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

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Glomerular hyperfiltration: part 1 - defining the threshold - is the sky the limit?

peer reviewedGlomerular hyperfiltration (GHF) is an increase in single-nephron glomerular filtration rate (GFR) that occurs in both physiological states and pathological states. Whole-kidney GHF is often used as a surrogate for single-nephron hyperfiltration since determining single-nephron GFR is impossible in routine clinical care. A clear definition (read threshold) of GHF is lacking. The aim of the first part of this review was to find evidence for defining the threshold for GHF, based on literature review, including systematic reviews and meta-analysis data, with both measured and estimated GFR. The consensus pediatric threshold for GHF as obtained from reviews, measured and estimated GFR studies, can reliably be set to 135 mL/min/1.73 m2 for children aged > 2 years. Diagnosing GHF from SCr-based estimated GFR is not reliable in subjects with reduced muscle mass. In these cases, it could be of interest to confirm the state of GHF using cystatin C-based eGFR, or preferably, by measured GFR, using methods that are accurate in the high GFR-range

Glomerular hyperfiltration: part 2-clinical significance in children.

peer reviewedGlomerular 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. In this review, we explore the pathophysiological mechanisms of GHF in relation to various clinical conditions in the pediatric population. In addition, we discuss the role and mechanism of action of important factors such as gender, low birth weight, and race in the pathogenesis of GHF. Finally, in this current review, we further highlight the consequences of GHF in the progression of kidney disease

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. In this review, we summarize the methodology for establishing human podocyte and PTEC cell lines from urine and highlight their importance as kidney disease cell models. We explore the well-established and recent techniques of cell isolation, quantification, immortalization and characterization, and we describe their current and future applications

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.status: publishe