Reversal of Lesions of Diabetic Nephropathy After Pancreas Transplantation

KIDNEY TRANSPLANTATION AND RENOVASCULAR HYPERTENSION

daclizumab reduces the frequency of acute rejection with no increase in immunosuppression related morbidity. Longer followup is needed to determine the impact on intermediate and long-term graft survival. Andrew C. Novick, M.D. Reversal of Lesions of Diabetic Nephropathy After Pancreas Transplantation

P. F I O R E ~ M. O , W. STEFFES, D. E. R. SUTHERLAND, F. C. GOETZAND M. MAUER,Department of Internal Medicine and Center for Study of Aging of National Research Council, University of Padua Medical School, Padua, Italy, and Departments of Laboratory Medicine and Pathology, Surgery, Medicine and Pediatrics, University of Minnesota School of Medicine, Minneapolis, Minnesota New Engl. J. Med., 339 69-75,1998 Background: In patients with type 1diabetes mellitus who do not have uremia and have not received a kidney transplant, pancreas transplantation does not ameliorate established lesions of diabetic nephropathy within five years after transplantation, but the effects of longer periods of normoglycemia are unknown. Methods: We studied kidney function and performed renal biopsies before pancreas transplantation and 5 and 10 years thereafter in eight patients with type 1 diabetes but without uremia who had mild to advanced lesions of diabetic nephropathy at the time of transplantation. The biopsy samples were analyzed morphometrically. Results: All patients had persistently normal glycosylated hemoglobin values after transplantation. The median urinary albumin excretion rate was 103 mg per day before transplantation, 30 mg per day 5 years after transplantation, and 20 mg per day 10 years after transplantation (P = 0.07 for the comparison of values at base line and at 5 years; P = 0.11 for the comparison between base line and 10 years). The mean (LSD) creatinine clearance rate declined from 108 2 20 ml per minute per 1.73 m2 of body-surface area at base line to 74 5 16 ml per minute per 1.73 m2 at 5 years (P <0.001) and 74 2 14 ml per minute per 1.73 m2 at 10 years (P <0.001). The thickness of the glomerular and tubular basement membranes was similar at 5 years (570 5 64 and 928 5 173 nm, respectively) and at base line (594 5 81 and 911 t 133 nm, respectively) but had decreased by 10 years (to 404 % 38 and 690 5 111nm, respectively; P <0.001 and P = 0.004 for the comparisons with the base-line values). The mesangial fractional volume (the proportion of the glomerulus occupied by the mesangium) increased from base line (0.33 % 0.07) to 5 years (0.39 -t 0.10, P = 0.02) but had decreased at 10 years (0.27 5 0.02, P = 0.05 for the comparison with the base-line value and P = 0.006 for the comparison with the value at 5 years), mostly because of a reduction in mesangial matrix. Conclusions: Pancreas transplantation can reverse the lesions of diabetic nephropathy, but reversal requires more than five years of normoglycemia. Reprinted with permission from Massachusetts Medical Society. Editorial Comment: This study is the first to confirm that long-term normoglycemia after pancreas transplantation can ameliorate the glomerular and tubular lesions that characterize diabetic nephropathy in patients with type I diabetes who have not undergone renal transplantation. That it took 10 years for the lesions to be reversed is consistent with their slow development. It is known that diabetic renal lesions develop for at least a decade after the onset of diabetes before causing any functional renal abnormalities. The findings in this study are not a consequence of long-term immunosuppression, since in patients with diabetes who have undergone renal transplantation, nephropathic lesions develop at rates similar to those in diabetic patients with their o w n kidneys. While these data are encouraging, the limited long-term efficacy and significant morbidity of isolated pancreas transplantation are such that insulin treatment is still preferable for most patients with type I diabetes who do not have uremia. Isolated pancreas transplantation in this setting is best reserved for select patients with brittle diabetes in whom glucose control is difficult to achieve. Andrew C. Novick, M.D. Primary Immunosuppression With Tacrolimus and Mycophenolate Mofetil for Renal Allograft Recipients

D. ROTH,J. COLONA, G. W. BURKE, G. CIANCIO, V. ESQUENAZI AND J. MILLER, Departments of Medicine, Surgery, and Microbiology and Immunology, University of Miami School of Medicine and Miami Veterans Adrninistration Hospital, Miami, Florida Transplantation, 6 5 248-252, 1998 Background. Studies using tacrolimus and corticosteroids or the combination of cyclosprine, mycophenolate mofetil, and corticosteroids have been shown to reduce the incidence of biopsy-proven acute rejection episodes in cadaveric kidney recipients compared with cyclosporine-based immunosuppression. The current study is a retrospective analysis of our experience with tacrolimus combined with mycophenolate mofetil and steroids as primary immunosuppression for kidney transplant recipients. Methods. In a retrospective analysis, 72 patients who received primary therapy with tamolimus, myco-

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