Journal Article

Biomarkers of inflammation and repair in kidney disease progression

Bhatraju, Pavan K., Liu, Kathleen D., Cantley, Lloyd G., Puthumana, Jeremy, Kimmel, Paul L., Ware, Lorraine B., Xu, Leyuan, Kaufman, James S., Chinchilli, Vernon M., Thiessen-Philbrook, Heather, Coca, Steven G., Siew, Edward D., Garg, Amit X., Himmelfarb, Jonathan, Ikizler, T. Alp, Parikh, Chirag R., Go, Alan S.

2021

Overview

INTRODUCTIONAcute kidney injury and chronic kidney disease (CKD) are common in hospitalized patients. To inform clinical decision making, more accurate information regarding risk of long-term progression to kidney failure is required.METHODSWe enrolled 1538 hospitalized patients in a multicenter, prospective cohort study. Monocyte chemoattractant protein 1 (MCP-1/CCL2), uromodulin (UMOD), and YKL-40 (CHI3L1) were measured in urine samples collected during outpatient follow-up at 3 months. We followed patients for a median of 4.3 years and assessed the relationship between biomarker levels and changes in estimated glomerular filtration rate (eGFR) over time and the development of a composite kidney outcome (CKD incidence, CKD progression, or end-stage renal disease). We paired these clinical studies with investigations in mouse models of renal atrophy and renal repair to further understand the molecular basis of these markers in kidney disease progression.RESULTSHigher MCP-1 and YKL-40 levels were associated with greater eGFR decline and increased incidence of the composite renal outcome, whereas higher UMOD levels were associated with smaller eGFR declines and decreased incidence of the composite kidney outcome. A multimarker score increased prognostic accuracy and reclassification compared with traditional clinical variables alone. The mouse model of renal atrophy showed greater Ccl2 and Chi3l1 mRNA expression in infiltrating macrophages and neutrophils, respectively, and evidence of progressive renal fibrosis compared with the repair model. The repair model showed greater Umod expression in the loop of Henle and correspondingly less fibrosis.CONCLUSIONSBiomarker levels at 3 months after hospitalization identify patients at risk for kidney disease progression.FUNDINGNIH.

• Publisher: American Society for Clinical Investigation
• Subject: Acute Kidney Injury - urine / Acute phase reaction / Acute renal failure / Aged / Animal models / Animals / Atrophy / Biological markers / Biomarkers / Biomarkers - urine / Biomedical research / Chemokine CCL2 - urine / Chitinase-3-Like Protein 1 - urine / Clinical decision making / Clinical Medicine / Decision making / Development and progression / Disease Models, Animal / Disease Progression / End-stage renal disease / Epidermal growth factor receptors / Female / Fibrosis / Follow-Up Studies / Gene expression / Glomerular Filtration Rate / Health aspects / Hospitalization / Humans / Inflammation / Inflammation - urine / Kidney diseases / Leukocytes (neutrophilic) / Loop of Henle / Macrophages / Male / Mice / Middle Aged / Monocyte chemoattractant protein / Monocyte chemoattractant protein 1 / Monocytes / Mortality / Patients / Physiological aspects / Prognosis / Reclassification / Renal failure / Renal Insufficiency, Chronic - urine / Urine