Methods to estimate baseline creatinine and define acute kidney injury in lean Ugandan children with severe malaria: a prospective cohort study

Anthony Batte,Chandy C John,John M Ssenkusu,Andrew L Schwaderer,Michelle C Starr,Andrea L Conroy,Erika S Phelps Nishiguchi,Robert O Opoka,Ruth Namazzi

doi:10.1186/s12882-020-02076-1

Abstract

BackgroundAcute kidney injury (AKI) is increasingly recognized as a consequential clinical complication in children with severe malaria. However, approaches to estimate baseline creatinine (bSCr) are not standardized in this unique patient population. Prior to wide-spread utilization, bSCr estimation methods need to be evaluated in many populations, particularly in children from low-income countries.MethodsWe evaluated six methods to estimate bSCr in Ugandan children aged 6 months to 12 years of age in two cohorts of children with severe malaria (n = 1078) and healthy community children (n = 289). Using isotope dilution mass spectrometry (IDMS)-traceable creatinine measures from community children, we evaluated the bias, accuracy and precision of estimating bSCr using height-dependent and height-independent estimated glomerular filtration (eGFR) equations to back-calculate bSCr or estimating bSCr directly using published or population-specific norms.ResultsWe compared methods to estimate bSCr in healthy community children against the IDMS-traceable SCr measure. The Pottel-age based equation, assuming a normal GFR of 120 mL/min per 1.73m2, was the more accurate method with minimal bias when compared to the Schwartz height-based equation. Using the different bSCr estimates, we demonstrated the prevalence of KDIGO-defined AKI in children with severe malaria ranged from 15.6–43.4%. The lowest estimate was derived using population upper levels of normal and the highest estimate was derived using the mean GFR of the community children (137 mL/min per 1.73m2) to back-calculate the bSCr. Irrespective of approach, AKI was strongly associated with mortality with a step-wise increase in mortality across AKI stages (p < 0.0001 for all). AKI defined using the Pottel-age based equation to estimate bSCr showed the strongest relationship with mortality with a risk ratio of 5.13 (95% CI 3.03–8.68) adjusting for child age and sex.ConclusionsWe recommend using height-independent age-based approaches to estimate bSCr in hospitalized children in sub-Saharan Africa due to challenges in accurate height measurements and undernutrition which may impact bSCr estimates. In this population the Pottel-age based GFR estimating equation obtained comparable bSCr estimates to population-based estimates in healthy children.

Highlights

Acute kidney injury (AKI) is increasingly recognized as a consequential clinical complication in children with severe malaria
There was a sex difference in community children compared to children with severe malaria with 51.2% of community children female compared to 42.2% of children with severe malaria
There was no difference in height-for-age z scores between the community children and children with severe malaria

Summary

Introduction

Acute kidney injury (AKI) is increasingly recognized as a consequential clinical complication in children with severe malaria. 1.7 million people die from acute kidney injury (AKI) every year and 80% of deaths occur in low-and middle-income countries (LMIC) [1]. The most commonly used approach is to assume a normal estimated glomerular filtration rate (eGFR) of 120 mL/min per 1.73m2 and use the Bedside Schwartz equation to back-calculate bSCr [6, 8,9,10]. This approach has been used in large multinational studies [10], but has not been validated in LMIC settings where there are limited population-based estimates of creatinine in children

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