Small-fiber Neuropathy in Chronic Kidney Disease

Neurological dysfunction is a common complication of late stage chronic kidney disease (CKD) and peripheral nerve system is often involved in such complication. Sensory disturbances such as paresthesia and hypoesthesia are the predominant symptoms in uremic polyneuropathy and it is traditionally thought the uremic polyneuropathy mainly involve large-diameter sensory nerves. However in uremic patients the abnormal thermal thresholds, the sensory symptoms like numbness, burning, paradoxical heat, cold or freezing, and pain, and the frequent symptoms of autonomic dysfunction suggest that small-fiber neuropathy should be a clinical entity in patients of CKD. But there are still few investigations with emphasis on the changes of small-fiber nerves in CKD, and little is known about the characteristics and mechanism of small-fiber neuropathy in CKD. Skin biopsy with evaluation of epidermal nerve density and the morphology of epidermal nerves and the subepidermal nerve plexus is an effective and minimally invasive test for assessment of small-fiber neuropathy. Contact heat evoked potential (CHEP) recording the brain responses evoked by contact heat stimuli on the skin is a non-invasive technique to investigate the thermo-nociceptive pathways mediated by small-fiber nerves. In the current study, we will use an integrated approach by combining the skin biopsy, quantitative sensory testing, autonomic function tests, and CHEP to investigate the pathological, psychophysical and physiological aspects of small-fiber neuropathy in patients of CKD. The aims of the current study is to address the following issues: (1) the changes of small fiber nerves in uremia and CKD of different stage; (2) the correlation of skin innervation with clinical manifestations, thermal thresholds, and autonomic function; (3) the influence of dialysis therapy, the type of dialysis therapy, or renal transplantation on the small fiber neuropathy in uremia; (4) the roles of blood chemical substances, metals, and endocrine profiles on the development of small-fiber neuropathy; (5) the relationship between the small-fiber neuropathy and pruritus or restless leg syndrome; and (6) the pathological and physiological correlates of painful symptoms by skin biopsy and CHEP in CKD related neuropathy. The results of the study will provide important insights in the understanding of the pathogenesis, and the prevention and new treatments of small-fiber neuropathy in CKD.

Study Overview

• Status: Unknown
• Conditions: Chronic Kidney Disease; Small-Fiber Neuropathy
• Intervention / Treatment: Other: Skin biopsy

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Sung-Tsang Hsieh, PhD; Phone Number: 88182 886-2-23123456; Email: shsieh@ntu.edu.tw
    • Principal Investigator: Chi-Chao Chao, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patients should fulfill the criteria of CKD according to renal function study and the patients of end-stage renal disease should receive regular dialysis therapy and follow-up at outpatient clinics.
• For disease comparison, patients with peripheral neuropathy of variable etiologies will also be recruited.

Exclusion Criteria:

• Poor control DM,
• Severe heart failure,
• Bleeding tendency,
• Severe lung disease with respiratory distress,
• Severe infection,
• Alcoholism,
• Amyloidosis,
• Poor wound healing history.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The pathology of skin biopsy	within 3 months after inclusion
Intraepidermal fiber density	within 3 months after inclusion
Autonomic function	within 3 months after inclusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Function of small-fiber sensory nerve	within 3 months after inclusion

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Study Director: Sung-Tsang Hsieh, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Anticipated): August 1, 2012

Study Registration Dates

• First Submitted: February 28, 2010
• First Submitted That Met QC Criteria: March 1, 2010
• First Posted (Estimate): March 2, 2010

Study Record Updates

• Last Update Posted (Estimate): March 2, 2010
• Last Update Submitted That Met QC Criteria: March 1, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: Chronic kidney disease; Autonomic neuropathy; Skin biopsy; Small-fiber neuropathy; Contact heat evoked potential; Neuropathy in late stage chronic kidney disease
• Additional Relevant MeSH Terms: Nervous System Diseases; Urologic Diseases; Renal Insufficiency; Neuromuscular Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Peripheral Nervous System Diseases; Small Fiber Neuropathy
• Other Study ID Numbers: 200812088R