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Kidney Week

Abstract: FR-PO433

Acid Retention Revealed by Urine Citrate Excretion Might Identify CKD Patients for Whom Dietary Alkali Is Kidney Protective

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression


  • Goraya, Nimrit, Baylor Scott & White Health, Temple, Texas, United States
  • Simoni, Jan, Texas Tech University Health Sciences Center, Lubbock, Texas, United States
  • Sager, Lauren N, Baylor Scott & White, Temple, Texas, United States
  • Madias, Nicolaos E., Tufts University School of Medicine, Boston, Massachusetts, United States
  • Wesson, Donald E., Diabetes Health and Wellness Institute, Dallas, Texas, United States

Despite data showing that dietary alkali slows eGFR decline in chronic kidney disease (CKD) stage 3 (CKD 3) patients with mild metabolic acidosis (plasma total CO2 [PTCO2] >22 mM) (Goraya, et al. KI 86:1031, 2014) and in CKD stage 2 (CKD 2) patients with H+ retention but no metabolic acidosis (PTCO2 >24.5 mM) (Wesson, et al. AJP 300:F830, 2011; Mahajan, et al. KI 78:303, 2010), KDIGO recommends alkali for only CKD patients with PTCO2 < 22 mM. We tested the hypothesis that urine excretion of the pH-sensitive metabolite citrate identifies H+ retention, a form of acid stress which causes GFR decline in animal models of CKD, in CKD patients for whom dietary alkali provides kidney protection but for whom current guidelines do not recommend alkali therapy.


Macroalbuminuric, non-diabetic subjects with CKD stage 1 (CKD 1) and PTCO2 > 24 mM (n=26), CKD 2 with PTCO2 > 24 mM (n=40), and CKD 3 with PTCO2 22-24 mM (n=36), had H+ retention measured by comparing observed to expected increase in PTCO2 in response to retained HCO3 (dose-urine excretion) two hours after oral NaHCO3 bolus (0.5 meq/Kg bw), assuming 50% bw HCO3 space of distribution. Specifically, H+ retention = [(retained HCO3/0.5 x body weight) – observed increase in plasma [HCO3]] x (0.5 x body weight). Eight-hour urine citrate excretion (8h UcitV) was measured after overnight fast.


PTCO2 was similar in CKD 2 (26.2±0.6 mM) and CKD 1 (26.8±0.7 mM) but was lower in CKD 3 (22.8±0.7 mM). Bonferroni correction required p-value significance < 0.0083 for within-group comparisons of H+ retention and 8h UcitV. H+ retention was greater in CKD 2 than CKD 1 (17.4±8.9 vs. 3.0±14 mM, p<0.0001) despite similar PTCO2 and that for CKD 3 (24.9±15.4 mM) was higher than both CKD 1 (p<0.0001) and CKD 2 (p=0.0079). Furthermore, 8h UcitV was less than CKD 1 (335±125 mg) for both CKD 2 (187±40 mg, p<0.0001) and CKD 3 (159±15 mg, p<0.0001).


Lower than CKD 1 8h UcitV identified H+ retention in CKD 2 and CKD 3 patients for whom alkali therapy has been kidney protective but whose PTCO2 was not low enough for alkali therapy by current guidelines. Urine citrate excretion is easily measurable in clinical settings and should be further explored as a strategy to identify CKD patients for whom alkali therapy might provide kidney protection.