Urine markers of kidney tubule cell injury and kidney function decline in sprint trial participants with ckd

Rakesh Malhotra, Ronit Katz, Vasantha Jotwani, Walter T. Ambrosius, Kalani L. Raphael, William Haley, Anjay Rastogi, Alfred K. Cheung, Barry I. Freedman, Henry Punzi, Michael V. Rocco, Joachim H. Ix, Michael G. Shlipak

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background and objectives 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). Design, setting, participants, & measurements 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. Results Mean participant age was 7369 (SD) years, 60% were men, 66% were white, and mean baseline eGFR was 46611 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 (20.91 ml/min per 1.73 m2 per year for highest versus lowest quartile; 95% CI, 21.44 to 20.38), a finding that was stronger in the standard arm of SPRINT. Conclusions Urine markers of tubule cell injury provide information about risk of subsequent loss of kidney function, beyond the eGFR and urine albumin.

Original languageEnglish (US)
Pages (from-to)349-358
Number of pages10
JournalClinical Journal of the American Society of Nephrology
Issue number3
StatePublished - Mar 6 2020

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation


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