Urinary ammonia and long-term outcomes in chronic kidney disease

Kidney Int. 2015 Jul;88(1):137-45. doi: 10.1038/ki.2015.52. Epub 2015 Mar 11.


Recent studies suggest that alkalinizing treatments improve the course of chronic kidney disease (CKD), even in patients without overt metabolic acidosis. Here, we tested whether a decreased ability in excreting urinary acid rather than overt metabolic acidosis may be deleterious to the course of CKD. We studied the associations between baseline venous total CO2 concentration or urinary ammonia excretion and long-term CKD outcomes in 1065 patients of the NephroTest cohort with CKD stages 1-4. All patients had measured glomerular filtration rate (mGFR) by (51)Cr-EDTA renal clearance. Median mGFR at baseline was 37.6 ml/min per 1.73 m(2). Urinary ammonia excretion decreased with GFR, whereas net endogenous acid production did not. After a median follow-up of 4.3 years, 201 patients reached end-stage renal disease (ESRD) and 114 died before ESRD. Twenty-six percent of the patients had mGFR decline rate greater than 10% per year. Compared with patients in the highest tertile of urinary ammonia excretion, those in the lowest tertile had a significantly increased hazard ratio for ESRD, 1.82 (95% CI, 1.06-3.13), and a higher odds ratio of fast mGFR decline, 1.84 (0.98-3.48), independent of mGFR and other confounders. Patients in the lowest tertile of venous total CO2 had significantly increased risk of fast mGFR decline but not of ESRD. None of these biomarkers was associated with mortality. Thus, these results suggest that the inability to excrete the daily acid load is deleterious to renal outcomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Ammonia / urine*
  • Biomarkers / blood
  • Biomarkers / urine
  • Carbon Dioxide / blood*
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • France / epidemiology
  • Glomerular Filtration Rate
  • Humans
  • Incidence
  • Kidney Failure, Chronic / epidemiology
  • Male
  • Middle Aged
  • Prospective Studies
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / urine*
  • Survival Rate
  • Time Factors


  • Biomarkers
  • Carbon Dioxide
  • Ammonia