PMID- 35973732 OWN - NLM STAT- MEDLINE DCOM- 20230113 LR - 20231002 IS - 1533-3450 (Electronic) IS - 1046-6673 (Print) IS - 1046-6673 (Linking) VI - 33 IP - 10 DP - 2022 Oct TI - Markers of Kidney Tubular Secretion and Risk of Adverse Events in SPRINT Participants with CKD. PG - 1915-1926 LID - 10.1681/ASN.2022010117 [doi] AB - 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: Among 2089 SPRINT (Systolic Blood Pressure Intervention Trial) participants with baseline eGFR <60 ml/min per 1.73 m(2), 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. CI - Copyright (c) 2022 by the American Society of Nephrology. FAU - Bullen, Alexander L AU - Bullen AL AUID- ORCID: 0000-0001-6864-0336 AD - Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California. AD - Division of Nephrology-Hypertension, University of California, San Diego, California. FAU - Ascher, Simon B AU - Ascher SB AUID- ORCID: 0000-0002-9031-9327 AD - Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California, San Francisco, California. AD - Division of Hospital Medicine, University of California Davis, Sacramento, California. FAU - Scherzer, Rebecca AU - Scherzer R AD - Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California, San Francisco, California. FAU - Garimella, Pranav S AU - Garimella PS AUID- ORCID: 0000-0002-6016-4715 AD - Division of Nephrology-Hypertension, University of California, San Diego, California. FAU - Katz, Ronit AU - Katz R AD - Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington. FAU - Hallan, Stein I AU - Hallan SI AD - Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. AD - Department of Nephrology, St Olav University Hospital, Trondheim, Norway. FAU - Cheung, Alfred K AU - Cheung AK AD - Division of Nephrology and Hypertension, University of Utah Health, Salt Lake City, Utah. AD - Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. FAU - Raphael, Kalani L AU - Raphael KL AUID- ORCID: 0000-0002-1378-2609 AD - Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University and VA Portland Health Care System, Portland, Oregon. FAU - Estrella, Michelle M AU - Estrella MM AD - Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California, San Francisco, California. FAU - Jotwani, Vasantha K AU - Jotwani VK AD - Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California, San Francisco, California. FAU - Malhotra, Rakesh AU - Malhotra R AUID- ORCID: 0000-0002-4352-2103 AD - Division of Nephrology-Hypertension, University of California, San Diego, California. FAU - Seegmiller, Jesse C AU - Seegmiller JC AD - Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota. FAU - Shlipak, Michael G AU - Shlipak MG AD - Kidney Health Research Collaborative, Department of Medicine, San Francisco Veterans Affairs Health Care System and University of California, San Francisco, California. FAU - Ix, Joachim H AU - Ix JH AD - Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California. AD - Division of Nephrology-Hypertension, University of California, San Diego, California. LA - eng GR - UL1 TR000433/TR/NCATS NIH HHS/United States GR - UL1 TR000445/TR/NCATS NIH HHS/United States GR - R01 DK098234/DK/NIDDK NIH HHS/United States GR - UL1 TR000064/TR/NCATS NIH HHS/United States GR - UL1 TR000075/TR/NCATS NIH HHS/United States GR - IK2 BX004986/BX/BLRD VA/United States GR - UL1 TR000093/TR/NCATS NIH HHS/United States GR - UL1 TR000003/TR/NCATS NIH HHS/United States GR - UL1 TR000050/TR/NCATS NIH HHS/United States GR - UL1 TR001420/TR/NCATS NIH HHS/United States GR - UL1 RR025755/RR/NCRR NIH HHS/United States GR - HHSN268200900048C/HL/NHLBI NIH HHS/United States GR - UL1 TR000005/TR/NCATS NIH HHS/United States GR - P30 DK079337/DK/NIDDK NIH HHS/United States GR - HHSN268200900040C/HL/NHLBI NIH HHS/United States GR - K24 DK110427/DK/NIDDK NIH HHS/United States GR - HHSN268200900046C/HL/NHLBI NIH HHS/United States GR - P30 GM103337/GM/NIGMS NIH HHS/United States GR - UL1 TR001064/TR/NCATS NIH HHS/United States GR - UL1 RR025752/RR/NCRR NIH HHS/United States GR - UL1 RR025771/RR/NCRR NIH HHS/United States GR - HHSN268200900049C/HL/NHLBI NIH HHS/United States GR - HHSN268200900047C/HL/NHLBI NIH HHS/United States GR - UL1 TR000439/TR/NCATS NIH HHS/United States GR - UL1 TR000073/TR/NCATS NIH HHS/United States GR - UL1 TR000002/TR/NCATS NIH HHS/United States GR - UL1 TR000105/TR/NCATS NIH HHS/United States GR - UL1 RR024134/RR/NCRR NIH HHS/United States GR - UL1 TR003142/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20220816 PL - United States TA - J Am Soc Nephrol JT - Journal of the American Society of Nephrology : JASN JID - 9013836 RN - 0 (Electrolytes) SB - IM CIN - J Am Soc Nephrol. 2022 Oct;33(10):1806-1808. PMID: 36630518 MH - Humans MH - *Hypertension/complications MH - Albuminuria MH - *Hyperkalemia/complications MH - Risk Factors MH - Blood Pressure/physiology MH - Glomerular Filtration Rate MH - *Renal Insufficiency, Chronic/complications MH - *Acute Kidney Injury/complications MH - Electrolytes MH - Kidney PMC - PMC9528325 OTO - NOTNLM OT - adverse events OT - biomarker OT - hypertension OT - tubular secretion EDAT- 2022/08/17 06:00 MHDA- 2023/01/14 06:00 PMCR- 2023/10/01 CRDT- 2022/08/16 20:42 PHST- 2022/01/27 00:00 [received] PHST- 2022/06/13 00:00 [accepted] PHST- 2022/08/17 06:00 [pubmed] PHST- 2023/01/14 06:00 [medline] PHST- 2022/08/16 20:42 [entrez] PHST- 2023/10/01 00:00 [pmc-release] AID - 00001751-202210000-00018 [pii] AID - 2022010117 [pii] AID - 10.1681/ASN.2022010117 [doi] PST - ppublish SO - J Am Soc Nephrol. 2022 Oct;33(10):1915-1926. doi: 10.1681/ASN.2022010117. Epub 2022 Aug 16.