| Abstract|| |
The aim of this work is to study the incidence of acute kidney injury (AKI) in neonates admitted to the neonatal intensive care unit (NICU) over a six-month period from September 2011 to March 2012. This prospective study was performed on 250 neonates admitted to the NICU at the Children's Hospital, Faculty of Medicine, Zagazig University. All neonates were subjected to detailed history taking, including pre-natal, natal and post-natal history, with stress on symptoms suggestive of AKI. All neonates were examined thoroughly and the following investigations were performed: Blood urea nitrogen (BUN), serum creatinine, sodium, potassium, calcium, complete blood count, C-reactive protein, arterial blood gases, urine sodium and urine creatinine. AKI was diagnosed in 27 cases (10.8%), including 12 females and 15 males. 40.7% of the AKI cases were born after full-term pregnancy while 59.3% were pre-term babies. 29.6% of the AKI cases had oliguria, and there was male sex predominance, with a male-female ratio of 1.3:1. The cause of AKI was pre-renal in 96.3% and intrinsic renal in 3.7% of the cases. The predisposing factors for AKI were sepsis in 63% of the cases, respiratory distress syndrome in 55.6%, mechanical ventilation in 51.9%, peri-natal asphyxia in 18.5%, dehydration in 14.8%, surgical operation in 11.1%, congenital heart disease in 7.4%, sub-galeal hematoma in 3.7%, polycythemia in 3.7% and intra-ventricular hemorrhage in 3.7% of the cases. Our data suggest that pre-renal failure was the most common form of AKI in our patients. Early recognition of risk factors such as sepsis, peri-natal asphyxia or peri-operative problems and rapid effective treatment of contributing conditions will reduce the incidence of AKI in the neonatal period.
|How to cite this article:|
Youssef D, Abd-Elrahman H, Shehab MM, Abd-Elrheem M. Incidence of acute kidney injury in the neonatal intensive care unit. Saudi J Kidney Dis Transpl 2015;26:67-72
|How to cite this URL:|
Youssef D, Abd-Elrahman H, Shehab MM, Abd-Elrheem M. Incidence of acute kidney injury in the neonatal intensive care unit. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2021 Mar 1];26:67-72. Available from: https://www.sjkdt.org/text.asp?2015/26/1/67/148738
| Introduction|| |
Acute kidney injury (AKI) is a common problem in the neonatal intensive care units (NICUs)  and has been shown to occur in 3.4-24% of neonates admitted to NICUs.  More recent studies have reported an incidence of AKI of 3-8% of all NICU admissions.  The most common form of AKI in neonates is prerenal failure due to renal hypo-perfusion or ischemia.  Pre-renal failure may result in intrinsic kidney failure if it is not treated promptly. The kidneys of neonates are particularly susceptible to hypo-perfusion because of the physiologic characteristics of neonatal kidneys, including high renal vascular resistance, high plasma renin activity, low glomerular filtration, decreased intra-cortical perfusion rate and decreased re-absorption of sodium in the proximal tubules in the first days of a neonate.  Thus, newborn infants are vulnerable to acute tubular necrosis or cortical necrosis. The cause of AKI in neonates is of multi-factorial etiology and, usually, there are one or more associated contributing factors.  In most studies, peri-natal asphyxia and sepsis are the most commonly associated conditions.  The other associated conditions for development of AKI in the newborns include respiratory distress syndrome, dehydration, congestive heart failure and nephrotoxic drugs. 
The short-term outcome of therapy for AKI in newborns is dependent on the underlying etiology of AKI, the involvement or otherwise of other organs and the availability of renal replacement therapy. As expected, mortality is more frequent and morbidity is much worse in neonates with multi-organ failure. 
The aim of this work was to study prospectively the incidence of AKI in neonates admitted to the NICU during the study period from September 2011 to March 2012. Two-hundred and fifty neonates admitted to the NICU were studied. The reason for admission was respiratory distress in 48.4%, pre-term delivery in 25.6%, sepsis in 10.4%, jaundice in 9.2%, hypoxic ischemic encephalopathy in 3.6%, vomiting and dehydration in 1.6% and severe anemia in 1.2% of the patients. Of the 250 neonates admitted, 33 (63%) were diagnosed to have AKI at admission and 37% after admission.
| Patients and Methods|| |
This is a prospective study involving 250 neonates admitted to the NICU in the Children's Hospital, Faculty of Medicine, Zagazig University, during the study period from September 2011 to March 2012. Their ages at admission ranged between 1 and 20 days and their weight at admission ranged between 750 and 3750 g.
The exclusion criteria were: (a) Neonates who died within the first 24 h of admission and (b) neonates with maternal history of kidney failure.
All neonates admitted to the NICU unit were subjected to full history taking (name, age, sex, weight at admission, gestational age, mode of delivery, maternal risk factors and associated contributing conditions, including (a) peri-natal asphyxia, (b) sepsis, (c) respiratory distress syndrome, (d) dehydration due to feeding problems, (e) oliguria, (f) heart failure, (g) nephrotoxic drug administration and its duration, (h) urologic anomalies, (i) history of surgical operation and reason for surgery and (j) mechanical ventilation and its duration). The serum creatinine and blood urea nitrogen (BUN) were tested on two separate occasions at least 12 h apart.
We examined all the neonates in detail. Additionally, all cases were subjected to the following investigations:
- Laboratory testing: Serum creatinine, BUN, serum sodium, potassium, calcium, complete blood count, C-reactive protein, arterial blood gases, urine sodium and urine creatinine.
- Radiological assessment when needed (renal imaging studies) to aid in the diagnosis of AKI (defined as plasma creatinine level higher than 1.5 mg/dL  or BUN level higher than 20 mg/dL on two separate occasions at least 12 h apart, while maternal renal function was normal .
| Statistical Analysis|| |
The collected data were tabulated and statistically analyzed using a computer and presentation of data was made using the SPSS software (Statistical Package for the Social Science, version 18.0). All quantitative data were expressed as mean ± standard deviation. The chi-square test was used for the comparison of frequency of mortality between the groups. A P-value < 0.05 was considered as being significant (incidence = number of positive new cases/number of population examined × 100).
| Results|| |
The mean post-natal age was 3.5 ± 5.3 days with a range of 1-20 days, and the mean weight at admission was 2179.6 ± 1000.6 g and the range was between 750 and 3750 g. AKI was diagnosed in 33 patients at admission, six of whom were excluded from the study according to the exclusion criteria of this study. A total of 63% of AKI cases were diagnosed at admission and 37% after admission [Table 1].
|Table 1: The incidence of acute kidney injury in neonates admitted to the neonatal intensive care unit.|
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The total number of patients with AKI studied were 27; 12 female (44.4%) and 15 male (55.6%), with frequency of occurrence of AKI of 10.8% in our NICU. 40.7% of AKI cases were born after full-term pregnancy, while 59.3% were pre-term; the mean age at admission was 3.5 ± 5.2 days (1-20 days), while their weight was 2179.6 ± 800.6 g (750-3750 g). Eight cases (29.6%) presented with oliguria and 19 cases (70.4%) presented with normal urine output. Pre-renal failure was diagnosed in 26 cases (96.3%) while intrinsic renal failure was seen in one case.
Of the 27 cases diagnosed with AKI, there were 19 cases with multi-factorial predisposing factors and eight cases with a single risk. The predisposing factors for AKI were peri-natal asphyxia in 18.5% of cases, sepsis in 63%, respiratory distress syndrome (RDS) in 55.6%, dehydration in 14.8%, congenital heart disease (CHD) in 7.4%, sub-galeal hematoma in 3.7%, mechanical ventilation in 51.9%, surgical operation in 11.1%, polycythemia in 3.7% and intra-ventricular hemorrhage in 3.7% of the cases [Table 2].
|Table 2: Predisposing factors for acute kidney injury in the study patients.|
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There was no significant difference in gender among cases who died (P = 0.193), while sepsis was not significantly more frequent in the patients who died (52.9%) than in those who survived (47.1%; P = 0.246). Of 14 patients who needed mechanical ventilation, nine died (64.3%). This rate was significantly higher than in those who did not need mechanical ventilation (23.1%) (P = 0.031) [Table 3].
| Discussion|| |
In our study, the occurrence of AKI was slightly higher than the 13.2% reported by Mortazavi et al;  in their study, the frequency of AKI cases diagnosed at admission was 63% and 37% after admission. However, other studies have reported that acute renal failure occurs in 3.4-24% of neonates admitted to NICUs.  In our study, there was male sex predominance and the male-female ratio was 1.3:1. Our study is in agreement with Mortazavi et al,  who reported a male-female ratio of 2:1 and with Airede et al,  who reported a male-female ratio of 3.3:1 in neonates with AKI. The high frequency of AKI in boys may be due to the susceptibility of boys to some peri-natal disorders such as sepsis and respiratory distress syndrome.  Regarding the gestational age, our study showed that the mean and standard deviation of gestational age in weeks was 34.1 ± 4.4; 40.7% of AKI cases were full-term while 59.3% were pre-term. This agrees with Steele et al,  who reported that pre-term infants with severe intrauterine growth retardation may be accompanied by renal failure, but this study disagrees with Mortazavi et al,  who reported that pre-term cases were less frequently accompanied by AKI (25.2%) than those who were full-term (70.2%). In our study, non-oliguric AKI was more frequent than oliguric AKI, with 29.6% of patients being oliguric. It is higher than that reported by Mathur et al,  who reported that the incidence of oliguria in neonatal sepsis was only 15%. However, Karlowicz and Adelman  reported that non-oliguric AKI was the most common type of AKI associated with perinatal asphyxia in full-term infants. On the other hand, this is different from the report of Mortazavi et al,  who reported that the incidence of oliguric AKI in neonates was 72.2% and Periera et al,  who reported that the incidence of oliguric AKI in neonates was 80%. Prompt management of predisposing conditions may lead to less-severe reduction in glomerular filtration rate (GFR) and better preservation of tubular function, and may account for the lower incidence of oliguria in the present study.
We found that pre-renal failure was more frequent than intrinsic renal failure (96.3% versus 3.7%); this finding is in agreement with Friedlich et al  and Vogt et al,  who reported that the most common form of AKI in neonates is pre-renal failure, which is due to renal hypo-perfusion or ischemia. On the other hand, our results disagree with Mortazavi et al,  who reported that intrinsic kidney failure was more frequent than pre-renal failure in neonates (52% versus 42.4%). In our study, three patients (11.1%) developed AKI following a surgical operation. The most common reason for surgery observed in our study was gastrointestinal anomalies, including tracheo-esophageal fistula, duodenal atresia and chronic hypertrophic pyloric stenosis in one patient each. Mortazavi et al  reported that 37.7% of their patients developed AKI following surgical operation. This shows the necessity of careful attention to peri-operative supportive management of neonates undergoing operation. Although surgery per se is not a predisposing factor of AKI, a constellation of associated risk factors such as dehydration, hypotension, hypoxia, nephrotoxic drugs, hemorrhage and infection may cause AKI in neonates undergoing surgery.  The most common predisposing factors for AKI in our patients were sepsis (63%), RDS (55.6%) and mechanical ventilation (51.9%). These findings are in agreement with Periera et al,  who reported that sepsis was the leading cause of AKI and Subramanian et al,  who reported that perinatal asphyxia and sepsis are the most common associated conditions, while Cuzzolin et al  reported that the cause of AKI in neonates is multi-factorial. However, sepsis was observed in 28.5% of the patients studied by Mortazavi et al  and in 22.2% of the patients studied by Agras et al.  A variety of mechanisms, including shock, disseminated intravascular coagulation, hemorrhage and cardiac failure may cause AKI in septic neonates. 
Moreover, in an Indian study, 26% of septic neonates developed AKI.  Peri-natal asphyxia was detected in 18.5% of our patients. This is similar to Nouri et al,  who observed AKI in
17.2% of neonates who were admitted for hypoxic ischemic encephalopathy. Renal involvement is frequent in neonates with perinatal asphyxia, which correlates with the severity of neurological damage. Mortazavi et al  reported that peri-natal asphyxia was detected in 29.8% of their patients. In addition, in the study of Airede et al, peri-natal asphyxia was found in 53.4% of AKI neonates.  Because AKI associated with asphyxia is predominantly non-oliguric, the serum creatinine level should be monitored daily in severely asphyxiated neonates.  If only urinary output is considered as an indicator of AKI, most kidney failure cases in asphyxiated neonates will be missed. Seventeen patients (63%) developed AKI at admission as discovered from their laboratory findings and ten patients (37%) developed AKI after admission, which may be due to the role of diseases and therapeutic interventions.
In this study, 14 patients (51.9%) had more than one associated contributing condition, and this may be an additional factor for the high mortality in our patients. The most common maternal risk factors observed in this study were premature rupture of membranes, diabetic mother and pre-eclampsia. In this study, the mortality rate of neonates with AKI was 44.4%. Our result was within the range of previous studies,  which have reported that the mortality rate of neonates admitted to the NICU with AKI was 35.4%.  Agras et al  reported a mortality rate of 24.4% in neonates with AKI in the NICU. In this study, the important risk factors for mortality were sepsis and mechanical ventilation. Of the 14 patients who needed mechanical ventilation, nine died (64.3%). This rate was significantly higher than in those who did not need mechanical ventilation (P = 0.031). Of 17 patients diagnosed with sepsis, nine died (52.9%). Sepsis was not significantly more frequent in the patients who died than in those who survived (P = 0.246). The mortality of AKI among septic neonates is high, and it is reported that 50-78% of the cases die. 
The main limitation of our study was the small number of cases.
| Conclusion|| |
AKI has a frequency of occurrence of 10.8% in neonates admitted to our NICU, with the pre-renal form being the most common, with variable contributing factors of which mechanical ventilation and sepsis were the most common. We can conclude that early recognition of risk factors for developing AKI may reduce the risk of its occurrence. Additionally, adequate nursing care is important for better outcome.
Conflict of interest: None
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Dr. Doaa Youssef
Department of Pediatrics, Zagazig University, Zagazig
[Table 1], [Table 2], [Table 3]