Low-dose cyclosporine therapy in triple-drug immunosuppression for heart transplant recipients

Abstract

The toxicity of long-term immunosuppressive therapy has become a major concern in long-term follow-up of heart transplant recipients. In this respect the quality of renal function is undoubtedly linked to cyclosporin A (CsA) drug levels. In cardiac transplantation, specific CsA trough levels have historically been maintained between 250 and 350 μg/L in many centers without direct evidence for the necessity of such high levels while using triple-drug intmunosuppression. This retrospective analysis compares the incidence of acute and chronic graft rejection as well as overall mortality between groups of patients with high (250 to 350 μg/L) and low (150 to 250 μg/L) specific CsA trough levels. A total of 332 patients who underwent heart transplantation between October 1985 and October 1992 with a minimum follow-up of 30 days were included in this study (46 women and 276 men; aged, 44± 12 years; mean follow-up, 1,122 ± 777 days). Standard triple-drug immunosuppression included firstyear specific CsA target trough levels of 250 to 300 μg/L. Patients were grouped according to their average creatinine level in the first postoperative year (group I, 1;30 μmol/L, n = 234; group II, 3≥130 μmol/L, n = 98). The overall 5-year survival excluding the early 30-day mortality was 92% (group I, 216/232) and 91% (group II, 89/98) with 75% of the mortality due to chronic rejection. The rate of rejection for the entire follow-up period was similar in both groups (first yean group I, 3.2 ± 2.6 rejection/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 1,240± 58 μg/L versus group II, 197± 51 μg/L; p < 0.05). The results show that in patients with preoperatively or perioperatively compromised renal function specific CsA levels can be lowered safely to less than 200 μg/L without an increased risk for acute or chronic graft rejection. This reduction often is associated with preservation or even improvement of renal function.