title: Levels of protein C and soluble thrombomodulin in critically ill patients with acute kidney injury: a multicenter prospective observational study.
abstract: Endothelial dysfunction contributes to the development of acute kidney injury (AKI) in animal models of ischemia reperfusion injury and sepsis. There are limited data on markers of endothelial dysfunction in human AKI. We hypothesized that Protein C (PC) and soluble thrombomodulin (sTM) levels could predict AKI. We conducted a multicenter prospective study in 80 patients to assess the relationship of PC and sTM levels to AKI, defined by the AKIN creatinine (AKI Scr) and urine output criteria (AKI UO). We measured marker levels for up to 10 days from intensive care unit admission. We used area under the curve (AUC) and time-dependent multivariable Cox proportional hazard model to predict AKI and logistic regression to predict mortality/non-renal recovery. Protein C and sTM were not different in patients with AKI UO only versus no AKI. On intensive care unit admission, as PC levels are usually lower with AKI Scr, the AUC to predict the absence of AKI was 0.63 (95%CI 0.44-0.78). The AUC using log10 sTM levels to predict AKI was 0.77 (95%CI 0.62-0.89), which predicted AKI Scr better than serum and urine neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, urine kidney injury molecule-1 and liver-fatty acid-binding protein. In multivariable models, PC and urine NGAL levels independently predicted AKI (p=0.04 and 0.02) and PC levels independently predicted mortality/non-renal recovery (p=0.04). In our study, PC and sTM levels can predict AKI Scr but are not modified during AKI UO alone. PC levels could independently predict mortality/non-renal recovery. Additional larger studies are needed to define the relationship between markers of endothelial dysfunction and AKI.
authors: Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, California, United States of America; Division of Nephrology, Department of Medicine, Université de Montréal, Montréal, Canada.
authors: Josée
authors: J
authors: Bouchard
authors: Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors: Rakesh
authors: R
authors: Malhotra
authors: Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors: Shamik
authors: S
authors: Shah
authors: Division of Biostatistics and Bioinformatics, University of California San Diego, San Diego, California, United States of America.
authors: Yu-Ting
authors: YT
authors: Kao
authors: Division of Biostatistics and Bioinformatics, University of California San Diego, San Diego, California, United States of America.
authors: Florin
authors: F
authors: Vaida
authors: Biotechnology Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, United States of America.
authors: Akanksha
authors: A
authors: Gupta
authors: Biotechnology Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, United States of America.
authors: David T
authors: DT
authors: Berg
authors: Biotechnology Discovery Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, United States of America.
authors: Brian W
authors: BW
authors: Grinnell
authors: Division of Nephrology, University of Alabama, Birmingham, Alabama, United States of America.
authors: Brenda
authors: B
authors: Stofan
authors: Division of Nephrology, University of Alabama, Birmingham, Alabama, United States of America.
authors: Ashita J
authors: AJ
authors: Tolwani
authors: Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, San Diego, California, United States of America.
authors: Ravindra L
authors: RL
authors: Mehta
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D016638:Critical Illness; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism*; D012995:Solubility; D018180:Thrombomodulin / Q000097:blood* / Q000737:chemistry*
chemical_list: D015415:Biomarkers; D011486:Protein C; C546931:THBD protein, human; D018180:Thrombomodulin