Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells

Recombinant human erythropoietin (rHuEPO) increases endothelin-1 release by endothelial cells. Hypertension is a major complication of rHuEPO therapy in hemodialysis (HD) patients. We have previously reported that patients receiving rHuEPO intravenously (i.v.) had higher mean arterial pressure (MAP) and plasma endothelin-1 (ET-1) levels than those in which the hormone was administered subcutaneously (s.c). To test whether the increased serum ET-1 levels associated with i.v. rHuEPO administration are the result of a direct effect of the hormone on ET-1 release by the endothelial cells (EC), we examined the effects of rHuEPO in vitro. Bovine pulmonary artery endothelial cells (BPAEC) were exposed to doses of rHuEPO of 0.8; 1.6; 3.3 and 6.6 U/ml. A 24 hour-time course showed maximal ET-1 production at 12 hours for all the doses tested. A significant increase in cell proliferation over controls was observed at 24 hours, for all rHuEPO doses, and no correlation was found between ET-1 values and cell proliferation. Inhibition of protein synthesis by cycloheximide (10 µg/ml) abolished the stimulation of ET-1 release by rHuEPO. Thrombin (4 U/ml) and angiotensin II (10-7 M), two potent stimulators of ET-1 release, had additive effects to those of rHuEPO. Specific thrombin and angiotensin II antagonists blocked these additive effects, reducing ET-1 release to the level of rHuEPO stimulation alone. In summary, rHuEPO stimulates vascular EC in culture to increase ET-1 release through an increase in synthesis and in a time dependent fashion. The routes of stimulation seem to differ from other known ET-1 secretogoges. Our data also confirm a significant mitogenic effect of rHuEPO on the endothelial cell

Statins and Cardiovascular Disease Outcomes in Chronic Kidney Disease: Reaffirmation vs. Repudiation

Cardiovascular disease (CVD) burden is several-fold higher in patients with chronic kidney disease (CKD). Although statins have been shown to provide significant CVD benefits in both the general population and patients with CKD, this has not translated into survival advantage in patients with advanced CKD or on dialysis. It has been reported that CVD risk continues to escalate as CKD progresses to end-stage kidney disease (ESKD); however, the CVD risk reduction by statins appears to decline as patients’ progress from the early to later stages of CKD. Statins have also been associated with a higher incidence of stroke in ESKD patients. Thus, the CVD benefits of statins in ESKD remain questionable

Role of hypoalbuminemia and hypocholesterolemia as copredictors of mortality in acute renal failure

Role of hypoalbuminemia and hypocholesterolemia as co-predictors of mortality in acute renal failure.BackgroundHypoalbuminemia (LA) and hypocholesterolemia (LC) have been reported to portend high mortality in both older patients and in patients with end-stage renal disease. Even though low levels have been reported in critically ill patients, they have not been clearly defined as predictors of mortality in acute renal failure (ARF). The impact of LA and LC on mortality in ARF is evaluated in this study.MethodsWe conducted a computer-assisted three-year retrospective review of all cases of de novo ARF seen at an inner city tertiary-care facility. One hundred cases met the criteria for inclusion in the study. We employed both univariate and multivariate logistic regression models to estimate the relative risks (RR) and 95% confidence intervals (CI) of mortality associated with several variables.ResultsPredictors associated with a high risk of death identified in this study include LC ≤ 150 mg/dl (≤ 3.9 mmol/liter; RR, 7.4; CI, 2.7 to 20.3), LA ≤ 35 g/liter (RR, 5.0; CI, 1.9 to 13.2), sepsis (RR, 9.4; CI, 3.7 to 23.9), mechanical ventilation (RR, 10.8; CI, 2.8 to 41.0), oliguria (RR 17.0; CI, 6.2 to 46.6), and multisystem organ failure (RR 24.7; CI, 10.3 to 59.1). The overall gross mortality was 39%, but mortality among intensive care unit patients was 82%. Survival was 82% among patients with serum albumin > 35 g/liter versus 48% among those with serum albumin ≤ 35 g/liter (χ2 = 11.9, P = 0.0006). Similarly, survival was higher among patients with cholesterol > 150 mg/dl (> 3.9 mmol/liter) than those whose levels were ≤ 150 mg/dl (≤ 3.9 mmol/liter; 85 vs. 44%, χ2 = 17.3, P < 0.0001). Significant association between LA and LC was observed (R = 0.4, P < 0.0001). Age, gender, level of plasma creatinine, and underlying chronic medical conditions were not predictive of mortality.ConclusionSurvival in ARF is significantly altered by the levels of albumin and cholesterol. Because both LC and LA can be cytokine mediated, their presence in ARF should be considered ominous

Detection of HIV-1 and Human Proteins in Urinary Extracellular Vesicles from HIV+ Patients

Background. Extracellular vesicles (EVs) are membrane bound, secreted by cells, and detected in bodily fluids, including urine, and contain proteins, RNA, and DNA. Our goal was to identify HIV and human proteins (HPs) in urinary EVs from HIV+ patients and compare them to HIV− samples. Methods. Urine samples were collected from HIV+ (n=35) and HIV− (n=12) individuals. EVs were isolated by ultrafiltration and characterized using transmission electron microscopy, tandem mass spectrometry (LC/MS/MS), and nanoparticle tracking analysis (NTA). Western blots confirmed the presence of HIV proteins. Gene ontology (GO) analysis was performed using FunRich and HIV Human Interaction database (HHID). Results. EVs from urine were 30–400 nm in size. More EVs were in HIV+ patients, P<0.05, by NTA. HIV+ samples had 14,475 HPs using LC/MS/MS, while only 111 were in HIV−. HPs in the EVs were of exosomal origin. LC/MS/MS showed all HIV+ samples contained at least one HIV protein. GO analysis showed differences in proteins between HIV+ and HIV− samples and more than 50% of the published HPs in the HHID interacted with EV HIV proteins. Conclusion. Differences in the proteomic profile of EVs from HIV+ versus HIV− samples were found. HIV and HPs in EVs could be used to detect infection and/or diagnose HIV disease syndromes