Abstract: FR-PO432

Acid Retention Worsens as CKD Progresses to More Advanced Stages

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Goraya, Nimrit, Texas A and M School of Medicine, 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
  • Wesson, Donald E., Diabetes Health and Wellness Institute, Dallas, Texas, United States
Background


Acid (H+) retention, even without metabolic acidosis by plasma acid-base parameters, mediates eGFR decline in animal models of chronic kidney disease (CKD) and worsens with declining GFR. Patients with reduced eGFR but no metabolic acidosis also have H+ retention (Wesson, et al. AJP 300:F830) and preliminary longitudinal studies showed that H+ retention worsened as eGFR decreased over 10 years (Goraya, et al. JASN 26:58A, 2015). Because recent studies support that dietary H+ reduction slows nephropathy progression, more advanced CKD patients might require more aggressive dietary H+ reduction if their H+ retention is indeed greater. Consequently, we further tested the hypothesis that H+ retention worsens with declining eGFR by comparing cross-sectional measurements of H+ retention across CKD stages 1 through 4.

Methods

Twenty-six CKD 1, 40 CKD 2, 36 CKD 3, and 36 CKD 4 macroalbuminuric, non-diabetic CKD subjects had H+ retention measured by comparing the observed to the expected increase in plasma [HCO3] in response to retained HCO3 (dose-urine excretion) two hours after an oral NaHCO3 bolus (0.5 meq/Kg bw), assuming 50% body weight 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). So, the greater the difference between the expected and observed increase in plasma [HCO3], the greater the amount of “unaccounted HCO3” which was assumed to have been HCO3 that had been titrated by retained H+.

Results


Cystatin C-calculated eGFR in ml/min/1.73m2 was as follows: CKD 1=101±8, CKD2=76±6, CKD 3=40±7, and CKD 4=23±5. The Bonferroni correction required a p-value of < 0.0083 for significance among group comparisons for H+ retention. Accordingly, H+ retention was greater in CKD 2 vs. CKD 1 (17.4±8.9 vs. 3.0 ± 14.0 mmol, p<0.0001), in CKD 3 vs. CKD 2 (24.9±15.4 vs. 17.4±8.9 mmol, p=0.0079), but not for CKD 4 vs. CKD 3 (32.2±10.5 vs. 24.9±15.4 mmol, p=0.0108).

Conclusion

These cross-sectional data show that H+ retention increased significantly and progressively from CKD stages 1 through 3 and, along with the previous longitudinal data, support that H+ worsens as eGFR decreases. Greater H+ retention in patients with lower eGFR might contribute to their faster eGFR decline and its resolution might require more aggressive dietary H+ reduction to optimize eGFR preservation .