Influence of Medications Containing Acid Salts on Serum Bicarbonate in CKD

Abstract

Background: Many medications are formulated with acid salts. Their effect on acid-base balance in CKD is unclear.

Methods: We calculated the acid load (meq/d) from medications prescribed to 74 United States veterans with diabetes and CKD to identify agents with high potential acid load. We also determined cross-sectional associations between the acid load from medications and acid-base parameters after adjusting for demographics, eGFR, protein intake, and other confounders.

Results: Of the 125 medications prescribed, 31 (25%) contained an acid salt. Metformin hydrochloride (15.4 meq/d at 2550 mg/d) and gabapentin hydrochloride (13.0 meq/d at 2700 mg/d) were identified as agents with a high potential acid load. Mean daily acid load from medications was 6.6 meq/d in the overall cohort, 14.2 meq/d in the high medication acid load group (≥7.7 meq/d, n=29), and 1.6 meq/d in the low medication acid load group (<7.7 meq/d, n=45). After adjusting for potential confounders, those in the high acid load group had 1.7 meq/L lower total carbon dioxide (CO2) and 2.2 meq/L higher anion gap than those in the low acid load group. Use of gabapentin alone was not associated with differences in total CO2 or anion gap. Use of metformin alone was associated with 0.7 meq/L lower total CO2 and 1.0 meq/L higher anion gap. Use of metformin with gabapentin was associated with 1.8 meq/L lower total CO2 and 2.4 meq/L higher anion gap. The higher anion gap was not explained by higher serum lactate levels. The acid load from medications was not associated with differences in urinary ammonium, titratable acid, or pH.

Conclusions: Medications containing acid salts, particularly metformin hydrochloride and gabapentin hydrochloride, are sources of an exogenous acid load. These agents may influence serum total CO2 levels and serum anion gap in individuals with CKD.

Clinical trial registry name and registration number: Investigations of the Optimum Serum Bicarbonate Level in Renal Disease, NCT01574157.

Keywords: acid-base equilibrium; acid/base and electrolyte disorders; acidosis; anion gap; bicarbonate; carbon dioxide; chronic; cross-sectional studies; diabetes mellitus; gabapentin; hydrochloric acid; metformin; polypharmacy; renal insufficiency.

Conflict of interest statement

K. Raphael received a one-time consulting fee from Tricida, Inc. in October 2016. J. Gardner and K. Tuttle have nothing to disclose.

Copyright © 2020 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

Twenty-nine individuals (39%) in the study had high potential acid load from medications.