experiences.

PubMed

Stock, K F; Klein, B S; Cong, M T Vo; Regenbogen, C; Kemmner, S; Büttner, M; Wagenpfeil, S; Matevossian, E; Renders, L; Heemann, U; Küchle, C

2011-01-01

Beyond the medical history, the clinical exam and lab findings, non-invasive ultrasound parameters such as kidney size and Doppler values (e.g. the resistive index) are important tools assisting clinical decision making in the monitoring of renal allografts. The gold standard for the diagnosis of renal allograft dysfunction remains the renal biopsy; while an invasive procedure, the justifiable necessity for this derives from its definitive nature a requirement beyond the synopses of all non-invasive tools. "Acoustic Radiation Force Impulse Imaging"(ARFI)-quantification is a novel ultrasound-based technology measuring tissue elasticity properties. So far experience related to this new method has not been reported in renal transplant follow-up. The purpose of this study was to evaluate changes in ARFI-measurements between clinically stable renal allografts and biopsy-proven transplant dysfunction. We employed "Virtual Touch™ tissue quantification" (Siemens Acuson, S2000) for the quantitative measurement of tissue stiffness in the cortex of transplant kidneys. We performed initial baseline and later disease-evaluative ultrasound examinations in 8 renal transplant patients in a prospective study design. Patients were first examined during stable allograft function with a routine post-transplant renal ultrasound protocol. A second follow-up examination was carried out on subsequent presentation with transplant dysfunction prior to allograft biopsy and histological evaluation. All patiens were examined using ARFI-quantification (15 measurements/kidney). Resistive indices (RI) were calculated using pulsed-wave Doppler ultrasound, and transplant kidney size was measured on B-mode ultrasound images. All biopsies were evaluated histologically by a reference nephropathologist unaware of the results of the ultrasound studies. Histopathological diagnoses were based on biopsy results, taking clinical and laboratory findings into account. Finally we calculated the relative changes in ARFI-quantification, resistive indices and the absolute change of kidney size on a percentage basis at these defined assessment times and compared the results with the final pathologic diagnosis. Histological results enumerated five cases of acute T-cell-mediated rejection, one case of calcineurin inhibitor toxicity and two cases of acute tubular necrosis. Calcineurin inhibitor toxicity and acute tubular necrosis were subsumed as "other pathologies". Mean ARFI-values showed an average increase of more than 15% percent in transplants with histologically proven acute rejection whereas no increase was seen in transplants with other pathologies. Mean RI-values showed no increase either in the diagnostic group of acute rejection, nor in the group with other pathologies. Kidney size showed a mean absolute increase of 0.5 centimetres in allografts with acute rejection, whereas a mean decrease of 0.17 centimetres was seen in the group with other pathologies. As shown before in other studies, RI values and kidney size are of doubtful utility in the evaluation of kidney allograft dysfunction. ARFI-based elasticity measurement shows promise as a complementary non-invasive parameter in follow-on diagnosis of renal allograft rejection.

CD147/basigin reflects renal dysfunction in patients with acute kidney injury.

PubMed

Nagaya, Hiroshi; Kosugi, Tomoki; Maeda-Hori, Mayuko; Maeda, Kayaho; Sato, Yuka; Kojima, Hiroshi; Hayashi, Hiroki; Kato, Noritoshi; Ishimoto, Takuji; Sato, Waichi; Yuzawa, Yukio; Matsuo, Seiichi; Kadomatsu, Kenji; Maruyama, Shoichi

2014-10-01

Acute tubular necrosis (ATN) describes a form of intrinsic acute kidney injury (AKI) that results from persistent hypoperfusion and subsequent activation of the immune system. A glycosylated transmembrane protein, CD147/basigin, is involved in the pathogenesis of renal ischemia and fibrosis. The present study investigated whether CD147 can reflect pathological features and renal dysfunction in patients with AKI. Plasma and spot urine samples were collected from 24 patients (12 controls and 12 with ATN) who underwent renal biopsy between 2008 and 2012. In another study, patients undergoing open surgery to treat abdominal aortic aneurysms (AAAs) were enrolled in 2004. We collected urine and plasma samples from seven patients with AKI and 33 patients without AKI, respectively. In these experiments, plasma and urinary CD147, and urinary L-fatty acid-binding protein (L-FABP) levels were measured, and the former expression in kidneys was examined by immunostaining. In biopsy tissues of ATN with severe histological features, CD147 induction was strikingly present in inflammatory cells such as macrophages and lymphocytes in the injured interstitium, but not in damaged tubules representing atrophy. Both plasma and urinary CD147 levels were strikingly increased in ATN patients; both values showed greater correlations with renal dysfunction compared to urinary L-FABP. In patients who had undergone open AAA surgery, urinary and plasma CD147 values in AKI patients were significantly higher than in non-AKI patients at post-operative day 1, similar to the profile of urinary L-FABP. CD147 was prominent in its ability to detect AKI and may allow the start of preemptive medication.

Silymarin protects against renal injury through normalization of lipid metabolism and mitochondrial biogenesis in high fat-fed mice.

PubMed

Bin Feng; Meng, Ran; Bin Huang; Bi, Yan; Shen, Shanmei; Zhu, Dalong

2017-09-01

Obesity is associated with an increased risk of chronic kidney diseases and the conventional treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors is not enough to prevent renal injury and prolong the progression of disease. Recently, silymarin has shown protective effects on renal tissue injury, but the underlying mechanisms remain elusive. The goal of this study was to investigate the potential capacity of silymarin to prevent renal injury during obesity induced by high fat diet (HFD) in mice. In vivo, male C57BL/6 mice received HFD (60% of total calories) for 12 weeks, randomized and treated orally with vehicle saline or silymarin (30mg/kg body weight/d) for 4 weeks. In vitro, human proximal tubular epithelial cells (HK2) were exposed to 300μM palmitic acid (PA) for 36h followed by silymarin administration at different concentrations. The administration of silymarin significantly ameliorated HFD induced glucose metabolic disorders, oxidative stress and pathological alterations in the kidney. Silymarin significantly mitigated renal lipid accumulation, fatty acid β-oxidation and mitochondrial biogenesis in HFD mice and PA treated HK2 cells. Furthermore, silymarin partly restored mitochondrial membrane potential of HK2 cells after PA exposure. In conclusion, silymarin can improve oxidative stress and preserve mitochondrial dysfunction in the kidney, potentially via preventing accumulation of renal lipids and fatty acid β-oxidation. Copyright © 2017. Published by Elsevier Inc.

Increased Blood Pressure Variability Prior to Chronic Kidney Disease Exacerbates Renal Dysfunction in Rats

PubMed Central

Freitas, Frederico F. C. T.; Araujo, Gilberto; Porto, Marcella L.; Freitas, Flavia P. S.; Graceli, Jones B.; Balarini, Camille M.; Vasquez, Elisardo C.; Meyrelles, Silvana S.; Gava, Agata L.

2016-01-01

Increased blood pressure variability (BPV), which can be experimentally induced by sinoaortic denervation (SAD), has emerged as a new marker of the prognosis of cardiovascular and renal outcomes. Considering that increased BPV can lead to organ-damage, the goal of the present study was to evaluate the effects of SAD on renal function in an experimental model of chronic kidney disease (CKD). SAD was performed in male Wistar rats 2 weeks before 5/6 nephrectomy and the animals were evaluated 4 weeks after the induction of CKD. Our data demonstrated that BPV was increased in SAD and CKD animals and that the combination of both conditions (SAD+CKD) exacerbated BPV. The baroreflex sensitivity index was diminished in the SAD and CKD groups; this reduction was more pronounced when SAD and CKD were performed together. 5/6 nephrectomy led to hypertension, which was higher in SAD+CKD animals. Regarding renal function, the combination of SAD and CKD resulted in reduced renal plasma and blood flow, increased renal vascular resistance and augmented uraemia when compared to CKD animals. Glomerular filtration rate and BPV were negatively correlated in SAD, CKD, and SAD+CKD animals. Moreover, SAD+CKD animals presented a higher level of glomerulosclerosis when compared to all other groups. Cardiac and renal hypertrophy, as well as oxidative stress, was also further increased when SAD and CKD were combined. These results show that SAD prior to 5/6 nephrectomy exacerbates renal dysfunction, suggesting that previous augmented BPV should be considered as an important factor to the progression of renal diseases. PMID:27721797

Reversal of renal dysfunction by targeted administration of VEGF into the stenotic kidney: a novel potential therapeutic approach.

PubMed

Chade, Alejandro R; Kelsen, Silvia

2012-05-15

Renal microvascular (MV) damage and loss contribute to the progression of renal injury in renovascular disease (RVD). Whether a targeted intervention in renal microcirculation could reverse renal damage is unknown. We hypothesized that intrarenal vascular endothelial growth factor (VEGF) therapy will reverse renal dysfunction and decrease renal injury in experimental RVD. Unilateral renal artery stenosis (RAS) was induced in 14 pigs, as a surrogate of chronic RVD. Six weeks later, renal blood flow (RBF) and glomerular filtration rate (GFR) were quantified in vivo in the stenotic kidney using multidetector computed tomography (CT). Then, intrarenal rhVEGF-165 or vehicle was randomly administered into the stenotic kidneys (n = 7/group), they were observed for 4 additional wk, in vivo studies were repeated, and then renal MV density was quantified by 3D micro-CT, and expression of angiogenic factors and fibrosis was determined. RBF and GFR, MV density, and renal expression of VEGF and downstream mediators such as p-ERK 1/2, Akt, and eNOS were significantly reduced after 6 and at 10 wk of untreated RAS compared with normal controls. Remarkably, administration of VEGF at 6 wk normalized RBF (from 393.6 ± 50.3 to 607.0 ± 45.33 ml/min, P < 0.05 vs. RAS) and GFR (from 43.4 ± 3.4 to 66.6 ± 10.3 ml/min, P < 0.05 vs. RAS) at 10 wk, accompanied by increased angiogenic signaling, augmented renal MV density, and attenuated renal scarring. This study shows promising therapeutic effects of a targeted renal intervention, using an established clinically relevant large-animal model of chronic RAS. It also implies that disruption of renal MV integrity and function plays a pivotal role in the progression of renal injury in the stenotic kidney. Furthermore, it shows a high level of plasticity of renal microvessels to a single-dose VEGF-targeted intervention after established renal injury, supporting promising renoprotective effects of a novel potential therapeutic intervention to treat chronic RVD.

Reversal of renal dysfunction by targeted administration of VEGF into the stenotic kidney: a novel potential therapeutic approach

PubMed Central

Kelsen, Silvia

2012-01-01

Renal microvascular (MV) damage and loss contribute to the progression of renal injury in renovascular disease (RVD). Whether a targeted intervention in renal microcirculation could reverse renal damage is unknown. We hypothesized that intrarenal vascular endothelial growth factor (VEGF) therapy will reverse renal dysfunction and decrease renal injury in experimental RVD. Unilateral renal artery stenosis (RAS) was induced in 14 pigs, as a surrogate of chronic RVD. Six weeks later, renal blood flow (RBF) and glomerular filtration rate (GFR) were quantified in vivo in the stenotic kidney using multidetector computed tomography (CT). Then, intrarenal rhVEGF-165 or vehicle was randomly administered into the stenotic kidneys (n = 7/group), they were observed for 4 additional wk, in vivo studies were repeated, and then renal MV density was quantified by 3D micro-CT, and expression of angiogenic factors and fibrosis was determined. RBF and GFR, MV density, and renal expression of VEGF and downstream mediators such as p-ERK 1/2, Akt, and eNOS were significantly reduced after 6 and at 10 wk of untreated RAS compared with normal controls. Remarkably, administration of VEGF at 6 wk normalized RBF (from 393.6 ± 50.3 to 607.0 ± 45.33 ml/min, P < 0.05 vs. RAS) and GFR (from 43.4 ± 3.4 to 66.6 ± 10.3 ml/min, P < 0.05 vs. RAS) at 10 wk, accompanied by increased angiogenic signaling, augmented renal MV density, and attenuated renal scarring. This study shows promising therapeutic effects of a targeted renal intervention, using an established clinically relevant large-animal model of chronic RAS. It also implies that disruption of renal MV integrity and function plays a pivotal role in the progression of renal injury in the stenotic kidney. Furthermore, it shows a high level of plasticity of renal microvessels to a single-dose VEGF-targeted intervention after established renal injury, supporting promising renoprotective effects of a novel potential therapeutic intervention to treat chronic RVD. PMID:22357917

Clinicopathological features of progressive renal involvement in TAFRO syndrome: A case report and literature review.

PubMed

Tanaka, Mari; Tsujimoto, Hiraku; Yamamoto, Kojiro; Shimoda, Saeko; Oka, Kazumasa; Takeoka, Hiroya

2017-10-01

TAFRO syndrome is a systemic inflammatory disease characterized by a constellation of symptoms: Thrombocytopenia, Anasarca, MyeloFibrosis, Renal dysfunction, and Organomegaly. Progressive renal insufficiency is a predominant symptom; however, the mechanism of acute kidney injury (AKI) remains unclear, probably because severe thrombocytopenia prevents kidney biopsy. We report a rare case of TAFRO syndrome with histologically confirmed renal involvement. A 70-year-old man developed fever, anasarca, AKI, thrombocytopenia, and hepatosplenomegaly. Plasma vascular endothelial growth factor and serum interleukin-6 levels were significantly elevated. The diagnosis of TAFRO syndrome was made based on his clinical and laboratory findings. Kidney biopsy was performed for the evaluation of AKI and provided a diagnosis of membranoproliferative glomerulonephritis-like lesions due to endothelial injury. Glomerular capillary lumens were extremely narrowed or occluded by endothelial swelling, and marked widening of the subendothelial space by electron-lucent material resulted in mesangiolysis and a double-contoured glomerular basement membrane with no immune complex deposits. The patient required temporary hemodialysis due to oliguric AKI, but steroid therapy rapidly improved renal function. Typically, patients with progressive renal involvement in TAFRO syndrome rapidly develop oliguric or anuric AKI. This report suggests that the reduction of glomerular perfusion by glomerular endothelial injury might be a primary factor in the progressive AKI of TAFRO syndrome. Our case and the literature review indicate that steroid and/or biological therapies result in highly favorable renal outcomes in patients with progressive AKI in TAFRO syndrome.

Renal mitochondrial dysfunction in spontaneously hypertensive rats is attenuated by losartan but not by amlodipine.

PubMed

de Cavanagh, Elena M V; Toblli, Jorge E; Ferder, León; Piotrkowski, Bárbara; Stella, Inés; Inserra, Felipe

2006-06-01

Mitochondrial dysfunction is associated with cardiovascular damage; however, data on a possible association with kidney damage are scarce. Here, we aimed at investigating whether 1) kidney impairment is related to mitochondrial dysfunction; and 2) ANG II blockade, compared with Ca2+ channel blockade, can reverse potential mitochondrial changes in hypertension. Eight-week-old male spontaneously hypertensive rats (SHR) received water containing losartan (40 mg.kg-1.day-1, SHR+Los), amlodipine (3 mg.kg-1.day-1, SHR+Amlo), or no additions (SHR) for 6 mo. Wistar-Kyoto rats (WKY) were normotensive controls. Glomerular and tubulointerstitial damage, systolic blood pressure, and proteinuria were higher, and creatinine clearance was lower in SHR vs. SHR+Los and WKY. In SHR+Amlo, blood pressure was similar to WKY, kidney function was similar to SHR, and renal lesions were lower than in SHR, but higher than in SHR+Los. In kidney mitochondria from SHR and SHR+Amlo, membrane potential, nitric oxide synthase, manganese-superoxide dismutase and cytochrome oxidase activities, and uncoupling protein-2 content were lower than in SHR+Los and WKY. In SHR and SHR+Amlo, mitochondrial H2O2 production was higher than in SHR+Los and WKY. Renal glutathione content was lower in SHR+Amlo relative to SHR, SHR+Los, and WKY. In SHR and SHR+Amlo, glutathione was relatively more oxidized than in SHR+Los and WKY. Tubulointerstitial alpha-smooth muscle actin labeling was inversely related to manganese-superoxide dismutase activity and uncoupling protein-2 content. These findings suggest that oxidant stress is associated with renal mitochondrial dysfunction in SHR. The mitochondrial-antioxidant actions of losartan may be an additional or alternative way to explain some of the beneficial effects of AT1-receptor antagonists.

Use of Abacavir and Risk of Cardiovascular Disease Among HIV-Infected Individuals.

PubMed

Marcus, Julia L; Neugebauer, Romain S; Leyden, Wendy A; Chao, Chun R; Xu, Lanfang; Quesenberry, Charles P; Klein, Daniel B; Towner, William J; Horberg, Michael A; Silverberg, Michael J

2016-04-01

Evidence is conflicting about the association of abacavir use and cardiovascular disease (CVD) among HIV-infected individuals. Previous studies may have been biased by the preferential initiation or continuation of abacavir in patients with renal dysfunction. We conducted a cohort study in Kaiser Permanente California during 1998-2011, following HIV-infected adults initiating antiretroviral therapy until the earliest of CVD (ie, coronary heart disease or ischemic stroke), health plan disenrollment, death, or end of study. We used inverse-probability weighting to fit marginal structural models to estimate hazard ratios (HRs) for CVD comparing regimens with and without abacavir. Propensity score models included demographics, HIV-specific factors, and CVD risk factors, including alcohol/drug use, smoking, overweight/obesity, diabetes, lipid-lowering and hypertension therapy, and renal dysfunction (ie, estimated glomerular filtration rate <60 mL·min·1.73 m). Among 8154 subjects, 178 had ≥1 CVD event, with 24/704 (3.4%) in the abacavir group and 154/7450 (2.1%) in the group initiating regimens without abacavir. Abacavir users had more renal dysfunction at antiretroviral therapy initiation (7.0% vs. 3.3%, P < 0.001). Compared with patients initiating regimens without abacavir, abacavir users had a 2.2-fold higher risk of CVD in intention-to-treat analysis [HR 2.2, 95% confidence interval (CI): 1.4 to 3.5], a 2.7-fold higher risk when remaining on their initial regimens for ≥1 year (HR 2.7, 95% CI: 1.5 to 5.0), and a 2.1-fold higher risk in per-protocol analysis (HR 2.1, 95% CI: 0.9 to 5.0). Abacavir was associated with an over 2-fold increased risk of CVD, which was not explained by renal dysfunction or other CVD risk factors.

Heart Rate Variability in Patients with Acute Ischemic Stroke at Different Stages of Renal Dysfunction: A Cross-sectional Observational Study.

PubMed

Wei, Lin; Zhao, Wen-Bo; Ye, Huan-Wen; Chen, Yan-Hua; Zhang, Xiao-Pei; Huang, Yan; Cai, Ye-Feng; Chen, Quan-Fu; Pan, Su-Yue

2017-03-20

Renal function is associated with mortality and functional disabilities in stroke patients, and impaired autonomic function is common in stroke, but little is known regarding its effects on stroke patients with renal dysfunction. This study sought to evaluate the association between autonomic function and stroke in patients with renal dysfunction. This study comprised 232 patients with acute ischemic stroke consecutively enrolled from February 2013 to November 2014 at Guangdong Provincial Hospital of Chinese Medicine in China. All patients recruited underwent laboratory evaluation and 24 h Holter electrocardiography (ECG). Autonomic function was measured based on the heart rate variability (HRV) using 24 h Holter ECG. Renal damage was assessed through the estimated glomerular filtration rate (eGFR), and stroke severity was rated according to the National Institutes of Health Stroke Scale (NIHSS). The Barthel index and modified Rankin score were also determined following admission. All the clinical covariates that could potentially affect autonomic outcome variables were adjusted with linear regression. In the patients with a mild or moderate decreased eGFR, the values for the standard deviation of the averaged normal-to-normal RR interval (SDANN) index (P = 0.022), very low frequency (VLF) (P = 0.043), low frequency (LF) (P = 0.023), and ratio of low-to-high frequency power (LF/HF) (P = 0.001) were significantly lower than those in the patients with a normal eGFR. A multinomial linear regression indicated that eGFR (t = 2.47, P = 0.014), gender (t = -3.60, P < 0.001), and a history of hypertension (t = -2.65, P = 0.008) were the risk factors of LF/HF; the NIHSS score (SDANN index: t = -3.83, P < 0.001; VLF: t = -3.07, P = 0.002; LF: t = -2.79, P = 0.006) and a history of diabetes (SDANN index: t = -3.58, P < 0.001; VLF: t = -2.54, P = 0.012; LF: t = -2.87, P = 0.004) were independent factors for the SDANN index, VLF, and LF; the Oxfordshire Community Stroke Project (t = -2.38, P = 0.018) was related to the SDANN index. Autonomic dysfunction is aggravated with the progression of eGFR stage in patients with acute ischemic stroke; the eGFR is an independent factor of LF/HF in the adjusted models. Stroke severity and a history of diabetes are more significantly associated with HRV in patients with acute ischemic stroke at different stages of renal dysfunction.

Nephrotoxicity testing in vitro--what we know and what we need to know.

PubMed Central

Pfaller, W; Gstraunthaler, G

1998-01-01

The kidney is affected by many chemicals. Some of the chemicals may even contribute to end-stage renal disease and thus contribute considerably to health care costs. Because of the large functional reserve of the kidney, which masks signs of dysfunction, early diagnosis of renal disease is often difficult. Although numerous studies aimed at understanding the mechanisms underlying chemicals and drugs that target various renal cell types have delivered enough understanding for a reasonable risk assessment, there is still an urgent need to better understand the mechanisms leading to renal cell injury and organ dysfunction. The increasing use of in vitro techniques using isolated renal cells, nephron fragments, or cell cultures derived from specific renal cell types has improved our insight into the molecular mechanisms involved in nephrotoxicity. A short overview is given on the various in vitro systems currently used to clarify mechanistic aspects leading to sublethal or lethal injury of the functionally most important nephron epithelial cells derived from various species. Whereas freshly isolated cells and nephron fragments appear to represent a sufficient basis to study acute effects (hours) of nephrotoxins, e.g., on cell metabolism, primary cultures of these cells are more appropriate to study long-term effects. In contrast to isolated cells and fragments, however, primary cultures tend to first lose several of their in vivo metabolic properties during culture, and second to have only a limited life span (days to weeks). Moreover, establishing such primary cultures is a time-consuming and laborious procedure. For that reason many studies have been carried out on renal cell lines, which are easy to cultivate in large quantities and which have an unlimited life span. Unfortunately, none of the lines display a state of differentiation comparable to that of freshly isolated cells or their primary cultures. Most often they lack expression of key functions (e.g., gluconeogenesis or organic anion transport) of their in vivo correspondents. Therefore, the use of cell lines for assessment of nephrotoxic mechanisms will be limited to those functions the lines express. Upcoming molecular biology approaches such as the transduction of immortalizing genes into primary cultures and the utilization of cells from transgenic animals may in the near future result in the availability of highly differentiated renal cells with markedly extended life spans and near in vivo characteristics that may facilitate the use of renal cell culture for routine screening of nephrotoxins. Images Figure 1 Figure 2 PMID:9599703

Eribulin Mesylate in Treating Patients With Locally Advanced or Metastatic Cancer of the Urothelium and Kidney Dysfunction

ClinicalTrials.gov

2018-04-24

Metastatic Urothelial Carcinoma; Recurrent Bladder Urothelial Carcinoma; Recurrent Urethral Urothelial Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Renal Failure; Stage III Bladder Urothelial Carcinoma AJCC v6 and v7; Stage IV Bladder Urothelial Carcinoma AJCC v7

Early detection of endothelial injury and dysfunction in conjunction with correction of hemodynamic maladjustment can effectively restore renal function in type 2 diabetic nephropathy.

PubMed

Futrakul, Narisa; Butthep, Punnee; Vongthavarawat, Varaphon; Futrakul, Prasit; Sirisalipoch, Sasitorn; Chaivatanarat, Tawatchai; Suwanwalaikorn, Sompongse

2006-01-01

This paper was aimed to investigate (1) the early marker of endothelial injury in type 2 diabetes, (2) the intrarenal hemodynamics and renal function, and (3) the therapeutic strategy aiming to restore renal function. Fifty patients (35 normoalbuminuric and 15 albuminuric type 2 diabetes) were examined. Blood was collected for determination of circulating vascular endothelial cells (CEC) and the serum was prepared for determination of transforming growth factor beta (TGFbeta), ratio of CEC/TGFbeta, and soluble vascular cell adhesion molecule. Intrarenal hemodynamics and renal function were also assessed. The results showed that increased number of circulating EC, elevated TGFbeta and depleted ratio of CEC/TGFbeta were significantly observed. Intrarenal hemodynamic study revealed a hemodynamic maladjustment characterized by preferential constriction of the efferent arteriole, intraglomerular hypertension and reduction in peritubular capillary flow. It was concluded that early marker of endothelial injury is reflected by increasing number of CEC. Such markers correlate with the glomerular endothelial dysfunction associated with hemodynamic maladjustment. Early detection of endothelial injury and appropriate correction of hemodynamic maladjustment by multidrug vasodilators can effectively restore renal function in type 2 diabetic nephropathy.

Acquired resistance to rechallenge injury in rats recovered from subclinical renal damage with uranyl acetate-Importance of proliferative activity of tubular cells

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

Sun, Yuan; Fujigaki, Yoshihide, E-mail: yf0516@hama-med.ac.j; Sakakima, Masanori

Animals recovered from acute renal failure are resistant to subsequent insult. We investigated whether rats recovered from mild proximal tubule (PT) injury without renal dysfunction (subclinical renal damage) acquire the same resistance. Rats 14 days after recovering from subclinical renal damage, which was induced by 0.2 mg/kg of uranyl acetate (UA) (sub-toxic dose), were rechallenged with 4 mg/kg of UA (nephrotoxic dose). Fate of PT cells and renal function were examined in response to nephrotoxic dose of UA. All divided cells after sub-toxic dose of UA insult were labeled with bromodeoxyuridine (BrdU) for 14 days then the number of PTmore » cells with or without BrdU-labeling was counted following nephrotoxic dose of UA insult. Rats recovered from subclinical renal damage gained resistance to nephrotoxic dose of UA with reduced renal dysfunction, less severity of peak damage (necrotic and TUNEL+ apoptotic cells) and accelerated PT cell proliferation, but with earlier peak of PT damage. The decrease in number of PT cells in the early phase of rechallenge injury with nephrotoxic UA was more in rats pretreated with sub-toxic dose of UA than vehicle pretreated rats. The exaggerated loss of PT cells was mainly caused by the exaggerated loss of BrdU+ divided cells. In contrast, accelerated cell proliferation in rats recovered from sub-toxic dose of UA was observed mainly in BrdU- non-divided cells. The findings suggest that rats recovered from subclinical renal damage showed partial acquired resistance to nephrotoxic insult. Accelerated recovery with increased proliferative activity of non-divided PT cells after subclinical renal damage may mainly contribute to acquired resistance.« less

Regulatory T-Cell Augmentation or Interleukin-17 Inhibition Prevents Calcineurin Inhibitor-Induced Hypertension in Mice.

PubMed

Chiasson, Valorie L; Pakanati, Abhinandan R; Hernandez, Marcos; Young, Kristina J; Bounds, Kelsey R; Mitchell, Brett M

2017-07-01

The immunosuppressive calcineurin inhibitors cyclosporine A and tacrolimus alter T-cell subsets and can cause hypertension, vascular dysfunction, and renal toxicity. We and others have reported that cyclosporine A and tacrolimus decrease anti-inflammatory regulatory T cells and increase proinflammatory interleukin-17-producing T cells; therefore, we hypothesized that inhibition of these effects using noncellular therapies would prevent the hypertension, endothelial dysfunction, and renal glomerular injury induced by calcineurin inhibitor therapy. Daily treatment of mice with cyclosporine A or tacrolimus for 1 week significantly decreased CD4 + /FoxP3 + regulatory T cells in the spleen and lymph nodes, as well as induced hypertension, vascular injury and dysfunction, and glomerular mesangial expansion in mice. Daily cotreatment with all-trans retinoic acid reported to increase regulatory T cells and decrease interleukin-17-producing T cells, prevented all of the detrimental effects of cyclosporine A and tacrolimus. All-trans retinoic acid also increased regulatory T cells and prevented the hypertension, endothelial dysfunction, and glomerular injury in genetically modified mice that phenocopy calcineurin inhibitor-treated mice (FKBP12-Tie2 knockout). Treatment with an interleukin-17-neutralizing antibody also increased regulatory T-cell levels and prevented the hypertension, endothelial dysfunction, and glomerular injury in cyclosporine A-treated and tacrolimus-treated mice and FKBP12-Tie2 knockout mice, whereas an isotype control had no effect. Augmenting regulatory T cells and inhibiting interleukin-17 signaling using noncellular therapies prevents the cardiovascular and renal toxicity of calcineurin inhibitors in mice. © 2017 American Heart Association, Inc.

Acute kidney injury: not just acute renal failure anymore?

PubMed

Dirkes, Susan

2011-02-01

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

Long-term treatment with EGFR inhibitor erlotinib attenuates renal inflammatory cytokines but not nephropathy in Alport syndrome mouse model.

PubMed

Omachi, Kohei; Miyakita, Rui; Fukuda, Ryosuke; Kai, Yukari; Suico, Mary Ann; Yokota, Tsubasa; Kamura, Misato; Shuto, Tsuyoshi; Kai, Hirofumi

2017-12-01

Alport syndrome (AS) is a hereditary kidney disease caused by mutation of type IV collagen. Loss of collagen network induces collapse of glomerular basement membrane (GBM) structure. The previous studies showed that upregulation of some tyrosine kinase receptors signaling accompanied GBM disorder in AS mouse model. EGFR signaling is one of the well-known receptor kinase signaling that is involved in glomerular diseases. However, whether EGFR signaling is relevant to AS progression is still uninvestigated. Here, we determined the involvement of EGFR in AS and the effect of suppressing EGFR signaling by erlotinib treatment on AS progression. Phosphorylated EGFR expression was investigated by Western blotting analysis and immunostaining of kidney tissues of Col4a5 mutant mice (a mouse model of X-linked AS). To check the effect of blocking EGFR signaling in AS, we administered erlotinib to AS mice once a day (10 mg/kg/day) orally for 18 weeks. Renal function parameters (proteinuria, serum creatinine, and BUN) and renal histology were assessed, and the gene expressions of inflammatory cytokines were analyzed in renal tissues. Phosphorylated EGFR expression was upregulated in AS mice kidney tissues. Erlotinib slightly reduced the urinary protein and suppressed the expression of renal injury markers (Lcn2, Lysozyme) and inflammatory cytokines (Il-6, Il-1β and KC). Erlotinib did not improve renal pathology, such as glomerular sclerosis and fibrosis. These findings suggest that EGFR signaling is upregulated in kidney, but although inhibiting this signaling pathway suppressed renal inflammatory cytokines, it did not ameliorate renal dysfunction in AS mouse model.

Soy-based renoprotection

PubMed Central

McGraw, Nancy J; Krul, Elaine S; Grunz-Borgmann, Elizabeth; Parrish, Alan R

2016-01-01

Chronic kidney disease (CKD) is a significant public health problem as risk factors such as advanced age, obesity, hypertension and diabetes rise in the global population. Currently there are no effective pharmacologic treatments for this disease. The role of diet is important for slowing the progression of CKD and managing symptoms in later stages of renal insufficiency. While low protein diets are generally recommended, maintaining adequate levels of intake is critical for health. There is an increasing appreciation that the source of protein may also be important. Soybean protein has been the most extensively studied plant-based protein in subjects with kidney disease and has demonstrated renal protective properties in a number of clinical studies. Soy protein consumption has been shown to slow the decline in estimated glomerular filtration rate and significantly improve proteinuria in diabetic and non-diabetic patients with nephropathy. Soy’s beneficial effects on renal function may also result from its impact on certain physiological risk factors for CKD such as dyslipidemia, hypertension and hyperglycemia. Soy intake is also associated with improvements in antioxidant status and systemic inflammation in early and late stage CKD patients. Studies conducted in animal models have helped to identify the underlying molecular mechanisms that may play a role in the positive effects of soy protein on renal parameters in polycystic kidney disease, metabolically-induced kidney dysfunction and age-associated progressive nephropathy. Despite the established relationship between soy and renoprotection, further studies are needed for a clear understanding of the role of the cellular and molecular target(s) of soy protein in maintaining renal function. PMID:27152261

Association of renal tubular damage with cardio-renal anemia syndrome in patients with heart failure.

PubMed

Otaki, Yoichiro; Watanabe, Tetsu; Takahashi, Hiroki; Narumi, Taro; Kadowaki, Shinpei; Honda, Yuki; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Kubota, Isao

2014-05-01

Cardio-renal anemia syndrome (CRAS) has begun to gather attention as a vicious circle since chronic heart failure (CHF), chronic kidney disease (CKD), and anemia are all able to be caused and exacerbated by each other. However, it remains unclear whether renal tubular damage (RTD), another type of kidney dysfunction, is associated with this vicious circle. The aim of the present study was to assess the association of RTD with CRAS in patients with CHF. We included 300 consecutive patients with CHF. RTD was defined as a urinary β2-microglobulin to creatinine ratio ≥ 300 μg/g. Patients with RTD had lower serum iron and higher levels of high sensitivity C-reactive protein than those without it. Multivariate logistic analysis showed that RTD was closely associated with anemia in patients with CHF, after adjustment for confounding factors. During a median period of 1,098 days, there were 86 cardiac events, including 14 cardiac deaths and 72 re-hospitalizations for worsening heart failure. Net reclassification improvement was significantly improved by addition of RTD to the model including age, New York Heart Association functional class, brain natriuretic peptide, anemia, and CKD. All patients were divided into 3 groups: CRAS+RTD group, CRAS group, and control group. Kaplan-Meier analysis demonstrated that CRAS+RTD had the greatest risk in patients with CHF. RTD was associated with normocytic anemia, accompanying iron deficiency and inflammation. RTD added prognostic information to conventional CRAS, suggesting the importance of RTD in cardio-renal anemia interaction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Plasma cystatin C is a predictor of renal dysfunction, acute-on-chronic liver failure, and mortality in patients with acutely decompensated liver cirrhosis.

PubMed

Markwardt, Daniel; Holdt, Lesca; Steib, Christian; Benesic, Andreas; Bendtsen, Flemming; Bernardi, Mauro; Moreau, Richard; Teupser, Daniel; Wendon, Julia; Nevens, Frederik; Trebicka, Jonel; Garcia, Elisabet; Pavesi, Marco; Arroyo, Vicente; Gerbes, Alexander L

2017-10-01

The development of acute-on-chronic liver failure (ACLF) in patients with liver cirrhosis is associated with high mortality rates. Renal failure is the most significant organ dysfunction that occurs in ACLF. So far there are no biomarkers predicting ACLF. We investigated whether cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) can predict development of renal dysfunction (RD), hepatorenal syndrome (HRS), ACLF, and mortality. We determined the plasma levels of CysC and NGAL in 429 patients hospitalized for acute decompensation of cirrhosis in the EASL-CLIF Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC) study. The patients were followed for 90 days. Patients without RD or ACLF at inclusion but with development of either had significantly higher baseline concentrations of CysC and NGAL compared to patients without. CysC, but not NGAL, was found to be predictive of RD (odds ratio, 9.4; 95% confidence interval [CI], 1.8-49.7), HRS (odds ratio, 4.2; 95% CI, 1.2-14.8), and ACLF (odds ratio, 5.9; 95% CI, 1.3-25.9). CysC at day 3 was not found to be a better predictor than baseline CysC. CysC and NGAL were both predictive of 90-day mortality, with hazard ratios for CysC of 3.1 (95% CI, 2.1-4.7) and for NGAL of 1.9 (95% CI, 1.5-2.4). Baseline CysC is a biomarker of RD, HRS, and ACLF and an independent predictor of mortality in patients with acutely decompensated liver cirrhosis, though determining CysC at day 3 did not provide any benefit; while NGAL is also associated with short-term mortality, it fails to predict development of RD, HRS, and ACLF. Baseline CysC may help to identify patients at risk earlier and improve clinical management. (Hepatology 2017;66:1232-1241). © 2017 by the American Association for the Study of Liver Diseases.

Plantar Fascia Thickness is Longitudinally Associated with Retinopathy and Renal Dysfunction: A Prospective Study from Adolescence to Adulthood

PubMed Central

Benitez-Aguirre, Paul Z.; Craig, Maria E.; Jenkins, Alicia J.; Gallego, Patricia H.; Cusumano, Janine; Duffin, Anthony C.; Hing, Stephen; Donaghue, Kim C.

2012-01-01

Aim The aim was to study the longitudinal relationship between plantar fascia thickness (PFT) as a measure of tissue glycation and microvascular (MV) complications in young persons with type 1 diabetes (T1DM). Methods We conducted a prospective longitudinal cohort study of 152 (69 male) adolescents with T1DM who underwent repeated MV complications assessments and ultrasound measurements of PFT from baseline (1997–2002) until 2008. Retinopathy was assessed by 7-field stereoscopic fundal photography and nephropathy by albumin excretion rate (AER) from three timed overnight urine specimens. Longitudinal analysis was performed using generalized estimating equations (GEE). Results Median (interquartile range) age at baseline was 15.1 (13.4–16.8) years, and median follow-up was 8.3 (7.0–9.5) years, with 4 (3–6) visits per patient. Glycemic control improved from baseline to final visit [glycated hemoglobin (HbA1c) 8.5% to 8.0%, respectively; p = .004]. Prevalence of retinopathy increased from 20% to 51% (p < .001) and early elevation of AER (>7.5 µg/min) increased from 26% to 29% (p = .2). A greater increase in PFT (mm/year) was associated with retinopathy at the final assessment (ΔPFT 1st vs. 2nd–4th quartiles, χ2 = 9.87, p = .02). In multivariate GEE, greater PFT was longitudinally associated with retinopathy [odds ratio (OR) 4.6, 95% confidence interval (CI) 2.0–10.3] and early renal dysfunction (OR 3.2, CI 1.3–8.0) after adjusting for gender, blood pressure standard deviation scores, HbA1c, and total cholesterol. Conclusions In young people with T1DM, PFT was longitudinally associated with retinopathy and early renal dysfunction, highlighting the importance of early glycemic control and supporting the role of metabolic memory in MV complications. Measurement of PFT by ultrasound offers a noninvasive estimate of glycemic burden and tissue glycation. PMID:22538146

Plantar fascia thickness is longitudinally associated with retinopathy and renal dysfunction: a prospective study from adolescence to adulthood.

PubMed

Benitez-Aguirre, Paul Z; Craig, Maria E; Jenkins, Alicia J; Gallego, Patricia H; Cusumano, Janine; Duffin, Anthony C; Hing, Stephen; Donaghue, Kim C

2012-03-01

The aim was to study the longitudinal relationship between plantar fascia thickness (PFT) as a measure of tissue glycation and microvascular (MV) complications in young persons with type 1 diabetes (T1DM). We conducted a prospective longitudinal cohort study of 152 (69 male) adolescents with T1DM who underwent repeated MV complications assessments and ultrasound measurements of PFT from baseline (1997-2002) until 2008. Retinopathy was assessed by 7-field stereoscopic fundal photography and nephropathy by albumin excretion rate (AER) from three timed overnight urine specimens. Longitudinal analysis was performed using generalized estimating equations (GEE). Median (interquartile range) age at baseline was 15.1 (13.4-16.8) years, and median follow-up was 8.3 (7.0-9.5) years, with 4 (3-6) visits per patient. Glycemic control improved from baseline to final visit [glycated hemoglobin (HbA1c) 8.5% to 8.0%, respectively; p = .004]. Prevalence of retinopathy increased from 20% to 51% (p < .001) and early elevation of AER (>7.5 μg/min) increased from 26% to 29% (p = .2). A greater increase in PFT (mm/year) was associated with retinopathy at the final assessment (ΔPFT 1st vs. 2nd-4th quartiles, χ(2) = 9.87, p = .02). In multivariate GEE, greater PFT was longitudinally associated with retinopathy [odds ratio (OR) 4.6, 95% confidence interval (CI) 2.0-10.3] and early renal dysfunction (OR 3.2, CI 1.3-8.0) after adjusting for gender, blood pressure standard deviation scores, HbA1c, and total cholesterol. In young people with T1DM, PFT was longitudinally associated with retinopathy and early renal dysfunction, highlighting the importance of early glycemic control and supporting the role of metabolic memory in MV complications. Measurement of PFT by ultrasound offers a noninvasive estimate of glycemic burden and tissue glycation. © 2012 Diabetes Technology Society.

Obesity and kidney protection.

PubMed

Chandra, Aravind; Biersmith, Michael; Tolouian, Ramin

2014-07-01

Obesity, both directly and indirectly, increases the risk for a variety of disease conditions including diabetes, hypertension, liver disease, and certain cancers, which in turn, decreases the overall lifespan in both men and women. Though the cardiovascular risks of obesity are widely acknowledged, less often identified is the relationship between obesity and renal function. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO and Web of Science has been searched. The concept of the "Metabolic Syndrome" helps us to understand this close link between obesity, diabetes, hypertension, and renal dysfunction. An elevated body mass index has shown to be one of the major determinants of glomerular hyperfiltration that lead to the development of chronic kidney disease. Interestingly, weight loss can lead to attenuation of hyperfiltration in severely obese patients suggesting a possible therapeutic option to combat obesity-related hyperfiltration. Various treatment strategies had been suggested to decrease impact of obesity on kidneys. These are blood pressure controling, inhibition of the renin-angiotensinaldosterone axis, improving glycemic control, improving dyslipidemia, improving protein uriaand lifestyle modifications. Regardless of the numerous pharmacotherapies, the focus should be on the root cause: obesity.

Effect of resveratrol and rosuvastatin on experimental diabetic nephropathy in rats.

PubMed

Hussein, Mohamed M A; Mahfouz, Mohamed K

2016-08-01

The development of diabetic nephropathy (DN) relays mainly on control of blood glucose and restrains hyperglycemic-induced oxidative stress. Hence, the effect administration of resveratrol (RSV) (5mg/kg) alone or in combination with rosuvastatin (RSU) (10mg/kg) on development and progression of diabetic nephropathy (DN) was evaluated. Oral treatment of diabetic rats with RSV alone or co-administered with RSU improved renal dysfunction indicated by a significant decrease in serum creatinine, urinary protein and urinary TGF-β1 when compared with diabetic control rats. Also, a significant increase in body weight, relative kidney weight with a significant decrease in serum glucose and glycated hemoglobin in diabetic treated groups when compared with diabetic control group. Hyperglycemic-induced oxidative stress in diabetic control rats indicated by a significant decrease in renal activities of catalase, superoxide dismutase, glutathione peroxidase and reduced glutathione level with a significant increase in malondialdehyde levels. However, oral treatment of diabetic rats with RSV alone or co-administered with RSU improved the antioxidant status back to control values. Similarly, mRNA analysis of quantitative real time-PCR substantiated that RSV with RSU notably normalizes the renal expression of TGF-β1, fibronectin, NF-κB/p65, Nrf2, Sirt1 and FoxO1 in the diabetic group of rats. The histopathological observations of the combined treated diabetic rats effectively protect the kidneys from hyperglycemic-induced oxidative damage. These findings confirmed the renoprotective effects of RSV with RSU treatment through improving glycemic control and attenuating oxidative stress damage in renal tissues of diabetic rats. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Extracorporeal shock wave therapy does not improve hypertensive nephropathy.

PubMed

Caron, Jonathan; Michel, Pierre-Antoine; Dussaule, Jean-Claude; Chatziantoniou, Christos; Ronco, Pierre; Boffa, Jean-Jacques

2016-06-01

Low-energy extracorporeal shock wave therapy (SWT) has been shown to improve myocardial dysfunction, hind limb ischemia, erectile function, and to facilitate cell therapy and healing process. These therapeutic effects were mainly due to promoting angiogenesis. Since chronic kidney diseases are characterized by renal fibrosis and capillaries rarefaction, they may benefit from a proangiogenic treatment. The objective of our study was to determine whether SWT could ameliorate renal repair and favor angiogenesis in L-NAME-induced hypertensive nephropathy in rats. SWT was started when proteinuria exceeded 1 g/mmol of creatinine and 1 week after L-NAME removal. SWT consisted of implying 0.09 mJ/mm(2) (400 shots), 3 times per week. After 4 weeks of SWT, blood pressure, renal function and urinary protein excretion did not differ between treated (LN + SWT) and untreated rats (LN). Histological lesions including glomerulosclerosis and arteriolosclerosis scores, tubular dilatation and interstitial fibrosis were similar in both groups. In addition, peritubular capillaries and eNOS, VEGF, VEGF-R, SDF-1 gene expressions did not increase in SWT-treated compared to untreated animals. No procedural complications or adverse effects were observed in control (C + SWT) and hypertensive rats (LN + SWT). These results suggest that extracorporeal kidney shock wave therapy does not induce angiogenesis and does not improve renal function and structure, at least in the model of hypertensive nephropathy although the treatment is well tolerated. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Calpain 10 homology modeling with CYGAK and increased lipophilicity leads to greater potency and efficacy in cells.

PubMed

Smith, Matthew A; McInnes, Campbell; Whitaker, Ryan M; Lindsey, Christopher C; Comer, Richard F; Beeson, Craig C; Schnellmann, Rick G

2012-08-17

Calpain 10 is a ubiquitously expressed mitochondrial and cytosolic Ca(2+)-regulated cysteine protease in which overexpression or knockdown leads to mitochondrial dysfunction and cell death. We previously identified a potent and specific calpain 10 peptide inhibitor (CYGAK), but it was not efficacious in cells. Therefore, we created a homology model using the calpain 10 amino acid sequence and calpain 1 3-D structure and docked CYGAK in the active site. Using this model we modified the inhibitor to improve potency 2-fold (CYGAbuK). To increase cellular efficacy, we created CYGAK-S-phenyl-oleic acid heterodimers. Using renal mitochondrial matrix CYGAK, CYGAK-OC, and CYGAK-ON had IC(50)'s of 70, 90, and 875 nM, respectively. Using isolated whole renal mitochondria CYGAK, CYGAK-OC, and CYGAK-ON had IC(50)'s of 95, 196, and >10,000 nM, respectively. Using renal proximal tubular cells (RPTC) in primary culture, 30 min exposures to CYGAK-OC and CYGAbuK-OC decreased cellular calpain activity approximately 20% at 1 μM, and concentrations up to 100 μM had no additional effect. RPTC treated with 10 μM CYGAK-OC for 24 h induced accumulation of ATP synthase β and NDUFB8, two calpain 10 substrates. In summary, we used molecular modeling to improve the potency of CYGAK, while creating CYGAK-oleic acid heterodimers to improve efficacy in cells. Since calpain 10 has been implicated in type 2 diabetes and renal aging, the use of this inhibitor may contribute to elucidating the role of calpain 10 in these and other diseases.

Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction).

PubMed

Schroten, Nicolas F; Damman, Kevin; Hemmelder, Marc H; Voors, Adriaan A; Navis, Gerjan; Gaillard, Carlo A J M; van Veldhuisen, Dirk J; Van Gilst, Wiek H; Hillege, Hans L

2015-05-01

We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF are associated with increased mortality. Aliskiren can provide additional renin-angiotensin-aldosterone system inhibition and increases RBF in healthy individuals. Patients with left ventricular ejection fraction ≤45% and estimated GFR 30 to 75 mL/min per 1.73 m(2) on optimal medical therapy were randomized 2:1 to receive aliskiren 300 mg once daily or placebo. Renal blood flow and GFR were measured using radioactive-labeled (125)I-iothalamate and (131)I-hippuran at baseline and 26 weeks. After 41 patients were included, the trial was halted based on an interim safety analysis showing futility. Mean age was 68 ± 9 years, 82% male, GFR (49 ± 16 mL/min per 1.73 m(2)), RBF (294 ± 77 mL/min per 1.73 m(2)), and NT-proBNP 999 (435-2040) pg/mL. There was a nonsignificant change in RBF after 26 weeks in the aliskiren group compared with placebo (-7.1 ± 30 vs +14 ± 54 mL/min per 1.73 m(2); P = .16). However, GFR decreased significantly in the aliskiren group compared with placebo (-2.8 ± 6.0 vs +4.4 ± 9.6 mL/min per 1.73 m(2); P = .01) as did filtration fraction (-2.2 ± 3.3 vs +1.1 ± 3.1%; P = .01). There were no significant differences in plasma aldosterone, NT-proBNP, urinary tubular markers, or adverse events. Plasma renin activity was markedly reduced in the aliskiren group versus placebo throughout the treatment phase (P = .007). Adding aliskiren on top of optimal HFREF medical therapy did not improve RBF and was associated with a reduction of GFR and filtration fraction. Copyright © 2015 Mosby, Inc. All rights reserved.

[Left ventricular dysfunction measured in diabetic patients with chronic renal failure on continuous ambulatory peritoneal dialysis].

PubMed

Díaz-Arrieta, Gustavo; Mendoza-Hernández, María Elsa; Pacheco-Aranda, Erika; Rivas-Duro, Miguel; Robles-Parra, Héctor Manuel; Espinosa-Vázquez, Raúl Arturo; Hernández-Cabrera, Jorge

2010-01-01

In diabetic patients with chronic renal failure (CRF) treated with dialysis, the diastolic and systolic left ventricular dysfunction is frequent. The aim was to assess by echocardiography the prevalence of diastolic and systolic ventricular dysfunction in diabetic patients with CRF treated with continuous ambulatory peritoneal dialysis (CAPD). Sixty diabetic patients with CRF in CAPD were studied. The mean age was 54.5 +/- 12 years (27-78 years). The left ventricular filling pattern (LVFP) as a diastolic function parameter and left ventricular ejection fraction (LVEF) as a systolic function parameter were measured by transthoracic echocardiography. Descriptive statistical analysis was used. 27 (45 %) patients were women and 33 (55 %) were men. In 55 (91.7 %) left ventricular concentric hypertrophy was observed. Fifty-two patients (86.7 %) showed LVFP type I; three (5 %) had the type II; two (3.3 %) showed pseudonormal pattern and three (5 %) had a normal LVFP. The LVEF was 0.63 +/- 0.09 (CI = 0.41-0.82). Forty nine (81.7 %) patients had LVEF equal or greater than 0.55. The prevalence of diastolic left ventricular dysfunction was 95 % and the prevalence of systolic left ventricular dysfunction was 18.3%.

Fiber optic probe enabled by surface-enhanced Raman scattering for early diagnosis of potential acute rejection of kidney transplant

NASA Astrophysics Data System (ADS)

Chi, Jingmao; Chen, Hui; Tolias, Peter; Du, Henry

2014-06-01

We have explored the use of a fiber-optic probe with surface-enhanced Raman scattering (SERS) sensing modality for early, noninvasive and, rapid diagnosis of potential renal acute rejection (AR) and other renal graft dysfunction of kidney transplant patients. Multimode silica optical fiber immobilized with colloidal Ag nanoparticles at the distal end was used for SERS measurements of as-collected urine samples at 632.8 nm excitation wavelength. All patients with abnormal renal graft function (3 AR episodes and 2 graft failure episodes) who were clinically diagnosed independently show common unique SERS spectral features in the urines collected just one day after transplant. SERS-based fiber-optic probe has excellent potential to be a bedside tool for early diagnosis of kidney transplant patients for timely medical intervention of patients at high risk of transplant dysfunction.

Systematic implantation of dedifferentiated fat cells ameliorated monoclonal antibody 1-22-3-induced glomerulonephritis by immunosuppression with increases in TNF-stimulated gene 6.

PubMed

Maruyama, Takashi; Fukuda, Noboru; Matsumoto, Taro; Kano, Koichiro; Endo, Morito; Kazama, Minako; Kazama, Tomohiko; Ikeda, Jin; Matsuda, Hiroyuki; Ueno, Takahiro; Abe, Masanori; Okada, Kazuyoshi; Soma, Masayoshi; Matsumoto, Koichi; Kawachi, Hiroshi

2015-04-16

Implantation of mesenchymal stem cells (MSCs) has recently been reported to repair tissue injuries through anti-inflammatory and immunosuppressive effects. We established dedifferentiated fat (DFAT) cells that show identical characteristics to MSCs. We examined the effects of 10(6) of DFAT cells infused through renal artery or tail vein on monoclonal antibody (mAb) 1-22-3-induced glomerulonephritis (as an immunological type of renal injury) and adriamycin-induced nephropathy (as a non-immunological type of renal injury) in rats. The mAb 1-22-3-injected rats were also implanted with 10(6) of DFAT cells transfected with TSG-6 siRNA through tail vein. Although DFAT cells transfused into blood circulation through the tail vein were trapped mainly in lungs without reaching the kidneys, implantation of DFAT cells reduced proteinuria and improved glomerulosclerosis and interstitial fibrosis. Implantation of DFAT cells through the tail vein significantly decreased expression of kidney injury molecule-1, collagen IV and fibronectin mRNAs, whereas nephrin mRNA expression was increased. Implantation of DFAT cells did not improve adriamycin-induced nephropathy, but significantly decreased the glomerular influx of macrophages, common leukocytes and pan T cells. However, the glomerular influx of helper T cells, was increased. Implantation of DFAT cells decreased expression of interleukin (IL)-6 and IL-12β mRNAs and increased expression of TNF-stimulated gene (TSG)-6 mRNA in renal cortex from mAb 1-22-3-injected rats. The basal level of TSG-6 protein was significantly higher in DFAT cells than in fibroblasts. Expression of TSG-6 mRNA in MCs cocultured with DFAT cells was significantly higher than in mesangial cells or DFAT cells alone. Systematic implantation of DFAT cells with TSG-6 siRNA through tail vein did not improve proteinuria, renal dysfunction and renal degeneration in the mAb 1-22-3-injected rats. Systematic implantation of DFAT cells effectively ameliorated mAb 1-22-3-induced glomerulonephritis through immunosuppressive effects accompanied by the suppression of macrophage infiltration and expression of IL-6, IL-10 and IL-12β, and increased production of serum and renal TSG-6 that improved the mAb 1-22-3-induced renal degeneration by the immunosuppressive effects of TSG-6. Thus DFAT cells will be suitable cell source for the treatment of immunological progressive renal diseases.

Population Pharmacokinetics and Therapeutic Efficacy of Febuxostat in Patients with Severe Renal Impairment.

PubMed

Hira, Daiki; Chisaki, Yugo; Noda, Satoshi; Araki, Hisazumi; Uzu, Takashi; Maegawa, Hiroshi; Yano, Yoshitaka; Morita, Shin-Ya; Terada, Tomohiro

2015-01-01

The aim of the present study was to determine the influence of severe renal dysfunction (estimated glomerular filtration rate <30 ml/min/1.73 m(2), including hemodialysis) on the pharmacokinetics and therapeutic effects of febuxostat using a population pharmacokinetic analysis. This study recruited patients with hyperuricemia who were initially treated with allopurinol, but were switched to febuxostat, and it consists of 2 sub-studies: a pharmacokinetic study (26 patients) and retrospective efficacy evaluation study (51 patients). The demographic and clinical data of patients were collected from electronic medical records. Plasma febuxostat concentrations were obtained at each hospital visit. Population pharmacokinetic modeling was performed with NONMEM version 7.2. A total of 128 plasma febuxostat concentrations from 26 patients were used in the population pharmacokinetic analysis. The data were best described by a 1-compartment model with first order absorption. Covariate analysis revealed that renal function did not influence the pharmacokinetics of febuxostat, whereas actual body weight significantly influenced apparent clearance and apparent volume of distribution. The retrospective efficacy analysis showed the favorable therapeutic response of febuxostat switched from allopurinol in patients with moderate to severe renal impairment. No serious adverse event associated with febuxostat was observed irrespective of renal function. The population pharmacokinetic analysis and therapeutic analysis of febuxostat revealed that severe renal dysfunction had no influence on the pharmacokinetic parameters of febuxostat. These results suggest that febuxostat is tolerated well by patients with severe renal impairment. © 2015 S. Karger AG, Basel.

Effects of palmitoylethanolamide and silymarin combination treatment in an animal model of kidney ischemia and reperfusion.

PubMed

Impellizzeri, Daniela; Bruschetta, Giuseppe; Ahmad, Akbar; Crupi, Rosalia; Siracusa, Rosalba; Di Paola, Rosanna; Paterniti, Irene; Prosdocimi, Marco; Esposito, Emanuela; Cuzzocrea, Salvatore

2015-09-05

The aim of this study was to investigate the efficacy of PEA+silymarin as a combination treatment in a mouse model of renal I/R and to verify whether PEA+silymarin could exert more potent effects compared to the single substances even if administered at lower doses. Mice were subjected to bilateral renal artery occlusion (30min) and reperfusion (6h) and received intraperitoneally silymarin (100, 30 and 10mg/kg) or PEA (1mg/kg) or PEA (1mg/kg)+silymarin (10mg/kg) 15min before release of clamps. Specific indicators of renal dysfunction, tubular injury, myeloperoxidase activity and malondialdehyde levels were measured. The nuclear factor κB pathway and apoptotic mechanisms were also investigated. The treatment with silymarin reduced kidney dysfunction, histological damage, neutrophil infiltration and oxidative stress in a dose dependent manner. Furthermore, PEA+silymarin showed a significant potentiated effect. Therefore, NF-κB and apoptosis pathways were also significantly inhibited. Our results clearly demonstrate that PEA+silymarin treatment attenuated the degree of renal inflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

[Organ transplantation and blood transfusion].

PubMed

Matignon, M; Bonnefoy, F; Lang, P; Grimbert, P

2011-04-01

Pretransplant blood transfusion remains a controversial subject and its history can summarize the last 40 years of transplantation. Until 1971, transfusions were widely used in patients awaiting transplantation, especially due to the anemia induced by the chronic renal dysfunction. Then, a noxious effect of preformed anti-HLA antibodies on renal grafts survival was reported and pretransplant transfusions were stopped. Between 1972 and 1977, improvement of renal graft survival in patients who received pretransplant transfusions was noted. Therefore, from 1978 on, a systematic policy of pretransplant transfusions was adopted by almost all centres of transplantation. During the eighties, it was again abandoned for several reasons: absence of graft survival improvement in patients treated by cyclosporine, HLA immunization leading to an increased incidence of acute graft rejection, risk of viral diseases transmission and human recombinant erythropoietin development. The lack of improvement in graft survival for ten years has been leading the transplant community to look for antigen-specific immunosuppressive strategies to achieve transplantation tolerance. Donor-specific transfusion may have clinical benefits, as long-term grafts survival improvement, through modulation of the recipient's cellular immune system and has been recently reconsidered, especially before living donor transplantation. The immunological mechanisms inducing a tolerance-gaining effect of transfusions are still misunderstood, but the recent discovery of immunomodulatory effects of the apoptotic cells present in cellular products could enlighten our comprehension of pretransplant transfusions benefits and could help to develop specific tolerance induction strategies in solid organ transplantation. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Activated renal tubular Wnt/β-catenin signaling triggers renal inflammation during overload proteinuria.

PubMed

Wong, Dickson W L; Yiu, Wai Han; Chan, Kam Wa; Li, Ye; Li, Bin; Lok, Sarah W Y; Taketo, Makoto M; Igarashi, Peter; Chan, Loretta Y Y; Leung, Joseph C K; Lai, Kar Neng; Tang, Sydney C W

2018-06-01

Imbalance of Wnt/β-catenin signaling in renal cells is associated with renal dysfunction, yet the precise mechanism is poorly understood. Previously we observed activated Wnt/β-catenin signaling in renal tubules during proteinuric nephropathy with an unknown net effect. Therefore, to identify the definitive role of tubular Wnt/β-catenin, we generated a novel transgenic "Tubcat" mouse conditionally expressing stabilized β-catenin specifically in renal tubules following tamoxifen administration. Four weeks after tamoxifen injection, uninephrectomized Tubcat mice displayed proteinuria and elevated blood urea nitrogen levels compared to non-transgenic mice, implying a detrimental effect of the activated signaling. This was associated with infiltration of the tubulointerstitium predominantly by M1 macrophages and overexpression of the inflammatory chemocytokines CCL-2 and RANTES. Induction of overload proteinuria by intraperitoneal injection of low-endotoxin bovine serum albumin following uninephrectomy for four weeks aggravated proteinuria and increased blood urea nitrogen levels to a significantly greater extent in Tubcat mice. Renal dysfunction correlated with the degree of M1 macrophage infiltration in the tubulointerstitium and renal cortical up-regulation of CCL-2, IL-17A, IL-1β, CXCL1, and ICAM-1. There was overexpression of cortical TLR-4 and NLRP-3 in Tubcat mice, independent of bovine serum albumin injection. Finally, there was no fibrosis, activation of epithelial-mesenchymal transition or non-canonical Wnt pathways observed in the kidneys of Tubcat mice. Thus, conditional activation of renal tubular Wnt/β-catenin signaling in a novel transgenic mouse model demonstrates that this pathway enhances intrarenal inflammation via the TLR-4/NLRP-3 inflammasome axis in overload proteinuria. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Evaluation of renal function change during first-line tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma.

PubMed

Ishihara, Hiroki; Kondo, Tsunenori; Fukuda, Hironori; Yoshida, Kazuhiko; Omae, Kenji; Takagi, Toshio; Iizuka, Junpei; Kobayashi, Hirohito; Tanabe, Kazunari

2017-12-01

The change in renal function induced by first-line tyrosine kinase inhibitor therapy for metastatic renal cell carcinoma remains unclear. One hundred and thirty-four patients were evaluated. Sunitinib (SU) and sorafenib (SO) were administered to 91 (67.9%) and 43 (32.1%) patients, respectively. The change in estimated glomerular filtration rate (ΔeGFR) was calculated as [(eGFR at each time point - pre-treatment eGFR)/pre-treatment eGFR] × 100. ΔeGFR was compared between SU- and SO users using a mixed-effects model for repeated measures data with two or greater. Additionally, predictors for ΔeGFR ≤ -10% at 6 months after therapy initiation were evaluated using multivariate logistic regression analysis. Throughout the 24 months after therapy initiation, ΔeGFR was negatively greater in SU users, compared with that in SO users (P < 0.0001). In SU users, renal dysfunction was observed regardless of pre-treatment chronic kidney disease (CKD) status, whereas the magnitude of renal dysfunction was milder in SO users. In SO users without pre-treatment CKD, renal function did not significantly deteriorate. Moreover, ΔeGFR ≤ -10% was more frequently observed in SU users after 3 months (P = 0.0121) and 6 months (P = 0.0009). Finally, SU usage was an independent predictor for ΔeGFR ≤ -10% at 6 months (odds ratio 8.87, P = 0.0053), along with pre-treatment hypertension (odds ratio 4.69, P = 00072). Deterioration of renal function was stronger with SU than SO. During SU therapy, renal function should be monitored and pre-treatment kidney function should be taken into consideration for therapy selection. © The Author 2017. Published by Oxford University Press.

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.

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.

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

Modeling and Simulation for Estimating the Influence of Renal Dysfunction on the Hypouricemic Effect of Febuxostat in Hyperuricemic Patients Due to Overproduction or Underexcretion of Uric Acid.

PubMed

Hirai, Toshinori; Kimura, Toshimi; Echizen, Hirotoshi

2016-01-01

Whether renal dysfunction influences the hypouricemic effect of febuxostat, a xanthine oxidase (XO) inhibitor, in patients with hyperuricemia due to overproduction or underexcretion of uric acid (UA) remains unclear. We aimed to address this question with a modeling and simulation approach. The pharmacokinetics (PK) of febuxostat were analyzed using data from the literature. A kinetic model of UA was retrieved from a previous human study. Renal UA clearance was estimated as a function of creatinine clearance (CLcr) but non-renal UA clearance was assumed constant. A reversible inhibition model for bovine XO was adopted. Integrating these kinetic formulas, we developed a PK-pharmacodynamic (PK-PD) model for estimating the time course of the hypouricemic effect of febuxostat as a function of baseline UA level, febuxostat dose, treatment duration, body weight, and CLcr. Using the Monte Carlo simulation method, we examined the performance of the model by comparing predicted UA levels with those reported in the literature. We also modified the models for application to hyperuricemia due to UA overproduction or underexcretion. Thirty-nine data sets comprising 735 volunteers or patients were retrieved from the literature. A good correlation was observed between the hypouricemic effects of febuxostat estimated by our PK-PD model and those reported in the articles (observed) (r=0.89, p<0.001). The hypouricemic effect was estimated to be augmented in patients with renal dysfunction irrespective of the etiology of hyperuricemia. While validation in clinical studies is needed, the modeling and simulation approach may be useful for individualizing febuxostat doses in patients with various clinical characteristics.

Cardiorenal Syndrome Type 5 in Sepsis: Role of Endotoxin in Cell Death Pathways and Inflammation.

PubMed

Virzì, Grazia Maria; Clementi, Anna; Brocca, Alessandra; de Cal, Massimo; Marcante, Stefano; Ronco, Claudio

2016-01-01

Cardiorenal Syndrome Type 5 (CRS Type 5) is characterized by concomitant cardiac and renal dysfunction in the setting of different systemic disorders, such as sepsis. In this study, we investigated the possible relationship between endotoxin levels, renal cell death and inflammation in septic patients with CRS Type 5. We enrolled 11 patients with CRS Type 5. CRS Type 5 was defined according to the current classification system. AKI was defined by Acute Kidney Injury Network (AKIN) criteria. Acute cardiac dysfunction was documented by echocardiography as acute left and/or right ventricular dysfunction leading to decreased ejection fraction. Endotoxin activity was measured by the Endotoxin Activity Assay (EAA). Plasma from CRS Type 5 patients was incubated with renal tubular cells (RTCs) and cell death levels were evaluated. Plasma cytokines levels were measured as well. Accordingly to EAA levels, patients were divided into two groups: 45.4% of patients had low endotoxin activity level (negative EAA), while 54.5% of patients showed high endotoxin activity (positive EAA). RTCs incubated with plasma from EAA positive patients showed significantly higher apoptosis levels and higher caspase-3 activation compared to cells incubated with plasma from EAA negative patients, and a significant positive correlation was observed between EAA levels and RTC apoptosis levels. Furthermore, IL-6 and IFN-γ levels were significantly higher in CRS Type 5 patients with positive EAA. Our data suggest a possible relationship between endotoxin levels and renal cell death in septic patients with CRS Type 5. Furthermore, this study highlights the presence of renal apoptosis, the immune deregulation and the strong inflammation in CRS Type 5 patients, especially in those with high endotoxin activity. © 2017 S. Karger AG, Basel.

Renal Dysfunction Induced by Kidney-Specific Gene Deletion of Hsd11b2 as a Primary Cause of Salt-Dependent Hypertension.

PubMed

Ueda, Kohei; Nishimoto, Mitsuhiro; Hirohama, Daigoro; Ayuzawa, Nobuhiro; Kawarazaki, Wakako; Watanabe, Atsushi; Shimosawa, Tatsuo; Loffing, Johannes; Zhang, Ming-Zhi; Marumo, Takeshi; Fujita, Toshiro

2017-07-01

Genome-wide analysis of renal sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess. However, these genetic variations in extrarenal tissue can be involved in developing hypertension, as demonstrated in former studies using global and brain-specific Hsd11b2 knockout rodents. To re-examine the importance of renal dysfunction on developing hypertension, we generated kidney-specific Hsd11b2 knockout mice. The knockout mice exhibited systemic hypertension, which was abolished by reducing salt intake, suggesting its salt-dependency. In addition, we detected an increase in renal membrane expressions of cleaved epithelial sodium channel-α and T53-phosphorylated Na + -Cl - cotransporter in the knockout mice. Acute intraperitoneal administration of amiloride-induced natriuresis and increased urinary sodium/potassium ratio more in the knockout mice compared with those in the wild-type control mice. Chronic administration of amiloride and high-KCl diet significantly decreased mean blood pressure in the knockout mice, which was accompanied with the correction of hypokalemia and the resultant decrease in Na + -Cl - cotransporter phosphorylation. Accordingly, a Na + -Cl - cotransporter blocker hydrochlorothiazide significantly decreased mean blood pressure in the knockout mice. Chronic administration of mineralocorticoid receptor antagonist spironolactone significantly decreased mean blood pressure of the knockout mice along with downregulation of cleaved epithelial sodium channel-α and phosphorylated Na + -Cl - cotransporter expression in the knockout kidney. Our data suggest that kidney-specific deficiency of 11β-HSD2 leads to salt-dependent hypertension, which is attributed to mineralocorticoid receptor-epithelial sodium channel-Na + -Cl - cotransporter activation in the kidney, and provides evidence that renal dysfunction is essential for developing the phenotype of apparent mineralocorticoid excess. © 2017 American Heart Association, Inc.

Current Management of Calcific Aortic Stenosis

PubMed Central

Lindman, Brian R.; Bonow, Robert O.; Otto, Catherine M.

2014-01-01

Calcific aortic stenosis (AS) is a progressive disease with no effective medical therapy that ultimately requires aortic valve replacement (AVR) for severe valve obstruction. Echocardiography is the primary diagnostic approach to define valve anatomy, measure AS severity and evaluate the left ventricular (LV) response to chronic pressure overload. In asymptomatic patients, markers of disease progression include the degree of leaflet calcification, hemodynamic severity of stenosis, adverse LV remodeling, reduced LV longitudinal strain, myocardial fibrosis and pulmonary hypertension. The onset of symptoms portends a predictably high mortality rate unless AVR is performed. In symptomatic patients, AVR improves symptoms, improves survival and, in patients with LV dysfunction, improves systolic function. Poor outcomes after AVR are associated with low-flow low-gradient AS, severe ventricular fibrosis, oxygen dependent lung disease, frailty, advanced renal dysfunction and a high comorbidity score. However, in most patients with severe symptoms, AVR is lifesaving. Bioprosthetic valves are recommended for patients over the age of 65 years. Transcatheter AVR is now available for patients with severe comorbidities, is recommended in patients who are deemed inoperable and is a reasonable alternative to surgical AVR in high risk patients. PMID:23833296

[A case of rhabdomyolysis caused by saw palmetto of healthy foods].

PubMed

Hanaka, Minako; Yoshii, Chiharu; Yatera, Kazuhiro; Ito, Chiyo; Chojin, Yasuo; Nagata, Shuya; Yamasaki, Kei; Nishida, Chinatsu; Kawanami, Toshinori; Kawanami, Yukiko; Ishimoto, Hiroshi; Mukae, Hiroshi

2012-06-01

An 82-year-old man visited our hospital when he developed a fever of over 38 degrees C after having consumed 5 types of health foods. He had previously been treated for chronic obstructive pulmonary disease, hypertension and hyperuricemia. Blood examination on admission revealed renal dysfunction, marked elevation of C-reactive protein, and an elevated level of serum creatine kinase. According to the laboratory data and his clinical history, rhabdomyolysis complicated by acute renal failure was suspected, but his condition improved and his fever was reduced with fluid infusion. As a drug lymphocyte stimulation test was positive for only saw palmetto in the 5 health foods, we diagnosed the case as rhabdomyolysis induced by saw palmetto. We believe that this is the first case of a health food being the cause of rhabdomyolysis.

Hashimoto Thyroiditis and Nephrocalcinosis in a Child with Down Syndrome

PubMed Central

Spahiu, Lidvana; Jashari, Haki; Mulliqi-Kotori, Vjosa; Elezi-Rugova, Blerta; Merovci, Besart

2016-01-01

Introduction: Hypothyroidism has been reported to affect renal function and structure. However, the association of hypothyroidism with distal renal tubular acidosis (dRTA) is rarely reported in children. Case Presentation: We present a 6-year-boy with Down syndrome admitted in our department due to vomiting, weakness, polyuria, polydipsia, irritability and weight loss in the last few weeks. Investigations revealed features of hypokalemia, metabolic acidosis and alkaline urine consistent with dTRA. Abdominal ultrasound found nephrocalcinosis. In addition, Antithyroid peroxidase antibodies were positive, suggesting an autoimmune background for the pathogenesis of the tubular dysfunction. Treatment for dRTA and hypothyroidism was started and symptomatic improve was noticed. Conclusion: dRTA should be excluded in children with autoimmune disorders who develop weakness, polyuria, polydipsia or growth failure. Early diagnosis would reduce long-term complications. PMID:27147809

MicroRNA-29a Promotion of Nephrin Acetylation Ameliorates Hyperglycemia-Induced Podocyte Dysfunction

PubMed Central

Lin, Chun-Liang; Lee, Pei-Hsien; Hsu, Yung-Chien; Lei, Chen-Chou; Ko, Jih-Yang; Chuang, Pei-Chin; Huang, Yu-Ting; Wang, Shao-Yu; Wu, Shin-Long; Chen, Yu-Shan; Chiang, Wen-Chih; Reiser, Jochen

2014-01-01

Podocyte dysfunction is a detrimental feature in diabetic nephropathy, with loss of nephrin integrity contributing to diabetic podocytopathy. MicroRNAs (miRs) reportedly modulate the hyperglycemia-induced perturbation of renal tissue homeostasis. This study investigated whether regulation of histone deacetylase (HDAC) actions and nephrin acetylation by miR-29 contributes to podocyte homeostasis and renal function in diabetic kidneys. Hyperglycemia accelerated podocyte injury and reduced nephrin, acetylated nephrin, and miR-29a levels in primary renal glomeruli from streptozotocin-induced diabetic mice. Diabetic miR-29a transgenic mice had better nephrin levels, podocyte viability, and renal function and less glomerular fibrosis and inflammation reaction compared with diabetic wild-type mice. Overexpression of miR-29a attenuated the promotion of HDAC4 signaling, nephrin ubiquitination, and urinary nephrin excretion associated with diabetes and restored nephrin acetylation. Knockdown of miR-29a by antisense oligonucleotides promoted HDAC4 action, nephrin loss, podocyte apoptosis, and proteinuria in nondiabetic mice. In vitro, interruption of HDAC4 signaling alleviated the high glucose–induced apoptosis and inhibition of nephrin acetylation in podocyte cultures. Furthermore, HDAC4 interference increased the acetylation status of histone H3 at lysine 9 (H3K9Ac), the enrichment of H3K9Ac in miR-29a proximal promoter, and miR-29a transcription in high glucose–stressed podocytes. In conclusion, hyperglycemia impairs miR-29a signaling to intensify HDAC4 actions that contribute to podocyte protein deacetylation and degradation as well as renal dysfunction. HDAC4, via epigenetic H3K9 hypoacetylation, reduces miR-29a transcription. The renoprotective effects of miR-29a in diabetes-induced loss of podocyte integrity and renal homeostasis highlights the importance of post-translational acetylation reactions in podocyte microenvironments. Increasing miR-29a action may protect against diabetic podocytopathy. PMID:24578127

Isolated heart and liver transplant recipients are at low risk for polyomavirus BKV nephropathy.

PubMed

Puliyanda, Dechu P; Amet, Nurmamet; Dhawan, Archana; Hilo, Lara; Radha, Raju K; Bunnapradist, Suphamai; Czer, Lawrence; Martin, Paul; Jordan, Stanley; Toyoda, Mieko

2006-01-01

BKV infection and nephropathy is a significant cause of allograft dysfunction in kidney transplantation. BKV viremia, rather than viruria, corresponds to BKV nephropathy. The prevalence of BKV viremia in non-renal solid organ transplants has not been systematically evaluated. We determined prevalence of BKV viremia in kidney, combined kidney-heart, kidney-liver, kidney-pancreas, kidney-heart-liver, and heart and liver transplant recipients using BKV-PCR. Seven out of 173 (4%) kidney transplant recipients had BKV viremia, with BKV>2 x 10(5) copies/mL in 6/7 and 1.9 x 10(3) in the remaining one patient. BKV viremia was not found in 24 heart transplant recipients, whereas 1/37 (2.7%) liver transplants showed low copy numbers (< or =10(3)). BKV-PCR< or =10(3) copies/mL were also found in one of each combined kidney-heart and kidney-liver transplant recipients. BKV nephropathy was proven by biopsy in 4/6 patients with high BKV viral loads. All six patients showed renal dysfunction, requiring reduction in immunosuppression and antiviral therapy. All four patients with low BKV viral loads (1.9 x 10(3) or < or =10(3)) showed stable renal function after reduction of immunosuppression or no treatment, respectively. Higher BKV levels in plasma are associated with renal dysfunction. Kidney transplant recipients are at high risk compared with recipients of isolated heart or liver allografts, for development of BKV nephropathy.

Clinical update on the pharmacology, efficacy and safety of transdermal buprenorphine.

PubMed

Kress, Hans G

2009-03-01

Buprenorphine was not used widely in clinical practice over many years, mainly due to analgesic potency and clinical safety concerns based on misinterpreted animal data. Contrary to previous concerns, however, no analgesic ceiling effect and no antagonism of combined pure mu-opioid receptor agonists is seen within the therapeutic dose range. In recent studies, buprenorphine could be effectively and safely combined with full mu-agonists, and switching between buprenorphine and another opioid provided comparable pain relief based on equianalgesic doses. Moreover, buprenorphine exerts an antihyperalgesic effect, which is due -- at least in part -- to antagonistic activity at kappa-opioid receptors. Buprenorphine pharmacokinetics are not altered by advanced age or renal dysfunction. In addition, the risk of respiratory depression is lower than with other opioids including morphine, hydromorphone, methadone and fentanyl. Unlike morphine and fentanyl, there is no immunosuppressive activity with buprenorphine at therapeutic analgesic doses. Transdermal buprenorphine has significantly improved the clinical use of the drug, providing continuous buprenorphine release for up to 96 h. In clinical trials, patients receiving transdermal buprenorphine experienced significantly greater pain relief, better sleep, and a reduced need for rescue therapy, compared to placebo. Large-scale post-marketing studies have confirmed the effectiveness of transdermal buprenorphine in treating moderate-to-severe cancer and non-cancer pain including neuropathic syndromes. Finally, the comparably low incidence of CNS adverse events and constipation, and the possibility of use in severe renal dysfunction without a need for dose adjustment make buprenorphine well suited for chronic pain management in at-risk patients, such as diabetics, elderly or renally impaired individuals including those requiring haemodialysis.

Hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose adefovir dipivoxil: a case report and literature review suggesting ethnic predisposition.

PubMed

Wu, C; Zhang, H; Qian, Y; Wang, L; Gu, X; Dai, Z

2013-08-01

Adefovir dipivoxil (ADV) is one of the commonly used antiviral agents in the treatment of chronic hepatitis B (CHB) infection. Safety of a daily dose of 10 mg ADV is advocated by the registration trials. We report a case of severe hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose ADV in a CHB-related cirrhosis patient, and discuss the case through a thorough review of other cases reported in the literature. A 48-yr-old Chinese man with CHB-related cirrhosis developed severe progressive generalized bone pain and muscle weakness after receiving ADV 10 mg daily for 54 months. The laboratory results showed severe hypophosphatemia and features of proximal renal tubule dysfunction. Imaging studies were consistent with osteomalacia. After discontinuation of ADV, his symptoms resolved, laboratory abnormalities normalized and imaging studies showed improvement. In addition to our case, 12 other patients have been reported to have developed hypophosphatemic osteomalacia induced by low-dose ADV. Most of the reported cases were of subjects of East-Asian ethnicity. After discontinuation or reduction of ADV, serum phosphate level increased and clinical symptoms significantly improved in all cases. Hypophosphatemic osteomalacia and renal Fanconi syndrome can be associated with low-dose ADV. Clinicians treating CHB patients with ADV 10 mg daily over long periods of time should be aware of this infrequent but serious complication. © 2013 John Wiley & Sons Ltd.

Synergistic Effects of Perioperative Complications on 30-Day Mortality Following Hepatopancreatic Surgery.

PubMed

Merath, Katiuscha; Chen, Qinyu; Bagante, Fabio; Akgul, Ozgur; Idrees, Jay J; Dillhoff, Mary; Cloyd, Jordan M; Pawlik, Timothy M

2018-06-18

Data on the interaction effect of multiple concurrent postoperative complications relative to the risk of short-term mortality following hepatopancreatic surgery have not been reported. The objective of the current study was to define the interaction effect of postoperative complications among patients undergoing HP surgery on 30-day mortality. Using the ACS-NSQIP Procedure Targeted Participant Use Data File, patients who underwent HP surgery between 2014 and 2016 were identified. Hazard ratios (HRs) for 30-day mortality were estimated using Cox proportional hazard models. Two-way interaction effects assessing combinations of complications relative to 30-day mortality were calculated using the relative excess risk due to interaction (RERI) in separate adjusted Cox models. Among 26,824 patients, 10,886 (40.5%) experienced at least one complication. Mortality was higher among patients who experienced at least one complication versus patients who did not experience a complication (3.0 vs 0.1%, p < 0.001). The most common complications were blood transfusion (16.9%, n = 4519), organ space infection (12.2%, n = 3273), and sepsis/septic shock (8.2%, n = 2205). Combinations associated with additive effect on mortality included transfusion + renal dysfunction (RERI 12.3, 95% CI 5.2-19.4), pulmonary dysfunction + renal dysfunction (RERI 60.9, 95% CI 38.6-83.3), pulmonary dysfunction + cardiovascular complication (RERI 144.1, 95% CI 89.3-199.0), and sepsis/septic shock + renal dysfunction (RERI 11.5, 95% CI 4.4-18.7). Both the number and specific type of complication impacted the incidence of postoperative mortality among patients undergoing HP surgery. Certain complications interacted in a synergistic manner, leading to a greater than expected increase in the risk of short-term mortality.

Chronic renal failure and sexual functioning: clinical status versus objectively assessed sexual response.

PubMed

Toorians, A W; Janssen, E; Laan, E; Gooren, L J; Giltay, E J; Oe, P L; Donker, A J; Everaerd, W

1997-12-01

Sexual dysfunctions are common among patients with chronic renal failure. The prevalence was assessed in a population of 281 patients (20-60 years), and it was attempted to determine whether their mode of treatment (haemodialysis, peritoneal dialysis, or kidney transplantation), or biochemical and endocrine variables and neuropathy affect sexual functioning. Patients with rheumatoid arthritis served as a comparison group. Assessment included clinical history, physical and laboratory examinations, questionnaires measuring erotosexual dysfunctions, and a psychophysiological test procedure. The latter is a laboratory method which measures, in a waking state, subjective and physiological sexual arousal. Men on haemodialysis or peritoneal dialysis suffered significantly more often from 'Hypoactive Sexual Desire Disorder', 'Sexual Aversion Disorder' and 'Inhibited Male Orgasm' than men with kidney transplantation or rheumatoid arthritis. Interestingly, the prevalence of 'Male Erectile Disorder' did not differ significantly between the four groups and ranged between 17 and 43%. Of the women, transplanted patients suffered significantly less from 'Hypoactive Sexual Desire Disorder' than the other three groups; the prevalence of other sexual dysfunctions did not differ between the groups. Although 'Male Erectile Disorder' and 'Female Sexual Arousal Disorder' had a relatively high prevalence there were no differences in the four groups of patients in genital responses during psychophysiological testing. Genital responses during psychophysiological assessment had no relationship to the duration of renal replacement treatment, biochemical/endocrine variables, or the presence/ absence of neuropathy. The prevalence of sexual dysfunction was high. Sexual dysfunction in men on haemodialysis or peritoneal dialysis was not so much due to erectile failure but largely to loss of sexual interest, subjectively ascribed to fatigue. The latter was also found in women on haemodialysis or peritoneal dialysis.

Cardiac and renal function in patients with type 2 diabetes who have chronic kidney disease: potential effects of bardoxolone methyl.

PubMed

McCullough, Peter A; Ali, Sajid

2012-01-01

The intracellular and tissue balance of oxidant and antioxidant forces is a potential therapeutic target for a variety of agents in the treatment of complications due to chronic disease including diabetes mellitus and hypertension. There are a myriad of processes controlled at the level of genes, transcription factors, and protein messages that work to control the normal use of oxidative reactions within cells. Loss of control of these processes may lead to reversible dysfunction in many cell lines including the podocyte, renal tubular cells, and cardiac myocytes. Bardoxolone methyl is a novel nuclear regulator factor (Nrf-2) activator which works to tip the balance of effects towards antioxidation and as an observation made serendipitously, improves renal filtration function in humans after approximately 12 weeks of therapy. The improvement in estimated glomerular filtration can be up to 30% in those with stage 3 and 4 chronic kidney disease. However, experimental evidence suggests there may be a consequence of relative hyperfiltration in diseased kidneys as well as potential adverse effects on skeletal and cardiac myocytes. Only large, prospective randomized trials with carefully collected and adjudicated clinical outcomes will inform the research community on the therapeutic risks and benefits of this important new agent.

Cardiac and renal function in patients with type 2 diabetes who have chronic kidney disease: potential effects of bardoxolone methyl

PubMed Central

McCullough, Peter A; Ali, Sajid

2012-01-01

The intracellular and tissue balance of oxidant and antioxidant forces is a potential therapeutic target for a variety of agents in the treatment of complications due to chronic disease including diabetes mellitus and hypertension. There are a myriad of processes controlled at the level of genes, transcription factors, and protein messages that work to control the normal use of oxidative reactions within cells. Loss of control of these processes may lead to reversible dysfunction in many cell lines including the podocyte, renal tubular cells, and cardiac myocytes. Bardoxolone methyl is a novel nuclear regulator factor (Nrf-2) activator which works to tip the balance of effects towards antioxidation and as an observation made serendipitously, improves renal filtration function in humans after approximately 12 weeks of therapy. The improvement in estimated glomerular filtration can be up to 30% in those with stage 3 and 4 chronic kidney disease. However, experimental evidence suggests there may be a consequence of relative hyperfiltration in diseased kidneys as well as potential adverse effects on skeletal and cardiac myocytes. Only large, prospective randomized trials with carefully collected and adjudicated clinical outcomes will inform the research community on the therapeutic risks and benefits of this important new agent. PMID:22787387

Impact of augmenting dialysis frequency and duration on cardiovascular function.

PubMed

Ly, Joseph; Chan, Christopher T

2006-01-01

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

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

PubMed

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

2016-03-01

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

Grape seed proanthocyanidins prevent DOCA-salt hypertension-induced renal injury and its mechanisms in rats.

PubMed

Lan, Chao-Zong; Ding, Ling; Su, Yi-Lin; Guo, Kun; Wang, Li; Kan, Hong-Wei; Ou, Yu-Rong; Gao, Shan

2015-07-01

Renal dysfunction is one of the major effects of DOCA (deoxycorticosterone acetate)-salt hypertension and there is an increasing amount of evidence that oxidative stress damages the function of the kidney. Grape seed proanthocyanidins (GSPE) have been reported to be potent anti-oxidants and free radical scavengers. The present study sought to investigate the ability of GSPE to prevent renal injury in DOCA-salt hypertensive rats and to explore the molecular mechanisms underlying its protective effects. A total of 54 Sprague Dawley (SD) rats were randomly divided into 7 groups: Sham group (n = 7), UnX-sham group (n = 8), DOCA-salt group (n = 8), GSPE150 group (150 mg kg(-1), n = 7), GSPE240 group (240 mg kg(-1), n = 8), GSPE384 group (384 mg kg(-1), n = 8) and ALM (amlodipine besylate tablets) group (5 mg kg(-1), n = 8), and treated for 4 weeks. Compared to sham group rats, renal injury was observed in DOCA-salt hypertensive group rats as the urine protein, KW/BW (kidney weight/body weight), degree of renal fibrosis, renal MDA (malondialdehyde) and Hyp (hydroxyproline) contents significantly increased (P < 0.01). Moreover, SOD (Superoxide Dismutase) activities decreased in the model group (P < 0.01). In contrast, DOCA-salt hypertensive rats treated with different dose of GSPE or ALM showed a significant improvement of renal injury with decreased urine protein, KW/BW, degree of renal fibrosis, renal total MDA and Hyp contents compared to the untreated group. In addition, SOD activities increased in the treatment group. Since the experimental modeling time was short, kidney damage occurs to a lesser extent. BUN (Blood Urea Nitrogen), Scr (Serum Creatinine) and UA (Uric Acid) contents did not appear significantly changed in all groups. Finally, the activation of JNK and p38 kinases in the kidney was suppressed in rats treated with GSPEs or ALM compared to the untreated group, suggesting that the inhibition of these kinase pathways by GSPE contributes to the improvement of renal function. Taking these results together, we conclude that the anti-hypertensive and anti-oxidative stress beneficial effects of GSPE on renal injury in rats with DOCA-salt hypertension occur via the attenuation of JNK and p38 activity.

A review of dietary supplement-induced renal dysfunction.

PubMed

Gabardi, Steven; Munz, Kristin; Ulbricht, Catherine

2007-07-01

Complementary and alternative medicine (CAM) is a multibillion-dollar industry. Almost half of the American population uses some form of CAM, with many using them in addition to prescription medications. Most patients fail to inform their health care providers of their CAM use, and physicians rarely inquire. Annually, thousands of dietary supplement-induced adverse events are reported to Poison Control Centers nationwide. CAM manufacturers are not responsible for proving safety and efficacy, because the Food and Drug Administration does not regulate them. However, concern exists surrounding the safety of CAM. A literature search using MEDLINE and EMBASE was undertaken to explore the impact of CAM on renal function. English-language studies and case reports were selected for inclusion but were limited to those that consisted of human subjects, both adult and pediatric. This review provides details on dietary supplements that have been associated with renal dysfunction and focuses on 17 dietary supplements that have been associated with direct renal injury, CAM-induced immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, and hepatorenal syndrome. It is concluded that it is imperative that use of dietary supplements be monitored closely in all patients. Health care practitioners must take an active role in identifying patients who are using CAM and provide appropriate patient education.

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.

Original Research: Potential of urinary nephrin as a biomarker reflecting podocyte dysfunction in various kidney disease models

PubMed Central

Wada, Yusuke; Moritani, Hiroshi; Mitori, Hikaru; Kondo, Mitsuhiro; Tanaka-Amino, Keiko; Eguchi, Megumi; Imasato, Akira; Inoki, Yutaka; Kajiyama, Hiroshi; Mimura, Toshihide; Tomura, Yuichi

2016-01-01

Urinary nephrin is a potential non-invasive biomarker of disease. To date, however, most studies of urinary nephrin have been conducted in animal models of diabetic nephropathy, and correlations between urinary nephrin-to-creatinine ratio and other parameters have yet to be evaluated in animal models or patients of kidney disease with podocyte dysfunction. We hypothesized that urinary nephrin-to-creatinine ratio can be up-regulated and is negatively correlated with renal nephrin mRNA levels in animal models of kidney disease, and that increased urinary nephrin-to-creatinine ratio levels are attenuated following administration of glucocorticoids. In the present study, renal nephrin mRNA, urinary nephrin-to-creatinine ratio, urinary protein-to-creatinine ratio, and creatinine clearance ratio were measured in animal models of adriamycin nephropathy, puromycin aminonucleoside nephropathy, anti-glomerular basement membrane glomerulonephritis, and 5/6 nephrectomy. The effects of prednisolone on urinary nephrin-to-creatinine ratio and other parameters in puromycin aminonucleoside (single injection) nephropathy rats were also investigated. In all models tested, urinary nephrin-to-creatinine ratio and urinary protein-to-creatinine ratio increased, while renal nephrin mRNA and creatinine clearance ratio decreased. Urinary nephrin-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA in almost all models, as well as a significant positive correlation with urinary protein-to-creatinine ratio and a significant negative correlation with creatinine clearance ratio. Urinary protein-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA. Following the administration of prednisolone to puromycin aminonucleoside (single injection) nephropathy rats, urinary nephrin-to-creatinine ratio was significantly suppressed and exhibited a significant positive correlation with urinary protein-to-creatinine ratio. In addition, the decrease in number of glomerular Wilms tumor antigen-1-positive cells was attenuated, and urinary nephrin-to-creatinine ratio exhibited a significant negative correlation in these cells. In conclusion, these results suggest that urinary nephrin-to-creatinine ratio level is a useful and reliable biomarker for predicting the amelioration of podocyte dysfunction by candidate drugs in various kidney disease models with podocyte dysfunction. This suggestion will also be validated in a clinical setting in future studies. PMID:27216597

Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction: A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study.

PubMed

Zheng, Ying; Cai, Guang-Yan; He, Li-Qun; Lin, Hong-Li; Cheng, Xiao-Hong; Wang, Nian-Song; Jian, Gui-Hua; Liu, Xu-Sheng; Liu, Yu-Ning; Ni, Zhao-Hui; Fang, Jing-Ai; Ding, Han-Lu; Guo, Wang; He, Ya-Ni; Wang, Li-Hua; Wang, Ya-Ping; Yang, Hong-Tao; Ye, Zhi-Ming; Yu, Ren-Huan; Zhao, Li-Juan; Zhou, Wen-Hua; Li, Wen-Ge; Mao, Hui-Juan; Zhan, Yong-Li; Hu, Zhao; Yao, Chen; Wei, Ri-Bao; Chen, Xiang-Mei

2017-10-20

Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD. The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min-1·1.73 m-2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis. A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the test and control groups, respectively (Z = 2.642, P = 0.008), and the median change in eGFR was -0.2 (-4.3-2.7) and -2.2 (-5.7-0.8) ml·min-1·1.73 m-2, respectively (Z = -2.408, P = 0.016). There were no significant differences in adverse events between the groups. Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction. Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102.

[Successful continuous renal replacement therapy in a neonate with early-onset group B streptococcal sepsis and multi-organ dysfunction syndrome].

PubMed

von Schnakenburg, C; Hufnagel, M; Superti-Furga, A; Rieger-Fackeldey, E; Berner, R

2009-01-01

Group B streptococcal early-onset sepsis (GBS EOS) in neonates has a mortality rate of approximately 5%, particularly in the presence of multi-organ dysfunction. Fluid management is crucial in these patients, and continuous venovenous haemofiltration (CVVH) should be considered a therapeutic option even in newborn babies. After an uneventful pregnancy within hours after birth, a female term infant presented with dyspnoea, irritability and cyanosis. The systemic inflammatory response syndrome (SIRS) progressed to multi-organ dysfunction with acute respiratory distress syndrome (ARDS), impaired myocardial contractility, pulmonary hypertension and fluid overload. The maximum PRISM score was 51. The child required maximal respiratory and inotropic support with high volume intravenous fluid administration. However, only by using of CVVH from day 5 to 14, we successfully resolved progressive pulmonary and cardiovascular dysfunction. The child improved directly after initiation of fluid removal, was extubated on day 17 and discharged without obvious sequelae on day 57. All microbiology studies revealed GBS. Perinatal GBS-infections remain a major life-threatening event for newborn babies. CVVH should be considered an option for reversing fluid overload even in neonates with overwhelming SIRS. Alternatively, extracorporeal membrane oxygenation (ECMO) is discussed.

Bilateral Renal Denervation Ameliorates Isoproterenol-Induced Heart Failure through Downregulation of the Brain Renin-Angiotensin System and Inflammation in Rat

PubMed Central

Li, Jian-Dong; Cheng, Ai-Yuan; Huo, Yan-Li; Fan, Jie; Zhang, Yu-Ping; Fang, Zhi-Qin; Sun, Hong-Sheng; Peng, Wei; Zhang, Jin-Shun

2016-01-01

Heart failure (HF) is characterized by cardiac dysfunction along with autonomic unbalance that is associated with increased renin-angiotensin system (RAS) activity and elevated levels of proinflammatory cytokines (PICs). Renal denervation (RD) has been shown to improve cardiac function in HF, but the protective mechanisms remain unclear. The present study tested the hypothesis that RD ameliorates isoproterenol- (ISO-) induced HF through regulation of brain RAS and PICs. Chronic ISO infusion resulted in remarked decrease in blood pressure (BP) and increase in heart rate and cardiac dysfunction, which was accompanied by increased BP variability and decreased baroreflex sensitivity and HR variability. Most of these adverse effects of ISO on cardiac and autonomic function were reversed by RD. Furthermore, ISO upregulated mRNA and protein expressions of several components of the RAS and PICs in the lamina terminalis and hypothalamic paraventricular nucleus, two forebrain nuclei involved in cardiovascular regulations. RD significantly inhibited the upregulation of these genes. Either intracerebroventricular AT1-R antagonist, irbesartan, or TNF-α inhibitor, etanercept, mimicked the beneficial actions of RD in the ISO-induced HF. The results suggest that the RD restores autonomic balance and ameliorates ISO-induced HF and that the downregulated RAS and PICs in the brain contribute to these beneficial effects of RD. PMID:27746855

Protective effect of Petroselinum crispum extract in abortion using prostadin-induced renal dysfunction in female rats.

PubMed

Rezazad, Maryam; Farokhi, Farah

2014-09-01

Present study investigated the effects of parsley extract on pregnant rat kidneys which have undergone clinical abortion using prostaglandins. The renal protective effect of parsley extract was evaluated in pregnant rats which had an abortion. Parsley was used due to its antioxidant properties. Fifty-four female rats were divided in 9 groups of 6: control pregnant, two pregnant groups which received parsley extract and prostadin, two non-pregnant groups treated with parsley extract and prostadin, a group administered with both treatments, and three groups which received parsley extract in pre-implantation, implantation, and post-implantation periods of embryos. Ethanolic extract (5 mg/kg) was given daily to animals for 18 days of pregnancy period. Parameters such as malondialdehyde (MDA), total antioxidant statues (TAS), creatinine, and urea were measured using biochemical assays. Histopathologic studies were also done with Hematoxylin-Eosin staining method. After 18 days of treatment, significant differences were observed in serum creatinine, urea, and MDA and TAS levels. Kidney cross-sections showed edema in prostadin-treated rats while improvements in parsley + prostadin -treated rats were observed. These results suggested that ethanolic extract of Petroselinum crispum reduced the dysfunction in rats kidney caused by prostadin-induced abortion and could have beneficial effect in reducing the progression of prostaglandin-induced edema.

Detrimental role of humoral signalling in cardio-renal cross-talk.

PubMed

Cantaluppi, Vincenzo; Dellepiane, Sergio; Quercia, Alessandro D; Ferrario, Silvia

2014-01-22

In critically ill patients, any acute organ injury is associated with a sudden change of circulating factors that may play a role in distant organ dysfunction through a complex cross-talk. In this issue, Virzì and colleagues discuss the relevance of humoral signalling between heart and kidney, focusing on type 1 and type 3 cardio-renal syndrome. We herein review the mechanisms of heart-kidney cross-talk, discussing the role of circulating detrimental mediators in the pathogenetic mechanisms of cardio-renal syndrome.

Automatic 3D kidney segmentation based on shape constrained GC-OAAM

NASA Astrophysics Data System (ADS)

Chen, Xinjian; Summers, Ronald M.; Yao, Jianhua

2011-03-01

The kidney can be classified into three main tissue types: renal cortex, renal medulla and renal pelvis (or collecting system). Dysfunction of different renal tissue types may cause different kidney diseases. Therefore, accurate and efficient segmentation of kidney into different tissue types plays a very important role in clinical research. In this paper, we propose an automatic 3D kidney segmentation method which segments the kidney into the three different tissue types: renal cortex, medulla and pelvis. The proposed method synergistically combines active appearance model (AAM), live wire (LW) and graph cut (GC) methods, GC-OAAM for short. Our method consists of two main steps. First, a pseudo 3D segmentation method is employed for kidney initialization in which the segmentation is performed slice-by-slice via a multi-object oriented active appearance model (OAAM) method. An improved iterative model refinement algorithm is proposed for the AAM optimization, which synergistically combines the AAM and LW method. Multi-object strategy is applied to help the object initialization. The 3D model constraints are applied to the initialization result. Second, the object shape information generated from the initialization step is integrated into the GC cost computation. A multi-label GC method is used to segment the kidney into cortex, medulla and pelvis. The proposed method was tested on 19 clinical arterial phase CT data sets. The preliminary results showed the feasibility and efficiency of the proposed method.

Impact of Preoperative Abdominal Visceral Adipose Tissue Area and Nutritional Status on Renal Function After Donor Nephrectomy in Japanese Living Donors for Renal Transplantation.

PubMed

Hori, Shunta; Miyake, Makito; Morizawa, Yosuke; Nakai, Yasushi; Onishi, Kenta; Iida, Kota; Gotoh, Daisuke; Anai, Satoshi; Torimoto, Kazumasa; Aoki, Katsuya; Yoneda, Tatsuo; Tanaka, Nobumichi; Yoshida, Katsunori; Fujimoto, Kiyohide

2018-05-29

BACKGROUND Living kidney donors face the risk of renal dysfunction, resulting in end-stage renal disease, cardiovascular disease, or cerebrovascular disease, after donor nephrectomy. Reducing this risk is important to increasing survival of living donors. In this study, we investigated the effect of preoperative distribution of abdominal adipose tissue and nutritional status on postoperative renal function in living donors. MATERIAL AND METHODS Seventy-five living donors were enrolled in this retrospective study. Preoperative unenhanced computed tomography images were used to measure abdominal adipose tissue parameters. Prognostic nutritional index (PNI) was used to assess preoperative nutritional status. Donors were divided into 2 groups according to abdominal visceral adipose tissue (VAT) area at the level of the fourth and fifth lumbar vertebrae (<80 or ≥80 cm²). Postoperative renal function was compared in the 2 groups, and prognostic factors for development of chronic kidney disease (CKD) G3b were identified using multivariate analysis. RESULTS Donors with a VAT area ≥80 significantly more often had hypertension preoperatively. Although there was no significant difference in preoperative estimated glomerular filtration rate (eGFR) between the 2 groups, postoperative renal function was significantly decreased in donors with a VAT area ≥80 compared to those with a VAT area <80. In multivariate analysis, VAT area ≥80 and PNI <54 were independent factors predicting the development of CKD G3b after 12 months. CONCLUSIONS Our findings suggest that preoperative VAT and PNI affect postoperative renal function. Further research is required to establish appropriate exercise protocols and nutritional interventions during follow-up to improve outcomes in living donors.

Severe acute copper sulphate poisoning: a case report.

PubMed

Sinkovic, Andreja; Strdin, Alenka; Svensek, Franci

2008-03-01

As copper sulphate pentahydrate (CSP) is a common compound used in agriculture and industry, chronic occupational exposures to CSP are well known, but acute poisoning is rare in the Western world. This case report describes acute poisoning of a 33-year-old woman who attempted suicide by ingesting an unknown amount of CSP. On admission to the hospital, she had symptoms and signs of severe hemorrhagic gastroenteritis, dehydration, renal dysfunction and methaemoglobinaemia with normal serum copper level. Therapy included early gastric lavage, fluid replacement, vasoactive drugs, furosemide, antiemetic drugs, ranitidine, and antidotes methylene blue and 2,3-dimercaptopropane-1-sulphonate (DMPS). However, the patient developed severe intravascular haemolysis, acute severe hepatic and renal failure, as well as adrenal insufficiency. After prolonged, but successful hospital treatment, including haemodialysis and IV hydrocortisone, the patient was discharged with signs of mild renal and liver impairment. Our conclusion is that in severe cases of copper poisoning early supportive measures are essential. In addition, antidotes such as methylene blue for methaemoglobinaemia and chelating agent such as DMPS improve morbidity and survival of severely poisoned victims.

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.

[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.

Effect of renal function on the pharmacokinetics of LCZ696 (sacubitril/valsartan), an angiotensin receptor neprilysin inhibitor.

PubMed

Ayalasomayajula, Surya P; Langenickel, Thomas H; Jordaan, Pierre; Zhou, Wei; Chandra, Priyamvada; Albrecht, Diego; Pal, Parasar; Rajman, Iris; Sunkara, Gangadhar

2016-09-01

LCZ696 (sacubitril/valsartan), an angiotensin receptor neprilysin inhibitor, is indicated for chronic heart failure (HF) and reduced ejection fraction (HFrEF) to reduce the risk of cardiovascular death and hospitalization for HF. Following oral administration, LCZ696 provides systemic exposure to valsartan and sacubitril (a prodrug), and its metabolite sacubitrilat (the active neprilysin inhibitor, formerly named as LBQ657), which is eliminated primarily via renal route. Since renal dysfunction is a common comorbidity in patients with HF, two open-label studies assessing the effect of mild, moderate, and severe renal impairment were conducted. Patients with mild (N = 8; creatinine clearance [CrCl] 50 to ≤80 mL/min), moderate (N = 8; CrCl 30 to <50 mL/min), and severe (N = 6; CrCl <30 mL/min) renal impairment and matching healthy subjects (CrCl >80 mL/min) for each severity group were enrolled to assess the pharmacokinetics of LCZ696 analytes following administration of LCZ696 400 mg once daily (QD) on days 1 and 5. The steady-state Cmax and AUC0-24h of sacubitril and valsartan were unchanged in patients with renal impairment compared with healthy subjects. However, the steady-state Cmax of sacubitrilat was increased by ∼60 % in patients irrespective of degree of renal impairment; half-life increased from 12 h (in healthy subjects) to 21.1, 23.7, and 38.5 h, respectively; and AUC0-24h was increased 2.10-, 2.24-, and 2.70-fold, respectively, in patients with mild, moderate, and severe renal impairment. Renal dysfunction increases exposure to sacubitrilat while not impacting sacubitril and valsartan exposure. LCZ696 was generally well tolerated in patients with renal impairment.

Optical cryoimaging for assessment of radiation-induced injury to rat kidney metabolic state

NASA Astrophysics Data System (ADS)

Mehrvar, Shima; Funding la Cour, Mette; Medhora, Meetha; Camara, Amadou K. S.; Ranji, Mahsa

2018-02-01

Objective: This study utilizes fluorescence cryoimaging to quantitatively assess the effect of a high dose of irradiation on rat renal metabolism through redox state. Introduction: Exposure to high doses of irradiation could lead to death, in part, due to renal dysfunction. The kidney is one of the most sensitive organs that exhibit delayed injuries in survivors of acute radiation syndrome. In this study, optical cryoimaging was utilized to examine the potential for renal mitochondrial dysfunction after partial-body irradiation (PBI) and the mitigating effect of lisinopril-treatment, an angiotensin converting enzyme inhibitor that is FDA-approved for other indications. Materials and methods: Rats were exposed to a single dose of 13 Gy leg-out partial body irradiation (PBI, by X-rays). Rats (n = 5/group) received no further treatment, or lisinopril started one week after irradiation and continued at 24 mg/m2 /day. The non-irradiated siblings were used as controls. After 150 days, the rats were sacrificed, and their kidneys harvested and snap frozen in liquid nitrogen for later cryoimaging. The 3D images of metabolic indices (NADH and FAD) were captured, and the redox ratio i.e. NADH/FAD was calculated. The mitochondrial redox state of three groups of rat kidneys were quantified by calculating the volumetric mean of redox ratio images (RR). Results: 3D cryoimaging revealed that in PBI only kidneys, the metabolic marker (RR) decreased significantly by 78% compared to non-irradiated controls. Treatment with lisinopril significantly improved the RR by 93% in groups exposed to PBI. Conclusion: This study aimed at quantifying the level of the mitochondrial redox state of irradiated rat kidneys compared to non-irradiated kidneys (controls) and the efficacy of lisinopril to preserve kidney metabolism after irradiation. PBI oxidized the metabolic state of kidneys and lisinopril mitigated the radiation-induced injury on renal mitochondria.

The Beneficial Effects of Allicin in Chronic Kidney Disease Are Comparable to Losartan

PubMed Central

García Trejo, Ehécatl Miguel Ángel; Arellano Buendía, Abraham Said; Sánchez Reyes, Omegar; García Arroyo, Fernando Enrique; Arguello García, Raúl; Loredo Mendoza, María Lilia; Tapia, Edilia; Sánchez Lozada, Laura Gabriela; Osorio Alonso, Horacio

2017-01-01

Recent studies suggest that allicin may play a role in chronic kidney disease (CKD), reducing hypertension and oxidative stress and improving renal dysfunction. In the present study, CKD was induced by 5/6 nephrectomy and the animals were divided into four treatment groups as follows: control (C), CKD, CKD+allicin (40 mg/kg pathway oral) (CKDA), and CKD+Losartan (20 mg/kg) (CKDL). After CKD induction, the rats developed hypertension from week 3 to the end of the study. This was associated with increased creatinine and blood urea nitrogen (BUN) levels in serum, increased albuminuria, increased urinary excretion of N-acetyl-β-d-glucosaminidase (NAG), increased nephrin expression, and incrased histological alterations in the cortex. The levels of angiotensin receptors and endothelial nitric oxide synthase (eNOS) were decreased in the renal cortex from the CKD group. Otherwise, lipid and protein oxidation were higher in the CKD group than in the control group. A disturbance was observed in the expression levels of the nuclear factor erythroid 2-related factor 2/Kelch ECH associating protein 1 system (Nrf2/keap1) and the antioxidant enzymes catalase, superoxide dismutase, and heme oxygenase-1. Allicin or losartan treatments relieved renal dysfunction, hypertension, and oxidative stress. In addition, both treatments showed the same efficacy on the expression of angiotensin receptors, the nephrin, Nrf2/keap1 pathway, and eNOS. Further in silico analyses suggest that allicin and losartan could have a common mechanism involving interaction with AT1 receptors. Allicin showed antihypertensive, antioxidant, and nephroprotective effects. The beneficial effects showed by allicin are similar, or even better, than those of losartan. In fact, the effect of allicin on blood pressure and renal function is comparable to reductions seen with losartan, a prescription drug commonly used as a first-line therapy. PMID:28926934

Non-Exertional Heatstroke: A Case Report and Review of the Literature

PubMed Central

Mozzini, Chiara; Xotta, Giovanni; Garbin, Ulisse; Pasini, Anna Maria Fratta; Cominacini, Luciano

2017-01-01

Patient: Female, 41 Final Diagnosis: Heatstroke Symptoms: Coma Medication: — Clinical Procedure: Intensive Care Unit-Internal Medicine Specialty: Critical Care Medicine Objective: Rare co-existance of disease or pathology Background: Heatstroke (HS) is a life-threatening condition characterized by an elevation of the core body temperature above 40°C, central nervous system dysfunction, and possible multi-organ failure. HS can trigger systemic inflammation, disseminated intravascular coagulation (DIC), rhabdomyolysis, cerebral edema and seizures, pulmonary edema, heart dysfunctions, and renal and hepatic failure. Case Report: We report the case of a 41-year-old Romanian woman with a history of alcoholism who developed HS after arriving by bus in Verona, Italy in June 2016. The patient developed consecutive multi-organ dysfunction, including liver and renal failure, rhabdomyolysis, DIC, and arrhythmia. The patient was successfully treated with conservative measures. After 17 days, she recovered completely. Conclusions: The exact mechanism of HS-related multiple organ dysfunction is not completely understood and its pathogenesis is complex. It involves inflammation, oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. Development of a model in which chronic alcohol abuse alters oxidative, inflammatory, and ER stress response could also be a conceivable solution to the positive prognosis of severe HS patients, in which liver failure has a prominent role. PMID:28974669

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

PubMed

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

2017-01-01

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

Prevalence of Hyponatremia, Renal Dysfunction, and Other Electrolyte Abnormalities Among Runners Before and After Completing a Marathon or Half Marathon

PubMed Central

Mohseni, Michael; Silvers, Scott; McNeil, Rebecca; Diehl, Nancy; Vadeboncoeur, Tyler; Taylor, Walt; Shapiro, Shane; Roth, Jennifer; Mahoney, Sherry

2011-01-01

Background: Prior reports on metabolic derangements observed in distance running frequently have small sample sizes, lack prerace laboratory measures, and report sodium as the sole measure. Hypothesis: Metabolic abnormalities—hyponatremia, hypokalemia, renal dysfunction, hemoconcentration—are frequent after completing a full or half marathon. Clinically significant changes occur in these laboratory values after race completion. Study Design: Observational, cross-sectional study. Methods: Consenting marathon and half marathon racers completed a survey as well as finger stick blood sampling on race day of the National Marathon to Fight Breast Cancer (Jacksonville, Florida, February 2008). Parallel blood measures were obtained before and after race completion (prerace, n = 161; postrace, n = 195). Results: The prevalence of prerace and postrace hyponatremia was 8 of 161 (5.0%) and 16 of 195 (8.2%), respectively. Hypokalemia was not present prerace but was present in 1 runner postrace (1 of 195). Renal dysfunction occurred prerace in 14 of 161 (8.7%) and postrace in 83 of 195 (42.6%). Among those with postrace renal dysfunction, 45.8% (38 of 83) were classified as moderate or severe. Hemoconcentration was present in 2 of 161 (1.2%) prerace and 6 of 195 (3.1%) postrace. The mean changes in laboratory values were (postrace minus prerace): sodium, 1.6 mmol/L; potassium, −0.2 mmol/L; blood urea nitrogen, 2.8 mg/dL; creatinine, 0.2 mg/dL; and hemoglobin, 0.3 g/dL for 149 pairs (except blood urea nitrogen, n = 147 pairs). Changes were significant for all comparisons (P < 0.01) except potassium (P = 0.08) and hemoglobin (P = 0.01). Conclusions: Metabolic abnormalities are common among endurance racers, and they may be present prerace, including hyponatremia. The clinical significance of these findings is unknown. Clinical relevance: It is unclear which runners are at risk for developing clinically important metabolic derangements. Participating in prolonged endurance exercise appears to be safe in the majority of racers. PMID:23016001

Hospitalized hemorrhagic stroke patients with renal insufficiency: clinical characteristics, care patterns, and outcomes.

PubMed

Ovbiagele, Bruce; Schwamm, Lee H; Smith, Eric E; Grau-Sepulveda, Maria V; Saver, Jeffrey L; Bhatt, Deepak L; Hernandez, Adrian F; Peterson, Eric D; Fonarow, Gregg C

2014-10-01

There is a paucity of information on clinical characteristics, care patterns, and clinical outcomes for hospitalized intracerebral hemorrhage (ICH) patients with chronic kidney disease (CKD). We assessed characteristics, care processes, and in-hospital outcome among ICH patients with CKD in the Get With the Guidelines-Stroke (GWTG-Stroke) program. We analyzed 113,059 ICH patients hospitalized at 1472 US centers participating in the GWTG-Stroke program between January 2009 and December 2012. In-hospital mortality and use of 2 predefined ICH performance measures were examined based on glomerular filtration rate. Renal dysfunction was categorized as a dichotomous (+CKD = estimated glomerular filtration rate <60) or rank ordered variable as CKD (<60), and by clinical stage: (normal [≥90], mild [≥60-<90], moderate [≥30-<60], severe [≥15-<30], and/or kidney failure [<15 or dialysis]). There were 33,219 (29%) ICH patients with CKD. Patients with CKD were more likely to be older, female, and with comorbid conditions such as diabetes. Compared with patients with normal kidney function, those with CKD were slightly less likely to receive deep venous thrombosis (DVT) prophylaxis but similarly received discharge smoking cessation intervention. Inpatient mortality was also higher for those with CKD (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.42-1.52), mild dysfunction (adjusted OR, 1.12; 95% CI, 1.08-1.16), moderate dysfunction (adjusted OR, 1.46; 95% CI, 1.39-1.53), severe dysfunction (adjusted OR, 1.96; 95% CI, 1.81-2.12), and kidney failure (adjusted OR, 2.22; 95% CI, 2.04-2.43) relative to those with normal renal function. Chronic kidney disease is present in nearly a third of patients hospitalized with ICH and is associated with slightly worse care and substantially higher mortality than those with normal renal function. Copyright © 2014 National Stroke Association. Published by 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

Hyperosmolarity induced by high glucose promotes senescence in human glomerular mesangial cells.

PubMed

del Nogal, Maria; Troyano, Nuria; Calleros, Laura; Griera, Mercedes; Rodriguez-Puyol, Manuel; Rodriguez-Puyol, Diego; Ruiz-Torres, María P

2014-09-01

Hyperglycemia is involved in the diabetic complication of different organs and can elevate serum osmolarity. Here, we tested whether hyperosmolarity promoted by high glucose levels induces cellular senescence in renal cells. We treated Wistar rats with streptozotocin to induce diabetes or with consecutive daily injections of mannitol to increase serum osmolarity and analyzed p53 and p16 genes in renal cortex by immunohistochemistry. Both diabetic and mannitol treated rats showed a significant increase in serum osmolarity, without significant signs of renal dysfunction, but associated with increased staining for p53 and p16 in the renal cortex. An increase in p53 and p16 expression was also found in renal cortex slices and glomeruli isolated from healthy rats, which were later treated with 30 mM glucose or mannitol. Intracellular mechanisms involved were analyzed in cultured human glomerular mesangial cells treated with 30 mM glucose or mannitol. After treatments, cells showed increased p53, p21 and p16 expression and elevated senescence-associated β-galactosidase activity. Senescence was prevented when myo-inositol was added before treatment. High glucose or mannitol induced constitutive activation of Ras and ERK pathways which, in turn, were activated by oxidative stress. In summary, hyperosmolarity induced renal senescence, particularly in glomerular mesangial cells, increasing oxidative stress, which constitutively activated Ras-ERK 1/2 pathway. Cellular senescence could contribute to the organ dysfunction associated with diabetes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Association between markers of endothelial dysfunction and early signs of renal dysfunction in pediatric obesity and type 1 diabetes.

PubMed

Marcovecchio, M L; de Giorgis, T; Di Giovanni, I; Chiavaroli, V; Chiarelli, F; Mohn, A

2017-06-01

To evaluate whether circulating markers of endothelial dysfunction, such as intercellular adhesion molecule-1 (ICAM-1) and myeloperoxidase (MPO), are increased in youth with obesity and in those with type 1 diabetes (T1D) at similar levels, and whether their levels are associated with markers of renal function. A total of 60 obese youth [M/F: 30/30, age: 12.5 ± 2.8 yr; body mass index (BMI) z-score: 2.26 ± 0.46], 30 with T1D (M/F: 15/15; age: 12.9 ± 2.4 yr; BMI z-score: 0.45 ± 0.77), and 30 healthy controls (M/F: 15/15, age: 12.4 ± 3.3 yr, BMI z-score: -0.25 ± 0.56) were recruited. Anthropometric measurements were assessed and a blood sample was collected to measure ICAM-1, MPO, creatinine, cystatin C and lipid levels. A 24-h urine collection was obtained for assessing albumin excretion rate (AER). Levels of ICAM-1 and MPO were significantly higher in obese [ICAM-1: 0.606 (0.460-1.033) µg/mL; MPO: 136.6 (69.7-220.8) ng/mL] and T1D children [ICAM-1: 0.729 (0.507-0.990) µg/mL; MPO: 139.5 (51.0-321.3) ng/mL] compared with control children [ICAM-1: 0.395 (0.272-0.596) µg/mL MPO: 41.3 (39.7-106.9) ng/mL], whereas no significant difference was found between T1D and obese children. BMI z-score was significantly associated with ICAM-1 (β = 0.21, p = 0.02) and MPO (β = 0.41, p < 0.001). A statistically significant association was also found between ICAM-1 and markers of renal function (AER: β = 0.21, p = 0.03; e-GFR: β = 0.19, p = 0.04), after adjusting for BMI. Obese children have increased markers of endothelial dysfunction and early signs of renal damage, similarly to children with T1D, confirming obesity to be a cardiovascular risk factor as T1D. The association between ICAM-1 with e-GFR and AER confirm the known the association between general endothelial and renal dysfunction. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An integrated lipidomics and metabolomics reveal nephroprotective effect and biochemical mechanism of Rheum officinale in chronic renal failure

PubMed Central

Zhang, Zhi-Hao; Vaziri, Nosratola D.; Wei, Feng; Cheng, Xian-Long; Bai, Xu; Zhao, Ying-Yong

2016-01-01

Chronic renal failure (CRF) is a major public health problem worldwide. Earlier studies have revealed salutary effects of rhubarb extracts in CRF. In this study, we employed lipidomic and metabolomic approaches to identify the plasma biomarkers and to determine the effect of treatment with petroleum ether, ethyl acetate and n-butanol extracts of rhubarb in a rat model of CRF with adenine-induced chronic tubulointerstitial nephropathy. In addition, clinical biochemistry, histological evaluation and pro-fibrotic protein expression were analyzed. Significant changes were found between the CRF and control groups representing characteristic phenotypes of rats with CRF. Treatment with the three rhubarb extracts improved renal injury and dysfunction, either fully or partially reversed the plasma metabolites abnormalities and attenuated upregulation of pro-fibrotic proteins including TGF-β1, α-SMA, PAI-1, CTGF, FN and collagen-1. The nephroprotective effect of ethyl acetate extract was better than other extracts. The differential metabolites were closely associated with glycerophospholipid, fatty acid and amino acid metabolisms. The results revealed a strong link between renal tubulointerstitial fibrosis and glycerophospholipid metabolism and L-carnitine metabolism in the development of CRF. Amelioration of CRF with the three rhubarb extracts was associated with the delayed development and/or reversal the disorders in key metabolites associated with adenine-induced CRF. PMID:26903149

Urinary tract infections in children after renal transplantation.

PubMed

John, Ulrike; Kemper, Markus J

2009-06-01

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

Reversible posterior leucoencephalopathy syndrome associated with bone marrow transplantation.

PubMed

Teive, H A; Brandi, I V; Camargo, C H; Bittencourt, M A; Bonfim, C M; Friedrich, M L; de Medeiros, C R; Werneck, L C; Pasquini, R

2001-09-01

Reversible posterior leucoencephalopathy syndrome (RPLS) has previously been described in patients who have renal insufficiency, eclampsia, hypertensive encephalopathy and patients receiving immunosuppressive therapy. The mechanism by which immunosuppressive agents can cause this syndrome is not clear, but it is probably related with cytotoxic effects of these agents on the vascular endothelium. We report eight patients who received cyclosporine A (CSA) after allogeneic bone marrow transplantation or as treatment for severe aplastic anemia (SSA) who developed posterior leucoencephalopathy. The most common signs and symptoms were seizures and headache. Neurological dysfunction occurred preceded by or concomitant with high blood pressure and some degree of acute renal failure in six patients. Computerized tomography studies showed low-density white matter lesions involving the posterior areas of cerebral hemispheres. Symptoms and neuroimaging abnormalities were reversible and improvement occurred in all patients when given lower doses of CSA or when the drug was withdrawn. RPLS may be considered an expression of CSA neurotoxicity.

Interaction of Gender and Hepatitis C in Risk of Chronic Renal Failure After Liver Transplantation.

PubMed

Ip, Stephen; Hussaini, Trana; Daulat, Aliya; Partovi, Nilufar; Erb, Siegfried R; Yoshida, Eric M; Marquez, Vladimir

2017-01-01

Chronic renal failure (CRF) is a significant cause of morbidity and mortality in post-liver transplantation (LT) recipients. The risk factors associated with the development of renal dysfunction are not clearly elucidated. To examine the risk factors in the development of CRF in these patients. Retrospective case-cohort of liver transplant patients without baseline kidney dysfunction who developed chronic renal failure during their follow-up. Of 370 patients, 254 met the inclusion criteria. 30% (76) of these patients had CRF of which 57% (43) were male. Age, estimated glomerular filtration rate (eGFR) at discharge, and HCV infection were found to be risk factors for CRF post-LT. The odds ratio of developing CRF was 1.4 (0.6-3.3) in males with HCV, 1.6 (0.7-3.9) in females without HCV and 4.4 (1.5-13.2) among females with HCV when compared to men without HCV. In this cohort of LT receipients of a major Canadian city, age, eGFR, and HCV infection were risk factors for CRF. Female gender and HCV increased this odds by a factor of more than 4.

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

Emergency management of renal and genitourinary trauma: best practices update [digest].

PubMed

Bryant, Whitney K; Shewakramani, Sanjay; Zaurova, Milana

2017-08-22

In up to 10% of patients who experience abdominal trauma, renal and urogenital systems will be involved. In polytrauma patients with other potentially life-threatening injuries, renal and genitourinary trauma may be overlooked initially, but a delayed or missed diagnosis of these injuries may result in preventable complications. This review provides a best-practice approach to the diagnosis and management of renal and genitourinary injuries, with an emphasis on the systematic approach needed to identify subtle injuries and avoid long-term urinary sequelae such as hypertension, incontinence, erectile dysfunction, chronic kidney disease, and nephrectomy. [Points & Pearls is a digest of Emergency Medicine Practice.].

Obesity and kidney protection

PubMed Central

Chandra, Aravind; Biersmith, Michael; Tolouian, Ramin

2014-01-01

Context: Obesity, both directly and indirectly, increases the risk for a variety of disease conditions including diabetes, hypertension, liver disease, and certain cancers, which in turn, decreases the overall lifespan in both men and women. Though the cardiovascular risks of obesity are widely acknowledged, less often identified is the relationship between obesity and renal function. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO and Web of Science has been searched. Results: The concept of the “Metabolic Syndrome“ helps us to understand this close link between obesity, diabetes, hypertension, and renal dysfunction. An elevated body mass index has shown to be one of the major determinants of glomerular hyperfiltration that lead to the development of chronic kidney disease. Interestingly, weight loss can lead to attenuation of hyperfiltration in severely obese patients suggesting a possible therapeutic option to combat obesity-related hyperfiltration. Conclusions: Various treatment strategies had been suggested to decrease impact of obesity on kidneys. These are blood pressure controling, inhibition of the renin-angiotensinaldosterone axis, improving glycemic control, improving dyslipidemia, improving protein uriaand lifestyle modifications. Regardless of the numerous pharmacotherapies, the focus should be on the root cause: obesity. PMID:25093156

A low plasma 1,25(OH)2 vitamin D/PTH (1-84) ratio predicts worsening of renal function in patients with chronic heart failure.

PubMed

Masson, Serge; Barlera, Simona; Colotta, Francesco; Magnoli, Michela; Bonelli, Fabrizio; Moro, Milena; Marchioli, Roberto; Tavazzi, Luigi; Tognoni, Gianni; Latini, Roberto

2016-12-01

Dysregulation of the vitamin D system promotes renal dysfunction and has direct detrimental effects on the heart. Progressive deterioration of renal function is common in patients with chronic heart failure (HF) and is invariably associated with unfavorable outcomes which can be improved by early identification and timely interventions. We examined the relation between two plasma markers of vitamin D metabolism and worsening of renal function (WRF) in a large cohort of patients with chronic HF. Plasma levels of 1,25-dihydroxyvitamin D (1,25(OH) 2 D) and parathyroid hormone PTH (1-84) were measured in 1237 patients with clinical evidence of chronic and stable HF enrolled in the multicentre GISSI-HF trial and followed for 3.9years. We examined the relation of 1,25(OH) 2 D, PTH(1-84), and their ratio with WRF, defined as first increase in serum creatinine concentration ≥0.3mg/dL and ≥25% at two consecutive measurements at any time during the study. Lower 1,25(OH) 2 D/PTH(1-84) ratio was associated with a higher baseline serum concentration of creatinine, winter season, female sex and older age; 335 patients (29.6%) experienced an episode of WRF. After adjustment, a lower 1,25(OH) 2 D/PTH(1-84) ratio remained significantly associated with a higher risk of WRF (HR=0.75 [0.62-0.90], p=0.002) and correctly reclassified events. This ratio also independently predicted mortality and admission to hospital for cardiovascular reasons. The plasma 1,25(OH) 2 D/PTH(1-84) ratio is a promising indicator of future risk of deterioration of renal function in patients with chronic HF and mild renal impairment, that may serve to optimize therapies and improve outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

The role of platelets and ε-aminocaproic acid in arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome associated hemorrhage

PubMed Central

Weyand, Angela C.; Lombel, Rebecca M.; Pipe, Steven W.; Shavit, Jordan A.

2015-01-01

Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome is a rare disorder associated with platelet abnormalities resembling Gray Platelet Syndrome. Affected patients have normal platelet numbers but abnormal morphology and function. Bleeding symptomatology ranges from post-procedural to spontaneous life-threatening hemorrhage. We report a patient with ARC syndrome and compound heterozygous mutations in VPS33B who presented with significant bleeding requiring numerous admissions and transfusions. She was treated with prophylactic platelet transfusions and ε-aminocaproic acid. This was well tolerated and significantly decreased transfusion requirements and admissions for bleeding. Our experience provides support for consideration of prophylactic measures in these patients as well as the possibility of using prophylaxis in related disorders. PMID:26505894

Management of Chronic Kidney Disease Patients in the Intensive Care Unit: Mixing Acute and Chronic Illness.

PubMed

De Rosa, Silvia; Samoni, Sara; Villa, Gianluca; Ronco, Claudio

2017-01-01

Patients with chronic kidney disease (CKD) are at high risk for developing critical illness and for admission to intensive care units (ICU). 'Critically ill CKD patients' frequently develop an acute worsening of renal function (i.e. acute-on-chronic, AoC) that contributes to long-term kidney dysfunction, potentially leading to end-stage kidney disease (ESKD). An integrated multidisciplinary effort is thus necessary to adequately manage the multi-organ damage of those kidney patients and contemporaneously reduce the progression of kidney dysfunction when they are critically ill. The aim of this review is to describe (1) the pathophysiological mechanisms underlying the development of AoC kidney dysfunction and its role in the progression toward ESKD; (2) the most common clinical presentations of critical illness among CKD/ESKD patients; and (3) the continuum of care for CKD/ESKD patients from maintenance hemodialysis/peritoneal dialysis to acute renal replacement therapy performed in ICU and, vice-versa, for AoC patients who develop ESKD. © 2017 S. Karger AG, Basel.

[Simultaneous Hepatorenal Transplantation from a Brain-Dead Donor for Graft Dysfunction and Renal Insufficiency in a Liver Transplant Recipient : A Case Report].

PubMed

Takada, Hideaki; Kobayashi, Takashi; Ogawa, Kohei; Miyata, Hitomi; Sawada, Atsuro; Akamatsu, Shusuke; Negoro, Hiromitsu; Saito, Ryoichi; Terada, Naoki; Yamasaki, Toshinari; Inoue, Takahiro; Teramoto, Yuki; Shibuya, Shinsuke; Haga, Hironori; Kaido, Toshimi; Uemoto, Shinji; Ogawa, Osamu

2017-08-01

We report a case of lethal hepatorenal insufficiency in a 52-year-old man who received successful simultaneous hepatorenal transplantation from a deceased donor. The patient had undergone live-donor liver transplantation for type-C hepatitis and liver cirrhosis 11 years before he developed graft liver dysfunction due to recurrent viral hepatitis and cirrhosis. At that instance, he also developed end-stage renal dysfunction due to calcineurin inhibitor nephropathy and hepatorenal syndrome. Although he needed three open hemostases and abundant blood transfusion, he was withdrawn from continuous hemodiafiltration on the 55th day and discharged from the hospital on the 272nd day postoperatively. Simultaneous hepatorenal transplantation was reported to be associated with more favorable outcomes of graft function, lower rejection rates, but higher perioperative complication rates compared with liver transplantation alone in patients on hemodialysis. Particularly, close attention should be paid for hemostasis since patients have a hemorrhagic tendency until the recovery of graft liver function.

Protective Effects of the Third Generation Vasodilatory Βeta - Blocker Nebivolol against D-Galactosamine - Induced Hepatorenal Syndrome in Rats

PubMed Central

Atwa, Ahmed; Hegazy, Rehab; Mohsen, Rania; Yassin, Neamat; Kenawy, Sanaa

2017-01-01

BACKGROUND: Renal dysfunction is very common in patients with advanced liver cirrhosis and portal hypertension. The development of renal failure in the absence of clinical, anatomical or pathological causes renal of failure is termed hepatorenal syndrome (HRS). AIM: The present study was constructed to investigate the possible protective effects of nebivolol (Nebi) against D-galactosamine (Gal)-induced HRS in rats. MATERIAL AND METHODS: Rats were treated with Nebi for ten successive days. On the 8th day of the experiment, they received a single dose of Gal. Serum levels of Cr, BUN, Na+ and K+ as well as AST, ALT, total bilirubin (TB), NH3 and endothelin-1 (ET-1) were determined following Gal administration. Moreover, renal and liver contents of MDA, GSH, F2-isoprostanes (F2-IPs), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa-B (NF-κB), total nitric oxide (NO), in addition to activities of caspase-3 (Cas-3), heme oxygenase-1 (HO-1), inducible and endothelial NO synthase (iNOS and eNOS) enzymes were also assessed. Finally, histopathological examination was performed. RESULTS: Nebi attenuated Gal-induced renal and hepatic dysfunction. It also decreased the Gal-induced oxidative stress and inflammatory recruitment. CONCLUSION: Results demonstrated both nephroprotective and hepatoprotective effects of Nebi against HRS and suggested a role of its antioxidant, anti-inflammatory, anti-apoptotic and NO-releasing properties. PMID:29362613

Pulmonary Catherization Data Correlate Poorly with Renal Function in Heart Failure.

PubMed

Masha, Luke; Stone, James; Stone, Danielle; Zhang, Jun; Sheng, Luo

2018-04-10

The mechanisms of renal dysfunction in heart failure are poorly understood. We chose to explore the relationship of cardiac filling pressures and cardiac index (CI) in relation to renal dysfunction in advanced heart failure. To determine the relationship between renal function and cardiac filling pressures using the United Network of Organ Sharing (UNOS) pulmonary artery catherization registry. Patients over the age of 18 years who were listed for single-organ heart transplantation were included. Exclusion criteria included a history of mechanical circulatory support, previous transplantation, any use of renal replacement therapy, prior history of malignancy, and cardiac surgery, amongst others. Correlations between serum creatinine (SCr) and CI, pulmonary capillary wedge pressure (PCWP), pulmonary artery systolic pressure (PASP), and pulmonary artery diastolic pressure (PADP) were assessed by Pearson correlation coefficients and simple linear regression coefficients. Pearson correlation coefficients between SCr and PCWP, PASP, and PADP were near zero with values of 0.1, 0.07, and 0.08, respectively (p < 0.0001). A weak negative correlation coefficient between SCr and CI was found (correlation coefficient, -0.045, p = 0.027). In a subgroup of young patients unlikely to have noncardiac etiologies, no significant correlations between these values were identified. These findings suggest that, as assessed by pulmonary artery catherization, none of the factors - PCWP, PASP, PADP, or CI - play a prominent role in cardiorenal syndromes. © 2018 S. Karger AG, Basel.

Impact of renal dysfunction on outcomes of coronary artery bypass surgery: results from the Society of Thoracic Surgeons National Adult Cardiac Database.

PubMed

Cooper, William A; O'Brien, Sean M; Thourani, Vinod H; Guyton, Robert A; Bridges, Charles R; Szczech, Lynda A; Petersen, Rebecca; Peterson, Eric D

2006-02-28

Although patients with end-stage renal disease are known to be at high risk for mortality after coronary artery bypass graft (CABG) surgery, the impact of lesser degrees of renal impairment has not been well studied. The purpose of this study was to compare outcomes in patients undergoing CABG with a range from normal renal function to dependence on dialysis. We reviewed 483,914 patients receiving isolated CABG from July 2000 to December 2003, using the Society of Thoracic Surgeons National Adult Cardiac Database. Glomerular filtration rate (GFR) was estimated for patients with the use of the Modification of Diet in Renal Disease study formula. Multivariable logistic regression was used to determine the association of GFR with operative mortality and morbidities (stroke, reoperation, deep sternal infection, ventilation >48 hours, postoperative stay >2 weeks) after adjustment for 27 other known clinical risk factors. Preoperative renal dysfunction (RD) was common among CABG patients, with 51% having mild RD (GFR 60 to 90 mL/min per 1.73 m2, excludes dialysis), 24% moderate RD (GFR 30 to 59 mL/min per 1.73 m2, excludes dialysis), 2% severe RD (GFR <30 mL/min per 1.73 m2, excludes dialysis), and 1.5% requiring dialysis. Operative mortality rose inversely with declining renal function, from 1.3% for those with normal renal function to 9.3% for patients with severe RD not on dialysis and 9.0% for those who were dialysis dependent. After adjustment for other covariates, preoperative GFR was one of the most powerful predictors of operative mortality and morbidities. Preoperative RD is common in the CABG population and carries important prognostic importance. Assessment of preoperative renal function should be incorporated into clinical risk assessment and prediction models.

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

PubMed

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

2016-06-01

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

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

PubMed Central

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

2016-01-01

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

Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.

PubMed

Adedara, Isaac A; Ojuade, Temini Jesu D; Olabiyi, Bolanle F; Idris, Umar F; Onibiyo, Esther M; Ajeigbe, Olufunke F; Farombi, Ebenezer O

2017-02-01

Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.

R1 autonomic nervous system in acute kidney injury.

PubMed

Hering, Dagmara; Winklewski, Pawel J

2017-02-01

Acute kidney injury (AKI) is a rapid loss of kidney function resulting in accumulation of end metabolic products and associated abnormalities in fluid, electrolyte and acid-base homeostasis. The pathophysiology of AKI is complex and multifactorial involving numerous vascular, tubular and inflammatory pathways. Neurohumoral activation with heightened activity of the sympathetic nervous system and renin-angiotensin-aldosterone system play a critical role in this scenario. Inflammation and/or local renal ischaemia are underlying mechanisms triggering renal tissue hypoxia and resultant renal microcirculation dysfunction; a common feature of AKI occurring in numerous clinical conditions leading to a high morbidity and mortality rate. The contribution of renal nerves to the pathogenesis of AKI has been extensively demonstrated in a series of experimental models over the past decades. While this has led to better knowledge of the pathogenesis of human AKI, therapeutic approaches to improve patient outcomes are scarce. Restoration of autonomic regulatory function with vagal nerve stimulation resulting in anti-inflammatory effects and modulation of centrally-mediated mechanisms could be of clinical relevance. Evidence from experimental studies suggests that a therapeutic splenic ultrasound approach may prevent AKI via activation of the cholinergic anti-inflammatory pathway. This review briefly summarizes renal nerve anatomy, basic insights into neural control of renal function in the physiological state and the involvement of the autonomic nervous system in the pathophysiology of AKI chiefly due to sepsis, cardiopulmonary bypass and ischaemia/reperfusion experimental model. Finally, potentially preventive experimental pre-clinical approaches for the treatment of AKI aimed at sympathetic inhibition and/or parasympathetic stimulation are presented. © 2016 John Wiley & Sons Australia, Ltd.

Effects of a switch from tenofovir- to abacavir-based antiretroviral therapy, with or without atazanavir, on renal function.

PubMed

Guillemi, Silvia A; Ling, Sean H; Dahlby, Julia S; Yip, Benita; Zhang, Wendy; Hull, Mark W; Lima, Viviane Dias; Hogg, Robert S; Werb, Ronald; Montaner, Julio S; Harris, Marianne

2016-01-01

Tenofovir disoproxil fumarate (TDF)-associated renal dysfunction may abate when TDF is replaced with abacavir (ABC). The extent to which the third drug atazanavir contributes to renal dysfunction is unclear. A retrospective analysis was conducted on adults who had plasma viral load (pVL)<200 copies/mL for≥six months while receiving TDF/lamivudine (3TC) - or TDF/emtricitabine (FTC)-based antiretroviral therapy (ART), then switched to ABC/3TC while retaining the third drug in the ART regimen. CD4, pVL, creatinine, estimated glomerular filtration rate (eGFR), serum phosphorus, urine albumin to creatinine ratio and serum lipids were compared between pre-switch baseline and 3, 6 and 12 months after the switch to ABC. A total of 286 patients switched from TDF to ABC between 2004 and 2014: 232 (81%) male, median age 48 years (interquartile range (IQR) 42, 56). The third drug was atazanavir (± ritonavir) in 141 (49%) cases. The pVL was<50 copies/mL in 93 to 96% at all time points. Median serum creatinine was 93 µmol/L (IQR 80-111) at baseline and decreased to 88 µmol/L (IQR 78-98) at 12 months after the switch to ABC. Median eGFR increased from 74 (IQR 60-88) mL/min at baseline to 80 mL/min (IQR 69-89) at 12 months. Results were not significantly different between patients on atazanavir versus those on another third drug. Viral suppression was maintained among patients who switched from TDF/3TC or TDF/FTC to ABC/3TC. Serum creatinine and eGFR improved up to 12 months after switching to ABC/3TC, irrespective of whether or not patients were also receiving atazanavir±ritonavir.

Tenofovir Nephrotoxicity: 2011 Update

PubMed Central

Fernandez-Fernandez, Beatriz; Montoya-Ferrer, Ana; Sanz, Ana B.; Sanchez-Niño, Maria D.; Izquierdo, Maria C.; Poveda, Jonay; Sainz-Prestel, Valeria; Ortiz-Martin, Natalia; Parra-Rodriguez, Alejandro; Selgas, Rafael; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto

2011-01-01

Tenofovir is an acyclic nucleotide analogue reverse-transcriptase inhibitor structurally similar to the nephrotoxic drugs adefovir and cidofovir. Tenofovir is widely used to treat HIV infection and approved for treatment of hepatitis B virus. Despite initial cell culture and clinical trials results supporting the renal safety of tenofovir, its clinical use is associated with a low, albeit significant, risk of kidney injury. Proximal tubular cell secretion of tenofovir explains the accumulation of the drug in these mitochondria-rich cells. Tenofovir nephrotoxicity is characterized by proximal tubular cell dysfunction that may be associated with acute kidney injury or chronic kidney disease. Withdrawal of the drug leads to improvement of analytical parameters that may be partial. Understanding the risk factors for nephrotoxicity and regular monitoring of proximal tubular dysfunction and serum creatinine in high-risk patients is required to minimize nephrotoxicity. Newer, structurally similar molecular derivatives that do not accumulate in proximal tubules are under study. PMID:21716719

Ciliary dysfunction and obesity.

PubMed

Mok, C A; Héon, E; Zhen, M

2010-01-01

Obesity associates with increased health risks such as heart disease, stroke and diabetes. The steady rise in the obese population worldwide poses an increasing burden on health systems. Genetic factors contribute to the development of obesity, and the elucidation of their physiological functions helps to understand the cause, and improve the prevention, diagnosis and treatment for this disorder. Primary cilia are evolutionarily conserved organelles whose dysfunctions lead to human disorders now defined as ciliopathies. Human ciliopathies present pleiotropic and overlapping phenotypes that often include retinal degeneration, cystic renal anomalies and obesity. Increasing evidence implicates an intriguing involvement of cilia in lipid/energy homeostasis. Here we discuss recent studies in support of the key roles of ciliary genes in the development and pathology of obesity in various animal models. Genes affecting ciliary development and function may pose promising candidate underlying genetic factors that contribute to the development of common obesity.

Spectrum of Clinical Diseases Caused By Disorders of Primary Cilia

PubMed Central

Aygun, Meral Gunay-; Hildebrandt, Friedhelm

2011-01-01

The ciliopathies are a category of diseases caused by disruption of the physiological functions of cilia. Ciliary dysfunction results in a broad range of phenotypes, including renal, hepatic, and pancreatic cyst formation; situs abnormalities; retinal degeneration; anosmia; cerebellar or other brain anomalies; postaxial polydactyly; bronchiectasis; and infertility. The specific clinical features are dictated by the subtype, structure, distribution, and function of the affected cilia. This review highlights the clinical variability caused by dysfunction of motile and nonmotile primary cilia and emphasizes the genetic heterogeneity and phenotypic overlap that are characteristics of these disorders. There is a need for additional research to understand the shared and unique functions of motile and nonmotile cilia and the pathophysiology resulting from mutations in cilia, basal bodies, or centrosomes. Increased understanding of ciliary biology will improve the diagnosis and management of primary ciliary dyskinesia, syndromic ciliopathies, and cilia-related cystic diseases. PMID:21926397

Atgl gene deletion predisposes to proximal tubule damage by impairing the fatty acid metabolism

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

Chen, Wen; Zhang, Qiong; Cheng, Shiwu

Fibrosis is the final common pathway of chronic kidney disease (CKD). Normal lipid metabolism is integral to renal physiology, and disturbances of renal lipid metabolism are increasingly being linked with CKD, including the fibrosis. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of lipolysis. In the present study, we used Atgl{sup −/−} mice to investigate whether ATGL played a role in the regulation of proximal convoluted tubule (PCT) lipid metabolism and renal fibrosis development. ATGL deficiency led to lipid vacuolation of PCT and tubulointerstitial fibrosis, accompanied by massive albuminuria and decreased creatinine clearance rate (Ccr). In vitro experiments indicated that inhibitionmore » of ATGL in proximal tubular cell line HK-2 promoted intracellular lipid deposition, reactive oxygen species (ROS) accumulation and cell apoptosis. Both in vitro and in vivo experiments showed that ATGL inhibition decreased the renal peroxisome proliferator-activated receptorα(PPARα) expression, which implied the suppressed lipid metabolism. The antioxidant N-acetylcysteine (NAC) could partially reverse the effect of ROS accumulation and cell apoptosis, but could not restore the PPARαdecrease. These data raise the possibility that ATGL deficiency could impair the renal fatty acid metabolism though inhibiting PPARαexpression, which may lead to lipid deposition and cell apoptosis of PCT, and finally contribute to the renal fibrosis and dysfunction. - Highlights: • Atgl{sup −/−} mice develop tubulointerstitial damage and renal dysfunction. • ATGL deficiency results in lipid accumulation and apoptosis of proximal tubular cells. • ROS scavenger alleviates the ATGL-knockdown mediated lipid accumulation and apoptosis. • PPARαdown-regulation is the reason of ROS elevating in ATGL-knockdown HK-2 cells.« less

How to manage intravenous vinflunine in cancer patients with renal impairment: results of a pharmacokinetic and tolerability phase I study

PubMed Central

Isambert, Nicolas; Delord, Jean Pierre; Tourani, Jean Marc; Fumoleau, Pierre; Ravaud, Alain; Pinel, Marie Claire; Petain, Aurelie; Nguyen, Thierry; Nguyen, Laurent

2014-01-01

Aims Vinflunine (VFL) ditartrate, a novel tubulin-targeted inhibitor, is registered for the treatment of patients with advanced or metastatic urothelial transitional cell carcinoma. This phase I study assessed the effect of renal impairment on the pharmacokinetics and tolerability of VFL. Methods VFL was infused in patients with advanced/metastatic solid tumours once every 3 weeks with anticipated dose reduction on the first cycle stratified according to the creatinine clearance (CLcr) values. Pharmacokinetic data were collected on the first two cycles in renally impaired patients (CLcr ≤ 60 ml min−1) and were compared with a control cohort of patients (CLcr > 60 ml min−1). Results Thirty-three patients (46–86 years) were treated, 13 in group 1 (40 ml min−1 ≤ CLcr ≤ 60 ml min−1) and 20 in group 2 (20 ml min−1 ≤ CLcr < 40 ml min−1). The renal dysfunction induced a mean decrease in VFL clearance of 12% in group 1 and 28% in group 2, compared with the control group. The anticipated dose reduction given in renally impaired patients (i.e. 280 mg m−2 and 250 mg m−2 in groups 1 and 2, respectively) yielded similar drug exposure to control patients. The tolerance profile of VFL in patients with renal dysfunction was similar to that observed in patients with CLcr > 60 ml min−1. Conclusion In conclusion, the recommended doses of intravenous VFL administered once every 3 weeks in cancer patients with renal impairment are 280 mg m−2 when CLcr is between 40 and 60 ml min−1 and 250 mg m−2 when CLcr is between 20 and <40 ml min−1. PMID:24283925

Effect of Febuxostat on the Endothelial Dysfunction in Hemodialysis Patients: A Randomized, Placebo-Controlled, Double-Blinded Study.

PubMed

Alshahawey, Mona; Shahin, Sara Mahmoud; Elsaid, Tamer Wahid; Sabri, Nagwa Ali

2017-01-01

Endothelial dysfunction is an important risk factor for cardiovascular diseases to occur in end-stage renal disease patients. Febuxostat, being a novel xanthine oxidase inhibitor, is apparently having a beneficial role in improving the endothelial dysfunction; however, data among hemodialysis patients are still limited. A prospective, placebo-controlled, block-randomized, double-blinded study was carried out to evaluate the effect of oral febuxostat on the endothelial dysfunction in hemodialysis patients. Fifty-seven eligible hemodialysis patients were randomly assigned to either the drug group (40 mg thrice weekly) or the placebo group. Serum Asymmetric dimethylarginine (ADMA), Serum uric acid (UA), and serum high sensitivity C-reactive protein (hsCRP) were measured at baseline and at the end of a 2-month study. Serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and the occurrence of pancytopenia were tested as safety parameters at baseline and at the end of study. Serum UA significantly decreased from 7.5 ± 0.8 to 5.1 ± 1.2 mg/dL in the febuxostat group, while it did not change significantly in the placebo group. Treatment with febuxostat resulted in a significant decrease in the serum ADMA level from 1.027 ± 0.116 to 0.944 ± 0.104 µmol/L and the serum hsCRP level from 12.5 ± 1.65 to 12.1 ± 1.70 mg/L. Testing of serum ALT, serum AST, and pancytopenia revealed no significant difference in both groups. Febuxostat appears to improve hyperuricemia and endothelial dysfunction and ameliorate inflammation in hemodialysis patients with no safety concerns. © 2017 S. Karger AG, Basel.

Complications of transplantation. Part 1: renal transplants.

PubMed

Khaja, Minhaj S; Matsumoto, Alan H; Saad, Wael E

2014-10-01

Vascular complications after solid-organ transplantation are not uncommon and may lead to graft dysfunction and ultimately graft loss. A thorough understanding of the surgical anatomy, etiologies, and types of vascular complications, their presentation, and the options for management are important for managing these complex patients. This article reviews the basic surgical anatomy, vascular complications, and endovascular management options of vascular complications in patients with renal transplants.

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

[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.

Manifestations of Renal Impairment in Fructose-induced Metabolic Syndrome.

PubMed

Bratoeva, Kameliya; Stoyanov, George S; Merdzhanova, Albena; Radanova, Mariya

2017-11-07

Introduction International studies show an increased incidence of chronic kidney disease (CKD) in patients with metabolic syndrome (MS). It is assumed that the major components of MS - obesity, insulin resistance, dyslipidemia, and hypertension - are linked to renal damage through the systemic release of several pro-inflammatory mediators, such as uric acid (UA), C-reactive protein (CRP), and generalized oxidative stress. The aim of the present study was to investigate the extent of kidney impairment and manifestations of dysfunction in rats with fructose-induced MS. Methods We used a model of high-fructose diet in male Wistar rats with 35% glucose-fructose corn syrup in drinking water over a duration of 16 weeks. The experimental animals were divided into two groups: control and high-fructose drinking (HFD). Serum samples were obtained from both groups for laboratory study, and the kidneys were extracted for observation via light microscopy examination. Results All HFD rats developed obesity, hyperglycemia, hypertriglyceridemia, increased levels of CRP and UA (when compared to the control group), and oxidative stress with high levels of malondialdehyde and low levels of reduced glutathione. The kidneys of the HFD group revealed a significant increase in kidney weight in the absence of evidence of renal dysfunction and electrolyte disturbances. Under light microscopy, the kidneys of the HFD group revealed amyloid deposits in Kimmelstiel-Wilson-like nodules and the walls of the large caliber blood vessels, early-stage atherosclerosis with visible ruptures and scarring, hydropic change (vacuolar degeneration) in the epithelial cells covering the proximal tubules, and increased eosinophilia in the distant tubules when compared to the control group. Conclusion Under the conditions of a fructose-induced metabolic syndrome, high serum UA and CRP correlate to the development of early renal disorders without a clinical manifestation of renal dysfunction. These phenomena are of particular importance for assessing the risk of developing future CKD.

Aldosterone Contributes to Sympathoexcitation in Renovascular Hypertension.

PubMed

Lincevicius, Gisele S; Shimoura, Caroline G; Nishi, Erika E; Perry, Juliana C; Casarini, Dulce E; Gomes, Guiomar N; Bergamaschi, Cássia T; Campos, Ruy R

2015-09-01

Although angiotensin II (Ang II) is essential to the development of renovascular hypertension, aldosterone plays a role as well. Recent studies have demonstrated a cross-talk between Ang II type 1 and mineralocorticoid receptors in the brain and kidneys. However, the role of aldosterone in the autonomic and renal dysfunction of renovascular hypertension is not well understood. The current study evaluated whether aldosterone contributes to cardiovascular and renal dysfunction in the 2 kidney-1 clip (2K1C) model. Mean arterial pressure (MAP) and baroreceptor reflex for control of the heart rate were evaluated in 2K1C treated or not treated with spironolactone (200mg/kg/day, 7 days). Tonic and reflex control of renal sympathetic nerve activity (rSNA) were assessed in urethane-anaesthetized rats. Plasma renin activity (PRA), kidney renin protein expression, renal injury, and central AT1 receptor protein expression were assessed. Spiro reduced MAP (198±4 vs. 170±9mm Hg; P < 0.05), normalized rSNA (147±9 vs. 96±10 pps; P < 0.05), and increased renal baroreceptor reflex sensitivity in the 2K1C rats. Spiro reduced α-smooth muscle actin expression in the nonclipped kidney in the 2K1C group (5±0.6 vs. 1.1±0.2%; P < 0.05). There was no change in PRA; however, a decrease in renin protein expression in the nonclipped kidney was found in the 2K1C treated group (217±30 vs. 160±19%; P < 0.05). Spiro treatment decreased AT1 receptor in the central nervous system (CNS) only in 2K1C rats (138±10 vs. 84±12%; P < 0.05). Aldosterone contributes to autonomic dysfunction and intrarenal injury in 2K1C, these effects are mediated by the CNS. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[The role of percutaneous renal biopsy in kidney transplant].

PubMed

Manfro, R C; Lee, J Y; Lewgoy, J; Edelweiss, M I; Gonçalves, L F; Prompt, C A

1994-01-01

Percutaneous renal biopsy (PRB) is an useful tool for diagnostic and therapeutic orientation in renal transplantation. PURPOSE--To evaluate the current role of PRB in post-transplant acute renal dysfunction (ARD) of renal allografts. METHODS--Sixty-five renal transplant patients were submitted to 95 valid renal biopsies with no major complications. RESULTS--There was disagreement between the clinical and the pathological diagnosis in 28 occasions (29.5%). In 36 cases (37.9%) the results of the pathological examination led to a modification in patient's management. These modifications were most commonly the avoidance or witholding of a steroid pulse (8 cases); nephrectomy of the renal allograft (8 cases); witholding or decrease of cyclosporine dosage (6 cases); giving a steroid pulse (5 cases) and giving antibiotics to treat acute pyelonephritis in 4 cases. The use of kidneys from cadaveric donors was significantly associated with an increased number of biopsies (p < 0.05). CONCLUSION--These results demonstrate that even though several less invasive procedures are currently employed, renal biopsy is still an indispensable method to the management of ARD in renal transplant patients.

Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Gualano, Bruno; Ugrinowitsch, Carlos; Novaes, Rafael Batista; Artioli, Guilherme Gianini; Shimizu, Maria Heloisa; Seguro, Antonio Carlos; Harris, Roger Charles; Lancha, Antonio Herbert

2008-05-01

Creatine (CR) supplementation is commonly used by athletes. However, its effects on renal function remain controversial. The aim of this study was to evaluate the effects of creatine supplementation on renal function in healthy sedentary males (18-35 years old) submitted to exercise training. A randomized, double-blind, placebo-controlled trial was performed. Subjects (n = 18) were randomly allocated to receive treatment with either creatine (CR) ( approximately 10 g day(-1) over 3 months) or placebo (PL) (dextrose). All subjects undertook moderate intensity aerobic training, in three 40-min sessions per week, during 3 months. Serum creatinine, serum and urinary sodium and potassium were determined at baseline and at the end of the study. Cystatin C was assessed prior to training (PRE), after 4 (POST 4) and 12 weeks (POST 12). Cystatin C levels (mg L(-1)) (PRE CR: 0.82 +/- 0.09; PL: 0.88 +/- 0.07 vs. POST 12 CR: 0.71 +/- 0.06; PL: 0.75 +/- 0.09, P = 0.0001) were decreased over time, suggesting an increase in glomerular filtration rate. Serum creatinine decreased with training in PL but was unchanged with training in CR. No significant differences were observed within or between groups in other parameters investigated. The decrease in cystatin C indicates that high-dose creatine supplementation over 3 months does not provoke any renal dysfunction in healthy males undergoing aerobic training. In addition, the results suggest that moderate aerobic training per se may improve renal function.

Original Research: Potential of urinary nephrin as a biomarker reflecting podocyte dysfunction in various kidney disease models.

PubMed

Wada, Yusuke; Abe, Masaki; Moritani, Hiroshi; Mitori, Hikaru; Kondo, Mitsuhiro; Tanaka-Amino, Keiko; Eguchi, Megumi; Imasato, Akira; Inoki, Yutaka; Kajiyama, Hiroshi; Mimura, Toshihide; Tomura, Yuichi

2016-10-01

Urinary nephrin is a potential non-invasive biomarker of disease. To date, however, most studies of urinary nephrin have been conducted in animal models of diabetic nephropathy, and correlations between urinary nephrin-to-creatinine ratio and other parameters have yet to be evaluated in animal models or patients of kidney disease with podocyte dysfunction. We hypothesized that urinary nephrin-to-creatinine ratio can be up-regulated and is negatively correlated with renal nephrin mRNA levels in animal models of kidney disease, and that increased urinary nephrin-to-creatinine ratio levels are attenuated following administration of glucocorticoids. In the present study, renal nephrin mRNA, urinary nephrin-to-creatinine ratio, urinary protein-to-creatinine ratio, and creatinine clearance ratio were measured in animal models of adriamycin nephropathy, puromycin aminonucleoside nephropathy, anti-glomerular basement membrane glomerulonephritis, and 5/6 nephrectomy. The effects of prednisolone on urinary nephrin-to-creatinine ratio and other parameters in puromycin aminonucleoside (single injection) nephropathy rats were also investigated. In all models tested, urinary nephrin-to-creatinine ratio and urinary protein-to-creatinine ratio increased, while renal nephrin mRNA and creatinine clearance ratio decreased. Urinary nephrin-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA in almost all models, as well as a significant positive correlation with urinary protein-to-creatinine ratio and a significant negative correlation with creatinine clearance ratio. Urinary protein-to-creatinine ratio exhibited a significant negative correlation with renal nephrin mRNA. Following the administration of prednisolone to puromycin aminonucleoside (single injection) nephropathy rats, urinary nephrin-to-creatinine ratio was significantly suppressed and exhibited a significant positive correlation with urinary protein-to-creatinine ratio. In addition, the decrease in number of glomerular Wilms tumor antigen-1-positive cells was attenuated, and urinary nephrin-to-creatinine ratio exhibited a significant negative correlation in these cells. In conclusion, these results suggest that urinary nephrin-to-creatinine ratio level is a useful and reliable biomarker for predicting the amelioration of podocyte dysfunction by candidate drugs in various kidney disease models with podocyte dysfunction. This suggestion will also be validated in a clinical setting in future studies. © 2016 by the Society for Experimental Biology and Medicine.

Dengue fever in renal transplant patients: a systematic review of literature.

PubMed

Weerakkody, Ranga Migara; Patrick, Jean Ansbel; Sheriff, Mohammed Hussain Rezvi

2017-01-13

Dengue fever in renal transplanted patients has not been studied well, and we review all the literature about episodes dengue fever in renal transplant patients. The aim was to describe clinico-pathological characteristics, immunosuppressive protocols, need renal outcome and mortality. PubMed, LILACS, Google Scholar and Research Gate were searched for "Dengue" and "Renal/Kidney Transplantation" with no date limits. Hits were analyzed by two researchers separately. Fever, myalgia, arthralgia and headache was significantly lower than normal population, while pleural effusions and ascites were observed more. Incidence of severe dengue is significantly higher among transplant patients in this review, as well as they had a significantly higher mortality (8.9% vs 3.7%, p = 0.031). Age, period after transplantation and immunosuppressive profile had no effect on disease severity, mortality or graft out come. Presence of new bleeding complications and ascites was associated with more severe disease (p < 0.001 and p = 0.005), death (p = 0.033) or graft loss (p = 0.035). Use of tacrolimus was associated with new bleeding complications (p = 0.027), and with ascites (p = 0.021), but not with thrombocytopenia. 25% of patients with primary disease fail to mount an IgG response by 15 weeks of the illness. 58.9% had graft dysfunction during illness. Postoperative transplanted patients were at risk of severe disease and unfavorable outcome. The physical and laboratory findings in dengue fever in renal transplanted patients differ from the general population. Some degree of graft dysfunction is common during the illness, but only a minority develops graft failure.

Optimal conditions of LDR to protect the kidney from diabetes

PubMed Central

Cheng, Jie; Li, Fengsheng; Cui, Jiuwei; Guo, Weiying; Li, Cai; Li, Wei; Wang, Guixia; Xing, Xiao; Gao, Ying; Ge, Yuanyuan; Wang, Guanjun; Cai, Lu

2014-01-01

Aims We reported the attenuation of diabetes-induced renal dysfunction by exposure to multiple low-dose radiation (LDR) at 25 mGy every other day via suppressing renal oxidative damage. We here explored the optimal conditions of LDR to protect the kidney from diabetes. Main methods Type 1 diabetic mice were induced with multiple injections of low-dose streptozotocin in male C57BL/6J mice. Diabetic mice received whole body X-irradiation at dose of 12.5, 25 or 50 mGy every other day for either 4 or 8 weeks. Age-matched normal mice were similarly irradiated at the dose of 25 mGy for 4 or 8 weeks. The renal function and histopathological changes were examined at the 4th and 8th week of the study. Key findings Diabetes induced renal dysfunction, shown by the decreased creatinine and increased microalbumin in urinary. Renal oxidative damage, detected by protein nitration and lipid oxidation, and remodeling, reflected by increased expression of connective tissue growth factor, collagen IV and fibronectin, were significantly increased in diabetic mice. All these renal pathological and function changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens, among which, however, exposure to LDR at 12.5 mGy for 8 weeks provided the best preventive effect on the kidney of diabetic mice. Significance Our results suggest that whole-body LDR at 12.5 mGy every other day for 8 weeks is the optimal condition of LDR to protect the kidney from diabetes. PMID:24631139

Novel Renal Biomarkers to Assess Cardiorenal Syndrome

PubMed Central

Brisco, Meredith A.; Testani, Jeffrey M.

2014-01-01

Renal dysfunction (RD) in heart failure portends adverse outcomes and often limits aggressive medical and decongestive therapies. Despite the high prevalence in this population, not all forms of RD are prognostically or mechanistically equivalent: RD can result from irreversible nephron loss secondary to diabetic or hypertensive kidney disease or it can develop secondary to the HF itself, i.e. the cardiorenal syndrome. Furthermore, filtration is only one aspect of renal performance such that significant renal impairment secondary to cardiorenal syndrome can exist despite a normal glomerular filtration rate. Renal biomarkers have the potential to inform some of the intricacies involved in accurately assessing cardiorenal interactions. This article discusses novel biomarkers for cardiorenal syndrome and their utility in prognosis, diagnosis, and targeted treatment of heart failure-induced RD. PMID:25239434

[Cardio-renal axis: pathophysiological evidences and clinical implications].

PubMed

Di Lullo, Luca; Ronco, Claudio

2017-03-01

According to the recent definition proposed by the Consensus conference on Acute Dialysis Quality Initiative Group, the term cardio-renal syndrome CRS has been used to define different clinical conditions in which heart and kidney dysfunction overlap. Type 1 CRS acute cardio - renal syndrome is characterized by acute worsening of cardiac function leading to AKI in the setting of active cardiac disease such as ADHF, while type - 2 CRS occurs in a setting of chronic heart disease. Type 3 CRS is closely link to acute kidney injury, while type 4 represent cardiovascular involvement in chronic kidney disese patients. Type 5 CRS represent cardiac and renal involvement in several diseases such as sepsis, hepato - renal syndrome and immune - mediated diseases. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

Assessment of endothelial dysfunction: the role of symmetrical dimethylarginine and proinflammatory markers in chronic kidney disease and renal transplant recipients.

PubMed

Memon, Lidija; Spasojevic-Kalimanovska, Vesna; Bogavac-Stanojevic, Natasa; Kotur-Stevuljevic, Jelena; Simic-Ogrizovic, Sanja; Giga, Vojislav; Dopsaj, Violeta; Jelic-Ivanovic, Zorana; Spasic, Slavica

2013-01-01

The study was designed to evaluate associations between symmetric dimethylarginine (SDMA), inflammation, and superoxide anion (O2∙-) with endothelial function and to determine their potential for screening of endothelial dysfunction in patients with chronic kidney disease (CKD) and renal transplant (RT) recipients. We included 64 CKD and 52 RT patients. Patients were stratified according to brachial artery flow-mediated dilation (FMD). Logistic regression analysis showed that high SDMA and high sensitive C-reactive protein (hs-CRP) were associated with impaired FMD in CKD and RT patients, after adjustment for glomerular filtration rate. The ability of inflammation, SDMA, and O2∙- to detect impaired FMD was investigated by receiving operative characteristic analysis. Hs-CRP (area under the curves (AUC) = 0.754, P < 0.001), IL-6 (AUC = 0.699, P = 0.002), and SDMA (AUC = 0.689, P = 0.007) had the highest ability to detect impaired FMD. SDMA in combination with inflammatory parameters and/or O2∙- had better screening performance than SDMA alone. Our results indicate a strong predictable association between hs-CRP, SDMA, and endothelial dysfunction in CKD patients and RT recipients. The individual marker that showed the strongest discriminative ability for endothelial dysfunction is hs-CRP, but its usefulness as a discriminatory marker for efficient diagnosis of endothelial dysfunction should be examined in prospective studies.

Albumin reduces paracentesis-induced circulatory dysfunction and reduces death and renal impairment among patients with cirrhosis and infection: a systematic review and meta-analysis.

PubMed

Kwok, Chun Shing; Krupa, Lukasz; Mahtani, Ash; Kaye, Duncan; Rushbrook, Simon M; Phillips, Martin G; Gelson, William

2013-01-01

Studies have suggested that albumin has a value in cirrhotic patients undergoing paracentesis but its value in infection and sepsis is less clear. We planned to perform a meta-analysis of the risk of adverse outcomes in cirrhotic patients with and without albumin use. We searched MEDLINE and EMBASE in January 2013 for randomized studies of cirrhotic patients that reported the risk of adverse events and mortality with albumin and no albumin exposure. We performed random effects meta-analysis and assessed heterogeneity using the I² statistic. Our review included 16 studies covering 1,518 patients. The use of albumin in paracentesis was associated with significantly reduced risk of paracentesis-induced circulatory dysfunction (OR 0.26 95%, CI 0.08-0.93) and there was a nonsignificant difference in death, encephalopathy, hyponatraemia, readmission, and renal impairment. Compared to the other volume expanders, albumin use showed no difference in clinical outcomes. In cirrhotic patients with any infection, there was a significant reduction in mortality (OR 0.46 95%, CI 0.25-0.86) and renal impairment (OR 0.34 95%, CI 0.15-0.75) when albumin was used. The use of albumin in cirrhotic patients is valuable in patients with any infection and it reduces the risk of circulatory dysfunction among patients undergoing paracentesis.

Albumin Reduces Paracentesis-Induced Circulatory Dysfunction and Reduces Death and Renal Impairment among Patients with Cirrhosis and Infection: A Systematic Review and Meta-Analysis

PubMed Central

Krupa, Lukasz; Mahtani, Ash; Kaye, Duncan; Rushbrook, Simon M.; Phillips, Martin G.

2013-01-01

Background. Studies have suggested that albumin has a value in cirrhotic patients undergoing paracentesis but its value in infection and sepsis is less clear. We planned to perform a meta-analysis of the risk of adverse outcomes in cirrhotic patients with and without albumin use. Methods. We searched MEDLINE and EMBASE in January 2013 for randomized studies of cirrhotic patients that reported the risk of adverse events and mortality with albumin and no albumin exposure. We performed random effects meta-analysis and assessed heterogeneity using the I2 statistic. Results. Our review included 16 studies covering 1,518 patients. The use of albumin in paracentesis was associated with significantly reduced risk of paracentesis-induced circulatory dysfunction (OR 0.26 95%, CI 0.08–0.93) and there was a nonsignificant difference in death, encephalopathy, hyponatraemia, readmission, and renal impairment. Compared to the other volume expanders, albumin use showed no difference in clinical outcomes. In cirrhotic patients with any infection, there was a significant reduction in mortality (OR 0.46 95%, CI 0.25–0.86) and renal impairment (OR 0.34 95%, CI 0.15–0.75) when albumin was used. Conclusion. The use of albumin in cirrhotic patients is valuable in patients with any infection and it reduces the risk of circulatory dysfunction among patients undergoing paracentesis. PMID:24222902

Bcl-2 protects tubular epithelial cells from ischemia reperfusion injury by inhibiting apoptosis.

PubMed

Suzuki, Chigure; Isaka, Yoshitaka; Shimizu, Shigeomi; Tsujimoto, Yoshihide; Takabatake, Yoshitsugu; Ito, Takahito; Takahara, Shiro; Imai, Enyu

2008-01-01

Ischemia followed by reperfusion leads to severe organ injury and dysfunction. Inflammation is considered to be the most important cause of graft dysfunction in kidney transplantation subjected to ischemia. The mechanism that triggers inflammation and renal injury after ischemia remains to be elucidated; however, cellular stress may induce apoptosis during the first hours and days after transplantation, which might play a crucial role in early graft dysfunction. Bcl-2 is known to inhibit apoptosis induced by the etiological factors promoting ischemia and reperfusion injury. Accordingly, we hypothesized that an augmentation of the antiapoptotic factor Bcl-2 may thus protect tubular epithelial cells by inhibiting apoptosis, thereby ameliorating the subsequent tubulointerstitial injury. We examined the effects of Bcl-2 overexpression on ischemia-reperfusion (I/R) injury using Bcl-2 transgenic mice (Bcl-2 TG) and their wild-type littermates (WT). To investigate the effects of I/R injury, the left renal artery and vein were clamped for 45 min, followed by reperfusion for 0-96 h. Bcl-2 TG exhibited decreased active caspase protein in the tubular cells, which led to a reduction in TUNEL-positive apoptotic cells. Consequently, interstitial fibrosis and phenotypic changes were ameliorated in Bcl-2 TG. In conclusion, Bcl-2 augmentation protected renal tubular epithelial cells from I/R, and subsequent interstitial injury by inhibiting tubular apoptosis.

Environmental exposure to cadmium at a level insufficient to induce renal tubular dysfunction does not affect bone density among female Japanese farmers.

PubMed

Horiguchi, Hyogo; Oguma, Etsuko; Sasaki, Satoshi; Miyamoto, Kayoko; Ikeda, Yoko; Machida, Munehito; Kayama, Fujio

2005-01-01

Some recent research suggests that environmental exposure to cadmium, even at low levels, may increase the risk of osteoporosis, and that the bone demineralization is not just a secondary effect of renal dysfunction induced by high doses of cadmium as previously reported. To investigate the effect of exposure to cadmium at a level insufficient to induce kidney damage on bone mineral density (BMD) and bone metabolism, we conducted health examinations on 1380 female farmers from five districts in Japan who consumed rice contaminated by low-to-moderate levels of cadmium. We collected peripheral blood and urine samples and medical and nutritional information, and measured forearm BMD. Analysis of the data for subjects grouped by urinary cadmium level and age-related menstrual status suggested that cadmium accelerates both the increase of urinary calcium excretion around the time of menopause and the subsequent decrease in bone density after menopause. However, multivariate analyses showed no significant contribution of cadmium to bone density or urinary calcium excretion, indicating that the results mentioned above were confounded by other factors. These results indicate that environmental exposure to cadmium at levels insufficient to induce renal dysfunction does not increase the risk of osteoporosis, strongly supporting the established explanation for bone injury induced by cadmium as a secondary effect.

Protective effect of Petroselinum crispum extract in abortion using prostadin-induced renal dysfunction in female rats

PubMed Central

Rezazad, Maryam; Farokhi, Farah

2014-01-01

Objective: Present study investigated the effects of parsley extract on pregnant rat kidneys which have undergone clinical abortion using prostaglandins. The renal protective effect of parsley extract was evaluated in pregnant rats which had an abortion. Parsley was used due to its antioxidant properties. Materials and Methods: Fifty-four female rats were divided in 9 groups of 6: control pregnant, two pregnant groups which received parsley extract and prostadin, two non-pregnant groups treated with parsley extract and prostadin, a group administered with both treatments, and three groups which received parsley extract in pre-implantation, implantation, and post-implantation periods of embryos. Ethanolic extract (5 mg/kg) was given daily to animals for 18 days of pregnancy period. Parameters such as malondialdehyde (MDA), total antioxidant statues (TAS), creatinine, and urea were measured using biochemical assays. Histopathologic studies were also done with Hematoxylin-Eosin staining method. Results: After 18 days of treatment, significant differences were observed in serum creatinine, urea, and MDA and TAS levels. Kidney cross-sections showed edema in prostadin-treated rats while improvements in parsley + prostadin -treated rats were observed. Conclusion: These results suggested that ethanolic extract of Petroselinum crispum reduced the dysfunction in rats kidney caused by prostadin-induced abortion and could have beneficial effect in reducing the progression of prostaglandin-induced edema. PMID:25386393

Nationwide survey of Arima syndrome: revised diagnostic criteria from epidemiological analysis.

PubMed

Itoh, Masayuki; Iwasaki, Yuji; Ohno, Kohsaku; Inoue, Takehiko; Hayashi, Masaharu; Ito, Shuichi; Matsuzaka, Tetsuo; Ide, Shuhei; Arima, Masataka

2014-05-01

We have never known any epidemiological study of Arima syndrome since it was first described in 1971. To investigate the number of Arima syndrome patients and clarify the clinical differences between Arima syndrome and Joubert syndrome, we performed the first nationwide survey of Arima syndrome, and herein report its results. Furthermore, we revised the diagnostic criteria for Arima syndrome. As a primary survey, we sent out self-administered questionnaires to most of the Japanese hospitals with a pediatric clinic, and facilities for persons with severe motor and intellectual disabilities, inquiring as to the number of patients having symptoms of Arima syndrome, including severe psychomotor delay, agenesis or hypoplasia of cerebellar vermis, renal dysfunction, visual dysfunction and with or without ptosis-like appearance. Next, as the second survey, we sent out detailed clinical questionnaires to the institutes having patients with two or more typical symptoms. The response rate of the primary survey was 72.7% of hospitals with pediatric clinic, 63.5% of national hospitals and 66.7% of municipal and private facilities. The number of patients with 5 typical symptoms was 13 and that with 2-4 symptoms was 32. The response rate of the secondary survey was 52% (23 patients). After reviewing clinical features of 23 patients, we identified 7 Arima syndrome patients and 16 Joubert syndrome patients. Progressive renal dysfunction was noticed in all Arima syndrome patients, but in 33% of those with Joubert syndrome. It is sometimes difficult to distinguish Arima syndrome from Joubert syndrome. Some clinicians described a patient with Joubert syndrome and its complications of visual dysfunction and renal dysfunction, whose current diagnosis was Arima syndrome. Thus, the diagnosis of the two syndromes may be confused. Here, we revised the diagnostic criteria for Arima syndrome. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Dysfunctions of the Iga system: a common link between intestinal and renal diseases

PubMed Central

Papista, Christina; Berthelot, Laureline; Monteiro, Renato C

2011-01-01

Immunoglobulin A (Iga)-isotype antibodies play an important role in immunity owing to their structure, glycosylation, localization and receptor interactions. Dysfunctions in this system can lead to multiple types of pathology. This review describes the characteristics of Iga and discusses the involvement of abnormalities in the Iga system on the development of celiac disease and Iga nephropathy. PMID:21278767

Cardiovascular-renal and metabolic characterization of a rat model of polycystic ovary syndrome.

PubMed

Yanes, Licy L; Romero, Damian G; Moulana, Mohaddetheh; Lima, Roberta; Davis, Deborah D; Zhang, Huimin; Lockhart, Rachel; Racusen, Lorraine C; Reckelhoff, Jane F

2011-04-01

Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is also associated with increased risk of cardiovascular disease when PCOS first occurs and later in life. Hypertension, a common finding in women with PCOS, is a leading risk factor for cardiovascular disease. The mechanisms responsible for hypertension in women with PCOS have not been elucidated. This study characterized the cardiovascular-renal consequences of hyperandrogenemia in a female rat model. Female Sprague-Dawley rats (aged 4-6 weeks) were implanted with dihydrotestosterone or placebo pellets lasting 90 days. After 10 to 12 weeks, blood pressure (by radiotelemetry), renal function (glomerular filtration rate, morphology, protein, and albumin excretion), metabolic parameters (plasma insulin, glucose, leptin, cholesterol, and oral glucose tolerance test), inflammation (plasma tumor necrosis factor-α), oxidative stress (mRNA expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, p22(phox), p47(phox), gp91(phox), and NOX4), nitrate/nitrite excretion and mRNA expression of components of the renin-angiotensin system (angiotensinogen, angiotensin-I-converting enzyme [ACE], and AT1 receptor) were determined. Plasma dihydrotestosterone increased 3-fold in hyperandrogenemic female (HAF) rats, whereas plasma estradiol levels did not differ compared with control females. HAF rats exhibited estrus cycle dysfunction. They also had increased food intake and body weight, increased visceral fat, glomerular filtration rate, renal injury, insulin resistance and metabolic dysfunction, oxidative stress, and increased expression of angiotensinogen and ACE and reduced AT1 receptor expression. The HAF rat is a unique model that exhibits many of the characteristics of PCOS in women and is a useful model to study the mechanisms responsible for PCOS-mediated hypertension. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma.

PubMed

Catino, Anna B; Hubbard, Rebecca A; Chirinos, Julio A; Townsend, Ray; Keefe, Stephen; Haas, Naomi B; Puzanov, Igor; Fang, James C; Agarwal, Neeraj; Hyman, David; Smith, Amanda M; Gordon, Mary; Plappert, Theodore; Englefield, Virginia; Narayan, Vivek; Ewer, Steven; ElAmm, Chantal; Lenihan, Daniel; Ky, Bonnie

2018-03-01

Sunitinib, used widely in metastatic renal cell carcinoma, can result in hypertension, left ventricular dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood. In a multicenter prospective study of 84 metastatic renal cell carcinoma patients, echocardiography, arterial tonometry, and BNP (B-type natriuretic peptide) measures were performed at baseline and at 3.5, 15, and 33 weeks after sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and left ventricular ejection fraction, longitudinal strain, diastolic function (E/e'), and BNP. After 3.5 weeks of sunitinib, mean systolic blood pressure increased by 9.5 mm Hg (95% confidence interval, 2.0-17.1; P =0.02) and diastolic blood pressure by 7.2 mm Hg (95% confidence interval, 4.3-10.0; P <0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid-femoral pulse wave velocity) and resistive load (total peripheral resistance and arterial elastance; all P <0.05) and changes in pulsatile load (total arterial compliance and wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (left ventricular ejection fraction and longitudinal strain). However, baseline total peripheral resistance, arterial elastance, and aortic impedance were associated with worsening diastolic function and filling pressures over time. In patients with metastatic renal cell carcinoma, sunitinib resulted in early, significant increases in blood pressure, arterial stiffness, and resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic but not systolic function. © 2018 American Heart Association, Inc.

Historical perspectives on cadmium toxicology

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

Nordberg, Gunnar F.

2009-08-01

The first health effects of cadmium (Cd) were reported already in 1858. Respiratory and gastrointestinal symptoms occurred among persons using Cd-containing polishing agent. The first experimental toxicological studies are from 1919. Bone effects and proteinuria in humans were reported in the 1940's. After World War II, a bone disease with fractures and severe pain, the itai-itai disease, a form of Cd-induced renal osteomalacia, was identified in Japan. Subsequently, the toxicokinetics and toxicodynamics of Cd were described including its binding to the protein metallothionein. International warnings of health risks from Cd-pollution were issued in the 1970's. Reproductive and carcinogenic effects weremore » studied at an early stage, but a quantitative assessment of these effects in humans is still subject to considerable uncertainty. The World Health Organization in its International Program on Chemical Safety, WHO/IPCS (1992) (Cadmium. Environmental Health Criteria Document 134, IPCS. WHO, Geneva, 1-280.) identified renal dysfunction as the critical effect and a crude quantitative evaluation was presented. In the 1990's and 2000 several epidemiological studies have reported adverse health effects, sometimes at low environmental exposures to Cd, in population groups in Japan, China, Europe and USA (reviewed in other contributions to the present volume). The early identification of an important role of metallothionein in cadmium toxicology formed the basis for recent studies using biomarkers of susceptibility to development of Cd-related renal dysfunction such as gene expression of metallothionein in peripheral lymphocytes and autoantibodies against metallothionein in blood plasma. Findings in these studies indicate that very low exposure levels to cadmium may give rise to renal dysfunction among sensitive subgroups of human populations such as persons with diabetes.« less

The basic data for residents aged 16 years or older who received a comprehensive health check examinations in 2011-2012 as a part of the Fukushima Health Management Survey after the great East Japan earthquake.

PubMed

Kawasaki, Yukihiko; Hosoya, Mitsuaki; Yasumura, Seiji; Ohira, Tetsuya; Satoh, Hiroaki; Suzuki, Hitoshi; Sakai, Akira; Ohtsuru, Akira; Takahashi, Atsushi; Ozasa, Kotaro; Kobashi, Gen; Kamiya, Kenji; Yamashita, Shunichi; Abe, Masafumi

2014-01-01

To assist in the long-term health management of residents and evaluate health impacts after the Tokyo Electric Power Company's Fukushima Daiichi Nuclear Power Plant accident in Fukushima Prefecture, the Fukushima prefectural government decided to conduct the Fukushima Health Management Survey. This report describes the results for residents aged 16 years or older who received the health check examinations and evaluates the data obtained from 2011 and 2012. The target group consisted of residents aged 16 years or older who had lived in the evacuation zone. The health check examinations were performed on receipt of an application for a health check examination from any of the residents. The examinations, including measurements of height, weight, abdominal circumference/body mass index (BMI), blood pressure, biochemical laboratory findings, and peripheral blood findings, were performed as required. 1) A total of 56,399 (30.9%) and 47,009 (25.4%) residents aged 16 years or older received health checks in 2011 and 2012, respectively. 2) In both years, a number of male and female residents in the 16-39 year age group were found to suffer obesity, hyperlipidemia, hyperuricemia, or liver dysfunction, and the prevalence of obesity and hyperlipidemia among residents increased with age. Furthermore, the proportion of residents with hypertension, glucose metabolic abnormalities or renal dysfunction was higher in those aged 40 years or older. 3) The frequencies of obesity, hypertension and hyperlipidemia among residents in 2012 were lower than those in 2011. However, the prevalence of liver dysfunction, hyperuricemia, glucose metabolic abnormalities and renal dysfunction among residents was higher in 2012 than in 2011. These results suggested the number of residents who had lived in the evacuation zone with obesity, hyperlipidemia, hyperuricemia, liver dysfunction, hypertension, glucose metabolic abnormalities, or renal dysfunction increased with age in all age groups. Therefore, we think that it is necessary to continue with health check examinations for these residents in order to ameliorate lifestyle-related disease.

The macro- and microcirculation of the kidney.

PubMed

Guerci, Philippe; Ergin, Bulent; Ince, Can

2017-09-01

Acute kidney injury (AKI) remains one of the main causes of morbidity and mortality in the intensive care medicine today. Its pathophysiology and progress to chronic kidney disease is still under investigation. In addition, the lack of techniques to adequately monitor renal function and microcirculation at the bedside makes its therapeutic resolution challenging. In this article, we review current concepts related to renal hemodynamics compromise as being the event underlying AKI. In doing so, we discuss the physiology of the renal circulation and the effects of alterations in systemic hemodynamics that lead to renal injury specifically in the context of reperfusion injury and sepsis. The ultimate key culprit of AKI leading to failure is the dysfunction of the renal microcirculation. The cellular and subcellular components of the renal microcirculation are discussed and how their injury contributes to AKI is described. Copyright © 2017. Published by Elsevier Ltd.

[Renal dysfunction in patients with myocardial infarction concurrent with type 2 diabetes mellitus].

PubMed

Evseeva, M V; Karetnikova, V N; Barbarash, O L

2015-01-01

Carbohydrate metabolic disturbances are an independent risk factor for not only the development, but also poor course of cardiovascular diseases, particularly those concurrent with renal dysfunction (RD). This factor acquires particular relevance due to the fact that the incidence of type 2 diabetes mellitus significantly continues to rise worldwide. The review considers the main mechanisms and common components of the pathogenesis of RD, as well as the constituents forming its basis in the presence of carbohydrate metabolic disturbances. Moreover, it highlights the timely detection of RD, a search for new biomarkers of prognostic value for cardiovascular events, and the early diagnosis of RD. The review unveils the present view of optimal diagnostic and management tactics for patients with myocardial infarction concurrent with background diseases.

The Role of Platelets and ε-Aminocaproic Acid in Arthrogryposis, Renal Dysfunction, and Cholestasis (ARC) Syndrome Associated Hemorrhage.

PubMed

Weyand, Angela C; Lombel, Rebecca M; Pipe, Steven W; Shavit, Jordan A

2016-03-01

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is a rare disorder associated with platelet abnormalities resembling gray platelet syndrome. Affected patients have normal platelet numbers but abnormal morphology and function. Bleeding symptomatology ranges from postprocedural to spontaneous life-threatening hemorrhage. We report a patient with ARC syndrome and compound heterozygous mutations in VPS33B (vacuolar protein sorting 33B) who presented with significant bleeding requiring numerous admissions and transfusions. She was treated with prophylactic platelet transfusions and ε-aminocaproic acid. This was well-tolerated and significantly decreased transfusion requirements and admissions for bleeding. Our experience provides support for consideration of prophylactic measures in these patients as well as the possibility of using prophylaxis in related disorders. © 2015 Wiley Periodicals, Inc.

Protein kinase C-ε activation induces mitochondrial dysfunction and fragmentation in renal proximal tubules

PubMed Central

Bakajsova, Diana; Samarel, Allen M.

2011-01-01

PKC-ε activation mediates protection from ischemia-reperfusion injury in the myocardium. Mitochondria are a subcellular target of these protective mechanisms of PKC-ε. Previously, we have shown that PKC-ε activation is involved in mitochondrial dysfunction in oxidant-injured renal proximal tubular cells (RPTC; Nowak G, Bakajsova D, Clifton GL Am J Physiol Renal Physiol 286: F307–F316, 2004). The goal of this study was to examine the role of PKC-ε activation in mitochondrial dysfunction and to identify mitochondrial targets of PKC-ε in RPTC. The constitutively active and inactive mutants of PKC-ε were overexpressed in primary cultures of RPTC using the adenoviral technique. Increases in active PKC-ε levels were accompanied by PKC-ε translocation to mitochondria. Sustained PKC-ε activation resulted in decreases in state 3 respiration, electron transport rate, ATP production, ATP content, and activities of complexes I and IV and F0F1-ATPase. Furthermore, PKC-ε activation increased mitochondrial membrane potential and oxidant production and induced mitochondrial fragmentation and RPTC death. Accumulation of the dynamin-related protein in mitochondria preceded mitochondrial fragmentation. Antioxidants blocked PKC-ε-induced increases in the oxidant production but did not prevent mitochondrial fragmentation and cell death. The inactive PKC-ε mutant had no effect on mitochondrial functions, morphology, oxidant production, and RPTC viability. We conclude that active PKC-ε targets complexes I and IV and F0F1-ATPase in RPTC. PKC-ε activation mediates mitochondrial dysfunction, hyperpolarization, and fragmentation. It also induces oxidant generation and cell death, but oxidative stress is not the mechanism of RPTC death. These results show that in contrast to protective effects of PKC-ε activation in cardiomyocytes, sustained PKC-ε activation is detrimental to mitochondrial function and viability in RPTC. PMID:21289057

Impaired Lysosomal Function Underlies Monoclonal Light Chain–Associated Renal Fanconi Syndrome

PubMed Central

Luciani, Alessandro; Sirac, Christophe; Terryn, Sara; Javaugue, Vincent; Prange, Jenny Ann; Bender, Sébastien; Bonaud, Amélie; Cogné, Michel; Aucouturier, Pierre; Ronco, Pierre

2016-01-01

Monoclonal gammopathies are frequently complicated by kidney lesions that increase the disease morbidity and mortality. In particular, abnormal Ig free light chains (LCs) may accumulate within epithelial cells, causing proximal tubule (PT) dysfunction and renal Fanconi syndrome (RFS). To investigate the mechanisms linking LC accumulation and PT dysfunction, we used transgenic mice overexpressing human control or RFS-associated κLCs (RFS-κLCs) and primary cultures of mouse PT cells exposed to low doses of corresponding human κLCs (25 μg/ml). Before the onset of renal failure, mice overexpressing RFS-κLCs showed PT dysfunction related to loss of apical transporters and receptors and increased PT cell proliferation rates associated with lysosomal accumulation of κLCs. Exposure of PT cells to RFS-κLCs resulted in κLC accumulation within enlarged and dysfunctional lysosomes, alteration of cellular dynamics, defective proteolysis and hydrolase maturation, and impaired lysosomal acidification. These changes were specific to the RFS-κLC variable (V) sequence, because they did not occur with control LCs or the same RFS-κLC carrying a single substitution (Ala30→Ser) in the V domain. The lysosomal alterations induced by RFS-κLCs were reflected in increased cell proliferation, decreased apical expression of endocytic receptors, and defective endocytosis. These results reveal that specific κLCs accumulate within lysosomes, altering lysosome dynamics and proteolytic function through defective acidification, thereby causing dedifferentiation and loss of reabsorptive capacity of PT cells. The characterization of these early events, which are similar to those encountered in congenital lysosomal disorders, provides a basis for the reported differential LC toxicity and new perspectives on LC-induced RFS. PMID:26614382

Albumin Overload and PINK1/Parkin Signaling-Related Mitophagy in Renal Tubular Epithelial Cells.

PubMed

Tan, Jin; Xie, Qi; Song, Shuling; Miao, Yuyang; Zhang, Qiang

2018-03-01

BACKGROUND Albumin, as a major urinary protein component, is a risk factor for chronic kidney disease progression. Mitochondrial dysfunction is one of the main causes of albumin-induced proximal tubule cells injury. Mitophagy is considered as a pivotal protective mechanism for the elimination of dysfunctional mitochondria. The objective of this research was to determine whether albumin overload-induced mitochondrial dysfunction can activate PINK1/Parkin-mediated mitophagy in renal tubular epithelial cells (TECs). MATERIAL AND METHODS Immunofluorescence assay and Western blot assay were used to detect the effects of albumin overload on autophagy marker protein LC3. Transmission electron microscopy and Western blot assay were used to investigate the role of albumin in mitochondrial injury. Western blot assay and co-localization of acidic lysosomes and mitochondria assay were employed to detect the activation of mitophagy induced by albumin. Finally, we explored the role of PINK1/Parkin signaling in albumin-induced mitophagy by inhibiting mitophagy by knockdown of PARK2 (Parkin) level. RESULTS Immunofluorescence and Western blot results showed that the expression level of LC3-II increased, and the maximum increase point was observed after 8 h of albumin treatment. Transmission electron microscopy results demonstrated that albumin overload-induced mitochondrial injury and quantity of autophagosomes increased. Additionally, expression of PINK1 and cytosolic cytochrome C increased and mitochondria cytochrome C decreased in the albumin group. The co-localization of acidic lysosomes and mitochondria demonstrated that the number of albumin overload-induced mitophagy-positive dots increased. The transient transfection of PARK2 siRNA result showed knockdown of the expression level of PARK2 can inhibit mitophagy induced by albumin. CONCLUSIONS In conclusion, our study suggests that mitochondrial dysfunction activates the PINK1/Parkin signaling and mitophagy in renal tubular epithelial cells under albumin overload condition.

Mutations in HPSE2 cause urofacial syndrome.

PubMed

Daly, Sarah B; Urquhart, Jill E; Hilton, Emma; McKenzie, Edward A; Kammerer, Richard A; Lewis, Malcolm; Kerr, Bronwyn; Stuart, Helen; Donnai, Dian; Long, David A; Burgu, Berk; Aydogdu, Ozgu; Derbent, Murat; Garcia-Minaur, Sixto; Reardon, Willie; Gener, Blanca; Shalev, Stavit; Smith, Rupert; Woolf, Adrian S; Black, Graeme C; Newman, William G

2010-06-11

Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. UFS individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. Whole-genome SNP mapping in one affected individual defined an autozygous region of 16 Mb on chromosome 10q23-q24, within which a 10 kb deletion encompassing exons 8 and 9 of HPSE2 was identified. Homozygous exonic deletions, nonsense mutations, and frameshift mutations in five further unrelated families confirmed HPSE2 as the causative gene for UFS. Mutations were not identified in four additional UFS patients, indicating genetic heterogeneity. We show that HPSE2 is expressed in the fetal and adult central nervous system, where it might be implicated in controlling facial expression and urinary voiding, and also in bladder smooth muscle, consistent with a role in renal tract morphology and function. Our findings have broader implications for understanding the genetic basis of lower renal tract malformations and voiding dysfunction.

Mutations in HPSE2 Cause Urofacial Syndrome

PubMed Central

Daly, Sarah B.; Urquhart, Jill E.; Hilton, Emma; McKenzie, Edward A.; Kammerer, Richard A.; Lewis, Malcolm; Kerr, Bronwyn; Stuart, Helen; Donnai, Dian; Long, David A.; Burgu, Berk; Aydogdu, Ozgu; Derbent, Murat; Garcia-Minaur, Sixto; Reardon, Willie; Gener, Blanca; Shalev, Stavit; Smith, Rupert; Woolf, Adrian S.; Black, Graeme C.; Newman, William G.

2010-01-01

Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. UFS individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. Whole-genome SNP mapping in one affected individual defined an autozygous region of 16 Mb on chromosome 10q23-q24, within which a 10 kb deletion encompassing exons 8 and 9 of HPSE2 was identified. Homozygous exonic deletions, nonsense mutations, and frameshift mutations in five further unrelated families confirmed HPSE2 as the causative gene for UFS. Mutations were not identified in four additional UFS patients, indicating genetic heterogeneity. We show that HPSE2 is expressed in the fetal and adult central nervous system, where it might be implicated in controlling facial expression and urinary voiding, and also in bladder smooth muscle, consistent with a role in renal tract morphology and function. Our findings have broader implications for understanding the genetic basis of lower renal tract malformations and voiding dysfunction. PMID:20560210

Association between left ventricular dysfunction, anemia, and chronic renal failure. Analysis of the Heart Failure Prevalence and Predictors in Turkey (HAPPY) cohort.

PubMed

Kepez, A; Mutlu, B; Degertekin, M; Erol, C

2015-06-01

Anemia and chronic renal failure (CRF) are frequent comorbidities in patients with heart failure (HF), and they have been reported to be associated with increased mortality and hospitalization rates. HF, anemia, and CRF have been reported to interact with each other forming a vicious cycle termed cardio-renal-anemia syndrome. The aim of the present study was to evaluate the association of HF, anemia, and CRF using data from the large-scale"Heart Failure Prevalence and Predictors in Turkey (HAPPY)" study. Among the HAPPY cohort, 3,369 subjects who had either left ventricular dysfunction (LVD) or normal left ventricular function on echocardiography or normal serum NT-proBNP levels were included in this analysis. The prevalence of anemia and CRF was significantly higher in patients with LVD compared with subjects with normal ventricular function (20.7 % vs. 4.0 % and 19.0 % vs. 3.7 %, respectively; p < 0.001 for each). Binary logistic regression analyses for the presence of LVD, anemia, and CRF demonstrated that each one was an independent predictor for the presence of the others. These findings point to the presence of cardio-renal-anemia syndrome and the necessity of treating these comorbidities in patients with HF.

A Case Report of Parvovirus B19 Infection in a Renal Allograft.

PubMed

Oramas, Diana M; Setty, Suman; Yeldandi, Vijay; Cabrera, Julio; Patel, Tushar

2017-10-01

Parvovirus B19 infection is undiagnosed in recipients undergoing solid organ transplantation. It is usually responsible for unexplained acute and chronic red blood cell aplasia that does not respond to erythropoietin therapy. Cases of parvovirus B19 infection associated with pancytopenia, solid organ dysfunction, and allograft rejection have been described in the literature. The deterioration of the immune system as a result of severe immunotherapy favors the reactivation of a previous infection or the acquisition of a new one. We present a case of a 32-year-old woman with a 1-year history of renal allograft transplant and previous cytomegalovirus (CMV) infection who presented with chest pain, polyarthritis, pancytopenia, and renal dysfunction. A serum sample using polymerase chain reaction showed a parvovirus titer of 13.8 trillion IU/mL and a CMV titer of 800 IU/mL. The renal biopsy revealed nucleomegaly with focal viral inclusions, along with changes associated with immunotherapy toxicity. Electron microscopy demonstrated capillary and tubular epithelial cells with "viral factories," thereby confirming the diagnosis. Thus, screening for parvovirus B19 is advised in high-risk patients who present with refractory anemia to avoid the complications of a chronic infection associated with the fatal rejection of the transplanted organ.

Potential immunotoxic effects of trichloroethylene-induced IV allergic reaction in renal impairment

PubMed Central

Yu, Jun-Feng; Feng, Yan-Yan

2017-01-01

Trichloroethylene (TCE) is known to induce allergic contact dermatitis and subsequent occupational medicamentosa-like dermatitis (OMLD) with multi-system injuries, including liver, kidney, and skin injuries. However, the mechanisms underlying immune system dysfunction that result in organ injury have not yet been clearly elucidated. In the present study, we measured the levels of secreted cytokines by effect or T cells in TCE-treated guinea pigs to better understand the contribution of allergic disorders in renal injuries. We immunized guinea pigs with trichloroethylene using the Guinea Pig Maximization Test (GPMT) and scored the inflammation on the guinea pigs’ skin. The kidney function and ultra-structural changes in the kidneys were detected using biochemical methods and electron microscopy. The deposition of cytokines was determined using immunohistochemistry. The sensitization rate was 63.16% in the TCE-sensitized groups. The electron microscopy results showed tubular epithelial cell mitochondrial swelling, vacuolar degeneration, and atrophy of the microvillus in the sensitized groups. A high degree of cytokine deposition was observed in the renal tubular proximal epithelial cells in the TCE-sensitized groups. As observed in this study, the variation in the level of immune system activation not only indicates that TCE can largely magnify the immune reaction but also suggests a potential role of immune dysfunction in renal impairment. PMID:28867961

Phellinus rimosus improves mitochondrial energy status and attenuates nephrotoxicity in diabetic rats.

PubMed

Rony, K A; Ajith, T A; Kuttikadan, Tony A; Blaze, R; Janardhanan, K K

2017-09-26

Mitochondrial dysfunction and increase in reactive oxygen species during diabetes can lead to pathological consequences in kidneys. The present study was aimed to investigate the effect of Phellinus rimosus in the streptozotocin (STZ)-induced diabetic rat renal mitochondria and the possible mechanism of protection. Phellinus rimosus (50 and 250 mg/kg, p.o) was treated after inducing diabetes by STZ (45 mg/kg, i.p) in rats. The serum samples were subjected to creatinine and urea estimation. Mitochondrial antioxidant status such as mitochondrial superoxide dismutase, glutathione peroxidase, and reduced glutathione; adenosine triphosphate level; and lipid peroxidation were measured. The activities of Krebs cycle enzymes such as isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase as well as mitochondrial complexes I, III, and IV in kidney mitochondria were also determined. Administration of P. rimosus (250 mg/kg b.wt) once daily for 30 days, significantly (p<0.05) enhanced the activities of Krebs cycle dehydrogenases, mitochondrial electron transport chain complexes, and ATP level. Further, P. rimosus had significantly protected the renal mitochondrial antioxidant status and lipid peroxidation. The results of the study concluded that by limiting the extent of renal mitochondrial damage in the hyperglycemic state, P. rimosus alleviated nephrotoxicity.

Role of bioimpedance vectorial analysis in cardio-renal syndromes.

PubMed

Aspromonte, Nadia; Cruz, Dinna N; Ronco, Claudio; Valle, Roberto

2012-01-01

The cardio-renal syndromes (CRS) are the result of complex bidirectional organ cross-talk between the heart and kidney, with tremendous overlap of diseases such as coronary heart disease, heart failure (HF), and renal dysfunction in the same patient. Volume overload plays an important role in the pathophysiology of CRS. The appropriate treatment of overhydration, particularly in HF and in chronic kidney disease, has been associated with improved outcomes and blood pressure control. Clinical examination alone is often insufficient for accurate assessment of volume status because significant volume overload can exist even in the absence of peripheral or pulmonary edema on physical examination or radiography. Bioelectrical impedance techniques increasingly are being used in the management of patients with HF and those on chronic dialysis. These methods provide more objective estimates of volume status in such patients. Used in conjunction with standard clinical assessment and biomarkers such as the natriuretic peptides, bioimpedance analysis may be useful in guiding pharmacologic and ultrafiltration therapies and subsequently restoring such patients to a euvolemic or optivolemic state. In this article, we review the use of these techniques in CRS. Copyright © 2012 Elsevier Inc. All rights reserved.

Recent analytical approaches to detect exhaled breath ammonia with special reference to renal patients.

PubMed

Krishnan, Sanduru Thamarai; Devadhasan, Jasmine Pramila; Kim, Sanghyo

2017-01-01

The ammonia odor from the exhaled breath of renal patients is associated with high levels of blood urea nitrogen. Typically, in the liver, ammonia and ammonium ions are converted into urea through the urea cycle. In the case of renal dysfunction, urea is unable to be removed and that causes a buildup of excessive ammonia. As small molecules, ammonia and ammonium ions can be forced into the blood-lung barrier and occur in exhaled breath. Therefore, people with renal failure have an ammonia (fishy) odor in their exhaled breath. Thus, exhaled breath ammonia can be a potential biomarker for monitoring renal diseases during hemodialyis. In this review, we have summarized the source of ammonia in the breath of end-stage renal disease patient, cause of renal disorders, exhaled breath condensate, and breath sampling. Further, various biosensor approaches to detect exhaled ammonia from renal patients and other ammonia systems are also discussed. We conclude with future perspectives, namely colorimetric-based real-time breathing diagnosis of renal failure, which might be useful for prospective studies.

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.

Contribution of the amiloride-sensitive component and the Na+/H+ exchanger to renal responsiveness to vasoconstrictors.

PubMed

Vargas, Pablo; Wangensteen, Rosemary; Rodríguez-Gómez, Isabel; Perez-Abud, Rocío; Osuna, Antonio; Quesada, Andrés; Vargas, Félix

2011-01-01

This study analyzed the role of the amiloride-sensitive component and the participation of the Na(+)/H(+) exchanger in renal responsiveness to vasoconstrictors in the isolated perfused rat kidney. The renal responses to vasoconstrictors (angiotensin II, phenylephrine, vasopressin and KCl) were studied under baseline conditions and after the administration of amiloride (10 and 100 μmol/l) or the specific Na(+)/H(+) exchange inhibitor ethylisopropylamiloride (EIPA, 10 μmol/l). The effects of amiloride and EIPA on renal responsiveness to vasoconstrictors were also analyzed in endothelium-denuded preparations. Amiloride reduced renal responsiveness to all vasoconstrictors in a dose-related manner, whereas EIPA did not affect the renal pressor response to KCl. The inhibitory effects of amiloride and EIPA on renal responsiveness to vasoconstrictors persisted after endothelium removal. These results indicate that the amiloride-sensitive component and the Na(+)/H(+) exchanger play an important role in responsiveness to the main endogenous vasoconstrictors in the renal vasculature. These results also suggest that amiloride might be useful as an inhibitor of renal vasoconstriction, even in diseases with endothelial dysfunction. Copyright © 2011 S. Karger AG, Basel.

Renal mechanoreceptor dysfunction: an intermediate phenotype in spontaneously hypertensive rats.

PubMed

DiBona, G F; Jones, S Y; Kopp, U C

1999-01-01

This study tested the hypothesis that decreased responsiveness of renal mechanosensitive neurons constitutes an intermediate phenotype in spontaneously hypertensive rats (SHR). Decreased responsiveness of these sensory neurons would contribute to increased renal sympathetic nerve activity and sodium retention, characteristic findings in hypertension. A backcross population, developed by mating borderline hypertensive rats with Wistar-Kyoto rats (WKY) (the F1 of a cross between an SHR and a normotensive WKY), was fed 8% NaCl food for 12 weeks from age 4 to 16 weeks. Responses to increases in ureteral pressure to 20 and 40 mm Hg in 80 backcross rats instrumented for measurement of mean arterial pressure and afferent renal nerve activity were determined. Mean arterial pressure ranged from 110 to 212 mm Hg and was inversely correlated with the magnitude of the increase in afferent renal nerve activity during increased ureteral pressure. Thus, decreased responsiveness of renal mechanosensitive neurons cosegregated with hypertension in this backcross population. This aspect of the complex quantitative trait of altered renal sympathetic neural control of renal function, ie, decreased renal mechanoreceptor responsiveness, is part of an intermediate phenotype in SHR.

Guidewire exchange vs new site placement for temporary dialysis catheter insertion in ICU patients: is there a greater risk of colonization or dysfunction?

PubMed

Coupez, Elisabeth; Timsit, Jean-François; Ruckly, Stéphane; Schwebel, Carole; Gruson, Didier; Canet, Emmanuel; Klouche, Kada; Argaud, Laurent; Bohe, Julien; Garrouste-Orgeas, Maïté; Mariat, Christophe; Vincent, François; Cayot, Sophie; Cointault, Olivier; Lepape, Alain; Darmon, Michael; Boyer, Alexandre; Azoulay, Elie; Bouadma, Lila; Lautrette, Alexandre; Souweine, Bertrand

2016-07-30

Intensive care unit (ICU) patients require dialysis catheters (DCs) for renal replacement therapy (RRT). They carry a high risk of developing end-stage renal disease, and therefore their vascular access must be preserved. Guidewire exchange (GWE) is often used to avoid venipuncture insertion (VPI) at a new site. However, the impact of GWE on infection and dysfunction of DCs in the ICU is unknown. Our aim was to compare the effect of GWE and VPI on DC colonization and dysfunction in ICU patients. Using data from the ELVIS randomized controlled trial (RCT) (1496 ICU adults requiring DC for RRT or plasma exchange) we performed a matched-cohort analysis. Cases were DCs inserted by GWE (n = 178). They were matched with DCs inserted by VPI. Matching criteria were participating centre, simplified acute physiology score (SAPS) II +/-10, insertion site (jugular or femoral), side for jugular site, and length of ICU stay before DC placement. We used a marginal Cox model to estimate the effect of DC insertion (GWE vs. VPI) on DC colonization and dysfunction. DC colonization rate was not different between GWE-DCs and VPI-DCs (10 (5.6 %) for both groups) but DC dysfunction was more frequent with GWE-DCs (67 (37.6 %) vs. 28 (15.7 %); hazard ratio (HR), 3.67 (2.07-6.49); p < 0.01). Results were similar if analysis was restricted to DCs changed for dysfunction. GWE for DCs in ICU patients, compared with VPI did not contribute to DC colonization or infection but was associated with more than twofold increase in DC dysfunction. This study is registered with ClinicalTrials.gov, number NCT00563342 . Registered 2 April 2009.

Mannitol increases renal blood flow and maintains filtration fraction and oxygenation in postoperative acute kidney injury: a prospective interventional study.

PubMed

Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2012-08-17

Acute kidney injury (AKI), which is a major complication after cardiovascular surgery, is associated with significant morbidity and mortality. Diuretic agents are frequently used to improve urine output and to facilitate fluid management in these patients. Mannitol, an osmotic diuretic, is used in the perioperative setting in the belief that it exerts reno-protective properties. In a recent study on uncomplicated postcardiac-surgery patients with normal renal function, mannitol increased glomerular filtration rate (GFR), possibly by a deswelling effect on tubular cells. Furthermore, experimental studies have previously shown that renal ischemia causes an endothelial cell injury and dysfunction followed by endothelial cell edema. We studied the effects of mannitol on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2), and extraction (RO2Ex) in early, ischemic AKI after cardiac surgery. Eleven patients with AKI were studied during propofol sedation and mechanical ventilation 2 to 6 days after complicated cardiac surgery. All patients had severe heart failure treated with one (100%) or two (73%) inotropic agents and intraaortic balloon pump (36%). Systemic hemodynamics were measured with a pulmonary artery catheter. RBF and renal filtration fraction (FF) were measured by the renal vein thermo-dilution technique and by renal extraction of chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), respectively. GFR was calculated as the product of FF and renal plasma flow RBF × (1-hematocrit). RVO2 and RO2Ex were calculated from arterial and renal vein blood samples according to standard formulae. After control measurements, a bolus dose of mannitol, 225 mg/kg, was given, followed by an infusion at a rate of 75 mg/kg/h for two 30-minute periods. Mannitol did not affect cardiac index or cardiac filling pressures. Mannitol increased urine flow by 61% (P < 0.001). This was accompanied by a 12% increase in RBF (P < 0.05) and a 13% decrease in renal vascular resistance (P < 0.05). Mannitol increased the RBF/cardiac output (CO) relation (P = 0.040). Mannitol caused no significant changes in RO2Ext or renal FF. Mannitol treatment of postoperative AKI induces a renal vasodilation and redistributes systemic blood flow to the kidneys. Mannitol does not affect filtration fraction or renal oxygenation, suggestive of balanced increases in perfusion/filtration and oxygen demand/supply.

Mannitol increases renal blood flow and maintains filtration fraction and oxygenation in postoperative acute kidney injury: a prospective interventional study

PubMed Central

2012-01-01

Introduction Acute kidney injury (AKI), which is a major complication after cardiovascular surgery, is associated with significant morbidity and mortality. Diuretic agents are frequently used to improve urine output and to facilitate fluid management in these patients. Mannitol, an osmotic diuretic, is used in the perioperative setting in the belief that it exerts reno-protective properties. In a recent study on uncomplicated postcardiac-surgery patients with normal renal function, mannitol increased glomerular filtration rate (GFR), possibly by a deswelling effect on tubular cells. Furthermore, experimental studies have previously shown that renal ischemia causes an endothelial cell injury and dysfunction followed by endothelial cell edema. We studied the effects of mannitol on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2), and extraction (RO2Ex) in early, ischemic AKI after cardiac surgery. Methods Eleven patients with AKI were studied during propofol sedation and mechanical ventilation 2 to 6 days after complicated cardiac surgery. All patients had severe heart failure treated with one (100%) or two (73%) inotropic agents and intraaortic balloon pump (36%). Systemic hemodynamics were measured with a pulmonary artery catheter. RBF and renal filtration fraction (FF) were measured by the renal vein thermo-dilution technique and by renal extraction of chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), respectively. GFR was calculated as the product of FF and renal plasma flow RBF × (1-hematocrit). RVO2 and RO2Ex were calculated from arterial and renal vein blood samples according to standard formulae. After control measurements, a bolus dose of mannitol, 225 mg/kg, was given, followed by an infusion at a rate of 75 mg/kg/h for two 30-minute periods. Results Mannitol did not affect cardiac index or cardiac filling pressures. Mannitol increased urine flow by 61% (P < 0.001). This was accompanied by a 12% increase in RBF (P < 0.05) and a 13% decrease in renal vascular resistance (P < 0.05). Mannitol increased the RBF/cardiac output (CO) relation (P = 0.040). Mannitol caused no significant changes in RO2Ext or renal FF. Conclusions Mannitol treatment of postoperative AKI induces a renal vasodilation and redistributes systemic blood flow to the kidneys. Mannitol does not affect filtration fraction or renal oxygenation, suggestive of balanced increases in perfusion/filtration and oxygen demand/supply. PMID:22901953

Nitrooleic acid protects against cisplatin nephropathy: role of COX-2/mPGES-1/PGE2 cascade.

PubMed

Wang, Haiping; Jia, Zhanjun; Sun, Jing; Xu, Liang; Zhao, Bing; Yu, Kezhou; Yang, Meng; Yang, Tianxin; Wang, Rong

2015-01-01

Nitrooleic acid (OA-NO2) is an endogenous lipid product which has novel signaling properties, particularly the activation of peroxisome proliferator-activated receptors. The current study aimed to evaluate the protective effects of OA-NO2 against cisplatin-induced kidney injury in mice. Mice were pretreated with OA-NO2 for 48 h before cisplatin administration, and the cisplatin-caused nephrotoxicity was evaluated. After the cisplatin treatment (72 h), the vehicle-treated mice displayed renal dysfunction, as evidenced by the elevated plasma urea and creatinine, which was consistent with the histological damage, such as tubular necrosis, dilation, protein cast, and desquamation of epithelial cells. In contrast, the severity of the renal dysfunction and histological change were reduced in the OA-NO2 pretreated mice. The renal COX-2 and mPGES-1 mRNAs and their respective proteins expression, together with the renal PGE2 amounts, were induced by the cisplatin treatment, but their initiation was reduced by OA-NO2. Moreover, the circulating TNF-α, renal TNF-α, IL-1β, MCP-1, ICAM-1, and VACAM-1 mRNA levels were higher in the cisplatin-treated mice, compared with the controls, but they were attenuated in the OA-NO2 pretreatment group. In summary, the pretreatment with OA-NO2 remarkably ameliorated the cisplatin-induced kidney injury in mice, possibly via the inhibition of the inflammatory response, associated with the COX-2/mPGES-1/PGE2 cascade.

The effect of maleate induced proximal tubular dysfunction on the renal handling of Tc-99m DMSA in the rat

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

Provoost, A.P.; Van Aken, M.

1984-01-01

In the healthy kidney Tc-99m DMSA accumulates in the proximal tubular cells. Consequently, impairment of the reabsorptive function of these cells may alter the renal handling of this static renal imaging agent. The authors investigated in rats the effects of a sodiummaleate (Ma) (2mmol/kg iv) induced proximal tubular dysfunction on the renal accumulation and excretion of Tc-99m DMSA. Such a treatment results in a moderate fall of the glomerular filtration rate, glycosuria, aminoaciduria and a tubular proteinuria. In 7 adult male Wistar rats, Tc-99m DMSA scans were taken before Ma, on the day of treatment, and 1 week thereafter. Themore » accumulation of Tc-99m DMSA in kidneys (Ki) and bladder (Bl) was determined at 1, 2, 4, and 24 hours after i.v. injection. The results, expressed as a percentage of the injected dose, are presented. The findings show that a reversible Ma induced impairment of the proximal reabsorptive capacity severely alters the renal tubular handling of Tc-99m DMSA. In contrast to the control situation, only a small fraction of the DMSA is retained in the kidney and the majority is transported directly to the urinary bladder. When similar alterations are observed in clinical Tc-99m DMSA scans, this may be an indication of an impairment of the proximal tubular function.« less

Tolvaptan in Patients Hospitalized With Acute Heart Failure: Rationale and Design of the TACTICS and the SECRET of CHF Trials.

PubMed

Felker, G Michael; Mentz, Robert J; Adams, Kirkwood F; Cole, Robert T; Egnaczyk, Gregory F; Patel, Chetan B; Fiuzat, Mona; Gregory, Douglas; Wedge, Patricia; O'Connor, Christopher M; Udelson, James E; Konstam, Marvin A

2015-09-01

Congestion is a primary reason for hospitalization in patients with acute heart failure (AHF). Despite inpatient diuretics and vasodilators targeting decongestion, persistent congestion is present in many AHF patients at discharge and more severe congestion is associated with increased morbidity and mortality. Moreover, hospitalized AHF patients may have renal insufficiency, hyponatremia, or an inadequate response to traditional diuretic therapy despite dose escalation. Current alternative treatment strategies to relieve congestion, such as ultrafiltration, may also result in renal dysfunction to a greater extent than medical therapy in certain AHF populations. Truly novel approaches to volume management would be advantageous to improve dyspnea and clinical outcomes while minimizing the risks of worsening renal function and electrolyte abnormalities. One effective new strategy may be utilization of aquaretic vasopressin antagonists. A member of this class, the oral vasopressin-2 receptor antagonist tolvaptan, provides benefits related to decongestion and symptom relief in AHF patients. Tolvaptan may allow for less intensification of loop diuretic therapy and a lower incidence of worsening renal function during decongestion. In this article, we summarize evidence for decongestion benefits with tolvaptan in AHF and describe the design of the Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure Study (TACTICS) and Study to Evaluate Challenging Responses to Therapy in Congestive Heart Failure (SECRET of CHF) trials. © 2015 American Heart Association, Inc.

1,[Formula: see text]2,[Formula: see text]3,[Formula: see text]4,[Formula: see text]6-Penta-O-Galloyl-β-D-Glucose from Galla rhois Ameliorates Renal Tubular Injury and Microvascular Inflammation in Acute Kidney Injury Rats.

PubMed

Park, Ji Hun; Kho, Min Chol; Oh, Hyun Cheol; Kim, Youn Chul; Yoon, Jung Joo; Lee, Yun Jung; Kang, Dae Gill; Lee, Ho Sub

2018-05-13

Renal ischemia-reperfusion injury (IRI), an important cause of acute kidney injury (AKI), causes increased renal tubular injury and microvascular inflammation. 1,[Formula: see text]2,[Formula: see text]3,[Formula: see text]4,[Formula: see text]6-penta-O-galloyl-[Formula: see text]-D-glucose (PGG) from Galla rhois has anticancer, anti-oxidation and angiogenesis effects. We examined protective effects of PGG on IRI-induced acute AKI. Clamping both renal arteries for 45[Formula: see text]min induced isechemia and then reperfusion. Treatment with PGG (10[Formula: see text]mg/kg/day and 50[Formula: see text]mg/kg/day for four days) significantly ameliorated urine volume, urine osmolality, creatinine clearance (Ccr) and blood urea nitrogen (BUN). In addition, PGG increased aquaporine 1/2/3, Na[Formula: see text]-K[Formula: see text]-ATPase and urea transporter (UT-B) and decreased ICAM-1, MCP-1, and HMGB-1 expression. In this histopathologic study, PGG improved glomerular and tubular damage. Immunohistochemistry results showed that PGG increased aquaporine 1/2, and Na[Formula: see text]-K[Formula: see text] ATPase and decreased ICAM-1 expression. These findings suggest that PGG ameliorates tubular injury including tubular dysfunction and microvascular inflammation in IRI-induced AKI rats.

A retrospective 15-year review: survival advantage after switching to sirolimus in hepatitis C virus infected liver graft recipients.

PubMed

Shah, M; Shankar, A; Gee, I; Nash, K; Hoare, M; Gibbs, P; Davies, S; Alexander, G J M

2015-02-01

The use of sirolimus-based immune suppression in liver transplantation, particularly in hepatitis C virus (HCV)-infected recipients, remains contentious. There is some evidence that sirolimus retards hepatic fibrosis, is renal sparing and may be of benefit in preventing hepatocellular carcinoma (HCC) recurrence. Sirolimus has not been adopted by many transplant centres because of persistent concerns regarding an increased risk of hepatic artery thrombosis, graft loss and death with de novo sirolimus. To review the impact of switching to sirolimus monotherapy in HCV-infected liver recipients with respect to survival, graft loss and hepatic fibrosis. A retrospective review of 190 patients from a single centre undergoing first liver transplantation for HCV over 15 years. 113 patients were switched from calcineurin inhibitor (CNI)-based therapy to low-dose sirolimus monotherapy at a median of 15 months after transplantation for HCV-related fibrosis (72%), renal impairment (14%) or high-risk HCC (5%). Patients switched to sirolimus had improved survival (P < 0.001) and slower progression to cirrhosis (P = 0.001). In patients with HCC (n = 91), sirolimus duration rather than strategy was an independent predictor of survival (P = 0.001) and extended time to HCC recurrence (33 vs. 16 months). Patients switched for renal dysfunction showed improvement in serum creatinine (140-108 μmol/L, P = 0.001). Those remaining on CNI-therapy were more likely to develop post-transplant diabetes (P = 0.03). These data suggest selective switching to low-dose sirolimus monotherapy in HCV-positive liver recipients improves clinical outcome. © 2014 John Wiley & Sons Ltd.

The prevalence and implications of BK virus replication in non-renal solid organ transplant recipients: A systematic review.

PubMed

Viswesh, Velliyur; Yost, Sarah E; Kaplan, Bruce

2015-07-01

The significance of BK viruria and viremia in non-renal solid organ transplants is poorly understood. A systematic review was performed reviewing the incidence and implications of BK virus replication in non-renal solid organ transplants. Ninety-seven studies were identified, of which 18 including lung, heart, liver and pancreas transplants were included. The overall incidence of BK viruria and viremia was 20% and 3% respectively and 17 cases of BK nephropathy were identified. Heart transplant recipients had a higher overall incidence of BK viremia than other non-renal organ types, and the majority of cases of BK virus-associated nephropathy were in heart transplant recipients. The incidence of BK viremia was significantly lower in non-renal solid organ transplants than that of renal transplant recipients and BK virus-associated nephropathy was rare. BK virus-associated nephropathy may be considered in heart transplant recipients who have unexplained and persistent renal dysfunction not attributable to other causes. Copyright © 2015 Elsevier Inc. All rights reserved.

Reducing VEGF-B Signaling Ameliorates Renal Lipotoxicity and Protects against Diabetic Kidney Disease.

PubMed

Falkevall, Annelie; Mehlem, Annika; Palombo, Isolde; Heller Sahlgren, Benjamin; Ebarasi, Lwaki; He, Liqun; Ytterberg, A Jimmy; Olauson, Hannes; Axelsson, Jonas; Sundelin, Birgitta; Patrakka, Jaakko; Scotney, Pierre; Nash, Andrew; Eriksson, Ulf

2017-03-07

Diabetic kidney disease (DKD) is the most common cause of severe renal disease, and few treatment options are available today that prevent the progressive loss of renal function. DKD is characterized by altered glomerular filtration and proteinuria. A common observation in DKD is the presence of renal steatosis, but the mechanism(s) underlying this observation and to what extent they contribute to disease progression are unknown. Vascular endothelial growth factor B (VEGF-B) controls muscle lipid accumulation through regulation of endothelial fatty acid transport. Here, we demonstrate in experimental mouse models of DKD that renal VEGF-B expression correlates with the severity of disease. Inhibiting VEGF-B signaling in DKD mouse models reduces renal lipotoxicity, re-sensitizes podocytes to insulin signaling, inhibits the development of DKD-associated pathologies, and prevents renal dysfunction. Further, we show that elevated VEGF-B levels are found in patients with DKD, suggesting that VEGF-B antagonism represents a novel approach to treat DKD. Copyright © 2017 Elsevier Inc. All rights reserved.

A Unified Theory of Sepsis-Induced Acute Kidney Injury: Inflammation, microcirculatory dysfunction, bioenergetics and the tubular cell adaptation to injury

PubMed Central

Gomez, Hernando; Ince, Can; De Backer, Daniel; Pickkers, Peter; Payen, Didier; Hotchkiss, John; Kellum, John A.

2014-01-01

Given that the leading clinical conditions associated with Acute kidney injury (AKI), namely, sepsis, major surgery, heart failure and hypovolemia, are all associated with shock, it is tempting to attribute all AKI to ischemia on the basis of macro-hemodynamic changes. However, an increasing body of evidence has suggested that in many patients, AKI can occur in the absence of overt signs of global renal hypoperfusion. Indeed, sepsis-induced AKI can occur in the setting of normal or even increased renal blood flow. Accordingly, renal injury may not be entirely explained solely on the basis of the classic paradigm of hypoperfusion, and thus other mechanisms must come into play. Herein, we put forward a “unifying theory” to explain the interplay between inflammation and oxidative stress, microvascular dysfunction, and the adaptive response of the tubular epithelial cell to the septic insult. We propose that this response is mostly adaptive in origin, that it is driven by mitochondria and that it ultimately results in and explains the clinical phenotype of sepsis induced AKI. PMID:24346647

Role of adipose tissue-derived stem cells in the progression of renal disease.

PubMed

Donizetti-Oliveira, Cassiano; Semedo, Patricia; Burgos-Silva, Marina; Cenedeze, Marco Antonio; Malheiros, Denise Maria Avancini Costa; Reis, Marlene Antônia Dos; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

2011-03-01

To analyze the role of adipose tissue-derived stem cells in reducing the progression of renal fibrosis. adipose tissue-derived stem cells were isolated from C57Bl/6 mice and characterized by cytometry and differentiation. Renal fibrosis was established after unilateral clamping of the renal pedicle for 1 hour. Four hours after reperfusion, 2.105 adipose tissue-derived stem cells were administered intraperitoneally and the animals were followed for 24 hours during 6 weeks. In another experimental group, 2.105adipose tissue-derived stem cells were administered only after 6 weeks of reperfusion, and they were euthanized and studied 4 weeks later. Twenty-four hours after reperfusion, the animals treated with adipose tissue-derived stem cells displayed reduced renal and tubular dysfunction and an increase of the regenerative process. Renal expression of IL-6 and TNF mRNA were decreased in the animals treated with adipose tissue-derived stem cells, while the levels of IL-4, IL-10, and HO-1 were increased, despite the fact that adipose tissue-derived stem cells were not observed in the kidneys via SRY analysis. In 6 weeks, the kidneys of non-treated animals decreased in size, and the kidneys of the animals treated with adipose tissue-derived stem cells remained at normal size and display less deposition of type 1 collagen and FSP-1. The renal protection observed in animals treated with adipose tissue-derived stem cells was followed by a drop in serum levels of TNF-α, KC, RANTES, and IL-1a. Treatment with adipose tissue-derived stem cells after 6 weeks, when the animals already displayed established fibrosis, demonstrated an improvement in functional parameters and less fibrosis analyzed by Picrosirius stain, as well as a reduction of the expression of type 1 collagen and vimentin mRNA. Treatment with adipose tissue-derived stem cells may deter the progression of renal fibrosis by modulation of the early inflammatory response, likely via reduction of the epithelial-mesenchymal transition.

Comparative study on the protective role of vitamin C and L-arginine in experimental renal ischemia reperfusion in adult rats.

PubMed

Mohamed, Abd El-Hamid A; Lasheen, Noha N

2014-01-01

Ischemia reperfusion (I/R) injury is a main cause of transplanted kidney dysfunction and rejection. Reactive oxygen species (ROS) play a causal role in cellular damage induced by I/R. Antioxidant vitamins and Nitric oxide (NO) were postulated to play renoprotective effects against I/R. This study compares the protective effects of vitamin C with that of the nitric oxide donor, L-arginine, on renal I/R injury in adult rats. The study was performed on 50 adult Wistar rats of both sexes, divided into 5 groups: I: Control group, receive daily intraperitoneal (i.p.) saline for 3 days. II: Renal I/R group, received i.p saline for 3 days and subjected to renal I/R. III: L-arginine Pretreated, 400 mg/kg/day i.p. for 3 days prior to I/R. IV: Vitamin C Pretreated, 500 mg/kg/day i.p. 24 hours prior to I/R. V: combined L-arginine and Vitamin C Pretreated, exposed to Renal I/R group. At the end of the experiment, plasma urea and creatinine were determined. Kidney tissue malondialdehyde (MDA), NO, catalase and superoxide dismutase (SOD) activity were measured and kidneys were examined histologically. I/R group showed significant increase in plasma urea, creatinine, and renal MDA, and a significant decrease in renal catalase with marked necrotic epithelial cells and infiltration by inflammatory cells in kidney section compared to the control group. All the treated groups showed significant decrease in urea, creatinine, and MDA, and a significant increase in catalase with less histopathological changes in kidney sections compared to I/R group. However, significant improvements in urea, MDA, and catalase were found in vitamin C pretreated and combined treated groups than L-arginine pretreated group. Oxidative stress is the primary element involved in renal I/R injury. So, antioxidants play an important renoprotective effects than NO donors.

Urinary β2 microglobulin can predict tenofovir disoproxil fumarate-related renal dysfunction in HIV-1-infected patients who initiate tenofovir disoproxil fumarate-containing antiretroviral therapy.

PubMed

Nishijima, Takeshi; Kurosawa, Takuma; Tanaka, Noriko; Kawasaki, Yohei; Kikuchi, Yoshimi; Oka, Shinichi; Gatanaga, Hiroyuki

2016-06-19

In nephrotoxicity induced by tenofovir disoproxil fumarate (TDF), tubular dysfunction precedes the decline in GFR, suggesting that tubular markers are more sensitive than estimated glomerular filtration rate (eGFR). The hypothesis that urinary β2 microglobulin (β2 M), a tubular function marker, can predict TDF-renal dysfunction in HIV-1-infected patients was tested. A single-center observational study. The inclusion criteria were: HIV-1-infected patients who started TDF-containing antiretroviral therapy from 2004 to 2013, urinary β2 M after and closest to the day of TDF initiation within 180 days (termed 'β2 M after TDF') was measured. The associations between 'β2 M after TDF' and four renal end points (>10 ml/min per 1.73 m decrement in eGFR relative to baseline, >20 decrement, >25% decrement, and eGFR < 60) were estimated with logistic regression model. The association between 'β2 M after TDF' and longitudinal changes in eGFR after initiation of TDF was estimated with a mixed-model. A total 655 study patients were analyzed (96% men, median age 38, median CD4 238 cells/μl, 63% treatment naïve). The median baseline eGFR was 117 ml/min per 1.73 m (IQR 110-125), and the median duration of TDF use was 3.32 years (IQR 2.02-5.31). 'β2 M after TDF' was significantly associated with more than 20 decrement in eGFR (P = 0.024) and more than 25% decrement (P = 0.014), and was marginally associated with eGFR less than 60 (P = 0.076). It was also significantly associated with the longitudinal eGFR after initiation of TDF (P < 0.0001). 'β2 M after TDF' of 1700 μg/l was identified as the optimal cutoff value for the prediction of longitudinal eGFR. Urinary β2 M measured within 180 days after initiation of TDF predicts renal dysfunction related to long-term TDF use.

HPLC determination of plasma dimethylarginines: method validation and preliminary clinical application.

PubMed

Ivanova, Mariela; Artusi, Carlo; Boffa, Giovanni Maria; Zaninotto, Martina; Plebani, Mario

2010-11-11

Asymmetric dimethylarginine (ADMA) has been suggested as a possible marker of endothelial dysfunction, and interest in its use in clinical practice is increasing. However, the potential role of symmetric dimethylarginine (SDMA) as an endogenous marker of renal function, has been less widely investigated. The aims of the present study were therefore to determine reference values for dimethylarginines in plasma after method validation, and to ascertain ADMA plasma concentrations in patients with disorders characterized by endothelial dysfunction; a further end-point was to investigate the relationship between SDMA plasma concentrations and estimated GFR (eGFR) as well as plasmatic creatinine in patients with chronic kidney disease (CKD). HPLC with fluorescence detection was used for the determination of plasma dimethylarginines. To verify the clinical usefulness of ADMA and SDMA, values from 4 groups of patients at a high risk of cardiovascular complications as well renal dysfunction (chronic heart failure n=126; type II diabetes n=43; pulmonary arterial hypertension n=17; chronic kidney disease n=42) were evaluated, and compared with the reference values, obtained from 225 blood donors. The intra- and inter-assay CVs (<5.2%), the absolute and relative recoveries (96-106%) were highly satisfactory. ADMA levels were significantly elevated in all groups of patients compared with controls (p<0.001) with the exception of samples from patients with type II diabetes. SDMA levels were significantly elevated both in the patients with chronic kidney disease and in the patients with type II diabetes complicated by renal insufficiency, the values being closely correlated with both eGFR (R=0.740) and plasmatic creatinine (R=0.700). The findings made in the present study shows that ADMA levels are significantly increased in patients with diseases associated with endothelial dysfunction This molecule might, therefore, be used as a biochemical marker for the evaluation of endothelial function. Furthermore, the preliminary results reported suggest that SDMA might be a reliable marker of renal function, especially in peadiatric populations, for which the use of eGFR is not recommended. 2010 Elsevier B.V. All rights reserved.

Nonsteroidal Anti-Inflammatory Drugs and the Kidney

PubMed Central

Hörl, Walter H.

2010-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the isoenzymes COX-1 and COX-2 of cyclooxygenase (COX). Renal side effects (e.g., kidney function, fluid and urinary electrolyte excretion) vary with the extent of COX-2-COX-1 selectivity and the administered dose of these compounds. While young healthy subjects will rarely experience adverse renal effects with the use of NSAIDs, elderly patients and those with co-morbibity (e.g., congestive heart failure, liver cirrhosis or chronic kidney disease) and drug combinations (e.g., renin-angiotensin blockers, diuretics plus NSAIDs) may develop acute renal failure. This review summarizes our present knowledge how traditional NSAIDs and selective COX-2 inhibitors may affect the kidney under various experimental and clinical conditions, and how these drugs may influence renal inflammation, water transport, sodium and potassium balance and how renal dysfunction or hypertension may result. PMID:27713354

Early Post-Operative Outcomes and Blood Product Utilization in Adult Cardiac Surgery- The Post Aprotinin Era

PubMed Central

DeSantis, Stacia; Toole, J. Matthew; Kratz, John M.; Uber, Walter E.; Wheat, Margaret J.; Stroud, Martha R.; Ikonomidis, John S.; Spinale, Francis G.

2011-01-01

Background Aprotinin was a commonly utilized pharmacological agent for homeostasis in cardiac surgery but was discontinued resulting in the extensive use of lysine analogues. This study tested the hypothesis that early post-operative adverse events and blood product utilization would affected in this post-aprotinin era. Methods/Results Adult patients (n=781) undergoing coronary artery bypass (CABG), valve replacement, or both from November 1, 2005-October 31, 2008 at a single institution were included. Multiple logistic regression modeling and propensity scoring were performed on 29 pre-operative and intra-operative variables in patients receiving aprotinin (n=325) or lysine analogues (n=456). The propensity adjusted relative risk (RR;95% confidence interval;CI) for the intra-operative use of packed red blood cells (RR:0.75;CI:0.57–0.99), fresh frozen plasma (RR:0.37;0.21–0.64), and cryoprecipitate (RR:0.06;CI:0.02–0.22) were lower in the aprotinin versus lysine analogue group (all p<0.05). The risk for mortality (RR:0.53;CI:0.16–1.79) and neurological events (RR:0.87;CI:0.35–2.18) remained similar between groups, whereas a trend for reduced risk for renal dysfunction was observed in the aprotinin group. Conclusions In the post-aprotinin era with the exclusive use of lysine analogues, the relative risk of early post-operative outcomes such as mortality and renal dysfunction have not improved, but the risk for the intra-operative use of blood products has increased. Thus, improvements in early post-operative outcomes have not been realized with the discontinued use of aprotinin, but rather increased blood product utilization has occurred with the attendant costs and risks inherent with this strategy. PMID:21911820

Factors affecting mortality and resource use for hospitalized patients with cirrhosis

PubMed Central

Charatcharoenwitthaya, Phunchai; Soonthornworasiri, Ngamphol; Karaketklang, Khemajira; Poovorawan, Kittiyod; Pan-ngum, Wirichada; Chotiyaputta, Watcharasak; Tanwandee, Tawesak; Phaosawasdi, Kamthorn

2017-01-01

Abstract Hospitalizations for advanced liver disease are costly and associated with significant mortality. This population-based study aimed to evaluate factors associated with in-hospital mortality and resource use for the management of hospitalized patients with cirrhosis. Mortality records and resource utilization for 52,027 patients hospitalized with cirrhosis and/or complications of portal hypertension (ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, or hepatorenal syndrome) were extracted from a nationally representative sample of Thai inpatients covered by Universal Coverage Scheme during 2009 to 2013. The rate of dying in the hospital increased steadily by 12% from 9.6% in 2009 to 10.8% in 2013 (P < .001). Complications of portal hypertension were independently associated with increased in-hospital mortality except for ascites. The highest independent risk for hospital death was seen with hepatorenal syndrome (odds ratio [OR], 5.04; 95% confidence interval [CI], 4.38–5.79). Mortality rate remained high in patients with infection, particularly septicemia (OR, 4.26; 95% CI, 4.0–4.54) and pneumonia (OR, 2.44; 95% CI, 2.18–2.73). Receiving upper endoscopy (OR, 0.29; 95% CI, 0.27–0.32) and paracentesis (OR, 0.93; 95% CI, 0.87–1.00) were associated with improved patient survival. The inflation-adjusted national annual costs (P = .06) and total hospital days (P = .07) for cirrhosis showed a trend toward increasing during the 5-year period. Renal dysfunction, infection, and sequelae of portal hypertension except for ascites were independently associated with increased resource utilization. Renal dysfunction, infection, and portal hypertension-related complications are the main factors affecting in-hospital mortality and resource utilization for hospitalized patients with cirrhosis. The early intervention for modifiable factors is an important step toward improving hospital outcomes. PMID:28796076

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

PubMed

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

2015-07-01

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

Testicular dysfunction in experimental chronic renal insufficiency: a deficiency of nocturnal pineal N-acetyltransferase activity.

PubMed Central

Holmes, E. W.; Hojvat, S. A.; Kahn, S. E.; Bermes, E. W.

1989-01-01

Biochemical correlates of neuroendocrine/gonadal function and nocturnal levels of serotonin N-acetyltransferase (NAT) activity were determined in partially nephrectomized (PNx), male, Long Evans rats following a 5-week period of chronic renal insufficiency (CRI). PNx animals demonstrated two to four-fold elevations in urea nitrogen and three to four-fold reductions (P less than 0.02) in plasma total testosterone concentrations as compared to sham-operated controls. The pituitary LH contents of PNx rats were decreased to approximately 60% of the control value (P less than 0.05). There were no differences in plasma prolactin levels between the control and PNx groups either at mid-day or in the middle of the night. Nocturnal pineal NAT activity in PNx rats was markedly reduced to approximately 20% of the control value (P less than 0.001). Similar evidence of gonadal dysfunction (reduced plasma total testosterone and testes testosterone content) and a significant decrease in night-time levels of pineal NAT activity were also observed after 13 weeks of CRI in PNx rats of the Sprague-Dawley strain that were housed under a different photoperiod. These results suggest that pineal gland dysfunction is a feature of CRI in the PNx model. Such an abnormality might contribute to the pathogenesis of gonadal dysfunction in CRI. PMID:2765391

The Association Between Inflammatory Markers and Hypertension. A Call for Anti-Inflammatory Strategies?

PubMed Central

García, Néstor H.; Juncos, Luis I.

2006-01-01

The most important goal of antihypertensive therapy is to prevent the complications associated with hypertension (stroke, myocardial infarction, end-stage renal disease, etc). For this, secondary targets such as left ventricular hypertrophy, proteinuria, dementia, and other signs of hypertension-induced organ damage help the physician to assess risks and monitor treatment efficacy. New treatment targets may be arising, however. One such target may be endothelial dysfunction. In effect, endothelial dysfunction not only may precede the elevation of blood pressure, but may also pave the way to conditions often associated with hypertension, such as diabetes, arteriosclerosis, microalbuminuria, congestive heart failure, and tissue hypertrophy. Because inflammation often accompanies endothelial dysfunction, approaches to counteract inflammation are now being evaluated. For this, antagonists of the renin-angiotensin-aldosterone system, statins, and beta blockers are all being tested. All of these agents seem to prevent or delay the induction of proinflammatory molecules aside from, and in addition to, their specific effects on blood pressure. The focus of this review is to update some of the animal and human research showing that hypertension sets off an inflammatory state and also to consider some of the anti-inflammatory approaches that may prevent the development of endothelial dysfunction, and the subsequent renal and cardiovascular damage.

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.

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.

Apparent renal disease due to elevated creatinine levels associated with the use of boldenone.

PubMed

Winnett, Georgia; Cranfield, Lesley; Almond, Michael

2011-02-01

The widespread use of reporting estimated glomerular filtration rate (eGFR) alongside serum creatinine has led to a heightened appreciation of renal disease. However, creatinine is recognized as an insensitive marker of true GFR and therefore can lead to misdiagnosis of renal dysfunction in the absence of true pathology. We report the case of a 37-year-old male referred due to abnormal eGFR and creatinine in the absence of clinical signs, symptoms or other biochemical abnormalities of renal disease. Subsequent investigations based on a high index of suspicion for exogenous substance abuse led to a novel observation of significantly raised creatinine due to the presence of boldenone, an equine anabolic steroid commonly abused in body building.

Iodinated contrast media and the role of renal replacement therapy.

PubMed

Weisbord, Steven D; Palevsky, Paul M

2011-05-01

Iodinated contrast media are among the most commonly used pharmacologic agents in medicine. Although generally highly safe, iodinated contrast media are associated with several adverse effects, most significantly the risk of acute kidney injury, particularly in patients with underlying renal dysfunction. By virtue of their pharmacokinetic characteristics, these contrast agents are efficiently cleared by hemodialysis and to a lesser extent, hemofiltration. This has led to research into the capacity for renal replacement therapies to prevent certain adverse effects of iodinated contrast. This review examines the molecular and pharmacokinetic characteristics of iodinated contrast media and critically analyzes data from past studies on the role of renal replacement therapy to prevent adverse effects of these diagnostic agents. Published by Elsevier Inc.

[Acute renal failure secondary to hemolytic uremic syndrome in a pregnant woman with pre-eclampsia].

PubMed

García-Miguel, F J; Mirón Rodríguez, M F; Alsina Aser, M J

2009-02-01

Acute renal failure is a serious complication of pregnancy associated with a high rate of morbidity and mortality; the incidence is currently 1 per 10,000 pregnancies. The most common causes are gestational hypertension, bleeding, sepsis, and intrinsic renal disease. Other less common pregnancy-related syndromes, such as HELLP syndrome or thrombotic microangiopathy, may also lead to kidney failure. Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura are forms of thrombotic microangiopathy and although neither is specific to pregnancy, the incidence of these entities rises during gestation. The classic symptoms are fever, hemolytic microangiopathic anemia, thrombopenia, neurologic dysfunction, and kidney abnormalities. When renal involvement is the predominant manifestation, the diagnosis is usually hemolytic uremic syndrome.

[Primary vesicoureteral reflux with renal failure in adults].

PubMed

Hagen, R H; Klevmark, B

1991-05-30

The present article describes the case of two men, 18 and 30 years respectively, in whom renal insufficiency was discovered incidently. In the two cases renography showed 46 and 30% of expected function given two healthy kidneys. They had neither experienced clinical symptoms of urinary tract disorder, been operated upon, nor endoscopically examined. Micturition was normal without any sign of vesicourethral dysfunction. Micturition cystography revealed severe vesicoureteral reflux in both patients. They were treated by bilateral ureterovesical reimplantation. The cases presented here show that primary vesicoureteral reflux complicated by impaired renal function can be revealed in adults who have had no symptoms of urinary tract disorder. In these cases the probable cause of renal damage is the mechanical effect of reflux ("water-hammer effect") alone.

Megabladder mouse model of congenital obstructive nephropathy: genetic etiology and renal adaptation.

PubMed

McHugh, Kirk M

2014-04-01

Congenital obstructive nephropathy remains one of the leading causes of chronic renal failure in children. The direct link between obstructed urine flow and abnormal renal development and subsequent dysfunction represents a central paradigm of urogenital pathogenesis that has far-reaching clinical implications. Even so, a number of diagnostic, prognostic, and therapeutic quandaries still exist in the management of congenital obstructive nephropathy. Studies in our laboratory have characterized a unique mutant mouse line that develops in utero megabladder, variable hydronephrosis, and progressive renal failure. Megabladder mice represent a valuable functional model for the study of congenital obstructive nephropathy. Recent studies have begun to shed light on the genetic etiology of mgb (-/-) mice as well as the molecular pathways controlling disease progression in these animals.

An Extract of Rhodobacter sphaeroides Reduces Cisplatin-Induced Nephrotoxicity in Mice

PubMed Central

Chang, Wen-Wei; Liu, Jau-Jin; Liu, Chi-Fan; Liu, Wen-Sheng; Lim, Yun-Ping; Cheng, Yu-Jung; Lee, Che-Hsin

2013-01-01

Cisplatin is used as a treatment for various types of solid tumors. Renal injury severely limits the use of cisplatin. Renal cell apoptosis, oxidative stress, and inflammation contribute to cisplatin-induced nephrotoxicity. Previously, we found that an extract of Rhodobacter sphaeroides (Lycogen™) inhibited proinflammatory cytokines and the production of nitric oxide in activated macrophages in a dextran sodium sulfate (DSS)-induced colitis model. Here, we evaluated the effect of Lycogen™, a potent anti-inflammatory agent, in mice with cisplatin-induced renal injury. We found that attenuated renal injury correlated with decreased apoptosis due to a reduction in caspase-3 expression in renal cells. Oral administration of Lycogen™ significantly reduced the expression of tumor necrosis factor-α and interleukin-1β in mice with renal injury. Lycogen™ reduces renal dysfunction in mice with cisplatin-induced renal injury. The protective effects of the treatment included blockage of the cisplatin-induced elevation in serum urea nitrogen and creatinine. Meanwhile, Lycogen™ attenuated body weight loss and significantly prolonged the survival of mice with renal injury. We propose that Lycogen™ exerts anti-inflammatory activities that represent a promising strategy for the treatment of cisplatin-induced renal injury. PMID:24335753

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.

Congenital renal anomalies in cloacal exstrophy: Is there a difference?

PubMed

Suson, K D; Inouye, B; Carl, A; Gearhart, J P

2016-08-01

Cloacal exstrophy (CE) is the most severe manifestation of the epispadias-exstrophy spectrum. Previous studies have indicated an increased rate of renal anomalies in children with classic bladder exstrophy (CBE). Given the increased severity of the CE defect, it was hypothesized that there would be an even greater incidence among these children. The primary objective was to characterize renal anatomy in CE patients. Two secondary objectives were to compare these renal anatomic findings in male and female patients, and female patients with and without Müllerian anomalies. An Institutional Review Board-approved retrospective review of 75 patients from an institutional exstrophy database. Data points included: age at analysis, sex, and renal and Müllerian anatomy. Abnormal renal anatomy was defined as a solitary kidney, malrotation, renal ectopia, congenital cysts, duplication, and/or proven obstruction. Abnormal Müllerian anatomy was defined as uterine or vaginal duplication, obstruction, and/or absence. The Summary Table presents demographic data and renal anomalies. Males were more likely to have renal anomalies. Müllerian anomalies were present in 65.7% of female patients. Girls with abnormal Müllerian anatomy were 10 times more likely to have renal anomalies than those with normal Müllerian anatomy (95% CI 1.1-91.4, P = 0.027). Patients with CE had a much higher rate of renal anomalies than that reported for CBE. Males and females with Müllerian anomalies were at greater risk than females with normal uterine structures. Mesonephric and Müllerian duct interaction is required for uterine structures to develop normally. It has been proposed that women with both Müllerian and renal anomalies be classified separately from other uterine malformations on an embryonic basis. In these patients, an absent or dysfunctional mesonephric duct has been implicated as potentially causal. This provided an embryonic explanation for uterine anomalies in female CE patients. There were also clinical implications. Women with renal agenesis and uterine anomalies were more likely to have endometriosis than those with isolated uterine anomalies, but were also more likely to have successful pregnancies. Males may have had an analogous condition with renal agenesis and seminal vesicle cysts. Future research into long-term kidney function in this population, uterine function, and possible male sexual duct malformation is warranted. Congenital renal anomalies occurred frequently in children with CE. They were more common in boys than in girls. Girls with abnormal Müllerian anatomy were more likely to have anomalous renal development. Mesonephric duct dysfunction may be embyologically responsible for both renal and Müllerian maldevelopment. Copyright © 2016 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion injury in vivo: role for xanthine oxidoreductase.

PubMed

Tripatara, Pinpat; Patel, Nimesh S A; Webb, Andrew; Rathod, Krishnaraj; Lecomte, Florence M J; Mazzon, Emanuela; Cuzzocrea, Salvatore; Yaqoob, Mohammed M; Ahluwalia, Amrita; Thiemermann, Christoph

2007-02-01

In normal conditions, nitric oxide (NO) is oxidized to the anion nitrite, but in hypoxia, this nitrite may be reduced back to NO by the nitrite reductase action of deoxygenated hemoglobin, acidic disproportionation, or xanthine oxidoreductase (XOR). Herein, is investigated the effects of topical sodium nitrite administration in a rat model of renal ischemia/reperfusion (I/R) injury. Rats were subjected to 60 min of bilateral renal ischemia and 6 h of reperfusion in the absence or presence of sodium nitrite (30 nmol) administered topically 1 min before reperfusion. Serum creatinine, serum aspartate aminotransferase, creatinine clearance, fractional excretion of Na(+), and plasma nitrite/nitrate concentrations were measured. The nitrite-derived NO-generating capacity of renal tissue was determined under acidic and hypoxic conditions by ozone chemiluminescence in homogenates of kidneys that were subjected to sham, ischemia-only, and I/R conditions. Nitrite significantly attenuated renal dysfunction and injury, an effect that was abolished by previous treatment of rats with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide (2.5 mumol intravenously 5 min before ischemia and 50 nmol topically 6 min before reperfusion). Renal tissue homogenates produced significant amounts of NO from nitrite, an effect that was attenuated significantly by the xanthine oxidoreductase inhibitor allopurinol. Taken together, these findings demonstrate that topically administered sodium nitrite protects the rat kidney against I/R injury and dysfunction in vivo via the generation, in part, of xanthine oxidoreductase-catalyzed NO production. These observations suggest that nitrite therapy might prove beneficial in protecting kidney function and integrity during periods of I/R such as those encountered in renal transplantation.

Renal function in hepatosplenic schistosomiasis--an assessment of renal tubular disorders.

PubMed

Duarte, Daniella Bezerra; Vanderlei, Lucas Alexandre; Bispo, Raianne Kívia de Azevêdo; Pinheiro, Maria Eliete; da Silva, Geraldo Bezerra; Martins, Alice Maria Costa; Meneses, Gdayllon Cavalcante; Daher, Elizabeth De Francesco

2014-01-01

Renal involvement in Schistosoma mansoni infection is not well studied. The aim of this study is to investigate the occurrence of renal abnormalities in patients with hepatosplenic schistosomiasis (HSS), especially renal tubular disorders. This is a cross-sectional study with 20 consecutive patients with HSS followed in a medical center in Maceió, Alagoas, Brazil. Urinary acidification and concentration tests were performed using calcium chloride (CaCl2) after a 12-h period of water and food deprivation. The biomarker monocyte chemoattractant protein 1 (MCP-1) was quantified in urine. Fractional excretion of sodium (FENa+), transtubular potassium gradient (TTKG) and solute-free water reabsorption (TcH2O) were calculated. The HSS group was compared to a group of 17 healthy volunteers. Patients' mean age and gender were similar to controls. Urinary acidification deficit was found in 45% of HSS patients. Urinary osmolality was significantly lower in HSS patients (588 ± 112 vs. 764 ± 165 mOsm/kg, p = 0,001) after a 12-h period of water deprivation. TcH2O was lower in HSS patients (0.72 ± 0.5 vs. 1.1 ± 0.3, p = 0.04). Urinary concentration deficit was found in 85% of HSS patients. The values of MCP-1 were higher in HSS group than in control group (122 ± 134 vs. 40 ± 28 pg/mg-Cr, p = 0.01) and positively correlated with the values of microalbuminuria and proteinuria. HSS is associated with important kidney dysfunction. The main abnormalities found were urinary concentrating ability and incomplete distal acidification defect, demonstrating the occurrence of tubular dysfunction. There was also an increase in urinary MCP-1, which appears to be a more sensitive marker of renal damage than urinary albumin excretion rate.

Optimal conditions of LDR to protect the kidney from diabetes: exposure to 12.5 mGy X-rays for 8 weeks efficiently protects the kidney from diabetes.

PubMed

Cheng, Jie; Li, Fengsheng; Cui, Jiuwei; Guo, Weiying; Li, Cai; Li, Wei; Wang, Guixia; Xing, Xiao; Gao, Ying; Ge, Yuanyuan; Wang, Guanjun; Cai, Lu

2014-05-08

We reported the attenuation of diabetes-induced renal dysfunction by exposure to multiple low-dose radiation (LDR) at 25 mGy every other day by suppressing renal oxidative damage. We here explored the optimal conditions of LDR to protect the kidney from diabetes. Male C57BL/6J mice with type 1 diabetes were induced with multiple injections of low-dose streptozotocin. Diabetic mice received whole body X-irradiation at a dose of 12.5, 25 or 50 mGy every other day for either 4 or 8 weeks. Age-matched normal mice were similarly irradiated at the dose of 25 mGy for 4 or 8 weeks. The renal function and histopathological changes were examined at the 4th and 8th weeks of the study. Diabetes induced renal dysfunction is shown by the decreased creatinine and increased microalbumin in the urine. Renal oxidative damage, detected by protein nitration and lipid oxidation, and remodeling, reflected by increased expression of connective tissue growth factor, collagen IV and fibronectin, were significantly increased in diabetic mice. All these renal pathological and function changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens, among which, however, exposure to LDR at 12.5 mGy for 8 weeks provided the best protective effect on the kidney of diabetic mice. Our results suggest that whole-body LDR at 12.5 mGy every other day for 8 weeks is the optimal condition of LDR to protect the kidney from diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.

Abnormal distal renal tubular acidification in patients with low bone mass: prevalence and impact of alkali treatment.

PubMed

Sromicki, Jerzy Jan; Hess, Bernhard

2017-06-01

Chronic acid retention is known to promote bone dissolution. In this study, 23 % of patients with osteopenia/osteoporosis were diagnosed with abnormal distal renal tubular acidification (dRTA), a kidney dysfunction leading to chronic acid retention. Treating those patients with alkali-therapy shows improvement in bone density. To evaluate the prevalence of abnormal distal renal tubular acidification in patients with low bone mass (LBM) and the impact of additional alkali treatment on bone density in patients with concomitant LBM and dRTA,183 patients referred for metabolic evaluation of densitometrically proven low bone mass were screened for abnormal distal renal tubular acidification between 2006 and 2013. In all LBM urine pH (U-pH) was measured in the 2nd morning urines after 12 h of fasting. If U-pH was ≥5.80, LBM underwent a 1-day ammonium chloride loading, and U-pH was remeasured the next morning. If U-pH after acid loading did not drop below 5.45, patients were diagnosed with abnormal distal renal tubular acidification. Normal values were obtained from 21 healthy controls. All LBM with dRTA were recommended alkali citrate in addition to conventional therapy of LBM, and follow-up DXAs were obtained until 2014. 85 LBM underwent NH 4 Cl loading. 42 LBM patients were diagnosed with incomplete dRTA (idRTA; prevalence 23.0 %). During follow-up (1.6-8 years) of idRTA-LBM patients, subjects adhering to alkali treatment tended to improve BMD at all sites measured, whereas BMD of non-adherent idRTA patients worsened/remained unchanged. (1) About one out of four patients with osteopenia/osteoporosis has idRTA. (2) Upon NH 4 Cl loading, idRTA patients do not lower urine pH normally, but show signs of increased acid-buffering by bone dissolution. (3) In idRTA patients with low bone mass on conventional therapy, additional long-term alkali treatment improves bone mass at lumbar spine and potentially at other bone sites. (4) All patients with low bone mass undergoing metabolic evaluation should be screened for idRTA.

Prevalence and risk factors of mild chronic renal failure in HIV-infected patients: influence of female gender and antiretroviral therapy.

PubMed

Cristelli, Marina Pontello; Trullàs, Joan Carles; Cofán, Federico; Rico, Naira; Manzardo, Christian; Ambrosioni, Juan; Bedini, Josep Lluis; Moreno, Asunción; Diekmann, Fritz; Miro, Jose Maria

2018-05-18

In people living with HIV, much is known about chronic kidney disease, defined as a glomerular filtration rate under 60mL/min. However, there is scarce data about prevalence and risk factors for milder impairment (60-89mL/min). The present study aims to assess the influence of sex, antiretroviral therapy, and classical risk factors on the occurrence of mild decreased renal function in a large Spanish cohort of HIV-infected patients. Cross-sectional, single center study, including all adult HIV-1-infected patients under antiretroviral treatment with at least two serum creatinine measures during 2014, describing the occurrence of and the risk factors for mildly decreased renal function (eGFR by CKD-EPI creatinine equation of 60-89mL/min). Among the 4337 patients included, the prevalence rate of mildly reduced renal function was 25%. Independent risk factors for this outcome were age older than 50 years (OR 3.03, 95% CI 2.58-3.55), female sex (OR 1.23, 95% CI 1.02-1.48), baseline hypertension (OR 1.57, 95% CI 1.25-1.97) or dyslipidemia (OR 1.48, 95% CI 1.17-1.87), virologic suppression (OR 1.88, 95% CI 1.39-2.53), and exposure to tenofovir disoproxil-fumarate (OR 1.67, 95% CI 1.33-2.08) or ritonavir-boosted protease-inhibitors (OR 1.19, 95% CI 1.03-1.39). Females and patients over 50 seem to be more vulnerable to renal impairment. Potentially modifiable risk factors and exposure to tenofovir disoproxil-fumarate or ritonavir-boosted protease-inhibitors are present even in earlier stages of chronic kidney dysfunction. It remains to be determined whether early interventions including antiretroviral therapy changes (tenofovir alafenamide, cobicistat) or improving comorbidities management will improve the course of chronic kidney disease. Copyright © 2018 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

Management of Bladder Cancer After Renal Transplantation.

PubMed

Demirdag, C; Citgez, S; Talat, Z; Onal, B

2017-03-01

In renal transplant recipients, the risk of developing bladder cancer and rate of diagnosis of advanced staged bladder cancer are generally higher than the general population. Also, it is more challenging to treat renal transplant recipients than the regular patient population. We aimed to evaluate the efficacy and safety of radical cystectomy (RC) and urinary diversion with ileal conduit in renal transplant recipients. We identified 2 patients with prior history of renal transplantation who underwent RC and ileal conduit urinary diversion for bladder cancer. Preoperative clinical and demographic data were presented and outcomes were assessed. The RC and ileal conduit urinary diversion were performed in the first patient 56 months after renal transplantation and in the second patient 64 months after renal transplantation. Clinical staging was high-grade T2 transitional cell cancer of the bladder for patient 1 and T2 with pure squamous cell cancer of the bladder for patient 2. No perioperative or postoperative complication and no graft dysfunction occurred in either patient. Our experience demonstrated that RC with ileal conduit reconstruction in renal transplant recipients is safe and feasible. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of a protocol for vancomycin administration in critically patients with and without kidney dysfunction.

PubMed

Spadaro, Savino; Berselli, Angela; Fogagnolo, Alberto; Capuzzo, Maurizia; Ragazzi, Riccardo; Marangoni, Elisabetta; Bertacchini, Sara; Volta, Carlo Alberto

2015-06-27

Administration of vancomycin in critically ill patients needs close regulation. While subtherapeutical vancomycin serum concentration (VSC) is associated with increased mortality, accumulation is responsible for nephrotoxicity. Our study aimed to estimate the efficacy of a vancomycin-dosing protocol in reaching appropriate serum concentration in patients with and without kidney dysfunction. This was a retrospective study in critically ill patients treated with continuous infusion of vancomycin. Patients with creatinine clearance > 50 ml/min (Group A) were compared to those with creatinine clearance ≤ 50 ml/min (Group B). 348 patients were enrolled (210 in Group A, 138 in Group B). At first determination, patients with kidney dysfunction (Group B) had a statistically higher percentage of vancomycin in target range, while the percentage of patients with a VSC under the range was almost equal. These percentages differed at the subsequent measurements. The number of patients with low vancomycin concentration progressively decreased, except in those with augmented renal clearance; the percentage of patients with VSC over 30 mg/L was about 28 %, irrespective of the presence or absence of kidney dysfunction. Patients who reached a subtherapeutic level at the first VSC measurement had a significant correlation with in-hospital mortality. Our protocol seems to allow a rapid achievement of a target VSC particularly in patients with kidney dysfunction. In order to avoid subtherapeutical VSC, our algorithm should be implemented by the estimation of the presence of an augmented renal clearance.

Assessment of Endothelial Dysfunction: The Role of Symmetrical Dimethylarginine and Proinflammatory Markers in Chronic Kidney Disease and Renal Transplant Recipients

PubMed Central

Giga, Vojislav; Dopsaj, Violeta; Jelic-Ivanovic, Zorana

2013-01-01

Objectives. The study was designed to evaluate associations between symmetric dimethylarginine (SDMA), inflammation, and superoxide anion (O2∙−) with endothelial function and to determine their potential for screening of endothelial dysfunction in patients with chronic kidney disease (CKD) and renal transplant (RT) recipients. Materials and Methods. We included 64 CKD and 52 RT patients. Patients were stratified according to brachial artery flow-mediated dilation (FMD). Results. Logistic regression analysis showed that high SDMA and high sensitive C-reactive protein (hs-CRP) were associated with impaired FMD in CKD and RT patients, after adjustment for glomerular filtration rate. The ability of inflammation, SDMA, and O2∙− to detect impaired FMD was investigated by receiving operative characteristic analysis. Hs-CRP (area under the curves (AUC) = 0.754, P < 0.001), IL-6 (AUC = 0.699, P = 0.002), and SDMA (AUC = 0.689, P = 0.007) had the highest ability to detect impaired FMD. SDMA in combination with inflammatory parameters and/or O2∙− had better screening performance than SDMA alone. Conclusions. Our results indicate a strong predictable association between hs-CRP, SDMA, and endothelial dysfunction in CKD patients and RT recipients. The individual marker that showed the strongest discriminative ability for endothelial dysfunction is hs-CRP, but its usefulness as a discriminatory marker for efficient diagnosis of endothelial dysfunction should be examined in prospective studies. PMID:24167363

[Retinal vasculopathy with cerebral leukoencephalopathy carrying TREX1 mutation diagnosed by the intracranial calcification: a case report].

PubMed

Komaki, Ryouhei; Ueda, Takehiro; Tsuji, Yukio; Miyawaki, Toko; Kusuhara, Sentaro; Hara, Shigeo; Toda, Tatsushi

2018-02-28

A 40-year-old woman with renal dysfunction for 2 years was admitted to our hospital suffering from a headache. Family history revealed that her mother had a headache, renal dysfunction, and brain infarction in younger age. She had a retinal hemorrhage, a retinal atrophy, pitting edema in her lower extremities. Her neurological findings were unremarkable. Brain imaging showed multiple white matter lesions accompanied with calcifications and slightly enhancement. Kidney biopsy showed the thrombotic microangiopathy, Gene analysis demonstrated a causative mutation in three-prime repair exonuclease-1 (TREX1) gene, c.703_704insG (p.Val235GlyfsX6), thereby we diagnosed her as retinal vasculopathy with cerebral leukoencephalopathy (RVCL). RVCL is an autosomal dominant condition caused by C-terminal frame-shift mutation in TREX1. TREX1 protein is a major 3' to 5' DNA exonuclease, which are important in DNA repair. While TREX1 mutations identified in Aicardi-Goutieres syndrome patients lead to a reduction of enzyme activity, it is suggested that mutations in RVCL alter an intracellular location of TREX1 protein. There are no treatments based evidences in RVCL. We administered cilostazol to protect endothelial function, and her brain lesions and renal function have not become worse for 10 months after. It is necessary to consider RVCL associated with TREX1 mutation if a patient has retinal lesions, white matter lesions accompanied with calcifications, and multiple organ dysfunction.

Alport syndrome and pregnancy: a case series and literature review.

PubMed

Brunini, Francesca; Zaina, Barbara; Gianfreda, Davide; Ossola, Wally; Giani, Marisa; Fedele, Luigi; Messa, Piergiorgio; Moroni, Gabriella

2018-06-01

To assess pregnancy outcome in women with Alport syndrome and the impact of pregnancy on the disease progression. We describe one of the largest series of pregnancies in Alport syndrome. Seven pregnancies of six women were monitored by a multidisciplinary team of nephrologists and gynecologists. After delivery, patients were followed for at least 3 years. We compare our results with those in the literature. Pregnancy course was uneventful in the patient with isolated microscopic hematuria. In the other cases, all presenting mild proteinuria at conception, some complications occurred. Proteinuria worsened during the last trimester, reaching nephrotic ranges in five out of six pregnancies and was associated with fluid overload leading to hospitalizations and early delivery. The majority of the newborns had a low birth weight. The two patients with arterial hypertension at conception and twin pregnancy developed pre-eclampsia and renal function deterioration persisted after delivery. The one with pre-pregnancy renal dysfunction reached end-stage renal disease. In the other patients, in which renal function and blood pressure were and remained normal, proteinuria improved after delivery and no signs of disease progression were recorded at last observation. Our observations suggest that Alport syndrome should be considered a potential risk factor for pregnancy in proteinuric patients due to the development of pre-eclampsia, renal function deterioration, and/or full-blown nephrotic syndrome that results in anasarca, slowing of fetal growth and pre-term delivery. Thus, all women with Alport syndrome should receive pre-conceptional counseling and be kept in close follow-up during pregnancy.

Spontaneous bacterial peritonitis

PubMed Central

Koulaouzidis, Anastasios; Bhat, Shivaram; Saeed, Athar A

2009-01-01

Since its initial description in 1964, research has transformed spontaneous bacterial peritonitis (SBP) from a feared disease (with reported mortality of 90%) to a treatable complication of decompensated cirrhosis, albeit with steady prevalence and a high recurrence rate. Bacterial translocation, the key mechanism in the pathogenesis of SBP, is only possible because of the concurrent failure of defensive mechanisms in cirrhosis. Variants of SBP should be treated. Leucocyte esterase reagent strips have managed to shorten the ‘tap-to-shot’ time, while future studies should look into their combined use with ascitic fluid pH. Third generation cephalosporins are the antibiotic of choice because they have a number of advantages. Renal dysfunction has been shown to be an independent predictor of mortality in patients with SBP. Albumin is felt to reduce the risk of renal impairment by improving effective intravascular volume, and by helping to bind pro-inflammatory molecules. Following a single episode of SBP, patients should have long-term antibiotic prophylaxis and be considered for liver transplantation. PMID:19266595

Improvement in late renal allograft survival between 1990 and 2002 in Spain: results from a multicentre case-control study.

PubMed

Moreso, Francesc; Alonso, Angel; Gentil, Miguel A; González-Molina, Miguel; Capdevila, Lluis; Marcén, Roberto; Pascual, Julio; Serón, Daniel

2010-09-01

Epidemiological studies have failed to show an improvement in graft survival beyond 1 year after kidney transplantation possibly because of an increased number of expanded donors and older recipients. Thus, we performed a case-control study matching patients transplanted in different eras by donor and recipient characteristics. We considered renal transplant recipients included in the database of the Spanish Chronic Allograft Dysfunction Study Group in 1990, 1994, 1998 and 2002 (n = 4842). We matched patients from these cohorts considering the following variables: donor and recipient age, cause of donor death, hepatitis C virus, panel reactive antibodies and re-transplantation. We identified a total of 896 patients distributed in four cohorts of 224 matched patients. Between 1990 and 2002, the use of cyclosporin decreased (96%, 94%, 80% and 23% respectively, P = 0.001), while the use of tacrolimus increased (0%, 1%, 15% and 63% respectively, P = 0.001) and the prevalence of acute rejection decreased (46%, 37.9%, 20.6% and 15.8% respectively, P < 0.001). One-year serum creatinine was 1.63 +/- 0.66, 1.64 +/- 0.70, 1.44 +/- 0.52 and 1.38 +/- 0.75 respectively, P = 0.001. Graft survival beyond the first year between 1990 and 2002 significantly improved while patient survival did not. Transplant outcome has improved between 1990 and 2002 when donors and recipients of similar characteristics are compared.

Polyacetylene glycoside attenuates ischemic kidney injury by co-inhibiting inflammation, mitochondria dysfunction and lipotoxicity.

PubMed

Zhou, Yijie; Du, Dan; Liu, Shuyun; Zhao, Meng; Yuan, Yujia; Li, Lan; Chen, Younan; Lu, Yanrong; Cheng, Jingqiu; Liu, Jingping

2018-07-01

Ischemic acute kidney injury (AKI) is a serious clinical problem and no efficient therapeutics is available in clinic now. Natural polyacetylene glycosides (PGAs) had shown antioxidant and anti-inflammatory properties, but their effects on kidney injury have not been evaluated. This study aimed to investigate the protective effect of PGA on ischemic kidney injury in renal tubular epithelial cells (TECs) and mice. Hypoxic HK-2 cells and renal ischemia/reperfusion injury (IRI) mice were treated with PGA from Coreopsis tinctoria, and the cell viability, renal function, apoptosis, inflammation, mitochondrial injury, lipids metabolism were analyzed. In vitro results showed that PGA improved cell viability and reduced oxidative stress, pro-apoptotic/pro-inflammatory factors expression and NFκB activation in TECs under hypoxia/reperfusion (H/R). Moreover, PGA reduced mitochondria oxidative stress and improved ATP production, ΔΨm and mitochondria biogenesis, and inhibited lipids uptake, biosynthesis and accumulation in hypoxic TECs. In vivo, PGA significantly attenuated kidney injury and reduced blood urea nitrogen (BUN), serum creatinine (CREA) and urinary albumin (Alb), and increased creatinine clearance (CC) in IRI mice. PGA also decreased cell apoptosis, mitochondria oxidative stress, inflammatory response and lipid droplets accumulation, and promoted ATP generation in kidney of IRI mice. Our results proved that PGA ameliorated ischemic kidney injury via synergic anti-inflammation, mitochondria protection and anti-lipotoxicity actions, and it might be a promising multi-target therapy for ischemic AKI. Copyright © 2018. Published by Elsevier Inc.

The effect of non-diabetic chronic renal failure on olfactory function.

PubMed

Koseoglu, S; Derin, S; Huddam, B; Sahan, M

2017-05-01

In chronic renal failure (CRF), deterioration of glomerular filtration results in accumulation of metabolites in the body which affect all organs. This study was performed to investigate the olfactory functions, and determine if hemodialysis or peritoneal dialysis improves olfactory function in non-diabetic CRF patients. The olfactory functions were analyzed in CRF patients not on a dialysis program and had a creatinine level≥2mg/dL, in CRF patients on hemodialysis or peritoneal dialysis, and in healthy controls. Diabetic patients were excluded since diabetes alone is a cause of olfactory dysfunction. The study group consisted of a total of 107 individuals including 38CRF patients on a hemodialysis program, 15 CRF patients on peritoneal dialysis, 30 patients with a creatinine level ≥ 2mg/dL without any need for dialysis, and 24 healthy controls with normal renal functions. Olfactory functions were analyzed with "Sniffin' sticks" test, and the groups were compared for the test results. All test parameters were impaired in patients with CRF. The median TDI scores of the patients with CRF and the healthy subjects were 24.75 (13-36) and 32.5 (27.75-37.75), respectively, with a statistically significant difference in between (P<0.001). The olfactory functions for the dialysis patients were better than those for the CRF patients not on a dialysis program (P=0.020). Non-diabetic CRF affects olfactory functions negatively. Dialysis improves olfactory functions in those patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A Review of Podocyte Biology.

PubMed

Garg, Puneet

2018-05-31

Podocyte biology is a developing science that promises to help improve understanding of the mechanistic nature of multiple diseases associated with proteinuria. Proteinuria in nephrotic syndrome has been linked to mechanistic dysfunctions in the renal glomerulus involving the function of podocyte epithelial cells, including podocyte foot process effacement. Developments in imaging technology are improving knowledge of the detailed structure of the human renal glomerulus and cortex. Podocyte foot processes attach themselves to the glomerular capillaries at the glomerular basement membrane (GBM) forming intercellular junctions that form slit diaphragm filtration barriers that help maintain normal renal function. Damage in this area has been implicated in glomerular disease. Injured podocytes undergo effacement whereby they lose their structure and spread out, leading to a reduction in filtration barrier function. Effacement is typically associated with the presence of proteinuria in focal segmental glomerulosclerosis, minimal change disease, and diabetes. It is thought to be due to a breakdown in the actin cytoskeleton of the foot processes, complex contractile apparatuses that allow podocytes to dynamically reorganize according to changes in filtration requirements. The process of podocyte depletion correlates with the development of glomerular sclerosis and chronic kidney disease. Focal adhesion complexes that interact with the underlying GBM bind the podocytes within the glomerular structure and prevent their detachment. Key Messages: Knowledge of glomerular podocyte biology is helping to advance our understanding of the science and mechanics of the glomerular filtering process, opening the way to a variety of new potential applications for clinical targeting. © 2018 S. Karger AG, Basel.

Total protein, albumin and low-molecular-weight protein excretion in HIV-positive patients.

PubMed

Campbell, Lucy J; Dew, Tracy; Salota, Rashim; Cheserem, Emily; Hamzah, Lisa; Ibrahim, Fowzia; Sarafidis, Pantelis A; Moniz, Caje F; Hendry, Bruce M; Poulton, Mary; Sherwood, Roy A; Post, Frank A

2012-08-10

Chronic kidney disease is common in HIV positive patients and renal tubular dysfunction has been reported in those receiving combination antiretroviral therapy (cART). Tenofovir (TFV) in particular has been linked to severe renal tubular disease as well as proximal tubular dysfunction. Markedly elevated urinary concentrations of retinal-binding protein (RBP) have been reported in patients with severe renal tubular disease, and low-molecular-weight proteins (LMWP) such as RBP may be useful in clinical practice to assess renal tubular function in patients receiving TFV. We analysed 3 LMWP as well as protein and albumin in the urine of a sample of HIV positive patients. In a cross-sectional fashion, total protein, albumin, RBP, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were quantified in random urine samples of 317 HIV positive outpatients and expressed as the ratio-to-creatinine (RBPCR, CCR and NGALCR). Exposure to cART was categorised as none, cART without TFV, and cART containing TFV and a non-nucleoside reverse-transcriptase-inhibitor (TFV/NNRTI) or TFV and a protease-inhibitor (TFV/PI). Proteinuria was present in 10.4 % and microalbuminuria in 16.7 % of patients. Albumin accounted for approximately 10 % of total urinary protein. RBPCR was within the reference range in 95 % of patients while NGALCR was elevated in 67 % of patients. No overall differences in urine protein, albumin, and LMWP levels were observed among patients stratified by cART exposure, although a greater proportion of patients exposed to TFV/PI had RBPCR >38.8 μg/mmol (343 μg/g) (p = 0.003). In multivariate analyses, black ethnicity (OR 0.43, 95 % CI 0.24, 0.77) and eGFR <75 mL/min/1.73 m2 (OR 3.54, 95 % CI 1.61, 7.80) were independently associated with upper quartile (UQ) RBPCR. RBPCR correlated well to CCR (r2 = 0.71), but not to NGALCR, PCR or ACR. In HIV positive patients, proteinuria was predominantly of tubular origin and microalbuminuria was common. RBPCR in patients without overt renal tubular disease was generally within the reference range, including those receiving TFV. RBP therefore appears a promising biomarker for monitoring renal tubular function in patients receiving TFV and for distinguishing patients with normal tubular function or mild tubular dysfunction from those with severe renal tubular disease or Fanconi syndrome.

Soy Protein Alleviates Hypertension and Fish Oil Improves Diastolic Heart Function in the Han:SPRD-Cy Rat Model of Cystic Kidney Disease.

PubMed

Ibrahim, Naser H M; Thandapilly, Sijo J; Jia, Yong; Netticadan, Thomas; Aukema, Harold

2016-05-01

Abnormalities in cardiac structure and function are very common among people with chronic kidney disease, in whom cardiovascular disease is the major cause of death. Dietary soy protein and fish oil reduce kidney disease progression in the Han:SPRD-Cy model of cystic renal disease. However, the effects of these dietary interventions in preventing alterations in cardiac structure and function due to kidney disease (reno-cardiac syndrome) in a cystic kidney disease model are not known. Therefore, weanling Han:SPRD-Cy diseased (Cy/+) and normal (+/+) rats were given diets containing either casein or soy protein, and either soy or fish oil in a three-way design for 8 weeks. Diseased rats had larger hearts, augmented left ventricular mass, and higher systolic and mean arterial blood pressure compared to the normal rats. Assessment of cardiac function using two-dimensional guided M-mode and pulse-wave Doppler echocardiography revealed that isovolumic relaxation time was prolonged in the diseased compared to normal rats, reflecting a diastolic heart dysfunction, and fish oil prevented this elevation. Soy protein resulted in a small improvement in systolic and mean arterial pressure but did not improve diastolic heart function, while fish oil prevented diastolic heart dysfunction in this model of cystic kidney disease.

Henoch-Schönlein Purpura Complicated by Hepatocellular Carcinoma.

PubMed

Akizue, Naoki; Suzuki, Eiichiro; Yokoyama, Masayuki; Inoue, Masanori; Wakamatsu, Toru; Saito, Tomoko; Kusakabe, Yuko; Ogasawara, Sadahisa; Ooka, Yoshihiko; Tawada, Akinobu; Maru, Yugo; Matsue, Hiroyuki; Chiba, Tetsuhiro

2017-11-15

Although Henoch-Schönlein purpura (HSP) is known to be accompanied by malignancies, cases with hepatobiliary cancer are extremely rare. A 62-year-old man with palpable purpura rapidly extending to both lower legs was admitted to our hospital. He was undergoing follow-up for cirrhosis caused by chronic hepatitis B virus infection and hepatocellular carcinoma (HCC). He had renal dysfunction with hematuria and proteinuria and abdominal pain. Based on the clinical presentation and skin biopsy findings, he was diagnosed with HSP. The administration of steroids resulted in the rapid improvement of the patient's symptoms and he was discharged 12 days after admission.

Heme oxygenase: the key to renal function regulation

PubMed Central

Cao, Jian; Sacerdoti, David; Li, Xiaoying; Drummond, George

2009-01-01

Heme oxygenase (HO) plays a critical role in attenuating the production of reactive oxygen species through its ability to degrade heme in an enzymatic process that leads to the production of equimolar amounts of carbon monoxide and biliverdin/bilirubin and the release of free iron. The present review examines the beneficial role of HO-1 (inducible form of HO) that is achieved by increased expression of this enzyme in renal tissue. The influence of the HO system on renal physiology, obesity, vascular dysfunction, and blood pressure regulation is reviewed, and the clinical potential of increased levels of HO-1 protein, HO activity, and HO-derived end products of heme degradation is discussed relative to renal disease. The use of pharmacological and genetic approaches to investigate the role of the HO system in the kidney is key to the development of therapeutic approaches to prevent the adverse effects that accrue due to an impairment in renal function. PMID:19570878

Early audit of renal complications in a new cardiac surgery service in Australia.

PubMed

Bolsin, Stephen N; Stow, Peter; Bucknell, Sarah

2004-09-01

To assess the incidence of renal failure in a cardiac surgery service commencing in Australia. Prospective data collection and retrospective database analysis. A tertiary referral, university teaching hospital in the state of Victoria, Australia. The first 502 patients undergoing cardiac surgery in this institution from commencement of the service. The overall rate of renal failure was low in comparison to other studies at 0.2% (95% CI 0.04-1.3%). The rate of postoperative renal dysfunction was also low at 4.2% (95% CI 2.7-6.5%). The safety of the new service with respect to this complication of cardiac surgery was good when compared with published data. However the lack of uniform definitions of renal failure following cardiac surgery make comparisons between studies difficult. Uniform reporting of this complication would facilitate comparisons between units and quality assurance activities in this field.

Serum cystatin C is independently associated with renal impairment and high sensitivity C-reactive protein in systemic lupus erythematosus.

PubMed

Chew, Christine; Pemberton, Philip W; Husain, Awal Al-M; Haque, Sahena; Bruce, Ian N

2013-01-01

In systemic lupus erythematosus (SLE) patients, glomerular filtration rate (GFR) is usually estimated using the modified Cockcroft-Gault (mCG) and Modification of Diet in Renal Disease (MDRD) equations. We aimed to study cystatin C (sCysC) in SLE to assess its agreement with standard renal indices and investigate factors affecting sCysC in SLE. SLE patients (≥4 ACR criteria) and healthy women from Greater Manchester were recruited and clinical assessments were undertaken. SCysC was measured using R & D Systems' ELISA. Agreement between renal measures was assessed using Deming plots and factors associated with sCysC in SLE were examined by multiple linear regression analyses. 178 patients and 68 controls had median (IQR) ages of 53 (46-61) and 50 (39-60) years, respectively. In an age-adjusted analysis, SLE patients had higher sCysC (1.16 [0.98-1.36] vs. 0.950 [0.73-1.13] mg/l; p<0.0001) and within SLE those with a history of lupus nephritis had higher sCysC (1.31 [1.10-1.66] vs. 1.11 [0.95-1.29] mg/l; p<0.005). SCysC correlated positively with serum creatinine, and inversely to renal measures (r=-0.530; p<0.0001 [mCG], and r=-0.620; p<0.0001 [MDRD]). There was closer agreement between the two eGFR measures than between either eGFR measures and sCysC. In addition to age and serum creatinine, a multivariate analysis (β, p) found that high-sensitivity C-reactive protein (hs-CRP) (0.03, 0.026) was also independently associated with sCysC in SLE. In SLE, sCysC may be influenced by low grade inflammation as well as by renal dysfunction. Therefore, SCysC should not supplant current assessment of renal dysfunction in SLE.

Renal outcomes of simultaneous liver-kidney transplantation compared to liver transplant alone for candidates with renal dysfunction.

PubMed

Brennan, Todd V; Lunsford, Keri E; Vagefi, Parsia A; Bostrom, Alan; Ma, Michael; Feng, Sandy

2015-01-01

It is unclear whether a concomitant kidney transplant grants survival benefit to liver transplant (LT) candidates with renal dysfunction (RD). We retrospectively studied LT candidates without RD (n = 714) and LT candidates with RD who underwent either liver transplant alone (RD-LTA; n = 103) or simultaneous liver-kidney transplant (RD-SLKT; n = 68). RD was defined as renal replacement therapy (RRT) requirement or modification of diet in renal disease (MDRD)-glomerular filtration rate (GFR) <25 mL/min/1.73 m(2) . RD-LTAs had worse one-yr post-transplant survival compared to RD-SLKTs (79.6% vs. 91.2%, p = 0.05). However, RD-LTA recipients more often had hepatitis C (60.2% vs. 41.2%, p = 0.004) and more severe liver disease (MELD 37.9 ± 8.1 vs. 32.7 ± 9.1, p = 0.0001). Twenty RD-LTA recipients died in the first post-transplant year. Evaluation of the cause and timing of death relative to native renal recovery revealed that only four RD-LTA recipients might have derived survival benefit from RD-SLKT. Overall, 87% of RD-LTA patients recovered renal function within one month of transplant. One yr after RD-LTA or RD-SLKT, serum creatinine (1.5 ± 1.2 mg/dL vs. 1.4 ± 0.5 mg/dL, p = 0.63) and prevalence of stage 4 or 5 chronic kidney disease (CKD; 5.9% vs. 6.8%, p = 0.11) were comparable. Our series provides little evidence that RD-SLKT would have yielded substantial short-term survival benefit to RD-LTA recipients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Vascular calcification and cardiac function according to residual renal function in patients on hemodialysis with urination.

PubMed

Shin, Dong Ho; Lee, Young-Ki; Oh, Jieun; Yoon, Jong-Woo; Rhee, So Yon; Kim, Eun-Jung; Ryu, Jiwon; Cho, Ajin; Jeon, Hee Jung; Choi, Myung-Jin; Noh, Jung-Woo

2017-01-01

Vascular calcification is common and may affect cardiac function in patients with end-stage renal disease (ESRD). However, little is known about the effect of residual renal function on vascular calcification and cardiac function in patients on hemodialysis. This study was conducted between January 2014 and January 2017. One hundred six patients with residual renal function on maintenance hemodialysis for 3 months were recruited. We used residual renal urea clearance (KRU) to measure residual renal function. First, abdominal aortic calcification score (AACS) and brachial-ankle pulse wave velocity (baPWV) were measured in patients on hemodialysis. Second, we performed echocardiography and investigated new cardiovascular events after study enrollment. The median KRU was 0.9 (0.3-2.5) mL/min/1.73m2. AACS (4.0 [1.0-10.0] vs. 3.0 [0.0-8.0], p = 0.05) and baPWV (1836.1 ± 250.4 vs. 1676.8 ± 311.0 cm/s, p = 0.01) were significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than a KRU ≥ 0.9 mL/min/1.73m2. Log-KRU significantly negatively correlated with log-AACS (ß = -0.29, p = 0.002) and baPWV (ß = -0.19, P = 0.05) after factor adjustment. The proportion of left ventricular diastolic dysfunction was significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than with a KRU ≥ 0.9 mL/min/1.73m2 (67.9% vs. 49.1%, p = 0.05). Patients with a KRU < 0.9 mL/min/1.73m2 showed a higher tendency of cumulative cardiovascular events compared to those with a KRU ≥ 0.9 ml/min/1.73m2 (P = 0.08). Residual renal function was significantly associated with vascular calcification and left ventricular diastolic dysfunction in patients on hemodialysis.

[Diagnosis and treatment of symptomatic hydronephrosis in pregnancy].

PubMed

Simonsen, Jane Angel; Graumann, Ole; Toft, Anja; Henriques, Carsten Ulrik; Walter, Steen

2015-09-14

Hydronephrosis in pregnancy is common in the second and third trimester. Only a few cases are symptomatic, caused by a ureteric stone or by the pregnancy itself. The clinical dilemma is when to treat and when not to treat. We propose a multidisciplinary management based on renal ultrasonography to verify hydronephrosis and renography to diagnose obstructive hydronephrosis. Obstruction with a high intra-renal pressure must be treated to avoid kidney dysfunction. Patients with pyonephrosis need immediate treatment.

The effect of methoxyflurane analgesia on renal function in burned patients: an investigation

PubMed Central

Laird, S. M.; Chrystal, Kathleen M. R.

1972-01-01

This paper reports an investigation into evidence of renal dysfunction following methoxyflurane analgesia for burns dressings. Twelve patients were studied and small increases in serum uric acid were observed in all of them. This increase may have been dose-related. Four patients had small but consistent increases in blood urea nitrogen and serum creatinine on the third post-dressing day. No definite conclusions can be adduced and further research is needed. PMID:5024150

The International Scoring System (ISS) for multiple myeloma remains a robust prognostic tool independently of patients' renal function.

PubMed

Dimopoulos, M A; Kastritis, E; Michalis, E; Tsatalas, C; Michael, M; Pouli, A; Kartasis, Z; Delimpasi, S; Gika, D; Zomas, A; Roussou, M; Konstantopoulos, K; Parcharidou, A; Zervas, K; Terpos, E

2012-03-01

The International Staging System (ISS) is the most widely used staging system for patients with multiple myeloma (MM). However, serum β2-microglobulin increases in renal impairment (RI) and there have been concerns that ISS-3 stage may include 'up-staged' MM patients in whom elevated β2-microglobulin reflects the degree of renal dysfunction rather than tumor load. In order to assess the impact of RI on the prognostic value of ISS, we analyzed 1516 patients with symptomatic MM and the degree of RI was classified according to the Kidney Disease Outcomes Quality Initiative-Chronic Kidney Disease (CKD) criteria. Forty-eight percent patients had stages 3-5 CKD while 29% of patients had ISS-1, 38% had ISS-2 and 33% ISS-3. The frequency and severity of RI were more common in ISS-3 patients. RI was associated with inferior survival in univariate but not in multivariate analysis. When analyzed separately, ISS-1 and ISS-2 patients with RI had inferior survival in univariate but not in multivariate analysis. In ISS-3 MM patients, RI had no prognostic impact either in univariate or multivariate analysis. Results were similar, when we analyzed only patients with Bence-Jones >200 mg/day. ISS remains unaffected by the degree of RI, even in patients with ISS-3, which includes most patients with renal dysfunction.

Myeloid-Derived Suppressor Cells Ameliorate Cyclosporine A-Induced Hypertension in Mice.

PubMed

Chiasson, Valorie L; Bounds, Kelsey R; Chatterjee, Piyali; Manandhar, Lochana; Pakanati, Abhinandan R; Hernandez, Marcos; Aziz, Bilal; Mitchell, Brett M

2018-01-01

The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice. Daily interleukin-33 treatment, which increased MDSC levels, completely prevented CsA-induced hypertension and vascular and renal toxicity. Adoptive transfer of MDSCs from control mice into CsA-treated mice after hypertension was established dose-dependently reduced blood pressure and vascular and glomerular injury. CsA treatment of aortas and kidneys isolated from control mice for 24 hours decreased relaxation responses and increased inflammation, respectively, and these effects were prevented by the presence of MDSCs. MDSCs also prevented the CsA-induced increase in fibronectin in microvascular and glomerular endothelial cells. Last, CsA dose-dependently reduced the number of MDSCs by inhibiting calcineurin and preventing cell proliferation, as other direct calcineurin signaling pathway inhibitors had the same dose-dependent effect. These data suggest that augmenting MDSCs can reduce the cardiovascular and renal toxicity and hypertension caused by CsA. © 2017 American Heart Association, Inc.

Sorting Nexin 1 Loss Results in D5 Dopamine Receptor Dysfunction in Human Renal Proximal Tubule Cells and Hypertension in Mice*

PubMed Central

Villar, Van Anthony M.; Jones, John Edward; Armando, Ines; Asico, Laureano D.; Escano, Crisanto S.; Lee, Hewang; Wang, Xiaoyan; Yang, Yu; Pascua-Crusan, Annabelle M.; Palmes-Saloma, Cynthia P.; Felder, Robin A.; Jose, Pedro A.

2013-01-01

The peripheral dopaminergic system plays a crucial role in blood pressure regulation through its actions on renal hemodynamics and epithelial ion transport. The dopamine D5 receptor (D5R) interacts with sorting nexin 1 (SNX1), a protein involved in receptor retrieval from the trans-Golgi network. In this report, we elucidated the spatial, temporal, and functional significance of this interaction in human renal proximal tubule cells and HEK293 cells stably expressing human D5R and in mice. Silencing of SNX1 expression via RNAi resulted in the failure of D5R to internalize and bind GTP, blunting of the agonist-induced increase in cAMP production and decrease in sodium transport, and up-regulation of angiotensin II receptor expression, of which expression was previously shown to be negatively regulated by D5R. Moreover, siRNA-mediated depletion of renal SNX1 in C57BL/6J and BALB/cJ mice resulted in increased blood pressure and blunted natriuretic response to agonist in salt-loaded BALB/cJ mice. These data demonstrate a crucial role for SNX1 in D5R trafficking and that SNX1 depletion results in D5R dysfunction and thus may represent a novel mechanism for the pathogenesis of essential hypertension. PMID:23152498

Mortality predictors in renal transplant recipients with severe sepsis and septic shock.

PubMed

de Carvalho, Mônica Andrade; Freitas, Flávio Geraldo Rezende; Silva Junior, Hélio Tedesco; Bafi, Antônio Toneti; Machado, Flávia Ribeiro; Pestana, José Osmar Medina

2014-01-01

The growing number of renal transplant recipients in a sustained immunosuppressive state is a factor that can contribute to increased incidence of sepsis. However, relatively little is known about sepsis in this population. The aim of this single-center study was to evaluate the factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit (ICU) with severe sepsis and septic shock. Patient demographics and transplant-related and ICU stay data were retrospectively collected. Multiple logistic regression was conducted to identify the independent risk factors associated with hospital mortality. A total of 190 patients were enrolled, 64.2% of whom received kidneys from deceased donors. The mean patient age was 51 ± 13 years (males, 115 [60.5%]), and the median APACHE II was 20 (16-23). The majority of patients developed sepsis late after the renal transplantation (2.1 [0.6-2.3] years). The lung was the most common infection site (59.5%). Upon ICU admission, 16.4% of the patients had ≤ 1 systemic inflammatory response syndrome criteria. Among the patients, 61.5% presented with ≥ 2 organ failures at admission, and 27.9% experienced septic shock within the first 24 hours of ICU admission. The overall hospital mortality rate was 38.4%. In the multivariate analysis, the independent determinants of hospital mortality were male gender (OR = 5.9; 95% CI, 1.7-19.6; p = 0.004), delta SOFA 24 h (OR = 1.7; 95% CI, 1.2-2.3; p = 0.001), mechanical ventilation (OR = 30; 95% CI, 8.8-102.2; p<0.0001), hematologic dysfunction (OR = 6.8; 95% CI, 2.0-22.6; p = 0.002), admission from the ward (OR = 3.4; 95% CI, 1.2-9.7; p = 0.02) and acute kidney injury stage 3 (OR = 5.7; 95% CI,1.9-16.6; p = 0.002). Hospital mortality in renal transplant patients with severe sepsis and septic shock was associated with male gender, admission from the wards, worse SOFA scores on the first day and the presence of hematologic dysfunction, mechanical ventilation or advanced graft dysfunction.

Low serum zinc is associated with elevated risk of cadmium nephrotoxicity

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

Lin, Yu-Sheng, E-mail: Lin.Yu-Sheng@epa.gov; Ho, Wen-Chao; Caffrey, James L.

Background: Despite animal evidence suggests that zinc modulates cadmium nephrotoxicity, limited human data are available. Objective: To test the hypothesis that low serum zinc concentrations may increase the risk of cadmium-mediated renal dysfunction in humans. Methods: Data from 1545 subjects aged 20 or older in the National Health and Nutrition Examination Survey (NHANES), 2011–2012 were analyzed. Renal function was defined as impaired when estimated glomerular filtration rate (eGFR) fell below 60 ml/min/1.73 m{sup 2} and/or the urinary albumin-to-creatinine ratio surpassed 2.5 in men and 3.5 mg/mmol in women. Results: Within the study cohort, 117 subjects had reduced eGFR and 214more » had elevated urinary albumin. After adjusting for potential confounders, subjects with elevated blood cadmium (>0.53 μg/L) were more likely to have a reduced eGFR (odds ratio [OR]=2.21, 95% confidence interval [CI]: 1.09–4.50) and a higher urinary albumin (OR=2.04, 95% CI: 1.13–3.69) than their low cadmium (<0.18 μg/L) peers. In addition, for any given cadmium exposure, low serum zinc is associated with elevated risk of reduced eGFR (OR=3.38, 95% CI: 1.39–8.28). A similar increase in the odds ratio was observed between declining serum zinc and albuminuria but failed to reach statistical significance. Those with lower serum zinc/blood cadmium ratios were likewise at a greater risk of renal dysfunction (p<0.01). Conclusions: This study results suggest that low serum zinc concentrations are associated with an increased risk of cadmium nephrotoxicity. Elevated cadmium exposure is global public health issue and the assessment of zinc nutritional status may be an important covariate in determining its effective renal toxicity. - Highlights: • Blood cadmium was associated with increased risk of nephrotoxicity. • Low serum zinc may exacerbate risk of cadmium-mediated renal dysfunction. • Both zinc deficiency and elevated cadmium exposure are global public health issues. • Nutritional status is important in the assessment of cadmium nephrotoxicity.« less

Detection of relationships between SUDOSCAN with estimated glomerular filtration rate (eGFR) in Chinese patients with type 2 diabetes.

PubMed

Mao, Fei; Zhu, Xiaoming; Lu, Bin; Li, Yiming

2018-04-01

SUDOSCAN (Impeto Medical, Paris, France) has been proved to be a new and non-invasive method in detecting renal dysfunction in type 2 diabetes mellitus (T2DM) patients. In this study, we sought to compare the result of diabetic kidney dysfunction score (DKD-score) of SUDOSCAN with estimated glomerular filtration rate (eGFR) by using quantile regression analysis, which was completely different from previous studies. A total number of 223 Chinese T2DM patients were enrolled in the study. SUDOSCAN, renal function test (including blood urea nitrogen, creatinine and uric acid) and 99 mTc-diethylenetriamine pentaacetic acid ( 99 mTc-DTPA) renal dynamic imaging were performed in all T2DM patients. DKD-score of SUDOSCAN was compared with eGFR detected by 99 mTc-DTPA renal dynamic imaging through quantile regression analysis. Its validation and utility was further determined through bias and precision test. The quantile regression analysis demonstrated the relationship with eGFR was inverse and significant for almost all percentiles of DKD-score. The coefficients decreased as the percentile of DKD-score increased. And in validation data set, both the bias and precision were increased with the eGFR (median difference, -21.2 ml/min/1.73 m 2 for all individuals vs. -4.6 ml/min/1.73 m 2 for eGFR between 0 and 59 ml/min/1.73 m 2 ; interquartile range [IQR] for the difference, -25.4 ml/min/1.73 m 2 vs. -14.7 ml/min/1.73 m 2 ). The eGFR category misclassification rate were 10% in eGFR 0-59 ml/min/1.73 m 2 group, 57.3% in 60-90 group, and 87.2% in eGFR > 90 ml/min/1.73 m 2 group. DKD-score of SUDOSCAN could be used to detect renal dysfunction in T2DM patients. A higher prognostic value of DKD-score was detected when eGFR level was lower. Copyright © 2018 Elsevier B.V. All rights reserved.