Urine citrate excretion as a marker of acid retention in patients with chronic kidney disease without overt metabolic acidosis

Kidney Int. 2019 May;95(5):1190-1196. doi: 10.1016/j.kint.2018.11.033. Epub 2019 Mar 1.


Acid (H+) retention appears to contribute to progressive decline in glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD), including some patients without metabolic acidosis. Identification of patients with H+ retention but without metabolic acidosis could facilitate targeted alkali therapy; however, current methods to assess H+ retention are invasive and have little clinical utility. We tested the hypothesis that urine excretion of the pH-sensitive metabolite citrate can identify H+ retention in patients with reduced GFR but without overt metabolic acidosis. H+ retention was assessed based on the difference between observed and expected plasma total CO2 after an oral sodium bicarbonate load. The association between H+ retention and urine citrate excretion was evaluated in albuminuric CKD patients with eGFR 60-89 ml/min/1.73m2 (CKD 2, n=40) or >90 ml/min/1.73m2 (CKD 1, n = 26) before and after 30 days of base-producing fruits and vegetables. Baseline H+ retention was higher in CKD 2, while baseline urine citrate excretion was lower in CKD 2 compared to CKD 1. Base-producing fruits and vegetables decreased H+ retention in CKD 2 and increased urine citrate excretion in both groups. Thus, H+ retention is associated with lower urine citrate excretion, and reduction of H+ retention with a base-producing diet is associated with increased urine citrate excretion. These results support further exploration of the utility of urine citrate excretion to identify H+ retention in CKD patients with reduced eGFR but without metabolic acidosis, to determine their candidacy for kidney protection with dietary H+ reduction or alkali therapy.

Keywords: GFR; acidosis; bicarbonate; chronic kidney disease; diet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid-Base Equilibrium / physiology
  • Acidosis / diagnosis*
  • Acidosis / etiology
  • Acidosis / urine
  • Adult
  • Biomarkers / urine
  • Citric Acid / metabolism
  • Citric Acid / urine*
  • Disease Progression
  • Feasibility Studies
  • Female
  • Glomerular Filtration Rate / physiology
  • Humans
  • Kidney / physiopathology*
  • Male
  • Middle Aged
  • Renal Elimination / physiology*
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / physiopathology
  • Renal Insufficiency, Chronic / urine


  • Biomarkers
  • Citric Acid