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Tubular Secretion and Estimated GFR Decline in the Jackson Heart Study

INTRODUCTION: Secretion of solutes by the proximal tubules represents an intrinsic kidney function not directly reflected by the glomerular filtration rate (GFR). The early loss of secretory clearance may reflect unrecognized kidney dysfunction, portending future disease progression. METHODS: We des...

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Autores principales: Granda, Michael L., Zelnick, Leila R., Prince, David K., Hoofnagle, Andrew, Young, Bessie A., Kestenbaum, Bryan R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727527/
https://www.ncbi.nlm.nih.gov/pubmed/36506244
http://dx.doi.org/10.1016/j.ekir.2022.09.008
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author Granda, Michael L.
Zelnick, Leila R.
Prince, David K.
Hoofnagle, Andrew
Young, Bessie A.
Kestenbaum, Bryan R.
author_facet Granda, Michael L.
Zelnick, Leila R.
Prince, David K.
Hoofnagle, Andrew
Young, Bessie A.
Kestenbaum, Bryan R.
author_sort Granda, Michael L.
collection PubMed
description INTRODUCTION: Secretion of solutes by the proximal tubules represents an intrinsic kidney function not directly reflected by the glomerular filtration rate (GFR). The early loss of secretory clearance may reflect unrecognized kidney dysfunction, portending future disease progression. METHODS: We designed a nested case-control study within the Jackson Heart Study (JHS), a prospective study of African American adults in Mississippi, to associate baseline differences in proximal tubular secretion of 5 endogenously produced solutes with future estimated glomerular rate (eGFR) decline. We matched 127 pairs by creatinine-eGFR, age, diabetes, and sex among the patients who provided a 24-hour urine collection; cases had a ≥25% decline in eGFR compared to <10% in controls over 10 years of follow-up. We measured baseline plasma and urine concentrations of secretory solutes using liquid chromatography-mass spectrometry to determine the odds ratio of kidney disease progression. RESULTS: Mean age was 60 years; 76% were women; 30% had diabetes; mean baseline eGFR was 94±20 ml/min per 1.73 m(2). The eGFR decline over 10 years was 38±13% in cases and 0±10% in controls. After adjustment for the matching variables plus albuminuria, systolic blood pressure, body mass index, and smoking, each 50% lower kidney clearance of isovalerylglycine, kynurenic acid, and xanthosine were associated with 1.4 to 2.2 greater odds of eGFR decline. Kynurenic acid exhibited the strongest association; each 50% lower clearance of this secretory solute was associated with 2.20-fold higher odds of eGFR decline (95% confidence interval [CI] 1.32–3.67). CONCLUSION: We found that in this community-based study of adults without significant kidney disease, lower proximal tubular secretory solute clearance is associated with future eGFR decline.
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spelling pubmed-97275272022-12-08 Tubular Secretion and Estimated GFR Decline in the Jackson Heart Study Granda, Michael L. Zelnick, Leila R. Prince, David K. Hoofnagle, Andrew Young, Bessie A. Kestenbaum, Bryan R. Kidney Int Rep Clinical Research INTRODUCTION: Secretion of solutes by the proximal tubules represents an intrinsic kidney function not directly reflected by the glomerular filtration rate (GFR). The early loss of secretory clearance may reflect unrecognized kidney dysfunction, portending future disease progression. METHODS: We designed a nested case-control study within the Jackson Heart Study (JHS), a prospective study of African American adults in Mississippi, to associate baseline differences in proximal tubular secretion of 5 endogenously produced solutes with future estimated glomerular rate (eGFR) decline. We matched 127 pairs by creatinine-eGFR, age, diabetes, and sex among the patients who provided a 24-hour urine collection; cases had a ≥25% decline in eGFR compared to <10% in controls over 10 years of follow-up. We measured baseline plasma and urine concentrations of secretory solutes using liquid chromatography-mass spectrometry to determine the odds ratio of kidney disease progression. RESULTS: Mean age was 60 years; 76% were women; 30% had diabetes; mean baseline eGFR was 94±20 ml/min per 1.73 m(2). The eGFR decline over 10 years was 38±13% in cases and 0±10% in controls. After adjustment for the matching variables plus albuminuria, systolic blood pressure, body mass index, and smoking, each 50% lower kidney clearance of isovalerylglycine, kynurenic acid, and xanthosine were associated with 1.4 to 2.2 greater odds of eGFR decline. Kynurenic acid exhibited the strongest association; each 50% lower clearance of this secretory solute was associated with 2.20-fold higher odds of eGFR decline (95% confidence interval [CI] 1.32–3.67). CONCLUSION: We found that in this community-based study of adults without significant kidney disease, lower proximal tubular secretory solute clearance is associated with future eGFR decline. Elsevier 2022-09-12 /pmc/articles/PMC9727527/ /pubmed/36506244 http://dx.doi.org/10.1016/j.ekir.2022.09.008 Text en © 2022 International Society of Nephrology. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Clinical Research
Granda, Michael L.
Zelnick, Leila R.
Prince, David K.
Hoofnagle, Andrew
Young, Bessie A.
Kestenbaum, Bryan R.
Tubular Secretion and Estimated GFR Decline in the Jackson Heart Study
title Tubular Secretion and Estimated GFR Decline in the Jackson Heart Study
title_full Tubular Secretion and Estimated GFR Decline in the Jackson Heart Study
title_fullStr Tubular Secretion and Estimated GFR Decline in the Jackson Heart Study
title_full_unstemmed Tubular Secretion and Estimated GFR Decline in the Jackson Heart Study
title_short Tubular Secretion and Estimated GFR Decline in the Jackson Heart Study
title_sort tubular secretion and estimated gfr decline in the jackson heart study
topic Clinical Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727527/
https://www.ncbi.nlm.nih.gov/pubmed/36506244
http://dx.doi.org/10.1016/j.ekir.2022.09.008
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