Evaluation of eGFR methods in a sub-Saharan African community-based pediatric population.

BACKGROUND: Accurate assessment of the estimated glomerular filtration rate (eGFR) plays a pivotal role in the early detection, management, and optimal medication dosing for chronic kidney disease (CKD). However, validation of eGFR, utilizing cystatin C-based equations, is limited in African children and adolescents with CKD. We evaluate the agreement of eGFR equations incorporating both cystatin C and creatinine in this specific population. METHODS: This community-based study assessed CKD in children (2-15 years) using cystatin C and serum creatinine. eGFR agreement with the reference was evaluated with Bland-Altman plots, ROC curves, and Lin's CCC, using the Under-25 serum creatinine-cystatin C equation as the reference standard. Pairwise ROC comparisons assess the statistical differences in estimation equation agreement. RESULTS: Among 666 children (mean age, 7.8 ± 3.8 years; 48.6% male), CKD prevalence was 11.6% (95% CI, 9.2-14.2%). Notably, the Chehade equation, using combined biomarkers, aligned best with the reference, displaying the lowest mean deviation (- 0.59; 95% CI, - 1.19 to 0.01), superior agreement (P10, 91.0%; P30, 96.70%), and highest discriminatory power (0.989). In contrast, CKD-EPI 2012 cystatin C had the highest mean deviation (- 35.90) and lowest discriminatory power (0.79). Equations combining creatinine and cystatin C (Schwartz, Chehade, Full Age Spectrum) demonstrated strong positive Lin's CCC with CKiD U25 creatinine-cystatin C, while Bouvet showed a notably weak correlation (Lin's CCC, 0.22). CONCLUSION: In African children with CKD, the Chehade, CKiD Under 25 creatinine-based equations, and the Full Age Spectrum equations show promise for CKD diagnosis. However, a measured GFR is essential to identifying the most accurate eGFR equation in this population.

Efficacy and safety of dual intravenous artesunate plus quinine compared to intravenous artesunate for cerebral malaria in a triple blinded parallel multisite randomized controlled trial in Nigerian children: DUAL PAQ TRIAL Protocol.

BACKGROUND: Evidence exists as to the criticality of the first 24 h in the management of cerebral malaria. The morbidity and the mortality rate (35%) with the current intravenous monotherapy for the initial treatment of cerebral malaria are unacceptably high. Combination therapy and a shorter course of effective medication have been shown to improve outcomes in human participants in the treatment of other diseases. This study outlines a protocol to conduct a triple blinded parallel randomized controlled trial on cerebral malaria using dual intravenous medications compared to the current standard of monotherapy. METHODS: This is a parallel multi-site randomized controlled superiority triple blinded trial consisting of intravenous artesunate plus quinine and a control arm of intravenous artesunate only. Eligible and assenting children aged 6 months to 17 years will be recruited from 4 tertiary hospitals by random selection from the list of tertiary hospitals in Nigeria. Participants will be randomized and assigned in parallel into two arms using random numbers generated from GraphPad Prism (version 9) by a clinical pharmacologist who has no link with the investigators, the patients, or the statistician. The primary measurable outcome is survival at 12, 24, and 48 h post-randomization. A composite secondary outcome consists of the number of children that regained consciousness, parasitaemia and defervescence at 12 and 24 h post-randomization and haematological and inflammatory markers at 24 and 48 h post-randomization. Adverse events both solicited and unsolicited are recorded all through the study post-randomization. The study is approved by the State Research Ethics Review Committee. Data analysis will be performed in GraphPad Prism version 9. DISCUSSION: The outcome of this analysis will give insight into the efficacy and safety of dual intravenous antimalaria in the treatment of cerebral malaria among Nigerian children compared with the standard of care. The safety profile of this intervention will also be highlighted. This may help inform physicians on the optimal treatment for cerebral malaria to improve outcomes and reduce recrudescence and treatment failure. TRIAL REGISTRATION: Pan Africa Clinical Trial Registry PACTR202102893629864 . 23/02/2021.

Long-term survival of children following acute peritoneal dialysis in a resource-limited setting.

BACKGROUND: There is a paucity of data on long term-outcomes of children who undergo acute peritoneal dialysis (PD) in resource-limited settings. We reviewed the outcomes of children who underwent PD after 18 months of follow-up. METHODS: We conducted a prospective cohort study in children with acute kidney injury (AKI) who underwent PD. Diagnosis of AKI was based on the 2012 Kidney Disease: Improving Global Outcomes definition. We assessed outcomes of in-hospital mortality, 18-month post-dialysis survival, factors associated with survival, and progression to chronic kidney disease (CKD). RESULTS: Twenty-nine children with a median age of 6 (3 to 11) years underwent acute PD. In-hospital mortality was 3/29 (10.3%) and rose to 27.6% during follow-up. Seven (24.1%) children were lost to follow-up. Of the 14 remaining children, six (42.9%) experienced full recovery of renal function, while eight (57.1%) progressed to CKD. Among those who experienced full recovery, median (interquartile range) estimated glomerular filtration rate (eGFR) rose from 12.67 (7.05, 22.85) mL/min/1.73 m2 to 95.56 (64.50, 198.00) mL/min/1.73 m2, P = 0.031. No significant changes in median eGFR from baseline were observed among those who progressed to CKD (P = 0.383) or in non-survivors (P = 0.838). According to Kaplan-Meier curve analyses, 18-month survival during follow-up was 66.0% (95% CI, 45.0% to 86.5%). Age < 5 was associated with greater likelihood of survival (OR, 3.217; 95% CI, 1.240 to 8.342). CONCLUSION: Progression of post-PD AKI to CKD occurred in more than half of survivors. Age < 5 was associated with greater likelihood of survival.

Peritoneal dialysis in childhood acute kidney injury: experience in southwest Nigeria.

BACKGROUND: The choices for renal replacement therapy (RRT) in childhood acute kidney injury (AKI) are limited in low-resource settings. Peritoneal dialysis (PD) appears to be the most practical modality for RRT in young children with AKI in such settings. Data from sub-Saharan Africa on the use of PD in childhood AKI are few. METHODS: We performed a retrospective study of children who underwent PD for AKI at a tertiary-care hospital in southwest Nigeria from February 2004 to March 2011 (85 months). RESULTS: The study included 27 children (55.6% female). Mean age was 3.1 ± 2.6 years, with the youngest being 7 days, and the oldest, 9 years. The causes of AKI were intravascular hemolysis (n = 11), septicemia (n = 8), acute glomerulonephritis (n = 3), gastroenteritis (n = 3), and hemolytic uremic syndrome (n = 2). Peritoneal dialysis was performed manually using percutaneous or adapted catheters. Duration of PD ranged from 6 hours to 12 days (mean: 5.0 ± 3.3 days). The main complications were peritonitis (n = 10), pericatheter leakage (n = 9), and catheter outflow obstruction (n = 5). Of the 27 patients, 19 (70%) survived till discharge. CONCLUSIONS: In low-resource settings, PD can be successfully performed for the management of childhood AKI. In our hospital, the use of adapted catheters may have contributed to the high complication rates. Peritoneal dialysis should be promoted for the management of childhood AKI in low-resource settings, and access to percutaneous or Tenckhoff catheters, dialysis fluid, and automated PD should be increased.

Diagnosing renal failure due to diethylene glycol in children in a resource-constrained setting.

BACKGROUND: In 2008, several Nigerian children developed acute kidney injury (AKI) after ingesting teething syrup contaminated with diethylene glycol (DEG). Because there are limited diagnostic facilities in resource-constrained countries, this study investigated whether AKI associated with DEG could be identified by other means. METHODS: This was a multicenter study. Information was obtained from hospital records. Clinicopathological features of all children with AKI over a 6-month period were reviewed. RESULTS: Sixty (50.4%) of 119 children ingested "My pikin" teething syrup. Compared to children who had not ingested it, they were significantly (p < 0.05) younger (11.95 vs. 31 months), more were anuric (98.3 vs. 74.6%), hypertensive (84 vs. 52%), had severe metabolic acidosis (46.7 vs. 20.5%), and died (96.6 vs. 71.2%). They developed increasing metabolic acidosis and multiorgan dysfunction despite peritoneal dialysis. Late presentation, financial difficulties, inadequate facilities for toxicology, and hemodialysis complicated management. CONCLUSIONS: Identifying AKI associated with DEG is difficult. Detailed drug history, increasing metabolic acidosis, and multiorgan deterioration despite peritoneal dialysis should arouse suspicion. Simple diagnostic tests need to be developed and facilities for hemodialysis of infants and financial support provided. Recurrences can be prevented by creating awareness, improving manufacturing practices, field-testing of drugs, and international monitoring of pharmaceuticals imported for manufacture.