title: Urinary ammonia and long-term outcomes in chronic kidney disease.
abstract: 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.
authors.affiliation: 1] Université Paris-Descartes, Paris, France [2] Departments of Physiology and Nephrology, Hopital Européen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Vallet
authors.affiliation: 1] INSERM U1018, Centre for Research in Epidemiology and Population Health (CESP), Diabetes, Obesity, and Chronic Kidney Disease Epidemiology Team, Villejuif, France [2] Université Paris-Sud, UMRS 1018, Villejuif, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Metzger
authors.affiliation: 1] Departments of Physiology and Nephrology, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France [2] Université Pierre et Marie Curie, Paris, France [3] INSERM UMR 1155, Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Haymann
authors.affiliation: 1] Departments of Physiology and Nephrology, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France [2] Université Paris Diderot, Paris, France [3] INSERM UMR S 1149, Paris, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Flamant
authors.affiliation: 1] Departments of Physiology and Nephrology, Hopital Européen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France [2] INSERM U1018, Centre for Research in Epidemiology and Population Health (CESP), Diabetes, Obesity, and Chronic Kidney Disease Epidemiology Team, Villejuif, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Gauci
authors.affiliation: 1] Departments of Physiology and Nephrology, Hopital Européen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France [2] INSERM UMR S 970, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Thervet
authors.affiliation: 1] Université Pierre et Marie Curie, Paris, France [2] INSERM UMR 1155, Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Boffa
authors.affiliation: 1] Departments of Physiology and Nephrology, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France [2] Université Paris Diderot, Paris, France [3] INSERM UMR S 1149, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Vrtovsnik
authors.affiliation: INSERM U1018, Centre for Research in Epidemiology and Population Health (CESP), Diabetes, Obesity, and Chronic Kidney Disease Epidemiology Team, Villejuif, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Froissart
authors.affiliation: 1] INSERM U1018, Centre for Research in Epidemiology and Population Health (CESP), Diabetes, Obesity, and Chronic Kidney Disease Epidemiology Team, Villejuif, France [2] Université Paris-Sud, UMRS 1018, Villejuif, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Stengel
authors.affiliation: 1] Departments of Physiology and Nephrology, Hopital Européen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France [2] Sorbonne Universités, UPMC Univ Paris 06, INSERM, Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, CNRS ERL_8228, Paris, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Houillier
mesh_terms: D000368:Aged; D000641:Ammonia / Q000652:urine*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002245:Carbon Dioxide / Q000097:blood*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005602:France / Q000453:epidemiology; D005919:Glomerular Filtration Rate; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000652:urine*; D015996:Survival Rate; D013997:Time Factors
chemical_list: D015415:Biomarkers; D002245:Carbon Dioxide; D000641:Ammonia