G1 and G2 variants of apolipoprotein L1 among Central African population in Trypanosoma brucei gambiense endemic rural area.

Introduction: Apolipoprotein L1 (APOL1) risk variants (G1, G2) are known to enhance the protective ability against human African trypanosomiasis (HAT), in addition to their role in kidney and cardiovascular disease. The effects of these variants on trypanosome infection could differ regionally owing to local adaptations of the host and pathogen. This study explored APOL1 risk variants distribution in HAT-infected and non-infected populations from a rural Trypanosoma brucei gambiense (T.

Relevance of repeated analyses of albuminuria and glomerular filtration rate in African children with sickle cell anaemia.

Glomerular hyperfiltration and albuminuria are frequent kidney abnormalities in children with sickle cell anaemia (SCA). However, little is known about their persistence in African SCA children. This prospective study included 600 steady-state SCA children aged 2-18 years from the Democratic Republic of Congo.

Modeling complement activation on human glomerular microvascular endothelial cells.

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare kidney disease caused by dysregulation of the complement alternative pathway. The complement dysregulation specifically leads to damage to the glomerular endothelium. To further understand aHUS pathophysiology, we validated an model for measuring complement deposition on both control and patient human glomerular microvascular endothelial cells (GMVECs).

Functional evaluation of complement factor I variants by immunoassays and SDS-PAGE.

Factor I (FI) is an essential regulator of the complement system. Together with co-factors, FI degrades C3b, which inhibits further complement activation. Genetic mutations in FI are associated with pathological conditions like age-related macular degeneration and atypical hemolytic uremic syndome.

Glomerular hyperfiltration: part 2-clinical significance in children.

Glomerular hyperfiltration (GHF) is a phenomenon that can occur in various clinical conditions affecting the kidneys such as sickle cell disease, diabetes mellitus, autosomal dominant polycystic kidney disease, and solitary functioning kidney. Yet, the pathophysiological mechanisms vary from one disease to another and are not well understood. More so, it has been demonstrated that GHF may occur at the single-nephron in some clinical conditions while in others at the whole-kidney level.

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).

Benefits and Toxicity of Disulfiram in Preclinical Models of Nephropathic Cystinosis.

Nephropathic cystinosis is a rare disease caused by mutations of the CTNS gene that encodes for cystinosin, a lysosomal cystine/H+ symporter. The disease is characterized by early-onset chronic kidney failure and progressive development of extra-renal complications related to cystine accumulation in all tissues. At the cellular level, several alterations have been demonstrated, including enhanced apoptosis, altered autophagy, defective intracellular trafficking, and cell oxidation, among others.

Clinical and genetic factors are associated with kidney complications in African children with sickle cell anaemia.

Clinical and genetic factors have been reported as influencing the development of sickle cell nephropathy (SCN). However, such data remain limited in the paediatric population. In this cross-sectional study, we enrolled 361 sickle cell disease children from the Democratic Republic of Congo.

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

Apolipoprotein L1 () 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 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.

Urine-Derived Epithelial Cells as Models for Genetic Kidney Diseases.

Epithelial cells exfoliated in human urine can include cells anywhere from the urinary tract and kidneys; however, podocytes and proximal tubular epithelial cells (PTECs) are by far the most relevant cell types for the study of genetic kidney diseases. When maintained in vitro, they have been proven extremely valuable for discovering disease mechanisms and for the development of new therapies. Furthermore, cultured patient cells can individually represent their human sources and their specific variants for personalized medicine studies, which are recently gaining much interest.

Sickle cell nephropathy: insights into the pediatric population.

The life expectancy of individuals with sickle cell disease has increased over the years, majorly due to an overall improvement in diagnosis and medical care. Nevertheless, this improved longevity has resulted in an increased prevalence of chronic complications such as sickle cell nephropathy (SCN), which poses a challenge to the medical care of the patient, shortening the lifespan of patients by 20-30 years. Clinical presentation of SCN is age-dependent, with kidney dysfunction slowly beginning to develop from childhood, progressing to chronic kidney disease and kidney failure during the third and fourth decades of life.

Long-term treated HIV infection is associated with platelet mitochondrial dysfunction.

HIV infection and antiretroviral therapy have been linked to mitochondrial dysfunction. The role of platelet mitochondrial dysfunction in thrombosis, immunoregulation and age-related diseases is increasingly appreciated. Here, we studied platelet mitochondrial DNA content (mtDNA) and mitochondrial function in people living with HIV (PLHIV) and related this to platelet function.

Mitochondrial Disease and the Kidney With a Special Focus on CoQ Deficiency.

Mitochondrial cytopathies include a heterogeneous group of diseases that are characterized by impaired oxidative phosphorylation, leading to multi-organ involvement and progressive clinical deterioration. Most mitochondrial cytopathies that cause kidney symptoms are characterized by tubular defects, but glomerular, tubulointerstitial, and cystic diseases have also been described. Mitochondrial cytopathies can result from mitochondrial or nuclear DNA mutations.

The impact of COVID-19 pandemic on the diagnosis and management of inborn errors of metabolism: A global perspective.

Quantitative estimates for the global impact of COVID-19 on the diagnosis and management of patients with inborn errors of metabolism (IEM) are lacking. We collected relevant data from 16 specialized medical centers treating IEM patients in Europe, Asia and Africa. The median decline of reported IEM related services in March 1st-May 31st 2020 compared to the same period in 2019 were as high as 60-80% with a profound impact on patient management and care for this vulnerable patient group.

Chitotriosidase as a Novel Biomarker for Therapeutic Monitoring of Nephropathic Cystinosis.

Background: Nephropathic cystinosis, a hereditary lysosomal storage disorder caused by dysfunction of the lysosomal cotransporter cystinosin, leads to cystine accumulation and cellular damage in various organs, particularly in the kidney. Close therapeutic monitoring of cysteamine, the only available disease-modifying treatment, is recommended. White blood cell cystine concentration is the current gold standard for therapeutic monitoring, but the assay is technically demanding and is available only on a limited basis.

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.

Safety evaluation of conditionally immortalized cells for renal replacement therapy.

End-stage kidney disease represents irreversible kidney failure. Dialysis and transplantation, two main treatment options currently available, present various drawbacks and complications. Innovative cell-based therapies, such as a bioartificial kidney, have not reached the clinic yet, mostly due to safety and/or functional issues.

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

Introduction: Apolipoprotein-L1 () 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 risk variants and to assess the association between these variants and early-stage CKD in the general pediatric population and HIV-infected children.

Nephrotic syndrome in a dish: recent developments in modeling in vitro.

Nephrotic syndrome is a heterogeneous disease, and one of the most frequent glomerular disorders among children. Depending on the etiology, it may result in end-stage renal disease and the need for renal replacement therapy. A dysfunctional glomerular filtration barrier, comprising of endothelial cells, the glomerular basement membrane and podocytes, characterizes nephrotic syndrome.

Potentiation of complement regulator factor H protects human endothelial cells from complement attack in aHUS sera.

Mutations in the gene encoding for complement regulator factor H (FH) severely disrupt its normal function to protect human cells from unwanted complement activation, resulting in diseases such as atypical hemolytic uremic syndrome (aHUS). aHUS presents with severe hemolytic anemia, thrombocytopenia, and renal disease, leading to end-stage renal failure. Treatment of severe complement-mediated disease, such as aHUS, by inhibiting the terminal complement pathway, has proven to be successful but at the same time fails to preserve the protective role of complement against pathogens.