Abstract | Introduction: 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 m2 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 [α1m]) 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 m2, 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]), α1m (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 α1m for associations with ESKD. Conclusion: Among adults with diabetes and eGFR <60 ml/min per 1.73 m2, higher urine KIM-1, α1m, and MCP-1 are independently associated with incident ESKD, providing insight into kidney disease progression in persons with diabetes and CKD.
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Authors | Jonathan G Amatruda, Ronit Katz, Mark J Sarnak, Orlando M Gutierrez, Jason H Greenberg, Mary Cushman, Sushrut Waikar, Chirag R Parikh, Jeffrey R Schelling, Manasi P Jogalekar, Joseph V Bonventre, Ramachandran S Vasan, Paul L Kimmel, Michael G Shlipak, Joachim H Ix, CKD Biomarkers Consortium |
Journal | Kidney international reports
(Kidney Int Rep)
Vol. 7
Issue 7
Pg. 1514-1523
(Jul 2022)
ISSN: 2468-0249 [Electronic] United States |
PMID | 35812302
(Publication Type: Journal Article)
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Copyright | © 2022 International Society of Nephrology. Published by Elsevier Inc. |