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

Abstract

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.