Skin denervation and its clinical significance in late-stage chronic kidney disease

Objective: To investigate the skin innervation and its clinical significance in late-stage chronic kidney disease (CKD). Design: Case series. Setting: National Taiwan University Hospital, Taipei, Taiwan. Patients: Forty consecutive nondiabetic patients with late-stage CKD (14 female and 26 male; mean [SD] age, 60.7 [12.3] years), including 2 cases with stage 3 CKD, 6 with stage 4 CKD, and 32 with stage 5 CKD, ie, end-stage kidney disease. Interventions: Clinical evaluation of neurological deficits, nerve conduction study, autonomic function tests, and a 3-mm-diameter skin biopsy specimen taken from the distal leg. Main Outcome Measures: Quantitation of epidermal innervation, parameters of nerve conduction study, R-R interval variability, and sympathetic skin response. Results: Clinically, 21 patients (52.5%) were symptomatic with paresthesia over the limbs or autonomic symptoms. The intraepidermal nerve fiber (IENF) density was markedly reduced in patients with CKD compared with age and sex-matched controls (mean [SD], 2.8 [2.0] vs 8.6 [2.8] fibers/mm; P<.001). Skin denervation was observed in 27 patients (67.5%). Fifteen patients (37.5%) had abnormalities on nerve conduction studies, and 29 patients (72.5%) had abnormal results on autonomic function tests. By analysis with multiple regression models, the IENF density was negatively correlated with the duration of renal disease (P=.02). Additionally, the R-R interval variability at rest was linearly correlated with the IENF density (P=.02) and the absence of sympathetic skin responses at the soles was associated with reduced IENF density (P=.03). Conclusions: Small-fiber sensory and autonomic neuropathies constitute the major form of neuropathy in latestage CKD. Furthermore, skin denervation was associated with the duration of renal disease. ?2011 American Medical Association. All rights reserved.