Asian Journal of Pediatric Nephrology

ORIGINAL ARTICLE
Year
: 2021  |  Volume : 4  |  Issue : 1  |  Page : 14--18

Occurrence and outcome of acute kidney injury in very low birth weight neonates


Mohd Ashraf1, Younus Ramzan Khan2, Parvez Ahmed2,  
1 Department of Pediatric Nephrology, Government Medical College, Srinagar, Jammu and Kashmir, India
2 Department of Pediatrics, Government Medical College, Srinagar, Jammu and Kashmir, India

Correspondence Address:
Mohd Ashraf
Lecturer Pediatric Nephrology, Department of Pediatrics, Government Medical College, Srinagar, Jammu and Kashmir
India

Abstract

Background: Neonatal acute kidney injury (AKI) carries significant morbidity and mortality, particularly among very low birth weight (VLBW) neonates. We aimed to evaluate the short-term outcomes and the risk factors of AKI in VLBW infants. Methods: All extramural VLBW neonates without AKI and congenital renal abnormalities were enrolled. Serum creatinine (SCr) was estimated on days 0, 4, and 10. Neonatal AKI was defined an increase in SCr by ≥0.3 mg/dL from the previous value within a period of 48 h or >1.5 time from baseline within 7 days. Results: Neonatal AKI developed in 26 (13.8%) out of 189 neonates studied. Among AKI group, 5 (19.2%) had stage 1, 9 (34.4%) neonates reached stage 2, and 12 (46.1%) neonates reached stage 3 AKI. Neonates with AKI had a significantly lower gestational age and birth weight (P < 0.001). Mortality in VLBW neonates with AKI was significantly higher as compared to those without AKI (crude hazard ratio 6.2; 95% confidence interval: 2.36–15.79, P <0.05). Conclusions: AKI is common in extramural VLBW neonates, is inversely correlated with gestational age and birth weight, and carries poor outcome.



How to cite this article:
Ashraf M, Khan YR, Ahmed P. Occurrence and outcome of acute kidney injury in very low birth weight neonates.Asian J Pediatr Nephrol 2021;4:14-18


How to cite this URL:
Ashraf M, Khan YR, Ahmed P. Occurrence and outcome of acute kidney injury in very low birth weight neonates. Asian J Pediatr Nephrol [serial online] 2021 [cited 2022 Jan 17 ];4:14-18
Available from: https://www.ajpn-online.org/text.asp?2021/4/1/14/320187


Full Text



 Introduction



Acute kidney injury (AKI) is a common and serious health problem that affects all ages and carries high rates of morbidity and mortality. AKI in critically ill preterm infants is worse since they are more susceptible to hemodynamic alternations, perinatal stress, nosocomial infections, and multiple nephrotoxic medications during hospitalization.[1]

The prevalence of neonatal AKI in retrospective studies is reported to range from 8% to 24%,[2] while a recent multicenter international observational cohort demonstrated AKI in 30% neonates in intensive care unit.[3] The incidence of neonatal AKI varies with gestational age, birth weight, underlying medical or surgical condition, and treatment modalities. Few single center studies have estimated the incidence of AKI in very low birth weight (VLBW) neonates to range from 12.5% to 39.8%.[4],[5],[6] Rates of mortality in newborns with AKI are reported to be between 10% and 28%.[3],[7] However, mortality in VLBW infants with AKI is ranging from 42% to 69%, higher than those without AKI or in normal weight neonates[5],[8] and carries a high risk of chronic kidney disease (CKD).[9],[10],[11]

Since information on the incidence and outcomes of AKI in VLBW neonates in India is limited, this study was conducted to understand its incidence and risk factors in a tertiary care setting.

 Methods



This prospective observational study was conducted between November 2017 and April 2019 at the Postgraduate Department of Pediatrics, GB Pant General hospital, an associated hospital of Government Medical College, Srinagar. The study was approved by the institutional ethical committee and review board. All VLBW (500–1499 g) extramural neonates with or without AKI, admitted during the study period in the unit of Neonatology, Department of Pediatrics, were enrolled. Neonates with congenital malformations of kidneys and urinary tract and those who died before 48 h of life were excluded.

Definitions and terminology

Neonatal acute kidney injury

Neonatal AKI was diagnosed on the basis of an increase in serum creatinine (SCr) by ≥0.3 mg/dL or an increase in SCr to 150%–200% from previous baseline[2] based on modified Kidney Disease Improving Global Outcome (KDIGO) 2012 criteria.[2] Patients were grouped as no AKI and AKI; AKI in the latter group of patients was further classified into three stages: (i) Stage 1 AKI: increase in SCr by ≥0.3 mg/dL within 48 h or to 1.5–1.9 times the baseline value within 7 days; (ii) Stage 2 AKI: increase of SCr by 2.0–2.9 times the baseline value; and (iii) Stage 3 AKI: increase in SCr to >3 times the baseline value, or to >2.5 mg/dL, or need for renal replacement therapy (RRT). The absence of signs of AKI was graded as KDIGO stage 0.[12]

Prenatal care

Adequate prenatal care was defined as a minimum of 3 scheduled antenatal visits to their health-care providers for the maternal and fetal well-being and usually includes a detailed history, physical examination, nutritional supplementation, immunization and certain blood, urine and imaging tests, depending on the stage of the pregnancy.

Chorioamnionitis

Chorioamnionitis was defined as the presence of fever, tender uterus, an elevated blood granulocyte count, and bacteria and/or inflammatory cells in amniotic fluid in any pregnant women during near-term or term labor.[13]

Antenatal steroids

Antenatal steroid therapy was considered complete when two doses of betamethasone acetate, given as intramuscular injections, were administered 24 h apart, and at least 24 h before birth.[14]

Intermittent positive pressure ventilation

Intermittent positive pressure ventilation is a breathing mode that was considered given if the ventilator was set to provide a predetermined number of ventilatory breaths irrespective of the fact whether the infant did or did not breathe spontaneously.[15]

Data collection

After detailed history and thorough clinical examination, demographic parameters such as gestational age in completed weeks, birth weight (g), sex, 1- and 5-min Apgar scores, antibiotic exposure, mechanical ventilation, inotrope use, exchange transfusion, and umbilical arterial/venous catheterization, along with maternal characteristics such as maternal age, prenatal care, diabetes, hypertension, antenatal steroids, smoking, preeclampsia, multiple birth, and chorioamnionitis, were recorded in a predesigned pro-forma. Neonates were grouped based on birth weight into two groups (weighing 1000–1499 g vs. 500–999 g) and based on gestational age into three groups (24–27 weeks, 28–32 weeks, and 33 weeks and above).

Laboratory measurements and follow-up

Enrolled neonates underwent peripheral blood sampling for SCr on days 1, 4, and 10 of life. Maternal SCr was also recorded. In patients with diagnosed AKI, SCr levels were monitored daily. SCr estimation was done by kinetic Jaffe method using Siemen's analyzer.

All the patients enrolled were followed till discharge or outcome; patients with AKI were followed for 3 months.

Sample size

Using G*Power 3.0.10 software (v 3.0.10; Franz Faul, Kiel University, Kiel, Germany), it was estimated that the least number of patients required to estimate the prevalence of AKI in VLBW neonates, with 90% power, effect size of 0.231 and 5% significance level, was 189.

Statistical methods

The recorded data were compiled and entered in a spreadsheet (Microsoft Excel) and then exported to data editor of SPSS Version 20.0 (SPSS Inc., Chicago, Illinois, USA). Continuous normally distributed variables were expressed as mean ± standard deviation or median (interquartile range), and categorical variables were summarized as frequencies and percentages. Normally distributed continuous variables were compared using student t-test, and non-normally distributed variables were analyzed using Mann–Whitney U-test. Chi-square test or Fisher exact test, whichever appropriate, was employed for comparing categorical variables. The association between AKI and survival was performed by Cox proportional hazard analysis. All P values were two tailed and a value < 0.05 was considered statistically significant.

 Results



Based on the modified KDIGO definition, 5 (19.2%) neonates reached stage 1, 9 (34.4%) neonates reached stage 2, and 12 (46.1%) neonates reached stage 3 AKI [Figure 1]. Five patients had deranged renal functions at the time of discharge which normalized within 8 weeks of life in all except one patient who developed CKD and later on died during readmission for complications of CKD.

The demographic and clinical characteristics of the study population are shown in [Table 1]. In comparison to the VLBW neonates without AKI, those with AKI had a significantly lower gestational age and birth weight. Neonates with AKI had lower Apgar scores at 1 and 5 min, higher exposure to antibiotics, inotropes, and mechanical ventilation during hospitalization than among those without AKI [Table 1].

Table 2 shows that there was a statistically significant difference in mortality between VLBW neonates with and without AKI (crude hazard ratio 6.2; 95% confidence interval: 2.36–15.79; P < 0.05).

At 3-month follow-up, 19.2% of the surviving neonates with AKI had raised SCr; one had glomerular filtration rate <60 mL/min/1.73 m2 as calculated by Schwartz formula, along with blood pressure between 75th and 90th centile and no proteinuria. This VLBW neonate later died at 4.5 months of age with a diagnosis of CKD, sepsis, and respiratory failure.

 Discussion



Using a modified KDIGO definition,[2] the incidence of AKI in the present study population of VLBW neonates was 13.8%, while the mortality was 38.5%. In a multicenter, multinational, observational AWAKEN cohort study,[3] almost 30% of neonates suffered AKI. Koralkar et al.,[5] in their study found that AKI occurred in 18% of VLBW infants while Carmody et al.[6] in their study observed that AKI occurred in 40% VLBW infants. A recent study by Shalaby et al.[7] observed that 56% (120/214) of neonates suffered AKI. On comparison with these studies, the lower AKI incidence in the present study is explained by exclusion of 25 VLBW neonates who died just within 48 h of their admission; their inclusion in the AKI group would raise the AKI incidence closer to that in the AWAKEN[3] study and mortality up to 68.6%.

The present study included extramural VLBW neonates who have inherent risk factor (s) for AKI, such as transport stress, cold stress, hypoxemia, apnea, seizures and, at times, substandard neonatal transport that may increase the occurrence of neonatal AKI. Previous studies have demonstrated that sepsis and birth asphyxia are well-known risk factors for AKI in near-term and term infants.[16],[17] In preterm and low birth weight infants, low Apgar Score and lower gestational age are among the major risk factors associated with AKI,[18],[19] which is in conformity with our findings. The higher incidence of AKI in VLBW infants with a lower gestational age may be due to higher chances of multiple AKI risk factors.

Some studies[20],[21] have evaluated the impact of AKI in VLBW neonates, sick neonates, and asphyxiated neonates and observed that AKI is common and associated with high mortality rates.[8],[22] In the present study, 10/26 (38.5%) VLBW neonates with AKI died, compared to 28/163 (17.2%) VLBW neonates without AKI, an observation which is in conformity with earlier studies. Stojanović et al.[8] reported that patients with neonatal AKI had significantly higher mortality rate than those without AKI (69.2 vs. 13.5%, P < 0.001), and mortality rate reached to 83.3%–100% among VLBW neonates with stage 3 AKI. In another study on preterm infants with gestational age lower than 33 weeks, Bruel et al.[22] found that rise in SCr level to more than 1.6 mg/dL at gestational age of 24–27 weeks, more than 1.1 mg/dL at gestational age of 28–29 weeks, and more than 1 mg/dL at gestational age of 30–32 weeks is associated with increased mortality. Our study shows a strong association between AKI and neonatal mortality, with crude hazard ratio of more than 6 [Table 2]. A similar pattern was observed by Koralkar et al.,[5] who reported higher mortality in VLBW infants with AKI than those without AKI (42% vs. 5%; P < 0.001), even after adjusting for potential confounders (hazard ratio 2.4; 95% CI 0.95–6.0; P < 0.06). Analyzing mortality in ELBW with AKI, Viswanathan et al.[4] reported significantly higher mortality rates than controls (70% vs. 22%, respectively), while reinforcing similar findings. Carmody et al.[6] observed that AKI was independently associated with increased mortality (odds ratio 4.0; 95% CI 1.4–11.5) and length of stay (11.7 days; 95% CI: 5.1–18.4 days).

Recent KDIGO practice guidelines recommend that all patients with AKI should be evaluated after 3 months,[23] as they are at risk of CKD in long term. In their study, Shalaby et al. found 25% of neonates in the AKI group had raised SCr (>65 μmol/L) on discharge, with low index of pediatric nephrologist referral (<10%). In contrast, in the present study, 19.2% neonates with AKI had raised SCr in follow-up, of whom one child, with CKD 3, succumbed later. In an observational prospective study by Schiffl et al.,[24] of 425 critically ill patients without prior CKD and with severe AKI requiring RRT, 238 (56%) had complete renal recovery and none among them developed CKD during follow-up. However, 90% of discharged patients with renal impairment had ongoing CKD during long-term follow-up among whom 5% progressed to end-stage renal disease.

Various limitations were present. Exclusion of critically ill infants who died within 48 hours, the definition of AKI by serum creatinine levels alone, and omitting the urine output criteria, all might have underestimated the occurrence of AKI and mortality rate among the VLBW neonates. In addition, limited follow-up for 3 months only, is not reason enough to draw a conclusion about the long-term consequences of neonatal AKI.

 Conclusions



Among extramural VLBW neonates, the proportions with AKI, mortality, and impaired renal function at discharge were 13.8%, 38.5%, and 19.2%, respectively. These outcomes were more often among lower end of gestational age and birth weight. The study underscores the importance of careful monitoring of renal function among VLBW and/or premature neonates and the follow-up of patients with AKI to enable timely diagnosis of CKD which might improve the long-term outcomes.

Ethical clearance

Ref. No. 114/ETH/GMC, Dated 30/03/2017.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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