Early Predictive Value Of Urinary Renin For Acute Kidney Injury And Its Correlation With Prognosis In Critically Ill Children

Objective:Acute kidney injury(AKI)is a common clinical syndrome and an independent risk factor for death in critically ill children.At present,the diagnosis of AKI is mainly based on serum creatinine and urine volume.Howerer serum creatinine and urine volume assessmenthave low sensitivity and many influencing factors.The diagnosis of AKI in children,especially early diagnosis is obviously inadequate.While the prognosis of AKI is closely related to early diagnosis and early intervention treatment.Therefore,finding and discovering biomarkers which can predict AKI early is the hot spots and focus of current AKI research,which is of great significance to improve the prognosis of critically ill children.Renin-angiotensin-aldosterone system(RAAS)plays an important role in regulating renal hemodynamics and function as well as the pathophysiology of renal disease.Studies have shown that the activation of RAAS emerged as the major risk factors for AKI.Renin is a RAAS rate-limiting enzyme and studies have shown that urinary renin is an indicator of renal RAAS activity.A study of adults showed that increased urinary renin was associated with severe AKI in patients with AKI after heart surgery.However there are few reports on the effect of renin on AKI and its prognosis in children.The aim of this study was to investigate the predictive value of urinary renin in children in the pediatric intensive care unit(PICU)for early diagnosis and prognosis of acute kidney injury in critically ill children.Methods:This prospective study included children admitted to the pediatric intensive care unit(PICU)of Children’s Hospital of Soochow University from October to December 2016 and December 2017 to January 2018.Critical ill children date collected inclued sex,age,body weight,length of stay in PICU,length of stay in hospital,serum creatinine,blood urea nitrogen,blood gas analysis,albumin,serum electrolytes,lactate,blood glucose;the use and duration of mechanical ventilation(MV),renal replacement therapy(RRT),furosemide,steroids,antibiotics,positive inotropic agents,sepsis,multiple organ dysfunction syndrome(MODS),shock,disseminated intravascular coagulation(DIC)and mortality were also recorded.The score of the pediatric risk of mortality Ⅲ(PRISM Ⅲ)was calculated on the day of PICU admission.Urine samples were collected during the first 24 hours in PICU.The urinary concentrations of CysC and Cr were measured on an automatic biochemical analyzer.The concentrations of urinary renin was measured using enzyme linked immunosorbent assay(ELISA).Diagnosis of AKI was based on the diagnosis criteria developed by Kidney Disease Improving Global Outcomes(KDIGO)in 2012Results:The prospective study involved 318 critically ill children.Urinary renin concentration decreased with increasing body weight(β=-0.062,S.E.=0.0133,p<0.001);but increased with increasing PRISM Ⅲ(β=0.031,S.E.=0.0103,p=0.003).There was no correlation between urinary renin concentration and sex(p=0.539)or age(p=0.089).Meanwhile,urinary renin concentration increased with decreasing serum sodium concentration(β=-0.049,S.E.=0.0133,p<0.001).Part 1:Association between urinary renin and AKI.(1)Among 318 critically ill children,51(16.04%)developed AKI,including 13 who fulfilled the criteria for AKI stage 1,21 who fulfilled the criteria for AKI stage 2,and 17 who fulfilled the criteria for AKI stage 3.The differences in Age and body weight were significant among non-AKI,AKI stage 1,AKI stage 2,and AKI stage 3 group(p<0.05).The PRISM Ⅲ score;incidence of sepsis,MODS,shock/DIC;use of mechanical ventilation,RRT,furosemide,meropenem/imipenem,positive inotropic agents;urinary CysC,urinary renin were significant among non-AKI,AKI stage 1,AKI stage 2,and AKI stage 3 group(p<0.05),which were all significantly the highest in the AKI stage 3 group(p<0.05).(2)Univariate logistic regression analysis showed that urinary renin was significantly correlated with AKI stage 3(OR=1.032,95%CI:1.008-1.057,p=0.009),Multivariate logistic regression analysis showed that urinary renin was still significantly correlated with AKI stage 3 after adjusting for sex,age,body weight and PRISM III score(AOR=1.026,95%CI:1.01-1.052,p=0.042).(3)The AUC of urinary renin for predicting AKI stage 3 was 0.726(95%CI:0.578-0.875,p=0.002).The AUC of combined urinary renin with PRISM III for predicting AKI stage 3 was 0.805(95%CI:0.724-0.885,p<0.001),which was higher than the AUCs of urinary rennin(0.726)and PRISM Ⅲ score(0.79,95%CI:0.715-0.873,p<0.001).The AUC of combined urinary renin with urinary CysC for predicting AKI stage 3 was 0.757(95%CI:0.611-0.902,P<0.001),which was not significantly higher than that of urinary renin(0.726)or urinary CysC(0.776)alone.However the incidence of AKI stage 3 was significantly increased in children with increased levels of both urinary renin and urinary CysC(P<0.001).Part 2:Association between urinary renin and PICU mortality.(1)Among 318 critically ill children,28(8.81%)died;and among children with AKI,12(23.5%)died.The urinary renin was significantly higher in non-survivors as compared with survivors(P=0.001).(2)Univariate logistic regression analysis showed that urinary renin was significantly associated with mortality in critically ill children(OR=1.038,95%CI:1.014-1.061,p=0.001).Multivariate logistic regression analysis showed that urinary renin was still significantly associated with mortality after adjusting for age,body weight,PRISM Ⅲ(AOR=1.026,95%CI:1.002-1.051,p=0.036).(3)The AUC of urinary rennin(0.734,95%CI:0.638-0.829,p<0.001)for predicting mortality was worse than that of the PRISM Ⅲ(AUC=0.824,95%CI:0.743-0.905,p<0.001)or urinary CysC(AUC=0.826,95%CI:0.753-0.900,P<0.001)in critically ill children.The AUC of combined urinary renin with urinary CysC for predicting mortality was 0.782(95%CI=0.692-0.871,p<0.001),which did not improve over that of urinary renin(AUC=0.734)or urinary CysC(AUC=0.826)alone.However,the mortality was significantly increased in children with increased levels of both urinary renin and urinary CysC(P<0.001).(4)The AUC of urinary renin for predicting mortality in critically ill children with AKI stage 3 was 0.806(95%CI=0.662-0.950,p=0.003),which was higher than that of predicting AKI stage 3(AUC=0.726)or predicting mortality(AUC=0.734)alone.Conclusion:(1)The level of urinary renin was significantly correlated with body weightand disease severity PRISM Ⅲ score,but not associated with sex or age.(2)Urinary renin lever was significantly regulated by serum sodium level.(3)Urinary renin is an independent predictor of AKI stage 3 in critically ill children,and has early predictive value.(4)Urinary renin is an independent risk factor of mortality in critically ill children.Urinary renin has a better predictive value of mortality in children with AKI stage 3 than that of AKI stage 3 or mortality.The AUC of urinary renin for predicting mortality in critically ill children with AKI stage 3 was higher than that of predicting AKI stage 3 or predicting mortality alone.