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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?

SUBMITTER: Batte A

PROVIDER: S-EPMC7526147 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Project description:BackgroundCerebral malaria is the most severe neurological complication of falciparum malaria and a leading cause of death and neuro-disability in sub-Saharan Africa. This study aimed to describe functional deficits and behaviour problems in children who survived cerebral malaria with severe neurological sequelae and identify patterns of brain injury.FindingsRecords of children attending a specialist child neurology clinic in Uganda with severe neurological sequelae following cerebral malaria between January 2007 and December 2008 were examined to describe deficits in gross motor function, speech, vision and hearing, behaviour problems or epilepsy. Deficits were classified according to the time of development and whether their distribution suggested a focal or generalized injury. Any resolution during the observation period was also documented.Thirty children with probable exposure to cerebral malaria attended the clinic. Referral information was inadequate to exclude other diagnoses in 7 children and these were excluded. In the remaining 23 patients, the commonest severe deficits were spastic motor weakness (14), loss of speech (14), hearing deficit (9), behaviour problems (11), epilepsy (12), blindness (12) and severe cognitive impairment (9). Behaviour problems included hyperactivity, impulsiveness and inattentiveness as in attention deficit hyperactivity disorder (ADHD) and conduct disorders with aggressive, self injurious or destructive behaviour. Two patterns were observed; a) immediate onset deficits present on discharge and b) late onset deficits. Some deficits e.g. blindness, resolved within 6 months while others e.g. speech, showed little improvement over the 6-months follow-up.ConclusionsIn addition to previously described neurological and cognitive sequelae, severe behaviour problems may follow cerebral malaria in children. The observed differences in patterns of sequelae may be due to different pathogenic mechanisms, brain regions affected or extent of injury. Cerebral malaria may be used as a new model to study the pathogenesis of ADHD.

Project description:BackgroundRecent studies suggest that adjustment of measures of lean mass for adiposity improves associations with physical function. Our objective was to develop and test a method to adjust appendicular lean mass for adiposity.MethodsWhole-body DXA data in 14,850 adults in the National Health and Nutrition Examination Survey were used to generate sex-, and race-specific standard deviation scores (Z-Scores relative to age and T-scores relative to 25 year-olds) for appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI, kg/m2). Correlations between ALMI and FMI Z- and T-Scores were assessed within demographic categories. Fat-adjusted ALMI (ALMIFMI) scores were determined using residual methods. Sarcopenia was defined as a T-Score <-2.0 and low lean for age as a Z-Score <-1.0. Correlations with physical function were assessed in an at-risk population.ResultsPositive associations between ALMI and FMI Z- and T-Scores were significant (R >0.50; p<0.001) within all demographic categories. The impact of a unit greater FMI Z-score on ALMI Z-score was less in the elderly, men, white subjects, and among individuals with lower FMI (all tests for interaction p<0.001). There was fair agreement between ALMI and ALMIFMI estimates of sarcopenia and low lean for age [Kappa: 0.46, 0.52, respectively (p<0.0001)]. Elderly subjects were likely to be re-classified as sarcopenic while young subjects were likely to be re-classified as normal using ALMIFMI. ALMIFMI T-scores resulted in approximately twice the number of subjects defined as sarcopenic, compared with ALMI T-Scores. (1299 v. 534). Among rheumatoid arthritis patients, ALMIFMI Z-scores correlated with physical function (Health Assessment Questionnaire: rho = -0.22, p = 0.04; Short Physical Performance Battery: rho = 0.27, p = 0.01); however, the ALMI Z-Score did not.ConclusionsAdjustment of ALMI for the confounding association with FMI impacts the definition of lean mass deficits. These methods provide a practical tool for investigators and clinicians based on population-based reference data.

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

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