Significant Renal Dysfunction Research Articles

Renal function changes after fenestrated endovascular aneurysm repair

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 11.7months. A total of 206 renal stents were placed, with a mean aneurysm size of 62.9mm (range, 45-105mm) and a mean neck length of 4.1mm. 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± 19.6mL/min/1.73m2. 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 1year 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.

Transcatheter Mitral Valve Implantation: 30-day Outcome of First-in-Man Experience With an Apically Tethered Device.

A small number of transcatheter mitral valve implants (TMVIs) have been reported using devices designed to treat secondary mitral regurgitation (MR). However, MR has many etiologies, and patients have a broad spectrum of annular size, geometry, and lesions. There are a number of technical challenges for TMVI including left ventricular outflow tract obstruction and paravalvular MR. Thirty days' outcome of first-in-man implants with a novel TMVI device is reported. The Tendyne TMVI system consists of a porcine pericardial valve in a tethered nitinol frame. An apical tether fixed to an epicardial pad stabilizes the device. The device is fully repositionable and retrievable even after complete deployment. Preoperative assessment was performed with 3-dimensional (3D) transesophageal echocardiogram and multislice computed tomography to define annular dimensions, geometry, and guide surgical access. Three patients were deemed not to be candidates for conventional surgery or for treatment with any Conformitè Européenne-marked device by Heart Team Evaluation. They were a 68-year-old woman with prior coronary artery bypass grafts and severe functional MR; a 75-year-old man with prior coronary bypass grafts, significant renal dysfunction, and severe degenerative MR; and a frail 86-year-old man with severe degenerative MR. Each had a TMVI via a transapical approach through a left minithoracotomy. Apical tether tension was adjusted to optimize device position. Implantation was guided by 2D and 3D transesophageal echocardiogram. The apical pad facilitated LV apical closure. There were no procedural complications. No patient had hemodynamically significant residual MR or left ventricular outflow tract obstruction, and there was no significant mitral gradient. All patients were discharged to their own home (the third on the fifth postoperative day), all with significant improvement in their symptoms. All were alive and well 30 days after implant. Two patients with existing conduction abnormalities had cardiac resynchronisation therapy after the procedure, and one patient had para valvular leak (PVL) with evidence of hemolysis at 30 days, which reduced in severity with conservative treatment. The first-in-man experience with the Tendyne TMVI system is promising. Valve stabilization by an apical tether is a novel way to address some of the challenges of TMVI. The unique Tendyne design features may offer potential for its use across a wide range of mitral valve pathologies.

Analysis of 25-Hydroxyvitamin D Status According to Age, Gender, and Seasonal Variation.

The effects of age, gender, and seasonal variation on human levels of 25-hydroxyvitamin D (25(OH)D) are not well understood. In this study, we aimed to investigate 25(OH)D status according to these factors in a Korean population. A total of 303,943 serum 25(OH)D levels were measured using an electrochemiluminescence immunoassay between October 2011 and May 2014. Potential participants were ineligible for the study if they had significant renal, hepatic, or thyroid dysfunction, as well as any major ongoing disease that could influence serum 25(OH)D levels. A total of 95,137 subjects (49,662 men and 45,475 women) were included in this study. The mean 25(OH)D levels were higher in men (42.4 nmol/l) than in women (32.9 nmol/l, P < 0.001). Among the men and women, 73.0% and 88.9%, respectively, had 25(OH)D levels <50 nmol/l, whereas only 3.8% of men and 1.4% of women had levels >75 nmol/l. The highest mean 25(OH)D value was noted in individuals aged ≥70 for both genders. The proportion of those with 25(OH)D levels <50 nmol/l appeared to be higher among younger subjects (P < 0.001). Lastly, there were significant differences between 25(OH)D levels in individuals during summer to fall and winter to spring in both genders, indicating seasonal periodicity (P < 0.001). Serum 25(OH)D status varied according to gender, age, and season. Therefore, analyses of vitamin D status require individualized gender, age, and seasonally adjusted thresholds. Clinicians should consider these factors when determining optimal serum 25(OH)D levels in clinical practice.

Anaesthesia for nephrectomy

### Key points This paper will summarize the perioperative anaesthetic considerations for patients undergoing nephrectomy for both non-neoplastic and neoplastic disease of the kidney. It does not include the management of patients undergoing living donor nephrectomy. Nephrectomy for patients with renal cell carcinoma (RCC) was first described in 1969.1 Surgical treatment varies with the pathology. Simple nephrectomy is the preferred option for those with non-neoplastic disease (e.g. trauma, non-functioning kidney with chronic infection) with radical nephrectomy being preferred in those with neoplastic disease. Radical nephrectomy implies resection of the whole of Gerota's fascia, including the perinephric fat, lymphatics, and the ipsilateral adrenal gland. The vast majority (∼90%) of solid renal masses are RCC; the remainder comprising mainly of transitional cell carcinoma or Wilm's tumour (in children). RCC accounts for between 1% and 3% of all visceral malignancies. It is twice as common in men when compared with women and most commonly presents in the seventh decade of life. The main environmental risk factor is cigarette smoking, contributing to one-third of all cases. Other important risk factors include obesity, hypertension, asbestos exposure, and acquired polycystic kidney disease. If symptomatic, presentation is usually with haematuria, loin pain, and a palpable mass. Non-specific symptoms such as malaise, …

Renin-angiotensin system inhibitors and fibrosis in chronic liver disease: a systematic review.

The renin-angiotensin system (RAS) has an important role in hepatic fibrosis and portal hypertension. RAS inhibitors are already accepted in clinical fields for antihypertensive management, but their effects on hepatic fibrosis are controversial. The aim of this study was to systematically review the effects of RAS inhibitors on hepatic fibrosis based on histological assessment. We performed a systematic review and meta-analysis (MA) of the literature using the Ovid-MEDLINE, EMBASE, and Cochrane Library databases (up to January 2015) to identify clinical studies evaluating the effects of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on hepatic fibrosis or cirrhosis patients based on histological assessment. Of the 455 studies identified, we analyzed 7, including a total of 1066 patients, which met our selection criteria. According to the MA, patients treated with RAS inhibitors had significantly lower fibrosis scores (SMD -0.68, 95% CI -1.03, -0.34, I (2)=0%, p<0.0001) and smaller fibrosis areas (SMD -0.80, 95% CI -1.18, -0.41, I (2)=0%, p<0.0001) than controls. Serum fibrosis markers such as TGF-β1, collagen I, IV, TIMP-1, and MMP2 were significantly reduced in the intervention group. In two studies, mean arterial pressures were significantly decreased in RAS inhibitor users, but there were no reports about symptoms related to decreased blood pressure. No significant difference was found in serum creatinine levels between the intervention and control groups, and significant renal dysfunction was not observed after administration of RAS inhibitors. RAS inhibitors are potential therapeutic agents for hepatic fibrosis, which can be safely used in patients with chronic liver disease.

Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

The pathogenesis of renal impairment in chronic liver diseases (CLDs) has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy), autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet–fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the pathophysiological mechanisms of sublethal tubular cell injury.

Segmental strain analysis by deformation of a mesh model: comparison of segmental strain metrics and late gadolinium enhancement quantification in myocardial infarction

Background The presence and transmurality of posterolateral scar within the left ventricle by late gadolinium enhancement (LGE) imaging has been shown to portend poor response to cardiac resynchronization therapy due to placement of the LV lead in this region. Unfortunately, the use of gadolinium is contraindicated in patients with significant renal dysfunction due to the risk of nephrogenic systemic fibrosis. Alternative measures of regional myocardial non-viability by 4D strain analysis may be highly useful for CRT evaluation in patients with heart failure and renal dysfunction.

Therapeutic insight into molsidomine, a nitric oxide donor in streptozotocin-induced diabetic nephropathy in rats.

Background:Diabetes-induced oxidative stress and hypertension play a major role in the development of nephropathy. Hence, the present study was undertaken to evaluate the protective effects of molsidomine, a nitric oxide donor in streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats.Materials and Methods:Type 1 diabetes was induced through a single dose of STZ (52 mg/kg, i.p.) in male Wistar rats and then treated with molsidomine (5 and 10 mg/kg; p.o.) for 8 weeks. Physical parameters, vital and renal function test including blood glucose, albuminuria, blood urine nitrogen, serum creatinine, and kidney index were determined. Oxidative stress and lipid peroxidation were assessed in the kidney homogenate by means of antioxidant enzymes and malondialdehyde levels.Results:DN rats exhibited a significant renal dysfunction with a reduction in body weight, excessive oxidative stress, and pathological changes. Molsidomine treatment significantly improved vital sign, renal functions, and oxidative stress in DN rats in a dose-dependent manner. The protective effect of molsidomine was also substantiated by pathological changes in the architect of the kidney.Conclusion:Molsidomine shows a significant beneficial effect in Type 1 DN in rats.

Combined Lung-Kidney Transplantation: An Analysis of the UNOS/OPTN Database

Poor outcomes after thoracic transplantation with concurrent renal dysfunction are well described: without transplantation or with thoracic-only transplantation, patients face unacceptably high mortality. Outcomes after combined lung-kidney transplantation (LKT) remain largely uninvestigated. The United Network for Organ Sharing/Organ Procurement and Transplantation Network database was queried to identify all LKTs, lung transplantations (LTs), and kidney transplantations (KTs) performed in the United States from 1995 to 2013. Survival was calculated using the Kaplan-Meier method and compared using log-rank tests or Cox regression models. Thirty-one LKTs were performed. Mean recipient age was 45.4 ± 13.5 years; 48.3 per cent were male. Retransplantation for graft failure was the leading indication for LT (n = 13) and the most common renal indication was calcineurin inhibitor nephrotoxicity (n = 11). Mean lung allocation score was 46.6 ± 14.4, mean creatinine was 3.7 ± 2.8 g/dL, and glomerular filtration rate was 23.1 (interquartile range 11.9, 38.3) mL/min/1.7 m(2), and 11 (35.5%) were dialysis dependent. Patient survival after LKT was 92.9 per cent, 71.0 per cent, and 71.0 per cent at one month, six months, and one year, with a median survival of 95.2 months. One- and five-year survival after LKT, 71.0 per cent and 59.9 per cent, were similar to LT (n = 23,913), 81.7 per cent and 51.4 per cent (P = 0.061 and 0.55), and inferior to KT (n = 175,269), 94.9 per cent and 82.8 per cent (P < 0.0001), respectively. Patient survival after LKT was similar to isolated LT, and these results suggest that LKT is a feasible therapeutic option for LT candidates with significant renal dysfunction.

Risk factors for renal dysfunction after total hip joint replacement; a retrospective cohort study.

Background and purpose of the studyRenal 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 hip joint replacement surgery.MethodsA retrospective study was conducted among 599 consecutive primary hip joint replacements performed between January 2011 and December 2013. According to the RIFLE criteria, increased postoperative serum creatinine was considered indicative of postoperative renal injury. The Welch two-sample test, chi-square test, and Fisher exact test were used for statistical analysis.ResultsEighty-one patients (13.8 %) had significant moderate or severe postoperative renal dysfunction in which 10 patients (1.7 %) acquired severe and permanent renal impairment.ConclusionWe identified advanced age, hypertension, general anesthesia, high ASA scores, low intra-operative systolic BP, and prophylactic dicloxacillin as significant risk factors. Low baseline systolic BP, low baseline diastolic blood pressure, and hip fracture diagnosis were independent risk factors for postoperative increase in serum creatinine. Smoking, diabetes mellitus, high BMI, gender, and duration of surgery were not identified as significant risk factors.

Single baseline serum creatinine measurements predict mortality in critically ill patients hospitalized for acute heart failure.

BackgroundAcute heart failure (AHF) is a leading cause of death in critically ill patients and is often accompanied by significant renal dysfunction. Few data exist on the predictive value of measures of renal dysfunction in large cohorts of patients hospitalized for AHF.MethodsSix hundred and eighteen patients hospitalized for AHF (300 male, aged 73.3 ± 10.3 years, 73% New York Heart Association Class 4, mean hospital length of stay 12.9 ± 7.7 days, 97% non‐ischaemic AHF) were included in a retrospective single‐centre data analysis. Echocardiographic data, serum creatinine/urea levels, estimated glomerular filtration rate (eGFR), and clinical/laboratory markers were recorded. Mean follow‐up time was 2.9 ± 2.1 years. All‐cause mortality was recorded, and univariate/multivariate analyses were performed.ResultsNormal renal function defined as eGFR > 90 mL/min/1.73 m2 was noted in only 3% of AHF patients at baseline. A significant correlation of left ventricular ejection fraction with serum creatinine levels and eGFR (all P < 0.002) was noted. All‐cause mortality rates were 12% (90 days) and 40% (at 2 years), respectively. In a multivariate model, increased age, higher New York Heart Association class at admission, higher total cholesterol levels, and lower eGFR independently predicted death. Patients with baseline eGFR < 30 mL/min/1.73 m2 had an exceptionally high risk of death (odds ratio 2.80, 95% confidence interval 1.52–5.15, P = 0.001).ConclusionsIn a large cohort of patients with mostly non‐ischaemic AHF, enhanced serum creatinine levels and reduced eGFR independently predict death. It appears that patients with eGFR < 30 mL/min/1.73 m2 have poorest survival rates. Our data add to mounting data indicating that impaired renal function is an important risk factor for non‐survival in patients hospitalized for AHF.

The effects of palladium nanoparticles on the renal function of female Wistar rats

A number of studies have shown that palladium nanoparticles are able to exert some adverse health effects, such as concentration-dependent cytotoxicity, induction of apoptosis and alterations of the release and expression of numerous cytokines. Nevertheless, our current knowledge of the potential toxic effects induced by exposure to these nanoparticles is far from being complete. For this reason, the present study assessed the possible renal toxicity of palladium nanoparticles by investigating urinary excretion of retinol binding protein, β2-microglobulin and albumin in female Wistar rats intravenously exposed to different nanoparticle concentrations (0.012, 0.12, 1.2 and 12 µg/kg) and by carrying out a morphological observation of the kidneys of treated animals. Results showed a significant increase in urinary retinol binding protein and β2-microglobulin levels in rats that were administered 12 µg/kg compared to controls. Moreover, an ultrastructural study of the kidneys revealed significant alterations in the proximal and distal tubular epithelium were observed, with a range of severity, in all experimental conditions. Collectively, our findings suggest that exposure to palladium nanoparticles is able to induce a significant renal tubular dysfunction, whereas it does not seem to affect kidney glomerular filtration. However, further studies are needed to confirm our results, to understand the molecular mechanisms of toxic action and to evaluate the potential adverse effects of these nanoparticles also on the glomerular section of the kidney.

Update on glycemic control for the treatment of diabetic kidney disease.

Diabetic kidney disease (DKD) is a common, complex condition that has become a significant public health problem. The beneficial effects of intensive glycemic control in type 1 diabetes mellitus on development of DKD are proven; however, the evidence for nephroprotection in patients with type 2 diabetes is conflicting. Moreover, a strategy of intensive glycemic control increases the risk for adverse effects (hypoglycemic episodes) with no obvious impact on macrovascular events or mortality in recent large randomized controlled trials. The risk for hypoglycemia with intensive therapy is heightened in patients with significant renal dysfunction, due to decreased renal clearance of insulin. Establishing an ideal level of glycemic control in patients requires an individualized approach taking into account duration of diabetes and presence of coexisting comorbidities and pre-existing DKD. In this article, we review the available evidence from both observational studies and randomized controlled trials and provide suggestions about evaluating the potential benefits and harm from intensive glycemic control in patients. We also discuss how in the future, a personalized approach using biomarkers might help identify patients most likely to respond as well as those most susceptible to harm. We believe that using the optimal level of glycemic control in diabetic patients using a multi-pronged strategy will improve individual patient outcomes and decrease the overall burden of morbidity and mortality.

(670) - Assessment of Human Lungs Recovered From Uncontrolled Donation After Circulatory Determination of Death (uDCDD) Donors By Ex-Vivo Lung Perfusion (EVLP) and CT Scan

s S247 Methods: The UNOS/OPTN database was queried to identify all LKT, LT, and KT performed in the U.S. from 1995-2013. Survival was calculated using the Kaplan-Meier method & compared using log-rank tests or Cox regression models. Results: Thirty-one LKT, including 3 heart-lung-kidney transplants, were performed. Median follow-up was 14.46 months (19 days 8.51 years). The mean age of LKT recipients was 44.8 ± 13.1 years & 48% were male. Redo lung transplant for graft failure was the leading indication for LT (n= 13), followed by cystic fibrosis (n= 4). The most common renal indication was calcineurin inhibitor nephrotoxicity (n= 11). Mean lung allocation score (LAS) was 46.6 ± 14.4. No patient required extracorporeal membrane oxygenation. Mean creatinine was 3.7 ± 2.8 mg/dL, MDRD estimated GFR was 26.1 ± 17.6 mL/min/1.73m2, & 11 patients were dialysis-dependent. Ischemic time for lung & kidney grafts was 4.6 ± 1.7 & 12.6 ± 8.1 hours. Patient survival after LKT was 93%, 71%, & 71% at 1 month, 6 months, & 1 year with median survival 95.2 months. Relative to single-organ transplant, 1 & 5 year survival after LKT, 71% & 60%, were similar to LT (n= 23,913), 82% & 51% (p = 0.061 & 0.55), & inferior to KT (n= 175,269), 95% & 83% (p < 0.0001). Outcomes improved in the LAS era: 1 & 5 year survival for LKT (n= 23) were 78% & 72% & remained similar to LT (n= 12,755), 84% & 53% (p = 0.30 & 0.88). Redo status did not increase mortality after LKT at 1 (HR 1.05, 95% CI [0.28, 3.93] & 4 years (HR 1.18 [0.36, 3.88]), in contrast to significantly increased mortality after LT: HR 1.89 [1.68, 2.14] & HR 1.75 [1.60,1.92]. Conclusion: This is the first study to describe outcomes after lung-kidney transplantation. Patient survival following lung-kidney transplant is similar to lung-only transplant & is an acceptable option for lung-transplant candidates with significant renal dysfunction.

(667) - Frailty Is Associated With Increased Mortality and Hospitalization in COPD

s S247 Methods: The UNOS/OPTN database was queried to identify all LKT, LT, and KT performed in the U.S. from 1995-2013. Survival was calculated using the Kaplan-Meier method & compared using log-rank tests or Cox regression models. Results: Thirty-one LKT, including 3 heart-lung-kidney transplants, were performed. Median follow-up was 14.46 months (19 days 8.51 years). The mean age of LKT recipients was 44.8 ± 13.1 years & 48% were male. Redo lung transplant for graft failure was the leading indication for LT (n= 13), followed by cystic fibrosis (n= 4). The most common renal indication was calcineurin inhibitor nephrotoxicity (n= 11). Mean lung allocation score (LAS) was 46.6 ± 14.4. No patient required extracorporeal membrane oxygenation. Mean creatinine was 3.7 ± 2.8 mg/dL, MDRD estimated GFR was 26.1 ± 17.6 mL/min/1.73m2, & 11 patients were dialysis-dependent. Ischemic time for lung & kidney grafts was 4.6 ± 1.7 & 12.6 ± 8.1 hours. Patient survival after LKT was 93%, 71%, & 71% at 1 month, 6 months, & 1 year with median survival 95.2 months. Relative to single-organ transplant, 1 & 5 year survival after LKT, 71% & 60%, were similar to LT (n= 23,913), 82% & 51% (p = 0.061 & 0.55), & inferior to KT (n= 175,269), 95% & 83% (p < 0.0001). Outcomes improved in the LAS era: 1 & 5 year survival for LKT (n= 23) were 78% & 72% & remained similar to LT (n= 12,755), 84% & 53% (p = 0.30 & 0.88). Redo status did not increase mortality after LKT at 1 (HR 1.05, 95% CI [0.28, 3.93] & 4 years (HR 1.18 [0.36, 3.88]), in contrast to significantly increased mortality after LT: HR 1.89 [1.68, 2.14] & HR 1.75 [1.60,1.92]. Conclusion: This is the first study to describe outcomes after lung-kidney transplantation. Patient survival following lung-kidney transplant is similar to lung-only transplant & is an acceptable option for lung-transplant candidates with significant renal dysfunction.

(668) - 100 Lung Transplants Delivered in Ireland

s S247 Methods: The UNOS/OPTN database was queried to identify all LKT, LT, and KT performed in the U.S. from 1995-2013. Survival was calculated using the Kaplan-Meier method & compared using log-rank tests or Cox regression models. Results: Thirty-one LKT, including 3 heart-lung-kidney transplants, were performed. Median follow-up was 14.46 months (19 days 8.51 years). The mean age of LKT recipients was 44.8 ± 13.1 years & 48% were male. Redo lung transplant for graft failure was the leading indication for LT (n= 13), followed by cystic fibrosis (n= 4). The most common renal indication was calcineurin inhibitor nephrotoxicity (n= 11). Mean lung allocation score (LAS) was 46.6 ± 14.4. No patient required extracorporeal membrane oxygenation. Mean creatinine was 3.7 ± 2.8 mg/dL, MDRD estimated GFR was 26.1 ± 17.6 mL/min/1.73m2, & 11 patients were dialysis-dependent. Ischemic time for lung & kidney grafts was 4.6 ± 1.7 & 12.6 ± 8.1 hours. Patient survival after LKT was 93%, 71%, & 71% at 1 month, 6 months, & 1 year with median survival 95.2 months. Relative to single-organ transplant, 1 & 5 year survival after LKT, 71% & 60%, were similar to LT (n= 23,913), 82% & 51% (p = 0.061 & 0.55), & inferior to KT (n= 175,269), 95% & 83% (p < 0.0001). Outcomes improved in the LAS era: 1 & 5 year survival for LKT (n= 23) were 78% & 72% & remained similar to LT (n= 12,755), 84% & 53% (p = 0.30 & 0.88). Redo status did not increase mortality after LKT at 1 (HR 1.05, 95% CI [0.28, 3.93] & 4 years (HR 1.18 [0.36, 3.88]), in contrast to significantly increased mortality after LT: HR 1.89 [1.68, 2.14] & HR 1.75 [1.60,1.92]. Conclusion: This is the first study to describe outcomes after lung-kidney transplantation. Patient survival following lung-kidney transplant is similar to lung-only transplant & is an acceptable option for lung-transplant candidates with significant renal dysfunction.

Renal function in survivors of nonsyndromic Wilms tumor treated with unilateral radical nephrectomy.

Partial nephrectomy is considered by some for children with unilateral Wilms tumor (UWT) to avoid the theoretical complication of renal insufficiency. In the current study, the authors evaluated the prevalence of hypertension and impaired renal function in long-term survivors of nonsyndromic UWT who were treated without nephrotoxic chemotherapy or ionizing radiation. Eligibility included age ≤15 years at the time of diagnosis of nonsyndromic UWT, treatment receipt before 2002, and maintenance of disease remission after unilateral nephrectomy without receipt of abdominal irradiation or nephrotoxic chemotherapy. Renal function was assessed by urinalysis and estimated glomerular filtration rate (eGFR). Patients receiving antihypertensive medication or those with blood pressure readings of >140/90 mm Hg were considered to be hypertensive. A total of 75 patients with a median age at diagnosis of 3.2 years (range, 0.2-12.1 years) met eligibility criteria. The median length of follow-up was 19.6 years (range, 10.0-32.8 years). All but 1 patient had stage I/II disease. Sixty-eight patients (90.7%) patients had WT with favorable histology and 7 patients had anaplastic histology. Sixteen patients (21.3%) had an eGFR <90 mL/minute/1.73m(2), 2 of whom also had proteinuria (12.5%). No patient had an eGFR <60 mL/minute/1.73m(2). Five patients (6.7%) had hypertension, 3 of whom were receiving antihypertensive medications. At the time of last follow-up, no patient had developed end-stage renal disease. Patients with UWT who were treated with unilateral radical nephrectomy without nephrotoxic chemotherapy or ionizing radiation appear to be at low risk of developing significant long-term renal dysfunction. For this patient population, the routine use of partial nephrectomy does not appear justified. However, monitoring and counseling are important for identifying the rare patient who develops subtle renal insufficiency and therefore might be at an increased risk of adverse cardiovascular sequelae.

BAY 11-7082 ameliorates diabetic nephropathy by attenuating hyperglycemia-mediated oxidative stress and renal inflammation via NF-κB pathway

Diabetic nephropathy is a serious microvascular complication for patients associated with diabetes mellitus. Recent studies have suggested that NF-κB is the main transcription factor for the inflammatory response mediated progression of diabetic nephropathy. Hence, the present study is hypothesized to explore the renoprotective nature of BAY 11-7082 an IκB phosphorylation inhibitor on Streptozotocin (STZ) induced diabetic nephropathy in Sprague-Dawley (SD) rats. Male SD rats were divided into five groups, group I sham control, group II drug control, group III diabetic control (STZ 50mg/kg), group IV and V are test drug groups to which a single dose of STZ 50mg/kg was injected initially and later received BAY 11-7082 1mg/kg and 3mg/kg, respectively from 5th to 8th week. Eight weeks after STZ injection, diabetic rats exhibited significant renal dysfunction, as evidenced by reduced creatinine clearance, increased blood glucose, urea nitrogen and creatinine, which were reversed to near normal by BAY 11-7082. BAY 11-7082 treated rats showed significant improvement in the decreased enzymatic antioxidant SOD, non-enzymatic antioxidant GSH levels, and elevated lipid peroxidation and nitric oxide levels as observed in the diabetic rats. BAY 11-7082 treatment was found to significantly recover kidney histological architecture in the diabetic rats. Altered levels of inflammatory cytokines like TNF-α, IL-1β, IL-6 and nuclear transcriptional factor subunit NF-κB p65 were reverted to the normal level upon treatment with BAY 11-7082. Our results suggest that by limiting the activation of NF-κB, thereby reducing the expression of inflammatory cytokines and by inhibiting the oxidative damage BAY 11-7082 protect the rats against diabetic nephropathy.

Дисфункция почек у больных ишемической болезнью сердца

We studied effects of various forms of coronary heart disease on the progression of renal dysfunction. Three groups of patients were examined: 1--patients with exertional angina (n = 29), 2--patients with old myocardial infarction (postinfarction cardiosclerosis) and exertional angina (n = 22), 3--patients with atrial fibrillation and exertional angina (n = 21). Most pronounced anatomic and functional abnormalities of cardiac action and respective statistically more significant renal dysfunction were revealed in group 3.

Predictors of Hyperkalemia Risk after Hypertension Control with Aldosterone Blockade according to the Presence or Absence of Chronic Kidney Disease

Background/Aims: Aldosterone antagonists have been proven to be efficient in the management of hypertension and the reduction of proteinuria; however, they are not widely used because of the risk of hyperkalemia. We assessed the predictors of hyperkalemia risk following hypertension control using aldosterone blockade in the presence or absence of chronic kidney disease (CKD). Methods: A total of 6,575 patients with hypertension treated between January 1, 2000, and November 30, 2012, were evaluated for the safety of an aldosterone-blocking agent (spironolactone) added to preexisting blood pressure-lowering regimens. Hyperkalemia was defined as a serum potassium level ≥5.0 mEq/l. All patients used 3 mechanistically complementary antihypertensive agents, including a diuretic and a RAAS blocker. Patients were evaluated after 4 and 8 weeks of treatment. The incidence of hyperkalemia, significant renal dysfunction [a reduction of the estimated glomerular filtration rate (eGFR) ≥30%], and adverse effects was assessed. Results: The incidence of hyperkalemia in the presence or absence of CKD was 50.4 and 42.6% after 4 weeks (p = 0.001) and 3.8 and 3.0% after 8 weeks, respectively (p = 0.371). A logistic regression analysis revealed that medication, CKD, basal hyperkalemia, reduction in eGFR, and diabetes were all predictive of a hyperkalemia risk following spironolactone use. Conclusion: Spironolactone was well tolerated by selected CKD patients. The risk of serious hyperkalemia or a significant reduction of eGFR appears to be low. Strict monitoring over the first month of treatment followed by standard surveillance for angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers is suggested.