|Year : 2018 | Volume
| Issue : 4 | Page : 237-242
Prevalence and factors affecting prognosis in neonates with acute kidney injury in a neonatal intensive care unit
Deepti Damayanty Pradhan1, Bijay Kumar Meher2, Santosh Kumar Panda1, Duryodhan Samal1
1 Department of Pediatrics, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha, India
2 Department of Pediatrics, Bhima Bhoi Medical College, Balangir, Odisha, India
|Date of Web Publication||15-Oct-2018|
Dr. Bijay Kumar Meher
C/455, Sec-6, CDA, Cuttack - 753 014, Odisha
Source of Support: None, Conflict of Interest: None
Objective: To study the prevalence of acute kidney injury (AKI) in a neonatal intensive care unit (NICU) and to determine the prognostic factors affecting outcomes. Design: This was a prospective, observational study. Setting: The study was conducted at the NICU of a tertiary care hospital. Patients: Seven hundred and two neonates aged between 0 and 28 days were admitted to the NICU between February and November 2017. Of these, 53 had AKI (serum creatinine ≥1.5 mg/dL), and after applying the exclusion criteria, 50 neonates were analyzed. Methods: Frequency distribution was computed using frequency or descriptive statistics procedure. Association of factors was studied by Chi-square test of association and independent sample t-test. Main Outcome Measures: The measures were prevalence of AKI, predisposing factors, complications, need for mechanical ventilation, duration of NICU stay, and mortality. Results: The prevalence of AKI was 7.54%, with a mean age at diagnosis of 4.24 ± 2.58 days. Dehydration was present in 30% of the neonates and nephrotoxic drug use was found in 54%. Birth asphyxia was present in 50%, 78% were septicemic, and 6% had respiratory distress syndrome. The mean serum creatinine level at diagnosis was 2.15 ± 1.23 mg/dL. The mortality rate was 18%. There was no difference in mortality by sex, gestational age, birth weight, presence of sepsis, birth asphyxia, dehydration, hyponatremia, or metabolic acidosis. However, oliguria, high mean serum creatinine levels, and mechanical ventilation were associated with mortality (P < 0.05). Hyperkalemia at diagnosis of AKI was associated with higher mortality, but this was not statistically significant (P = 0.055). Decrease in urea and creatinine levels over 48 h was associated with survival (P < 0.05). Conclusions: The prevalence of AKI in the NICU is high, with poor prognostic factors including oliguria, high mean serum creatinine level, and mechanical ventilation.
Keywords: Acute kidney injury, mortality, neonatal intensive care unit, newborn, prognosis
|How to cite this article:|
Pradhan DD, Meher BK, Panda SK, Samal D. Prevalence and factors affecting prognosis in neonates with acute kidney injury in a neonatal intensive care unit. J Clin Neonatol 2018;7:237-42
|How to cite this URL:|
Pradhan DD, Meher BK, Panda SK, Samal D. Prevalence and factors affecting prognosis in neonates with acute kidney injury in a neonatal intensive care unit. J Clin Neonatol [serial online] 2018 [cited 2018 Dec 16];7:237-42. Available from: http://www.jcnonweb.com/text.asp?2018/7/4/237/243337
| Introduction|| |
Acute kidney injury (AKI) is a major contributor toward neonatal mortality and morbidity., While the exact prevalence is unknown, available data show a variable incidence of 6%–24% in neonatal intensive care units (NICUs) worldwide., The kidneys of neonates are particularly susceptible to hypoperfusion because of high renal vascular resistance, high plasma renin activity, low glomerular filtration, decreased intracortical perfusion rate, and decreased reabsorption of sodium in the proximal tubules in the first few days of life., Evaluation of the impact of AKI in very low birth weight (LBW), extremely LBW, sick near-term/term, and asphyxiated neonates demonstrated that AKI is common and associated with poor outcomes.,,,
The present study was designed to determine the prevalence of AKI in our NICU and to determine the factors affecting the outcome in these neonates.
| Methods|| |
This was a prospective, observational study carried out at Levels II and III of the NICU of a tertiary care hospital at Bhubaneswar, India. Approval was obtained from the Institutional Ethical Committee. Informed consent was obtained from the parents before enrolling the neonates in the study.
All neonates between 0 and 28 days of life admitted to the Level II and Level III NICUs were included. AKI was defined as a serum creatinine level ≥1.5 mg/dL at any time during NICU stay within the first 28 days of life.,, Neonates with multiple congenital anomalies, chromosomal anomalies, antenatally diagnosed hydronephrosis, and mothers with acute or chronic renal disease were excluded. Neonates who were referred to other hospital were excluded from the analysis. However, those babies who are in moribund condition with life support measures and left against medical advice (LAMA) on the ground of financial constraints were considered nonsurvivors and analyzed accordingly.
After obtaining written informed consent from the parents, neonates admitted to the NICU were selected for the study according to the inclusion and exclusion criteria. Serum creatinine levels were measured in all clinically suspected cases of AKI or as part of routine screening per unit protocol (those admitted before 72 h of life were screened at 72 h of life and those admitted after 72 h were screened at admission). AKI was diagnosed on the basis of serum creatinine levels.
Detailed demographic details including name, sex, gestational age (GA), mode of delivery, birth and admission weights, day of life at admission, and day of life at diagnosis of AKI were recorded. The neonates were classified as appropriate for GA (AGA), small for GA (SGA), and large for GA in accordance with the revised Fenton growth charts. Dehydration was assessed by measuring the admission weight of the neonate with respect to birth weight. A neonate was considered dehydrated if the percentage of dehydration was >3%/day; cumulative >10% in neonates with a GA ≥34 weeks, or cumulative >15% in neonates with GA <34 weeks. The clinical characteristics of the patients were also recorded. Sepsis screening and blood culture (BacT-ALERT) were performed in all patients with AKI. A diagnosis of perinatal asphyxia was made on the basis of the National Neonatal Perinatal Database Network definition in inborn babies; in the case of outborn babies, this diagnosis was made on the basis of the referral sheet or on the basis of a history of delayed cry at birth and/or symptom of seizure at presentation. A classification of birth asphyxia was made as proposed by Sarnat and Sarnat in babies at ≥36 weeks' gestation. Hypoxic-ischemic encephalopathy (HIE) Grades 0 and I represented no or mild asphyxia, whereas HIE Grades II and III represented moderate-to-severe asphyxia. Urine output was monitored and recorded from the time of diagnosis of AKI to the following 48 h. Urine output was measured by weighing the wet nappies in uncatheterized neonates and calculating it over a period of 24 h in the form of mL/kg/h. Oliguria was defined by urine output of <1 mL/kg/h.
The neonates were managed according to the unit protocols with judicious fluid and electrolyte administration, minimization of nephrotoxin exposure, and peritoneal dialysis.
Serum creatinine levels were estimated with an AU480 Analyzer (Beckman Coulter Inc., Brea, CA, USA) and by the enzymatic IFCC-IDMS method. Serum urea, creatinine, and electrolyte estimation were repeated over the next 24–48 h according to the clinical condition of the neonate and the results were recorded after 48 h. Arterial blood gas analysis was performed by radial artery puncture on the Eschweiler gas analyzer at the time of diagnosis of AKI. It was repeated over the next 24–48 h as required. Urine microscopy was performed to detect the presence of pus cells, red blood cells, and nitrites; and urine culture was also performed. Urine samples were collected by urine suprapubic aspiration. Ultrasonography of the abdomen was performed with special reference to the kidney, ureter, and bladder in all cases of AKI.
The outcomes recorded were duration of mechanical ventilation, discharge, death, LAMA, and duration of hospital stay.
Assuming a confidence level (1− α) of 95%, anticipated population proportions (P) of 50%, and absolute precision (d) of 4%, the minimum sample size required was computed to be 600. A total of 702 patients were screened for AKI during the study period between February and November 2017. AKI was diagnosed in 53 neonates. After applying the exclusion criteria, 50 neonates were included in the study.
The data were coded and entered into IBM® SPSS® Statistics 24. The frequency distribution of categorical variables was computed using a frequency procedure, and descriptive statistics were computed using a descriptive statistics procedure. The association of factors affecting mortality was studied by the cross-tabulation procedure and Chi-square test of association (categorical variables) and independent sample t-test (scale variables). For testing of hypothesis of significant difference, the cutoff P value was taken as <0.05.
| Results|| |
Of the 702 neonates admitted to the NICU during the study period, AKI was diagnosed in 53 with an estimated prevalence of 7.54% in the study population. After excluding neonates based on the exclusion criteria, 50 neonates with AKI were included for the study.
The male-to-female ratio was 2.57:1, with a mean GA at delivery of 37.2 ± 3.55 weeks [Table 1]. Twenty-six (52%) neonates were admitted on the first day of life, 27 (54%) were LBW, and 23 (46%) were SGA. Delivery by lower uterine segment cesarean section was performed in 27 (54%) neonates. The mean age at diagnosis of AKI was 4.24 ± 2.58 days. Dehydration was present in 15 (30%) neonates at the time of diagnosis of AKI. In the neonates with AKI, 39 (78%) were septicemic, 25 (50%) were asphyxiated at birth, 21 (42%) were born preterm, and 3 (6%) had respiratory distress syndrome (RDS). Culture-proven urinary tract infection was present in 2 (4%) neonates. Three neonates (6%) had structural renal disease and 17 (34%) had medical renal disease on ultrasound.
In the neonates with AKI, the mean serum creatinine level was 2.15 ± 1.23 mg/dL. Severe acidosis (pH <7.0), hyponatremia (serum sodium ≤135 mg/dL), and hyperkalemia (serum potassium >5.5 mg/dL) were seen in 9 (18%), 28 (56%), and 18 (36%) neonates, respectively. The causes for the AKI were sepsis, nephrotoxic drug use, asphyxia, and dehydration in 39 (78%), 27 (54%), 25 (50%), and 15 (30%) neonates, respectively. Twenty neonates (40%) had oliguria, and the underlying etiology did not play a role in the presence or absence of oliguria [Table 2]. The final outcomes were recovery to discharge in 31 (62%) and death in 9 (18%) due to different conditions. Renal replacement therapy (peritoneal dialysis) was offered to four neonates as per the unit protocol.
|Table 2: Oliguria in neonate with acute kidney injury with reference to etiology|
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[Table 3] shows the different parameters affecting mortality. Of the 50 neonates with AKI, 31 (62%) were discharged from the NICU. There was no difference in mortality by sex, GA, birth weight, presence of sepsis, birth asphyxia, dehydration, hyponatremia, or metabolic acidosis. However, the presence of oliguria, high mean serum creatinine level, and use of mechanical ventilation were significantly associated with high mortality. Hyperkalemia at diagnosis of AKI was associated with higher mortality, but this was not statistically significant.
[Table 4] shows the mean changes in laboratory parameters and urine output over the next 48 h following diagnosis of AKI, and a comparison between these changes in the group who survived and the group who did not. Babies who were LAMA were critically ill neonates and discontinued treatment due to different social and financial reasons, and therefore, their outcome was analyzed as nonsurvivors. Decreasing serum urea and creatinine over 48 h was associated with a decrease in mortality (P = 0.013, 0.039 respectively). However, changes in serum sodium, potassium, and urine output did not affect mortality.
|Table 4: Mean changes in laboratory parameters and urinary output predicting outcome in neonate with acute kidney injury|
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| Discussion|| |
This study reports the prevalence of AKI in a tertiary-care NICU and evaluates the different factors affecting mortality.
The prevalence of AKI in our study was 7.54%, which was comparable to that in the study by Timovska et al., who reported a prevalence of 6.5%. In contrast, Youssef et al. reported a higher prevalence of 10.8%, whereas a Turkish study reported a lower prevalence of 3.4%., In a study period of 24 years, Vachvanichsanong et al. reported a prevalence of 0.9%–6.3%. A previous study from India found the incidence of AKI in newborns to be 3.9/1000 live births and 34.5/1000 newborns admitted to the NICU.
In the present study, 29 (58%) neonates were born full term, compared to 40.7% in the study by Youssef et al. This may be because of a large number of term babies referred to our unit for sepsis and asphyxia. The major predisposing factors for AKI were reported by Timovska et al. to be asphyxia, sepsis, and prematurity. These findings were similar to those of our study. Similarly, Askenazi et al. reported predisposing factors for AKI to be sepsis, RDS, mechanical ventilation, perinatal asphyxia, dehydration, and surgical operations in 63%, 55.6%, 51.9%, 18.5%, 14.8%, and 11.1%, respectively. However, Timovska et al. reported use of nephrotoxic drugs in 92% of neonates in their study.
The mortality rate in our study was 38%, similar to that in the study by Timovska et al., who reported a mortality rate of 32% in 770 neonates with AKI admitted to their NICU, and higher in the group with congenital heart disease and those on assisted ventilation. In a multicenter, multinational, observational cohort study on incidence and outcomes of neonatal AKI (AWKEN) by Jetton et al. infants with AKI had higher mortality (9.7%) compared to those without AKI. In the present study, we found 10 (20%) of patients LAMA. In this part of the world, a significant group (10%–15%) of critically sick neonate got LAMA mostly due to financial constraint and poor outcome of the neonates., In a study by Tellier et al., oliguria and multi-organ failure were shown to be prognostic factors. Agras et al. demonstrated that intrinsic AKI, need for dialysis, and mechanical ventilation were associated with higher mortality rates, whereas no significant correlation was found between mortality rate and prematurity, serum blood urea nitrogen, creatinine levels, and perinatal factors. A study by Esfandiar et al. described hyaline membrane disease, use of mechanical ventilation, need for surfactant use, low Apgar score, high blood PCO2 level, high serum creatinine level, and LBW as being related to mortality. We observed an association between mortality and the need for mechanical ventilation, oliguria, and serum creatinine in neonates with AKI. Several theories have been proposed in support of this hypothesis. Major mechanisms involved compromised renal blood flow because of hypercapnia or hypoxemia and barotrauma-induced pulmonary inflammatory reaction, leading to a secondary systemic inflammatory reaction. A recent NICU study from Turkey also reported a similar association between oliguria and mechanical ventilation.
| Conclusion|| |
The limitations of the study are as follows: (1) It is a single-center NICU study and thus does not reflect the prevalence of AKI in the community or hospital. (2) The recent definition of AKI utilizes baseline creatinine levels, rising creatinine levels, and urine output; however, in resource-poor settings, documentation is practically difficult, and the present study used a single criterion of serum creatinine level ≥1.5 mg/dL for diagnosis of AKI. (3) Risk factor analysis was beyond the scope of the study; thus, the controls were not analyzed. (4) Due to the small sample size, regression analysis could not be performed to find out different parameters affecting prognosis independently.
The prevalence of AKI in the NICU was high, with a high mortality rate. Sepsis, nephrotoxic drug use, asphyxia, and dehydration were causative factors for neonatal AKI. There was no difference in mortality in neonates with AKI with respect to sex, GA, birth weight, presence of sepsis, birth asphyxia, dehydration, hyponatremia, or metabolic acidosis. However, oliguria, high mean serum creatinine level, and mechanical ventilation were significantly associated with mortality. Hyperkalemia at diagnosis of AKI was also associated with higher mortality although this was not statistically significant. A decrease in serum urea and creatinine levels over 48 h was significantly associated with decreased mortality.
We thank Dr. Bijay Bhusan Nanda for his statistical guidance and Mr. Francis Satpathy for his help for drafting the manuscript. We would like to thank Editage (www.editage.com) for English language editing.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]