Elevated serum anion gap in adults with moderate chronic kidney disease increases risk for progression to end-stage renal disease

Tanushree Banerjee, Deidra C. Crews, Donald E. Wesson, Charles E. McCulloch, Kirsten L. Johansen, Sharon Saydah, Nilka Rios Burrows, Rajiv Saran, Brenda Gillespie, Jennifer Bragg-Gresham, Neil R. Powe

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Abstract

Banerjee T, Crews DC, Wesson DE, McCulloch CE, Johansen KL, Saydah S, Rios Burrows N, Saran R, Gillespie B, Bragg-Gresham J, Powe NR. Elevated serum anion gap in adults with moderate chronic kidney disease increases risk for progression to end-stage renal disease. Am J Physiol Renal Physiol 316: F1244– F1253, 2019. First published March 25, 2019; doi:10.1152/ajprenal. 00496.2018.—Acid retention associated with reduced glomerular filtration rate (GFR) exacerbates nephropathy progression in partial nephrectomy models of chronic kidney disease (CKD) and might be reflected in patients with CKD with reduced estimated GFR (eGFR) by increased anion gap (AG). We explored the presence of AG and its association with CKD in 14,924 adults aged ≥20 yr with eGFR ≥ 15 ml·min-1·1.73 m-2 enrolled in the National Health and Nutrition Examination Survey III, 1988–1994, using multivariable regression analysis. The model was adjusted for sociodemographic characteristics, diabetes, and hypertension. We further examined the association between AG and incident end-stage renal disease (ESRD) using frailty models, adjusting for demographics, clinical factors, body mass index, serum albumin, bicarbonate, eGFR, and urinary albumin-to-creatinine ratio by following 558 adults with moderate CKD for 12 yr via the United States Renal Data System. Laboratory measures determined AG using the traditional, albumin-corrected, and full AG definitions. Individuals with moderate CKD (eGFR: 30–59 ml·min-1·1.73 m-2) had a greater AG than those with eGFR ≥ 60 ml·min-1·1.73 m-2 in multivariable regression analysis with adjustment for covariates. We found a graded relationship between the adjusted mean for all three definitions of AG and eGFR categories (P trend < 0.0001). During followup, 9.2% of adults with moderate CKD developed ESRD. Those with AG in the highest tertile had a higher risk of ESRD after adjusting for covariates in a frailty model [relative hazard (95% confidence interval) for traditional AG: 1.76 (1.16–2.32)] compared with those in the middle tertile. The data suggest that high AG, even after adjusting for serum bicarbonate, is a contributing acid-base mechanism to CKD progression in adults with moderate chronic kidney disease.

Original languageEnglish (US)
Pages (from-to)F1244-F1253
JournalAmerican Journal of Physiology - Renal Physiology
Volume316
Issue number6
DOIs
StatePublished - Jun 2019

Keywords

  • Acid-base
  • Anion gap
  • Chronic kidney disease
  • Progression

ASJC Scopus subject areas

  • Physiology
  • Urology

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    Banerjee, T., Crews, D. C., Wesson, D. E., McCulloch, C. E., Johansen, K. L., Saydah, S., Burrows, N. R., Saran, R., Gillespie, B., Bragg-Gresham, J., & Powe, N. R. (2019). Elevated serum anion gap in adults with moderate chronic kidney disease increases risk for progression to end-stage renal disease. American Journal of Physiology - Renal Physiology, 316(6), F1244-F1253. https://doi.org/10.1152/ajprenal.00496.2018