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Abstract: PO2518

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

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Goraya, Nimrit, Baylor Scott and White Central Texas, Temple, Texas, United States
  • Simoni, Jan, Texas Tech University Health Sciences Center, Lubbock, Texas, United States
  • Mamun, Abdullah A., Baylor Scott & White Health, Dallas, Texas, United States
  • Wesson, Donald E., Texas A and M College of Medicine, Dallas, Texas, United States
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