Abstract

Introduction: Severe malaria is a major cause of morbidity and is frequently complicated by Acute Kidney Injury (AKI). This study aimed to identify the factors associated with AKI in children with severe malaria at the Borgou and Alibori Departmental Teaching Hospital (CHUD-B/A) in Benin.

Methods: We conducted a prospective observational study from June 1 to August 31, 2024. All children aged 1 month to 15 years hospitalized for severe Plasmodium falciparum malaria were enrolled consecutively. AKI was defined and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 criteria. Bivariate analysis was performed to identify factors associated with AKI.

Results: Of the 204 children with severe malaria, 43 (21.1%) developed AKI. The mean age was 57.1 ± 37.6 months. AKI was classified as Stage 1 in 46.5% of cases, Stage 2 in 4.7%, and Stage 3 in 48.8%. Oliguria was observed in 86.0% of patients with AKI. The development of AKI was significantly associated with the presence of hepatomegaly (OR=11.1, p<0.001), splenomegaly (OR=2.8, p=0.004), coma (OR=2.8, p=0.001), jaundice (OR=5.4, p=0.03), and hemoglobinuria (OR=4.8, p<0.001).

Conclusion: AKI is a frequent and severe complication of pediatric malaria in this setting, strongly associated with clinical markers of high parasite burden and hemolysis. Early identification of these risk factors is crucial for improving patient outcomes.

Keywords

Acute Kidney Injury; Child; Severe Malaria; Benin

Introduction

Malaria is a parasitic, feverish disease that is transmitted to humans by the bite of the female Anopheles mosquito [1]. According to the World Health Organization in 2022, the number of malaria cases and the number of deaths due to malaria was estimated at 249 million and 608,000 respectively in 85 countries [2]. Malaria is the leading reason for consultation and hospitalization according to health statistics from the Ministry of Health in Benin [3]. It is indeed a real public health problem. Among the five species responsible for malaria, P falciparum is the most formidable and the cause of several complications including acute renal failure [4].

The pathophysiology of malaria-associated AKI is complex and multifactorial. The primary mechanisms are thought to involve a combination of hemodynamic disturbances, such as the mechanical obstruction of renal microvasculature by parasitized red blood cells; immune-mediated glomerular injury; and severe metabolic disruptions [5-7]. The clinical manifestation of these processes can range from electrolyte imbalances to glomerulonephritis, with AKI being the most frequently described functional impairment [8,9]. The incidence of AKI in severe malaria varies widely in the literature, from 0.56% to 64% [10,11], and a previous study in Benin found a frequency as high as 43.90% in children with severe malaria [4].

Clinical signs such as hepatomegaly and splenomegaly are indicators of a high systemic parasite burden and extensive sequestration, a process which can cause renal microcirculatory plugging and ischemia [5,6]. Similarly, hypoglycemia is a marker of severe metabolic distress and hepatic dysfunction, which can further compromise renal function [7]. Given this complex interplay, we hypothesized that these key clinical markers of disease severity would be significant predictors of AKI in children with severe malaria.

Therefore, the objective of this study was to investigate the factors associated with an increased risk of acute kidney injury in children treated for severe malaria at the Borgou and Alibori Departmental Teaching Hospital in Benin in 2024.

Methods

Study design and setting

This was a prospective observational study conducted in the pediatric department of the Borgou and Alibori Departmental Teaching Hospital (CHUD-B/A) in Parakou, Benin. Data were collected over a three-month period from June 1, 2024, to August 31, 2024.

Study population and sampling

All children hospitalized for severe malaria during the study period were prospectively screened for eligibility. A consecutive sampling method was used, wherein all patients meeting the inclusion criteria were enrolled.

Inclusion criteria:

• Age between 1 month and 15 years.

• A diagnosis of severe Plasmodium falciparum malaria.

• Written informed consent provided by a parent or legal guardian.

Exclusion criteria:

• Patients for whom serum creatinine could not be measured at baseline (Day 0) and at 48 hours (Day 2).

• Patients for whom urine output could not be reliably collected and monitored.

Definitions

Severe malaria

The diagnosis of severe malaria was defined according to the World Health Organization (WHO) 2000 criteria, requiring a positive thick and thin blood smear for Plasmodium falciparum along with at least one clinical or laboratory sign of severity [9].

Acute Kidney Injury (AKI): The presence and staging of AKI were defined using the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 criteria [12]. AKI was diagnosed based on at least one of the following:

• An increase in serum creatinine by ≥ 0.3 mg/dL (≥ 26.5 µmol/L) within 48 hours.

• An increase in serum creatinine to ≥1.5 times the baseline value.

• Urine volume <0.5 mL/kg/h for at least 6 hours.

• The stages of AKI were classified as follows [12]:

• Stage 1: Increase in serum creatinine to 1.5-1.9 times baseline OR a urine output of <0.5 mL/kg/h for 6-12 hours.

• Stage 2: Increase in serum creatinine to 2.0-2.9 times baseline OR a urine output of <0.5 mL/kg/h for ≥12 hours.

• Stage 3: Increase in serum creatinine to ≥3.0 times baseline, OR initiation of renal replacement therapy, OR a urine output of <0.3 mL/kg/h for ≥24 hours or anuria for ≥12 hours.

Data Collection

Data were collected using a standardized survey form. Sociodemographic data were collected through face-to-face interviews with the parents or guardians. Clinical data were obtained from the medical history and a physical examination upon admission.

Laboratory investigations included

• Blood samples: Thick and thin blood smears for parasite density, complete blood count, blood glucose, urea, serum creatinine, and electrolytes.

• Urine samples: Urinalysis by dipstick and microscopic examination of the urinary sediment.

Serum creatinine was measured at admission (Day 0) and again at 48 hours (Day 2) using the Jaffé method [13]. Urine was collected using sterile containers or pediatric urine collection bags, with collection supervised by the healthcare team.

Statistical Analysis

Data were entered and managed using Microsoft Excel 2019 and analyzed with SPSS software, version 28.0.1.0. Categorical variables were described as frequencies and percentages, while continuous variables were described using means and Standard Deviations (SD) or medians and Interquartile Ranges (IQR).

To identify factors associated with AKI, bivariate analyses were performed. The Chi-square test or Fisher’s exact test was used to compare proportions. Unadjusted Odds Ratios (OR) and their 95% Confidence Intervals (CI) were calculated to assess the strength of association. A p-value of <0.05 was considered statistically significant.

A multivariate logistic regression analysis was planned to identify the independent predictors of AKI. However, it was pre-specified that this analysis would only be performed if the number of cases in the subgroups was sufficient to ensure the stability and reliability of the model (a common rule of thumb is at least 10 events per predictor variable).

Ethical Considerations

The study protocol was reviewed and approved by the Local Ethics Committee for Biomedical Research of the University of Parakou (Reference No. 500/2024/CLERB-UP/P/SP/R/SA). Authorization was obtained from the hospital administration before the study began. Written informed consent was obtained from a parent or legal guardian for each child prior to enrollment in the study. Participants were assured of the anonymity and confidentiality of their data.

Results

Study population and cohort characteristics

During the study period, a total of 488 children were admitted to the pediatric department. Of these, 204 were diagnosed with severe malaria, corresponding to a hospital frequency of 41.8% for this condition.

The mean age of the 204 children with severe malaria was 57.1 ± 37.6 months. The cohort included 101 females (49.5%), with a maleto-female sex ratio of 1.06. A majority of the children (141/204, 69.1%) resided in rural areas.

Frequency and severity of acute kidney injury (AKI)

Among the 204 children with severe malaria, 43 developed AKI, resulting in an overall incidence of 21.1%.

The severity of AKI, according to the KDIGO 2012 staging criteria, was distributed as follows: stage 1 (46.5%), stage 2 (4.7%), and stage 3 (48.8%).

Comparison of patient characteristics

The sociodemographic, clinical, and laboratory characteristics of patients who developed AKI (n=43) were compared to those who did not (n=161). Children who developed AKI were significantly more likely to present with signs of severe disease, including coma, jaundice, hemoglobinuria, and hepatosplenomegaly. Coma was significantly more frequent among children with AKI (51.2% vs. 13.7%, p < 0.001), as were jaundice (9.3% vs. 1.9%, p = 0.03), hemoglobinuria (62.8% vs. 6.8%, p < 0.001), and hepatomegaly (79.1% vs. 16.1%, p < 0.001). Splenomegaly was also more prevalent in the AKI group (34.9% vs. 21.1%, p = 0.05). While severe anemia, hypoglycemia, and hyperparasitemia were observed in both groups, differences were not statistically significant. Notably, hyponatremia was found in 50% of tested AKI cases, compared to only 2.5% in the non-AKI group (p < 0.001).

The baseline characteristics of both groups are detailed in [Table 1].

	No AKI (n = 161)	AKI (n = 43)	p-value
Sociodemographic
Age (months), mean ± SD	57.0 ± 37.7	57.3 ± 37.6	0.96
Male sex, n (%)	78 (48.4)	25 (58.1)	0.26
Rural residence, n (%)	116 (72.0)	25 (58.1)	0.08
Clinical Presentation
Coma, n (%)	22 (13.7)	22 (51.2)	<0.001
Jaundice, n (%)	3 (1.9)	4 (9.3)	0.03
Hemoglobinuria, n (%)	11 (6.8)	27 (62.8)	<0.001
Hepatomegaly, n (%)	26 (16.1)	34 (79.1)	<0.001
Splenomegaly, n (%)	34 (21.1)	15 (34.9)	0.05
Laboratory Findings
Severe anemia (<5 g/ dL), n (%)	25 (15.5)	10 (23.3)	0.22
Hypoglycemia (<0.7 g/ dL), n/N (%)	5/161 (3.1)	2/43 (4.7)	0.65
Hyperparasitemia (>250,000/µL), n (%)	22 (13.7)	9 (20.9)	0.23
Hyponatremia (<135 mmol/L), n/N (%)	4/161 (2.5)	4/8 (50.0)	<0.001
Thrombocytopenia (<150 G/L), n (%)	87 (54.0)	28 (65.1)	0.19

Table 1: Baseline Characteristics of Children with Severe Malaria, By AKI Status.

Urine output and urinary sediment in AKI patients

Among the 43 patients with AKI, 41 (95.3%) exhibited abnormal diuresis. Oliguria was observed in 37 patients (86.0%) and anuria in 4 patients (9.3%). Microscopic examination of urinary sediment in the AKI group revealed granular casts (41.9%), white blood cells (32.6%), tubular cells (23.3%), and pigment casts (7.0%).

Therapeutic management of AKI patients

All 43 patients with AKI were treated with intravenous artesunate. Supportive care included antipyretics (81.4%), packed red blood cell transfusions (83.7%), anticonvulsants (46.5%), and nutritional supplements (32.6%). Fluid management consisted of fluid restriction in 51.2% of cases and hydration in 40.8%.

Factors associated with Acute Kidney Injury

In bivariate analysis, several clinical factors were significantly associated with the odds of developing AKI. While a multivariate analysis was initially planned, it was not performed because the number of patients in key predictor subgroups was insufficient to generate a stable and reliable model. The unadjusted Odds Ratios (OR) for factors associated with AKI is presented in [Table 2].

	Odds Ratio (OR)	95% Confidence Interval (CI)	p-value
Clinical Signs
Hepatomegaly	11.1	4.9 – 25.0	<0.001
Splenomegaly	2.8	1.4 – 6.2	0.004
Coma	2.8	1.3 – 5.7	0.001
Jaundice	5.4	1.2 – 25.1	0.03
Hemoglobinuria	4.8	2.2 – 10.3	<0.001
Prostration	0.3	0.2 – 0.7	0.001
Malaria Forms
Cerebral Malaria	8	3.5 – 18.3	<0.001
Hemolytic Malaria	6.1	2.8 – 13.2	<0.001
Neurological Malaria	0.1	0.01 – 0.4	<0.001

Table 2: Bivariate Analysis of Factors Associated with Acute Kidney Injury.

Discussion

This study investigated the risk factors associated with Acute Kidney Injury (AKI) in children with severe malaria in Parakou, Benin. Our findings indicate a high incidence of AKI (21.1%) in this population. The primary factors associated with the development of AKI were clinical markers of high parasite burden and sequestration (hepatomegaly, splenomegaly, coma) and severe hemolysis (jaundice, hemoglobinuria).

Incidence of acute kidney injury

The 21.1% incidence of AKI in our cohort is consistent with the 20.3% reported by Condé et al. in Guinea [14] but lower than the 64% found by Conroy et al. in a Ugandan reference hospital [11]. Other studies have reported significantly lower frequencies, such as 0.6% in Cotonou, Benin [10], 0.7% in Gabon [15], 2% in Ghana [16], and 6.6% in Niger [17]. This wide variation in reported incidence is likely attributable to differences in study populations, the specific criteria used to define AKI (e.g., KDIGO vs. RIFLE), the biomarkers measured, and the baseline level of healthcare available in the study settings.

Sociodemographic factors

The mean age of children with AKI in our study was approximately 4.7 years (57.3 ± 37.6 months), with the 2-to-5-year-old age group being the most represented (46.5%). The literature presents heterogeneous findings regarding age, some authors reported a higher mean age, such as 7 years and 1 month reported by Lalya et al. in Benin [10] and 102.7 ± 67.7 months reported by Essola et al. in Gabon [15]. A study in Senegal in 2022 found a median age of 93.3 months [18]. Conversely, a lower mean age of 2.5 ± 0.75 years was observed in a 2017 study in Niamey [17]. This variability suggests that while age may influence susceptibility, all pediatric age groups are at risk of developing AKI during a severe malaria episode.

Interpretation of factors associated with AKI

Our bivariate analysis identified several key factors associated with an increased risk of AKI, providing insight into the underlying pathophysiology.

The strong association between hepatomegaly (p<0.001) and splenomegaly (p=0.004) and the development of AKI supports our primary hypothesis. These clinical signs reflect extensive parasite sequestration within the reticuloendothelial system. This process mirrors the mechanical obstruction occurring in the renal microvasculature, leading to reduced blood flow, ischemia, and subsequent tubular injury [4,19].

Similarly, the association with clinical markers of severe hemolysis, such as jaundice (p=0.03) and hemoglobinuria (p<0.001), underscores the critical role of this pathway. Massive intravascular hemolysis releases large amounts of cell-free hemoglobin, which can induce direct tubular toxicity and oxidative stress within the kidneys, a wellestablished mechanism of malaria-associated AKI.

Neurological impairment, particularly coma, was also significantly associated with AKI. This likely does not represent a direct causal link but rather indicates a shared pathophysiology of severe systemic disease. Both cerebral malaria and AKI are driven by systemic inflammation, endothelial activation, and widespread microcirculatory dysfunction. Therefore, coma serves as a marker for the overall severity of the disease process that also targets the kidneys.

Interestingly, while hypoglycemia has been identified as a predictor of AKI in other studies [20,21], it was not statistically significant in our bivariate analysis. This could be due to the limited number of hypoglycemic patients in our cohort or effective glucose management upon admission. Nevertheless, its established role in malaria driven by parasite glucose consumption and impaired hepatic gluconeogenesis means it remains a crucial indicator of severe disease [22,23].

Strengths and Limitations

This study has several strengths, including its prospective design and the use of the standardized, internationally recognized KDIGO criteria to define and stage AKI.

However, the study also has important limitations. First, as a singlecenter study, our findings may not be generalizable to all settings in Benin. Second, and most importantly, the limited sample size of our AKI group (n=43) prevented us from performing a multivariate logistic regression analysis. Consequently, we cannot rule out the influence of confounding variables and can only report associations rather than independent predictors. Future multi-center studies with larger cohorts are needed to build robust predictive models.

Conclusion

Acute kidney injury is a common and serious complication of severe malaria in children in our setting, with an observed incidence of 21.1%. The primary factors associated with AKI were clinical markers of severe disease, including hepatomegaly, splenomegaly, coma, and indicators of significant hemolysis. In resource-limited environments where access to laboratory diagnostics may be restricted, vigilant monitoring of these clinical signs and particularly of urine output remains an invaluable and cost-effective tool for the early detection and management of AKI. Strengthening clinical vigilance for these risk factors and ensuring prompt supportive care for children with severe malaria are critical steps to reduce AKI-related morbidity and mortality

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Article Information

Article Type: RESEARCH ARTICLE

Citation: Ahoui S, Kpanidja G, Dansou J, Saka S, Bossikponon L, et al. (2025) Factors Associated with Acute Kidney Injury during Malaria in Children at the Borgou and Alibori Departmental Teaching Hospital (Benin). Int J Nephrol Kidney Fail 11(3): dx.doi.org/10.16966/2380-5498.256

Copyright: ©2025 Ahoui S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication history: 

Received date: 12 May, 2025

Accepted date: 18 Jul, 2025

Published date: 28 Jul, 2025