The SPRINT trial suggests that markers of tubule cell function in the urine associate with risk of subsequent acute kidney injury while injury markers elevate after the injury

Alexander L. Bullen, R. Katz, Alexandra K. Lee, Cheryl A.M. Anderson, Alfred K. Cheung, Pranav S. Garimella, Vasantha Jotwani, William E. Haley, A. Ishani, James P. Lash, Javier A. Neyra, H. Punzi, A. Rastogi, Erik Riessen, Rakesh Malhotra, Chirag R. Parikh, Michael V. Rocco, Barry Wall, Udayan Y. Bhatt, Michael G. Shlipak & 2 others Joachim H. Ix, Michelle M. Estrella

Research output: Contribution to journalArticle

Abstract

Urine 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.

Original languageEnglish (US)
Pages (from-to)470-479
Number of pages10
JournalKidney International
Volume96
Issue number2
DOIs
StatePublished - Aug 1 2019

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Acute Kidney Injury
Urine
Blood Pressure
Glomerular Filtration Rate
Wounds and Injuries
Albuminuria
Uromodulin
Biomarkers
Kidney
Chitinases
Interleukin-18
Chemokine CCL2
Proportional Hazards Models
Causality
Proteins
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

The SPRINT trial suggests that markers of tubule cell function in the urine associate with risk of subsequent acute kidney injury while injury markers elevate after the injury. / Bullen, Alexander L.; Katz, R.; Lee, Alexandra K.; Anderson, Cheryl A.M.; Cheung, Alfred K.; Garimella, Pranav S.; Jotwani, Vasantha; Haley, William E.; Ishani, A.; Lash, James P.; Neyra, Javier A.; Punzi, H.; Rastogi, A.; Riessen, Erik; Malhotra, Rakesh; Parikh, Chirag R.; Rocco, Michael V.; Wall, Barry; Bhatt, Udayan Y.; Shlipak, Michael G.; Ix, Joachim H.; Estrella, Michelle M.

In: Kidney International, Vol. 96, No. 2, 01.08.2019, p. 470-479.

Research output: Contribution to journalArticle

Bullen, AL, Katz, R, Lee, AK, Anderson, CAM, Cheung, AK, Garimella, PS, Jotwani, V, Haley, WE, Ishani, A, Lash, JP, Neyra, JA, Punzi, H, Rastogi, A, Riessen, E, Malhotra, R, Parikh, CR, Rocco, MV, Wall, B, Bhatt, UY, Shlipak, MG, Ix, JH & Estrella, MM 2019, 'The SPRINT trial suggests that markers of tubule cell function in the urine associate with risk of subsequent acute kidney injury while injury markers elevate after the injury', Kidney International, vol. 96, no. 2, pp. 470-479. https://doi.org/10.1016/j.kint.2019.03.024
Bullen, Alexander L. ; Katz, R. ; Lee, Alexandra K. ; Anderson, Cheryl A.M. ; Cheung, Alfred K. ; Garimella, Pranav S. ; Jotwani, Vasantha ; Haley, William E. ; Ishani, A. ; Lash, James P. ; Neyra, Javier A. ; Punzi, H. ; Rastogi, A. ; Riessen, Erik ; Malhotra, Rakesh ; Parikh, Chirag R. ; Rocco, Michael V. ; Wall, Barry ; Bhatt, Udayan Y. ; Shlipak, Michael G. ; Ix, Joachim H. ; Estrella, Michelle M. / The SPRINT trial suggests that markers of tubule cell function in the urine associate with risk of subsequent acute kidney injury while injury markers elevate after the injury. In: Kidney International. 2019 ; Vol. 96, No. 2. pp. 470-479.
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AU - Haley, William E.

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AU - Wall, Barry

AU - Bhatt, Udayan Y.

AU - Shlipak, Michael G.

AU - Ix, Joachim H.

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