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Biomedical subjects

B L Kasiske

Publications and source records attributed to B L Kasiske.

At least 55 records · Page 3Linked to original sources
PubMed1997

The effects of dietary protein restriction on chronic progressive renal disease.

There have been a large number of clinical trials and two meta-analyses attempting to determine if dietary protein restriction retards the rate of renal disease progression. Indeed, in a systematic search of prospective, controlled trials examining the effects of protein restriction over at least 6 months, we located 23 published between 1980 and 1996. Only 12 of these trials were randomized and controlled. The results of the 23 studies were heterogeneous. Two meta-analyses combined the results of randomized, controlled trials. Although both meta-analyses concluded that dietary protein restriction significantly reduced the number of patients who died or required treatment for end-stage renal disease, the well-known effects of protein restriction on the signs and symptoms of uremia leave open the question of whether protein restriction had a substantial effect on renal disease progression per se. Adding to the uncertainty is the inconclusive result of the largest, best-designed clinical trial, the Modification of Diet in Renal Disease Study. In any case, the effect of protein restriction on the rate of decline in renal function is arguably modest, making it difficult to demonstrate statistical significance, even in large, well-designed clinical trials. All of these trials suggest that we need therapies that are more effective than dietary protein restriction to halt the progression of renal disease.

Chronic Disease↗
PubMed1997

Clinical correlates to chronic renal allograft rejection.

Chronic rejection is a clinical syndrome characterized by a progressive decline in renal allograft function and nonspecific histologic findings of interstitial fibrosis, glomerulosclerosis, and fibrointimal proliferation of intrarenal arteries. Most late allograft failure that is not due to death with a functioning allograft is caused by chronic rejection. Although the pathogenesis and treatment of chronic rejection are unknown, a number of epidemiological studies have examined clinical correlates for possible clues to its pathogenesis. Clinical correlates for chronic renal allograft rejection can be classified in two broad categories: immune (alloantigen-dependent) and non-immune (alloantigen-independent). The strongest evidence that chronic rejection is immune mediated comes from its association with acute rejection and the degree of histocompatibility mismatching. However, not all acute rejection leads to chronic rejection, and there is little evidence that newer immunosuppression regimens which effectively prevent acute rejection have reduced the incidence and severity of chronic rejection. Therefore, many clinical investigators have also looked for potential non-immune causes of chronic rejection. Putative non-immune risk factors include donor source (living-related vs. cadaveric), cold ischemia time, delayed graft function, size mismatching, donor age, donor and recipient gender, recipient race, hyperlipidemia, and hypertension. Although there is little evidence supporting a cause and effect relationship between any immune or non-immune risk factor and chronic rejection, these clinical associations suggest a number of potentially important areas for further study.

Chronic Disease↗
PubMed1997

Irbesartan lowers blood pressure and ameliorates renal injury in experimental non-insulin-dependent diabetes mellitus.

In the present study, we investigated the effects of the angiotensin (Ang) II receptor antagonist, irbesartan, on blood pressure and renal structural injury in obese Zucker rats (OZR), an experimental model of non-insulin-dependent diabetes mellitus (NIDDM). Twenty-six-week-old OZR with established renal disease were administered either low-dose (15 mg/kg) or high-dose (50 mg/kg) irbesartan in the drinking water for a period of 18 weeks. Irbesartan caused dose-related reductions in blood pressure, and reduced by 47 to 60% the percent of glomeruli with sclerosis at 44 weeks of age (P < 0.05). In addition, irbesartan at the higher dose reduced the tubulointerstitial injury score at 44 weeks by approximately 75% (P < 0.05). By contrast, irbesartan did not significantly reduce albuminuria in OZR. The results of the present study demonstrate that the Ang II receptor antagonist irbesartan can reduce blood pressure and ameliorate glomerular and tubulointerstitial injury in an experimental model of NIDDM.

Albuminuria↗
PubMed1997

Long-term results and complications of renal transplantation: the Hennepin experience.

Approximately one sixth of patients receiving renal transplants have a functioning kidney beyond 20 years. Chronic rejection is the predominant cause of late allograft loss. Malignancy, cardiovascular disease, hepatic failure, and infections are the major causes of late death. Early detection and control of the risk factors that contribute to patient death should favorably influence the long-term success of renal transplantation.

Adult↗
PubMed1996

Serum albumin and mortality after renal transplantation.

The incidence, causes, and consequences of hypoalbuminemia after renal transplantation are not well defined. We examined clinical correlates of serum albumin measured at 3 months, 6 months, 1 year, and annually thereafter in 706 renal transplant recipients who survived at least 6 months with a functioning allograft. Follow-up was 7.0 +/- 4.2 years. Hypoalbuminemia (< or = 3.5 g/dL) was most common at 3 months (31%, n = 692), least common at 1 year (12%, n = 656), and then became increasingly common among survivors, for example, 14% (n = 466) at 4 years, 20% (n = 204) at 8 years, and 29% (n = 77) at 12 years after transplantation. By multiple linear regression, variables that correlated (P < 0.05) with lower serum albumin at 3, 6, 12, and 24 months included age, diabetes, proteinuria, and cytomegalovirus infection. Other independent correlates on at least one of these occasions included renal function and chronic disease (malignancy, liver disease, and cardiovascular disease). Serum albumin, as a time-averaged and time-dependent covariate, was a strong independent risk factor for death using Cox proportional hazards analysis (relative risk for each g/dL increment, 0.26; 95% confidence interval, 0.16 to 0.44 [1.00 = no risk]). The effects of albumin on mortality were independent of age, diabetes, serum lipids, renal function, chronic liver disease, malignancies, and cardiovascular disease. The effects of albumin on mortality were evident even when the analysis was restricted to patients dying several years after albumin was measured. Thus, hypoalbuminemia is common and serum albumin is a strong independent risk factor for all-cause mortality after renal transplantation.

Actuarial Analysis↗
PubMed1996

Determination of residual renal function with iohexol clearance in hemodialysis patients.

Residual renal function (RRF) may contribute significantly to the total dialysis prescription. Conventional quantitation of RRF in hemodialysis (HD) patients is measured by urea clearance and requires a 24-hour urine collection which is often difficult to perform and inaccurate. The renal clearance of iohexol was evaluated as an alternative method for RRF assessment (iohexol-derived RRF) in hemodialysis patients. An intravenous bolus of iohexol (12 ml; 300 mg iodine/ml) was administered to 42 hemodialysis patients following routine HD. A single blood sample was obtained approximately 44 hours later (pre-HD) to determine the plasma clearance of iohexol using x-ray fluorescence methods. Total body clearance of iohexol (CTBio) and non-renal clearance of iohexol (CNRio) 2.87 +/- 0.3 ml/min (mean +/SEM) were used to calculate iohexol-derived RRF (CTBio-CNRio). Iohexol-derived RRF determinations were then compared to urea clearance-derived RRF measurements. The RRF contribution to the dialysis prescription was also calculated utilizing iohexol-derived RRF compared to urea-derived RRF. Iohexol-derived RRF did not differ from urea-derived RRF (2.48 +/- 0.3 vs. 2.64 +/- 0.4 ml/min, P = 0.21). The RRF contribution to the weekly dialysis prescription (Kt/V) did not differ when iohexol-derived RRF was compared to urea-derived RRF (0.94 +/- 0.1 vs. 0.93 +/- 0.1, P = 0.9). Additionally, the effect of iohexol on RRF was assessed in 17 HD patients. Urea-derived RRF determinations one week after iohexol exposure did not differ from those measured one week prior to iohexol exposure (3.17 +/- 0.6 vs. 2.91 +/- 0.5 ml/min, respectively). Thus, renal clearance of iohexol can be an accurate and safe measure of RRF in HD patients and potentially simplify delivery of the dialysis prescription.

Adult↗
PubMed1996

Chronic renal allograft rejection: immunologic and nonimmunologic risk factors.

The pathogenesis of chronic renal allograft rejection is unknown. It is also unclear why cyclosporine has failed to prevent chronic rejection. We examined possible risk factors for graft loss to chronic rejection among 706 renal transplants using the Cox proportional hazards model with fixed and time-dependent covariates. Both the number and the severity of acute rejection episodes were independent risk factors for chronic rejection [relative risk (95% confidence interval) 2.31 (2.04 to 2.60) and 1.53 (1.27 to 1.84), respectively]. Cyclosporine and cyclosporine withdrawal had no effect on chronic rejection. Acute rejections occurring within the first three months after transplantation, when cyclosporine most effectively prevented acute rejection, also had no effect on chronic rejection. Risk factors that were independent of acute rejection and not clearly attributable to immune mechanisms included serum albumin [0.20 (0.10 to 0.38) for each g/dl], proteinuria [1.42 (1.29 to 1.57) for each g/24 hr], and serum triglycerides -1.09 (1.03 to 1.16) for each 100 mg/dl-. These results suggest that the reduction in acute rejection episodes from cyclosporine has failed to reduce graft failure from chronic rejection, possibly because the early (within the first 3 months) and mild acute rejection episodes that are most effectively prevented by cyclosporine do not cause chronic rejection. In addition, the results suggest that there may be a number of nonimmunologic risk factors for chronic rejection.

Adolescent↗
PubMed1996

Hyperlipidemia and its management in renal disease.

Dyslipidemia is common in patients with renal disease, may contribute to the high incidence of cardiovascular disease, and may play a role in progressive renal injury. Recent studies have shown that newer antilipemic agents appear to be safe and effective in patients with renal disease. This should make it possible to conduct large, controlled clinical trials examining the effect of lipid-lowering strategies on cardiovascular disease, and on renal disease progression.

Humans↗
PubMed1996

Cardiovascular disease after renal transplantation.

Although cardiovascular disease is a major cause of morbidity and mortality after renal transplantation, its pathogenesis and treatment are poorly understood. We conducted separate analyses of risk factors for ischemic heart disease, cerebral, and peripheral vascular disease after 706 renal transplants, all of which functioned for at least 6 months. We used Cox proportional hazards analysis to examine the effects of multiple pretransplant and posttransplant risk factors and included time-dependent variables measured at 3, 6, and 12 months, and annually to last follow-up at 7.0 +/- 4.2 yr. The independent relative risk (RR) of diabetes was 3.25 for ischemic heart disease, 3.21 for cerebral vascular disease, and 28.18 peripheral vascular disease (P < 0.05). The RR of each acute rejection episode was 1.40 for ischemic heart disease and 1.24 for cerebral vascular disease. Among serum lipid levels, high-density lipoprotein cholesterol was the best predictor of ischemic heart disease (RR = 0.80 for each 10 mg/dL). Posttransplant ischemic heart disease was strongly predictive of cerebral (5.80) and peripheral vascular disease (5.22), whereas ischemic heart disease was predicted by posttransplant cerebral (8.25) and peripheral vascular disease (4.58). Other risk factors for vascular disease included age, gender, cigarette smoking, pretransplant splenectomy, and serum albumin. Hypertension and low-density lipoprotein cholesterol had no effect, perhaps because of aggressive pharmacologic treatment. Thus, the incidence of cardiovascular disease continues to be high after renal transplantation, and multiple risk factors suggest a number of possible strategies for more effective treatment and prevention.

Adult↗
PubMed1996

Post-transplant hyperlipidemia: mechanisms and management.

Hyperlipidemia is common after renal transplantation. In recent years, much progress has been made in understanding the causes and treatment of lipid abnormalities in renal transplant patients. Recently, short-term studies have shown that newer antilipemic agents appear to be safe and effective in treating hyperlipidemia in this population. Despite the absence of large, controlled clinical trials examining the effect of lipid-lowering strategies on cardiovascular disease and chronic renal allograft rejection, therapy appears to be warranted in renal transplant patients with an atherogenic lipid profile and multiple risk factors.

Cardiovascular Diseases↗
PubMed1996

Lovastatin inhibits lipopolysaccharide-induced NF-kappaB activation in human mesangial cells.

BACKGROUND: HMG-CoA reductase inhibitors have been shown to reduce glomerular injury in different models of progressive renal damage. The transcription factor NF-kappaB plays a major role in the induced expression of genes involved in cellular proliferation and inflammatory responses that could be important in the pathogenesis of glomerular injury. We therefore examined the effects of the HMG-CoA reductase inhibitor lovastatin on NFkappaB activation in human mesangial cells. METHODS: Cultured human mesangial cells were stimulated with bacterial lipopolysaccharide (LPS) in the presence or absence of lovastatin. NF-kappaB activity was measured by electrophoretic mobility shift assay (EMSA). RESULTS: LPS-stimulated mesangial cells exhibited an NF-kappaB-like activity as assessed by EMSA competition assays, and supershift assays with antibodies against the p50 and p65 subunits of NF-kappaB. Treatment of mesangial cells with lovstatin in the presence of exogenous cholesterol resulted in a significant reduction of the LPS-induced NF-kappaB activity. In the presence of either mevalonate or the mevalonate metabolite farnesyl pyrophosphate, the lovastatin inhibition of NF-kappaB activation was substantially reversed, supporting a role for mevalonate metabolites in LPS-induced mesangial cell NF-kappaB activation. CONCLUSIONS: These data suggest an additional mechanism by which HMG-CoA reductase inhibitors may reduce glomerular injury, namely, by inhibiting NF-kappaB activation and the subsequent proliferative and inflammatory responses.

Base Sequence↗