Working… Menu

Metabolic Acidosis in Renal Transplant Patients (MART)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00913796
Recruitment Status : Completed
First Posted : June 4, 2009
Last Update Posted : October 22, 2010
University of Texas Southwestern Medical Center
Swiss Federal Institute of Technology
Information provided by:
University of Zurich

Brief Summary:

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 or disease Intervention/treatment Phase
Renal Transplant Patients Metabolic Acidosis Physical Capacity Bone Disease Mineral Metabolism Drug: Potassium citrate Drug: Potassium chloride Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Metabolic Acidosis and Its Impact on Mineral Metabolism and Physical Performance in Renal Transplant Patients
Study Start Date : December 2007
Actual Primary Completion Date : March 2010
Actual Study Completion Date : March 2010

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Correction of metabolic acidosis [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Improvement in physical capacity [ Time Frame: 12 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   20 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00913796

Layout table for location information
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
Layout table for investigator information
Principal Investigator: Patrice M. Ambühl, M.D. University of Zurich
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Prof. Dr. Patrice Max Ambühl, University Hospital Zurich Identifier: NCT00913796    
Other Study ID Numbers: 3200B0-112299
First Posted: June 4, 2009    Key Record Dates
Last Update Posted: October 22, 2010
Last Verified: June 2009
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:
Layout table for MeSH terms
Bone Diseases
Musculoskeletal Diseases
Acid-Base Imbalance
Metabolic Diseases
Potassium Citrate
Natriuretic Agents
Physiological Effects of Drugs
Respiratory System Agents