Responding to the workforce crisis: consensus recommendations from the Second Workforce Summit of the American Society of Pediatric Nephrology.

Importance: Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care.

Objective: To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce.

Utility of kidney ultrasonography during initial evaluation of pediatric nephrotic syndrome.

Background: Current guidelines note a gap in high-quality evidence regarding utility of kidney ultrasonography (KUS) during initial evaluation of nephrotic syndrome (NS) due to presumed minimal change disease (pMCD). However, KUS is frequently obtained at our institution. This retrospective chart review assessed incidence and impact of abnormal sonographic findings in these patients.

Polygenic genetic variation affecting antibody formation underlies hypertensive renal injury in the stroke-prone spontaneously hypertensive rat.

During development of the spontaneously hypertensive rat (SHR), several distinct but closely related lines were generated. Most lines are resistant to hypertensive renal disease. However, the SHR-A3 line (stroke-prone SHR) experiences end-organ injury (EOI) and provides a model of injury susceptibility that can be used to uncover genetic causation.

Fetal Nephrology: A Quaternary Care Center Experience.

Key Points: Specialized fetal centers see a highly complex subset of patients with CAKUT with a predominance of complex or syndromic disease. The mortality rate for fetuses with complex developmental anomalies and CAKUTs or bilateral CAKUTs is high. Prenatal genetic testing was highly variable with limited diagnostic utility while focused postnatal genetic testing had much higher yield.

Fetal bladder morphology as a predictor of outcome in fetal lower urinary tract obstruction.

Objective: We evaluate survival of fetuses with severe Lower Urinary Tract Obstruction (LUTO) based on bladder morphology. We hypothesize that fetuses with a "floppy" appearing bladder on initial prenatal ultrasound will have worse infant outcomes than fetuses with full/rounded bladders.

Method: We retrospectively reviewed all cases of LUTO evaluated in our fetal center between January 2013 and December 2021.

Compound heterozygosity of a de novo submicroscopic deletion and an inherited frameshift pathogenic variant in the gene in a fetus with bilaterally enlarged and echogenic kidneys, enlarged abdomen and oligohydramnios.

We present a fetus with bilaterally enlarged and echogenic kidneys. Prenatal testing detected compound heterozygosity for a 0.676 Mb de novo deletion and an inherited pathogenic variant in .

Genetic diagnosis and renal biopsy findings in the setting of a renal genetics clinic.

As genetic testing becomes more available, its utilization as an early diagnostic tool in nephrology is more common. The objective of the study is to examine diagnostic agreement between the renal biopsy findings and genetic diagnoses. A retrospective study was conducted in February 2022.

Variants in genes coding for collagen type IV α-chains are frequent causes of persistent, isolated hematuria during childhood.

Background: Children with persistent, isolated microscopic hematuria typically undergo a limited diagnostic workup and are monitored for signs of kidney disease in long-term longitudinal follow-up, which can delay diagnosis and allow disease progression in some cases.

Methods: To determine the clinical utility of genetic screening in this population, we performed targeted genetic testing using a custom, 32-gene next-generation sequencing panel for progressive kidney disease on children referred to the Texas Children's Hospital Pediatric Nephrology clinic for persistent, microscopic hematuria (n = 30; cohort 1). Patients with microscopic hematuria identified by urinalysis on at least two separate occasions were eligible for enrollment, but those with other evidence of kidney disease were excluded.

Lupus Nephritis, Autoantibody Production and Kidney Outcomes in Males with Childhood-Onset Systemic Lupus Erythematosus.

Childhood-onset systemic lupus erythematosus (cSLE) only represents 20% of all SLE patients, and males with SLE only represent 10%. To study this rare SLE subset, males diagnosed with cSLE over a 30-year period were identified. Organ involvement, autoantibody production, hypocomplementemia, and kidney biopsy findings were compared to cSLE females.

Emerging Insights Into Chronic Renal Disease Pathogenesis in Hypertension From Human and Animal Genomic Studies.

The pathogenic links between elevated blood pressure and chronic kidney disease remain obscure. This article examines progress in population genetics and in animal models of hypertension and chronic kidney disease. It also provides a critique of the application of genome-wide association studies to understanding the heritability of renal function.

The effect of continuous venovenous hemodiafiltration on amino acid delivery, clearance, and removal in children.

Background: In critically ill children with acute kidney injury (AKI), continuous kidney replacement therapy (CKRT) enables nutrition provision. The magnitude of amino acid loss during continuous venovenous hemodiafiltration (CVVHDF) is unknown and needs accurate quantification. We investigated the mass removal and clearance of amino acids in pediatric CVVHDF.

Clinical Utility of Genetic Testing in the Precision Diagnosis and Management of Pediatric Patients with Kidney and Urinary Tract Diseases.

Background: As genetic testing increasingly integrates into the practice of nephrology, our understanding of the basis of many kidney disorders has exponentially increased. Given this, we recently initiated a Renal Genetics Clinic (RGC) at our large, urban children's hospital for patients with kidney disorders.

Methods: Genetic testing was performed in Clinical Laboratory Improvement Amendments-certified laboratories using single gene testing, multigene panels, chromosomal microarray, or exome sequencing.

Natural genetic variation in Stim1 creates stroke in the spontaneously hypertensive rat.

Similar to humans, the risk of cerebrovascular disease in stroke-prone spontaneously hypertensive rats (SHR-A3/SHRSP) arises from naturally occurring genetic variation. In the present study, we show the involvement of genetic variation affecting the store-operated calcium signaling gene, Stim1, in the pathogenesis of stroke in SHR. Stim1 is a key lymphocyte activation signaling molecule and contains functional variation in SHR-A3 that diverges from stroke-resistant SHR-B2.

Polymorphism Disrupts Immune Signaling and Creates Renal Injury in Hypertension.

Background Spontaneously hypertensive rats of the stroke-prone line (SHR-A3) develop hypertensive renal disease as a result of naturally occurring genetic variation. Our prior work identified a single-nucleotide polymorphism unique to SHR-A3 that results in truncation of the carboxy terminus of STIM1. The SHR-B2 line, which is also hypertensive but resists hypertensive renal injury, expresses the wild-type STIM1.

Correction: DYRK1A-related intellectual disability: a syndrome associated with congenital anomalies of the kidney and urinary tract.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Nephronophthisis due to a novel DCDC2 variant in a patient from African-Caribbean descent: A case report.

Nephronophthisis-19 (NPHP19) due to truncating mutations in the DCDC2 gene has only been described previously in two patients. We describe a new case in a patient from the island country of Saint Vincent and the Grenadines, in the West Indies. This condition is a renal-hepatic ciliopathy with phenotypic characteristics that include hepatosplenomegaly, hepatic fibrosis with bile cholestasis, increased kidney echogenicity, and end-stage renal disease.

Germ-line genetic variation in the immunoglobulin heavy chain creates stroke susceptibility in the spontaneously hypertensive rat.

The risk of cerebrovascular disease in stroke-prone spontaneously hypertensive rats (SHR-A3/SHRSP) arises from naturally occurring genetic variation. In the present study we show the involvement of SHR genetic variation that affects antibody formation and function in the pathogenesis of stroke. We have tested the involvement in susceptibility to stroke of genetic variation in , the gene encoding the immunoglobulin heavy chain by congenic substitution.

Characterization of the renal phenotype in RMND1-related mitochondrial disease.

Background: The nuclear encoded gene RMND1 (Required for Meiotic Nuclear Division 1 homolog) has recently been linked to RMND1-related mitochondrial disease (RRMD). This autosomal recessive condition characteristically presents with an infantile-onset multisystem disease characterized by severe hypotonia, global developmental delay, failure to thrive, sensorineural hearing loss, and lactic acidosis. Renal disease, however, appears to be one of the more prominent features of RRMD, affecting patients at significantly higher numbers compared to other mitochondrial diseases.

DYRK1A-related intellectual disability: a syndrome associated with congenital anomalies of the kidney and urinary tract.

Purpose: Haploinsufficiency of DYRK1A causes a recognizable clinical syndrome. The goal of this paper is to investigate congenital anomalies of the kidney and urinary tract (CAKUT) and genital defects (GD) in patients with DYRK1A variants.

Methods: A large database of clinical exome sequencing (ES) was queried for de novo DYRK1A variants and CAKUT/GD phenotypes were characterized.

Peritoneal dialysis catheter outcomes in infants initiating peritoneal dialysis for end-stage renal disease.

Background: End-stage renal disease (ESRD) although rare among infants presents many management challenges. We sought to evaluate factors associated with PD catheter failure among infants initiated on chronic PD.

Methods: A retrospective chart review of all children under two years of age who had PD catheters placed for initiation of chronic PD from 2002 to 2015.

Surgical interventions and anesthesia in the 1st year of life for lower urinary tract obstruction.

Background: Patients with a prenatal diagnosis of lower urinary tract obstruction (LUTO) may undergo prenatal interventions, such as vesicoamniotic shunt (VAS) placement, as a temporary solution for relieving urinary tract obstruction. A recent FDA communication has raised awareness of the potential neurocognitive adverse effects of anesthesia in children. We hypothesized as to whether a prenatal LUTO staging system was predictive of the number of anesthesia events for prenatally diagnosed LUTO patients.

Interventions in children with renovascular hypertension: A 27-year retrospective single-center experience.

Background: Renovascular hypertension (RVH) can be caused by renal artery stenosis (RAS) and/or middle aortic syndrome (MAS).

Methods: Patients who received surgical or transcatheter treatment for RVH between 1/1991 and 11/2017 were retrospectively reviewed using age = adjusted blood pressure ratio (BPR).

Results: Fifty-three patients diagnosed with RVH at a median age of 4.

Susceptibility to Hypertensive Renal Disease in the Spontaneously Hypertensive Rat Is Influenced by 2 Loci Affecting Blood Pressure and Immunoglobulin Repertoire.

High blood pressure exerts its deleterious effects on health largely through acceleration of end-organ diseases. Among these, progressive loss of renal function is particularly important, not only for the direct consequences of kidney damage but also because loss of renal function is associated with amplification of other adverse cardiovascular outcomes. Genetic susceptibility to hypertension and associated end-organ disease is non-Mendelian in both humans and in a rodent model, the spontaneously hypertensive rat (SHR).

Therapeutic Plasma Exchange Use in Pediatric Neurologic Disorders at a Tertiary Care Center: A 10-Year Review.

Pediatric neurologic conditions requiring therapeutic plasma exchange are rare in children and literature is sparse. The study aims to determine the outcomes, safety, and feasibility of therapeutic plasma exchange treatment in pediatric neurologic disorders. This retrospective analysis looked at the outcomes and safety of therapeutic plasma exchange in children (n = 50) with neurologic conditions.