TY - JOUR
T1 - Apolipoprotein L1 Genotypes and the Association of Urinary Potassium Excretion with CKD Progression
AU - Ilori, Titilayo O.
AU - Liu, Jing
AU - Rodan, Aylin R.
AU - Verma, Ashish
AU - Mills, Katherine T.
AU - He, Jiang
AU - Winkler, Cheryl A.
AU - Dupuis, Josee
AU - Anderson, Cheryl A.M.
AU - Waikar, Sushrut S.
N1 - Funding Information:
T.O. Ilori is funded by the Department of Medicine, Boston Medical Center, and National Institute of Diabetes and Digestive and Kidney Diseases grant K23DK119542. J. Liu is funded by Science and Technology Department of Sichuan Province, China Innovation Seedling Project grant 2021029. A.R. Rodan is funded by National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK110358. C.A. Winkler is funded by the National Institutes of Health and National Cancer Institute Intramural Research Program contract HHSN261201500003I. This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research under contract no. 75N91019D00024 and in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. This work was also supported by the Department of Health and Human Services and National Cancer Institute grant 75N91019D00024.
Funding Information:
reports serving as a National Institutes of Health grant reviewer and a National Science Foundation grant reviewer; serving on the American Society of Nephrology Nominating Committee; and serving on the editorial boards of American Journal of Physiology Renal Physiology and Kidney360. A. Verma reports serving on the editorial boards of Frontiers in Medicine and Therapeutic Advances in Chronic Disease and Therapeutic Advances in Endocrinology and Metabolism and serving as a contributor to BMJ Best Practices. S.S. Waikar reports consultancy agreements with Bain, BioMarin, CANbridge, GSK, Ikena, Regeneron, Senda Biosciences, Strataca/ 3ive, and Wolters Kluewer; ownership interest in Amazon, Apple, Boeing, Citigroup, Southwest Airlines, and Walt Disney; research funding from JNJ, Pfizer, and Vertex; and serving as an expert witness for litigation related to laboratory testing (DaVita), perfluorooctanoic acid (PFAO) exposure (Dechert LLP), and proton pump inhibitors (Pfizer). All remaining authors have nothing to disclose.
Funding Information:
The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organiza-tions imply endorsement by the US government. The Chronic Renal Insufficiency Cohort (CRIC) study was conducted by CRIC Investigators and supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The data from the CRIC study reported here were supplied by the NIDDK Central Reposi-tory. This manuscript was not prepared in collaboration with Investigators of the CRIC study and does not necessarily reflect the opinions or views of the CRIC study, the NIDDK Central Reposi-tory, or the NIDDK.
Publisher Copyright:
© 2022 by the American Society of Nephrology.
PY - 2022/10
Y1 - 2022/10
N2 - Background and objectives Progressive CKD in Black individuals is strongly associated with polymorphisms in the APOL1 gene, but it is unknown whether dietary risk factors for CKD progression vary in high-versus low-risk APOL1 genotypes. We investigated if APOL1 genotypes modify associations of dietary potassium and sodium with CKD progression and death. Design, setting, participants, & measurements We analyzed 1399 self-identified Black participants enrolled in the Chronic Renal Insufficiency Cohort from April 2003 to September 2008. Exposures were calibrated 24-hour urine potassium and sodium excretion. The primary outcome was CKD progression defined as the time to 50% decline in eGFR or kidney failure. The secondary outcome was CKD progression or death. We tested for an interaction between urinary potassium and sodium excretion and APOL1 genotypes. Results Median 24-hour urinary sodium and potassium excretions in Black participants were 150 mmol (interquartile range, 118–188) and 43 mmol (interquartile range, 35–54), respectively. Individuals with high-and low-risk APOL1 genotypes numbered 276 (20%) and 1104 (79%), respectively. After a median follow-up of 5.23 years, CKD progression events equaled 605, and after 7.29 years, CKD progression and death events equaled 868. There was significant interaction between APOL1 genotypes and urinary potassium excretion with CKD progression and CKD progression or death (P50.003 and P50.03, respectively). In those with high-risk APOL1 genotypes, higher urinary potassium excretion was associated with a lower risk of CKD progression (quartiles 2–4 versus 1: hazard ratio, 0.83; 95% confidence interval, 0.50 to 1.39; hazard ratio, 0.54; 95% confidence interval, 0.31 to 0.93; and hazard ratio, 0.50; 95% confidence interval, 0.27 to 0.93, respectively). In the low-risk APOL1 genotypes, higher urinary potassium excretion was associated with a higher risk of CKD progression (quartiles 2–4 versus 1: hazard ratio, 1.01; 95% confidence interval, 0.75 to 1.36; hazard ratio, 1.23; 95% confidence interval, 0.91 to 1.66; and hazard ratio, 1.53; 95% confidence interval, 1.12 to 2.09, respectively). We found no interaction between APOL1 genotypes and urinary sodium excretion with CKD outcomes. Conclusions Higher urinary potassium excretion was associated with lower versus higher risk of CKD progression in APOL1 high-risk and low-risk genotypes, respectively.
AB - Background and objectives Progressive CKD in Black individuals is strongly associated with polymorphisms in the APOL1 gene, but it is unknown whether dietary risk factors for CKD progression vary in high-versus low-risk APOL1 genotypes. We investigated if APOL1 genotypes modify associations of dietary potassium and sodium with CKD progression and death. Design, setting, participants, & measurements We analyzed 1399 self-identified Black participants enrolled in the Chronic Renal Insufficiency Cohort from April 2003 to September 2008. Exposures were calibrated 24-hour urine potassium and sodium excretion. The primary outcome was CKD progression defined as the time to 50% decline in eGFR or kidney failure. The secondary outcome was CKD progression or death. We tested for an interaction between urinary potassium and sodium excretion and APOL1 genotypes. Results Median 24-hour urinary sodium and potassium excretions in Black participants were 150 mmol (interquartile range, 118–188) and 43 mmol (interquartile range, 35–54), respectively. Individuals with high-and low-risk APOL1 genotypes numbered 276 (20%) and 1104 (79%), respectively. After a median follow-up of 5.23 years, CKD progression events equaled 605, and after 7.29 years, CKD progression and death events equaled 868. There was significant interaction between APOL1 genotypes and urinary potassium excretion with CKD progression and CKD progression or death (P50.003 and P50.03, respectively). In those with high-risk APOL1 genotypes, higher urinary potassium excretion was associated with a lower risk of CKD progression (quartiles 2–4 versus 1: hazard ratio, 0.83; 95% confidence interval, 0.50 to 1.39; hazard ratio, 0.54; 95% confidence interval, 0.31 to 0.93; and hazard ratio, 0.50; 95% confidence interval, 0.27 to 0.93, respectively). In the low-risk APOL1 genotypes, higher urinary potassium excretion was associated with a higher risk of CKD progression (quartiles 2–4 versus 1: hazard ratio, 1.01; 95% confidence interval, 0.75 to 1.36; hazard ratio, 1.23; 95% confidence interval, 0.91 to 1.66; and hazard ratio, 1.53; 95% confidence interval, 1.12 to 2.09, respectively). We found no interaction between APOL1 genotypes and urinary sodium excretion with CKD outcomes. Conclusions Higher urinary potassium excretion was associated with lower versus higher risk of CKD progression in APOL1 high-risk and low-risk genotypes, respectively.
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U2 - 10.2215/CJN.02680322
DO - 10.2215/CJN.02680322
M3 - Article
C2 - 36400568
AN - SCOPUS:85139457170
SN - 1555-9041
VL - 17
SP - 1477
EP - 1486
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 10
ER -