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Evaluation of Polyneuropathy Markers in Type 1 Diabetic Kidney Transplant Patients and Effects of Islet Transplantation

Neurophysiological and skin biopsy longitudinal analysis

¹ Department of Neurology and Clinical Neurophysiology, San Raffaele Scientific Institute, Milan, Italy
² Department of Medicine, San Raffaele Scientific Institute, Milan, Italy
³ Transplantation Research Center, Brigham and Women's Hospital/Children's Hospital/Harvard Medical School, Boston, Massachusetts
⁴ Department of Clinical Science, La Sapienza University Rome, Rome, Italy
⁵ Università Vita-Salute San Raffaele, Milan, Italy

Address correspondence and reprint requests to Paolo Fiorina, MD, Department of Medicine, San Raffaele Scientific Institute, Università Vita e Salute, Via Olgettina 60, 20132 Milan, Italy. E-mail: paolo.fiorina{at}hsr.it

OBJECTIVE—The purpose of this study was to evaluate whether islet transplantation may stabilize polyneuropathy in uremic type 1 diabetic patients (end-stage renal disease [ESRD] and type 1 diabetes), who received a successful islet-after-kidney transplantation (KI-s).

RESEARCH DESIGN AND METHODS—Eighteen KI-s patients underwent electroneurographic tests of sural, peroneal, ulnar, and median nerves: the nerve conduction velocity (NCV) index and amplitudes of both sensory action potentials (SAPs) and compound motor action potentials (CMAPs) were analyzed longitudinally at 2, 4, and 6 years after islet transplantation. Skin content of advanced glycation end products (AGEs) and expression of their specific receptors (RAGE) were also studied at the 4-year follow-up. Nine patients with ESRD and type 1 diabetes who received kidney transplantation alone (KD) served as control subjects.

RESULTS—The NCV score improved in the KI-s group up to the 4-year time point (P = 0.01 versus baseline) and stabilized 2 years later, whereas the same parameter did not change significantly in the KD group throughout the follow-up period or when a cross-sectional analysis between groups was performed. Either SAP or CMAP amplitudes recovered in the KI-s group, whereas they continued worsening in KD control subjects. AGE and RAGE levels in perineurium and vasa nervorum of skin biopsies were lower in the KI-s than in the KD group (P < 0.01 for RAGE).

CONCLUSIONS—Islet transplantation seems to prevent long-term worsening of polyneuropathy in patients with ESRD and type 1 diabetes who receive islets after kidney transplantation. No statistical differences between the two groups were evident on cross-sectional analysis. A reduction in AGE/RAGE expression in the peripheral nervous system was shown in patients receiving islet transplantation.

Abbreviations: AGE, advanced glycation end product • CMAP, compound motor action potential • CML, N-(carboxymethyl) lysine • DPN, diabetic polyneuropathy • ESRD, end-stage renal disease • NCV, nerve conduction velocity • RAGE, receptor for AGE • SAP, sensory action potential

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