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Acute kidney injury (AKI) is associated with increased mortality in hospitalized patients and incidence is highest in resource limited settings. The objective of this study was to assess sub-National regional differences in the incidence of AKI in children <5 years of age hospitalized with an acute febrile illness and hypoxemia.
This was a secondary analysis of a stepped wedge cluster randomized controlled trial, which enrolled children <5 years of age hospitalized with hypoxemia between 2019 and 2021. At least one measure of kidney function was available in 1452 children. A single creatinine was measured at enrolment in a sub-set of 495 children with serum stored and AKI defined using KDIGO criteria where baseline creatinine was estimated using the age-based Pottel equation assuming a normal glomerular filtration rate of 120mL/min per 1.73m2. Markers were divided into structural (uNGAL positive, proteinuria, hematuria) or functional (AKI, saliva urea nitrogen (SUN)) measures of kidney injury.
1452 children were included in this AKI sub-study (Figure 1). The mean age of participants was 1.49 years (standard deviation (SD), 1.21) and 55.7% were male (809/1452). Overall 2.6% of children died (38/1452). The majority of participants enrolled were from the West (31.3%) followed by the East (25.3%), North (24.1%), and Central (19.4%) regions. In general, 48.5% of children had AKI (240/495), the prevalence was highest in Eastern Uganda with 62.4% of children having AKI compared to 25.0% of children in Western Uganda, 44% in Central region and 53% in Northern region (p<0.001). Over a third of children had urine NGAL levels ≥150ng/mL, a marker of structural damage, irrespective of site and rates comparable across sites (p=0.095). Other measures of functional and structural kidney injury varied across sites, proteinuria ranged from 6.3% to 14.0% with rates lower in Central and Eastern Uganda compared to Northern and Western Uganda. Hematuria was over two times more common in Eastern and Northern Uganda compared to Central and Western Uganda. Of all the children 49.0 % were positive for malaria based on rapid diagnostic test (RDT) either as positive pLDH or both pLDH and HRP-2. The presence of a single band positive RDT for HRP-2 alone was associated with increased risk of AKI, severe AKI, elevated BUN, a positive SUN test and urinalysis positive for hematuria or urobilinogen (unadjusted p<0.05). Children with a 3-band positive RDT were more likely to have proteinuria, hematuria, bilirubinuria and urobilinogen by dipstick (unadjusted p<0.05). Regional differences in AKI persisted after adjusting for malaria, age, and sex.
As we move towards the ISN 0by25 initiative which aims to eliminate preventable deaths from AKI worldwide by 2025. This study provides key in-country data from a resource limited setting, demonstrating marked regional differences in the incidence of AKI in children hospitalized with hypoxaemia and malaria remains an important predictor of AKI. The substantial within-country heterogeneity of AKI highlights the need for further studies to evaluate regional contributors to local patterns of AKI.