sTREM-1: A Biomarker of Mortality in Severe Malaria Impacted by Acute Kidney Injury.

BACKGROUND: Malaria is an important cause of mortality in African children. Identification of biomarkers to identify children at risk of mortality has the potential to improve outcomes. METHODS: We evaluated 11 biomarkers of host response in 592 children with severe malaria. The primary outcome was biomarker performance for predicting mortality. Biomarkers were evaluated using receiver operating characteristic (ROC) curve analysis comparing the area under the ROC curve (AUROC). RESULTS: Mortality was 7.3% among children in the study with 72% of deaths occurring within 24 hours of admission. Among the candidate biomarkers, soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) had the highest AUROC (0.78 [95% confidence interval, .70-.86]), outperforming several other biomarkers including C-reactive protein and procalcitonin. sTREM-1 was the top-performing biomarker across prespecified subgroups (malaria definition, site, sex, nutritional status, age). Using established cutoffs, we evaluated mortality across sTREM-1 risk zones. Among children with acute kidney injury, 39.9% of children with a critical-risk sTREM-1 result had an indication for dialysis. When evaluated relative to a disease severity score, sTREM-1 improved mortality prediction (difference in AUROC, P = .016). CONCLUSIONS: sTREM-1 is a promising biomarker to guide rational allocation of clinical resources and should be integrated into clinical decision support algorithms, particularly when acute kidney injury is suspected.

Sex-disaggregated analysis of acute kidney injury in hospitalized children with sickle cell anemia in Uganda.

A growing body of research is categorizing sex differences in both sickle-cell anemia (SCA) and acute kidney injury (AKI), however, most of this work is being conducted in high-resource settings. Here, we evaluate risk factors and clinical parameters associated with AKI and AKI severity, stratified by sex, in a cohort of children hospitalized with SCA and vaso-occlusive pain crisis (VOC). The purpose of this study is to explore sex disparities in a high-risk, vulnerable population. This study is a secondary analysis of data collected from a cohort of Ugandan children between 2 and 18 years of age prospectively enrolled. A total of 185 children were enrolled in the primary study, 41.6% were female and 58.4% were male, with a median age of 8.9 years. Incident or worsening AKI (p=0.026) occurred more frequently in female compared to male children, despite no differences in AKI on admission. Female children also had altered markers of renal function including higher creatinine levels at admission (p=0.03), and higher peak creatinine (p=0.006); and higher urine NGAL at admission (p = 0.003) compared to male children. Female children had elevated total (p=0.045) and conjugated bilirubin at admission (p=0.02) compared to male children, and higher rates of hematuria at admission (p=0.004). Here we report sex differences in AKI in children with SCA and VOC, including increased incidence and worsening of AKI in female pediatric patients, in association with an increase in biological indicators of poor renal function including creatinine, estimated glomerular filtration rate (eGFR), and NGAL.

"My baby is fine, no need for more clinic visits." Facilitators and barriers for utilisation of follow-up services for children born preterm in low-resource setting: Parents' perceptions.

OBJECTIVES: We sought to understand the facilitators and barriers impacting utilisation of follow-up services for children born preterm as perceived by parents in a low-resource setting. METHODS: We conducted a qualitative study at Mulago Hospital, Uganda, with parents of children born preterm and aged 22-38 months at the time of the study. We collected data using five in-depth interviews and four focus group discussions. Data were analysed using thematic analysis informed by the social-ecological model. RESULTS: Ten subthemes emerged that could be grouped into three main themes: (1) Individual: parents' knowledge, parenting skills, perception of follow-up and infant's condition; (2) Relationship: support for the mother and information sharing; (3) Institution: facility setup, cost of care, available personnel and distance from the facility. Parents of preterm infants perceived receiving timely information, better understanding of prematurity and its complications, support from spouses, availability of free services and encouragement from health workers as facilitators for utilisation of follow-up services. Limited male involvement, parents' negative perception of follow-up, stable condition of infant, health facility challenges especially congestion at the hospital, distance and care costs were key barriers. CONCLUSION: An interplay of facilitators and barriers at individual, interpersonal and health system levels encourage or deter parents from taking their preterm children for follow-up services. Improving utilisation of services will require educating parents on the importance of follow-up even when children are not sick, eliciting maternal support from spouses and peers and addressing health system gaps that make follow-up unattractive and costly.

Nutritional status of young children born with low birthweight in a low resource setting: an observational study.

OBJECTIVE: Every year, an estimated 20 million babies are born with low birthweight and this number is increasing globally. Survivors are at risk of lifelong morbidities like undernutrition. We assessed the growth and nutritional status for children born with low birthweight at Mulago Hospital, Uganda. METHODS: We conducted a cross sectional study to describe the nutritional status of children aged between 22 and 38 months and born weighing ≤ 2000 g. Anthropometric measurements; weight for height, height for age and weight for age z-scores were generated based on the World Health Organization standards to define wasting, stunting and underweight respectively. Data was collected using a structured questionnaire and analysis was done using STATA version 14. RESULTS: Of the 251 children, 129 (51.4%) were male, mean age was 29.7 months SD 4.5) and maternal mean age was 29.9 (SD 5.3). A total of 101(40.2%) had normal nutritional status. The prevalence of wasting, underweight and stunting were: 8 (3.2%), 36 (14.4%) and 106 (42.2%) respectively. CONCLUSION: Six of ten children born with low birthweight were at risk of undernutrition in early childhood: underweight and stunting were higher than the national prevalence. Targeted interventions are needed for children with very low birth weight.

Acute Kidney Injury Interacts With Coma, Acidosis, and Impaired Perfusion to Significantly Increase Risk of Death in Children With Severe Malaria.

BACKGROUND: Mortality in severe malaria remains high in children treated with intravenous artesunate. Acute kidney injury (AKI) is a common complication of severe malaria, but the interactions between AKI and other complications on the risk of mortality in severe malaria are not well characterized. METHODS: Between 2014 and 2017, 600 children aged 6-48 months to 4 years hospitalized with severe malaria were enrolled in a prospective clinical cohort study evaluating clinical predictors of mortality in children with severe malaria. RESULTS: The mean age of children in this cohort was 2.1 years (standard deviation, 0.9 years) and 338 children (56.3%) were male. Mortality was 7.3%, and 52.3% of deaths occurred within 12 hours of admission. Coma, acidosis, impaired perfusion, AKI, elevated blood urea nitrogen (BUN), and hyperkalemia were associated with increased mortality (all P < .001). AKI interacted with each risk factor to increase mortality (P < .001 for interaction). Children with clinical indications for dialysis (14.4% of all children) had an increased risk of death compared with those with no indications for dialysis (odds ratio, 6.56; 95% confidence interval, 3.41-12.59). CONCLUSIONS: AKI interacts with coma, acidosis, or impaired perfusion to significantly increase the risk of death in severe malaria. Among children with AKI, those who have hyperkalemia or elevated BUN have a higher risk of death. A better understanding of the causes of these complications of severe malaria, and development and implementation of measures to prevent and treat them, such as dialysis, are needed to reduce mortality in severe malaria.

Neutrophil gelatinase-associated lipocalin is elevated in children with acute kidney injury and sickle cell anemia, and predicts mortality.

Urine neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury that has been adapted to a urine dipstick test. However, there is limited data on its use in low-and-middle-income countries where diagnosis of acute kidney injury remains a challenge. To study this, we prospectively enrolled 250 children with sickle cell anemia aged two to 18 years encompassing 185 children hospitalized with a vaso-occlusive pain crisis and a reference group of 65 children attending the sickle cell clinic for routine care follow up. Kidney injury was defined using serial creatinine measures and a modified-Kidney Disease Improving Global Outcome definition for sickle cell anemia. Urine NGAL was measured using the NGAL dipstick and a laboratory reference. The mean age of children enrolled was 8.9 years and 42.8% were female. Among hospitalized children, 36.2% had kidney injury and 3.2% died. Measured urine NGAL levels by the dipstick were strongly correlated with the standard enzyme-linked immunosorbent assay for urine NGAL (hospitalized children, 0.71; routine care reference, 0.88). NGAL levels were elevated in kidney injury and significantly increased across injury stages. Hospitalized children with a high-risk dipstick test (300ng/mL and more) had a 2.47-fold relative risk of kidney injury (95% confidence interval 1.68 to 3.61) and 7.28 increased risk of death (95% confidence interval 1.10 to 26.81) adjusting for age and sex. Thus, urine NGAL levels were found to be significantly elevated in children with sickle cell anemia and acute kidney injury and may predict mortality.

Acute kidney injury in hospitalized children with sickle cell anemia.

BACKGROUND: Children with sickle cell anemia (SCA) are at increased risk of acute kidney injury (AKI) that may lead to death or chronic kidney disease. This study evaluated AKI prevalence and risk factors in children with SCA hospitalized with a vaso-occlusive crisis (VOC) in a low-resource setting. Further, we evaluated whether modifications to the Kidney Disease: Improving Global Outcomes (KDIGO) definition would influence clinical outcomes of AKI in children with SCA hospitalized with a VOC. METHODS: We prospectively enrolled 185 children from 2 - 18 years of age with SCA (Hemoglobin SS) hospitalized with a VOC at a tertiary hospital in Uganda. Kidney function was assessed on admission, 24-48 h of hospitalization, and day 7 or discharge. Creatinine was measured enzymatically using an isotype-dilution mass spectrometry traceable method. AKI was defined using the original-KDIGO definition as ≥ 1.5-fold change in creatinine within seven days or an absolute change of ≥ 0.3 mg/dl within 48 h. The SCA modified-KDIGO (sKDIGO) definition excluded children with a 1.5-fold change in creatinine from 0.2 mg/dL to 0.3 mg/dL. RESULTS: Using KDIGO, 90/185 (48.7%) children had AKI with 61/185 (33.0%) AKI cases present on admission, and 29/124 (23.4%) cases of incident AKI. Overall, 23 children with AKI had a 1.5-fold increase in creatinine from 0.2 mg/dL to 0.3 m/dL. Using the sKDIGO-definition, 67/185 (36.2%) children had AKI with 43/185 (23.2%) cases on admission, and 24/142 (16.9%) cases of incident AKI. The sKDIGO definition, but not the original-KDIGO definition, was associated with increased mortality (0.9% vs. 7.5%, p = 0.024). Using logistic regression, AKI risk factors included age (aOR, 1.10, 95% CI 1.10, 1.20), hypovolemia (aOR, 2.98, 95% CI 1.08, 8.23), tender hepatomegaly (aOR, 2.46, 95% CI 1.05, 5.81), and infection (aOR, 2.63, 95% CI 1.19, 5.81) (p < 0.05). CONCLUSION: These results demonstrate that AKI is a common complication in children with SCA admitted with VOC. The sKDIGO definition of AKI in children with SCA was a better predictor of clinical outcomes in children. There is need for promotion of targeted interventions to ensure early identification and treatment of AKI in children with SCA.

Prevalence and predictors of ocular complications among children undergoing nephrotic syndrome treatment in a resource-limited setting.

BACKGROUND: Nephrotic syndrome is the most common glomerulopathy among children aged 2-18 years and high dose corticosteroids are the backbone of its management. Potentially blinding ocular complications often result from nephrotic syndrome and/or its treatment. We conducted a study to determine the prevalence and predictors of ocular complications among children undergoing nephrotic syndrome treatment at Mulago National Referral Hospital. METHODS: This was a cross-sectional study conducted for three [3] months at the pediatric renal unit of Mulago National Referral Hospital (MNRH). Data from a consecutive sample of 100 children was collected using a semi-structured questionnaire, entered into Epi-data 4.4.2 and exported to STATA 14 for analysis at univariate, bivariate and multivariate levels. A robust Poisson regression model was used to identify predictors of ocular complications. RESULTS: Out of 100 patients examined, 80(80%) had ocular complications. The median age was 10 (IQR: 7-12) and 52 (52%) were girls. The most frequent complications were hypertrichosis and refractive errors in 71% (95%CI 61.1-79.6) and 56% (95%CI 45.7-65.9) of the patients respectively. Age above 10 years was the predictor for ocular complications with a RR = 1.37 (95%CI:1.14-1.64) p = 0.001. CONCLUSIONS: We found a high prevalence of ocular complications among children with nephrotic syndrome in this tertiary hospital. The predictor of ocular complications was age greater than 10 years. We recommend that all children with nephrotic syndrome undergo a baseline ocular examination prior to commencement of treatment and be reviewed periodically by an ophthalmologist.

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

BACKGROUND: Acute kidney injury (AKI) disproportionately affects individuals in low-and middle-income countries (LMIC). However, LMIC-particularly countries in sub-Saharan Africa- are under-represented in global AKI research. A critical barrier in diagnosing AKI is access to reliable serum creatinine results. We evaluated the utility of a point-of-care test to measure creatinine and diagnose AKI in Ugandan children with malaria. METHODS: Paired admission creatinine was assessed in 539 Ugandan children 6 months to 4 years of age hospitalized with severe malaria based on blood smear or rapid diagnostic test. Creatinine levels were measured using isotope dilution mass spectrometry (IDMS)-traceable methods. The reference creatinine was measured using the modified Jaffe method by a certified laboratory and the point-of-care testing was conducted using an i-STAT blood analyzer (i-STAT1, with and without adjustment for the partial pressure of carbon dioxide). AKI was defined and staged using the Kidney Disease: Improving Global Outcomes criteria. RESULTS: The mean age of children was 2.1 years, and 21.6% of children were stunted. Mortality was 7.6% in-hospital. Over the entire range of measured creatinine values (<0.20mg/dL-8.4mg/dL), the correlation between the reference creatinine and adjusted and unadjusted point-of-care creatinine was high with R2 values of 0.95 and 0.93 respectively; however, the correlation was significantly lower in children with creatinine values <1mg/dL (R2 of 0.44 between the reference and adjusted and unadjusted i-STAT creatinine). The prevalence of AKI was 45.5% using the reference creatinine, and 27.1 and 32.3% using the unadjusted and adjusted point-of-care creatinine values, respectively. There was a step-wise increase in mortality across AKI stages, and all methods were strongly associated with mortality (p<0.0001 for all). AKI defined using the reference creatinine measure was the most sensitive to predict mortality with a sensitivity of 85.4% compared to 70.7 and 63.4% with the adjusted and unadjusted point-of-care creatinine values, respectively. CONCLUSIONS: Point-of-care assessment of creatinine in lean Ugandan children <4 years of age underestimated creatinine and AKI compared to the clinical reference. Additional studies are needed to evaluate other biomarkers of AKI in LMIC to ensure equitable access to AKI diagnostics globally.

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

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.

Mortality among children under five years admitted for routine care of severe acute malnutrition: a prospective cohort study from Kampala, Uganda.

BACKGROUND: Mortality among children under 5 years of age admitted to malnutrition units in sub-Saharan Africa remains high. The burden of HIV infection, a major risk factor for mortality among patients with severe acute malnutrition (SAM), has reduced due to concerted prevention and treatment strategies. None the less, anecdotal reports from the malnutrition unit at Uganda's National Referral Hospital (NRH) indicate that there is high mortality among patients with severe acute malnutrition (SAM) in routine care. Uganda has recently adopted the revised World Health Organization (WHO) treatment guidelines for SAM to improve outcomes. The mortality among children with SAM in routine care has not been recently elucidated. We report the magnitude and factors associated with mortality among children under 5 years of age admitted to the NRH for routine care of SAM. METHODS: This was a cohort study of all severely malnourished children admitted to the NRH between June and October 2017. The primary outcome was two-week mortality. Mortality was calculated using simple proportions and Cox regression analysis was used to determine factors associated with time to mortality. Data was entered into Epidata and analysed using Stata v14. RESULTS: Two-hundred-sixty (98.5%) children: 59.6% male; mean age 14.4 (SD 9.4) months, completed two weeks of follow-up. Of these, 25.2% (95% CI 19.9-30.4%) died. In-hospital mortality was 20.7% (95% CI15.9-25.6%). The prevalence of HIV infection was 12.2%. Factors associated with mortality included: positive HIV status (AHR 2.2, (95% CI; 1.2-4.2), p = 0.014), bacteraemia (AHR 9 (95% CI 3.4-23.0), p < 0.001, and low glomerular filtration rate (eGFR), AHR 3.2; (95% CI 1.7-6.3), p = 0.001). CONCLUSIONS: A 25% mortality among children with severe malnutrition remains unacceptably high despite significant reduction in HIV prevalence. Children with SAM who are HIV infected, have eGFR below 60 mL/min/1.73m2 or have bacteraemia, are more likely to die. Further studies to explore the relationship between eGFR and mortality among children with SAM are needed. Studies to establish efficacious antibiotics are urgently required to inform treatment guidelines for children with SAM.

Wasting, underweight and stunting among children with congenital heart disease presenting at Mulago hospital, Uganda.

BACKGROUND: Children with congenital heart disease are at increased risk of malnutrition. The aim of this study was to describe the prevalence of wasting, underweight and stunting among children with congenital heart disease attending Mulago National Referral Hospital, Uganda. METHODS: A cross-sectional study among 194 children aged 0-15 years was conducted between August 2013 and March 2014. Anthropometric measurements and clinical assessments were carried out on all children. Anthropometric z-scores based on WHO 2007 reference ranges were generated for each child. Weight-for-height z-scores were generated for children 0-5 years, weight-for-age z-scores for children 0-10 years, and height-for-age and BMI-for-age z-scores for all children. Risk factors associated with malnutrition were determined by Poisson regression. RESULTS: One hundred and forty five (74.7%) children were aged 0-5 years; and 111 of 194 (57.2%) were female. Forty five of 145 (31.5%) children aged 0-5 years were wasted; 77 of 181 (42.5%) children aged 0-10 years were underweight; 88 of 194 (45.4%) children were stunted; and 53 of 194 (27.3%) children were thin (BMI for age z score < -2). Moderate to severe anaemia (RR 1.11, 95% CI: 1.01-1.22) and moderate to severe heart failure (RR 1.24, 95% CI: 1.13-1.36) were associated with wasting and underweight respectively. Stunting was associated with moderate to severe heart failure (RR 1.11, 95% CI: 1.01-1.21) while thinness was associated with moderate to severe heart failure (RR 1.12, 95% CI: 1.04-1.21) and moderate to severe anaemia (RR 1.15, 95% CI: 1.06-1.25). CONCLUSION: Malnutrition is common in children with congenital heart disease, and is associated with anaemia and heart failure. There is need to integrate strategies to identify and manage malnutrition during the care of children with congenital heart disease.

Prevalence of arrhythmias among children below 15 years of age with congenital heart diseases attending Mulago National Referral Hospital, Uganda.

BACKGROUND: In Uganda, few children with congenital heart diseases (CHD) benefit from early corrective cardiac surgery. These children are at high risk of developing heart failure and electrolyte imbalances; factors which increase their risk of developing arrhythmias. This study aimed to determine the prevalence and factors associated with arrhythmias among children with congenital heart diseases receiving care at Mulago Hospital. METHODS: This was a cross-sectional study carried out from August 2013 to March 2014 at Mulago Hospital. Children were consecutively enrolled into the study. Standard 12-lead electrocardiograms (ECGs) were performed on 194 children with CHD (age range 10 days-15 years). Data was analysed using SPSS 16.0. RESULTS: Out of 194 children studied, 53/194 (27.3 %, 95 % CI 21.0 - 33.6) children had arrhythmias. Of the CHD children, 44/194 (22.7 %, 95 % CI 16.8 - 28.6) had first degree AV block while 9/194 (4.6 %, 95 % CI 1.7 - 7.6) children had either ectopic atrial rhythm, premature atrial contractions, junctional rhythm, complete atrioventricular (AV) dissociation or premature ventricular contractions. Children using digoxin were more likely to have first degree AV block (OR 3.75, 95 % CI 1.60-8.86) while those aged 5 years and below were less likely to have first degree AV block (OR 0.16, 95 % CI 0.07-0.37). CONCLUSION: Arrhythmias are common among children with CHD receiving care from Mulago Hospital. These are associated with digoxin use, child's age and electrolyte imbalances; factors which can easily be assessed, managed and where possible modified in these children during their care.

Disclosure of HIV test results by women to their partners following antenatal HIV testing: a population-based cross-sectional survey among slum dwellers in Kampala Uganda.

BACKGROUND: Disclosure of HIV status by women to their partners is the backbone for prevention of HIV transmission among couples as well as promotion of the prevention of mother to child transmission of HIV interventions. The aim of this study was to determine the prevalence and factors associated with disclosure of HIV test results by women to their sexual partners following antenatal HIV testing in Kamwokya slum community, Kampala, Uganda. METHODS: This was a population based cross-sectional study carried out from October to November 2011. A total of 408 randomly selected women aged 18-45 years, who had delivered a child within 2 years prior to the study, and had tested for HIV during antenatal care were recruited from Kamwokya community. A standardised interviewer- administered questionnaire was used to collect data. Data was entered into Epidata 2.1b and analysed using SPSS software version 16.0 and StatsDirect version 2.8.0. RESULTS: Overall 83.8% (95% CI: 79.9- 87.1) of the women reported that they had disclosed their HIV status to their sexual partners. Disclosure was significantly higher among women whose partners had also tested for HIV (OR=24.86, 95% CI: 5.30 - 116.56). Other factors that were associated with disclosure were secondary education or above (OR=2.66, 95% CI: 1.34 - 5.30), having attended 3 or more antenatal care visits (OR=3.62, 95% CI: 1.70 - 7.72), being married/cohabiting (OR=8.76, 95% CI: 4.06 - 18.81) and whether or not they would opt not to disclose a family member's HIV status (OR=1.61, 95% CI: 1.003 - 2.58). Overall, stigma was not significantly associated with disclosure. CONCLUSIONS: Disclosure of HIV test results to sexual partners in this group of women was relatively high. The results suggest that having a sexual partner who had also tested probably made it easier to disclose the woman's HIV status. Other predictors of disclosure were secondary education and above and having attended more antenatal care visits. These findings suggest the need for promotion of sexual partner HIV testing, improvement of literacy levels of women, and encouragement of women to attend antenatal care, as key factors in promoting disclosure of HIV results.

Prevalence and factors associated with Acute Kidney Injury among children aged 6month- 12years passing dark urine admitted at Soroti Regional Referral Hospital: A cross-sectional study.

Introduction: Acute Kidney Injury (AKI) is associated with a high mortality yet survivors are at risk for Hypertension, chronic kidney disease, long term neurocognitive and behavioural problems. Early recognition of patients with possible AKI is crucial for better treatment outcome, hence a need for evidence to guide targeted screening of patients with a risk factor for AKI. We sought to determine the prevalence and factors associated with AKI among children passing dark urine since haemoglobinuria, which presents as dark urine is a known risk factor for AKI. Methodology: This was a cross sectional study conducted at Soroti Regional Referral Hospital, among children aged 6month to 12years, who presented with dark urine. Urine colour was assessed using the Hammer Smith colour urine chart, only children with urine colour grade ≥ 5 were recruited. Serum creatinine analysis was done on the day of admission, within 48 hours and at day 7 or discharge. AKI was defined as a ≥ 1.5-fold increase in serum creatininefrom the baseline. Bivariate and multivariate analysis was used to determine factors associates with AKI with p values <0.05 level of significance. Results: Between January 2022 - July 2022, we enrolled a total of 255 participantswith median age of 4.0 (IQR, 2.0-6.58) years. About two thirds of the participants were males 157 (61.6%) and majority 111 (43.5%) presented with grade 8 of the urine colour. The prevalence of AKI was 38% (95% CI 32.3% - 44.2%). The factors found to be associated with AKI were grade of the urine colour ≥ 9 (aOR, 3.120 (95% CI 1.34-6.78) and reduced urine output (aOR, 3.226 (95% CI 1.10-9.81). Conclusion: The prevalence of AKI among children passing dark urine was high (38%). AKI was more likely to occur if the child was passing urine that is profoundly black and if there is history of reduced urine output. These findings reiterate the need for close monitoring of urine output of hospitalized children particularly those passing dark urine. Screening of those with profoundly black urine or reduced urine output should be done.

Infections and Acute Kidney Injury: A Global Perspective.

Globally, there are an estimated 13.3 million cases of acute kidney injury (AKI) annually. Although infections are a common cause of AKI globally, most infection-associated AKI occurs in low- and lower-middle-income countries. There are marked differences in the etiology of infection-associated AKI across age groups, populations at risk, and geographic location. This article provides a global overview of different infections that are associated commonly with AKI, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus, malaria, dengue, leptospirosis, tick-borne illnesses, and viral hemorrhagic fevers. Further discussion focuses on infectious conditions associated with AKI including sepsis, diarrheal diseases and pregnancy, peripartum and neonatal AKI. This article also discusses the future of infection-associated AKI in the framework of climate change. It explores how increased investment in achieving the sustainable development goals may contribute to the International Society of Nephrology's 0 by 25 objective to curtail avoidable AKI-related fatalities by 2025.

Renin as a Biomarker of Acute Kidney Injury and Mortality in Children With Severe Malaria or Sickle Cell Disease.

BACKGROUND: Globally, a very high percentage of acute kidney injury (AKI) occurs in low- and middle-income countries (LMICs) where late recognition contributes to increased mortality. There are challenges with using existing biomarkers of AKI in LMICs. Emerging evidence suggests renin may serve as a biomarker of kidney injury that can overcome limitations in creatinine-based diagnostics. METHODS: Two study populations in Uganda were assessed. Cohort #1 was a two-site, prospective cohort study enrolling 600 children with severe malaria (SM). Cohort #2 was a prospective cohort study enrolling 185 children with sickle cell disease (SCD) hospitalized with a vaso-occlusive crisis. Plasma or serum renin concentrations were measured in both cohorts of children at the time of hospital admission using Luminex® (Luminex Corporation, Austin, Texas, United States) or enzyme-linked immunosorbent assay (ELISA), respectively. We assessed the ability of renin to discriminate between children with or without AKI and between children who survived and children who died using receiver operating characteristic curves. RESULTS: In both cohorts, renin concentrations were strongly associated with AKI and mortality. Renin was able to discriminate between children with or without AKI with an area under the curve (AUC) of 0.70 (95%CI, 0.65-0.74) in children with SM and 0.72 (95%CI, 0.6co3-0.81) in children with SCD. Renin was able to discriminate between children who survived and children who died with an AUC of 0.73 (95%CI, 0.63-0.83) in children with SM and 0.94 (95%CI, 0.89-0.99) in children with SCD. In Cohort #2, we compared renin against urine neutrophil gelatinase-associated lipocalin (NGAL) as the leading biomarker of AKI, and it had comparable performance in discriminating AKI and predicting mortality. CONCLUSIONS: In two independent populations of children at risk of AKI with key differences in the etiology of kidney injury, renin was strongly associated with AKI and mortality and had moderate to good diagnostic performance to predict mortality.

Prevalence and predictors of hypertension among adults in Mbarara City, Western Uganda.

OBJECTIVE: The study aim was to evaluate the prevalence and predictors of hypertension among an urban adult population in Mbarara city, Western Uganda. METHODS: We evaluated blood pressure measurements, social demographic and clinical parameters of adults living in Mbarara city, Uganda. These parameters were extracted from medical records of adults who participated in the Uganda World Kidney Day 2020 health screening activities. A total of 302 adults were evaluated for hypertension using the American College of Cardiology/American Heart Association 2017 (blood pressure threshold 130/80 mmHg) and International Society of Hypertension 2020 guidelines (threshold 140/90 mmHg). RESULTS: The mean age of the participants was 42.5 years (standard deviation: 15.1) and majority were male 195/302 (64.6%). Using American College of Cardiology/American Heart Association 2017 guidelines, 156/302 (51.7%) adults were newly diagnosed with hypertension compared to 68/302 (22.5%) newly diagnosed with hypertension using International Society of Hypertension 2020 guidelines. Only 23/302 (7.6%) were on treatment. Based on American College of Cardiology/American Heart Association 2017 guidelines, age ≥40 years and overweight/obesity were statistically significant predictors of hypertension (p < 0.05 for all) at multivariate analysis. Using the International Society of Hypertension 2020 guidelines, age ≥40 years predicted hypertension. DISCUSSION: The prevalence of hypertension is high among this urban adult population irrespective of the guidelines used, highlighting the need for hypertension prevention interventions.

Cerebrospinal fluid biomarkers provide evidence for kidney-brain axis involvement in cerebral malaria pathogenesis.

Introduction: Cerebral malaria is one of the most severe manifestations of malaria and is a leading cause of acquired neurodisability in African children. Recent studies suggest acute kidney injury (AKI) is a risk factor for brain injury in cerebral malaria. The present study evaluates potential mechanisms of brain injury in cerebral malaria by evaluating changes in cerebrospinal fluid measures of brain injury with respect to severe malaria complications. Specifically, we attempt to delineate mechanisms of injury focusing on blood-brain-barrier integrity and acute metabolic changes that may underlie kidney-brain crosstalk in severe malaria. Methods: We evaluated 30 cerebrospinal fluid (CSF) markers of inflammation, oxidative stress, and brain injury in 168 Ugandan children aged 18 months to 12 years hospitalized with cerebral malaria. Eligible children were infected with Plasmodium falciparum and had unexplained coma. Acute kidney injury (AKI) on admission was defined using the Kidney Disease: Improving Global Outcomes criteria. We further evaluated blood-brain-barrier integrity and malaria retinopathy, and electrolyte and metabolic complications in serum. Results: The mean age of children was 3.8 years (SD, 1.9) and 40.5% were female. The prevalence of AKI was 46.3% and multi-organ dysfunction was common with 76.2% of children having at least one organ system affected in addition to coma. AKI and elevated blood urea nitrogen, but not other measures of disease severity (severe coma, seizures, jaundice, acidosis), were associated with increases in CSF markers of impaired blood-brain-barrier function, neuronal injury (neuron-specific enolase, tau), excitatory neurotransmission (kynurenine), as well as altered nitric oxide bioavailability and oxidative stress (p < 0.05 after adjustment for multiple testing). Further evaluation of potential mechanisms suggested that AKI may mediate or be associated with CSF changes through blood-brain-barrier disruption (p = 0.0014), ischemic injury seen by indirect ophthalmoscopy (p < 0.05), altered osmolality (p = 0.0006) and through alterations in the amino acids transported into the brain. Conclusion: In children with cerebral malaria, there is evidence of kidney-brain injury with multiple potential pathways identified. These changes were specific to the kidney and not observed in the context of other clinical complications.