• Alexander L Bullen, Ronit Katz, Alexandra K Lee, AndersonCheryl A MCAMDivision of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, California, USA; Division of Preventive Medicine, Department of Family Medicine and Public Health, University of Californi, Alfred K Cheung, Pranav S Garimella, Vasantha Jotwani, William E Haley, Areef Ishani, James P Lash, Javier A Neyra, Henry Punzi, Anjay Rastogi, Erik Riessen, Rakesh Malhotra, Chirag R Parikh, Michael V Rocco, Barry M Wall, Udayan Y Bhatt, Michael G Shlipak, Joachim H Ix, and Michelle M Estrella.
• Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, California, USA.
• Kidney Int. 2019 Aug 1; 96 (2): 470-479.

AbstractUrine markers can quantify tubular function including reabsorption (α-1 microglobulin [α1m]) and β-2-microglobulin [β2m]) and protein synthesis (uromodulin). Individuals with tubular dysfunction may be less able to compensate to insults than those without, despite similar estimated glomerular filtration rate (eGFR) and albuminuria. Among Systolic Blood Pressure Intervention Trial (SPRINT) participants with an eGFR under 60 ml/min/1.73m2, we measured urine markers of tubular function and injury (neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule-1 [KIM-1], interleukin-18 [IL-18], monocyte chemoattractant protein-1, and chitinase-3-like protein [YKL-40]) at baseline. Cox models evaluated associations with subsequent acute kidney injury (AKI) risk, adjusting for clinical risk factors, baseline eGFR and albuminuria, and the tubular function and injury markers. In a random subset, we remeasured biomarkers after four years, and compared changes in biomarkers in those with and without intervening AKI. Among 2351 participants, 184 experienced AKI during 3.8 years mean follow-up. Lower uromodulin (hazard ratio per two-fold higher (0.68, 95% confidence interval [0.56, 0.83]) and higher α1m (1.20; [1.01, 1.44]) were associated with subsequent AKI, independent of eGFR and albuminuria. None of the five injury markers were associated with eventual AKI. In the random subset of 947 patients with repeated measurements, the 59 patients with intervening AKI versus without had longitudinal increases in urine NGAL, IL-19, and YKL-40 and only 1 marker of tubule function (α1m). Thus, joint evaluation of tubule function and injury provided novel insights to factors predisposing to AKI, and responses to kidney injury.Published by Elsevier Inc.

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