1.     INTRODUCTION:

                  India contributes 23–24% of global average of preterm births. Studies have reported that 8-24% of all critically ill newborns in neonatal intensive care units may develop AK. In first week of life, incidence of AKI in premature infants is reported to be between 12.5-39.8%. 

        AKI is defined by Kidney Disease: Improving Global Outcomes(KDIGO) as increase in serum creatinine(sCr) above 0.3 mg/dL or 50% from baseline and/or urine output of <0.5 mL/kg/h for at least six hours. Serum creatinine constitutes a poor biomarker to predict early lesions as it is susceptible to several factors, including muscle mass, gestational age and sex,  serum creatinine changes indicate late consequences of injury and neonatal serum creatinine reflect maternal levels up to 72 hour post-birth. AKI diagnosis based on urine output is also problematic as this is often clinically difficult to monitor in neonates and non- oliguric renal failure is common in preterm. 

        This study is devised to test Human neutrophil gelatinase-associated lipocalin(NGAL), in its ability to detect AKI in preterm and to compare it with serum creatinine and urine output. Regenerating tubular epithelial cells express higher levels of NGAL following injury of kidney and high NGAL levels often occur before appearance of other renal markers involved in determining kidney function.

        Studies have demonstrated that three to five years after an initial AKI episode, over 50% of children had at least one sign of CKD. We hope that findings of this study will help in identifying renal insult in high risk newborns like preterm babies and stimulate development of screening protocol for this cohort vulnerable to development of long term renal morbidity. 

2.     SIGNIFICANCE OF THE PROJECT

·      Early detection and intervention: 

·      Improved treatment:

·      Long-term benefits in reducing burden of end stage renal disease (ESRD). 

3.     OBJECTIVES

Primary:

To identify kidney injury in preterm newborns by estimating urinary NGAL levels. 

Secondary:

·      Compare the efficacy of urinary NGAL levels vs serum creatinine and urine output levels in detecting AKI in preterm newborns.

·      To observe clinical outcomes of newborn at different values of NGAL levels.

·      To identify risk factors for acute kidney injury in preterm births. 

4.     METHODS

Sample: Preterm(gestational age <37 completed weeks) admitted to SNCU(sick newborn care unit) in Government Medical college of Prayagraj. 

Study design:  Observational Prospective Study

Study setting: Study would be conducted in the SNCU of Government medical college of Prayagraj district for a period of two years.

Sampling Procedure: All consecutive neonates admitted to the departmental SNCU will be included in the study if they qualify the inclusion criteria. 

Ø  Inclusion criteria

o   Neonates will be included consecutively only if informed consent will be given by their caregivers.

o   Neonates admitted within first day of life. 

Ø  Exclusion criteria

o   Known renal or any other congenital anomalies, sepsis, metabolic disease, hyperbilirubinemia

o   Receiving diuretics and other drugs that can affect kidney in the first 48 hours of admission.

o   If they did not survive beyond the first three days of life 

o   If mother of the newborn who had chronic kidney disease, hypertension, severe systemic disease, diabetes mellitus or some other chronic disease will be excluded from the research to eliminate the adverse impact of their illness on infant stress and kidney function. 

A form for written informed consent will be distributed to parents/guardians of all children. Only children whose parents/guardians consent to participation in the study will be included. The study is approved by Institutional Ethical Committee. Clinical data would be collected  from government approved case record of admitted newborns. Data on health of mothers will be obtained through retrospective review of medical records of respective mothers. Biochemical analysis of urinary samples will be done in Pathology department of the college. 

Assessment tools

Gestational age(GA) will be determined by calculation from last menstrual period and/or antenatal ultrasonography and will be confirmed by Ballard score in postnatal period.

Laboratory investigators will be blinded to clinical outcomes. Laboratory investigations, including complete blood count, C-reactive protein, blood urea nitrogen and serum Creatinine will be determined on admission. Urinary sample for uNGAL will be collected in sterile container attached near the perineum of baby. All urine samples will be received at room temperature and centrifuged (2000rpm for 5 minutes) within 4 hour of arriving at the laboratory and then frozen at −80°C until assayed. uNGAL>6.6 ng/ml (IQR 2.8–17) will be the cut off for abnormal uNGAL values. General supportive care will be applied according to government recommended facility based newborn care(FBNC) protocol. The length of SNCU stay and final outcome of the baby will be recorded. 

    AKI will be defined according to the contemporary definition modified for neonates, similar to Kidney Disease: Improving Global Outcome (KDIGO); by which a serum Creatinine rise by ≥ 26.5 μmol/L(equal to 0.3 mg/dl) from baseline defines AKI in the third day of life. The lowest previous serum Creatinine serves as the baseline serum Creatinine. AKI patients will be subsequently discriminated according to the increase of serum Creatinine into AKIN1 (serum Creatinine increase up to 1.9 times the baseline) and AKIN2 (serum Creatinine increase from 2.0 to 2.9 times the baseline) groups. 

Data analysis:

   Data were entered into Excel spreadsheets for each newborn separately. All entries will be cross-checked for any possible keyboard errors. Incidence data will be expressed as percentages and compared using the chi-square test. An ROC will be prepared using the uNGAL for all the newborns. AUC will be calculated and cut-offs with the most agreeable sensitivity and specificity will be derived. Using these cut-offs a 2x2 table will be created to calculate the following for the selected cut-off: sensitivity, specificity, positive predictive value and negative predictive value. The significance level will be set at p < 0.05 for all statistical tests.

Limitations:

One limitation of this study is that it the sample consists of preterm from a single SNCU which might limit the generalizability of the findings to other populations. 

Confidentiality

Confidentiality of data of each subject would be maintained throughout the study.

Project Time Line