Global health systems have been significantly impacted by the COVID-19 pandemic brought on by SARS-CoV-2. At first, it was thought that children's illness progression was less severe than that of adults'. But further research showed that children who had underlying chronic conditions, such as nephrotic syndrome, chronic kidney disease (CKD), or immunosuppressive treatments, are more vulnerable to severe COVID-19 and its consequences.

In hospitalised COVID-19 patients, acute kidney injury (AKI) has become a serious consequence, especially in adults. There is a dearth of information on paediatric AKI in relation to COVID-19, particularly in LMICs. To enhance clinical treatment and results, it is crucial to comprehend the burden, risk factors, and consequences of AKI in hospitalised children with COVID-19.

Objectives

1. To estimate the prevalence of AKI in hospitalised children from 1 month to 18 years with confirmed COVID-19 infection.

2. To study the risk factors and immediate outcome of AKI in hospitalised children with COVID19 infection.

Study Design

Retrospective descriptive study.

Study Period

January 2022 to August 2022.

Study Setting

Indira Gandhi Institute of Child Health, Bangalore.

Study Population

All hospitalized children aged 1 month to 18 years with confirmed COVID-19 by RT-PCR were included.

Inclusion Criteria

• Children aged 1 month to 18 years.
• Confirmed COVID-19 by RT-PCR.

Exclusion Criteria

• Suspected COVID-19 cases with negative RT-PCR.
• Patients discharged against medical advice.
• CKD stage V patients.
• Patients with bilirubin >5 mg/dl.

Data Collection

Detailed history, clinical examination, investigations and treatment provided including dialysis details were recorded in a standardized proforma.

Demographic, socioeconomic details, symptoms and severity of COVID -19, history of contact, systemic symptoms, were noted.

AKI Definition

The Kidney Disease Improving Global Outcomes (KDIGO) criteria from 2012, which were based on variations in serum creatinine, were used to classify AKI. Some patients did not have access to baseline serum creatinine, thus the Hoste's equation was used to approximate it. During the epidemic, logistical limitations prevented the adoption of urine output parameters.

Investigations

• Hemogram
• Metabolic profile
• Serum creatinine (Erba Mannheim XL system packs)
• Inflammatory markers (CRP, ferritin, D-dimer, etc.)
• Chest X-ray (where indicated)

Management Protocols

• COVID-19 management followed WHO guidelines.
• AKI management included supportive therapy, fluid management, and renal replacement therapy when indicated.
• Shock was managed per Pediatric Advanced Life Support (PALS) guidelines.
• Pneumonia was managed with appropriate antibiotics per institutional protocol.
• MIS-C was diagnosed per CDC criteria and managed with intravenous immunoglobulin and methylprednisolone.

Outcomes Assessed

• Prevalence of AKI.
• Predictors of AKI.
• Mortality and discharge rates.
• Need for dialysis or intensive care.
• Length of hospital stay.

Statistical Analysis

Data were entered into Microsoft Excel 2010 and analyzed using SPSS version 19.

• Descriptive statistics: mean, standard deviation, and proportions.
• Inferential statistics: unpaired t-test and Fisher’s exact test.
• Univariate and multivariate regression analyses to identify risk factors for AKI and mortality.
• Significance threshold: p-value <0.05.

Table 1: Baseline Characteristics of Study Population (N=210)

The baseline characteristics of the study cohort, which comprised 210 children with COVID-19, are compiled in Table 1. There was a small male predominance (58%), and the mean age was 7.6 ± 4.2 years. 8.5% of children had pre-existing chronic kidney disease (CKD), and 7.6% had nephrotic syndrome that required immunosuppressants. In 14.2% of cases, children had multisystem inflammatory syndrome (MIS-C), In 21% of instances, severe COVID-19 was recorded, Hospital stays lasted 8.2 ± 3.5 days on average. An overview of the research cohort’s underlying medical problems and illness severity is given by these baseline characteristics.

Table 2: Prevalence of Acute Kidney Injury (AKI) in COVID-19-Positive Children

The frequency and severity of acute kidney damage (AKI) in children infected with COVID-19 are shown in Table 2. AKI developed in 38 children (18.1%) out of all hospitalised cases. Most had Stage 1 AKI (63.2%), followed by Stage 2 (21.1%) and Stage 3 (15.7%) according to KDIGO staging. Notably, 6 children (15.7%) needed dialysis, suggesting that a fraction of individuals had substantial renal failure. These results demonstrate that although a considerable percentage of children with COVID-19 had AKI, the majority of cases were mild to moderate, with a lower proportion developing severe symptoms that need dialysis.

Table 3: Risk Factors for AKI in Hospitalized COVID-19-Positive Children

The risk factors for acute kidney damage (AKI) in children hospitalised with COVID-19 are shown in Table 3. The AKI group had a considerably higher prevalence of severe COVID-19 (52.6%) compared to the non-AKI group (13.9%) (p=0.001). Additionally, children with AKI had a higher prevalence of multisystem inflammatory syndrome (MIS-C) (26.3%) than children without AKI (11.6%) (p=0.005). Compared to the non-AKI group, 15.8% of children with AKI had pre-existing chronic kidney disease (CKD) (p=0.02). Furthermore, there was a significant correlation between an elevated incidence of AKI and nephrotic syndrome on immunosuppressants (13.2% vs. 6.4%, p=0.03). These results demonstrate that hospitalised COVID-19-positive children are more likely to develop AKI if they had pre-existing renal diseases and comorbidities.

Table 4: Outcomes of COVID-19-Positive Children with and without AKI

The results of COVID-19-positive children with and without acute kidney damage (AKI) are shown in Table 4. The AKI group saw a considerably greater rate of intensive care unit hospitalisation (57.9%) than the non-AKI group (17.4%) (p=0.001). Additionally, children with AKI had a longer mean hospital stay (11.4 ± 4.2 days) than children without AKI (7.5 ± 2.8 days) (p=0.003). Furthermore, none of the kids in the non-AKI group needed dialysis, but 15.8% of the kids in the AKI group did (p=0.001). The AKI group had a significantly higher mortality rate (21.1%) than the non-AKI group (3.5%) (p=0.004), suggesting that AKI is linked to worse clinical outcomes in children with COVID-19.

Important new information on Acute Kidney Injury (AKI) in hospitalised children with COVID-19 is provided by this study. Comparable to prior paediatric research on COVID-19-associated AKI, our results show that 18.1% of the study population acquired AKI. According to earlier studies, the prevalence of AKI in paediatric COVID-19 patients ranges from 15% to 25%, dependent on the severity of the illness, comorbidities, and hospital environment. Nicastro E et al., Natale P et al.^[1,2].

Prevalence and Severity of AKI

KDIGO Stage 1 was the most prevalent (63.2%) among the 38 children (18.1%) with an AKI diagnosis, whereas Stages 2 and 3 accounted for 21.1% and 15.7% of cases, respectively. These findings are in line with research by Morello W et al. and Gabarre P et al., which found that a greater percentage of paediatric COVID-19 patients had Stage 1 AKI ^[3,4]. Early detection, supportive care, and timely fluid resuscitation may have contributed to our cohort's comparatively decreased incidence of Stage 3 AKI. Nonetheless, dialysis was necessary in 15.7% of AKI patients, underscoring the serious consequences of renal failure in certain kids.

Risk Factors for AKI in COVID-19-Positive Children

Our study identified several significant risk factors for AKI, including severe COVID-19 (p=0.001), MIS-C (p=0.005), pre-existing CKD (p=0.02), hypertension (p=0.01), and diabetes mellitus (p=0.02).

• The greatest predictor of AKI was severe COVID-19, which affected 52.6% of children in the AKI group and 13.9% of children in the non-AKI group. This is consistent with findings by Ronco C et al., who discovered that severe COVID-19 exacerbates multi-organ failure and systemic inflammation, which leads to renal impairment.^[5].
• Multisystem Inflammatory Syndrome in Children (MIS-C) was found in 26.3% of instances with AKI, indicating a robust correlation between kidney damage and hyperinflammatory conditions. This result is consistent with earlier research by Li J et al. and Kwak BO et al., which discovered that endothelial damage, proinflammatory cytokines, and cardiac dysfunction all contribute to AKI in MIS-C patients.^[6,7].
• Nephrotic syndrome and pre-existing CKD were also important risk factors; in 15.8% of AKI patients, CKD was a history. According to Kikuchi K et al., CKD patients with COVID-19 have a greater risk of death and AKI because of their reduced renal reserve and heightened vulnerability to viral infections.^[8].

Outcomes of AKI in COVID-19 Children

Children who developed AKI had poorer clinical outcomes compared to those without AKI.

• The AKI group saw considerably higher ICU admission rates (57.9% vs. 17.4%, p=0.001). This result is in line with that of Gabarre et al.,^[4] who found that AKI dramatically raises the demand for intense supportive care and the load on the intensive care unit. ^[4].
• The AKI group had a substantially longer mean hospital stay (11.4 days vs. 7.5 days, p=0.003), suggesting that AKI helps paediatric COVID-19 patients recover more slowly. Research by Weinbrand-Goichberg et al. and Canpolat N et al. has also shown that consequences such fluid imbalances, metabolic abnormalities, and secondary infections caused by AKI result in extended hospital admissions.^[9,10].
• AKI was linked to a noticeably greater death rate (21.1% vs. 3.5%, p=0.004). This is consistent with research by Sanchez LO et al., which found that COVID-19 patients with AKI are more likely to die from complications associated to sepsis and multi-organ failure.^[11].

Comparison with Other Studies

Our findings are consistent with international data from large pediatric COVID-19 cohorts, where AKI prevalence ranges from 15%-25%^[3,5]. The strong association between MIS-C and AKI has been reported globally, with recent systematic reviews highlighting the role of hyperinflammation, endothelial injury, and cytokine storm in kidney dysfunction. Li J et al. ^[6], Kwak BO et al. ^[7].

However, compared to high-income countries, our study highlights the burden of AKI in a resource-limited setting, where limited access to advanced nephrology care, dialysis, and ICU support may exacerbate the impact of AKI on outcomes Chan L et al. ^[12].

Strengths and Limitations Our results are in line with global data from sizable paediatric COVID-19 cohorts, which show that the prevalence of AKI varies between 15% and 25% [3,5].  Global reports have shown a substantial correlation between MIS-C and AKI, and recent systematic reviews have highlighted the significance of cytokine storm, endothelial damage, and hyperinflammation in renal failure Li J et al. ^[6], Kwak BO et al. ^[7].

Our study, however, emphasises the burden of AKI in a resource-constrained situation, where inadequate access to advanced nephrology treatment, dialysis, and intensive care unit assistance may worsen the impact of AKI on outcomes, in contrast to high-income nations Chan L et al.^[12].

Advantages and Drawbacks

This study offers significant epidemiological insights as it is one of the rare paediatric studies from India to examine AKI in infants with COVID-19. The validity of our findings is reinforced by the large sample size (N=210) and the application of standardised KDIGO criteria.

This study is among the few pediatric studies from India to explore AKI in COVID-19 children, providing important epidemiological insights. The large sample size (N=210) and use of standardized KDIGO criteria strengthen the validity of our findings.

However, some limitations exist:

1. Retrospective design: Since the study relies on hospital records, information about fluid balance and urine output may be lacking.
2. Limited evaluation of biomarkers: Although creatinine was utilised to diagnose AKI, more recent biomarkers (such as NGAL and cystatin C) may enhance early identification.
3. Short-term follow-up: More research is required to determine the long-term renal outcomes in paediatric AKI survivors who have recovered from COVID-19.
   
   

Clinical Implications and Future Directions

Given the significant burden of AKI in pediatric COVID-19, this study underscores the need for early renal function monitoring in hospitalized children. Based on these findings, we recommend:

• All hospitalised COVID-19 children have routine serum creatinine testing both upon admission and during their stay.
• More thorough screening for AKI risk factors in kids with pre-existing CKD, MIS-C, or severe COVID-19.
• Post-COVID AKI survivors are monitored longitudinally to evaluate their long-term renal function and the development of chronic kidney disease.
• Additional prospective research with bigger sample sizes to confirm these results and improve paediatric AKI treatment protocols.

Important new information on the occurrence and consequences of AKI in children with COVID-19 is provided by this study. Pre-existing renal disorders and severe illness are important risk factors for AKI, which affects one in five hospitalised children.
Clinical Implications:

• In situations of severe COVID-19 and MIS-C, early AKI monitoring can enhance patient outcomes.
• When children with COVID-19 are admitted to hospitals, standard renal function screening should be taken into account.
• To develop evidence-based paediatric nephrology recommendations for COVID-19, further prospective trials are required.

1. Nicastro E, Verdoni L, Bettini LR, Zuin G, Balduzzi A, Montini G, Biondi A, D'Antiga L. COVID-19 in Immunosuppressed Children. Front Pediatr. 2021 Apr 29;9:629240. doi: 10.3389/fped.2021.629240.
2. Natale P, Zhang J, Scholes-Robertson N, Cazzolli R, White D, Wong G, Guha C, Craig J, Strippoli G, Stallone G, Gesualdo L, Jaure A. The Impact of the COVID-19 Pandemic on Patients With CKD: Systematic Review of Qualitative Studies. Am J Kidney Dis. 2023 Oct;82(4):395-409.e1. doi: 10.1053/j.ajkd.2023.04.001.
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