Kidney Week

Abstract: PO2518

Increasing Acid Retention with Progressive GFR Decline Is Associated with Decreasing Urine Ammonium Excretion

Session Information

• CKD: Metabolism, Epigenetics, and Signaling
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2103 CKD (Non-Dialysis): Mechanisms

Authors

• Goraya, Nimrit, Baylor Scott and White Central Texas, Temple, Texas, United States

Nimrit Goraya, MD, FASN

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

Jan Simoni,

• Mamun, Abdullah A., Baylor Scott & White Health, Dallas, Texas, United States

Abdullah A. Mamun,

• Wesson, Donald E., Texas A and M College of Medicine, Dallas, Texas, United States

Donald E. Wesson,

Background

Our laboratory showed that acid (H⁺) retention without metabolic acidosis increased as eGFR declined while plasma total CO₂ (PTCO₂) remained within normal ranges (AJP 314: F985, 2018) but the mechanisms for this potential accelerator of GFR decline were not explored. We now examine if changes in urine net acid excretion (UNAE) or its components associated with changes in H⁺ retention in longitudinally followed patients with CKD 2 (eGFR 60-89 ml/min/1.73 m²) without metabolic acidosis.

Methods

One hundred twenty macroalbuminuric, non-diabetic participants with CKD 2 (eGFR=73.4±6.1 ml/min/1.73 m²), 40 treated with 0.5 mEq/kg bw NaHCO₃, 40 with 0.5 mEq/kg bw NaCl, and 40 with usual care (UC) were evaluated annually for 5 years. We assessed H⁺ retention by comparing observed to expected increase in plasma [HCO₃] in response to retained HCO₃ (dose-urine excretion) 2 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). We measured 8-hour urine NAE as the sum of ammonium (8h UNH₄⁺V), titratable acidity (8h UTAV) and bicarbonate (UHCO₃V).

Results

Although 5-year vs. baseline H⁺ retention was higher in UC (19.2±10.2 vs. 17.4±9.7 mmol, p<0.05) and NaCl (23.2±13.8 vs. 19.2±16.4 mmol, p<0.05) but was lower in NaHCO₃ (16.0±12.8 vs. 18.1±14.6 mmol, p<0.05), 5-year vs. baseline 8h UNAE was not different for any group and was not different among groups at baseline or at 5 years. Nevertheless, longitudinal change in 8h UNH₄⁺V was inversely associated with change in H⁺ retention for UC (p<0.01, R²=0.82), NaCl (p<0.01, R²=0.71), and NaHCO₃ (p<0.01, R²=0.20). Combining all three groups, the change in 8h UNH₄⁺V was also inversely associated with the change in H⁺ retention (p<0.01, R²=0.48) but the longitudinal change in 8h UTAV was directly associated with change in H⁺ retention (p<0.01, R²=0.19).

Conclusion

These longitudinal data support that less ability to maintain UNH₄⁺V as eGFR declines contributes to worsening H⁺ retention, despite maintenance of overall UNAE. Further studies will help determine reasons for individual variability in UNH₄⁺V with progressive eGFR decline and the apparent greater importance of UNH₄⁺V than greater UTAV in avoiding increasing H⁺ retention.

Funding

• Private Foundation Support