Evaluation of polyneuropathy markers in type 1 diabetic kidney transplant patients and effects of islet transplantation: neurophysiological and skin biopsy longitudinal analysis.
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).


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.
Del Carro
Ubaldo
U
Department of Neurology and Clinical Neurophysiology, San Raffaele Scientific Institute, Milan, Italy.
Fiorina
Paolo
P
Amadio
Stefano
S
De Toni Franceschini
Luisa
L
Petrelli
Alessandra
A
Menini
Stefano
S
Martinelli Boneschi
Filippo
F
Ferrari
Stefania
S
Pugliese
Giuseppe
G
Maffi
Paola
P
Comi
Giancarlo
G
Secchi
Antonio
A
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000601:surgery*; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D004594:Electrophysiology; D006801:Humans; D016381:Islets of Langerhans Transplantation; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation; D008137:Longitudinal Studies; D008875:Middle Aged; D010525:Peripheral Nerves / Q000503:physiopathology; D012867:Skin / Q000473:pathology*