112 research outputs found
Use of urine specific gravity to improve screening for albuminuria
Use of urine specific gravity to improve screening for albuminuria. The albumin to creatinine ratio (ACR) can be used to measure urine albumin excretion rates, but is inconvenient and expensive. More rapid and less expensive screening methods estimate only albumin concentration and are subject to errors caused by variation in urine volume. We examined whether urine specific gravity could be used in place of urine creatinine to correct albumin concentration for differences in urine volume in 50 patients. Urine specific gravity accurately estimated urine creatinine concentration (r = 0.79, P < 0.001). The albumin estimated-creatinine ratio (ACestR) in a random spot urine sample correlated with urine albumin excretion measured in a 24-hour urine collection (r = 0.98, P < 0.001), as did the ACR (r = 0.95, P < 0.001). For determining microalbuminuria, the sensitivity (0.88) and specificity (0.93) of the ACestR were similar to those of ACR (0.89 and 0.93, respectively). Unfortunately, the sensitivity (0.63) of the Micral-Test was relatively poor, and was only slightly improved by correcting for urine specific gravity (0.69) in this small sample of patients. Nevertheless, these results suggest that as rapid methods for measuring urine albumin concentration improve, combining them with urine specific gravity might produce a less expensive and more convenient alternative to the ACR
Effects of lovastatin on expression of cell cycle regulatory proteins in vascular smooth muscle cells
Effects of lovastatin on expression of cell cycle regulatory proteins in vascular smooth muscle cells.BackgroundThe sequential appearance of cyclins D and E is thought to initiate subsequent DNA synthesis in proliferating cells. Previous studies have reported that DNA synthesis in cultured rat vascular smooth muscle cells (VSMCs) was suppressed by the HMG-CoA reductase inhibitor lovastatin. The effects of lovastatin on cell cycle regulatory proteins in proliferating VSMCs, however, are largely unknown. Thus, we investigated the sequential expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 4, CDK2, and p27Kip1 in cultured rat VSMCs stimulated by platelet-derived growth factor (PDGF)-BB in the presence or absence of lovastatin.MethodsQuiescent VSMCs, with and without lovastatin (20 ÎĽ M) pretreatment for nine hours, were stimulated by PDGF-BB (25 ng/ml). The incorporation of tritiated thymidine was done to assess DNA synthesis. VSMC lysates were obtained every 6 hours for up to 36 hours after stimulation and were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis using relevant polyclonal antibodies. Autoradiograms were analyzed using a densitometer.ResultsThe peak expression of cyclins D1 and E occurred at 18 and 30 hours of PDGF stimulation, respectively. Concomitant expression of CDK4 and CDK2 was also observed. The expression of p27Kip1, by contrast, was reduced in association with DNA synthesis. Lovastatin suppressed DNA synthesis and reduced the expression of cyclin D1 and cyclin E, whereas p27Kip1 expression was strongly induced by lovastatin pretreatment. CDK4 and CDK2 expression was unaffected by lovastatin treatment.ConclusionsPDGF-BB induces cyclins D1 and E prior to the onset of DNA synthesis in VSMCs. Lovastatin may suppress DNA synthesis in VSMCs by inducing p27Kip1 and reducing expression of cyclins D1 and E
Long-term effects of reduced renal mass in humans
Long-term effects of reduced renal mass in humans. The long-term risks of kidney donation have not been well defined. We carried out a meta-analysis of investigations that examined the long-term effects of reduced renal mass in humans. We used multiple linear regression to combine studies and adjust for differences in the duration of follow-up, the reason for reduced renal mass, the type of controls, age and gender. We analyzed 48 studies with 3124 patients and 1703 controls. Unilateral nephrectomy caused a decrement in glomerular filtration rate (-17.1 ml/min; 95% confidence interval -20.2 to -14.0 ml/min) that tended to improve with each 10 years of follow-up (1.4 ml/min/decade; 0.3 to 2.4 ml/min/decade). Patients with single kidneys had small, progressive increases in proteinuria (76 mg/day/decade; 52 to 101 mg/day/decade), but proteinuria was negligible after nephrectomy for trauma or kidney donation. Nephrectomy did not affect the prevalence of hypertension, but there was a small increase in systolic blood pressure (2.4 mm Hg; -0.3 to 5.1 mm Hg, P > 0.05) which rose further with duration of follow-up (1.1 mm Hg/decade; 0.0 to 2.2 mm Hg/decade). Diastolic blood pressure was higher after nephrectomy (3.1 mm Hg; 1.8 to 4.4 mm Hg), but this increment did not change with duration of follow-up. Thus, in normal individuals, unilateral nephrectomy does not cause progressive renal dysfunction, but may be associated with a small increase in blood pressure
A comparison of transplant outcomes in peritoneal and hemodialysis patients
A comparison of transplant outcomes in peritoneal and hemodialysis patients.BackgroundStudies examining the effect of pre-transplant dialysis modality on graft and patient survival after kidney transplantation have produced conflicting results. Therefore, we studied the effects of pre-transplant dialysis modality on outcomes in a large United States cohort.MethodsWe compared rates of transplantation between peritoneal dialysis and hemodialysis patients from the years 1995 to 1998 in the United States (N = 252,402) and outcomes after transplantation (N = 22,776), using data from the Centers for Medicare and Medicaid Services.ResultsIn a Cox proportional hazards analysis that was adjusted for multiple patient characteristics, kidney transplantation was 1.39 (95% CI = 1.35 to 1.43) times more likely in peritoneal dialysis vs. hemodialysis patients (P < 0.0001). Over the entire follow-up period, the adjusted risk for death-censored graft failure was 1.15 (1.04 to 1.26) times higher in peritoneal dialysis vs. hemodialysis (P < 0.05), but mortality and overall graft failure rates were not different. Pre-transplant dialysis modality did not affect outcomes for patients who survived with a functioning kidney for at least 3 months. However, in adjusted Cox analyses restricted to the first 3 months, peritoneal dialysis was associated with a 1.23 (1.09 to 1.39) times higher risk for early graft failure (P < 0.001) and a 1.33 (1.16 to 1.53) times higher risk for death-censored graft failure (P < 0.001). Peritoneal dialysis patients, however, were seen to have a lower incidence of delayed graft function. In a smaller sample of patients with data on causes of early graft failure, graft thrombosis was more commonly listed as a cause of graft failure among peritoneal dialysis patients, 41% (64/156), compared to hemodialysis patients, 30% (106/349), P < 0.05.ConclusionsKidney transplantation is more frequent in peritoneal dialysis than in hemodialysis patients, and transplantation in peritoneal dialysis patients is more frequently associated with early, but not late, graft failure. Delayed graft function was less common in peritoneal dialysis patients but this potential benefit appears to be offset by other factors which are associated with early graft loss. Additional studies are needed to determine what factors may help understand this early risk of graft failure
Human mesangial cell production of monocyte chemoattractant protein-1: Modulation by lovastatin
Human mesangial cell production of monocyte chemoattractant protein-1: Modulation by lovastatin. Macrophages play a critical role in the progression of clinical and experimental glomerular injury. Serum-stimulated human fetal mesangial cells in culture produce a chemotactic factor that is monocyte-selective. This chemotactic factor is most likely monocyte chemoattractant protein-1 (MCP-1) as a monoclonal antibody directed against MCP-1, but not an irrelevant antibody, suppressed the mesangial cell-derived chemotactic activity. Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase by lovastatin resulted in a reduction of the mesangial cell-derived chemotactic activity as well as MCP-1 mRNA expression. The inhibitory effects of lovastatin in the presence of exogenous cholesterol were reversed by mevalonate, suggesting a role for isoprenoid intermediates of the mevalonate pathway and/or isoprenylated proteins in mesangial cell MCP-1 regulation. These findings suggest an additional mechanism by which HMG-CoA reductase inhibition in vivo may reduce glomerular injury
Renal cell cytokine production stimulates HIV-1 expression in chronically HIV-1-infected monocytes
Renal cell cytokine production stimulates HIV-1 expression in chronically HIV-1-infected monocytes. Renal infiltration of human immunodeficiency virus type 1 (HIV-1)-infected monocytes might play an important role in the development of HIV-associated nephropathy (HIVAN). In the present study, we investigated the effects of cytokines produced by cultured human mesangial cells (HMC) and proximal tubular epithelial cells (PTEC) on HIV-1 expression in chronically HIV-1-infected promonocytes (U1 cells). Human mesangial cells constitutively secreted interleukin-6 (IL-6) but not tumor necrosis factor-alpha (TNF-α) into the culture medium, whereas PTEC constitutively secreted both IL-6 and TNF-α. Coculture of U1 cells with HMC or PTEC for 72 hours markedly stimulated HIV-1 expression, with the p24 antigen concentration in the coculture supernatants ranging from approximately 200 to 1850 pg/ml. The presence of anti-IL-6 antibody in the coculture medium nearly completely blocked HIV-1 expression in the HMC/U1 cell cocultures (P < 0.05). Anti-IL-6 antibody and anti-TNF-α antibody blocked HIV-1 expression in the PTEC/U1 cell cocultures by 40% and 53%, respectively (P < 0.05). Moreover, the combination of anti-IL-6 and anti-TNF-α antibodies additively reduced coculture HIV-1 expression by 87% (P < 0.05). We conclude that renal cell production of IL-6 and TNF-α might provide a potent stimulus for HIV-1 expression in HIV-1-infected monocytes that infiltrate the kidney, and that this may play an important role in the pathogenesis of HIVAN
Center-driven and clinically driven variation in US liver transplant maintenance immunosuppression therapy: A national practice patterns analysis
Center-driven and clinically driven variation in US liver transplant maintenance immunosuppression therapy: A national practice patterns analysis
Heart and lung organ offer acceptance practices of transplant programs are associated with waitlist mortality and organ yield
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145354/1/ajt14885.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145354/2/ajt14885_am.pd
The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report
The definition and classification for chronic kidney disease was proposed by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) in 2002 and endorsed by the Kidney Disease: Improving Global Outcomes (KDIGO) in 2004. This framework promoted increased attention to chronic kidney disease in clinical practice, research and public health, but has also generated debate. It was the position of KDIGO and KDOQI that the definition and classification should reflect patient prognosis and that an analysis of outcomes would answer key questions underlying the debate. KDIGO initiated a collaborative meta-analysis and sponsored a Controversies Conference in October 2009 to examine the relationship of estimated glomerular filtration rate (GFR) and albuminuria to mortality and kidney outcomes. On the basis of analyses in 45 cohorts that included 1,555,332 participants from general, high-risk, and kidney disease populations, conference attendees agreed to retain the current definition for chronic kidney disease of a GFR <60ml/min per 1.73m2 or a urinary albumin-to-creatinine ratio >30mg/g, and to modify the classification by adding albuminuria stage, subdivision of stage 3, and emphasizing clinical diagnosis. Prognosis could then be assigned based on the clinical diagnosis, stage, and other key factors relevant to specific outcomes. KDIGO has now convened a workgroup to develop a global clinical practice guideline for the definition, classification, and prognosis of chronic kidney disease
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