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

Abstract

Background Acute 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. Methods We 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. Results We 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. Conclusions We 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.

Malaria-Associated Acute Kidney Injury in African Children: Prevalence, Pathophysiology, Impact, and Management Challenges

“… 37 Thus, within the first week of life, a ≥0.3mg/dL rise in creatinine outperforms a percent creatinine change in predicting mortality in neonates (the Assessment of Worldwide Acute Kidney Epidemiology in Neonates, AWAKEN study). 37 While there have been attempts to evaluate normal baseline creatinine in populations of Ugandan children 6 months to 12 years of age, 38 additional research is needed to evaluate methods to estimate baseline creatinine across pediatric populations in LMIC, particularly infants <6 months of age.…”

“…The approach to estimate baseline serum creatinine can lead to substantial differences in AKI incidence and outcome associations. 38,39 There are two main approaches to estimate baseline creatinine: i) use a known measure from the child; or ii) use population-based estimates (discussed here 40 ). Patient-specific approaches are best suited in situations where underlying kidney disease is suspected or Figure 1 Incidence of AKI in African children with severe malaria.…”

“…In Ugandan and Nigerian children with severe malaria, younger children and children <2 years of age were shown to have a higher risk of AKI. 15 , 38 While it is possible that in lower transmission areas the risk of AKI is higher in older children, the perception of AKI being more common in older children and adults may reflect the serum creatinine threshold used to define AKI in prior studies. An adult with a baseline creatinine of 1.0 mg/dL requires a three-fold increase in serum creatinine to reach a threshold of 3 mg/dL, while a child with a baseline creatinine of 0.3 mg/dL requires a 10-fold increase in creatinine from baseline to meet the threshold for AKI.…”

Evaluating kidney function using a point-of-care creatinine test in Ugandan children with severe malaria: a prospective cohort study

“…Baseline SCr was estimated using a height-independent approach to back-calculate SCr using the Pottel age-based equation, where eGFR=107.3/(SCr/Q), assuming a normal GFR of 120mL/min per 1.73m 2 (height-independent), and Q=0.0270*age + 0.2329 [ 30 ]. This method was previously validated in Ugandan children and was the most accurate method to estimate baseline SCr with minimal bias [ 24 ]. A single SCr measure was available on admission, and data on urine output were not collected.…”

“…Although children with severe malaria frequently present with multiple severe malaria complications and multi-organ dysfunction [ 18 , 23 ], AKI is a common complication in children with severe malaria [ 17 , 18 ] and independently predicts mortality [ 17 – 19 , 23 ]. Diagnosis of AKI is dependent on the use of an appropriate estimate of baseline SCr [ 24 ] and an accurate measure of SCr. Access to SCr testing remains a critical barrier in many African health care settings [ 25 ], and increased availability of point-of-care devices to measure SCr across all levels of health care could substantially improve the recognition and management of AKI in resource-limited settings.…”