Biomarkers of inflammation and repair in kidney disease progression

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, pr...

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Veröffentlicht in:The Journal of clinical investigation Jg. 131; H. 3; S. 1 - 10
Hauptverfasser: Puthumana, Jeremy, Thiessen-Philbrook, Heather, Xu, Leyuan, Coca, Steven G., Garg, Amit X., Himmelfarb, Jonathan, Bhatraju, Pavan K., Ikizler, T. Alp, Siew, Edward D., Ware, Lorraine B., Liu, Kathleen D., Go, Alan S., Kaufman, James S., Kimmel, Paul L., Chinchilli, Vernon M., Cantley, Lloyd G., Parikh, Chirag R.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States American Society for Clinical Investigation 01.02.2021
Schlagworte:
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
United States
Nephrology
Chronic kidney disease
Inflammation
Molecular diagnosis
Clinical practice
ISSN:0021-9738, 1558-8238, 1558-8238
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0021-9738
1558-8238
1558-8238
DOI:10.1172/JCI139927