MART: Metabolic Acidosis in Renal Transplant Patients

Sponsor

University of Zurich (Other)

Overall Status

Completed

CT.gov ID

NCT00913796

Collaborator

University of Texas Southwestern Medical Center (Other), Swiss Federal Institute of Technology (Other)

Enrollment

Location

Arms

Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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

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

Study Design

Study Type:

Interventional

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 :

Dec 1, 2007

Actual Primary Completion Date :

Mar 1, 2010

Actual Study Completion Date :

Mar 1, 2010

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Correction of metabolic acidosis [12 months]

Secondary Outcome Measures

Improvement in physical capacity [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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