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Kidney Week

Abstract: FR-PO630

Medications Containing H+ Salts Are Associated with Lower Serum Total CO2 and Higher Serum Anion Gap in Patients With Non-Acidotic Diabetic Kidney Disease

Session Information

Category: Fluid and Electrolytes

  • 902 Fluid and Electrolytes: Clinical


  • Gardner, John W., VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Raphael, Kalani L., VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Tuttle, Kunani, VA Salt Lake City Health Care System, Salt Lake City, Utah, United States

Metabolic acidosis (MA) is associated with adverse clinical consequences in CKD. Many medications contain H+-salts which could contribute to development of MA. This study determined the association between H+ load from medications (med-H+ load) and acid-base indices in patients with diabetic kidney disease (DKD) but without MA.


We conducted this cross-sectional study in 74 US veterans with DKD (eGFR 51±18 ml/min/1.73m2) and serum tCO2 24±2 meq/L. None were treated with alkali. The daily H+ load from medications containing H+-salts was determined using the daily dose, molecular weight, and valence of the agents. Participants were categorized into a low or high med-H+ load group using a threshold of 7.7 meq/d, which is the equimolar amount of HCO3- in one 650mg NaHCO3 tablet required to mitigate this H+ load. We compared serum (tCO2 and anion gap) and urinary (NH4+, titratable acids [TA], and pH) acid base indices between groups using linear regression models adjusted for eGFR, ACR, protein intake, and other potential confounders.


40 of 123 (33%) medications prescribed contained H+-salts. Two agents contributed ≥1 meq/d of H+, metformin (9.7±3.3 meq/d) and gabapentin (5.9±3.7 meq/d). 29 of 74 (39%) participants were in the high med-H+ load group. In the high and low groups, 93% vs 13% received metformin and 55% vs 18% received gabapentin. Mean±SD med-H+ load was 14.2±4.3 in the high and 1.6±2.4 meq/d in the low group. Those in the high group had significantly lower tCO2 and higher serum anion gap after adjustment (table). Metformin use and gabapentin use (irrespective of dose) were modestly associated with lower serum tCO2 and higher anion gap. Med-H+ load did not seem to impact urinary acid excretion.


Medications containing H+-salts, particularly metformin and gabapentin, contribute to meaningful differences in serum tCO2 and anion gap in patients with non-acidotic DKD, suggesting that these agents may be novel risk factors for MA in DKD.

VariableHigh vs Low Acid LoadMetformin Use vs NoGabapentin Use vs No
Serum total CO2 (meq/L)-1.74
(-3.02 to -0.45)
(-2.41 to 0.04)
(-2.24 to 0.25)
Serum anion gap (meq/L)2.16
(0.88 to 3.44)
(0.47 to 2.91)
(-0.08 to 2.46)
Urinary NH4+ (meq/hr)0.15
(-0.20 to 0.50)
(-0.16 to 0.49)
(-0.22 to 0.44)
Urinary Titratable Acids (meq/hr)0.00
(-0.25 to 0.25)
(-0.35 to 0.11)
(-0.35 to 0.12)
Urine pH-0.08
(-0.33 to 0.17)
(-0.23 to 0.24)
(-0.27 to 0.20)


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