TY - JOUR
T1 - Performance of Serum Creatinine and Kidney Injury Biomarkers for Diagnosing Histologic Acute Tubular Injury
AU - Moledina, Dennis G.
AU - Hall, Isaac E.
AU - Thiessen-Philbrook, Heather
AU - Reese, Peter P.
AU - Weng, Francis L.
AU - Schröppel, Bernd
AU - Doshi, Mona D.
AU - Wilson, F. Perry
AU - Coca, Steven G.
AU - Parikh, Chirag R.
N1 - Funding Information:
We are tremendously grateful for the study participation of our collaborators at the following organ procurement organizations: Gift of Life Philadelphia, New York Organ Donor Network, Michigan Organ and Tissue Donation Program, New Jersey Sharing Network, and New England Organ Bank. A part of this study was presented as an oral presentation (SA-OR99) at the American Society of Nephrology meeting in San Diego, CA, November 7, 2015. Support: This work was supported by the National Institutes of Health (NIH; grant nos. RO1DK-93770 and K24DK090203 ), a Roche Organ Transplantation Research Foundation Award to Dr Parikh, an award from the American Heart Association to Dr Hall, National Institute of Diabetes and Digestive and Kidney Diseases grant K23-097201 to Dr Wilson, a Yale Kidney O’Brien Center Award (P30DK79337), and the Health Resources and Services Administration (contract no. 234-2005-37011C). Dr Moledina is supported by T32 training grant ( T32DK007276 ) from the NIH and by the Robert E. Leet and Clara Guthrie Patterson Trust Mentored Clinical Research Award; he is also a graduate student in the Yale Investigative Medicine PhD Program, which is supported by Clinical and Translational Science Award grant UL1 TR000142 from the National Center for Advancing Translational Science, a component of the NIH. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, and mention of trade names, commercial products, or organizations does not imply endorsement by the US government. These organizations were not involved in study design, analysis, interpretation, or manuscript creation. NGAL assays were donated by Abbott Diagnostics and measured at University of Ireland. L-FABP assays were donated by Sekisui Medical. The companies did not participate in design, analysis, or interpretation of study results. The data reported here have been supplied by UNOS as the contractor for the OPTN. The Health Resources and Services Administration provides oversight to the activities of the OPTN contractor. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy of or interpretation by the OPTN or the US government. Financial Disclosure: The authors declare that they have no other relevant financial interests. Contributions: Research idea and study design: DGM, IEH, CRP; data acquisition: IEH, HT-P, PPR, FLW, BS, MDD, CRP; data analysis/interpretation: DGM, IEH, HT-P, PPR, FLW, BS, MDD, FPW, SGC, CRP; statistical analysis: DGM, HT-P; supervision and mentorship: CRP. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. Peer Review: Evaluated by 3 external peer reviewers, a statistician, and an Acting Editor-in-Chief.
Publisher Copyright:
© 2017
PY - 2017/12
Y1 - 2017/12
N2 - Background The diagnosis of acute kidney injury (AKI), which is currently defined as an increase in serum creatinine (Scr) concentration, provides little information on the condition's actual cause. To improve phenotyping of AKI, many urinary biomarkers of tubular injury are being investigated. Because AKI cases are not frequently biopsied, the diagnostic accuracy of concentrations of Scr and urinary biomarkers for histologic acute tubular injury is unknown. Study Design Cross-sectional analysis from multicenter prospective cohort. Settings & Participants Hospitalized deceased kidney donors on whom kidney biopsies were performed at the time of organ procurement for histologic evaluation. Predictors (1) AKI diagnosed by change in Scr concentration during donor hospitalization and (2) concentrations of urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], liver-type fatty acid-binding protein [L-FABP], interleukin 18 [IL-18], and kidney injury molecule 1 [KIM-1]) measured at organ procurement. Outcome Histologic acute tubular injury. Results Of 581 donors, 98 (17%) had mild acute tubular injury and 57 (10%) had severe acute tubular injury. Overall, Scr-based AKI had poor diagnostic performance for identifying histologic acute tubular injury and 49% of donors with severe acute tubular injury did not have AKI. The area under the receiver operating characteristic curve (AUROC) of change in Scr concentration for diagnosing severe acute tubular injury was 0.58 (95% CI, 0.49-0.67) and for any acute tubular injury was 0.52 (95% CI, 0.45-0.58). Compared with Scr concentration, NGAL concentration demonstrated higher AUROC for diagnosing both severe acute tubular injury (0.67; 95% CI, 0.60-0.74; P = 0.03) and any acute tubular injury (0.60; 95% CI, 0.55-0.66; P = 0.005). In donors who did not have Scr-based AKI, NGAL concentrations were higher with increasing severities of acute tubular injury (subclinical AKI). However, compared with Scr concentration, AUROCs for acute tubular injury diagnosis were not significantly higher for urinary L-FABP, IL-18, or KIM-1. Limitations The spectrum of AKI cause in deceased donors may be different from that of a general hospitalized population. Conclusions Concentrations of Scr and kidney injury biomarkers (L-FABP, IL-18, and KIM-1) lack accuracy for diagnosing acute tubular injury in hospitalized deceased donors. Although urinary NGAL concentration had slightly higher discrimination for acute tubular injury than did Scr concentration, its overall AUROC was still modest.
AB - Background The diagnosis of acute kidney injury (AKI), which is currently defined as an increase in serum creatinine (Scr) concentration, provides little information on the condition's actual cause. To improve phenotyping of AKI, many urinary biomarkers of tubular injury are being investigated. Because AKI cases are not frequently biopsied, the diagnostic accuracy of concentrations of Scr and urinary biomarkers for histologic acute tubular injury is unknown. Study Design Cross-sectional analysis from multicenter prospective cohort. Settings & Participants Hospitalized deceased kidney donors on whom kidney biopsies were performed at the time of organ procurement for histologic evaluation. Predictors (1) AKI diagnosed by change in Scr concentration during donor hospitalization and (2) concentrations of urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], liver-type fatty acid-binding protein [L-FABP], interleukin 18 [IL-18], and kidney injury molecule 1 [KIM-1]) measured at organ procurement. Outcome Histologic acute tubular injury. Results Of 581 donors, 98 (17%) had mild acute tubular injury and 57 (10%) had severe acute tubular injury. Overall, Scr-based AKI had poor diagnostic performance for identifying histologic acute tubular injury and 49% of donors with severe acute tubular injury did not have AKI. The area under the receiver operating characteristic curve (AUROC) of change in Scr concentration for diagnosing severe acute tubular injury was 0.58 (95% CI, 0.49-0.67) and for any acute tubular injury was 0.52 (95% CI, 0.45-0.58). Compared with Scr concentration, NGAL concentration demonstrated higher AUROC for diagnosing both severe acute tubular injury (0.67; 95% CI, 0.60-0.74; P = 0.03) and any acute tubular injury (0.60; 95% CI, 0.55-0.66; P = 0.005). In donors who did not have Scr-based AKI, NGAL concentrations were higher with increasing severities of acute tubular injury (subclinical AKI). However, compared with Scr concentration, AUROCs for acute tubular injury diagnosis were not significantly higher for urinary L-FABP, IL-18, or KIM-1. Limitations The spectrum of AKI cause in deceased donors may be different from that of a general hospitalized population. Conclusions Concentrations of Scr and kidney injury biomarkers (L-FABP, IL-18, and KIM-1) lack accuracy for diagnosing acute tubular injury in hospitalized deceased donors. Although urinary NGAL concentration had slightly higher discrimination for acute tubular injury than did Scr concentration, its overall AUROC was still modest.
KW - Acute kidney injury (AKI)
KW - IL-18
KW - KIM-1
KW - L-FABP
KW - NGAL
KW - acute tubular injury (ATI)
KW - diagnostic performance
KW - kidney biopsy
KW - kidney histology
KW - kidney injury biomarker
KW - serum creatinine (Scr)
KW - subclinical AKI
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U2 - 10.1053/j.ajkd.2017.06.031
DO - 10.1053/j.ajkd.2017.06.031
M3 - Article
C2 - 28844586
AN - SCOPUS:85028314010
SN - 0272-6386
VL - 70
SP - 807
EP - 816
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 6
ER -