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.

Whole Exome Sequencing in a Population With Severe Congenital Anomalies of Kidney and Urinary Tract.

Fetal and neonatal interventions (e.g., amnioinfusions, amniotic shunting, and infant dialysis) have increased survival of infants with severe Congenital Anomalies of the Kidney and Urinary Tract (CAKUT), however, outcomes vary dramatically.

Pregnancy associated TMA in 13-year-old patient successfully treated with Eculizumab: case report.

Background: This report introduces an unusual cause of kidney failure in a previously healthy pediatric patient. She developed thrombotic microangiopathy (TMA) that was diagnosed post-partum, requiring dialysis and eculizumab, with eventual recovery of kidney function ([chronic kidney disease (CKD) stage 3].

Case Presentation: The patient was induced at term due to preeclampsia, with delivery complicated by severe postpartum hemorrhage from uterine atony.

Omentectomy reduces the need for peritoneal dialysis catheter revision in children: a study from the Pediatric Nephrology Research Consortium.

Background: There are no multi-center studies examining omentectomy and peritoneal dialysis (PD) catheter revision in the pediatric dialysis population.

Methods: We performed a retrospective study at eight centers within the Pediatric Nephrology Research Consortium (PNRC). Data review included all incident tunneled PD catheters placed between 1/1/2011 and 12/31/2016 in pediatric stage 5 chronic kidney disease (CKD 5) patients.

Hypervitaminosis A in Pediatric Patients With Advanced Chronic Kidney Disease.

Objective: Hypervitaminosis A is well-described but overlooked in chronic kidney disease (CKD) and has been associated with hypercalcemia, contributing to mineral bone disease. Our objective is to assess prevalence of hypervitaminosis A and its association with bone health in an advanced-CKD population.

Methods: We performed a retrospective review of 58 children with CKD 4-5 to examine the association between vitamin A levels and bone health and compared these values between a primarily formula-fed (FF) and nonprimarily formula-fed cohort (NFF).

Distinct urinary lipid profile in children with focal segmental glomerulosclerosis.

Background: Focal segmental glomerulosclerosis (FSGS) accounts for the majority of new-onset end-stage renal disease (ESRD) during adolescence. FSGS treatment is a great challenge for pediatric nephrologists due to intertwined molecular pathways underlining its complex pathophysiology. There is emerging evidence showing that perturbed lipid metabolism plays a role in the pathophysiology of FSGS.

Akt Links Insulin Signaling to Albumin Endocytosis in Proximal Tubule Epithelial Cells.

Diabetes mellitus (DM) has become an epidemic, causing a significant decline in quality of life of individuals due to its multisystem involvement. Kidney is an important target organ in DM accounting for the majority of patients requiring renal replacement therapy at dialysis units. Microalbuminuria (MA) has been a valuable tool to predict end-organ damage in DM but its low sensitivity has driven research efforts to seek other alternatives.

Akt recruits Dab2 to albumin endocytosis in the proximal tubule.

Proximal tubule epithelial cells have a highly sophisticated endocytic machinery to retrieve the albumin in the glomerular filtrate. The megalin-cubilin complex and the endocytic adaptor disabled-2 (Dab2) play a pivotal role in albumin endocytosis. We previously demonstrated that protein kinase B (Akt) regulates albumin endocytosis in the proximal tubule through an interaction with Dab2.

Atherosclerotic renal artery stenosis as a cause for hypertension in an adolescent patient.

Background: Atherosclerosis causing renal artery stenosis (RAS) is one of the most common secondary causes of hypertension in adults, but is rare in children.

Case-diagnosis/treatment: RAS associated with coronary artery stenosis was diagnosed in a teenage patient who presented with intermittent chest pain and elevated blood pressures for 6 years. The diagnosis of RAS was suspected after physical examination revealed an abdominal bruit.

Proteinuria and progression of glomerular diseases.

One of the major challenges of nephrology is to develop therapeutic strategies to halt the progression of kidney diseases. In clinical settings, nephrotic-range proteinuria correlates with the rate of progression, particularly in glomerular diseases. Hence, the degree of proteinuria has been utilized to monitor the response to treatment as well as to predict outcome.

PKB/Akt partners with Dab2 in albumin endocytosis.

Albumin in the glomerular filtrate is normally retrieved by concerted efforts of clathrin, LDL-type receptor megalin- and clathrin-associated sorting proteins. In glomerular diseases, albumin overload triggers a proapoptotic and inflammatory response contributing to tubulointerstitial fibrosis and tubular atrophy. The relationship between albumin overload-induced proximal tubule injury and albumin endocytosis remains to be discovered.

Pediatric living donor kidney transplantation under alemtuzumab pretreatment and tacrolimus monotherapy: 4-year experience.

Background: Alemtuzumab has been used in off-label studies of solid organ transplantation.

Methods: We analyzed the first 42 pediatric consecutive living donor kidney transplantations under alemtuzumab pretreatment with tacrolimus monotherapy and subsequent spaced weaning. We focused especially on the causes of recipient death and graft loss and the characteristics of rejection.

The AP-2 adaptor beta2 appendage scaffolds alternate cargo endocytosis.

The independently folded appendages of the large alpha and beta2 subunits of the endocytic adaptor protein (AP)-2 complex coordinate proper assembly and operation of endocytic components during clathrin-mediated endocytosis. The beta2 subunit appendage contains a common binding site for beta-arrestin or the autosomal recessive hypercholesterolemia (ARH) protein. To determine the importance of this interaction surface in living cells, we used small interfering RNA-based gene silencing.

Mitochondria are the major targets in albumin-induced apoptosis in proximal tubule cells.

Nephrotic-range proteinuria is considered a poor prognostic factor. A correlation between tubulointerstitial injury and the degree of proteinuria is well established. In an attempt to explain the tubular atrophy that is observed in advanced glomerulonephritides, this study investigated apoptotic mechanisms in cultured human proximal tubule cells (HKC-8) that were exposed to endotoxin-free albumin (5, 10, and 20 mg/ml).

Apoptotic response to albumin overload: proximal vs. distal/collecting tubule cells.

End-stage renal disease due to proteinuric states has a great impact on the quality of life by necessitating renal replacement therapy. Understanding the pathophysiologic consequences of proteinuria is crucial in order to develop treatment strategies to halt the progression. We have previously reported that cultured porcine proximal tubule cells respond to albumin overload by undergoing apoptosis.

Role of urinary supersaturation in the evaluation of children with urolithiasis.

Timed urine collections are a standard part of the evaluation for predisposition to stone formation in children with urolithiasis. Supersaturation is defined as the ratio of the concentration of dissolved salt to its solubility in urine. The purpose of the present study was to determine if adding supersaturation to the standard timed urine collection increased the ability to detect a metabolic predisposition to stone formation.

Induction of renal tubular cell apoptosis in focal segmental glomerulosclerosis: roles of proteinuria and Fas-dependent pathways.

The hypothesis that apoptosis represents a proximate mechanism by which tubule cells are damaged in FSGS was tested. Thirty kidney biopsy specimens from children with idiopathic early FSGS were studied retrospectively. Unexpected, apoptosis was evident in both proximal and distal tubule cells.

Thyroxine prevents reoxygenation injury in isolated proximal tubule cells.

Ischemia is characterized by cessation of blood flow and oxygen delivery to tissues that results in disruption of cellular structure and organelles. However, restoration of blood flow following ischemia causes reperfusion injury, characterized by further damage in the tissues mediated by reactive oxygen species. In the kidney, reactive oxygen molecules have been implicated in ischemic, toxic and immunological glomerular damage.

Role of nitric oxide, endothelin-1, and inflammatory cytokines in blood pressure regulation in hemodialysis patients.

Background: Altered regulation of blood pressure (BP) in hemodialysis patients is associated with increased morbidity and mortality. Regulation of BP is dependent in part on such vasoactive agents as nitric oxide (NO) and endothelin-1 (ET-1). Cytokine-mediated NO synthase activation during dialysis previously has been reported.