Metabolic Acidosis in Renal Transplant Patients
Condition: Renal Transplant Patients; Metabolic Acidosis; Physical Capacity; Bone Disease; Mineral Metabolism
MeSH terms: Bone Diseases; Acidosis
Study type: Interventional
Phase: Phase 2

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
    

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.
    

Intervention name(s): Potassium citrate; Potassium chloride
Intervention type(s): Drug; Drug
Intervention description(s): 2.41 gram of citrate b.i.d. for 12 months. Dosage to be adjusted according to serum potassium concentration.; 370 mg potassium t.i.d. for 12 months. Dosage to be adjusted according to serum postassium concentration.
Intervention MeSH terms: Potassium Citrate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Renal transplantation; Metabolic acidosis; Physical capacity; Bone histology; Bone histomorphometry; Parathyroid function; Calcium and phosphate metabolism