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Association between Urine Ammonium and Urine TGF-β1 in CKD.
Clin J Am Soc Nephrol. 2018 02 07; 13(2):223-230.CJ

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+Show Affiliations

Department of Internal Medicine, University of Utah Health, Salt Lake City, Utah; kalani.raphael@hsc.utah.edu. Medicine Section and Research Section, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah; and.Department of Internal Medicine, University of Utah Health, Salt Lake City, Utah.Department of Internal Medicine, Case Western Reserve School of Medicine, Cleveland, Ohio.Department of Internal Medicine, University of Utah Health, Salt Lake City, Utah.Department of Internal Medicine, University of Utah Health, Salt Lake City, Utah. Medicine Section and Research Section, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah; and.

Pub Type(s)

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.

Language

eng

PubMed ID

29146699

Citation

Raphael, Kalani L., et al. "Association Between Urine Ammonium and Urine TGF-β1 in CKD." Clinical Journal of the American Society of Nephrology : CJASN, vol. 13, no. 2, 2018, pp. 223-230.
Raphael KL, Gilligan S, Hostetter TH, et al. Association between Urine Ammonium and Urine TGF-β1 in CKD. Clin J Am Soc Nephrol. 2018;13(2):223-230.
Raphael, K. L., Gilligan, S., Hostetter, T. H., Greene, T., & Beddhu, S. (2018). Association between Urine Ammonium and Urine TGF-β1 in CKD. Clinical Journal of the American Society of Nephrology : CJASN, 13(2), 223-230. https://doi.org/10.2215/CJN.07510717
Raphael KL, et al. Association Between Urine Ammonium and Urine TGF-β1 in CKD. Clin J Am Soc Nephrol. 2018 02 7;13(2):223-230. PubMed PMID: 29146699.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association between Urine Ammonium and Urine TGF-β1 in CKD. AU - Raphael,Kalani L, AU - Gilligan,Sarah, AU - Hostetter,Thomas H, AU - Greene,Tom, AU - Beddhu,Srinivasan, Y1 - 2017/11/16/ PY - 2017/07/16/received PY - 2017/10/16/accepted PY - 2017/11/18/pubmed PY - 2019/9/17/medline PY - 2017/11/18/entrez KW - Aged KW - Ammonia KW - Ammonium Compounds KW - Animals KW - Bicarbonates KW - Cross-Sectional Studies KW - Humans KW - Hydrogen-Ion Concentration KW - Kidney Function Tests KW - Linear Models KW - Male KW - Models, Animal KW - Renal Insufficiency, Chronic KW - Transforming Growth Factors KW - chronic kidney disease KW - chronic metabolic acidosis KW - creatinine KW - diabetes mellitus KW - glomerular filtration rate KW - proteinuria KW - renal fibrosis SP - 223 EP - 230 JF - Clinical journal of the American Society of Nephrology : CJASN JO - Clin J Am Soc Nephrol VL - 13 IS - 2 N2 - 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. SN - 1555-905X UR - https://www.unboundmedicine.com/medline/citation/29146699/Association_between_Urine_Ammonium_and_Urine_TGF_β1_in_CKD_ L2 - https://cjasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=29146699 DB - PRIME DP - Unbound Medicine ER -