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B Kasiske

Publications and source records attributed to B Kasiske.

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Clinical practice guidelines for managing dyslipidemias in kidney transplant patients: a report from the Managing Dyslipidemias in Chronic Kidney Disease Work Group of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative.

The incidence of cardiovascular disease (CVD) is very high in patients with chronic kidney (CKD) disease and in kidney transplant recipients. Indeed, available evidence for these patients suggests that the 10-year cumulative risk of coronary heart disease is at least 20%, or roughly equivalent to the risk seen in patients with previous CVD. Recently, the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (K/DOQI) published guidelines for the diagnosis and treatment of dyslipidemias in patients with CKD, including transplant patients. It was the conclusion of this Work Group that the National Cholesterol Education Program Guidelines are generally applicable to patients with CKD, but that there are significant differences in the approach and treatment of dyslipidemias in patients with CKD compared with the general population. In the present document we present the guidelines generated by this workgroup as they apply to kidney transplant recipients. Evidence from the general population indicates that treatment of dyslipidemias reduces CVD, and evidence in kidney transplant patients suggests that judicious treatment can be safe and effective in improving dyslipidemias. Dyslipidemias are very common in CKD and in transplant patients. However, until recently there have been no adequately powered, randomized, controlled trials examining the effects of dyslipidemia treatment on CVD in patients with CKD. Since completion of the K/DOQI guidelines on dyslipidemia in CKD, the results of the Assessment of Lescol in Renal Transplantation (ALERT) Study have been presented and published. Based on information from randomized trials conducted in the general population and the single study conducted in kidney transplant patients, these guidelines, which are a modified version of the K/DOQI dyslipidemia guidelines, were developed to aid clinicians in the management of dyslipidemias in kidney transplant patients. These guidelines are divided into four sections. The first section (Introduction) provides the rationale for the guidelines, and describes the target population, scope, intended users, and methods. The second section presents guidelines on the assessment of dyslipidemias (guidelines 1-3), while the third section offers guidelines for the treatment of dyslipidemias (guidelines 4-5). The key guideline statements are supported mainly by data from studies in the general population, but there is an urgent need for additional studies in CKD and in transplant patients. Therefore, the last section outlines recommendations for research.

Adolescent↗

Glomerulosclerosis in aging humans is not influenced by gender.

Aging male rats develop progressive glomerulosclerosis, proteinuria, and loss of renal function, whereas females are remarkably resistant to the development of these abnormalities. Although sex hormones appear to contribute to gender-related differences in the development of glomerulosclerosis in aging rats, it is not clear that sexual dimorphism characterizes glomerular obsolescence in aging humans. To study this question further, the glomerular histology of males and females ranging in age from infancy to 90 years was compared in 250 autopsy specimens. We found no differences between the sexes in the development of glomerulosclerosis in aging humans. These data disprove the hypothesis that testosterone is an important factor contributing to progressive glomerulosclerosis in aging men. Conversely, any renoprotective effects of estrogen would be limited by the onset of menopause because significant glomerulosclerosis did not develop until after the age of 50 years.

Adult↗

Proteinuria is a risk factor for mortality over 10 years of follow-up. MRFIT Research Group. Multiple Risk Factor Intervention Trial.

Proteinuria has been shown to be strongly associated with the prevalence and incidence of cardiovascular disease. It has been difficult to determine if the link is causal and independent. The mortality follow-up for the Multiple Risk Factor Intervention Trial (MRFIT) randomized cohort provides an opportunity to examine these relationships. Between 1973 and 1975, 361,662 men, ages 35 to 57, were screened for blood pressure, serum cholesterol, and cigarette smoking. Patients receiving medication for diabetes were excluded. Men in the upper 10 to 15% of coronary heart disease (CHD) risk (12,866) were randomized into the MRFIT trial. Standard casual urine dipstick determinations (Labstix) for protein were done at baseline and annually for six years. Post-trial cause-specific mortality was ascertained using the National Death Index. During the trial, 2326 (18.1%) of participants had + or higher proteinuria, and 593 (4.6%) had +2 or higher proteinuria. The presence of proteinuria during the six years of follow-up was consistently associated with higher all cause, cardiovascular disease (CVD) and CHD mortality, even after adjusting for other risk factors. The higher and more persistent the proteinuria, the greater the risk. In this data set, proteinuria is a strong and independent risk factor for CVD mortality.

Cardiovascular Diseases↗

Clinical impact of replacing Minnesota antilymphocyte globulin with ATGAM.

In August 1992, we replaced Minnesota antilymphocyte globulin (MALG) with lymphocyte immune globulin, antithymocyte globulin (equine) (ATGAM) in our immunosuppression protocols. The clinical impression of increased graft rejection prompted our assessment of the effect of this change on patient and graft outcome. The initial study group consisted of 426 renal transplant recipients transplanted between October 1, 1987, and September 21, 1993. After exclusions, 388 transplant events, with a minimum 8-month follow-up, made up the final study cohort: 323 patients received MALG and 65 received ATGAM. Immunosuppression included intravenous methylprednisolone, oral prednisone, oral AZA, CsA in some cases, and intravenous MALG or ATGAM, 15 mg/kg/day, for 7 to 14 days. Acute rejection was treated with high dose intravenous steroids and steroid-resistant episodes were treated additionally with either MALG or OKT3. Statistical comparisons were stratified for multiple patient characteristics and treatment variations. There was a greater incidence of rejection in general, and a higher incidence of steroid-resistant episodes requiring subsequent antilymphocyte globulin therapy (P = 0.0073) in patients receiving ATGAM versus MALG. No difference was seen in the incidence of CMV infection or blood-borne sepsis. Lymphoma occurred in 3 MALG and 2 ATGAM recipients. MALG recipients were significantly less likely to experience rejection within the first 60 days after transplant (P = 0.0127 using unstratified data; P < 0.0001 when data were stratified for patient characteristics). The relative risk of acute rejection for posttransplant days 5, 7, 10, and 14 was consistently higher for ATGAM-treated patients. We conclude that MALG and ATGAM are not equivalent drugs, and that MALG is a more effective immunosuppressant, and is just as safe as ATGAM in our protocol environment.

Adult↗

Effect of long-term clofibric acid treatment on serum and tissue lipid and cholesterol levels in obese Zucker rats.

The long-term effects of clofibric acid (200 mg/kg body weight) injected subcutaneously from 6-36 weeks of age were assessed in obese, hyperlipemic Zucker rats. At 18 and 36 weeks of age, treated rats had significantly lower fasted serum cholesterol levels but triacylglycerol levels were not affected. Rats were killed at 36 weeks of age at which time there were no differences in body and kidney weights between control and clofibric acid-treated rats. Liver, spleen and heart weights were lowered by clofibric acid treatment. In liver there was an elevation of lipid/g due to treatment but there were no effects on cholesterol/g or on either total liver lipid or cholesterol levels. In the epididymal fat pad of clofibric acid-treated rats, there was a 21% elevation of cholesterol level on a per pad basis. In the other organs, there were no effects of treatment on lipid or cholesterol levels except for lowered total cholesterol in kidney. Several liver lipogenic enzymes were lowered by treatment but malic enzyme was two times higher.

Adipose Tissue↗

Adriamycin-induced chronic proteinuria: a structural and functional study.

Focal, segmental glomerulosclerosis is frequently associated with chronic proteinuria and progressively declining renal function in humans as well as in experimental models of glomerular disease. Although little is known regarding the pathogenesis of this lesion, persistent, massive proteinuria has been associated with a poor prognosis. The administration of adriamycin to rats results in proteinuria of glomerular origin. We used this model to study the glomerular functional and structural alterations associated with proteinuria of 4 to 5 weeks duration. Studies of single nephron function revealed a 34% reduction in nephron plasma flow and a 50% decline in the glomerular ultrafiltration coefficient in rats given adriamycin. Single nephron glomerular filtration rate, however, was only modestly reduced (27%), because of an 8.0 mm Hg elevation of mean transcapillary hydraulic pressure difference (P less than 0.05). Morphologically, glomeruli of adriamycin-treated rats demonstrated significantly increased mesangial matrix and cellularity. In addition, glomerular capillaries frequently appeared enlarged, and epithelial cell bleb formation was evident. Focal glomerulosclerosis, however, was only rarely seen. The functional and morphologic characteristics of chronic adriamycin nephrosis are different from those associated with chronic proteinuria induced by repetitive administration of aminonucleoside of puromycin. Comparison of the two models suggests that the development of focal glomerulosclerosis can be dissociated from proteinuria and elevations of intraglomerular hydraulic pressures.

Animals↗