LOW-DOSE CYCLOSPORINE THERAPY IN TRIPLE-DRUG IMMUNOSUPPRESSION FOR HEART-TRANSPLANT RECIPIENTS

The toxicity of long-term immunosuppressive therapy has become a major concern in long-term follow-up of heart transplant recipients. In thi s respect the quality of renal function is undoubtedly linked to cyclo sporin A (CsA) drug levels. In cardiac transplantation, specific CsA t rough levels have historically been maintained between 250 and 350 mu g/L in many centers without direct evidence for the necessity of such high levels while using triple-drug immunosuppression. This retrospect ive analysis compares the incidence of acute and chronic graft rejecti on as well as overall mortality between groups of patients with high ( 250 to 350 mu g/L) and low (150 to 250 mu g/L specific CsA trough leve ls. A total of 332 patients who underwent heart transplantation betwee n October 1985 and October 1992 with a minimum follow-up of 30 days we re included in this study (46 women and 276 men; aged, 44 +/- 12 years ; mean follow-up, 1,122 +/- 777 days). Standard triple-drug immunosupp ression included first-year specific CsA target trough levels of 250 t o 300 mu g/L. Patients were grouped according to their average creatin ine level in the first postoperative year (group I, <130 mu mol/L, n = 234; group II, greater than or equal to 130 mu mol/L, n = 98). The ov erall 5-year survival excluding the early 30-day mortality was 92% (gr oup I, 216/232) and 91% (group II, 89/98) with 75% of the mortality du e to chronic rejection. The rate of rejection for the entire follow-up period was similar in both groups (first year: group I ,3.2 +/- 2.6 r ejection/patient/year; group II, 3.6 +/- 2.7 rejection/ patient/year; p = not significant). The CsA levels were significantly lower in group II patients (CsA level: group I, 240 +/- 58 mu g/L versus group II, 1 97 +/- 51 mu g/L; p < 0.05). The results show that in patients with pr eoperatively or perioperatively compromised renal function specific Cs A levels can be lowered safely to less than 200 mu g/L without an incr eased risk for acute or chronic graft rejection. This reduction often is associated with preservation or even improvement of renal function.