American Journal of Nephrology

Patient-Oriented, Translational Research: Research Article

Goraya N. · Madias N.E. · Mamun A. · Simoni J. · Wesson D.E.

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Article / Publication Details Abstract

Introduction: Like metabolic acidosis, earlier stages of acid (H+) stress, including an ongoing H+ challenge in the form of dietary H+, without or with steady-state H+ accumulation but with normal plasma total CO2 (PTCO2) (the latter state known as eubicarbonatemic acidosis), are associated with augmented progression of chronic kidney disease (CKD) but diagnosis of this covert H+ stress is clinically problematic. Prior published studies to identify clinically practical biomarkers of covert H+ stress did not include assessments of either dietary H+ or H+ retention. Methods: We tested plasma pH (PpH), 8-hour urine excretion of citrate (UcitV) or ammonium (UNH4+V) as biomarkers of dietary H+ assessed as potential renal acid load (PRAL) and of steady-state H+ retention by comparing observed to expected PTCO2 increase two hours after an oral NaHCO3 bolus. We recruited 313 non-diabetic participants with PTCO2 ≥ 22 mM to exclude participants with metabolic acidosis and with eGFR [mean (SD), ml/min/1.73 m2] stages G1 [n=62, 99.2 (7.3)], G2 [n=167, 73.8 (6.3)], and G3 [n=84, 39.9 (6.7)]. We performed linear regressions (LR) between H+ retention or PRAL (dependent variables) and PpH, UcitV or UNH4+V (independent variables) after adjusting for eGFR. Results: Steady-state H+ retention [mean (SD), mmol] increased with stage [G1=3.8 (12.5), G2=18.2 (12.4), and G3=25.6 (9.0)]. PpH was not significantly associated with PRAL in any group and its association with H+ retention was significant only for G3 (p

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