Pos-173 Acute Kidney Injury And Renal Recovery In Ugandan Children With Severe Malaria

Abstract

Introduction: Acute kidney injury (AKI) is increasingly recognized as an important clinical complication in children with severe malaria associated with increased morbidity and mortality, including long-term neurocognitive and behavioral problems in surviving children. The objective of this study was to evaluate AKI and renal recovery in a prospective cohort study of children with severe malaria admitted to two hospitals in Uganda: Mulago National Referral Hospital in Kampala in Central Uganda and Jinja Regional Referral Hospital in Eastern Uganda. Methods: 598 children hospitalized with Plasmodium falciparum with clinical features of severe malaria and at least one creatinine measure were enrolled in the study and followed for 12 months. 118 healthy community children were enrolled to assess normal kidney function. Serum creatinine was measured using a Beckman Coulter AU5822 chemistry analyzer using the modified Jaffe colorimetric method on cryopreserved samples. Study definitions are described in Figure 1. Results: The prevalence of AKI was 45.3% and was more common in Jinja (57.5%) compared to Kampala (35.5%) (p<0.0001). The maximum AKI stage was Stage 1 in 23.9% of children, Stage 2 in 10.0% of children and Stage 3 in 11.4% of children. AKI was more common in children who reported use of herbal medications (Odds Ratio (OR), 3.64 95% CI 1.52 to 8.75, p=0.004), but was not associated with reported use of anti-malarial medications, antibiotics, or non-steroidal anti-inflammatory medications prior to admission (p>0.05 for all). Clinically, children with AKI were more likely to present with coma, retinal hemorrhages, jaundice, hemoglobinuria, respiratory distress, and a history of vomiting (p<0.05 for all). AKI was associated with a significant increase in in-hospital mortality (OR, 7.98 95% CI 3.14, 20.32, p<0.0001), neurologic deficits at discharge in survivors (OR, 1.83 95% CI 1.06 to 3.15, p=0.031) and a higher incidence of subsequent hospitalization (Incidence Rate Ratio (IRR), 1.26 95% CI, 1.02 to 1.56, p=0.031) adjusting for child age, sex, level of consciousness, presence of severe anemia and study site. At one month follow-up, 60 children (13.0%) had acute kidney disease (AKD) while 34 (7.4%) had hyperfiltration, defined as an estimated Glomerular filtration rate (eGFR)>185mL/min/1.73m2. There were distinct differences in the pattern of kidney injury over follow-up by site with hyperfiltration occurring in 12.4% of children from Kampala vs. 1.8% of children from Jinja while AKD occurred in 1.2% of children from Kampala compared to 26.0% of children from Jinja. The presence of AKD at one-month follow-up was associated with 4.74 fold increased odds of post-discharge mortality (95% CI, 1.33 to 16.98) adjusting for age, sex, and site. Conclusions: Additional research is needed to understand how AKI impacts long-term kidney function and to understand regional differences in kidney function in malaria-endemic settings.