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

• CKD: Risk Factors for Incidence and Progression - II
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Chronic Kidney Disease (Non-Dialysis)

• 301 CKD: Risk Factors for Incidence and Progression

Authors

• Goraya, Nimrit, Baylor Scott & White Health, Temple, Texas, United States

Nimrit Goraya,

• Simoni, Jan, Texas Tech University Health Sciences Center, Lubbock, Texas, United States

Jan Simoni,

• Sager, Lauren N, Baylor Scott & White, Temple, Texas, United States

Lauren N Sager,

• Madias, Nicolaos E., Tufts University School of Medicine, Boston, Massachusetts, United States

Nicolaos E. Madias,

• Wesson, Donald E., Diabetes Health and Wellness Institute, Dallas, Texas, United States

Donald E. Wesson,

Background

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.

Methods

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 U_citV) was measured after overnight fast.

Results

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 U_citV. 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 U_citV 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).

Conclusion

Lower than CKD 1 8h U_citV 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.