APOL1 Modulates Renin-Angiotensin System.

Patients carrying APOL1 risk alleles (G1 and G2) have a higher risk of developing Focal Segmental Glomerulosclerosis (FSGS); we hypothesized that escalated levels of miR193a contribute to kidney injury by activating renin-angiotensin system (RAS) in the APOL1 milieus. Differentiated podocytes (DPDs) stably expressing vector (V/DPD), G0 (G0/DPDs), G1 (G1/DPDs), and G2 (G2/DPDs) were evaluated for renin, Vitamin D receptor (VDR), and podocyte molecular markers (PDMMs, including WT1, Podocalyxin, Nephrin, and Cluster of Differentiation [CD]2 associated protein [AP]). G0/DPDs displayed attenuated renin but an enhanced expression of VDR and Wilms Tumor [WT]1, including other PDMMs; in contrast, G1/DPDs and G2/DPDs exhibited enhanced expression of renin but decreased expression of VDR and WT1, as well as other PDMMs (at both the protein and mRNA levels).

Assisting primary care teams and patients in a culturally diverse periphery: impact on medical students' future career choices.

Background: Medical students can assist in reducing healthcare disparities and promote health equity by engaging with rural communities and gaining insights into their unique healthcare needs. A two-arm student-delivered program was designed and implemented during COVID-19 in a social-geographic peripheral area to assist clinics with complex chronic and/or socially disadvantaged patients and improve preventive behavior in townships through home visits delivering community kits.

Methods: We conducted a pre-post design study which included weekly structured medical student reports and monthly structured telephone interviews with clinic directors and municipal partners.

APOL1 nephropathy - a population genetics success story.

Purpose Of Review: More than a decade ago, apolipoprotein L1 ( APOL1 ) risk alleles designated G1 and G2, were discovered to be causally associated with markedly increased risk for progressive kidney disease in individuals of recent African ancestry. Gratifying progress has been made during the intervening years, extending to the development and clinical testing of genomically precise small molecule therapy accompanied by emergence of RNA medicine platforms and clinical testing within just over a decade.

Recent Findings: Given the plethora of excellent prior review articles, we will focus on new findings regarding unresolved questions relating mechanism of cell injury with mode of inheritance, regulation and modulation of APOL1 activity, modifiers and triggers for APOL1 kidney risk penetrance, the pleiotropic spectrum of APOL1 related disease beyond the kidney - all within the context of relevance to therapeutic advances.

Comparative Analysis of the APOL1 Variants in the Genetic Landscape of Renal Carcinoma Cells.

Although the relative risk of renal cell carcinoma associated with chronic kidney injury is particularly high among sub-Saharan African ancestry populations, it is unclear yet whether the gene risk variants (RV) for kidney disease additionally elevate this risk. APOL1 G1 and G2 RV contribute to increased risk for kidney disease in black populations, although the disease mechanism has still not been fully deciphered. While high expression levels of all three APOL1 allelic variants, G0 (the wild type allele), G1, and G2 are injurious to normal human cells, renal carcinoma cells (RCC) naturally tolerate inherent high expression levels of APOL1.

Endoplasmic reticulum-translocation is essential for APOL1 cellular toxicity.

Two variants at the gene, encoding apolipoprotein L1, account for more than 70% of the increased risk for chronic kidney disease in individuals of African ancestry. While the initiating event for APOL1 risk variant cell injury remains to be clarified, we explored the possibility of blocking APOL1 toxicity at a more upstream level. We demonstrate that deletion of the first six amino acids of exon 4 abrogates APOL1 cytotoxicity by impairing APOL1 translocation to the lumen of ER and splicing of the signal peptide.

De novo mutation rates at the single-mutation resolution in a human gene region associated with adaptation and genetic disease.

Although it is known that the mutation rate varies across the genome, previous estimates were based on averaging across various numbers of positions. Here, we describe a method to measure the origination rates of target mutations at target base positions and apply it to a 6-bp region in the human hemoglobin subunit beta () gene and to the identical, paralogous hemoglobin subunit delta () region in sperm cells from both African and European donors. The region of interest (ROI) includes the site of the hemoglobin S (HbS) mutation, which protects against malaria, is common in Africa, and has served as a classic example of adaptation by random mutation and natural selection.

HIV Viremia Is Associated With Variants and Reduced JC-Viruria.

Variants in the () gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two risk alleles, a role in HIV infectivity has been postulated in the mechanism of associated kidney disease. Herein, we aim to explore the association between HIV viremia and genotype.

The Double Edge Sword of Testosterone's Role in the COVID-19 Pandemic.

COVID-19 is a complex disease with a multifaceted set of disturbances involving several mechanisms of health and disease in the human body. Sex hormones, estrogen, and testosterone, seem to play a major role in its pathogenesis, development, spread, severity, and mortalities. Examination of factors such as age, gender, ethnic background, genetic prevalence, and existing co-morbidities, may disclose the mechanisms underlying SARS-CoV-2 infection, morbidity, and mortality, paving the way for COVID-19 amelioration and substantial flattening of the infection curve.

A Personalized Approach to Chronic Kidney Disease and Cardiovascular Disease: JACC Review Topic of the Week.

Cardiovascular disease is the most common cause of death in patients with end-stage renal disease (ESRD). The initiation of dialysis for treatment of ESRD exacerbates chronic electrolyte and hemodynamic perturbations. Rapid large shifts in effective intravascular volume and electrolyte concentrations ultimately lead to subendocardial ischemia, increased left ventricular wall mass, and diastolic dysfunction, and can precipitate serious arrhythmias through a complex pathophysiological process.

Kinins and chymase: the forgotten components of the renin-angiotensin system and their implications in COVID-19 disease.

The unique clinical features of COVID-19 disease present a formidable challenge in the understanding of its pathogenesis. Within a very short time, our knowledge regarding basic physiological pathways that participate in SARS-CoV-2 invasion and subsequent organ damage have been dramatically expanded. In particular, we now better understand the complexity of the renin-angiotensin-aldosterone system (RAAS) and the important role of angiotensin converting enzyme (ACE)-2 in viral binding.

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.

ACE2, COVID-19 Infection, Inflammation, and Coagulopathy: Missing Pieces in the Puzzle.

Engulfed by the grave consequences of the coronavirus disease 2019 (COVID-19) pandemic, a better understanding of the unique pattern of viral invasion and virulence is of utmost importance. Angiotensin (Ang)-converting enzyme (ACE) 2 is a key component in COVID-19 infection. Expressed on cell membranes in target pulmonary and intestinal host cells, ACE2 serves as an anchor for initial viral homing, binding to COVID-19 spike-protein domains to enable viral entry into cells and subsequent replication.

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.