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Islet Transplantation Is Associated with Improvement of Renal Function among Uremic Patients with Type I Diabetes Mellitus and Kidney Transplants

Paolo Fiorina^*, Franco Folli^*, Gianpaolo Zerbini^*, Paola Maffi^*, Chiara Gremizzi^*, Valerio Di Carlo, Carlo Socci, Federico Bertuzzi^*, Michael Kashgarian and Antonio Secchi^*,

Departments of *Medicine and Surgery, San Raffaele Scientific Institute, Milan, Italy; Department of Pathology, Yale University, New Haven, Connecticut; and University Vita-Salute San Raffaele, Milan, Italy.

Correspondence to Dr. Antonio Secchi, Internal Medicine, San Raffaele Scientific Institute, University Vita-Salute San Raffaele, Via Olgettina 60, 20132, Milan, Italy. Phone: +39-02-26432805; Fax: +39-02-26437788;

ABSTRACT. The potential effects of islet transplantation on the renal function of 36 patients with type I diabetes mellitus and kidney transplants were studied with 4 yr of follow-up monitoring. Kidney-islet recipients were divided into two groups, i.e., patients with successful islet transplants (SI-K group) (n = 24, fasting C-peptide levels of >0.5 ng/ml for >1 yr) and patients with unsuccessful islet transplants (UI-K group) (n = 12, fasting C-peptide levels of <0.5 ng/ml). Kidney graft survival rates and function, urinary albumin excretion rates, and sodium handling were compared. Na⁺/K⁺-ATPase activity in protocol kidney biopsies and in red blood cells was cross-sectionally analyzed. The SI-K group demonstrated better kidney graft survival rates (100, 83, and 83% at 1, 4, and 7 yr, respectively) than did the UI-K group (83, 72, and 51% at 1, 4, and 7 yr, respectively; P = 0.02). The SI-K group demonstrated reductions in exogenous insulin requirements and higher C-peptide levels, compared with the UI-K group, whereas GFR values were similar. Microalbuminuria (urinary albumin index) increased significantly in the UI-K group only (UI-K, from 92.0 ± 64.9 to 183.8 ± 83.8, P = 0.05; SI-K, from 108.5 ± 53.6 to 85.0 ± 39.0, NS). In the SI-K group, but not in the UI-K group, natriuresis decreased at 2 and 4 yr (P < 0.01). The SI-K group demonstrated greater Na⁺/K⁺-ATPase immunoreactivity in renal tubular cells (P = 0.05) and higher activity in red blood cells (P = 0.03), compared with the UI-K group. The Na⁺/K⁺-ATPase activity in red blood cells was positively correlated with circulating C-peptide levels but not with glycated hemoglobin levels. Successful islet transplantation was associated with improvements in kidney graft survival rates and function among uremic patients with type I diabetes mellitus and kidney grafts. E-mail: antonio.secchi@hsr.it

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