Levels of Protein C and Soluble Thrombomodulin in Critically Ill Patients with Acute Kidney Injury: A Multicenter Prospective Observational Study

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...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	PloS one Ročník 10; číslo 3; s. e0120770
Hlavní autori:	Bouchard, Josée, Malhotra, Rakesh, Shah, Shamik, Kao, Yu-Ting, Vaida, Florin, Gupta, Akanksha, Berg, David T., Grinnell, Brian W., Stofan, Brenda, Tolwani, Ashita J., Mehta, Ravindra L.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Public Library of Science 19.03.2015 Public Library of Science (PLoS)
Predmet:	Acute Kidney Injury - blood Acute Kidney Injury - diagnosis Acute Kidney Injury - mortality Animal models Anticoagulants Bioinformatics Biomarkers Biomarkers - blood Biotechnology Cell cycle Creatinine Critical care Critical Illness Cystatin Cystatin C Family medical history Fatty acid-binding protein Fatty acids Female Gelatinase Hospitals Humans Hypertension Injury prevention Intensive care Ischemia Kidney diseases Kidneys Laboratories Lipocalin Liver Male Markers Mathematical models Medical research Medicine Middle Aged Mortality Nephrology Observational studies Patients Prognosis Prospective Studies Protein binding Protein C Protein C - metabolism Proteins Recovery Reperfusion Sepsis Short term memory Solubility Studies Thrombomodulin Thrombomodulin - blood Thrombomodulin - chemistry Urine California Alabama United States > US Indianapolis Indiana
ISSN:	1932-6203, 1932-6203
On-line prístup:	Získať plný text
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3 Competing Interests: This is an investigator-initiated study supported through a grant from Eli Lilly and Company. RLM received a research grant from Eli Lilly to conduct the study. AG, DTB, and BWG were employees of Eli Lilly and Company at the time of the study conduct. The company did not have any role in data collection, and interpretation of data. Soluble thrombomodulin levels were measured blinded at Eli Lily and Company. AG, DTB and BWG participated in writing of the manuscript but neither these authors nor the company had a role in the decision to submit the manuscript for publication. Conceived and designed the experiments: JB SS RLM. Performed the experiments: JB RM SS AG DTB BWG BS AJT RLM. Analyzed the data: JB YTK FV. Contributed reagents/materials/analysis tools: AG DTB BWG. Wrote the paper: JB RM SS YTK FV AG DTB BWG BS AJT RLM.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0120770