Correlation Study Of Urinary Nephrin With Acute Kidney Injury And Mortality In Critically Ill Neonates

Background and Objective: Acute kidney injury(AKI)is an independent risk factor for mortality in critically ill patients.Critically ill neonates with AKI are at a high risk of morbidity and mortality.Neonatal kidney is immature,and gestational age and birth weight might have an influence on renal function.Serum creatinine and urine output are the most commonly used in clinical measure of renal function,but they are poor markers for diagnosis of AKI,because both of them are influenced by various extrarenal factors.Nephrin is essential in maintaining the integrity of the glomerular podocyte slit diaphragm.The increased level of nephrin in urine may reflect podocyte injury.Previous studies on AKI are focus on biomarkers reflecting the renal tubular injury,such as urinary cystain C(CysC).As we know,when AKI develops,the renal tubular injury occurs first;with the development of AKI,glomerular filtration rate decreases.However,to the best of our knowledge,few studies have investigated the association between AKI and podocyte injury,and no study has investigated the correlation of urinary nephrin level with neonatal AKI and outcomes.Whether the combination of urinary nephrin and CysC could better predict the prognosis has not been tested.The aims of the present study were to evaluate whether urinary nephrin could serve as early predictor for AKI and mortality in critically ill neonates.Methods: This prospective study included neonates admitted to the neonatal intensive care unit(NICU)from July 2016 to October 2016 in Children's Hospital of Soochow University.Neonatal date collected included gestational age,postnatal age,sex,birth weight,Apgar score;serum electrolytes,albumin,serum creatinine(sCr)and blood urea nitrogen;disease diagnosis;the use and the duration of mechanical ventilation(MV),antibiotics,steroids,mannitol,vasoactive drugs,pulmonary surfactant and mortality were also recorded.Maternal date collected included pregnancy complication,medication,mode of delivery,and the presence of diabetes and pre-eclampsia during pregency.The score for neonatal acute physiology(SNAP)was calculated on the day of NICU admission.The urinary concentrations of CysC,Cr and microalbumin were measured on an automatic biochemical analyzer.The concentration of urinary nephrin was measured using enzyme linked immunosorbent assay.The initial and the peak values of urinary nephrin within the first 15 days after NICU admission were used for association analysis.Diagnosis criteria of neonatal AKI: 1)clinical diagnosis: a ?26.4 ?mol/L increase in absolute value of sCr or ?50% increase in the sCr level from baseline;and/or sCr >106.1 ?mol/L(1.2mg/dl)on the first 7 days of life(sustained at least 48 hour,the mother of the neonate had normal renal function).2)laboratory diagnosis: the ratio of uCys C/Cr ? 2500 ng/mg.Results: The prospective study involved 233 neonates.(1)Urinary concentration of the maximal and the first nephrin decreased with increasing gestational age and birth weight(r=-0.658,p<0.001;r=-0.459,p<0.001),but increased with increasing SNAP(r=0.308,p<0.001;r=0.233,p<0.001).There was no correlation between urinary concentrations of the maximal and the first nephrin and postnatal age(p=0.424).(2)Among 233 neonates,70(30.04%)developed AKI.The gestational age and birth weight were significantly lower in critically ill neonates with AKI as compared with non-AKI controls(p<0.001).The maximal and first urinary nephrin in AKI neonates were significant higher than that in nonAKI(p<0.001).Multivariate logistic regression analysis showed that both the maximal and the first urine nephrin were significantly correlated with the development of AKI in critically ill neonates.Moreover,the maximal and the first urinary nephrin were significantly associated with the development of AKI,even after adjusting for gestational age,birth weight and SNAP,which suggestes that urinary nephrin is independently associated with the development of AKI in critically ill neonates.The AUCs of the maximal and the first urine nephrin to predict AKI were 0.902(95%CI 0.86-0.95,p<0.001)and 0.820(95%CI 0.76-0.88,p<0.001),respectively,indicating that urinary nephrin is predictive of AKI in neonates.(3)Among all neonates,21(9.01%)died during the stay of NICU;and among neonates with AKI,16(22.9%)die.The maximal and the first urinary nephrin were significantly higher in non-survivors as compared with survivors(p<0.001).Logistic regression analysis revealed that the maximal and the first urine nephrin remained significantly associated with mortality after adjusting for gestational age and birth weight.The AUCs of the maximal(AUC 0.830,95%CI 0.75-0.91,p<0.001)and the first urinary nephrin(AUC 0.810,95%CI 0.72-0.90,p<0.001)for predicting mortality were better than that of the SNAP(AUC 0.749,95%CI 0.66-0.84,p<0.001)in critically ill neonates.When combining urinary nephrin with CysC,the predictive performance did not improve over that of urinary nephrin(AUC 0.830)or urinary CysC(AUC 0.865)alone.However,the mortality rate was significantly higher in neonates with increased urinary levels of both nephrin and CysC,as compared to those with urinary level of nephrin < 0.5ug/mg and/or CysC < 6521.04 ng/mg(p<0.001).Conclusion:(1)The level of urinary nephrin was significantly negatively correlated with gestational age and birth weight,and positively correlated with SNAP score,but not with postnatal age.(2)Urinary nephrin is significantly associated with AKI in critically ill neonates,and the maximal urinary nephrin is independently predictive of AKI in critically ill neonates.(3)Both the maximal and the first urinary nephrin are independently predictive of mortality in critically ill neonates.The AUCs of the maximal and the first urinary nephrin for predicting mortality were higher than that of SNAP.