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Biomedical subjects

B L Kasiske

Publications and source records attributed to B L Kasiske.

At least 73 records · Page 4Linked to original sources
PubMed1996

Risk factors for nephropathy and cardiovascular disease in diabetic Northern Minnesota American Indians.

Although complications of diabetes are common among Southwest American Indians, little is known about diabetes and associated risk factors for nephropathy and cardiovascular disease in other genetically distinct tribes. We conducted a retrospective analysis of 665 diabetic patients at two Chippewa Indian reservations in northern Minnesota to evaluate the prevalence of risk factors for diabetic nephropathy and cardiovascular disease. In 79 patients, a more detailed study was carried out, including an assessment of renal function and urinary albumin excretion (UAE). The overall prevalences of proteinuria and hypertension were 47.9% and 62.6%, respectively. Proteinuria was observed more often in hypertensive than in non-hypertensive patients (55.2% vs 44.4%, p < 0.05), and in patients with diabetes for longer than 10 years (57% vs 40% for diabetes less than 10 years, p < 0.05). Although hypercholesterolemia (total cholesterol > or = 200 mg/dl) was observed in 54% of patients, there was no relationship between hypercholesterolemia and proteinuria. In the 79 patients studied in more detail, UAE was greater in hypertensive patients compared to non-hypertensive patients (606 +/- 15600 mg/24h vs 101 +/- 157 mg/24 h, p < 0.05), and in patients with diabetes for 10 years or longer compared to patients in the first decade of disease (748 +/- 1732 mg/24 h vs 96 +/- 171 mg/24 h, p < 0.05). Hypercholesterolemia and elevated LDL-cholesterol (> 130 mg/dl) were observed in 56% and 49% of patients, respectively, but were not associated with increased UAE. In contrast, hypertriglyceridemia (> 250 mg/dl) was associated with an elevated UAE (932 +/- 2150 mg/24 h vs 245 +/- 735 mg/24h, p < 0.05). Increased lipoprotein(a) was found in patients with overt albuminuria. In summary, the prevalence of risk factors for diabetic nephropathy and associated cardiovascular disease is high in Chippewa American Indians in northern Minnesota. Although detecting abnormal UAE may be useful in identifying high-risk patients who may benefit from early intervention, traditional risk factors such as hypercholesterolemia may not explain the risk associated with increased UAE.

Adolescent↗
PubMed1995

Evaluation of living renal donors. The current practice of US transplant centers.

To examine practice patterns regarding how living donors are evaluated and selected in the U.S., a survey was sent to all 231 United Network of Organ Sharing (UNOS)-approved transplant centers. Respondents from 75% of centers completed the questionnaire, all of whom utilize living donors for renal transplantation. Although the use of living-unrelated donors is also widely accepted (in 92% of centers), only 31% of responding centers performed such transplants in 1992, indicating a discrepancy between acceptance and actual practice. Morbidity (0.23%) and mortality (0.03%) of kidney donation continue to be low. The long-term risk of renal insufficiency in kidney donors appears to be similar to, or lower than, that in the general population. There is substantial variability in how potential donors are evaluated and what they are told regarding the risk involved in renal donation. There is also variability in exclusion criteria such as the acceptance of older donors (> 55 years old); those with borderline-to-mild hypertension, and those with borderline low glomerular filtration rate. Larger centers tended to be less rigid in their exclusion criteria compared with smaller centers. While our results indicate widespread acceptance and use of living donors, they also highlight the need for future studies to examine the efficacy of tests used in the evaluation process and to determine the long-term risks of renal donation.

Adolescent↗
PubMed1995

Long-term effects of antihypertensive agents on proteinuria and renal function.

BACKGROUND: Although many studies have examined the effects of antihypertensive agents on proteinuria and glomerular filtration rate in patients with kidney disease, many questions remain unresolved. These questions include whether the effects of agents differ, whether their effects are similar in diabetic and nondiabetic patients with renal disease, and whether the effects of any agents are independent of blood pressure reductions. METHODS: We conducted a meta-analysis of studies obtained with MEDLINE and bibliographies from comprehensive reviews but included only investigations with follow-up times of at least 6 months. We combined data (1) in an analysis of randomized controlled trials, (2) in a separate univariate analysis of controlled and uncontrolled trials, and (3) using weighted multiple linear regression. RESULTS: In 14 randomized controlled trials, angiotensin-converting enzyme inhibitors caused a greater decrease in proteinuria (pooled mean [95% confidence intervals], -0.51[-0.68 to -0.35], ln [treatment/control]), improvement in glomerular filtration rate (0.13 mL/min per month [0.10 to 0.16 mL/min per month]), and decline in mean arterial pressure (-4.0 mm Hg [-4.9 to -3.0 mm Hg]) compared with controls. In a multivariate analysis of controlled and uncontrolled trials, each 10-mm Hg reduction in blood pressure decreased proteinuria (regression coefficient [95% confidence interval] -0.14 [-0.22 to -0.06] ln [after/before]), but angiotensin-converting enzyme inhibitors (-0.45 [-0.58 to -0.32]) and nondihydropyridine calcium antagonists (-0.38 [-0.70 to -0.06]) were associated with additional declines in proteinuria that were independent of blood pressure changes and diabetes. Each 10-mm Hg reduction in blood pressure caused a relative improvement in glomerular filtration rate (0.18 mL/min per month [0.04 to 0.31 mL/min per month]), but among diabetic patients there was a tendency for dihydropyridine calcium antagonists to cause a relative reduction in glomerular filtration rate (-0.68 mL/min per month [-1.31 to -0.04 mL/min per month]). CONCLUSIONS: Long-term beneficial effects of antihypertensive agents on proteinuria and glomerular filtration rate are proportional to blood pressure reductions and are similar in diabetic and nondiabetic patients with renal disease. In addition, angiotensin-converting enzyme inhibitors, and possibly nondihydropyridine calcium antagonists, have additional beneficial effects on proteinuria that are independent of blood pressure reductions.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Effects of antihypertensive therapy on serum lipids.

PURPOSE: To compare and contrast the effects of antihypertensive agents on serum lipids and blood pressure in different patient populations. DATA SOURCES: A MEDLINE search and bibliographies from recent comprehensive reviews were used to identify trials that provided sufficient data to calculate the change in one or more serum lipid values measured before and after antihypertensive therapy. STUDY SELECTION: 474 controlled and uncontrolled clinical trials investigated the effects of 85 antihypertensive agents on lipids and blood pressure in more than 65,000 patients. DATA EXTRACTION: Data on triglyceride and total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol levels; blood pressure; patient characteristics; and study design. DATA SYNTHESIS: Differences in the effects of agents, adjusted for differences in patient populations and study design, were examined using multiple linear regression analysis that was weighted by study quality and inverse variance. Diuretics caused relative increases in cholesterol levels (regression coefficient = 0.13 mmol/L; 95% CI, 0.09 to 0.18 mmol/L) that were greater with higher doses (additional effect of high dose, 0.12 mmol/L; CI, 0.04 to 0.20 mmol/L) and were worse in blacks than in nonblacks (additional effect in blacks, 0.13 mmol/L; CI, 0.01 to 0.26 mmol/L). Beta-blockers caused increases in triglyceride levels (0.35 mmol/L; CI, 0.31 to 0.39 mmol/L) that were substantially smaller for agents with intrinsic sympathomimetic activity (amelioration of beta-blocker increase, -0.21 mmol/L; CI, -0.27 to -0.16 mmol/L). When combined with cardioselectivity, beta-blockers with intrinsic sympathomimetic activity favorably affected lipids and reduced both total (-0.14 mmol/L; CI, -0.24 to -0.04 mmol/L) and LDL cholesterol levels (-0.17 mmol/L; CI, -0.28 to -0.07 mmol/L). alpha-Blockers beneficially affected total cholesterol (-0.23 mmol/L; CI, -0.28 to -0.18 mmol/L), LDL cholesterol (-0.20 mmol/L; CI, -0.25 to 0.15 mmol/L), triglycerides (-0.07 mmol/L; CI, -0.11 to -0.03 mmol/L), and, in younger persons, HDL cholesterol (0.02 mmol/L; 0.01 to 0.04 mmol/L). Converting enzyme inhibitors reduced triglycerides (-0.07 mmol/L; CI, -0.12 to -0.02 mmol/L), and, in patients with diabetes, total cholesterol (-0.22 mmol/L; CI, -0.34 to -0.10 mmol/L). Vasodilators reduced total (-0.22 mmol/l; CI, -0.30 to -0.10 mmol/L) and LDL cholesterol (-0.22 mmol/L; CI, -0.29 to -0.11 mmol/L) and increased HDL cholesterol (0.06 mmol/L; CI, 0.02 to 0.09 mmol/L). CONCLUSION: With the exception of calcium antagonists, nearly all antihypertensive agents affect serum lipids. These effects differ among patient populations.

Adult↗
PubMed1995

Early glomerular changes in rats with dietary-induced hypercholesterolemia.

Increasing evidence suggests that lipids may be important modulators of progressive glomerular injury. We previously reported the long-term glomerular changes in rats with dietary-induced hypercholesterolemia. In this work, we evaluated the early glomerular changes induced by hypercholesterolemia that precede the development of glomerulosclerosis. In cholesterol-fed rats, an early macrophage influx was observed. This was associated with an increase in glomerular size, mesangial matrix expansion, lipid deposits, and foam cell formation. Immunohistochemical techniques showed that type IV collagen, fibronectin, and laminin were increased in cholesterol-fed rats. The mRNA expression for the alpha 1 chain of type IV collagen and an inhibitor of type IV collagenase were increased, suggesting that both increased synthesis and reduced degradation may be involved in cholesterol-induced mesangial matrix accumulation. The glomerular mRNA expression of transforming growth factor-beta 1 was also upregulated, suggesting that transforming growth factor-beta 1 could be an important mediator for mesangial matrix accumulation in hypercholesterolemic states. The early cholesterol-induced changes in the glomerulus are reminiscent in many respects to the process leading to glomerulosclerosis in the vessel wall.

Animals↗
PubMed1995

Screening and management of microalbuminuria in patients with diabetes mellitus: recommendations to the Scientific Advisory Board of the National Kidney Foundation from an ad hoc committee of the Council on Diabetes Mellitus of the National Kidney Foundation.

All individuals with diabetes mellitus should be screened yearly with a spot urine albumin:creatinine ratio to identify those who are at increased risk for the development of complications of diabetes mellitus, including nephropathy, retinopathy, and cardiovascular disease. Once these high-risk individuals are appropriately identified, it is recommended that therapy with an angiotensin-converting enzyme (ACE) inhibitor be initiated. In addition, cardiovascular risk factors should be investigated, and when appropriate, therapeutic interventions should be initiated according to existing recommendations.

Albuminuria↗
PubMed1995

The evaluation and selection of living kidney donors.

As the number of living kidney donations in the United States increases, it is important to continue to assess the manner in which potential living donors are evaluated and selected. Ethical issues can be framed using principles that are understandable to patients and physicians. Existing evidence suggests that, for most suitable donors, the short- and long-term risks of kidney donation are small enough to be outweighed by the potential benefits to the donor and recipient. A thorough but efficient evaluation of potential living donors, as outlined in this review, can effectively minimize the risks. However, mechanisms to provide long-term follow-up of all living donors are still needed. Appropriate surveillance mechanisms not only will minimize any long-term risks to individuals who have already donated a kidney but will also provide the data needed to accurately assess the risk, however small, for future donors. With or without these data, living donations will likely continue to play an increasingly important role in renal transplantation.

Ethics, Medical↗
PubMed1995

Lipid-lowering therapy in patients with renal disease.

A growing number of clinical trials have examined the effects of different lipid lowering strategies in patients with renal disease. We carried out a meta-analysis to compare and contrast the relative efficacy of various antilipemic therapies in different renal disease settings. Studies that investigated one or more therapies designed to lower serum lipids were combined using weighted multiple linear regression. The analysis adjusted treatment effects for differences in baseline lipid levels and possible placebo effects. The results showed that antilipemic therapies generally had similar effects on lipids in different renal disease settings. In nephrotic syndrome the greatest and most consistent reductions in low density lipoprotein cholesterol (LDL) were seen with 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitors (regression coefficient with 95% confidence interval in mg/dl = -63, -79 to -46). Similar results were seen for LDL in renal transplant (-51, -57 to -45), renal insufficiency (-62, -82 to -42), hemodialysis (-65, -80 to -50) and continuous ambulatory peritoneal dialysis (CAPD) patients (-84, -104 to -64). Fibric acid analogues had less effect on LDL, but caused greater reductions in triglycerides: -132, -178 to -87, in nephrotic syndrome; -69, -93 to -45 in transplant: -107, -169 to -45 in renal insufficiency; -72, -120 to -24 in hemodialysis; and -96, -162 to -30 in CAPD. In general, the effects of diet and other therapies were less consistent. Despite possible limitations of this meta-analysis, the results provide a useful framework for choosing antilipemic therapy, and point to areas for future long-term studies examining the safety and efficacy of lipid lowering strategies in patients with renal disease.

Cholesterol, HDL↗
PubMed1995

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.

Cells, Cultured↗
PubMed1995

Long-term effects of reduced renal mass in humans.

The long-term risks of kidney donation have not been well defined. We carried out 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.

Blood Pressure↗
PubMed1995

The angiotensin II receptor antagonist losartan reduces blood pressure but not renal injury in obese Zucker rats.

Agents that interfere with the renin-angiotensin system (RAS) may ameliorate progressive renal injury, particularly in a setting where intrarenal RAS activity appears to be elevated. Whether RAS antagonists affect renal disease progression when intrarenal RAS activity is not increased is unclear. In this study, therefore, the effects of the angiotensin II receptor antagonist losartan on glomerular and tubulointerstitial injury were investigated in obese Zucker rats (OZR), an experimental model of progressive renal disease characterized by reduced intrarenal renin content and reduced plasma renin activity. Losartan (100 or 200 mg/L of drinking water) was administered to OZR beginning at 26 wk of age, when renal disease was established. At 38 and 44 wk of age, losartan-treated OZR demonstrated significant (P < 0.05) dose-related decreases in systolic blood pressure, compared with blood pressures in untreated, control OZR. Despite the reductions in blood pressure, losartan had no significant effects on albuminuria or glomerular or tubulointerstitial injury. At 44 wk of age, the percentage (mean +/- SE) of glomeruli with sclerosis was 51 +/- 11, 49 +/- 9, and 39 +/- 14% in control OZR, low-dose (100 mg/L) losartan-treated OZR, and high-dose (200 mg/L) losartan-treated OZR, respectively (P > 0.05). Similarly, the tubulointerstitial injury score (range, 0 to 4) in the three groups was, respectively, 1.7 +/- 0.4, 1.6 +/- 0.3, and 1.5 +/- 0.3 (P > 0.05). It was concluded that in a setting of chronic renal failure where intrarenal RAS activity does not appear to be increased, angiotensin II receptor antagonism may not be nephroprotective despite a reduction in blood pressure.

Angiotensin Receptor Antagonists↗
PubMed1995

Chronic renal allograft rejection and clinical trial design.

Both the choice of endpoints and the selection of patients will be critical study design features in randomized controlled trials needed to test the effectiveness of treatments for chronic renal allograft rejection. We examined the feasibility of carrying out clinical trials with different endpoints and patient inclusion criteria by analyzing data from a population of 627 cadaveric kidney transplant recipients who survived with a functioning allograft for at least six months. Among those who lost grafts to chronic rejection, decreases in renal function of 30% and 60% preceded graft loss by a median of only 1.1 and 0.7 years, respectively, suggesting that little would be gained in a clinical trial that used a predetermined reduction in renal function as a surrogate endpoint. Less clear is whether histologic changes could be used as a surrogate endpoint. At present, graft loss to chronic rejection and graft failure from any cause are the most reliable endpoints. Unfortunately, large numbers of patients are needed to demonstrate clinically relevant therapeutic effects on these endpoints. Limiting enrollment to patients who are at high risk for developing chronic rejection, by selecting patients who already have a decline in renal function, for example, may reduce the number of patients needed in a clinical trial. On the other hand, selecting patients with disease that is too advanced may diminish the effectiveness of therapy. In any case, it is impossible to accurately determine the number of patients needed for a definitive clinical trial without preliminary data demonstrating the expected magnitude of the treatment effect. Thus, well-designed pilot studies are needed to measure possible treatment effects before conducting large-scale clinical trials for chronic renal allograft rejection.

Clinical Trials as Topic↗
PubMed1995

Isoprenoids and Ras: potential role in chronic rejection.

Protein prenylation, the post-translational attachment of isoprenoids to certain cellular proteins, increases protein hydrophobicity and promotes protein-membrane interactions. Of the many cellular proteins that undergo protein prenylation, particular attention has been paid to the protooncogene product Ras. Prenylated Ras protein localizes to the inner cell membrane and appears to function as a "molecular switch" through which peptide growth factors such as PDGF, IGF-1, and FGF, and cytokines such as IL-2, IL-6, and GM-CSF stimulate intracellular events. Binding of these substances to their respective receptors on target cells can activate Ras, triggering intracellular signaling cascades which culminate in processes such as cell proliferation, differentiation, and T-cell activation. Protein prenylation inhibitors block Ras prenylation, prevent membrane localization of Ras, and inhibit growth and proliferation of a variety of cell types. Recent studies in our laboratory have begun to examine the possible role of Ras in chronic allograft rejection. Abdominal aorta segments from donor Lewis rats were transplanted into Buffalo recipient rats. Recipients treated with the HMG-CoA reductase inhibitor lovastatin, which inhibits isoprenoid production, showed significantly decreased allograft intimal area after 12 weeks, when compared with untreated recipients. In a separate study, recipients treated with the agent leflunomide, which inhibits growth factor receptor tyrosine kinases that can activate Ras, had significantly decreased allograft intimal area after 12 weeks. These results suggest that Ras may be important in chronic allograft rejection, and that agents that interfere with Ras protein prenylation or activation by growth factor receptors may ameliorate chronic rejection.

Animals↗
PubMed1995

Clinical correlation between renal allograft failure and hyperlipidemia.

Chronic rejection is the leading cause of late allograft failure, but its pathogenesis is poorly understood. The prominence of the vascular lesions and certain similarities with the pathological features of atherosclerosis suggest that lipids may be involved in the pathogenesis of chronic rejection. Studies have reported an association between different lipid abnormalities and several indicators of chronic renal allograft damage. However, other potential risk factors for the development of chronic rejection were present in most cases, and an independent association between lipids and chronic rejection has not been convincingly demonstrated. In our series of 706 consecutive renal transplants with long-term follow-up, increased post-transplant serum triglycerides, but not total cholesterol, were strong predictors of graft loss to chronic rejection. This effect was independent of other risk factors for chronic rejection such as age, acute rejections, proteinuria and hypoalbuminemia. These results add to existing evidence suggesting that lipid abnormalities may be involved in the pathogenesis of chronic renal allograft rejection.

Animals↗
PubMed1995

Clinical predictors of chronic renal allograft rejection.

Among both immune and nonimmune factors implicated in the pathogenesis of chronic renal allograft rejection, acute rejection episodes represent a strong and consistent predictor. However, all acute rejection episodes are not equally predictive of chronic renal allograft rejection. Early and mild acute rejection episodes do not usually cause chronic renal allograft rejection. On the other hand, late and severe acute rejection episodes occurring more than one year after transplantation are particularly strong predictors of chronic renal allograft rejection. The number of HLA mismatches is a risk factor, but its influence may not be independent of acute rejection and other risk factors. Proteinuria and recently hypoalbuminemia are also independent risk factors for chronic renal allograft rejection. However, whether these nonimmune factors are merely the result of chronic renal allograft rejection, or whether they contribute to the pathogenesis of renal injury in chronic renal allograft rejection is yet unclear. Better HLA matching, new strategies to decrease the severity of acute rejection, and measures to prevent late acute rejection, as well as prospective evaluation of the therapies to reduce proteinuria and other nonimmune risk factors for chronic renal allograft rejection are needed.

Graft Rejection↗