Urine citrate excretion identifies changes in acid retention as eGFR declines in patients with chronic kidney disease

Previous studies have shown that acid (H⁺) retention in patients with chronic kidney disease (CKD) but without metabolic acidosis increases as the estimated glomerular filtration rate (eGFR) decreases over time. The present study examined whether changes in urine excretion of the pH-sensitive metabolite citrate predicted changes in H⁺ retention over time in similar patients with CKD that were followed for 10 yr. We randomized 120 CKD2 nondiabetic, hypertension-associated nephropathy patients with plasma total CO₂ of >24 mM to receive 0.5 meq·kg body wt^-1·day^-1 NaHCO₃ ([Formula: see text]; n = 40), 0.5 meq·kg body wt^-1·day^-1 NaCl (NaCl; n = 40), or usual care (UC; n = 40). We assessed eGFR (CKD-EPI) and H⁺ retention by comparing the observed with expected plasma total CO₂ increase 2 h after an oral NaHCO₃ bolus (0.5 meq/kg body wt). Although 10 yr versus baseline eGFR was lower for each group, 10-yr eGFR was higher (P < 0.01) in [Formula: see text] (59.6 ± 4.8 ml·min^-1·1.73 m^-2) than NaCl and UC (52.1 ± 5.9 and 52.3 ± 4.1 ml·min^-1·1.73 m^-2, respectively) groups. Less eGFR preservation was associated with higher 10-yr versus baseline H⁺ retention in the NaCl group (26.5 ± 13.1 vs. 18.2 ± 15.3 mmol, P < 0.01) and UC group (24.8 ± 11.3 vs. 17.7 ± 10.9 mmol, P < 0.01) and with lower 10-yr versus baseline 8-h urine citrate excretion (U_citrateV) for the NaCl group (162 ± 47 vs. 196 ± 52 mg, respectively, P < 0.01) and UC group (153 ± 41 vs. 186 ± 42 mg, respectively, P < 0.01). Conversely, better eGFR preservation in the [Formula: see text] group was associated with no differences in 10-yr versus baseline H⁺ retention (14.2 ±13.5 vs. 16.1 ± 15.1 mmol, P = 1.00) or U_citrateV (212 ± 45 vs. 203 ± 49 mg, respectively, P = 0.74). An overall generalized linear model for repeated measures showed that U_citrateV predicted H⁺ retention (P < 0.01). Less eGFR preservation in patients with CKD2 without metabolic acidosis was associated with increased H⁺ retention that was predicted by decreased U_citrateV.