Metabolic Acidosis in Renal Transplant Patients (MART)

October 21, 2010 updated by: University of Zurich

Metabolic Acidosis and Its Impact on Mineral Metabolism and Physical Performance in Renal Transplant Patients

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Zurich, Switzerland, CH 8091
        • University Hospital of Zürich

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Correction of metabolic acidosis
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Improvement in physical capacity
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Zurich

Collaborators

University of Texas Southwestern Medical Center
Swiss Federal Institute of Technology

Investigators

  • Principal Investigator: Patrice M. Ambühl, M.D., University of Zurich

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (Actual)

March 1, 2010

Study Completion (Actual)

March 1, 2010

Study Registration Dates

First Submitted

April 1, 2009

First Submitted That Met QC Criteria

June 3, 2009

First Posted (Estimate)

June 4, 2009

Study Record Updates

Last Update Posted (Estimate)

October 22, 2010

Last Update Submitted That Met QC Criteria

October 21, 2010

Last Verified

June 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3200B0-112299

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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