Metabolic Acidosis in Renal Transplant Patients (MART)

This study has been completed.
Sponsor:
Collaborators:
University of Texas Southwestern Medical Center
Swiss Federal Institute of Technology
Information provided by:
University of Zurich
ClinicalTrials.gov Identifier:
NCT00913796
First received: April 1, 2009
Last updated: October 21, 2010
Last verified: June 2009
  Purpose

Acidosis (accumulation of acid in the body) may be an underrecognized problem in patients after renal transplantation. It may have consequences on physical performance due to negative effects on bone and muscle metabolism.

Therefore, the purpose of this study is

  1. to determine the status of physical capacity and bone structure in renal transplant patients with metabolic acidosis
  2. to study the effect of substituting base equivalents (citrate) on acid/base status of renal transplant patients with acidosis
  3. to compare the status of physical capacity and bone structure in renal transplant patients with metabolic acidosis before and after substitution with citrate

Condition Intervention Phase
Renal Transplant Patients
Metabolic Acidosis
Physical Capacity
Bone Disease
Mineral Metabolism
Drug: Potassium citrate
Drug: Potassium chloride
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Metabolic Acidosis and Its Impact on Mineral Metabolism and Physical Performance in Renal Transplant Patients

Resource links provided by NLM:


Further study details as provided by University of Zurich:

Primary Outcome Measures:
  • Correction of metabolic acidosis [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Improvement in physical capacity [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: December 2007
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Postassium citrate
Aim: correction of metabolic acidosis
Drug: Potassium citrate
2.41 gram of citrate b.i.d. for 12 months. Dosage to be adjusted according to serum potassium concentration.
Active Comparator: Potassium chloride
Potassium chloride is given to compensate for any possible effects of potassium in potassium citrate (primary treatment).
Drug: Potassium chloride
370 mg potassium t.i.d. for 12 months. Dosage to be adjusted according to serum postassium concentration.

Detailed Description:

Chronic kidney disease is developing to become one of the major health problems in the Western world with more than one million patients on renal replacement therapy, and many more expected in the years ahead [1]. Survival of patients with end stage renal disease has become possible with the introduction of dialysis therapy. Renal transplantation has resulted both in further reduction of mortality and improvement in quality of life for patients with end stage renal disease. Nevertheless, successful transplantation with regard to graft and patient survival is still associated with significant morbidity. Apart from infectious complications and cardiovascular disease, limitations in physical capacity from musculoskeletal disorders have become a relevant problem, resulting in reduced quality of life, poor physical functioning and inability to work.

Muscle and bone metabolism in chronic kidney disease are typically disturbed resulting in significant pathology and dysfunction of the affected tissues. They are associated with metabolic disorders related to renal insufficiency, among which metabolic acidosis is a major contributor. Metabolic acidosis is a well recognized problem in renal transplant patients. However, its prevalence, pathogenesis, course and sequelae are not well established. In particular, its relation to post-transplant bone and muscle disorders, and the impact on physical capabilities in renal transplant patients have not been comprehensively investigated so far.

The purpose of the proposed project is to examine the characteristics and pathogenesis of post-transplant metabolic acidosis, and its relation to bone and muscle pathologies and impact on physical capabilities in renal transplant patients. In particular, the following aims are proposed to investigate in de novo and long-term renal transplantation:

Aim # 1: To examine the type, degree and course of metabolic acidosis in renal transplant patients, early and long-term after transplantation

Aim # 2: To examine alterations in mineral and bone metabolism, and bone structure, and their relationship to the acid/base disorder

Aim # 3: To examine overall physical performance, exercise capacity and muscle energy content, and their relationship to the acid/base disorder

In order to analyze secondary effects of subclinical and overt acidosis on bone (Aim # 2) and muscle (Aim # 3), patients will be studied at baseline, and then be supplemented with base equivalents in order to achieve a stable plasma serum bicarbonate concentration of 24-26 mmol/l, and be reexamined thereafter. Completion of the three aims will allow to comprehensively analyze the pathogenesis of and interrelations between acid/base status, mineral metabolism, bone disorders and muscle function in renal transplant patients. This will be the first study to link metabolic alterations to structural and functional measures of the musculoskeletal system, and to the impact of the resulting pathologies on physical disabilities in patients with a kidney graft. We are in dire need to know the magnitude of the problem, whether to treat, and how aggressive to treat these patients. The results of this project will be indispensable regarding justification to rigorously evaluate and treat metabolic acidosis in patients with chronic renal insufficiency and after transplantation.

  Eligibility

Ages Eligible for Study:   20 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a renal graft having been transplanted within the previous 8 years and being at least 3 months post transplantation, or, patients scheduled to undergo transplantation from a living organ donor within the upcoming 3 months
  • Venous serum bicarbonate concentration < 24 mmol/L at time of baseline determination
  • Renal transplant function with a calculated glomerular filtration rate (GFR) greater or equal 30 ml/min according to the Cockcroft-Gault formula
  • Immunosuppressive therapy including a calcineurin inhibitor (cyclosporine A or tacrolimus)
  • Age 20 through 65 years of either sex
  • Written informed consent for study participation

Exclusion Criteria:

  • Acute rejection episode requiring specific therapy within 4 weeks before study inclusion
  • Severe impairment in general health and/or physical handicaps (malignant neoplasia, catabolic state, acute systemic infection requiring therapy)
  • Mental illness, psychiatric disorder
  • Tetracycline intolerance
  • Planned or "overt" pregnancy
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00913796

Locations
Switzerland
University Hospital of Zurich
Zurich, Switzerland, CH 8091
Sponsors and Collaborators
University of Zurich
University of Texas Southwestern Medical Center
Swiss Federal Institute of Technology
Investigators
Principal Investigator: Patrice M. Ambühl, M.D. University of Zurich
  More Information

No publications provided by University of Zurich

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Prof. Dr. Patrice Max Ambühl, University Hospital Zurich
ClinicalTrials.gov Identifier: NCT00913796     History of Changes
Other Study ID Numbers: 3200B0-112299
Study First Received: April 1, 2009
Last Updated: October 21, 2010
Health Authority: Switzerland: Swissmedic

Keywords provided by University of Zurich:
Renal transplantation
Metabolic acidosis
Physical capacity
Bone histology
Bone histomorphometry
Parathyroid function
Calcium and phosphate metabolism

Additional relevant MeSH terms:
Acidosis
Bone Diseases
Acid-Base Imbalance
Metabolic Diseases
Musculoskeletal Diseases
Citric Acid
Potassium Citrate
Anticoagulants
Cardiovascular Agents
Chelating Agents
Diuretics
Expectorants
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Sequestering Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014