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

Neurophysiological and skin biopsy longitudinal analysis

  1. Ubaldo Del Carro, MD1,
  2. Paolo Fiorina, MD, PHD23,
  3. Stefano Amadio, MD1,
  4. Luisa De Toni Franceschini, MD1,
  5. Alessandra Petrelli, MD2,
  6. Stefano Menini, PHD4,
  7. Filippo Martinelli Boneschi, MD, PHD1,
  8. Stefania Ferrari, MD1,
  9. Giuseppe Pugliese, MD, PHD4,
  10. Paola Maffi, MD2,
  11. Giancarlo Comi, MD15 and
  12. Antonio Secchi, MD25
  1. 1Department of Neurology and Clinical Neurophysiology, San Raffaele Scientific Institute, Milan, Italy
  2. 2Department of Medicine, San Raffaele Scientific Institute, Milan, Italy
  3. 3Transplantation Research Center, Brigham and Women's Hospital/Children's Hospital/Harvard Medical School, Boston, Massachusetts
  4. 4Department of Clinical Science, La Sapienza University Rome, Rome, Italy
  5. 5Università Vita-Salute San Raffaele, Milan, Italy
  1. 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.


  • Published ahead of print at http://care.diabetesjournals.org on 5 September 2007. DOI: 10.2337/dc07-0206.

    U.D.C. and P.F. contributed equally to this study.

    Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc07-0206.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted August 24, 2007.
    • Received January 31, 2007.
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  1. Diabetes Care vol. 30 no. 12 3063-3069
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