PMID- 28844586 OWN - NLM STAT- MEDLINE DCOM- 20171205 LR - 20181201 IS - 1523-6838 (Electronic) IS - 0272-6386 (Print) IS - 0272-6386 (Linking) VI - 70 IP - 6 DP - 2017 Dec TI - Performance of Serum Creatinine and Kidney Injury Biomarkers for Diagnosing Histologic Acute Tubular Injury. PG - 807-816 LID - S0272-6386(17)30845-4 [pii] LID - 10.1053/j.ajkd.2017.06.031 [doi] 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. CI - Published by Elsevier Inc. FAU - Moledina, Dennis G AU - Moledina DG AD - Program of Applied Translational Research, Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT. FAU - Hall, Isaac E AU - Hall IE AD - Division of Nephrology, Hypertension and Renal Transplantation, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT. FAU - Thiessen-Philbrook, Heather AU - Thiessen-Philbrook H AD - Program of Applied Translational Research, Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT. FAU - Reese, Peter P AU - Reese PP AD - Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, Philadelphia, PA. FAU - Weng, Francis L AU - Weng FL AD - Saint Barnabas Medical Center, Livingston, NJ. FAU - Schroppel, Bernd AU - Schroppel B AD - Section of Nephrology, University Hospital, Ulm, Germany. FAU - Doshi, Mona D AU - Doshi MD AD - Wayne State University, Detroit, MI. FAU - Wilson, F Perry AU - Wilson FP AD - Program of Applied Translational Research, Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, New Haven, CT. FAU - Coca, Steven G AU - Coca SG AD - Icahn School of Medicine at Mount Sinai, New York, NY. FAU - Parikh, Chirag R AU - Parikh CR AD - Program of Applied Translational Research, Section of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, CT; Veterans Affairs Connecticut Healthcare System, New Haven, CT. Electronic address: chirag.parikh@yale.edu. LA - eng GR - R01 HL085757/HL/NHLBI NIH HHS/United States GR - UL1 TR001863/TR/NCATS NIH HHS/United States GR - R01 DK093770/DK/NIDDK NIH HHS/United States GR - P30 DK079310/DK/NIDDK NIH HHS/United States GR - T32 DK007276/DK/NIDDK NIH HHS/United States GR - K23 DK097201/DK/NIDDK NIH HHS/United States GR - P30 DK079337/DK/NIDDK NIH HHS/United States GR - UL1 TR000142/TR/NCATS NIH HHS/United States GR - U01 DK082185/DK/NIDDK NIH HHS/United States GR - K24 DK090203/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20170824 PL - United States TA - Am J Kidney Dis JT - American journal of kidney diseases : the official journal of the National Kidney Foundation JID - 8110075 RN - 0 (Biomarkers) RN - 0 (FABP1 protein, human) RN - 0 (Fatty Acid-Binding Proteins) RN - 0 (HAVCR1 protein, human) RN - 0 (Hepatitis A Virus Cellular Receptor 1) RN - 0 (Interleukin-18) RN - 0 (LCN2 protein, human) RN - 0 (Lipocalin-2) RN - AYI8EX34EU (Creatinine) SB - IM MH - Acute Kidney Injury/diagnosis/*metabolism/pathology MH - Adult MH - Area Under Curve MH - Biomarkers/metabolism MH - Cohort Studies MH - Creatinine/*blood MH - Cross-Sectional Studies MH - Fatty Acid-Binding Proteins/*urine MH - Female MH - Hepatitis A Virus Cellular Receptor 1/*metabolism MH - Humans MH - Interleukin-18/*urine MH - Kidney Transplantation MH - Kidney Tubules/pathology MH - Lipocalin-2/*urine MH - Male MH - Middle Aged MH - Prospective Studies MH - ROC Curve MH - Severity of Illness Index MH - *Tissue Donors PMC - PMC5701867 MID - NIHMS897252 OTO - NOTNLM OT - Acute kidney injury (AKI) OT - IL-18 OT - KIM-1 OT - L-FABP OT - NGAL OT - acute tubular injury (ATI) OT - diagnostic performance OT - kidney biopsy OT - kidney histology OT - kidney injury biomarker OT - serum creatinine (Scr) OT - subclinical AKI COIS- Financial Disclosure: The authors declare that they have no other relevant financial interests. EDAT- 2017/08/29 06:00 MHDA- 2017/12/06 06:00 PMCR- 2018/12/01 CRDT- 2017/08/29 06:00 PHST- 2017/02/07 00:00 [received] PHST- 2017/06/23 00:00 [accepted] PHST- 2017/08/29 06:00 [pubmed] PHST- 2017/12/06 06:00 [medline] PHST- 2017/08/29 06:00 [entrez] PHST- 2018/12/01 00:00 [pmc-release] AID - S0272-6386(17)30845-4 [pii] AID - 10.1053/j.ajkd.2017.06.031 [doi] PST - ppublish SO - Am J Kidney Dis. 2017 Dec;70(6):807-816. doi: 10.1053/j.ajkd.2017.06.031. Epub 2017 Aug 24.