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B L Kasiske

Publications and source records attributed to B L Kasiske.

At least 37 records · Page 2Linked to original sources
PubMed1999

Importance of geranylgeranyl pyrophosphate for mesangial cell DNA synthesis.

BACKGROUND: Farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) are isoprenoid products of the intracellular mevalonate pathway used for prenylation of several low molecular weight G proteins, including Ras. It is likely that platelet-derived growth factor (PDGF) stimulation of mesangial cell proliferation requires prenylated, low molecular weight G proteins. The purpose of this study was to investigate the dependence of platelet-derived growth factor-stimulated mesangial cell DNA synthesis and cell membrane Ras incorporation on FPP and GGPP. METHODS: Quiescent human mesangial cells were exposed to PDGF (25 ng/ml) to stimulate DNA synthesis. Some cells were also treated with the HMG-CoA reductase inhibitor lovastatin (2.5 to 10.0 microM), which inhibits isoprenoid synthesis, in the presence or absence of exogenous FPP or GGPP. DNA synthesis was assessed by thymidine incorporation, and Western blot analysis was used to measure total cell membrane Ras. RESULTS: Stimulation of mesangial cells with PDGF did not increase total cell membrane Ras. Lovastatin reduced cell membrane Ras, and this was prevented by simultaneous exposure of mesangial cells to exogenous FPP (2.5 to 10.0 microM) or GGPP (1 to 5 microM). Lovastatin also reduced PDGF-stimulated mesangial cell DNA synthesis by 90%, and this was completely prevented by simultaneous exposure of cells to exogenous GGPP (1 microM), but not to FPP. CONCLUSIONS: The results of this study suggest that both FPP and GGPP can provide for mesangial cell membrane Ras localization and that PDGF-stimulated mesangial cell DNA synthesis requires the isoprenoid GGPP.

Blotting, Western↗
PubMed1999

Lipophilic statins induce apoptosis of human vascular smooth muscle cells.

BACKGROUND: The accumulation of vascular smooth muscle cells (VSMC) in the intima is an early feature of atherosclerosis that results from a balance of migration from the media, proliferation, and eventual death (including programmed cell death) of VSMC. Several reports have described that HMG-CoA reductase inhibitors (statins) attenuate both the migration and proliferation of VSMC. However, the potential effect of statins on VSMC programmed cell death has received little attention. METHODS: Human and rat VSMC were incubated with different concentration of statins in the presence of fetal bovine serum as a survival factor. The presence of apoptosis was evaluated by morphological criteria, flow cytometry and DNA electrophoresis. RESULTS: Lipophilic statins induced, in a dose-dependent manner the appearance of VSMC apoptosis. The effect of statins was fully reversed by mevalonate, farnesylpyrophosphate, and geranylgeranypyrophosphate, but not by cholesterol or other mevalonate metabolites, suggesting a role for isoprenoids in VSMC apoptosis. In addition, the induction of apoptosis by statins was associated with the inhibition of prenylation of Rho B. CONCLUSIONS: The present results suggest that protein prenylation inhibition by statins may be involved in statin-induced VSMC apoptosis. These data provide a new potential mechanism by which statins may modulate the evolution of atherosclerotic lesions.

Animals↗
PubMed1998

Successful renal transplantation in American Indians.

BACKGROUND: The incidence of end-stage renal disease is rapidly growing among American Indians, but there have been no detailed reports of outcomes after renal transplantation in this population. METHODS: We compared the effects of race on risks and outcomes for renal transplants performed at a single center. There were 68 transplants in American Indians, 55 in African-Americans, 32 in Asians, 33 in other races, and 1253 in Caucasians (total = 1441 transplants). RESULTS: American Indian transplant recipients had a high prevalence of risk factors. American Indians were more likely to be diabetic (45.6%) compared with African-Americans (21.8%), Asians (9.4%), other races (15.2%), and Caucasians (25.9%); overall P<0.001. American Indian transplant recipients were more likely to be obese (25.0% had body mass index >30 kg/m2) compared with African-Americans (12.7%), Asians (3.1%), other races (6.1%), and Caucasians (9.7%); overall P<0.01. The percent of patients with peak panel-reactive antibody >50% was higher for American Indian recipients (32.4%) compared with African-Americans (16.4%), Asians (21.9%), other races (27.3%) and Caucasians (15.6%); P<0.01. Despite these differences in risk, there were no statistically significant differences in the incidence of acute rejection, patient survival, or graft survival between American Indians and other racial groups in univariate survival analysis. In a Cox proportional hazards model that adjusted for multiple risk factors, graft survival was not different for American Indians (P=0.71), African-Americans (P=0.60), or other races (P=0.34) compared with Caucasians, whereas Asians were only 44% as likely to have graft failure (P=0.07). Patient survival was not different among races. CONCLUSION: Outcomes for renal transplantation are excellent for American Indians, despite a high prevalence of risk factors.

Adult↗
PubMed1998

The evaluation of prospective renal transplant recipients and living donors.

The evaluation of transplant candidates should be directed to ensuring that the risks of surgery and immunosuppression are acceptable. The evaluation should also attempt to determine the likelihood of the graft functioning well enough and long enough to improve the quality of life of the recipient. The primary goal in the evaluation of a potential living donor is to ensure the donor's safety. Both the short- and long-term risks of donation need to be carefully assessed.

Cadaver↗
PubMed1998

American Indian heritage and risk factors for renal injury.

BACKGROUND: Little is known about the causes and consequences of renal disease among American Indians in the Great Lakes region of the United States. METHODS: We examined clinical correlates of albumin/creatinine ratios among 1368 participants in the three tribal communities of the Inter-Tribal Heart Project using univariate and multivariate analysis. RESULTS: Compared to 1086 participants without albuminuria, the 240 with microalbuminuria (30 to 299 mg/g) and the 42 with macroalbuminuria (>300 mg/g) were more likely to report a history of a myocardial infarction (6.4%, 16.0%, and 23.8%, respectively, P < 0.001). Similarly, compared to patients without albuminuria, those with microalbuminuria and macroalbuminuria were more likely to report a history of stroke (2.3%, 8.4% and 26.2%, respectively, P < 0.001). In a multiple linear regression model, independent correlates of albumin excretion (P < 0.05) included: fasting blood sugar, treated diabetes, treated hypertension, higher systolic blood pressure, lower diastolic blood pressure, abnormal electrocardiogram, a history of stroke, the degree of American Indian heritage, and lower household income. CONCLUSIONS: Urinary albumin excretion is associated with cardiovascular disease outcomes and risk factors among American Indians of the Great Lakes region. Both heredity and socioeconomic status appear to play a role in the pathogenesis of renal injury in this population.

Adult↗
PubMed1998

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-alpha) into the culture medium, whereas PTEC constitutively secreted both IL-6 and TNF-alpha. 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-alpha 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-alpha antibodies additively reduced coculture HIV-1 expression by 87% (P < 0.05). We conclude that renal cell production of IL-6 and TNF-alpha 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.

AIDS-Associated Nephropathy↗
PubMed1998

Lovastatin reduces glomerular macrophage influx and expression of monocyte chemoattractant protein-1 mRNA in nephrotic rats.

Glomerular expression of monocyte chemoattractant protein-1 (MCP-1) and subsequent glomerular macrophage infiltration may play an important role in the development of glomerulosclerosis. Previous studies have shown that lovastatin ameliorates experimental renal disease and reduces MCP-1 expression in serum-stimulated, cultured mesangial cells. We investigated the effects of lovastatin on glomerular MCP-1 expression and macrophage infiltration in rats with puromycin aminonucleoside (PA) nephrosis, an experimental model of renal disease characterized by early macrophage infiltration. Male Sprague-Dawley rats were pretreated for 5 days with either lovastatin (4 mg/kg) or vehicle. At the end of pretreatment, the lovastatin-pretreated rats received a single i.v. injection of PA (50 mg/kg) and continued to receive daily lovastatin thereafter. The vehicle-pretreated rats received i.v. injections of either PA or saline, and continued to receive daily vehicle treatment thereafter. Ten days after PA injection, the vehicle-treated PA rats showed increased (P < 0.05) serum cholesterol (359 +/- 25 mg/100 mL) and urine albumin excretion (343 +/- 95 mg/24 hr), compared with the vehicle-treated control rats (61 +/- 3 mg/100 mL and 2.5 +/- 0.6 mg/24 hr, respectively). Serum cholesterol (193 +/- 22 mg/dL) and urine albumin excretion (255 +/- 68 mg/24 hr) were less in the lovastatin-treated PA rats than in the vehicle-treated PA rats. The number of glomerular macrophages, assessed as ED-1-positive cells, per glomerular profile was increased 77% in the vehicle-treated PA rats (3.3 +/- 0.2) compared with the vehicle-treated control rats (1.8 +/- 0.2) (P < 0.05). By contrast, the number of glomerular macrophages was not elevated in the lovastatin-treated PA rats (2.3 +/- 0.2). Thus, lovastatin in vivo can attenuate glomerular macrophage infiltration. This may represent one mechanism by which lovastatin ameliorates experimental glomerular disease.

Animals↗
PubMed1998

A meta-analysis of the effects of dietary protein restriction on the rate of decline in renal function.

Dietary protein restriction has been reported to delay the need for renal replacement therapy in clinical trials and meta-analyses. However, less clear is what effect dietary protein has on the rate of decline in renal function. We pooled the results of 13 randomized controlled trials (n = 1,919 patients) and found that dietary protein restriction reduced the rate of decline in estimated glomerular filtration rate by only 0.53 mL/min/yr (95% confidence interval [CI], 0.08 to 0.98 mL/min/yr). We also used weighted regression analysis to determine the reasons for the differences in the results of these 13 randomized trials along with 11 other nonrandomized controlled trials (n = 2,248 patients). The effect of dietary protein restriction (glomerular filtration rate decline in treatment minus control) was substantially less in randomized versus nonrandomized trials (regression coefficient, -5.2 mL/min/yr; 95% CI, -7.8 to -2.5 mL/min/yr; P < 0.05) and relatively greater among diabetic versus nondiabetic patients (5.4 mL/min/yr; 95% CI, 0.3 to 10.5 mL/min/yr; P < 0.05), while there was a trend toward a greater effect with each additional year of follow-up (2.1 mL/min/yr; 95% CI, -0.05 to 4.2 mL/min/yr; P = NS). However, the number of diabetic patients studied was small and the duration of follow-up was short in most trials. No other patient or study characteristics altered the effect of dietary protein restriction on the rate of decline in renal function. Thus, although dietary protein restriction retards the rate of renal function decline, the relatively weak magnitude of this effect suggests that better therapies are needed to slow the rate of renal disease progression.

Diabetic Nephropathies↗
PubMed1998

Race and socioeconomic factors influencing early placement on the kidney transplant waiting list.

This cohort study investigates whether there are inequities in the current system for listing patients for cadaveric renal transplantation, using univariate and multivariate analyses to identify factors associated with early registration before initiation of dialysis. It includes patient registrations for the kidney and kidney-pancreas waiting lists between April 1, 1994, and June 30, 1996 (n = 41,596) from all 238 United Network for Organ Sharing renal transplant centers. Patient and center factors predicting dialysis status (pre- or postdialysis initiation) at the time of registration were examined. Independent predictors of listing before dialysis (P < 0.001) included: female (odds ratio [OR] = 1.14, reference: male, i.e., listing before dialysis was 14% more likely in females than in males); age < or =17 and age 18 to 55 (OR = 1.91 and 1.14, respectively, reference: age >55); prior transplant (OR = 1.80, reference: no prior transplant); 0 to 8 yr education, attended college, and received a college degree (OR = 0.78, 1.18, and 1.37, respectively, reference: high school degree); black race, Hispanic, and Asian/other (OR = 0.47, 0.59, and 0.55, reference: white); full-time employment (OR = 1.98, reference: less than full time); payment with Medicare and private insurance (OR = 0.35 and 1.24, respectively, reference: other pay); receiving insulin (OR = 1.29, reference; not on insulin); listed for kidney-pancreas (OR = 1.43, reference: listed for kidney only); listed at a center with volume >400 (OR = 1.22, reference: volume <400). To remove possible bias for general access to health care and referral for transplantation, the analysis was limited to patients who had a previous transplant and found similar results. It is concluded that racial and ethnic minorities, those less well educated, and those with fewer financial resources are less likely than their counterparts to be listed for renal transplantation before dialysis. These results suggest there may be remediable inequities in the current system for registration for renal transplantation in the United States. Education efforts directed at patients and providers, as well as recently mandated uniform listing criteria for cadaveric organ transplantation, may help to reduce these inequities.

Adolescent↗
PubMed1997

A randomized trial comparing cyclosporine induction with sequential therapy in renal transplant recipients.

Calcium antagonists may reduce the nephrotoxicity of cyclosporine (CsA), allowing CsA to be introduced immediately after renal transplantation and thereby obviating the need for sequential induction therapy with a monoclonal or polyclonal antibody. To test this hypothesis, in a pilot feasibility trial 100 cadaveric or one-haplotype-mismatched living-related renal transplant recipients were randomized to either (1) sequential therapy with anti-thymocyte globulin (ATG) (ATGAM; Upjohn, Kalamazoo, MI) 20 mg/kg/d for 7 to 14 days until renal function was established and CsA (Sandimmune; Sandoz, East Hanover, NJ) was started, or (2) CsA 8 mg/kg/d begun immediately before surgery with diltiazem (Cardizem; Marion Merrell Dow, Kansas City, MO) 60 mg sustained release twice daily. Acute rejection episodes during the first 90 days were not different with ATG versus CsA induction (42% v 28%; P = 0.142 by chi-square analysis). Graft failures (10% v 16%; P = 0.372) and the incidence of delayed graft function (28% v 34%; P = 0.516) were also similar with ATG compared with CsA. ATG caused lower platelet counts (138 +/- 59 x 10(3) v 197 +/- 75 x 10(3) at 7 days; P < 0.001) and lower white blood cell counts (9.6 +/- 4.6 x 10(3) v 12.3 +/- 4.9 x 10(3) at 7 days; P = 0.003). Diltiazem reduced the dose of CsA required to maintain target blood levels (479 +/- 189 mg/d v 576 +/- 178 mg/d at 14 days; P = 0.015). There were no statistically significant differences between the groups in serum creatinine levels at days 1, 3, 5, 7, 14, 28, 60, or 90. The results of this pilot feasibility trial suggest that prophylactic treatment with CsA and diltiazem may be equally effective and less toxic than ATG induction after renal transplantation.

Adult↗
PubMed1997

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 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.

Adult↗