Effect of high-normal compared with low-normal arterial pH on protein balances in automated peritoneal dialysis patients

Abstract

Background: Although the protein catabolic effects of metabolic acidosis are well established, it is unclear whether the entire reference range of arterial pH (7.37-7.44) is equivalent for protein balance.

Objective: We undertook this study to test the hypothesis that in patients undergoing automated peritoneal dialysis, an arterial pH of 7.43-7.45, as compared with a pH of 7.36-7.38, is associated with more-positive nitrogen balances.

Design: Eight stable subjects (5 men) aged 43.1 +/- 15.3 y completed a randomized, crossover nitrogen balance study for >or=42 d. Arterial pH was varied by changing the daily doses of sodium citrate/citric acid and ammonium chloride.

Results: The subjects attained mean (+/-SD) arterial pH values of 7.37 +/- 0.01 and 7.44 +/- 0.02 during the low-normal and high-normal pH phases, respectively. The higher arterial pH was associated with higher net nitrogen balances (3.22 +/- 1.37 compared with 2.29 +/- 2.18 g/d; P = 0.06), lower serum urea nitrogen (54.1 +/- 13.7 compared with 64.4 +/- 20.2 mg/dL; P = 0.01), higher fasting leucine flux (P = 0.02), and increased fasting total-body protein synthesis (P = 0.01) and degradation (P = 0.02). In 7 of 8 study subjects, nitrogen balances were more positive at the higher arterial pH (P = 0.004). There were no significant changes in anthropometric measurements, other biochemical measurements, and the mRNA content of selected proteins in skeletal muscle.

Conclusion: This study suggests that in most stable automated peritoneal dialysis patients, a mean arterial pH of 7.44, as compared with 7.37, is associated with more-positive nitrogen balances. This trial was registered at clinical trials.gov as NCT00586131.

FIGURE 1

Summary of the key procedures and outcome measures for the outpatient and inpatient phases of the trial. GCRC, General Clinical Research Center.

FIGURE 2

Chart summarizing the flow of patients throughout the clinical trial.

FIGURE 3

Nitrogen (N) balances during the low-normal and high-normal arterial pH phases (P) for each of the individual patients enrolled in the clinical trial. In 7 of the 8 subjects, the net nitrogen balance was higher during the high-normal arterial pH phase of the study than during the low-normal arterial pH phase.