Nephrologists' Views on a Workflow for Returning Genetic Results to Research Participants.

Introduction: Returning research-based genetic results (gRoR) to participants in nephrology research can improve care; however, the practice raises implementational questions and no established guidelines for this process currently exist. Nephrologists' views on this issue can inform the process but are understudied.

Methods: We developed a conceptual workflow for gRoR from literature and experience, covering aspects such as which results to return, how, and by whom.

Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease.

African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers.

Strong protective effect of the p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease.

Black Americans have a significantly higher risk of developing chronic kidney disease (CKD), especially focal segmental glomerulosclerosis (FSGS), than European Americans. Two coding variants (G1 and G2) in the gene play a major role in this disparity. While 13% of Black Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers.

Rare Single Nucleotide and Copy Number Variants and the Etiology of Congenital Obstructive Uropathy: Implications for Genetic Diagnosis.

Significance Statement: Congenital obstructive uropathy (COU) is a prevalent human developmental defect with highly heterogeneous clinical presentations and outcomes. Genetics may refine diagnosis, prognosis, and treatment, but the genomic architecture of COU is largely unknown. Comprehensive genomic screening study of 733 cases with three distinct COU subphenotypes revealed disease etiology in 10.

The effect of genetic education on the referral of patients to genetic evaluation: Findings from a national survey of nephrologists.

Purpose: The success of genomic medicine hinges on the implementation of genetic knowledge in clinical settings. In novel subspecialties, it requires that clinicians refer patients to genetic evaluation or testing, however referral is likely to be affected by genetic knowledge.

Methods: An online survey was administered to self-identified nephrologists working in the United States.

Low nephron endowment increases susceptibility to renal stress and chronic kidney disease.

Preterm birth results in low nephron endowment and increased risk of acute kidney injury (AKI) and chronic kidney disease (CKD). To understand the pathogenesis of AKI and CKD in preterm humans, we generated potentially novel mouse models with a 30%-70% reduction in nephron number by inhibiting or deleting Ret tyrosine kinase in the developing ureteric bud. These mice developed glomerular and tubular hypertrophy, followed by the transition to CKD, recapitulating the renal pathological changes seen in humans born preterm.

Snapshots of nascent RNA reveal cell- and stimulus-specific responses to acute kidney injury.

The current strategy to detect acute injury of kidney tubular cells relies on changes in serum levels of creatinine. Yet serum creatinine (sCr) is a marker of both functional and pathological processes and does not adequately assay tubular injury. In addition, sCr may require days to reach diagnostic thresholds, yet tubular cells respond with programs of damage and repair within minutes or hours.

Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux.

Background: Vesicoureteral reflux (VUR) is a common, familial genitourinary disorder, and a major cause of pediatric urinary tract infection (UTI) and kidney failure. The genetic basis of VUR is not well understood.

Methods: A diagnostic analysis sought rare, pathogenic copy number variant (CNV) disorders among 1737 patients with VUR.

AKI in COVID-19-Associated Multisystem Inflammatory Syndrome in Children (MIS-C).

Background: Multisystem inflammatory syndrome in children (MIS-C) is a recently identified entity in association with COVID-19. AKI has been widely reported in patients with primary COVID-19 infection. However, there is a paucity of literature regarding renal injury in MIS-C.

Molecular regulation and function of FoxO3 in chronic kidney disease.

Purpose Of Review: FOXOs are transcription factors that regulate downstream target genes to counteract to cell stress. Here we review the function and regulation of FOXO transcription factors, the mechanism of FOXO3 activation in the kidney, and the role of FOXO3 in delaying the development of chronic kidney disease (CKD).

Recent Findings: Progressive renal hypoxia from vascular dropout and metabolic perturbation is a pathogenic factor for the initiation and development of CKD.

Restraining Lysosomal Activity Preserves Hematopoietic Stem Cell Quiescence and Potency.

Quiescence is a fundamental property that maintains hematopoietic stem cell (HSC) potency throughout life. Quiescent HSCs are thought to rely on glycolysis for their energy, but the overall metabolic properties of HSCs remain elusive. Using combined approaches, including single-cell RNA sequencing (RNA-seq), we show that mitochondrial membrane potential (MMP) distinguishes quiescent from cycling-primed HSCs.

FoxO3 activation in hypoxic tubules prevents chronic kidney disease.

Acute kidney injury (AKI) can lead to chronic kidney disease (CKD) if injury is severe and/or repair is incomplete. However, the pathogenesis of CKD following renal ischemic injury is not fully understood. Capillary rarefaction and tubular hypoxia are common findings during the AKI to CKD transition.

Author Correction: The copy number variation landscape of congenital anomalies of the kidney and urinary tract.

In the version of this article initially published, affiliation 38 incorrectly read "ICNU-Nephrology and Urology Department, Barcelona, Spain"; "Renal Division, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain" is the correct affiliation. The error has been corrected in the HTML and PDF versions of the article.

Patent ductus arteriosus is associated with acute kidney injury in the preterm infant.

Background: This study aimed to test the hypothesis that a patent ductus arteriosus (PDA) is independently associated with acute kidney injury (AKI) in neonates ≤ 28 weeks gestation.

Methods: Preterm infants with echocardiographic diagnosis of moderate-large PDA at age ≤ 30 days were studied retrospectively. AKI, the primary outcome, was defined and staged according to serum creatinine using Kidney Disease Improving Global Outcomes (KDIGO) neonatal criteria.

Efficiency and performance tests of the sorptive building materials that reduce indoor formaldehyde concentrations.

The adsorption of volatile organic compounds by building materials reduces the pollutant concentrations in indoor air. We collected three interior building materials with adsorption potentials-latex paint, micro-carbonized plywood, and moisture-buffering siding-used the sorptive building materials test (SBMT) to determine how much they reduced indoor formaldehyde (HCHO) concentrations, and then assessed the consequent reduction in human cancer risk from HCHO inhalation. Adsorption of HCHO by building materials significantly improved the effective ventilation efficiency.

The copy number variation landscape of congenital anomalies of the kidney and urinary tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genomic disorders (GD).

Sandwich Technique for Endovascular Repair of Acute Type A Aortic Dissection.

Overview: To describe a new endovascular procedure for acute type A aortic dissection (TAAD) repair.

Methods: Between 2013 and 2016, 12 patients (average age 54±9.6 years; 10 men) with acute TAAD (mean EURO score 11.

Forkhead box O3 (FoxO3) regulates kidney tubular autophagy following urinary tract obstruction.

Autophagy has been shown to be important for normal homeostasis and adaptation to stress in the kidney. Yet, the molecular mechanisms regulating renal epithelial autophagy are not fully understood. Here, we explored the role of the stress-responsive transcription factor forkhead box O3 (FoxO3) in mediating injury-induced proximal tubular autophagy in mice with unilateral ureteral obstruction (UUO).

A Modified and Less Invasive Procedure in Aortic Arch Replacement.

Circulation arrest is widely used during total aortic arch replacement. However, the conventional procedures have high morbidity and mortality. We modified the hybrid procedure by optimizing the sequence of anastomosis between the graft and aorta.