PMID- 34473302 OWN - NLM STAT- MEDLINE DCOM- 20220824 LR - 20230311 IS - 1460-2385 (Electronic) IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 37 IP - 9 DP - 2022 Aug 22 TI - Kidney tubule health, mineral metabolism and adverse events in persons with CKD in SPRINT. PG - 1637-1646 LID - 10.1093/ndt/gfab255 [doi] AB - BACKGROUND: Measures of kidney tubule health are risk markers for acute kidney injury (AKI) in persons with chronic kidney disease (CKD) during hypertension treatment, but their associations with other adverse events (AEs) are unknown. METHODS: Among 2377 Systolic Blood Pressure Intervention Trial (SPRINT) participants with CKD, we measured at baseline eight urine biomarkers of kidney tubule health and two serum biomarkers of mineral metabolism pathways that act on the kidney tubules. Cox proportional hazards models were used to evaluate biomarker associations with risk of a composite of pre-specified serious AEs (hypotension, syncope, electrolyte abnormalities, AKI, bradycardia and injurious falls) and outpatient AEs (hyperkalemia and hypokalemia). RESULTS: At baseline, the mean age was 73 +/- 9 years and mean estimated glomerular filtration rate (eGFR) was 46 +/- 11 mL/min/1.73 m2. During a median follow-up of 3.8 years, 716 (30%) participants experienced the composite AE. Higher urine interleukin-18, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein-1 (MCP-1), lower urine uromodulin (UMOD) and higher serum fibroblast growth factor-23 were individually associated with higher risk of the composite AE outcome in multivariable-adjusted models including eGFR and albuminuria. When modeling biomarkers in combination, higher NGAL [hazard ratio (HR) = 1.08 per 2-fold higher biomarker level, 95% confidence interval (CI) 1.03-1.13], higher MCP-1 (HR = 1.11, 95% CI 1.03-1.19) and lower UMOD (HR = 0.91, 95% CI 0.85-0.97) were each associated with higher composite AE risk. Biomarker associations did not vary by intervention arm (P > 0.10 for all interactions). CONCLUSIONS: Among persons with CKD, several kidney tubule biomarkers are associated with higher risk of AEs during hypertension treatment, independent of eGFR and albuminuria. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of ERA. All rights reserved. FAU - Ascher, Simon B AU - Ascher SB AD - Department of Medicine, Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, CA, USA. AD - Division of Hospital Medicine, University of California Davis, Sacramento, CA, USA. FAU - Scherzer, Rebecca AU - Scherzer R AD - Department of Medicine, Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, CA, USA. FAU - Estrella, Michelle M AU - Estrella MM AD - Department of Medicine, Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, CA, USA. FAU - Berry, Jarett D AU - Berry JD AD - Divison of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - de Lemos, James A AU - de Lemos JA AD - Divison of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Jotwani, Vasantha K AU - Jotwani VK AD - Department of Medicine, Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, CA, USA. FAU - Garimella, Pranav S AU - Garimella PS AD - Division of Nephrology-Hypertension, University of California San Diego, San Diego, CA, USA. FAU - Malhotra, Rakesh AU - Malhotra R AD - Division of Nephrology-Hypertension, University of California San Diego, San Diego, CA, USA. FAU - Bullen, Alexander L AU - Bullen AL AD - Division of Nephrology-Hypertension, University of California San Diego, San Diego, CA, USA. AD - Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA. FAU - Katz, Ronit AU - Katz R AD - Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA. FAU - Ambrosius, Walter T AU - Ambrosius WT AD - Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC, USA. FAU - Cheung, Alfred K AU - Cheung AK AD - Division of Nephrology and Hypertension, University of Utah Health, Salt Lake City, UT, USA. AD - Department of Medical Service, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, UT, USA. FAU - Chonchol, Michel AU - Chonchol M AD - Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, USA. FAU - Killeen, Anthony A AU - Killeen AA AUID- ORCID: 0000-0003-1629-9468 AD - Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA. FAU - Ix, Joachim H AU - Ix JH AD - Division of Nephrology-Hypertension, University of California San Diego, San Diego, CA, USA. AD - Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA. FAU - Shlipak, Michael G AU - Shlipak MG AD - Department of Medicine, Kidney Health Research Collaborative, San Francisco Veterans Affairs Health Care System and University of California San Francisco, San Francisco, CA, USA. CN - SPRINT Research Group 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 - 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 - K24 DK110427/DK/NIDDK NIH HHS/United States GR - HHSN268200900048C/HL/NHLBI NIH HHS/United States GR - UL1 TR000005/TR/NCATS NIH HHS/United States GR - HHSN268200900040C/HL/NHLBI NIH HHS/United States GR - UL1 TR002548/TR/NCATS 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 - R01 HL144112/HL/NHLBI NIH HHS/United States GR - UL1 TR000093/TR/NCATS 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 - Clinical Trial PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 0 (Biomarkers) RN - 0 (Lipocalin-2) RN - 0 (Minerals) RN - 0 (Uromodulin) SB - IM MH - *Acute Kidney Injury MH - Aged MH - Aged, 80 and over MH - Albuminuria/complications MH - Biomarkers MH - Blood Pressure/physiology MH - Glomerular Filtration Rate/physiology MH - Humans MH - *Hypertension MH - Kidney Tubules MH - Lipocalin-2 MH - Middle Aged MH - Minerals MH - *Renal Insufficiency, Chronic/complications MH - Uromodulin PMC - PMC9649818 OTO - NOTNLM OT - adverse events OT - biomarkers OT - chronic kidney disease OT - hypertension OT - kidney tubule EDAT- 2021/09/03 06:00 MHDA- 2022/08/25 06:00 PMCR- 2021/09/02 CRDT- 2021/09/02 12:26 PHST- 2021/05/19 00:00 [received] PHST- 2021/09/03 06:00 [pubmed] PHST- 2022/08/25 06:00 [medline] PHST- 2021/09/02 12:26 [entrez] PHST- 2021/09/02 00:00 [pmc-release] AID - 6362902 [pii] AID - gfab255 [pii] AID - 10.1093/ndt/gfab255 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2022 Aug 22;37(9):1637-1646. doi: 10.1093/ndt/gfab255.