Acid retention in chronic kidney disease is inversely related to GFR

Greater H⁺ retention in animal models of chronic kidney disease (CKD) mediates faster glomerular filtration rate (GFR) decline and dietary H⁺ reduction slows eGFR decline in CKD patients with reduced eGFR and H⁺ retention due to the high acid (H⁺) diets of developed societies. We examined if H⁺ retention in CKD is inversely associated with estimated GFR (eGFR) using cross-sectional and longitudinal analysis of individuals with CKD stage 1 (>90 ml·min^{− 1}·1.73 m⁻²), CKD stage 2 (60-89 ml/min per 1.73 m²), and CKD stage 3 (30-59 ml·min^{− 1}·1.73 m⁻²) eGFR. H⁺ retention was assessed using the difference between observed and expected plasma total CO2 2 h after 0.5 meq/kg body wt oral NaHCO₃. H⁺ retention was higher in CKD 2 vs. CKD 1 (P < 0.01) and in CKD 3 vs. CKD 2 (P < 0.02) at baseline and 5 yr, and was higher in CKD 2 vs. CKD 1 (P < 0.01) at 10 yr. All groups had lower eGFR at subsequent time points (P < 0.01) but H⁺ retention was not different among the three time points for CKD 1. By contrast, eGFR decrease was associated with higher H⁺ retention in CKD 2 at 5 yr (P = 0.04) and 10 yr (P < 0.01) and with higher H⁺ retention in CKD 3 at 5 yr (P < 0.01). Yearly eGFR decline rate was faster in CKD 2 vs. CKD 1 (P < 0.01) and in CKD 3 vs. CKD 2 (P < 0.01). The data show that H⁺ retention is inversely associated with eGFR, with faster eGFR decline, and support the need for greater dietary H⁺ reduction therapy for CKD individuals with lower eGFR.