Functional and metabolomic analysis of urinary extracellular vesicles from juvenile mice with renal compensatory hypertrophy.

Unilateral nephrectomy, a procedure reducing kidney mass, triggers a compensatory response in the remaining kidney, increasing its size and function to maintain a normal glomerular filtration rate (GFR). Recent research has highlighted the role of extracellular vesicles (EVs) in renal physiology and disease, although their involvement in unilateral nephrectomy has been underexplored. In this study, unilateral nephrectomy was performed on young mice, and urinary extracellular vesicles (uEVs) characterization and cargo were analyzed.

Dysregulation of kidney proteases in the pathogenesis of hypertension following unilateral nephrectomy in juvenile mice.

Background: Unliteral nephrectomy (UNX) results in the reduction of kidney mass. The remaining kidney undergoes compensatory renal growth via hypertrophy of the glomeruli and renal tubules to maintain a normal glomerular filtration rate (GFR). These compensatory mechanisms result in increased capillary pressure and glomerular hyperfiltration to increase single nephron GFR.

Thrombotic microangiopathy following systemic AAV administration is dependent on anti-capsid antibodies.

BACKGROUNDSystemic administration of adeno-associated virus (AAV) can trigger life-threatening inflammatory responses, including thrombotic microangiopathy (TMA), acute kidney injury due to atypical hemolytic uremic syndrome-like complement activation, immune-mediated myocardial inflammation, and hepatic toxicity.METHODSWe describe the kinetics of immune activation following systemic AAV serotype 9 (AAV9) administration in 38 individuals following 2 distinct prophylactic immunomodulation regimens. Group 1 received corticosteroids and Group 2 received rituximab plus sirolimus in addition to steroids to prevent anti-AAV antibody formation.

Does kidney biopsy in pediatric lupus patients "complement" the management and outcomes of silent lupus nephritis? Lessons learned from a pediatric cohort.

Background: Silent lupus nephritis (SLN) is systemic lupus erythematosus (SLE) without clinical and laboratory features of kidney involvement but with biopsy-proven nephritis. This study aims to describe and compare the baseline characteristics and outcomes of pediatric SLN with overt LN (OLN) and to identify associated risk factors and biochemical markers.

Methods: In this retrospective, observational study, multivariate logistic regression and receiver operating characteristic (ROC) analyses studied age, sex, race, serum complements, anti-double-stranded-DNA antibody, anti-Smith antibody, eGFR, and proliferative nephritis.

Extracellular vesicles from focal segmental glomerulosclerosis pediatric patients induce STAT3 activation and mesangial cell proliferation.

Introduction: Primary focal segmental glomerulosclerosis (FSGS), a major cause of end-stage kidney disease (ESKD) in adolescents and young adults, is attributable to recognized genetic mutations in a minority of cases. For the majority with idiopathic primary FSGS, the cause of the disease is unknown. We hypothesize that extracellular vesicle (EVs), that carry information between podocytes and mesangial cells, may play a key role in disease progression.

IgA-dominant infection-associated glomerulonephritis in the pediatric population.

Background: IgA-dominant infection-associated glomerulonephritis is well-documented in adults but has not been studied in depth in children. We assessed the incidence of pediatric IgA-dominant infection-associated glomerulonephritis and clinical and kidney biopsy findings.

Methods: Pediatric native kidney biopsies over a 10-year period with IgA dominance, strong C3, and findings indicative of infection-associated etiology were identified.

An international cohort study of autosomal dominant tubulointerstitial kidney disease due to REN mutations identifies distinct clinical subtypes.

There have been few clinical or scientific reports of autosomal dominant tubulointerstitial kidney disease due to REN mutations (ADTKD-REN), limiting characterization. To further study this, we formed an international cohort characterizing 111 individuals from 30 families with both clinical and laboratory findings. Sixty-nine individuals had a REN mutation in the signal peptide region (signal group), 27 in the prosegment (prosegment group), and 15 in the mature renin peptide (mature group).

Hypothyroidism Due to Iodine Overload in Children Receiving Peritoneal Dialysis: A Report of 4 Cases.

Children who receive peritoneal dialysis (PD) are at increased risk for thyroid dysfunction. A rarely appreciated cause is iodine overload. We report 4 children who developed iodine overload and secondary hypothyroidism.

BK virus encephalitis and end-stage renal disease in a child with hematopoietic stem cell transplantation.

BK virus encephalitis after HSCT is uncommon. Several reports of native kidney BKVN in patients with HSCT, hematologic malignancies, human immunodeficiency virus infection, and non-renal solid organ transplantation have been described. However, an uncommon combination of BK encephalitis and ESRD of native kidneys secondary to BK virus in a child with HSCT has not been described.

Tight metabolic control plus ACE inhibitor therapy improves GSD I nephropathy.

The onset of microalbuminuria (MA) heralds the onset of glomerulopathy in patients with glycogen storage disease (GSD) type I. Unlike tubulopathy, which responds to improved metabolic control, glomerulopathy in GSD I is considered refractory to medical intervention, and it is thought to inexorably progress to overt proteinuria and renal failure. Recent reports of reduced microalbuminuria following strict adherence to therapy counter this view.

Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?

Background: Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in SIOD remains unknown.

Methods: We reviewed the records of 65 patients with SMARCAL1 mutations.

Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus-specific database.

Renal coloboma syndrome, also known as papillorenal syndrome is an autosomal-dominant disorder characterized by ocular and renal malformations. Mutations in the paired-box gene, PAX2, have been identified in approximately half of individuals with classic findings of renal hypoplasia/dysplasia and abnormalities of the optic nerve. Prior to 2011, there was no actively maintained locus-specific database (LSDB) cataloguing the extent of genetic variation in the PAX2 gene and phenotypic variation in individuals with renal coloboma syndrome.

Severe calcification of the aorta (porcelain aorta) associated with sarcoidosis in a pediatric heart transplant recipient.

We report a unique case of severe calcification of the aorta, bilateral coronary ostial stenoses and calcification of the mitral valve and left ventricle due to sarcoidosis. The patient underwent neonatal orthotopic heart transplantation secondary to hypoplastic left heart syndrome and developed hypercalcemia with other features of sarcoidosis at 10 yr of age. The mechanism for severe extra-renal calcification localized to the allograft is poorly understood, but may involve discordant local immune modulation and/or calcification-regulation between graft and host tissues.

Schimke immunoosseous dysplasia: defining skeletal features.

Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive multisystem disorder characterized by prominent spondyloepiphyseal dysplasia, T cell deficiency, and focal segmental glomerulosclerosis. Biallelic mutations in swi/snf-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) are the only identified cause of SIOD, but approximately half of patients referred for molecular studies do not have detectable mutations in SMARCAL1. We hypothesized that skeletal features distinguish between those with or without SMARCAL1 mutations.

Exercise testing is useful to screen for residual coarctation in children.

Twenty-seven children (ages 8 to 18 years) who had a history of successful coarctation repair (mean transisthmic Doppler gradient [TI-D] <20 mmHg at rest) and had not received antihypertensive medications underwent echocardiogram at rest and immediately following peak exercise with a standard treadmill test. All were normotensive or had isolated systolic hypertension at rest. Right arm-ankle (RA-A) systolic blood pressure (SBP) difference and TI-D were measured.

Alemtuzumab (Campath-1H) induction in a pediatric heart transplant: successful outcome and rationale for its use.

Despite increasing clinical experience in adult transplantation, induction therapy with alemtuzumab (Campath-1H) has rarely been reported in pediatric solid-organ transplants, and has been limited to kidneys, intestine and multi-visceral organs. Basic science research and clinical observations reported from the adult experience suggest potential benefits of alemtuzumab in pediatric organ recipients. We report successful induction therapy with alemtuzumab and steroid-free maintenance therapy for cardiac transplantation in a teenager, and discuss its merits in this patient.

Midaortic syndrome presenting as neonatal hypertension.

We describe a case of mid-aortic syndrome presenting as systemic hypertension in infancy and early childhood. Angiography of the descending and abdominal aorta is the diagnostic test of choice to confirm the diagnosis of mid-aortic syndrome. Severity of hypertension is one of the major factors in determining the timing of intervention.

Acute sirolimus pulmonary toxicity in an infant heart transplant recipient: case report and literature review.

Sirolimus-associated pulmonary disease should be considered in the differential diagnosis of acute respiratory distress syndrome in transplant recipients receiving this drug. It represents a rare, potentially lethal, and yet reversible adverse effect. We report the case an infant who presented with acute respiratory distress 57 days after heart transplantation 3 days after starting sirolimus.

Schimke immunoosseous dysplasia: suggestions of genetic diversity.

Schimke immunoosseous dysplasia (SIOD), which is characterized by prominent spondyloepiphyseal dysplasia, T-cell deficiency, and focal segmental glomerulosclerosis, is a panethnic autosomal recessive multisystem disorder with variable expressivity. Biallelic mutations in switch/sucrose nonfermenting (swi/snf) related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1) are the only identified cause of SIOD. However, among 72 patients from different families, we identified only 38 patients with biallelic mutations in the coding exons and splice junctions of the SMARCAL1 gene.

Cardiac transplantation for pediatric giant cell myocarditis.

Giant cell myocarditis (GCM) is an organ-specific, autoimmune disease that infrequently affects children and generally has a more aggressive (often fatal) course than other forms of myocarditis. No data are available about the epidemiology of GCM in children. We describe a 13-year-old girl who presented with ventricular tachycardia and rapid hemodynamic deterioration that required extracorporeal membrane oxygenation (ECMO) as a bridge to heart transplantation.

Collapsing glomerulopathy in a 16-year-old girl with pulmonary tuberculosis: the role of systemic inflammatory mediators.

Idiopathic collapsing glomerulopathy is an aggressive variant of focal segmental glomerulosclerosis (FSGS) seen primarily in adults. Its etiology is unknown. Nearly identical pathology is seen in association with nephrotic syndrome in human immunodeficiency virus type 1 (HIV-1)-infected patients, raising the possibility that viral infection plays a role in pathogenesis.

Angiotensin II reduces calcium uptake into bone.

Children with neonatal Bartter syndrome (NBS) have hypercalciuria, nephrocalcinosis, and osteopenia. A complex of basic-fibroblast growth factor (b-FGF) and a naturally occurring glycosaminoglycan has been identified in the serum and urine of NBS patients. This complex increases bone resorption in a bone disc bioassay system.