PMID- 37841418 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240504 IS - 2590-0595 (Electronic) IS - 2590-0595 (Linking) VI - 5 IP - 11 DP - 2023 Nov TI - Plasma Biomarkers and Incident CKD Among Individuals Without Diabetes. PG - 100719 LID - 10.1016/j.xkme.2023.100719 [doi] LID - 100719 AB - RATIONALE & OBJECTIVE: Biomarkers of kidney disease progression have been identified in individuals with diabetes and underlying chronic kidney disease (CKD). Whether or not these markers are associated with the development of CKD in a general population without diabetes or CKD is not well established. STUDY DESIGN: Prospective observational cohort. SETTING & PARTICIPANTS: In the Atherosclerosis Risk in Communities) study, 948 participants were studied. EXPOSURES: The baseline plasma biomarkers of kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), soluble urokinase plasminogen activator receptor (suPAR), tumor necrosis factor receptor 1 (TNFR-1), tumor necrosis factor receptor 2 (TNFR-2), and human cartilage glycoprotein-39 (YKL-40) measured in 1996-1998. OUTCOME: Incident CKD after 15 years of follow-up defined as >/=40% estimated glomerular filtration rate decline to <60 mL/min/1.73 m(2) or dialysis dependence through United States Renal Data System linkage. ANALYTICAL APPROACH: Logistic regression and C statistics. RESULTS: There were 523 cases of incident CKD. Compared with a random sample of 425 controls, there were greater odds of incident CKD per 2-fold higher concentration of KIM-1 (OR, 1.49; 95% CI, 1.25-1.78), suPAR (OR, 2.57; 95% CI, 1.74-3.84), TNFR-1 (OR, 2.20; 95% CI, 1.58-3.09), TNFR-2 (OR, 2.03; 95% CI, 1.37-3.04). After adjustment for all biomarkers, KIM-1 (OR, 1.42; 95% CI, 1.19-1.71), and suPAR (OR, 1.86; 95% CI, 1.18-2.92) remained associated with incident CKD. Compared with traditional risk factors, the addition of all 6 biomarkers improved the C statistic from 0.695-0.731 (P < 0.01) and using the observed risk of 12% for incident CKD, the predicted risk gradient changed from 5%-40% (for the 1st-5th quintile) to 4%-44%. LIMITATIONS: Biomarkers and creatinine were measured at one time point. CONCLUSIONS: Higher levels of KIM-1, suPAR, TNFR-1, and TNFR-2 were associated with higher odds of incident CKD among individuals without diabetes. PLAIN-LANGUAGE SUMMARY: For people with diabetes or kidney disease, several biomarkers have been shown to be associated with worsening kidney disease. Whether these biomarkers have prognostic significance in people without diabetes or kidney disease is less studied. Using the Atherosclerosis Risk in Communities study, we followed individuals without diabetes or kidney disease for an average of 15 years after biomarker measurement to see if these biomarkers were associated with the development of kidney disease. We found that elevated levels of KIM-1, suPAR, TNFR-1, and TNFR-2 were associated with the development of kidney disease. These biomarkers may help identify individuals who would benefit from interventions to prevent the development of kidney disease. CI - (c) 2023 The Authors. FAU - Le, Dustin AU - Le D AD - Division of Nephrology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD. FAU - Chen, Jingsha AU - Chen J AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 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; Division of General Internal Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, California. FAU - Ix, Joachim H AU - Ix JH AD - Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, California; Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, California: Kidney Research Innovation Hub of San Diego, San Diego, California. FAU - Sarnak, Mark J AU - Sarnak MJ AD - Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA. FAU - Gutierrez, Orlando M AU - Gutierrez OM AD - Division of Nephrology, Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL. FAU - Schelling, Jeffrey R AU - Schelling JR AD - Department of Physiology and Biophysics and Medicine, Case Western Reserve University School of Medicine, Cleveland, OH. FAU - Bonventre, Joseph V AU - Bonventre JV AD - Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. FAU - Sabbisetti, Venkata S AU - Sabbisetti VS AD - Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. FAU - Schrauben, Sarah J AU - Schrauben SJ AD - Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Coca, Steven G AU - Coca SG AD - Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY. FAU - Kimmel, Paul L AU - Kimmel PL AD - Division of Kidney Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. FAU - Vasan, Ramachandran S AU - Vasan RS AD - Framingham Heart Study of the National Heart, Lung, and Blood Institute and Boston University School of Medicine, Framingham, MA. FAU - Grams, Morgan E AU - Grams ME AD - Division of Precision Medicine, Department of Medicine, New York University, NY. FAU - Parikh, Chirag AU - Parikh C AD - Division of Nephrology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD. FAU - Coresh, Josef AU - Coresh J AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. FAU - Rebholz, Casey M AU - Rebholz CM AD - Division of Nephrology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD. AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. CN - Chronic Kidney Disease Biomarkers Consortium LA - eng GR - R01 HL085757/HL/NHLBI NIH HHS/United States GR - 75N92022D00002/HL/NHLBI NIH HHS/United States GR - R01 DK093770/DK/NIDDK NIH HHS/United States GR - U01 DK106962/DK/NIDDK NIH HHS/United States GR - 75N92022D00004/HL/NHLBI NIH HHS/United States GR - R01 DK072381/DK/NIDDK NIH HHS/United States GR - UH3 DK114866/DK/NIDDK NIH HHS/United States GR - R01 HL153178/HL/NHLBI NIH HHS/United States GR - 75N92022D00005/HL/NHLBI NIH HHS/United States GR - 75N92022D00001/HL/NHLBI NIH HHS/United States GR - T32 HL007024/HL/NHLBI NIH HHS/United States GR - P30 DK079626/DK/NIDDK NIH HHS/United States GR - U01 DK085689/DK/NIDDK NIH HHS/United States GR - 75N92022D00003/HL/NHLBI NIH HHS/United States PT - Journal Article DEP - 20230825 PL - United States TA - Kidney Med JT - Kidney medicine JID - 101756300 PMC - PMC10568645 OTO - NOTNLM OT - Incident kidney disease OT - KIM-1 OT - MCP-1 OT - TNFR-1 OT - TNFR-2 OT - YKL-40 OT - chronic kidney disease OT - plasma biomarkers OT - sUPAR EDAT- 2023/10/16 06:48 MHDA- 2023/10/16 06:49 PMCR- 2023/08/25 CRDT- 2023/10/16 04:33 PHST- 2023/10/16 06:49 [medline] PHST- 2023/10/16 06:48 [pubmed] PHST- 2023/10/16 04:33 [entrez] PHST- 2023/08/25 00:00 [pmc-release] AID - S2590-0595(23)00137-1 [pii] AID - 100719 [pii] AID - 10.1016/j.xkme.2023.100719 [doi] PST - epublish SO - Kidney Med. 2023 Aug 25;5(11):100719. doi: 10.1016/j.xkme.2023.100719. eCollection 2023 Nov.