Morphology of cyclosporine nephrotoxicity in human heart transplant recipients

The morphologic findings of renal biopsies (four cases studied by electron microscopy) and renal specimens obtained from 44 autopsies of patients who died after heart transplantation are reviewed. Eight patients treated postoperatively with cyclosporine (serum concentration of 100 to 150 ng/ml), with a survival rate of 1 to 24 months, constantly had renal lesions of variable severity. Correlated with functional renal disturbances, these changes predominantly affect the proximal convoluted tubule: vacuolization, calcifications, and tubular atrophy. The interstitial fibrosis, increasing parallel to tubular alterations, occurs only after 3 months after transplantation. The hypertrophy of juxtaglomerular apparatus and the arteriolar sclerosis noted on and after the fourth month were associated with arterial hypertension. Among the other inconstant and mild lesions (attrition of vascular endothelium and arteriolar or glomerular thrombi), the partial sclerosis of glomerular flocculus, probably correlated with tubular lesions, seems more significant. Thus these findings corroborate the nephrotoxicity of cyclosporine (principally against the proximal convoluted tube), the increase of lesions with time, and the possible irreversibility of the lesions despite appropriately decreasing the dosage of cyclosporine to eliminate toxic side effects.