ACUTE RENAL FAILURE IN TERM NEWBORN FOLLOWING PERINATAL ASPHYXIA

Introduction: Perinatal asphyxia (PA) results in hypoxic damage to almost all organs, kidneys being most frequently (40%) affected. Objectives: was to determine the incidence of acute renal failure (ARF) in term neonates with PA and to correlate it with severity of hypoxic ischemic encephalopathy (HIE). Materials and methods: This prospective study of 54 term neonates with PA was performed in tertiary level neonatal intensive care unit at Pediatric Clinic Sarajevo from June 2014 to June 2016. The severe PA was defined as 5. minute Apgar score < 3 and moderate PA as 5. minute Apgar score 4-6. Criteria adopted for ARF were serum creatinine > 1.5 mg/dl (> 133 micromol/L) on 3rd day of life or urine output < 0.5 ml/kg/hr for > 6 hrs beyond 24 hrs of life. Results. Out of 54 neonates with PA, 22 (40.74%) had ARF. Most of them (63.6%) had non-oliguric ARF with mean renal output of 2.2 ± 0.5 ml/kg/h. Eight neonates (36.4%) had oliguric ARF with mean renal output of 0.35 ± 0.6 ml/kg/h. Most of the neonates with oliguric ARF (63.4%) had severe PAwhile in those with non-oliguric ARF moderate PA was predominant. ARF was highest in the neonates with HIE III (85.71 %) (Figure 1). This showed that as HIE stage progressed, more renal dysfunction was seen in asphyxiated babies and this difference in incidence was found statistically significant (p < 0.05). Conclusions. Neonates with severe PA had more frequent ARF and the predominant type of renal involvement was non oliguric. Neonates with HIE stage II and III had significantly higher incidence of ARF.


INTRODUCTION
Perinatal asphyxia (PA) is the major cause of neonatal mortality and long term neurological morbidity with an estimated incidence of 1-10/1000 live births (1).It results in hypoxic damage to almost all organs of the neonate; with kidneys being most frequently (40%) involved (1).The neonatal kidney is anatomically and functionally immature.Renal insufficiency manifests as early as 24 hours of life leading to irreversible cortical necrosis when prolonged.Detection of renal failure is vital in neonates with hypoxic ischemic encephalopathy (HIE) to sustain a stable biochemical milieu and initiate appropriate treatment (2).Neonatal acute renal failure (ARF) is a diagnostic and therapeutic challenge as clinical and laboratory parameters are not strictly defined yet (2).PA and birth injuries together contribute to almost 29% of neonatal deaths.World Health Organisation (WHO) defined birth asphyxia as "failure to initiate and sustain breathing at birth" with Apgar score of < 7 at 1. minute of life (1,3).American College of Obstetrics and Gynecologists (ACOG) and American Academy of Pediatrics (AAP) have laid down essential criteria to diagnose PA which include, prolonged metabolic or mixed acidemia (pH < 7.0 on cord arterial blood sample), persistence of an Apgar score of < 3 for 5 min or longer, clinical neurologic manifestation as seizures, hypotonia, coma or HIE in the immediate neonatal period coupled with multiorgan dysfunction (1,3).(4).All the neonates were evaluated clinically and their renal functions were assessed on 3 rd day.Renal profile was done by estimation of serum creatinine, urea, sodium and potassium.Assessment of fractional excretion of sodium was done to differ intrinsic from extrinsic renal failure.Criteria adopted for ARF were serum creatinine > 1.5 mg/dl (> 133 micromol/lit) on 3 rd day of life or urine output < 0.5 ml/kg/hr for > 6 hrs beyond 24 hours of life.Statistical analysis was conducted using statistical products and services solutions (SPSS) software version 17.0.
ARF was highest in the neonates with HIE III (85.71%).(Figure 1).This showed that as HIE stage progressed, more renal dysfunction was seen in asphyxiated babies and this difference in incidence was found statistically significant (p < 0.05).The mean values of serum values of urea, creatinine, Na and K are shown in Table 2.

Subjects Value
Gender FeNa (fractional excretion of sodium) >2.5% was considered as an indicator of intrinsic renal failure.

DISCUSSION
PA is an insult during the intrauterine or immediate extrauterine period to the fetus or the newborn due to hypoxic and/or ischemic damage to various organs of greater magnitude which leads to transitory or permanent functional and biochemical changes.Hypoxia and ischemia can result in impairment of every tissue and organ of the body, kidneys are extremely sensitive to oxygen deprivation.Neonates are more susceptible to acute kidney injury because they have low glomerular filtration rate, high renal vascular resistance, high plasma renin activity and decreased reabsorption of sodium in the proximal tubules.Renal insufficiency can manifest within 24 hours of a hypoxic ischemic episode, and if prolonged, may even lead to irreversible cortical necrosis (4).Difficulties in serum creatinine interpretation make it more difficult to achieve a consensus regarding ARF definition (3,5).Recent studies recognize that even small increments in serum creatinine levels increase morbidity and mortality (6,7,8).Studies by Jayshree (9), Nouri (10) and Gupta (2) chose the cut-off level of 90 ìmol / l for serum creatinine at 48 hours of life.We took the cut-off of 133 ìmol / l for creatinine at 72 hours of life.
In our study, incidence of ARF was 40.74% in asphyxiated babies.This is well matched with earlier studies (2,9,10).
The presence of PA and its severity significantly correlated with increasing incidence of ARF (4.5).Our study noted a 13.5 fold increase risk of developing ARF in HIE III compared to HIE I. ARF was the highest in the neonates with HIE III (71.43%) and the lowest in the neonates with HIE I (5.26%).The higher degree of HIE was also statistically significantly associated with oliguric type of ARF in comparison to non-oliguric type of ARF.This is also concordant to earlier studies (2,9,10).

Table 1 .
Basic characteristics of neonates included in our study