IRREVERSIBILITY OF CYCLOSPORINE-INDUCED RENAL-FUNCTION IMPAIRMENT IN HEART-TRANSPLANT RECIPIENTS

The use of cyclosporine therapy for heart transplant recipients has be en associated with a significant improvement of graft survival. Renal function impairment is a frequent finding in patients chronically trea ted with cyclosporine. The purpose of this prospective randomized stud y was to establish renal function in a group of heart transplant recip ients receiving chronic cyclosporine treatment and to test the hypothe sis of reversibility of cyclosporine-induced nephropathy by late reduc tion of cyclosporine. A total of 28 patients who underwent operation a t least 18 months before this study began were randomly assigned to ei ther group A (n = 14), in which the whole-blood polyclonal cyclosporin e target trough level was reduced from 400 to 600 mug/L to 200 to 400 mug/L, and group B (n = 14), in which the level was maintained at 400 to 600 mug/L. Renal and cardiac function were assessed by paraaminohip puric acid, inulin and lithium clearances and heart catheterization, r espectively, at entry and 4 months later. Cellular rejection in the tr ansplanted heart was monitored by at least four endomyocardial biopsie s every 14 days with the histologic Texas scale (grading: 0 to 10). In heart recipients renal blood flow (592 +/- 202 ml/min/1.73 m2) and gl omerular-filtration rate (74 +/- 33 ml/min/1.73 m2) were significantly lower (p < 0.01), and mean arterial blood pressure (109 +/- 13 mm Hg) and renal vascular resistance (22.4 +/- 9 mm Hg/dl/min/1.73 m2) were significantly higher than the corresponding values in normal controls (p < 0.01). Whole blood polyclonal cyclosporine levels at entry and en d of the trial were 519 +/- 83 and 238 +/- 101 mug/L (group Ap < 0.001 ) and 490 +/- 92 and 510 +/- 110 mug/L (group B, NS). During the cyclo sporine reduction trial no significant change occurred for all renal f unction parameters in both groups and particularly in patients with cy closporine reduction (group A). However, in patients of group A the Te xas-score rejection grade increased from 1.98 +/- 0.9 to 2.43 +/- 0.9 (p < 0.05). These data indicate that heart transplant recipients recei ving chronic cyclosporine therapy often have moderate renal function i mpairment. Late cyclosporine reduction as used in this study does not improve renal function impairment and may be associated with an increa sed risk of cellular rejection in the transplanted heart.