Kidney-specific methylation patterns correlate with kidney function and are lost upon kidney disease progression.

Background: Chronological and biological age correlate with DNA methylation levels at specific sites in the genome. Linear combinations of multiple methylation sites, termed epigenetic clocks, can inform us the chronological age and predict multiple health-related outcomes. However, why some sites correlating with lifespan, healthspan, or specific medical conditions remain poorly understood.

Effect of interleukin-1 antagonist on growth of children with colchicine resistant or intolerant FMF.

Introduction: Familial Mediterranean Fever (FMF) is the most common monogentic autoinflammatory disease. FMF results from mutations in MEFV, which lead to a pro-inflammatory state and increased production of Interleukin 1 beta subunit (IL-1b) by myeloid cells. Despite the overall positive results obtained with anti-IL-1 agents in FMF patients, little is known about the long-term growth impact of these drugs in the pediatric population.

The genetic basis of congenital anomalies of the kidney and urinary tract.

During the past decades, remarkable progress has been made in our understanding of the molecular basis of kidney diseases, as well as in the ability to pinpoint disease-causing genetic changes. Congenital anomalies of the kidney and urinary tract (CAKUT) are remarkably diverse, and may be either isolated to the kidney or involve other systems, and are notorious in their variable genotype-phenotype correlations. Genetic conditions underlying CAKUT are individually rare, but collectively contribute to disease etiology in ~ 16% of children with CAKUT.

[THE BIG CHALLENGES OF PEDIATRIC NEPHROLOGY AT THE OUTSET OF THE THIRD DECADE OF THE 21ST CENTURY].

Over the past few decades, there have been tremendous advancements in the field of nephrology due to developments in genetics and molecular biology, such as the ability to pinpoint the causative mutations in congenital syndromes involving the kidneys, animal models of kidney disease and an array of tools for manipulating nucleic acids. However, despite these achievements, in most cases, these sophisticated technologies have yet to translate into improved outcomes. Thus, there are still several important challenges in the field of pediatric nephrology, the most important of which are reviewed herein.

An Israeli tuberous sclerosis cohort: the efficacy of different anti-epileptic strategies.

Aim: We aimed to describe the experience of a large single-center cohort for the clinical, radiological, and genetic characteristics, as well as to determine the efficacy of different anti-epileptic strategies in children and adults with tuberous sclerosis complex (TSC).

Methods: We carried out a historical cohort study on 91 TSC patients treated in a single center between 2008 and 2018.

Results: Our cohort comprised 46 males and 45 females, with a median age of 15.

Protective effect of soluble Klotho in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass support-A pilot study.

Objective: The Klotho protein family plays important roles in several metabolic pathways. Soluble Klotho has been recently put forward as an antiaging protein, demonstrating renal and cardiovascular protective traits. Cardiopulmonary bypass (CPB) support during cardiac surgery has been implicated in several adverse outcomes in pediatric and adult patients.

Human Kidney Spheroids and Monolayers Provide Insights into SARS-CoV-2 Renal Interactions.

Background: Although coronavirus disease 2019 (COVID-19) causes significan t morbidity, mainly from pulmonary involvement, extrapulmonary symptoms are also major componen ts of the disease. Kidney disease, usually presenting as AKI, is particularly severe among patients with COVID-19. It is unknown, however, whether such injury results from direct kidney infection with COVID-19's causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or from indirect mechanisms.

Mixing Cells for Vascularized Kidney Regeneration.

The worldwide rise in prevalence of chronic kidney disease (CKD) demands innovative bio-medical solutions for millions of kidney patients. Kidney regenerative medicine aims to replenish tissue which is lost due to a common pathological pathway of fibrosis/inflammation and rejuvenate remaining tissue to maintain sufficient kidney function. To this end, cellular therapy strategies devised so far utilize kidney tissue-forming cells (KTFCs) from various cell sources, fetal, adult, and pluripotent stem-cells (PSCs).

Is the prognosis of congenital single functioning kidney benign? A population-based study.

Background: We investigated the risk of kidney injury among adolescents with and without a congenital single functioning kidney (SFK).

Methods: This retrospective study is based on a medical evaluation database of 17-year-old Israeli conscripts, born during 1989-1999. Those with congenital SFK diagnosis, verified by a pediatric nephrologist's review of the original military medical committee classifications, were compared to the rest of the cohort.

Childhood Cancer and the Risk of ESKD.

Background: Increasing cancer incidence among children alongside improved treatments has resulted in a growing number of pediatric cancer survivors. Despite childhood cancer survivors' exposure to various factors that compromise kidney function, few studies have investigated the association between childhood cancer and future kidney disease.

Methods: To assess the risk of ESKD among childhood cancer survivors, we conducted a nationwide, population-based, retrospective cohort study that encompassed all Israeli adolescents evaluated for mandatory military service from 1967 to 1997.

Acute pyelonephritis in children and the risk of end-stage kidney disease.

Background: Pyelonephritis is the most common serious bacterial infection during childhood. The long-term importance of kidney scarring is unclear.

Objective: To assess the risk of end-stage kidney disease (ESKD) in adolescents and young adults with history of pyelonephritis.

Kidney failure risk in type 1 vs. type 2 childhood-onset diabetes mellitus.

Background: Diabetic kidney disease (DKD) is becoming increasingly common among children. We aimed to estimate the risk of end-stage renal disease (ESKD) and mortality among adolescents with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) and normal renal function compared with non-diabetics. We hypothesized that childhood onset T1DM vs.

Successful Introduction of Human Renovascular Units into the Mammalian Kidney.

Background: Cell-based therapies aimed at replenishing renal parenchyma have been proposed as an approach for treating CKD. However, pathogenic mechanisms involved in CKD such as renal hypoxia result in loss of kidney function and limit engraftment and therapeutic effects of renal epithelial progenitors. Jointly administering vessel-forming cells (human mesenchymal stromal cells [MSCs] and endothelial colony-forming cells [ECFCs]) may potentially result in formation of vascular networks.

Ex Vivo Expanded 3D Human Kidney Spheres Engraft Long Term and Repair Chronic Renal Injury in Mice.

End-stage renal disease is a worldwide epidemic requiring renal replacement therapy. Harvesting tissue from failing kidneys and autotransplantation of tissue progenitors could theoretically delay the need for dialysis. Here we use healthy and end-stage human adult kidneys to robustly expand proliferative kidney epithelial cells and establish 3D kidney epithelial cultures termed "nephrospheres.

NCAM1/FGF module serves as a putative pleuropulmonary blastoma therapeutic target.

Pleuropulmonary blastoma (PPB) is a rare pediatric lung neoplasm that recapitulates developmental pathways of early embryonic lungs. As lung development proceeds with highly regulated mesenchymal-epithelial interactions, a DICER1 mutation in PPB generates a faulty lung differentiation program with resultant biphasic tumors composed of a primitive epithelial and mesenchymal stroma with early progenitor blastomatous cells. Deciphering of PPB progression has been hampered by the difficulty of culturing PPB cells, and specifically progenitor blastomatous cells.

Novel homozygous ENPP1 mutation causes generalized arterial calcifications of infancy, thrombocytopenia, and cardiovascular and central nervous system syndrome.

Generalized arterial calcifications of infancy (GACI) is caused by mutations in ENPP1. Other ENPP1-related phenotypes include pseudoxanthoma elasticum, hypophosphatemic rickets, and Cole disease. We studied four children from two Bedouin consanguineous families who presented with severe clinical phenotype including thrombocytopenia, hypoglycemia, hepatic, and neurologic manifestations.

In Vivo Expansion of Cancer Stemness Affords Novel Cancer Stem Cell Targets: Malignant Rhabdoid Tumor as an Example.

Cancer stem cell (CSC) identification relies on transplantation assays of cell subpopulations sorted from fresh tumor samples. Here, we attempt to bypass limitations of abundant tumor source and predetermined immune selection by in vivo propagating patient-derived xenografts (PDX) from human malignant rhabdoid tumor (MRT), a rare and lethal pediatric neoplasm, to an advanced state in which most cells behave as CSCs. Stemness is then probed by comparative transcriptomics of serial PDXs generating a gene signature of epithelial to mesenchymal transition, invasion/motility, metastasis, and self-renewal, pinpointing putative MRT CSC markers.

mTORC1 Inhibition Is an Effective Treatment for Sporadic Renal Angiomyolipoma.

Introduction: Renal angiomyolipoma (AML) is the most common benign renal tumor. Despite a generally benign histology, AML can result in significant morbidity, from intra-abdominal hemorrhage and reduction in kidney function. While classically associated with the autosomal dominant disorder tuberous sclerosis complex (TSC) or with pulmonary lymphangioleiomyomatosis, most AMLs are sporadic.

Peroxisome proliferator-activated receptor gamma (PPARγ) is central to the initiation and propagation of human angiomyolipoma, suggesting its potential as a therapeutic target.

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Increasing Prevalence of Nephrolithiasis in Association with Increased Body Mass Index in Children: A Population Based Study.

Purpose: Epidemiological studies demonstrate an association of increased body mass index and risk of kidney stone formation in adults. We conducted a population based pediatric study to examine the epidemiology of nephrolithiasis in Israeli children during a 30-year period, and to determine body mass index distribution during the same period.

Materials And Methods: We accessed data from the compulsory medical evaluations of 17-year-old military service candidates in Israel before their enlistment during 1980 to 2013.