HIV-associated nephropathy in children: challenges in a resource-limited setting.

HIV infection remains one of the leading causes of morbidity and mortality worldwide, especially in children living in resource-limited settings. Although the World Health Organization (WHO) recently recommended antiretroviral therapy (ART) initiation upon diagnosis regardless of the number of CD4, ART access remains limited, especially in children living in sub-Saharan Africa (SSA). HIV-infected children who do not receive appropriate ART are at increased risk of developing HIV-associated nephropathy (HIVAN). Although due to genetic susceptibility, SSA is recognized to be the epicenter of HIVAN, limited information is available regarding the burden of HIVAN in children living in Africa. The present review discusses the information available to date on the prevalence, pathogenesis, risk factors, diagnosis, and management of HIVAN in children, focusing on related challenges in a resource-limited setting.

Novel Human Podocyte Cell Model Carrying G2/G2 APOL1 High-Risk Genotype.

Apolipoprotein L1 (APOL1) high-risk genotypes (HRG), G1 and G2, increase the risk of various non-diabetic kidney diseases in the African population. To date, the precise mechanisms by which APOL1 risk variants induce injury on podocytes and other kidney cells remain unclear. Trying to unravel these mechanisms, most studies have used animal or cell models created by gene editing. We developed and characterised conditionally immortalised human podocyte cell lines derived from urine of a donor carrying APOL1 HRG G2/G2. Following induction of APOL1 expression by polyinosinic-polycytidylic acid (poly(I:C)), we assessed functional features of APOL1-induced podocyte dysfunction. As control, APOL1 wild type (G0/G0) podocyte cell line previously generated from a Caucasian donor was used. Upon exposure to poly(I:C), G2/G2 and G0/G0 podocytes upregulated APOL1 expression resulting in podocytes detachment, decreased cells viability and increased apoptosis rate in a genotype-independent manner. Nevertheless, G2/G2 podocyte cell lines exhibited altered features, including upregulation of CD2AP, alteration of cytoskeleton, reduction of autophagic flux and increased permeability in an in vitro model under continuous perfusion. The human APOL1 G2/G2 podocyte cell model is a useful tool for unravelling the mechanisms of APOL1-induced podocyte injury and the cellular functions of APOL1.

A focus on the association of Apol1 with kidney disease in children.

Individuals of African origin have an increased risk of developing various progressive chronic kidney diseases (CKD). This risk has been attributed to genetic variants (G1, G2) in apolipoprotein-L1 (APOL1) gene. In the pediatric population, especially in children affected by sickle cell disease (SCD), by human immunodeficiency virus (HIV), or with various glomerular diseases, APOL1 risk variants have been associated with the development of hypertension, albuminuria, and more rapid decline of kidney function. The present review focuses on existing APOL1-related epidemiological data in children with CKD. It also includes data from studies addressing racial disparities in CKD, the APOL1-related innate immunity, and the relationship between APOL1 and CKD and pathogenic pathways mediating APOL1-related kidney injury.

A promising pediatric peritoneal dialysis experience in a resource-limited setting with the support of saving young lives program.

In the Democratic Republic of Congo (DRC), acute kidney injury (AKI) contributes to the high rate of child mortality owing to the conjunction of poverty, deficiency of qualified health-care providers in pediatric nephrology, and the lack of pediatric dialysis programs. We aimed to describe the recent experience of the first pediatric acute peritoneal dialysis (PD) program in DRC. This is a retrospective cohort study on epidemiology, clinical features and outcomes of children admitted from January 2018 to January 2019 at the University Hospital of Kinshasa for AKI and treated with PD. This pediatric PD program started by a team of one physician and one nurse who were trained in the local production of PD fluids and bedside catheter insertion technique in Benin Republic. The training was jointly supported by the Flemish Inter-University Council (VLIR) TEAM project and Saving Young Lives (SYL) program of ISN, ISPD, EuroPD, and IPNA. From January 2018 to January 2019, 49 children (aged 4 months-15 years) were admitted for AKI mainly due to severe malaria and sepsis. Dialysis was indicated in 35 of 49 (71.4%), 32 of 35 (91.4%) were treated with PD, two with hemodialysis (HD) in adult ward and one died at admission. Data of the two patients transferred for HD were not available for follow-up. The main indications were uremia and prolonged anuria. Of 32 dialyzed patients, 24 (75%) recovered normal renal function 3 months after discharge. Peritonitis was observed in 2 of 32 (6.2%) patients and the mortality was 18.7%. This promising experience proves that with simple means including use of locally produced dialysis fluids and low peritonitis rates, we can effectively save lives of children suffering from AKI.

APOL1 Risk Genotypes Are Associated With Early Kidney Damage in Children in Sub-Saharan Africa.

INTRODUCTION: Apolipoprotein-L1 (APOL1) risk variants G1 and G2 increase the risk of chronic kidney disease (CKD), including HIV-related CKD, among African Americans. However, such data from populations living in Africa, especially children, remain limited. Our research aimed to determine the prevalence of APOL1 risk variants and to assess the association between these variants and early-stage CKD in the general pediatric population and HIV-infected children. METHODS: In a cross-sectional study, we enrolled 412 children from the general population and 401 HIV-infected children in Kinshasa, Democratic Republic of Congo (DRC). APOL1 high-risk genotype (HRG) was defined by the presence of 2 risk variants (G1/G1, G2/G2, or G1/G2), and low-risk genotype (LRG) by the presence of 0 or 1 risk variants. The main outcome was elevated albuminuria, defined as a urinary albumin/creatinine ratio ≥30 mg/g. RESULTS: APOL1 sequence analysis revealed that in the general population, 29 of 412 participants (7.0%) carried HRG, 84 of 412 (20.4%) carried the G1/G0 genotype, and 61 of 412 (14.8%) carried the G2/G0 genotype. In HIV-infected children, 23 of 401 (5.7%) carried HRG, and the same trend as in the general population was observed in regard to the prevalence of LRG. Univariate analysis showed that in the general population, 5 of 29 participants (17.2%) carrying HRG had elevated albuminuria, compared with 35 of 383 (9.0%) with LRG (odds ratio [OR] 2.1, 95% confidence interval [CI] 0.6-6.0; P = 0.13). In HIV-infected children, participants who carried APOL1 HRG had almost 22-fold increased odds of albuminuria compared to those with LRG. CONCLUSION: The APOL1 risk variants are prevalent in children living in DRC. HRG carriers have increased odds of early kidney disease, and infection with HIV dramatically increases this probability.

Prevalence and determinants of microalbuminuria in children suffering from sickle cell anemia in steady state.

BACKGROUND: Sickle cell anemia (SCA) is considered a major risk factor for renal complications. The main goal of this study was to determine the frequency of macroalbuminuria and microalbuminuria in Congolese children <18 years of age suffering from Sickle cell anemia and to identify associated factors. METHODS: The cross-sectional study was completed in 150 hemoglobin-SS children (77 boys and 73 girls). Microalbuminuria was defined by a urine albumin:creatinine ratio of 30-299 mg/g. RESULTS: The mean age of this group was 8.8 ± 4.3 years (range 2-18). Microalbuminuria was found in 27 children (18%). In multivariate logistic regression, only age emerged as a determinant of microalbuminuria odds ratio 1.11 (95% confidence interval 1.00-1.22); P = 0.042]. CONCLUSIONS: In our series, only age was a major determinant of the occurrence of microalbuminuria. These results confirm the need for early screening of microalbuminuria in Congolese children suffering from Sickle cell anemia in a context where access to renal and bone marrow transplant is nonexistent.

Albuminuria, serum antioxidant enzyme levels and markers of hemolysis and inflammation in steady state children with sickle cell anemia.

BACKGROUND: Oxidative stress is thought to be involved in the pathogenesis of microalbuminuria in Sickle cell anemia (SCA). Antioxidant enzymes such as glutathione peroxidase (GPx) and Cu-Zn superoxide dismutase (SOD) may play an important protective role. This study aimed to evaluate the association between albuminuria and these two antioxidant enzymes. METHODS: We consecutively recruited Steady state children aged between 2 and 18 years old with established diagnosis of homozygous SCA in two hospitals of Kinshasa/DR Congo. The relationship between Urinary Albumin Creatinine Ratio (UACR) and other variables of interest (age, systolic blood pressure, diastolic blood pressure, plasma GPx and Cu-Zn SOD, free plasmatic hemoglobin, LDH, indirect bilirubin, white blood cells (WBC), percentage of fetal hemoglobin, serum iron, ferritin, CRP) was analyzed by Bivariate correlation (Pearson's correlation coefficient). Microalbuminuria was defined by urine albumin/creatinine ratio between 30 and 299 mg/g. RESULTS: Seventy Steady state Black African children with SCA (56% boys; average age 9.9 ± 4.3 years; 53% receiving hydroxyurea) were selected. Prevalence of microalbuminuria was 11.8%. LDH (r = 0.260; p = 0.033) and WBC count (r = 0.264; p = 0.033) were positively correlated with UACR whereas GPx (- 0.328; p = 0.007) and Cu-Zn SOD (- 0.210; p = 0.091) were negatively correlated with UACR. CONCLUSIONS: Albuminuria is associated with decreased antioxidant capacity and increased levels of markers of hemolysis and inflammation. Therefore, strategies targeting the reduction of sickling and subsequent hemolysis, oxidative stress and inflammation could help preventing or at least delaying the progression of kidney disease in SCA children.

Microalbuminuria among HIV-infected antiretroviral therapy-naive children in the Democratic Republic of Congo.

BACKGROUND: To determine the prevalence of microalbuminuria and associated factors among Congolese human immunodeficiency virus (HIV)-infected children. METHODS: This was a cross-sectional study in which 77 HIV-infected antiretroviral therapy-naive children and 89 uninfected controls were enrolled. Microalbuminuria was assessed using the immune-turbidimetry method, and associated factors were studied by logistic regression. RESULTS/CONCLUSION: The prevalence of microalbuminuria was 18% in the HIV-infected children and 2% in the HIV-uninfected children. No common determinants of proteinuria were significantly associated with microalbuminuria.

Depression in children suffering from sickle cell anemia.

Sickle cell anemia is a chronic illness associated with important nonmedical complications. The prevalence of depression and its clinical profile among Congolese children suffering from sickle cell disease are unknown. We therefore conducted a cross-sectional study in children between 8 and 17 years. The main goal of this study was to describe prevalence and characteristics of depression in this population living in Kinshasa, the Democratic Republic of Congo. The cross-sectional survey is of patients attending 2 referral centers. Children aged 8 to 17 years old were evaluated by a semistructured interview and standardized scales for depression separated by age and sex, the Multiscore Depression Inventory for Children. Completed questionnaires were received from 81 respondents. There were 43 girls and 38 boys. Depression symptoms were observed in 70 (86.4%) cases. Among this group, 6 children (8.6%) were observed to have severe depression. The most common symptoms were observed to be social introversion (81.5%), defiance (77.8%), helplessness (76.5%), and sad mood (70.4%). Of the 70 subjects, 19 (23.5%) had suicidal ideation. In Kinshasa, the prevalence of depression was high to those reported in western countries. Psychological interventions for individuals with sickle cell disease might complement current medical treatment in our midst.

Prevalence of sickle cell disease in a pediatric population suffering from severe infections: a Congolese experience.

Neonatal screening for sickle cell anemia is not a common practice in the Democratic Republic of Congo (DRC). Children with sickle cell disease are known to have an increased risk of infections. We conducted a pilot study to determine the prevalence of sickle cell anemia during episodes of severe infection. A prospective study was conducted from July 2009 to July 2011. The study sites included four public hospitals at Kinshasa, DRC. The study population was selected from the source population using three-stage sampling. A total of 247 children with severe infection were consecutively recruited and screened for sickle cell disease. There were 124 boys (50.2%) and 123 girls (49.8%) with a sex-ratio of 1:1. More than two-thirds of patients (66.0%) were children between 1 and 24 months of age. Among these 247 children, 19 (7.7%) were homozygous sickle cell anemia patients (Hb SS). No patient had received Hemophilus influenzae, streptococcus pneumoniae and salmonella sp vaccines. Sepsis was the most common form of severe infection observed in 44.5% of patients. A total of 19 (7.7%) positive blood cultures were recorded. Most cases were reported in sickle cell patients (15.8%) compared to 6.1% in children who were negative for Hb S [ß6(A3)Glu→Val; HBB: c.20A>T] (p > 0.05). Of 247 children with severe infection, approximately 8.0% carried unknown sickle cell anemia mutations. Based on the findings in this study, opportunistic testing for sickle cell anemia is possible and worthwhile in children who present with severe infection in DRC until neonatal screening is universal.

A rare occurrence of hairy cell leukemia in a congolese child: a presentation and challenge of diagnosis in low resource settings.

BACKGROUND: Hairy cell leukemia is a rare form of leukemia and has been rarely reported in African and pediatric population. OBSERVATION: We are reporting a 4-year-old child who was received for investigation for persistent anemia, prolonged fever, and thrombocytopenia. Bone marrow aspiration showed hypercellular marrow with cells characterized by irregular windblown-appearing cell borders with pseudopod-like projections. Our patient presented with hairy cell leukemia. CONCLUSION: The diagnosis was thought to be most consistent with hairy cell leukemia based on the distinctive morphology of the cells.

Acute renal failure in Congolese children: a tertiary institution experience.

AIM: Published data on acute renal failure in children from the Democratic Republic of Congo are rare. The objective of this study was to review clinical manifestations, aetiologies and outcome in hospitalized children with acute renal failure. METHODS: A retrospective study at Pediatric Nephrology Unit of University Hospital of Kinshasa was carried out. RESULTS: Fifty-six children with acute renal failure were eligible. There were 31 boys (55.4%) and 25 girls (44.6%) with a sex ratio of 1.24. The median age was 6.7 years (range 1-13 years). Fever (80.3%), oligo-anuria (73.2%), jaundice (67.9%) were the common clinical presentation. Blackwater fever (42.8%) was the leading cause of Acute Renal Failure. The incidence of severe dehydration because of gastroenteritis was low (5.3%). Around 12.5% of patients' misused herbal plants. Acute Peritoneal Dialysis was indicated in 15/56 children and only performed in four patients. Fourteen children (25%) died. CONCLUSION: A wide spectrum of features was seen in hospitalized Acute Renal Failure children and limited access to Acute Peritoneal Dialysis remained an important mortality risk factor.

Nocturnal enuresis in children in Kinshasa, Democratic Republic of Congo.

AIM: To determine the prevalence of nocturnal enuresis in children of Kinshasa in Democratic Republic of Congo. METHODS: In all, 506 questionnaires were sent to parents of children aged 6-12 years randomly selected from four primary schools in Kinshasa, Democratic Republic of Congo. The questionnaire was designed to collect information about prevalence and factors associated with nocturnal enuresis. RESULTS: A total of 415 (82.0%) were correctly completed. In this series, 109 children were identified as nocturnal enuresis in which 50 boys and 56 girls (p > 0.05). Factors associated with nocturnal enuresis were deep sleep, young age and familial history of enuresis (p < 0.05). Only 11% of patients have been consulted by doctors. Twelve children (11.0%) were treated by healers traditional. In the other part, 43 children (39.4%) were frequently punished by their parents. The common self-help strategies were 79 children (72.5%) were submitted to fluid restrictions before going to sleep and 68 (62.4%) were waking the child at night to void. CONCLUSION: In Kinshasa, the prevalence of nocturnal enuresis was high to those reported in Asian and Western countries. Nocturnal enuresis remains an important clinical problem in children but only a small percentage of parents seek medical help.