PMID- 32111704 OWN - NLM STAT- MEDLINE DCOM- 20210531 LR - 20230425 IS - 1555-905X (Electronic) IS - 1555-9041 (Print) IS - 1555-9041 (Linking) VI - 15 IP - 3 DP - 2020 Mar 6 TI - Urine Markers of Kidney Tubule Cell Injury and Kidney Function Decline in SPRINT Trial Participants with CKD. PG - 349-358 LID - 10.2215/CJN.02780319 [doi] AB - BACKGROUND AND OBJECTIVES: eGFR and albuminuria primarily reflect glomerular function and injury, whereas tubule cell atrophy and interstitial fibrosis on kidney biopsy are important risk markers for CKD progression. Kidney tubule injury markers have primarily been studied in hospitalized AKI. Here, we examined the association between urinary kidney tubule injury markers at baseline with subsequent loss of kidney function in persons with nondiabetic CKD who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 2428 SPRINT participants with CKD (eGFR<60 ml/min per 1.73 m(2)) at baseline, we measured urine markers of tubule injury (IL-18, kidney injury molecule-1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL]), inflammation (monocyte chemoattractant protein-1 [MCP-1]), and repair (human cartilage glycoprotein-40 [YKL-40]). Cox proportional hazards models evaluated associations of these markers with the kidney composite outcome of 50% eGFR decline or ESKD requiring dialysis or kidney transplantation, and linear mixed models evaluated annualized change in eGFR. RESULTS: Mean participant age was 73+/-9 (SD) years, 60% were men, 66% were white, and mean baseline eGFR was 46+/-11 ml/min per 1.73 m(2). There were 87 kidney composite outcome events during a median follow-up of 3.8 years. Relative to the respective lowest quartiles, the highest quartiles of urinary KIM-1 (hazard ratio, 2.84; 95% confidence interval [95% CI], 1.31 to 6.17), MCP-1 (hazard ratio, 2.43; 95% CI, 1.13 to 5.23), and YKL-40 (hazard ratio, 1.95; 95% CI, 1.08 to 3.51) were associated with higher risk of the kidney composite outcome in fully adjusted models including baseline eGFR and urine albumin. In linear analysis, urinary IL-18 was the only marker associated with eGFR decline (-0.91 ml/min per 1.73 m(2) per year for highest versus lowest quartile; 95% CI, -1.44 to -0.38), a finding that was stronger in the standard arm of SPRINT. CONCLUSIONS: Urine markers of tubule cell injury provide information about risk of subsequent loss of kidney function, beyond the eGFR and urine albumin. CI - Copyright (c) 2020 by the American Society of Nephrology. FAU - Malhotra, Rakesh AU - Malhotra R AD - Division of Nephrology and Hypertension, Department of Medicine and. AD - Division of Nephrology and Hypertension, Imperial Valley Family Care Medical Group, El Centro, California. FAU - Katz, Ronit AU - Katz R AD - Kidney Research Institute, University of Washington, Seattle, Washington. FAU - Jotwani, Vasantha AU - Jotwani V AD - Kidney Health Research Collaborative, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, California. FAU - Ambrosius, Walter T AU - Ambrosius WT AD - Department of Biostatistics and Data Science, Division of Public Health Sciences and. FAU - Raphael, Kalani L AU - Raphael KL AD - Division of Nephrology and Hypertension, University of Utah Health and Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. FAU - Haley, William AU - Haley W AD - Division of Nephrology, Mayo Clinic, Jacksonville, Florida. FAU - Rastogi, Anjay AU - Rastogi A AD - Division of Nephrology, University of California Los Angeles, Los Angeles, California. FAU - Cheung, Alfred K AU - Cheung AK AD - Division of Nephrology and Hypertension, University of Utah Health and Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. FAU - Freedman, Barry I AU - Freedman BI AUID- ORCID: 0000-0003-0275-5530 AD - Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina. FAU - Punzi, Henry AU - Punzi H AD - Trinity Hypertension and Metabolic Research Instititute, Punzi Medical Center, Carrollton, Texas. FAU - Rocco, Michael V AU - Rocco MV AD - Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina. FAU - Ix, Joachim H AU - Ix JH AD - Division of Nephrology and Hypertension, Department of Medicine and. AD - Division of Preventive Medicine, Department of Family Medicine and Public Health, University of California San Diego, San Diego, California. AD - Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, California; and. FAU - Shlipak, Michael G AU - Shlipak MG AD - Kidney Health Research Collaborative, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, California. AD - Division of General Internal Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, California. LA - eng GR - UL1 TR000439/TR/NCATS NIH HHS/United States GR - R01 DK098234/DK/NIDDK NIH HHS/United States GR - UL1 TR000005/TR/NCATS NIH HHS/United States GR - UL1 TR000073/TR/NCATS NIH HHS/United States GR - UL1 TR000003/TR/NCATS NIH HHS/United States GR - UL1 TR000105/TR/NCATS NIH HHS/United States GR - UL1 RR025752/RR/NCRR NIH HHS/United States GR - K24 DK110427/DK/NIDDK NIH HHS/United States GR - UL1 TR002548/TR/NCATS NIH HHS/United States GR - HHSN268200900040C/HL/NHLBI NIH HHS/United States GR - UL1 RR024134/RR/NCRR NIH HHS/United States GR - HHSN268200900049C/HL/NHLBI NIH HHS/United States GR - HHSN268200900046C/HL/NHLBI NIH HHS/United States GR - UL1 TR001420/TR/NCATS NIH HHS/United States GR - UL1 TR000075/TR/NCATS NIH HHS/United States GR - P30 GM103337/GM/NIGMS NIH HHS/United States GR - UL1 TR000064/TR/NCATS NIH HHS/United States GR - HHSN268200900047C/HL/NHLBI NIH HHS/United States GR - UL1 TR000050/TR/NCATS NIH HHS/United States GR - UL1 RR025755/RR/NCRR NIH HHS/United States GR - UL1 TR000433/TR/NCATS NIH HHS/United States GR - UL1 TR000093/TR/NCATS NIH HHS/United States GR - HHSN268200900048C/HL/NHLBI NIH HHS/United States GR - UL1 TR000002/TR/NCATS NIH HHS/United States GR - UL1 TR001064/TR/NCATS NIH HHS/United States GR - UL1 TR000445/TR/NCATS NIH HHS/United States GR - UL1 TR003142/TR/NCATS NIH HHS/United States GR - UL1 RR025771/RR/NCRR 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 - 20200228 PL - United States TA - Clin J Am Soc Nephrol JT - Clinical journal of the American Society of Nephrology : CJASN JID - 101271570 RN - 0 (Biomarkers) RN - 0 (CCL2 protein, human) RN - 0 (CHI3L1 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chitinase-3-Like Protein 1) RN - 0 (HAVCR1 protein, human) RN - 0 (Hepatitis A Virus Cellular Receptor 1) RN - 0 (IL18 protein, human) RN - 0 (Interleukin-18) SB - IM CIN - Clin J Am Soc Nephrol. 2020 Mar 6;15(3):304-305. PMID: 32120346 MH - Aged MH - Aged, 80 and over MH - Albuminuria/diagnosis/etiology/physiopathology/*urine MH - Biomarkers/urine MH - Chemokine CCL2/*urine MH - Chitinase-3-Like Protein 1/*urine MH - Disease Progression MH - Female MH - *Glomerular Filtration Rate MH - Hepatitis A Virus Cellular Receptor 1/*metabolism MH - Humans MH - Hypertension/complications MH - Interleukin-18/*urine MH - Kidney Tubules/*metabolism/pathology/physiopathology MH - Male MH - Middle Aged MH - Predictive Value of Tests MH - Randomized Controlled Trials as Topic MH - Renal Insufficiency, Chronic/diagnosis/etiology/physiopathology/*urine MH - Risk Assessment MH - Risk Factors MH - Urinalysis PMC - PMC7057300 OTO - NOTNLM OT - acute kidney injury OT - albuminuria OT - blood pressure OT - chemokine CCL2 OT - chitinase-3-like protein 1 OT - chronic kidney disease OT - chronic renal insufficiency OT - confidence intervals OT - follow-up studies OT - glomerular filtration rate OT - hepatitis A virus cellular receptor 1 OT - human CCL2 protein OT - human CHI3L1 protein OT - human HAVCR1 protein OT - human LCN2 protein OT - humans OT - inflammation OT - interleukin-18 OT - kidney function decline OT - kidney transplantation OT - kidney tubules OT - lipocalin-2 OT - male OT - proportional hazards models OT - tubule injury biomarkers EDAT- 2020/03/01 06:00 MHDA- 2021/06/01 06:00 PMCR- 2021/03/06 CRDT- 2020/03/01 06:00 PHST- 2019/03/08 00:00 [received] PHST- 2020/01/17 00:00 [accepted] PHST- 2020/03/01 06:00 [pubmed] PHST- 2021/06/01 06:00 [medline] PHST- 2020/03/01 06:00 [entrez] PHST- 2021/03/06 00:00 [pmc-release] AID - 01277230-202003000-00010 [pii] AID - 02780319 [pii] AID - 10.2215/CJN.02780319 [doi] PST - ppublish SO - Clin J Am Soc Nephrol. 2020 Mar 6;15(3):349-358. doi: 10.2215/CJN.02780319. Epub 2020 Feb 28.