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

A retrospective chart analysis of 200 consecutive, cyclosporine-treate d, renal allograft recipients, transplanted between January 1988 and J une 1992, was conducted to determine the incidence of and the etiologi c variables for post-transplant hypercholesterolemia. In addition, the effectiveness of dietary intervention alone or in combination with ge mfibrozil (600 mg b.i.d.), in post-transplant hypercholesterolemia was evaluated. Hypercholesterolemia (greater than or equal to 240 mg/dl o n two separate determinations, while on maintenance immunosuppression) was present in 138 patients (Group A - 69%). When compared to the rem aining 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 t hese groups. Post-transplant hypercholesterolemia was significantly mo re prevalent in females, in recipients with higher baseline serum tota l 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 bl ood 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 hypercholesterol emia, 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 g rading of dietary compliance at each follow-up visit (Grade 1, <300 mg cholesterol; Grade 2, 300-500 mg cholesterol; Grade 3, >500 mg choles terol intake in 24 hours). Six months following dietary modification, there was no significant decrease in serum cholesterol lelvels, even w hen stratified for the grade of dietary compliance. Gemfibrozil therap y was initiated in 48 patients at an interval of 0.85+/-0.12 years aft er dietary intervention. When compared to baseline, 3-, 6-, and 12-mon th post-treatment serum total cholesterol levels had decreased by 9%, 8%, and 4% (only the former two were statistically significant), and t riglyceride levels had decreased by 26%, 34%, and 28% (all statistical ly significant), respectively. The most significant decline in serum t riglyceride level, in response to gemfibrozil therapy, occurred in pat ients who had moderate to severe elevations in their serum triglycerid e 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) a lone did not reduce serum total cholesterol levels, even in seemingly compliant patients, b) gemfibrozil therapy, even in combination with d ietary modification, has minimal effect on post-transplant hypercholes terolemia, although it has a modest sustained effect on hypertriglycer idemia. Other strategies, including pre-transplant therapy of hypercho lesterolemia, and/or the use of other lipid-lowering agents, need to b e investigated to avoid the long-term sequelae of hyperlipidemia.