Association between Urine Ammonium and Urine TGF-β1 in CKD
Copyright © 2018 by the American Society of Nephrology..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Clinical journal of the American Society of Nephrology : CJASN - 13(2018), 2 vom: 07. Feb., Seite 223-230 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Raphael, Kalani L [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.09.2019 Date Revised 13.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.2215/CJN.07510717 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM278129773 |
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| 100 | 1 | |a Raphael, Kalani L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Association between Urine Ammonium and Urine TGF-β1 in CKD |
| 264 | 1 | |c 2018 | |
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| 500 | |a Date Completed 16.09.2019 | ||
| 500 | |a Date Revised 13.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018 by the American Society of Nephrology. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSIONS: Urinary ammonium excretion but not serum bicarbonate is associated with higher urine TGF-β1/creatinine | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Aged | |
| 650 | 4 | |a Ammonia | |
| 650 | 4 | |a Ammonium Compounds | |
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Bicarbonates | |
| 650 | 4 | |a Cross-Sectional Studies | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a Hydrogen-Ion Concentration | |
| 650 | 4 | |a Kidney Function Tests | |
| 650 | 4 | |a Linear Models | |
| 650 | 4 | |a Male | |
| 650 | 4 | |a Models, Animal | |
| 650 | 4 | |a Renal Insufficiency, Chronic | |
| 650 | 4 | |a Transforming Growth Factors | |
| 650 | 4 | |a chronic kidney disease | |
| 650 | 4 | |a chronic metabolic acidosis | |
| 650 | 4 | |a creatinine | |
| 650 | 4 | |a diabetes mellitus | |
| 650 | 4 | |a glomerular filtration rate | |
| 650 | 4 | |a proteinuria | |
| 650 | 4 | |a renal fibrosis | |
| 650 | 7 | |a Ammonium Compounds |2 NLM | |
| 650 | 7 | |a Bicarbonates |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a TGFB1 protein, human |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta1 |2 NLM | |
| 650 | 7 | |a Creatinine |2 NLM | |
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| 700 | 1 | |a Gilligan, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Hostetter, Thomas H |e verfasserin |4 aut | |
| 700 | 1 | |a Greene, Tom |e verfasserin |4 aut | |
| 700 | 1 | |a Beddhu, Srinivasan |e verfasserin |4 aut | |
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