PMID- 35812302 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240503 IS - 2468-0249 (Electronic) IS - 2468-0249 (Linking) VI - 7 IP - 7 DP - 2022 Jul TI - Biomarkers of Kidney Tubule Disease and Risk of End-Stage Kidney Disease in Persons With Diabetes and CKD. PG - 1514-1523 LID - 10.1016/j.ekir.2022.03.033 [doi] AB - INTRODUCTION: Tubulointerstitial damage in diabetes and chronic kidney disease (CKD) is poorly captured by estimated glomerular filtration rate (eGFR) and albuminuria. Urine biomarkers of kidney health may better elucidate disease progression in persons with diabetes and CKD. METHODS: Per case-cohort design, we randomly selected a subcohort of 560 study participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study from 1092 adults with diabetes and baseline eGFR <60 ml/min per 1.73 m(2) and registered a total of 161 end-stage kidney disease (ESKD) cases (n = 93 from the subcohort; n = 68 from outside the subcohort) during 4.3 +/- 2.7 years mean follow-up. We measured urine biomarkers of kidney tubule injury (kidney injury molecule-1 [KIM-1]), inflammation and fibrosis (monocyte chemoattractant protein-1 [MCP-1]), repair (chitinase-3-like protein 1 [YKL-40]), and tubule function, including reabsorption (alpha-1-microglobulin [alpha1m]) and synthetic capacity (epidermal growth factor [EGF] and uromodulin [UMOD]). Weighted Cox regression models estimated ESKD risk adjusting for demographics, ESKD risk factors, and baseline eGFR and urine albumin. Least absolute shrinkage and selection operator (LASSO) regression identified a subset of biomarkers most strongly associated with ESKD. RESULTS: At baseline, subcohort participants had mean age of 70 +/- 9 years, mean eGFR of 40 +/-13 ml/min per 1.73 m(2), and median urine albumin-to-creatinine ratio of 33 (interquartile range 10-213) mg/g. Adjusting for baseline eGFR and albuminuria, each 2-fold higher urine KIM-1 (hazard ratio = 1.43 [95% CI: 1.17-1.75]), alpha1m (hazard ratio = 1.47 [1.19-1.82]), and MCP-1 (hazard ratio = 1.27 [1.06-1.53]) were independently associated with ESKD. LASSO retained KIM-1 and alpha1m for associations with ESKD. CONCLUSION: Among adults with diabetes and eGFR <60 ml/min per 1.73 m(2), higher urine KIM-1, alpha1m, and MCP-1 are independently associated with incident ESKD, providing insight into kidney disease progression in persons with diabetes and CKD. CI - (c) 2022 International Society of Nephrology. Published by Elsevier Inc. FAU - Amatruda, Jonathan G AU - Amatruda JG AD - Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, California, USA. AD - Kidney Health Research Collaborative, San Francisco VA Medical Center and University of California, San Francisco, San Francisco, California, USA. FAU - Katz, Ronit AU - Katz R AD - Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington, USA. FAU - Sarnak, Mark J AU - Sarnak MJ AD - Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts, USA. FAU - Gutierrez, Orlando M AU - Gutierrez OM AD - Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. AD - Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA. FAU - Greenberg, Jason H AU - Greenberg JH AD - Section of Nephrology, Department of Pediatrics, Clinical and Translational Research Accelerator, Yale University School of Medicine, New Haven, Connecticut, USA. FAU - Cushman, Mary AU - Cushman M AD - Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA. FAU - Waikar, Sushrut AU - Waikar S AD - Section of Nephrology, Department of Medicine, Boston Medical Center, Boston, Massachusetts, USA. FAU - Parikh, Chirag R AU - Parikh CR AD - Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA. FAU - Schelling, Jeffrey R AU - Schelling JR AD - Division of Nephrology, Department of Internal Medicine, MetroHealth System, Cleveland, Ohio, USA. AD - Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio. FAU - Jogalekar, Manasi P AU - Jogalekar MP AD - Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Bonventre, Joseph V AU - Bonventre JV AD - Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Vasan, Ramachandran S AU - Vasan RS AD - Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA. AD - Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA. FAU - Kimmel, Paul L AU - Kimmel PL AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. FAU - Shlipak, Michael G AU - Shlipak MG AD - Kidney Health Research Collaborative, San Francisco VA Medical Center and University of California, San Francisco, San Francisco, California, USA. AD - Department of Medicine, San Francisco VA Health Care System, San Francisco, California, USA. FAU - Ix, Joachim H AU - Ix JH AD - Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, California, USA. AD - Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, California, USA. CN - CKD Biomarkers Consortium LA - eng GR - U01 DK085660/DK/NIDDK NIH HHS/United States GR - F32 DK126381/DK/NIDDK NIH HHS/United States GR - UL1 TR001863/TR/NCATS NIH HHS/United States GR - U01 DK102730/DK/NIDDK NIH HHS/United States GR - U01 NS041588/NS/NINDS NIH HHS/United States GR - K24 DK110427/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20220405 PL - United States TA - Kidney Int Rep JT - Kidney international reports JID - 101684752 CIN - Kidney Int Rep. 2022 Jun 03;7(7):1458-1460. PMID: 35816655 PMC - PMC9263389 OTO - NOTNLM OT - biomarkers OT - chronic kidney disease OT - diabetes mellitus OT - end-stage kidney disease EDAT- 2022/07/12 06:00 MHDA- 2022/07/12 06:01 PMCR- 2022/04/05 CRDT- 2022/07/11 03:44 PHST- 2021/12/21 00:00 [received] PHST- 2022/03/18 00:00 [revised] PHST- 2022/03/28 00:00 [accepted] PHST- 2022/07/11 03:44 [entrez] PHST- 2022/07/12 06:00 [pubmed] PHST- 2022/07/12 06:01 [medline] PHST- 2022/04/05 00:00 [pmc-release] AID - S2468-0249(22)01253-0 [pii] AID - 10.1016/j.ekir.2022.03.033 [doi] PST - epublish SO - Kidney Int Rep. 2022 Apr 5;7(7):1514-1523. doi: 10.1016/j.ekir.2022.03.033. eCollection 2022 Jul.