POSTTRANSPLANT HYPERLIPIDEMIA - RISK-FACTORS AND RESPONSE TO DIETARY MODIFICATION AND GEMFIBROZIL THERAPY

A retrospective chart analysis of 200 consecutive, cyclosporine-treated, renal allograft recipients, transplanted between January 1988 and June 1992, was conducted to determine the incidence of and the etiologic variables for post-transplant hypercholesterolemia. In addition, the effectiveness of dietary intervention alone or in combination with gemfibrozil (600 mg b.i.d.), in post-transplant hypercholesterolemia was evaluated. Hypercholesterolemia (greater than or equal to 240 mg/dl on two separate determinations, while on maintenance immunosuppression) was present in 138 patients (Group A - 69%). When compared to the remaining 62 patients without hypercholesterolemia (Group B - 31%), there were no differences in mean age, body weight at transplantation, race, incidence of overt diabetes, systolic and diastolic blood pressure, or serial serum creatinine, albumin, and cyclosporine levels between these groups. Post-transplant hypercholesterolemia was significantly more prevalent in females, in recipients with higher baseline serum total cholesterol levels (mean+/-SEM, Group A=229.0+/-5.0 vs. Group B=192.0+/-6.1 mg/dl, p<0.001), and in recipients with an elevated fasting blood glucose at 1 year post-transplant (Group A=150.5+/-10.5 vs. Group B = 105.2+/-10.7 mg/dl, p<0.05). In all patients with hypercholesterolemia, a hypocaloric low fat and low cholesterol (<300 mg/day) diet was initiated at a mean of 0.59+/-0.06 years after transplantation with grading of dietary compliance at each follow-up visit (Grade 1, <300 mg cholesterol; Grade 2, 300-500 mg cholesterol; Grade 3, >500 mg cholesterol intake in 24 hours). Six months following dietary modification, there was no significant decrease in serum cholesterol lelvels, even when stratified for the grade of dietary compliance. Gemfibrozil therapy was initiated in 48 patients at an interval of 0.85+/-0.12 years after dietary intervention. When compared to baseline, 3-, 6-, and 12-month post-treatment serum total cholesterol levels had decreased by 9%, 8%, and 4% (only the former two were statistically significant), and triglyceride levels had decreased by 26%, 34%, and 28% (all statistically significant), respectively. The most significant decline in serum triglyceride level, in response to gemfibrozil therapy, occurred in patients who had moderate to severe elevations in their serum triglyceride levels at baseline. We also found a significant reduction in VLDL-C (28% reduction) at 12 months of gemfibrozil treatment. In conclusion, a) dietary modification (hypocaloric, low fat, low cholesterol diet) alone did not reduce serum total cholesterol levels, even in seemingly compliant patients, b) gemfibrozil therapy, even in combination with dietary modification, has minimal effect on post-transplant hypercholesterolemia, although it has a modest sustained effect on hypertriglyceridemia. Other strategies, including pre-transplant therapy of hypercholesterolemia, and/or the use of other lipid-lowering agents, need to be investigated to avoid the long-term sequelae of hyperlipidemia.