Endothelial Damage Signals Refractory Acute Kidney Injury in Critically Ill Patients

TY - JOUR

T1 - Endothelial Damage Signals Refractory Acute Kidney Injury in Critically Ill Patients

AU - Itenov, Theis S

AU - Jensen, Jens-Ulrik

AU - Ostrowski, Sisse R

AU - Johansson, Pär I

AU - Thormar, Katrin M

AU - Lundgren, Jens D

AU - Bestle, Morten H

AU - “Procalcitonin And Survival Study” study group

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Critically ill patients with acute kidney injury (AKI) are heterogeneous on pathophysiology and prognosis. The role of endothelial damage in the pathogenesis of refractory AKI has not been clarified. The aim was to determine if biomarkers of endothelial damage, independently of the inflammatory insult on the kidney, can predict recovery of acute kidney injury.METHODS: From the "Procalcitonin And Survival Study" multicenter intensive care unit cohort, followed for 28 days after admission, we included patients without chronic kidney disease, who survived >24 h after admission and with plasma samples at admission available for biomarker analysis. We defined AKI by the "Kidney Disease: Improving Global Outcomes" guidelines and recovery of prior kidney function as alive for five consecutive days after admission with no need for renal replacement therapy and creatinine levels consistently below ×1.5 the level before admission. We adjusted models for age, gender, vasopressor treatment, mechanical ventilation and levels of creatinine, procalcitonin, platelets, and bilirubin at admission.RESULTS: Of a total 213 with AKI at admission, 99 recovered prior kidney function during follow-up. Endothelial damage on admission, measured by Soluble Thrombomodulin (sTM), was the strongest predictor of a reduced chance of recovery of prior kidney function (sTM in the highest vs. three lower quartiles hazard ratio 0.39; 95% confidence interval 0.21-0.73, P = 0.003). In contrast, the degree of the initial inflammatory insult on the kidney, measured by neutrophil gelatinase-associated lipocalin (NGAL), failed to predict this outcome (NGAL in highest vs. three lower quartiles hazard ratio = 1.20; 95% CI 0.72-2.00; P = 0.48). Procalcitonin, a specific marker of bacterial infection, was also associated with the rate of recovery (PCT in highest vs. three lower quartiles hazard ratio = 0.59; 95% CI 0.36-0.98; P = 0.04).CONCLUSION: AKI patients with high levels of sTM had a reduced chance of recovering prior renal function. Our findings support disintegration of the endothelium as a critical point in the pathogenesis of AKI that is refractory to treatment.

AB - Critically ill patients with acute kidney injury (AKI) are heterogeneous on pathophysiology and prognosis. The role of endothelial damage in the pathogenesis of refractory AKI has not been clarified. The aim was to determine if biomarkers of endothelial damage, independently of the inflammatory insult on the kidney, can predict recovery of acute kidney injury.METHODS: From the "Procalcitonin And Survival Study" multicenter intensive care unit cohort, followed for 28 days after admission, we included patients without chronic kidney disease, who survived >24 h after admission and with plasma samples at admission available for biomarker analysis. We defined AKI by the "Kidney Disease: Improving Global Outcomes" guidelines and recovery of prior kidney function as alive for five consecutive days after admission with no need for renal replacement therapy and creatinine levels consistently below ×1.5 the level before admission. We adjusted models for age, gender, vasopressor treatment, mechanical ventilation and levels of creatinine, procalcitonin, platelets, and bilirubin at admission.RESULTS: Of a total 213 with AKI at admission, 99 recovered prior kidney function during follow-up. Endothelial damage on admission, measured by Soluble Thrombomodulin (sTM), was the strongest predictor of a reduced chance of recovery of prior kidney function (sTM in the highest vs. three lower quartiles hazard ratio 0.39; 95% confidence interval 0.21-0.73, P = 0.003). In contrast, the degree of the initial inflammatory insult on the kidney, measured by neutrophil gelatinase-associated lipocalin (NGAL), failed to predict this outcome (NGAL in highest vs. three lower quartiles hazard ratio = 1.20; 95% CI 0.72-2.00; P = 0.48). Procalcitonin, a specific marker of bacterial infection, was also associated with the rate of recovery (PCT in highest vs. three lower quartiles hazard ratio = 0.59; 95% CI 0.36-0.98; P = 0.04).CONCLUSION: AKI patients with high levels of sTM had a reduced chance of recovering prior renal function. Our findings support disintegration of the endothelium as a critical point in the pathogenesis of AKI that is refractory to treatment.

KW - Acute Kidney Injury/diagnosis

KW - Aged

KW - Aged, 80 and over

KW - Biomarkers/metabolism

KW - Critical Illness

KW - Endothelium/pathology

KW - Female

KW - Humans

KW - Intensive Care Units

KW - Lipocalins/metabolism

KW - Male

KW - Middle Aged

KW - Neutrophils/metabolism

KW - Prospective Studies

KW - Renal Replacement Therapy

KW - Thrombomodulin/metabolism

U2 - 10.1097/SHK.0000000000000804

DO - 10.1097/SHK.0000000000000804

M3 - Journal article

C2 - 28505627

SN - 1073-2322

VL - 47

SP - 696

EP - 701

JO - Shock

JF - Shock

IS - 6

ER -