Markers of Kidney Tubular Secretion and Risk of Adverse Events in SPRINT Participants with CKD
Year: 2022
Type: article
Abstract: BACKGROUND: Kidney tubular secretion is an essential mechanism for clearing many common antihypertensive drugs and other metabolites and toxins. It is unknown whether novel measures of tubular secretion are associated with adverse events (AEs) during hypertension treatment. METHODS: , we created a summary secretion score by averaging across the standardized spot urine-to-plasma ratios of ten novel endogenous tubular secretion measures, with lower urine-to-plasma ratios reflecting worse tubular secretion. Multivariable Cox proportional hazards models were used to evaluate associations between the secretion score and risk of a composite of prespecified serious AEs (hypotension, syncope, bradycardia, AKI, electrolyte abnormalities, and injurious falls). The follow-up protocol for SPRINT routinely assessed two laboratory monitoring AEs (hyperkalemia and hypokalemia). RESULTS: Overall, 30% of participants experienced at least one AE during a median follow-up of 3.0 years. In multivariable models adjusted for eGFR and albuminuria, lower (worse) secretion scores at baseline were associated with greater risk of the composite AE outcome (hazard ratio per 1-SD lower secretion score, 1.16; 95% confidence interval, 1.04 to 1.27). In analyses of the individual AEs, lower secretion score was associated with significantly greater risk of AKI, serious electrolyte abnormalities, and ambulatory hyperkalemia. Associations were similar across randomized treatment assignment groups. CONCLUSION: Among SPRINT participants with CKD, worse tubular secretion was associated with greater risk of AEs, independent of eGFR and albuminuria.
Institutions: University of California San Diego, VA San Diego Healthcare System, San Francisco VA Medical Center, University of California, San Francisco, San Francisco VA Health Care System, University of California Davis Medical Center, University of California, Davis, University of Washington, Norwegian University of Science and Technology, St Olav's University Hospital, University of Utah, VA Salt Lake City Healthcare System, University of Utah Health Care, Oregon Health & Science University, Portland VA Medical Center, VA Portland Health Care System, University of Minnesota
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Veterans Affairs, American Heart Association, National Institutes of Health, Veterans Affairs San Diego Healthcare System, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1057971779, Stanford Center for Clinical and Translational Education and Research (SCCTER)UL1, G1201304535, G130883262, G1346455397, G1452718737, G1534123016, G1575401839, G1815451664, The Ohio State University Center for Clinical and Translational Science (UL1), Tufts Clinical and Translational Research Institute, Kidney Tubular Damage and Dysfunction Identify a Novel Axis of Chronic Kidney Disease, Stanford Center for Clinical & Translational Education and Research (Spectrum), G3042542605, Translational Research in Hypertension and Renal Biology, UC Davis Clinical and Translational Science Center, G3759862710, Clinical and Translational Science Institute at Children's National, UF Clinical and Translational Science Award, G4559308260, G5068655555, G522538789, Institutional Clinical and Translational Science Award, G541758880, G576625284, G5831220822, Tufts Clinical and Translation Science Institute (UL1), G5971433106, UAB-UCSD O'Brien Center for Acute Kidney Injury Research, G742032275, Institutional Clinical and Translational Science Award, G7727018999, The Vanderbilt Institute for Clinical and Translational Research (VICTR), Clinical and Translational Science Collaborative of Cleveland, G8723760441, G884570035, G94668252
OpenAlex ID: W4292065920