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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 3  |  Issue : 2  |  Page : 58-63

A prospective study of acute kidney injury in outborn neonates admitted in a tertiary care center in Western Rajasthan


Department of Pediatrics, Dr. S.N. Medical College, Jodhpur, Rajasthan, India

Date of Submission01-May-2020
Date of Decision19-Jul-2020
Date of Acceptance09-Dec-2020
Date of Web Publication31-Dec-2020

Correspondence Address:
Mohan Makwana
E-22/10, Umaid Hospital Campus, Jodhpur - 342 001, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2589-9309.305898

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  Abstract 


Background: Acute kidney injury (AKI) is common in critically ill neonates and is associated with increased risk of morbidity and mortality. Methods: This study was conducted in a tertiary care hospital of western Rajasthan over a period of 1 year on neonates born elsewhere. Neonates fulfilling the neonatal Risk, Injury, Failure, Loss, and End-Stage (nRIFLE) criteria for AKI were included and and were investigated as per protocol. Results: Out of 3422 neonates admitted in neonatal ICUs, 983 (28.7%) neonates had AKI as per the nRIFLE criteria. The majority (83.6%) of the neonates with AKI were from rural background. Most (75.6%) infants were admitted within the first 7 days of life, with male predominance (ratio of boys to girls 1.7:1), and the mean admission weight was 2.4 ± 0.5 kg. The rate of neonatal AKI was highest during summer months. The highest AKI stages by the nRIFLE criteria were risk (R) in 57.9%, failure (F) in 24.6%, and injury (I) in 17.4% of the cases. Factors associated with AKI were dehydration (53.7%) related to high ambient temperatures, sepsis (35.7%), perinatal asphyxia (19.9%), and respiratory distress (15.8%). Mortality rates were 11.9%, 10.5%, and 20.2% in category R, I, and F, respectively. Conclusions: High prevalence of neonatal AKI in this centre was due to dehydration related to high ambient temperatures. AKI was associated with high rates of morbidity and mortality.

Keywords: Acute kidney injury, neonatal Risk, Injury, Failure, Loss, and End Stage, Risk, Injury, Failure, Loss, and End Stage, urine output


How to cite this article:
Mitharwal R, Makwana M, Mourya HK, Kumari S, Ram S. A prospective study of acute kidney injury in outborn neonates admitted in a tertiary care center in Western Rajasthan. Asian J Pediatr Nephrol 2020;3:58-63

How to cite this URL:
Mitharwal R, Makwana M, Mourya HK, Kumari S, Ram S. A prospective study of acute kidney injury in outborn neonates admitted in a tertiary care center in Western Rajasthan. Asian J Pediatr Nephrol [serial online] 2020 [cited 2021 Jan 23];3:58-63. Available from: https://www.ajpn-online.org/text.asp?2020/3/2/58/305898




  Introduction Top


Acute kidney injury (AKI) is a common event in critically ill children, with clinical manifestations ranging from mild dysfunction to complete oliguric kidney failure. AKI is common in critically ill neonates and associated with increased risk of morbidity and mortality. Information on neonatal AKI, particularly from developing countries, is limited.[1] While perinatal asphyxia and congenital renal anomalies are the chief etiology of neonatal kidney dysfunction in developed countries, sepsis is the major cause of AKI in India. Up to one-third of the cases of AKI in neonates present with normal urine output (UOP).[2] While serum creatinine level is the simplest and most commonly used indicator of neonatal kidney function, serum creatinine level immediately after birth reflects the maternal creatinine concentration. It gradually decreases from 1.1 mg/dl in term infants (1.3 mg/dl in preterm infants) to a mean value of 0.4 mg/dl within the first 2 weeks of life.[1] UOP is the most common and cost-effective bedside method to diagnose AKI.[3] This study describes the etiology and outcomes of AKI in outborn neonates admitted to a tertiary care center in western India.


  Methods Top


This prospective observational study was conducted in the neonatal wards of a tertiary care center in Jodhpur, Rajasthan, India, over a period of 1 year from November 2018 to October 2019. The primary objective was to study the prevalence of AKI in neonates and to determine the risk factors associated with AKI. The secondary objectives were to evaluate the severity of AKI and its progression among the neonatal Risk, Injury, Failure, Loss, and End-Stage (nRIFLE) stages, and to examine for seasonal trend in incidence in AKI, if any.

Participants

All outborn neonates admitted in the neonatal intensive care unit (NICU) were screened daily throughout the duration of hospital stay for development of AKI, using the Risk, Injury, Failure, Loss, and End-Stage (RIFLE) criteria, based on serum creatinine and UOP, and modified for use in neonates [Table 1].[3] Neonates fulfilling the modified nRIFLE criteria were enrolled, and their stage of AKI was classified. Exclusion criteria included major congenital malformations of the kidneys and urinary tract, detected by abdominal ultrasonography, therapy with nephrotoxic drugs, critical illness in mother, maternal therapy with nephrotoxic drug in antenatal period, and parental refusal of consent.
Table 1: Risk, Injury, Failure, Loss, and End-Stage criteria modified for use in neonates[3]

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Evaluation

All neonates with AKI underwent daily investigation of blood urea, serum creatinine and electrolytes, urinalysis, and measurement of UOP, until serum creatinine was <1 mg/dl, UOP was established at more than 1.5 ml/kg/hr, or the patient became unavailable for follow-up due to any reason. Twenty-four-hour UOP was measured by applying an adhesive sterile polyethylene urine collecting bag in boy infants, and in girls either by applying polyethylene urine collecting bag or by collecting on diaper and weighing the diaper before and after the collection.

Data were collected and recorded on predesigned case record forms on a daily basis, and included details of demographic features, clinical and laboratory findings, gestational age, birth weight/weight on admission, and relevant antenatal and perinatal history.

Statistical analysis and sample size

Standard statistical tests were used to report summative data. Continuous variables are reported and compared using parametric or nonparametric tests based on normality of their distribution. Chi-square test was applied for categorical data. P < 0.05 was considered statistically significant.

Mathur et al.[21] prospectively reported the occurrence of AKI in 26% of the term neonates with sepsis. The mortality rate was significantly higher in those with AKI than in those with no AKI (70.2% vs. 26%, P < 0.001). Using this estimate, at power of 80%, alpha error of 5%, and Z value of 95%, a total of 305 neonates were required to be enrolled to find a similar proportion with AKI.


  Results Top


Patient characteristics

Of 3422 neonates admitted in the extramural NICU during the 1-year study period, 983 (28.7%) were diagnosed with AKI [Figure 1]. The prevalence of AKI was highest in the hot summer months, including the most severe cases (stage F) of AKI [Table 2]. Most (83.6%) patients were from a rural area, with a rural-to-urban ratio of 5.1:1. The mean ± standard deviation of age of admission was 5.4 ± 5.8 days; most (75.6%) neonates were admitted within 7 days of life, and the age range on admission of 2–4 days had the highest number (37.0%) of AKI cases. The ratio of boys to girls was 1.7:1, with a prevalence of AKI being 63.3% and 36.6%, respectively. The mean age of admission for boy and girl newborns with AKI was 5.0 ± 5.3 and 6.1 ± 6.5 days, respectively (P < 0.0001).
Figure 1: Flow of patients with acute kidney injury

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Table 2: Month-wise prevalence of acute kidney injury by modified neonatal Risk, Injury, Failure, Loss, and End-Stage criteria and average daily temperature

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Most (95.4%) neonates were institutionally delivered, of which 92.8% of the patients were delivered by vaginal route. The weight at admission was 2.43 ± 0.58 kg, with a weight between 2.5 and 2.99 kg in 32.2% and 2.0–2.49 kg in 29.5% of the neonates. Preterm infants accounted for 21.2% of the AKI cases (P < 0.0001). While the majority of the patients were appropriate for age (90.8%), 9.4% and 0.1% of the cases were small and large for gestational age, respectively. Only 0.4% of the patients were postterm (>41 weeks' gestation).

[Table 3] provides the results of biochemical investigations in patients with AKI. [Table 4] shows that the most common comorbidities with AKI were dehydration (53.7%), septicemia (35.7%), perinatal asphyxia (19.9%), and respiratory distress (15.8%).
Table 3: Biochemistry in patients with acute kidney injury at admission

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Table 4: Determinants of adverse outcome

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The mean UOP on the 1st day of admission was 0.9 ± 0.4 ml/kg/hr. A majority (57.9%) of neonates with AKI had UOP in range of 1.0–1.5 ml/kg/hr; 24.6% of the patients had output below 0.7 ml/kg/hr.

Severity of acute kidney injury and course

Of all patients with AKI, 57.9% belonged to the “R” (risk) category, followed by 24.6% in “F” (failure) category and 17.4% in the “I” (injury) group [Figure 1]. The UOP was expectedly lower in higher categories of nRIFLE classes (1.2 ± 0.1 ml/kg/hr in R category and 0.8 ± 0.09 ml/kg/hr in I category). The duration of hospital stay in patients with AKI was 6.9 ± 5.3 days; it was 6.5 ± 5.5 days in R category, 6.7 ± 4.2 days in I category, and 7.8 ± 5.4 days in the F category.

Mortality and its determinants

Of 983 neonates with AKI, 135 (13.7%) died, of whom 107 (79.4%) were in early neonatal period (<7 days). Fatality rates were 11.9%, 10.5%, and 20.2% in R, I, and F categories, respectively. The duration of hospital stay was significantly higher in neonates who improved as compared to those who died (8.1 ± 5.3 days vs. 3.4 ± 3.6 days).

Mortality rates were related to ambient temperature: 50.4% of the deaths occurred during the hottest 3 months (March–June 2019) and 27.4% in the subsequent 3 months (July–October 2019). Mortality rates were higher for term (10.3%) than preterm (3.2%) neonates and for boys (15.9%) as compared to girls (10%).

Dehydration, neonatal sepsis, and icterus neonatorum were significantly associated with mortality [Table 4]. Mortality was also associated with increased levels of serum creatinine, serum potassium, and low UOP. Levels of both urea and creatinine were higher on days 1–7 in patients who died versus those who survived (data not shown).


  Discussion Top


The prevalence of AKI in neonates in studies from different parts of the world ranges widely from 1.5% to 29.9%, based on definition and criteria for diagnosis.[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14] AKI was present in 28.7% of the neonates in the present study, similar to that reported by the multicentric AWAKEN study.[4] The higher prevalence and severity of AKI in our study may be accounted for by high prevalence of dehydration due to high ambient temperature, coexistent sepsis and/or shock, and delayed evaluation due to referral from remote underserved areas of western Rajasthan with extreme climatic conditions.

We used the nRIFLE criteria to define and classify neonates on the basis of UOP and serum creatinine. Similar to findings in a previous study,[15] more than half of the cases were mild and in the R (risk) class. However, both the prevalence of AKI and that of severe AKI were highest in hot summer months. Almost half (43.2%) of the neonates with AKI were admitted during March–June, and another 31.6% were admitted through July–October; the month-wise prevalence was lowest in December and February [5.3% and 5.8%; [Table 2]]. The relative prevalence of AKI in stage F was highest for the months of May (44.5%), April (35.1%), and October (31.7%), during which the maximum environmental temperature was above 40°C, and most patients had concomitant dehydration. A similar finding of preponderance of neonatal AKI in summer season was reported by Kumar et al.[16] Borg et al. suggest that an increase in ambient temperature by 1°C was associated with an increased incidence for all kidney disease categories.[17]

We found that AKI was predominantly diagnosed in patients from rural areas, possibly due to delay in recognition of risk factors due to lack of availability of expert medical care and lower educational status of parents, higher prevalence of risk factors like sepsis due to poor socioeconomic status, and delayed management due to long traveling distances and delayed referral due to lack of access to medical services.

Most patients with AKI were admitted in the early neonatal period with an average age at admission of 5.4 ± 5.8 days. Girl newborns were older than boys at admission by approximately 1 day, similar to findings by Ali et al.[18] and Gharehbaghi and Peirovifar.[19] The prevalence of AKI was higher in boy than girl neonates, similar to findings by many authors.[4],[5],[6],[7],[8],[9],[11],[13],[18],[19] However, two studies have reported female predominance.[7] We found a preponderance of appropriate for gestational age infants in the normal weight range, similar to two past studies;[18],[19] however, another study found that these infants were low weight (mean: 2.0 kg). Unlike Ali et al. who found AKI chiefly in patients born by cesarean section,[18] most of our patients were delivered vaginally at institutions. Our finding that AKI chiefly affects term neonates is not unusual, and is reported by several authors.[7],[8],[9],[16],[18],[19] Various comorbidities, such as perinatal asphyxia, septicemia, and meconium aspiration syndrome, may predispose term neonates to AKI, while preterm neonates might have been referred early for prematurity itself or respiratory distress and other prematurity-related morbidities.

Expectedly, levels of blood urea and serum creatinine were high in neonates with AKI, rose progressively with advancing categories of AKI, and were significantly higher among neonates who died versus the survivors (data not shown). Likewise, UOP was low in infants with AKI, was progressively lower in R, I, and F categories of AKI, and was lower for neonates who died than in those who survived (data not shown). Newborns with AKI had progressively longer duration of hospital stay in our study, similar to findings in the AWAKEN study.[4] Likewise, the AWKEN study reported longer hospital stay in survivors of AKI compared to those who died with AKI.[4]

The mean serum sodium level at admission with AKI was 157 mEq/L, highlighting that dehydration was the chief contributing factor underlying AKI in our neonatal cohort. Other common risk factors associated with AKI were sepsis, perinatal asphyxia, and respiratory distress. In contrast to our findings, Kapoor et al.[6] reported sepsis, perinatal asphyxia, respiratory distress syndrome, and genitourinary anomalies as the chief underlying factors for neonatal AKI. Gharehbaghi and Peirovifar[19] linked AKI chiefly to surgery, perinatal asphyxia, sepsis, and respiratory distress, while Bokade and Meshram[20] attributed AKI to sepsis, perinatal asphyxia, respiratory distress, and jaundice. It is possible that the high rate and severity of AKI in our outborn newborns were contributed to by delayed referral from remote areas and various social taboos and cultural practices (such as poor maternal hygiene, delaying of breastfeeding, giving prelacteal feeds such as tea, goat milk, honey, or herbal extracts, reduced feeding of mothers, and application of cow dung to the umbilical cord) that might have further contributed occurrence of dehydration and/or sepsis.

The rates of mortality in outborn newborns with AKI were highest during the hottest months, corresponding closely to the relative prevalence of AKI and severe AKI. The rate of mortality in the present study is similar to other studies reporting death in 14%–14.9% of the neonates with AKI;[11],[18],[21],[22] however, Bokade and Meshram[20] reported a very high mortality rate (31.9%) for unexplained reasons.


  Conclusions Top


AKI is a common finding in outborn neonates in western Rajasthan, especially during summer months due to extreme environmental factors[23], leading to dehydration. Other factors contributing to AKI include neonatal septicemia and perinatal asphyxia. The most common risk factor for AKI, dehydration, is amenable to both prevention and intervention, and the associated AKI is likely to be reversible if intervened in a timely manner. However, delayed referral is associated with severe and often irreversible AKI. The duration of hospital stay and the likelihood of adverse renal and patient outcomes are increased for neonates with severe stages of AKI.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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