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Urine Markers of Kidney Tubule Cell Injury and Kidney Function Decline in SPRINT Trial Participants with CKD.

Authors
  • Malhotra, Rakesh1, 2
  • Katz, Ronit3
  • Jotwani, Vasantha4
  • Ambrosius, Walter T5
  • Raphael, Kalani L6
  • Haley, William7
  • Rastogi, Anjay8
  • Cheung, Alfred K6
  • Freedman, Barry I9
  • Punzi, Henry10
  • Rocco, Michael V9
  • Ix, Joachim H11, 12, 13
  • Shlipak, Michael G4, 14
  • 1 Division of Nephrology and Hypertension, Department of Medicine and.
  • 2 Division of Nephrology and Hypertension, Imperial Valley Family Care Medical Group, El Centro, California.
  • 3 Kidney Research Institute, University of Washington, Seattle, Washington.
  • 4 Kidney Health Research Collaborative, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, California.
  • 5 Department of Biostatistics and Data Science, Division of Public Health Sciences and.
  • 6 Division of Nephrology and Hypertension, University of Utah Health and Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah.
  • 7 Division of Nephrology, Mayo Clinic, Jacksonville, Florida.
  • 8 Division of Nephrology, University of California Los Angeles, Los Angeles, California.
  • 9 Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
  • 10 Trinity Hypertension and Metabolic Research Instititute, Punzi Medical Center, Carrollton, Texas.
  • 11 Division of Nephrology and Hypertension, Department of Medicine and [email protected]
  • 12 Division of Preventive Medicine, Department of Family Medicine and Public Health, University of California San Diego, San Diego, California.
  • 13 Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, California; and.
  • 14 Division of General Internal Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, California.
Type
Published Article
Journal
Clinical Journal of the American Society of Nephrology
Publisher
American Society of Nephrology
Publication Date
Mar 06, 2020
Volume
15
Issue
3
Pages
349–358
Identifiers
DOI: 10.2215/CJN.02780319
PMID: 32111704
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

eGFR and albuminuria primarily reflect glomerular function and injury, whereas tubule cell atrophy and interstitial fibrosis on kidney biopsy are important risk markers for CKD progression. Kidney tubule injury markers have primarily been studied in hospitalized AKI. Here, we examined the association between urinary kidney tubule injury markers at baseline with subsequent loss of kidney function in persons with nondiabetic CKD who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Among 2428 SPRINT participants with CKD (eGFR<60 ml/min per 1.73 m2) at baseline, we measured urine markers of tubule injury (IL-18, kidney injury molecule-1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL]), inflammation (monocyte chemoattractant protein-1 [MCP-1]), and repair (human cartilage glycoprotein-40 [YKL-40]). Cox proportional hazards models evaluated associations of these markers with the kidney composite outcome of 50% eGFR decline or ESKD requiring dialysis or kidney transplantation, and linear mixed models evaluated annualized change in eGFR. Mean participant age was 73±9 (SD) years, 60% were men, 66% were white, and mean baseline eGFR was 46±11 ml/min per 1.73 m2. There were 87 kidney composite outcome events during a median follow-up of 3.8 years. Relative to the respective lowest quartiles, the highest quartiles of urinary KIM-1 (hazard ratio, 2.84; 95% confidence interval [95% CI], 1.31 to 6.17), MCP-1 (hazard ratio, 2.43; 95% CI, 1.13 to 5.23), and YKL-40 (hazard ratio, 1.95; 95% CI, 1.08 to 3.51) were associated with higher risk of the kidney composite outcome in fully adjusted models including baseline eGFR and urine albumin. In linear analysis, urinary IL-18 was the only marker associated with eGFR decline (-0.91 ml/min per 1.73 m2 per year for highest versus lowest quartile; 95% CI, -1.44 to -0.38), a finding that was stronger in the standard arm of SPRINT. Urine markers of tubule cell injury provide information about risk of subsequent loss of kidney function, beyond the eGFR and urine albumin. Copyright © 2020 by the American Society of Nephrology.

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