Relationship of cyclosporin and sirolimus blood concentrations regarding the incidence and severity of hyperlipidemia after kidney transplantation

Abstract

The influence of drug concentrations on the development of persistent posttransplant hyperlipidemia was investigated in 82 patients who received cyclosporin A (CsA) and prednisone plus sirolimus (SRL) (52) or azathioprine (AZA) (30) during the first year after transplantation. Blood levels of CsA and SRL, daily doses of AZA and prednisone, and cholesterol, triglyceride, and glucose concentrations were determined during each visit (pretransplant and 30, 60, 90, 120, 180, and 360 days posttransplant). Persistent hyperlipidemia was defined as one-year average steady-state cholesterol (Cav CHOL ) or triglyceride (Cav TG ) concentrations above 240 and 200 mg/dL, respectively. Mean cholesterol and triglyceride concentrations increased after transplantation (P < 0.01) and were higher in patients receiving SRL compared to AZA (P < 0.001). Patients receiving SRL showed a significantly higher number of cholesterol (>229 or >274 mg/dL) and triglyceride (>198 or >282 mg/dL) determinations in the upper interquartile ranges. CsA and SRL interquartile ranges correlated with cholesterol concentrations (P = 0.001) whereas only SRL interquartile ranges correlated with triglyceride concentrations (P < 0.0001). Only pretransplant cholesterol concentration >205 mg/dL was independently associated with development of persistent hypercholesterolemia (Cav CHOL >240 mg/dL, relative risk (RR) = 20, CI 3.8-104.6, P = 0.0004) whereas pretransplant triglyceride concentration >150 mg/dL (RR = 7.2, CI 1.6-32.4, P = 0.01) or >211 mg/dL (RR = 19.8, CI 3.6-107.9, P = 0.0006) and use of SRL (RR = 3, CI 1.0-8.8, P = 0.0049) were independently associated with development of persistent hypertriglyceridemia (Cav TG >200 mg/dL). Persistent hypercholesterolemia was more frequent among patients with higher pretransplant cholesterol concentrations and was dependent on both CsA and SRL concentrations. Persistent hypertriglyceridemia was more frequent among patients with higher pretransplant triglyceride concentrations and was dependent on SRL concentrations.

Effect of isavuconazole on tacrolimus and sirolimus serum concentrations in allogeneic hematopoietic stem cell transplant patients: A drug‐drug interaction study

“…Two patients each had one sirolimus concentration >15 ng/mL (Figure ). Neither patient developed hypertriglyceridemia, which has been shown in previous studies to be correlated with elevated sirolimus serum concentrations . One patient experienced an increase in serum creatinine (from 0.95 to 1.32 mg/dL) the day following the elevated sirolimus serum concentration.…”

Severe Hypertriglyceridemia Induced by Sirolimus Treated With Medical Management Without Plasmapheresis: A Case Report

“…In contrast, other studies show a dose or trough dependence of sirolimus-induced hypertriglyceridemia. 8,9 Spinelli et al reported that triglyceride concentration was independently associated with sirolimus level (r 2 ¼ .03, P ¼ .005) regardless of cyclosporine level. 9 They concluded that sirolimus-induced hypertriglyceridemia was dependent on sirolimus level.…”

Lipid Profile Changes During the First Year After Kidney Transplantation: Risk Factors and Influence of the Immunosuppressive Drug Regimen

“…2 In addition to all of the risk factors of the general population, the presence of impaired allograft function, proteinuria, an acute rejection episode and its treatment with corticosteroids, new-onset diabetes mellitus after transplantation and various types and doses of immunosuppressive agents also contribute as risk factors among the kidney transplant population. 3,4 Several guidelines defining the type, severity, and targets for therapeutic interventions of dyslipidemia have been implemented. They focus on total cholesterol (TC) and/or low-density lipoprotein cholesterol (LDL-C) concentrations.…”