The Applications Value Of NGAL In Patients With Sepsis Associated Acute Kidney Injury

BackgroundSepsis is well known as a life-threatening syndrome that develops through systemic inflammatory response to infection;it remains the leading cause of death,with a 30-40%mortality rate in the intensive care unit(ICU).Acute kidney injury(AKI)is one of the leading causes of sepsis-related death in critically ill patients,and 50%of all cases of AKI are considered to be associated with sepsis.The exact pathogenesis and clinical characteristics leading to AKI in patients with sepsis still remain elusive and there is a lack of diagnostic tools that can detect AKI at an early stage,which may account for the very high morbidity and mortality rates of sepsis-associated AKI.SCr is recognized as a late marker of kidney injury.For these reasons,it is vital to identify other indicators that can be used for early diagnosis of sepsis-associated AKI.Numerous potential markers for the early diagnosis of AKI have been under study in the last decade.Among these biomarkers,neutrophil gelatinase-associated lipocalin(NGAL),cystatin(Cys-C),and soluble triggering receptor expressed on myeloid cells-1(sTREM-1)have received the most attention.Despite such extensive research into these markers,the diagnostic properties of NGAL,Cys-C,and sTREM-1 with regard to AKI occurrence in patients with sepsis need to be clarified.Part one:Early diagnostic and predictive value of neutrophil gelatinase-associated lipocalin in patients with sepsis-associated acute kidney injuryObjective:We aimed to determine the diagnostic properties of NGAL,Cys-C and sTREM-1for detecting AKI in critically ill patients with sepsis.Methods:This prospective observational study included was conducted at the general ICU.in the study,112 septic patients were divided into two groups:a non-AKI sepsis group(n = 57)and an AKI sepsis group(n = 55).The AKI sepsis group comprised patients with sepsis who developed AKI during the first week.The patients were SCreened daily for AKI occurrence for up to days 7.Upon admission to the ICU,data on the baseline characteristics were collected.Blood and urine samples were obtained on admission and every 24 h up to 72 h for measuring the NGAL,Cys-C and sTREM-1 levelsResults:Fifty-five septic patients(49.1%)developed AKI based on the KDIGO criteria during the 7-day observation period.The number of deaths increased with time during the first week in the non-AKI sepsis group and in the AKI sepsis group.Survival analysis exhibited the AKI sepsis group had a poor prognosis(Hazard ratio=0.43(95%CI,0.202-0.924),χ2=4.681,P=0.031).Both the plasma and urine NGAL,Cys-C and sTREM-1 levels(P<0.001 for all)were significantly different between the two groups.Of these biomarkers analyzed,there were significant associations with the endpoint(AKI occurrence)in septic patients(P<0.001)after adjustment of possible confounders.The differences of these biomarkers levels at these four different time points(on admission,24,48,72 h after admission)were statistically significant(P<0.01 for all),with the sepsis AKI patients having all-time higher values.The NGAL,Cys-C,and sTREM-1 levels in both the plasma and urine of AKI sepsis patients were found to be significantly elevated when compared with the non-AKI sepsis patients(P<0.001 for all).Results which the AUROCs and their 95%CIs of NGAL,Cys-C and sTREM-1 for AKI occurrence in septic patients indicate that plasma and urine NGAL(AUROC:0.823,95%CI:0.730～0.916;AUROC:0.855,95%CI:0.777～0.933,respectively)performed well for the diagnosis of AKI occurrence.Results which the AUROCs and their 95%CI for NGAL,Cys-C and sTREM-1 for AKI prediction at 24 h before AKI diagnosis in septic patients indicate that plasma and urine NGAL(AUROC:0.830,95%CI:0.741～0.919;AUROC:0.879,95%CI:0.793～0.948,respectively)performed well for the diagnosis of AKI occurrence,and plasma and urine(AUROC:0.737,95%CI:0.633～0.841;AUROC:0.741,95%CI:0.641～0.841,respectively).Conclusion:Sepsis-associated AKI patients show a continuous increase in both plasma and urine NGAL,Cys-C,and sTREM-1 levels up to 72 h.Sepsis-associated AKI patients exhibit markedly higher levels of plasma and urine NGAL,Cys-C,and sTREM-1 levels at diagnosis and 24 h before AKI diagnosis.Both plasma and urine NGAL,Cys-C and sTREM-1 showed a significant association with the development of AKI in septic patients,even after adjustment for possible confounders.The diagnostic and predictive values of plasma and urine NGAL were good,while those plasma and urine Cys-C and sTREM-1 were fair.Part two:The effect of continuous venovenous hemofiltration on neutrophil gelatinase-associated lipocalin plasma levels in patients with septic acute kidney injuryObjective:The purpose of this study was to determine the effect of CVVH on pNGAL in sepsis-induced AKI patients.Methods:Forty eight patients with septic acute kidney injury(SAKI)undergoing CVVH in the general ICU were consecutively enrolled in the study.Baseline patient data were collected on patient admission to the ICU.The white blood cell(WBC)count,C-reactive protein(CRP),and procalcitonin(PCT)levels were obtained at CVVH initiation.Clinical data necessary to calculate sequential organ failure assessment(SOFA)and acute physiology and chronic health evaluation II(APACHE II)scores were also collected.Prefilter,postfilter,and ultrafiltrate samples were obtained at the beginning of CRRT and again after 2,4,8,and 12 hours(T0,T2h,T4h,T8h,and T12h,respectively).Based on the mass conservation principle,NGAL total mass removal rate(Mtr),mass adsorption rate(Mad),sieving coefficient(SC),and plasma clearance(PC)were calculated.Results:Following initiation of CVVH,pNGAL in the ultrafiltrate decreased significantly,whereas levels at the inlet and outlet did not change(P>0.05 for both).Furthermore,no change was seen in the total mass removal rate,total mass adsorption rate,and PC over time(P>0.05 for all),while the SC significantly decreased(P=0.007).Conclusion:This study confirmed that pNGAL does not significantly decrease during CVVH in septic AKI.This means that the impact of CVVH does not need to be considered when pNGAL is used to judge renal progression in patients with septic AKI who are receiving CVVH.