Association between Urine Ammonium and Urine TGF-β1 in CKD.

Abstract

BACKGROUND AND OBJECTIVES:

Urinary ammonium excretion increases in response to nonvolatile acids to maintain normal systemic bicarbonate and pH. However, enhanced ammonia production promotes tubulointerstitial fibrosis in animal models. Therefore, a subset of individuals with CKD and normal bicarbonate may have acid-mediated kidney fibrosis that might be better linked with ammonium excretion than bicarbonate. We hypothesized that urine TGF-β1, as an indicator of kidney fibrosis, would be more tightly linked with urine ammonium excretion than serum bicarbonate and other acid-base indicators. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured serum bicarbonate and urinary ammonium, titratable acids, pH, and TGF-β1/creatinine in 144 persons with CKD. Multivariable-adjusted linear regression models determined the cross-sectional association between TGF-β1/creatinine and serum bicarbonate, urine ammonium excretion, urine titratable acids excretion, and urine pH.

RESULTS:

Mean eGFR was 42 ml/min per 1.73 m2, mean age was 65 years old, 78% were men, and 62% had diabetes. Mean urinary TGF-β1/creatinine was 102 (49) ng/g, mean ammonium excretion was 1.27 (0.72) mEq/h, mean titratable acids excretion was 1.14 (0.65) mEq/h, mean urine pH was 5.6 (0.5), and mean serum bicarbonate was 23 (3) mEq/L. After adjusting for eGFR, proteinuria, and other potential confounders, each SD increase of urine ammonium and urine pH was associated with a statistically significant 1.22-fold (95% confidence interval, 1.11 to 1.35) or 1.11-fold (95% confidence interval, 1.02 to 1.21) higher geometric mean urine TGF-β1/creatinine, respectively. Each SD increase of serum bicarbonate and urine titratable acids was associated with a nonsignificant 1.06-fold (95% confidence interval, 0.97 to 1.16) or 1.03-fold (95% confidence interval, 0.92 to 1.14) higher geometric mean urine TGF-β1/creatinine, respectively.

CONCLUSIONS:

Urinary ammonium excretion but not serum bicarbonate is associated with higher urine TGF-β1/creatinine.

• Authors: Kalani L Raphael, Sarah Gilligan, Thomas H Hostetter, Tom Greene, Srinivasan Beddhu
• Journal: Clinical journal of the American Society of Nephrology : CJASN (Clin J Am Soc Nephrol) Vol. 13 Issue 2 Pg. 223-230 (02 07 2018) ISSN: 1555-905X [Electronic] United States
• PMID: 29146699 (Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2018 by the American Society of Nephrology.

Chemical References

• Ammonium Compounds
• Bicarbonates
• Biomarkers
• TGFB1 protein, human
• Transforming Growth Factor beta1
• Creatinine

Topics

• Aged
• Aged, 80 and over
• Ammonium Compounds (urine)
• Bicarbonates (blood)
• Biomarkers (blood, urine)
• Creatinine (urine)
• Cross-Sectional Studies
• Female
• Fibrosis
• Glomerular Filtration Rate
• Humans
• Hydrogen-Ion Concentration
• Kidney (pathology, physiopathology)
• Male
• Middle Aged
• Renal Elimination
• Renal Insufficiency, Chronic (blood, diagnosis, physiopathology, urine)
• Transforming Growth Factor beta1 (urine)