Study setting and design
This retrospective, facility-based, unmatched case-control study was conducted in the Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. All children aged one month to 18 years who were admitted to the PICU (PICU) at Tikur Anbessa Specialized Hospital between January 2011 and December 2021 were included in this study.
Eligibility criteria
Children who had confirmed AKI were cases and unmatched non-AKI patients admitted to the same hospital during the study period were included. However, we excluded critically ill children who had short intensive care unit stays (<24h) and had no laboratory investigation of serum creatinine or urine output measurement during their PICU admission. Moreover, we excluded critically ill children admitted with known chronic renal diseases and those who underwent renal transplants.
Sample Size and procedure
The sample size was computed using the Statcalc software. The software application Epi–Info version 7.2.5.0. with the following assumptions: the proportion of mortality rate among controls to be 8.7% and of the cases 26.5 % [20], 95 % confidence interval, 90 % power of the study, control to case ratio of 2:1, and odds ratio of 3.78. We add a 10 % non-response rate of 23. Thus, the required sample size was 253 (85 cases and 168 controls).
The study was conducted at Tikur Anbessa specialized hospital in Addis Ababa, Ethiopia, and data were collected from the PICU. All cases were critically ill children with confirmed AKI who were admitted to the PICU between January 2011 and December 2021. For each case, two controls were selected using a systematic random sampling method. According to data obtained from the Tikur Anbessa specialized hospital intensive care unit, 2468 children were admitted to the PICU, of which 2374 children did not have AKI and 94 children had AKI. Of those 85 cases and 168 controls were selected.
Data collection
Data were collected through a review of medical records using a pre-tested structured data abstraction checklist developed and validated by experts. Case: Children with ≥0.3 mg/dL or ≥ 26.5 mmol/L serum creatinine level increase from the baseline within 48hrs, or 1.5 to 1.9 times increment in serum creatinine from the baseline within 7 days, or urine output < 0.5 ml/kg/h for 6-12hours [2]. Control: Children who had no increment of serum creatinine level or urine output and did not fulfill for AKI using kidney disease improving global outcomes criteria. Baseline creatinine: Take as normal serum creatinine of children to the age; 0.2-0.4 mg/dL for infants; 0.3-0.7 mg/dL for 1-12 years; 0.5- 1.0 mg/dL for 13-18 years [21,22].
Critically ill child: Child with two or more of the following signs and symptoms such as; impaired consciousness, shock, severe respiratory distress; (severe lower chest wall in drawing, cyanosis, grunting, stridor/wheezes, hypoxemia of SPO2 < 88% or those in gasping or apneic state) severe dehydration, generalized edema, acute bleeding, severe burn, severe pallor with signs of heart failure, severe malaria, anemia <5g/dl, and history of two or more episodes of convulsions [23].
Sepsis: two or more of the following systemic inflammatory response syndrome criteria; ( fever of more than 38°C or less than 36°C, heart rate >2SD per age group, respiratory >2SD breaths per minute, abnormal white blood cell count (>12,000/µL or <4,000/µL), an increase in C Reactive protein (CRP), or confirmed by blood culture).
Nephron toxic drugs: Drugs and agents considered to cause nephrotoxicity including non-steroidal anti-inflammatory drugs, antibiotics, amphotericin-B, antiviral agents, angiotensin-converting enzyme inhibitors, calcineurin inhibitors, radiocontrast media, and cytostatic agents.
Hypertension: Children’s blood pressure above the 95th percentile for the same age, sex, and height.
Data quality control
Data quality was assured through a wise and carefully designed standardized checklist. A pretest was carried out on 12 (5%) medical charts at St. Paul’s Hospital, Millennium Medical College, before actual data collection. The content validity index was calculated by seven experts, the result was 0.93. Two days of training were provided to all the data collectors and supervisors. The data collection process was closely supervised and the completeness of each questionnaire was checked daily by supervisors and the principal investigator. During the data cleaning, a logical checking technique was employed to identify errors. Finally, double data entry was performed to verify data consistency.
Ethical consideration
This study was conducted in accordance with the declaration of Helsinki. The study was ethically cleared and approved by the Ethical Review Committee of the Addis Ababa University College of Health Science, School of Nursing and Midwifery (Ref. No: AAUMF03-008). Following approval, an official written letter of cooperation was given to the administrative health bureau and facilities. Written informed consent was obtained from the parents of the children involved in the study. Confidentiality was ensured throughout the process.
Data processing and analysis
Data were entered using Epi data 3.1 version and analyzed using SPSS software 25.0 version. Cross-tabulation was performed to determine the sample characteristics. Descriptive statistics were used to describe the characteristics using tables, figures, and texts. AKI was labeled as Yes (coded as 1) for cases and No for controls (coded as 0). The factors associated with AKI were assessed using bivariate and multivariable logistic Regression analyses. All variables with a p-value <0.25 in the bi-variable regression were added to the multivariable analysis after checking for multicollinearity. Associations were described using an adjusted odds ratio (AOR) and with a 95% confidence interval (CI). Multi-collinearity was checked using a variance inflation factor (>10) and standard error (>2). Goodness-of-fit was checked using the Hosmer-Lemeshow test (>0.05). Finally, statistical significance was set at a p-value <0.05.