Dataset Information

Acute kidney injury is associated with impaired cognition and chronic kidney disease in a prospective cohort of children with severe malaria.

ABSTRACT:

Background

Acute kidney injury (AKI) is a recognized complication of pediatric severe malaria, but its long-term consequences are unknown.

Methods

Ugandan children with cerebral malaria (CM, n?=?260) and severe malaria anemia (SMA, n?=?219) or community children (CC, n?=?173) between 1.5 and 12?years of age were enrolled in a prospective cohort study. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to retrospectively define AKI and chronic kidney disease (CKD). Cognitive testing was conducted using the Mullen Scales of Early Learning in children ResultsThe prevalence of AKI was 35.1%, ranging from 25.1% in SMA to 43.5% in CM. In-hospital mortality was 11.9% in AKI compared to 4.2% in children without AKI (p?=?0.001), and post-discharge mortality was 4.7% in AKI compared to 1.3% in children without AKI (p?=?0.030) corresponding to an all-cause adjusted hazard ratio of 2.30 (95% CI 1.21, 4.35). AKI was a risk factor for short- and long-term neurocognitive impairment. At 1 week post-discharge, the frequency of neurocognitive impairment was 37.3% in AKI compared to 13.5% in children without AKI (adjusted odds ratio (aOR) 2.31 [95% CI 1.32, 4.04]); at 1-year follow-up, it was 13.3% in AKI compared to 3.4% in children without AKI (aOR 2.48 [95% CI 1.01, 6.10]), and at 2-year follow-up, it was 13.0% in AKI compared to 3.4% in children without AKI (aOR 3.03 [95% CI 1.22, 7.58]). AKI was a risk factor for CKD at 1-year follow-up: 7.6% of children with severe malaria-associated AKI had CKD at follow-up compared to 2.8% of children without AKI (p?=?0.038) corresponding to an OR of 2.81 (95% CI 1.02, 7.73). The presenting etiology of AKI was consistent with prerenal azotemia, and lactate dehydrogenase as a marker of intravascular hemolysis was an independent risk factor for AKI in CM and SMA (p?ConclusionsAKI is a risk factor for long-term neurocognitive impairment and CKD in pediatric severe malaria.

SUBMITTER: Conroy AL

PROVIDER: S-EPMC6528242 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Acute kidney injury is associated with impaired cognition and chronic kidney disease in a prospective cohort of children with severe malaria.

Conroy Andrea L AL Opoka Robert O RO Bangirana Paul P Idro Richard R Ssenkusu John M JM Datta Dibyadyuti D Hodges James S JS Morgan Catherine C John Chandy C CC

BMC medicine 20190521 1

<h4>Background</h4>Acute kidney injury (AKI) is a recognized complication of pediatric severe malaria, but its long-term consequences are unknown.<h4>Methods</h4>Ugandan children with cerebral malaria (CM, n = 260) and severe malaria anemia (SMA, n = 219) or community children (CC, n = 173) between 1.5 and 12 years of age were enrolled in a prospective cohort study. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to retrospectively define AKI and chronic kidney disease (CKD) ...[more]

PMID: 31109328

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Project description: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.

Project description:BackgroundGrowing evidence suggests that exposure to environmental chemicals, such as pesticides, impacts renal function and chronic kidney disease (CKD). However, it is not clear if pesticides may affect CKD progression and no studies exist in children.ObjectivesThe objective of this study was to examine associations between serially measured urinary OP pesticide metabolites and clinical and laboratory measures of kidney function over time among children with CKD.MethodsThis study used data on 618 participants enrolled in the CKD in Children study (CKiD), a cohort study of pediatric CKD patients from the US and Canada. Children were followed over an average of 3.0 years (standard deviation (SD) = 1.6) between 2005 and 2015. In serially collected urine samples over time, six nonspecific dialkyl phosphate (DAP) metabolites of OP pesticides were measured. Biomarkers of tubular injury (kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)) and oxidant stress (8-hydroxy-2'-deoxyguanosine (8-OHdG) and F2-isoprostane) were determined in the same specimens. Estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure were assessed annually.ResultsDAPs were associated with increased KIM-1 and 8-OHdG throughout follow-up. A standard deviation increase in ∑diethyl metabolites was associated with increases of 11.9% (95% Confidence Interval (CI): 4.8%, 19.4%) and 13.2% (95% CI: 9.3%, 17.2%) in KIM-1 and 8-OHdG over time, respectively. DAPs were associated with lower eGFR at baseline and higher eGFR over subsequent years.ConclusionsThese findings provide preliminary evidence suggesting that urinary DAP metabolites are associated with subclinical kidney injury among children with CKD, which may signal the potential for clinical events to manifest in the future. The results from this study are significant from both a clinical and public health perspective, given that OP pesticide exposure is a modifiable risk factor.

Project description:Rationale & objectiveChronic kidney disease (CKD) in children is associated with cognitive dysfunction that affects school performance and quality of life. The relationship between CKD-mineral and bone disorder and cognitive function in children is unknown.Study designObservational study.Participants702 children enrolled in the Chronic Kidney Disease in Children (CKiD) Study.PredictorsPlasma fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), calcium, phosphorus, 25 hydroxyvitamin D (25[OH]D), and 1,25 dihydroxyvitamin D (1,25[OH]2D).OutcomesNeurocognitive tests of intelligence, academic achievement, and executive functions.Analytical approachLinear regression models to analyze the cross-sectional associations between log2FGF-23, 25(OH)D, 1,25(OH)2D, PTH, calcium, and phosphorus z scores and the cognitive test scores of interest after adjustment for demographics, blood pressure, proteinuria, and kidney function.ResultsAt baseline, median age was 12 (95% CI, 8.3, 15.2) years and estimated glomerular filtration rate was 54 (40.5, 67.8) mL/min/1.73 m2. In fully adjusted analyses, 25(OH)D, 1,25(OH)2D, PTH, calcium, and phosphorus z scores did not associate with cognitive test scores. In fully adjusted analyses, log2FGF-23 was associated with abnormal test scores for attention regulation (P < 0.05); specifically, Conners' Continuous Performance Test II Errors of Omission (β = 2.3 [1.0, 3.6]), Variability (β=1.4 [0.4, -2.4]), and Hit Reaction Time (β = 1.3 [0.2, 2.4]). Children in the highest FGF-23 tertile group had 7% and 9% greater cognitive risk for Hit Reaction Time and Errors of Omission compared with those in the lowest tertile, respectively. In fully adjusted analyses, higher FGF-23 tertile was associated with increased cognitive risk (P < 0.05) for Errors of Omission (β = 0.4 [0.1, 0.7]) and Hit Reaction Time (β = 0.4 [0.1, 0.7]).LimitationsThe study does not assess the cumulative effects of FGF-23 excess on cognitive function over time. Within-population stratified analyses were not performed due to limited sample size.ConclusionsIn children with CKD, higher plasma FGF-23 level is associated with lower performance in targeted tests of executive function, specifically attention regulation, independent of glomerular filtration rate.

Project description:ObjectivesEvaluate the relationship between endothelial activation, malaria complications, and long-term cognitive outcomes in severe malaria survivors.DesignProspectively cohort study of children with cerebral malaria, severe malarial anemia, or community children.SettingMulago National Referral Hospital in Kampala, Uganda.SubjectsChildren 18 months to 12 years old with severe malaria (cerebral malaria, n = 253 or severe malarial anemia, n = 211) or community children (n = 206) were followed for 24 months.InterventionsNone.Measurements and main resultsChildren underwent neurocognitive evaluation at enrollment (community children) or a week following hospital discharge (severe malaria) and 6, 12, and 24 months follow-up. Endothelial activation was assessed at admission on plasma samples (von Willebrand factor, angiopoietin-1 and angiopoietin-2, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-Selectin, and P-Selectin). False discovery rate was used to adjust for multiple comparisons. Severe malaria was associated with widespread endothelial activation compared with community children (p < 0.0001 for all markers). Acute kidney injury was independently associated with changes in von Willebrand factor, soluble intercellular adhesion molecule-1, soluble E-Selectin, P-Selectin, and angiopoietin-2 (p < 0.0001 for all). A log10 increase in angiopoietin-2 was associated with lower cognitive z scores across age groups (children < 5, β -0.42, 95% CI, -0.69 to -0.15, p = 0.002; children ≥ 5, β -0.39, 95% CI, -0.67 to -0.11, p = 0.007) independent of disease severity (coma, number of seizures, acute kidney injury) and sociodemographic factors. Angiopoietin-2 was associated with hemolysis (lactate dehydrogenase, total bilirubin) and inflammation (tumor necrosis factor-α, interleukin-10). In children with cerebral malaria who had a lumbar puncture performed, angiopoietin-2 was associated with blood-brain barrier dysfunction, and markers of neuroinflammation and injury in the cerebrospinal fluid (tumor necrosis factor-α, kynurenic acid, tau).ConclusionsThese data support angiopoietin-2 as a measure of disease severity and a risk factor for long-term cognitive injury in children with severe malaria.

Project description:BackgroundThe progression from acute kidney injury (AKI) to chronic kidney disease (CKD) is not well understood in children.ObjectivesWe aimed to develop a pediatric CKD definition using administrative data and use it to evaluate the association between AKI in critically ill children and CKD 5 years after hospital discharge.DesignRetrospective cohort study using chart collection and administrative data.SettingTwo-center study in Montreal, Canada.PatientsChildren (?18 years old) admitted to two pediatric intensive care units (ICUs) between 2003 and 2005. We a priori excluded patients with end-stage renal disease or no health care number. Only the first admission during the study period was included. We excluded patients who could not be linked to administrative data, did not survive hospitalization, or had preexisting renal disease.MeasurementsAcute kidney injury was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patients were defined as having CKD 5 years post-discharge if they had ?1 CKD diagnostic code or ?1 CKD-specific medication prescription.MethodsChart data used to define the exposure (AKI) were merged with provincial administrative data used to define the outcome (CKD). Cox regression was used to evaluate the AKI-CKD association.ResultsA total of 2235 (56% male) patients were included, and the median admission age was 3.7 years. A total of 464 (21%) patients developed AKI during pediatric ICU admission. At 5 years post-discharge, 43 (2%) patients had a CKD diagnosis. Patients with both stage 1 and stage 2-3 AKI had increased risk of a CKD diagnosis, with the adjusted hazard ratios (95% confidence intervals) of 2.2 (1.1-4.5) and 2.5 (1.1-5.7), respectively (P < .001).LimitationsResults may not be generalizable to non-ICU patients. We were not able to control for post-discharge variables; future research should try to explore these additional potential risk factors further.ConclusionsAcute kidney injury is associated with 5-year post-discharge CKD diagnosis defined by administrative health care data.

Dataset Information

Acute kidney injury is associated with impaired cognition and chronic kidney disease in a prospective cohort of children with severe malaria.

Background

Methods

Publications

Acute kidney injury is associated with impaired cognition and chronic kidney disease in a prospective cohort of children with severe malaria.

Similar Datasets

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