Arterial pH and Total Body Nitrogen Balances in APD
Condition: End-stage Renal Disease
MeSH terms: Kidney Diseases; Kidney Failure, Chronic
Study type: Interventional
Phase: Phase 4

Summary: 
      This study will test the hypothesis that by slightly lowering the acidity of blood (or
      increasing the pH), dialysis patients utilize protein and amino acids more efficiently.
    

Detailed description: 
      The normal range of pH of the blood (measure of acid-base balance of body) is rather large.
      It is defined as a range of pH between 7.38 and 7.44. There is evidence to suggest that a
      high normal arterial pH (7.43-7.45) preserves nutritional status of individuals better than a
      low normal arterial pH (7.36-7.38). We will test this hypothesis in a small group of stable
      patients with end-stage renal disease undergoing automated peritoneal dialysis. It needs to
      be noted that all pH levels to be attained in this study are considered to be normal. The
      primary outcome measure for the study will be the N-balance. The changes in blood pH will be
      obtained by medications (ammonium chloride for lower pH and sodium bicarbonate for higher
      pH).

      Study Procedures: A total of eight subjects with end-stage renal disease undergoing automated
      peritoneal dialysis will be recruited. The initial study procedures will be for purposes of
      screening individuals for the study. The subjects will perform 24-hour collection of urine
      and dialysate to assess dialysis dose and a peritoneal equilibration test to evaluate the
      transport properties of the peritoneum. Only those subjects who receive the minimum dialysis
      dose and have an average peritoneal transport type will enter the study. During this phase,
      the subjects will maintain a food diary to evaluate dietary preferences and dietary calorie
      and protein intake. These data will be used to prepare the diets for the subjects when they
      are admitted to the GCRC. The next two weeks will be used to evaluate the response of
      arterial pH to the use of the low alkali solution. If, at the end of two weeks, the arterial
      pH is not in the desired range, the subjects will require ammonium chloride supplementation
      to achieve the lower pH. In such subjects, ammonium chloride supplementation will be used for
      all phases of the study.

      Qualifying subjects will be hospitalized in the GCRC for 41 days. The entire period of
      hospitalization will be divided into two equal phases of 20.5 days each: one will be the low
      pH phase (low alkali dialysis solution with/without ammonium chloride) and the second will be
      the high pH phase (high alkali dialysis solution with sodium bicarbonate with/without
      ammonium chloride). Nitrogen balance will be estimated during the entire period of
      hospitalization. N-intake is a sum of dietary and medicinal intake, while N-output will be
      N-losses in dialysate, urine and feces. The N-balance will be the difference between N-intake
      and N-output. The second outcome measure will be leucine turnover studies. Leucine turnover
      studies will be performed on days 21 and 41. Leucine turnover studies provide information
      regarding rates of total body protein synthesis and total body protein degradation as well as
      rates of leucine oxidation. The study will take 10 hours each - the initial 4 hours will be
      after an overnight fast and the last six hours will be while being fed. The third outcome
      measure will be the content of some proteins in a sample of muscle biopsy. Muscle biopsy will
      be performed on days 21 and 41 after the completion of leucine turnover studies. Finally,
      nutritional assessment will be performed at the time of patient admission, on day 21 and 41.
      On days 21 and 41, the nutritional assessment will be performed prior to the start of the
      leucine turnover studies.

      The subjects will be compensated for participation in this study -the amount of compensation
      will be dependent upon the degree of participation of subjects.

      Risk-benefit Assessment: The risks of the study include the risks of performing a muscle
      biopsy, discomfort associated with the placement of the feeding tube, emotional problems
      associated with prolonged hospitalization in the GCRC and risks associated with venipuncture.
      There are no direct benefits to the subjects as a result of their participation in this
      study. However, if we demonstrate that the higher arterial pH is better at preservation of
      nutritional status, it may have the potential of decreasing the prevalence and/or severity of
      protein-energy malnutrition in patients undergoing automated peritoneal dialysis.
    

Intervention name(s): ammonium chloride or sodium citrate/citric acid; Sodium citrate/citratic acid
Intervention type(s): Drug; Drug
Intervention description(s): Dose dictated by changes in pH; dictated by pH
Intervention MeSH terms: Citric Acid; Sodium Citrate
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Treatment with sodium citrate/citric acid or ammonium chloride chloride in each phase to achieve the desired arterial pH
Masking: None (Open Label)
Primary purpose: Other
Keywords: end-stage renal disease; automated peritoneal dialysis; metabolic acidosis; nitrogen balances