Microvascular changes in renal allografts associated with FK506 (Tacrolimus) therapy

Abstract

FK506 (Tacrolimus) recently has been shown to be an effective immunosuppressant after renal transplantation. It is associated with less hypertension, hypercholesterolemia and steroid use compared with cyclosporine. We report 10 patients on FK506 who showed fibrin thrombi within the glomerular capillaries and/or arterioles at renal allograft biopsy. These biopsies were generally performed to assess increasing serum creatinine levels; laboratory evidence of hemolytic uremic syndrome was present in one instance. Plasma or whole blood FK506 levels were elevated in eight of 10 cases. Reduction of immunosuppression led to clinical improvement or biopsy-proven resolution of thrombi in all cases. These observations suggest that FK506 may occasionally produce microvascular changes in the renal allograft. The estimated incidence of this occurrence (1%) is comparable with that reported with cyclosporine (3%).

FIG. 1

A partially occlusive fibrin thrombus seen within the afferent arteriole of a glomerulus. The capillary loops distal to the thrombus appear to be dilated.

FIG. 2

An isolated glomerular capillary loop thrombus (arrow) visualized by the Masson’s silver trichrome technique.

FIG. 3

A diffuse deposition of fibrin involving nearly all capillary loops was seen in this glomerulus.

FIG. 4

This afferent arteriole is completely occluded by a thrombus. The medial coat is permeated by a proteinaceous insudate and shows vacuolar change. A light periarteriolar infiltrate of lymphocyte is present, but there was no significant interstitial inflammation and no tubulitis. The patient responded to a reduction in drug dosage.

FIG. 5

Globules of a pink eosinophilic material were seen in the media of this small arteriole. The size of these globules and lack of proximity of this vessel to a glomerulus make it unlikely that the myocytes observed are a part of the juxtaglomerular apparatus. A similar lesion was reported in an experimental study on rats (11).

FIG. 6

An interlobular artery with focal coagulative necrosis of the media and nuclear karyorrhexis. The interpretation of FK506 toxicity in this biopsy sample was supported by a concomitantly high FK506 level and improvement in renal allograft function when immunosuppression was reduced. This case has been previously reported, and this illustration is reproduced with permission from the publishers (19).