Early arteriolopathy following "high-dose" cyclosporine in kidney transplantation

Thirty-seven consecutive kidney graft biopsies from 37 patients immunosuppressed with "high-dose" cyclosporine (CsA) were mixed with 37 random biopsies obtained from 37 patients given azathioprine and prednisone (Aza/P) and reexamined by light microscopy, without knowledge of the therapy, for occurrence of early arteriolopathy. All biopsies were taken within 35 days after transplantation. Arteriolopathy was demonstrated in 12 biopsies from 37 patients given CsA but in none of those from 37 patients on Aza/P. The specific alteration found in those 12 biopsies was glycogen storage in the muscular layer of the arterioles. The average donor was significantly older in those grafts in which arteriolopathy was shown than in those without arteriolopathy but also given CsA (p less than 0.001). All kidneys from donors more than 53 yr old had arteriolopathy. The occurrence of arteriolopathy was independent of the average CsA level from transplantation to biopsy, but the CsA level had never been below 380 ng/ml in those patients with arteriolopathy. The clinical course in grafts with arteriolopathy was characterized by poorer graft function as judged from the renograms, delayed onset of function and a high proportion of "never-functioning" grafts (50%). We concluded that patients receiving a cadaver graft from a donor older than 50 yr should not be treated with "high-dose" CsA. If the arteriolopathy is demonstrated in kidney graft biopsies within the first 5 weeks after transplantation in patients treated with CsA, one should consider a change or modification of the treatment strategy.