Podocyte depletion leads to glomerulosclerosis, but whether an impaired capacity of podocytes to respond to hypertrophic stress also causes glomerulosclerosis is unknown. We generated transgenic Fischer 344 rats that express a dominant negative AA-4E-BP1 transgene driven by the podocin promoter; a member of the mammalian target of rapamycin complex 1 (mTORC1) pathway, 4E-BP1 modulates cap-dependent translation, which is a key determinant of a cell's hypertrophic response to nutrients and growth factors. AA-4E-BP1 rat podocytes expressed the transgene and had normal kidney histology and protein excretion at 100 g of body weight but developed ESRD by 12 months. Proteinuria and glomerulosclerosis were linearly related to both increasing body weight and transgene dose. Uni-nephrectomy reduced the body weight at which proteinuria first developed by 40%-50%. The initial histologic manifestation of disease was the appearance of bare areas of glomerular basement membrane from the pulling apart of podocyte foot processes, followed by adhesions to the Bowman capsule. Morphometric analysis confirmed the mismatch between glomerular tuft volume and total podocyte volume (number 3 size) per tuft in relation to weight gain and nephrectomy. Proteinuria and glomerulosclerosis did not develop if dietary calorie restriction prevented weight gain and glomerular enlargement. In summary, failure of podocytes to match glomerular tuft growth in response to growth signaling through the mTORC1 pathway can trigger proteinuria, glomerulosclerosis, and progression to ESRD. Reducing body weight and glomerular growth may be useful adjunctive therapies to slow or prevent progression to ESRD.

Background and objectives Little is known regarding whether mortality among ESRD patients with SLE differs between those initiating with peritoneal dialysis (PD) versus hemodialysis (HD). This study compared the mortality risk of ESRD patients with SLE initiating with PD versus HD after matching their baseline sociodemographic and clinical factors.Design, setting, participants, & measurements Of 11,023 ESRD patients with SLE initiating dialysis with PD or HD between 1995 and 2006 with complete records in the US Renal Data System, 1352 pairs were matched on 13 predictors utilizing a predicted probability of group membership into the PD group using propensity score matching. The primary outcome was overall mortality. Secondary outcomes were cardiovascular-related and infection-related mortality. Outcomes were compared between groups with survival statistics. The period of observation ended on December 31, 2009. The median follow-up was 3 years.Results Matched pairs were predominantly women (86%) with a median age of 39 years. Matched pairs had a balance (P$0.05) of all baseline factors. Matched pairs had a similar risk of overall mortality (hazard ratio, 0.96 [95% confidence interval, 0.82 to 1.13]; mortality, 21.4% [290 to 1352] versus 22.5% [304 to 1352] for PD versus HD) within the first 3 years of observation. Matched pairs also had similar cardiovascular-related mortality (10.5% versus 9.5% for PD versus HD) and infection-related mortality (3% versus 4.4% for PD versus HD).Conclusions In ESRD patients with SLE, the mortality was similar among those initiating with PD versus HD after predictors were matched between groups.

The National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommends the routine use of hemodialysis arteriovenous (AV) access surveillance to detect hemodynamically significant stenoses and appropriately correct them to reduce the incidence of thrombosis and to improve accesses patency rates. Access blood flow monitoring is considered as one of the preferred surveillance method for both AV fistulas (AVF) and AV grafts (AVG); however, published studies have reported conflicting results of its utility that led healthcare professionals to doubt the benefits of this surveillance method. We performed a meta-analysis of the published randomized controlled trials (RCTs) of AV access surveillance using access blood flow monitoring. Our hypothesis was that access blood flow monitoring lowers the risk of AV access thrombosis and that the outcome differs between AVF and AVG. The estimated overall pooled risk ratio (RR) of thrombosis was 0.87 (95% confidence interval [CI], 0.67 to 1.13) favoring access blood flow monitoring. The pooled RR of thrombosis were 0.64 (95% CI, 0.41 to 1.01) and 1.06 (95% CI, 0.77 to 1.46) in the subgroups of only AVF and only AVG, respectively. Our results added to the uncertainty of access blood flow monitoring as a surveillance method of hemodialysis accesses.

Chronic graft-versus-host disease is a potentially life-threatening immunological complication which can occur any time after hematopoietic stem cell transplant. Many organ systems can be affected; however, kidneys are normally not and development of nephrotic syndrome is particularly rare. In our report, a 64 year old who was diagnosed with acute myelogenous leukemia developed acute kidney injury and nephrotic syndrome secondary to minimal change disease. The patient responded well to treatment with steroids and rituximab therapy. Our goal is to communicate that nephrotic syndrome should be suspected in patients with significant hypoalbuminemia after graft-versus-host disease and withdrawing immunosuppression.

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