Safety profile of abdominal magnetic resonance imaging (MRI) performed for renal disease surveillance in tuberous sclerosis complex patients with vagus nerve stimulation: Safety of MRI for TSC Patients with VNS.

Introduction: Individuals with tuberous sclerosis complex (TSC) often present with refractory epilepsy and may be undergoing treatment with vagus nerve stimulation (VNS) to control seizures. Surveillance magnetic resonance imaging (MRI) is necessary to monitor for the renal angiomyolipomas associated with TSC; however, MRI of the abdomen is not approved for patients withVNS therapy. We have many TSC patients with refractory epilelpsy who benefitted from VNS therapy, so we developed an MRI protocol that allows MRI of the abdomen to be performed in these patients to permit safe imaging of their kidneys.

Concomitant Wilms tumor and autosomal dominant polycystic kidney disease.

Background: Concomitant Wilms tumor (WT) and autosomal dominant polycystic kidney disease (ADPKD) is exceedingly rare, presenting a diagnostic and technical challenge to pediatric surgical oncologists. The simultaneous workup and management of these disease processes are incompletely described.

Procedure: We performed a retrospective analysis of patients treated at our institution with concomitant diagnoses of WT and ADPKD.

Tuberous Sclerosis Complex and the kidneys: what nephrologists need to know.

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of hamartomas in the central nervous system, heart, skin, lungs, and kidneys and other manifestations including seizures, cortical tubers, radial migration lines, autism and cognitive disability. The disease is associated with pathogenic variants in the TSC1 or TSC2 genes, resulting in the hyperactivation of the mTOR pathway, a key regulator of cell growth and metabolism. Consequently, the hyperactivation of the mTOR pathway leads to abnormal tissue proliferation and the development of solid tumors.

Epidemiology, Risk Factors, and Clinical Outcomes of AKI in Pediatric Hematopoietic Stem Cell Transplant Patients.

Key Points: The cumulative incidence of AKI diagnosis post–hematopoietic stem cell transplantation was 12.9%. Calcineurin inhibitor use was associated with the highest cumulative incidence, 21.

Acute kidney injury following treatment with CD19-specific CAR T-cell therapy in children, adolescent, and young adult patients with B-cell acute lymphoblastic leukemia.

Background: CD19-specific chimeric antigen receptor (CAR) T-cell therapy has shown promising disease responses in patients with high-risk B-cell malignancies. However, its use may be related to complications such as immune-mediated complications, infections, and end-organ dysfunction. The incidence of post-CAR T-cell therapy acute kidney injury (AKI) in the children, adolescent, and young adult (CAYA) patient population is largely unreported.

Clinical practice recommendations for kidney involvement in tuberous sclerosis complex: a consensus statement by the ERKNet Working Group for Autosomal Dominant Structural Kidney Disorders and the ERA Genes & Kidney Working Group.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the presence of proliferative lesions throughout the body. Management of TSC is challenging because patients have a multifaceted systemic illness with prominent neurological and developmental impact as well as potentially severe kidney, heart and lung phenotypes; however, every organ system can be involved. Adequate care for patients with TSC requires a coordinated effort involving a multidisciplinary team of clinicians and support staff.

Acute kidney injury following treatment with CD19-specific CAR T-cell therapy in children, adolescent and young adult patients with B-cell acute lymphoblastic leukemia.

CD19-specific chimeric antigen receptor (CAR) T-cell therapy has shown promising disease responses in patients with high-risk B-cell malignancies. Treatment with CD19-CAR T-cell therapy is also associated with the risk of morbidity and mortality, primarily related to immune-mediated complications (cytokine release syndrome [CRS] and neurotoxicity [NTX]), infections, and end-organ dysfunction. Despite these well-described systemic toxicities, the incidence of post-CAR T-cell therapy acute kidney injury (AKI) in the children, adolescent and young adult (CAYA) patient population is largely unreported.

Physiologically Based Pharmacokinetic Modeling of Extracellular Vesicles.

Extracellular vesicles (EVs) are lipid membrane bound-cell-derived structures that are a key player in intercellular communication and facilitate numerous cellular functions such as tumor growth, metastasis, immunosuppression, and angiogenesis. They can be used as a drug delivery platform because they can protect drugs from degradation and target specific cells or tissues. With the advancement in the technologies and methods in EV research, EV-therapeutics are one of the fast-growing domains in the human health sector.

Liquid Biopsy at the Frontier of Kidney Diseases: Application of Exosomes in Diagnostics and Therapeutics.

In the era of precision medicine, liquid biopsy techniques, especially the use of urine analysis, represent a paradigm shift in the identification of biomarkers, with considerable implications for clinical practice in the field of nephrology. In kidney diseases, the use of this non-invasive tool to identify specific and sensitive biomarkers other than plasma creatinine and the glomerular filtration rate is becoming crucial for the diagnosis and assessment of a patient's condition. In recent years, studies have drawn attention to the importance of exosomes for diagnostic and therapeutic purposes in kidney diseases.

Progress in Tuberous Sclerosis Complex Renal Disease.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects both fetal development and postnatal tissue growth, resulting in altered brain structures and a tumor predisposition syndrome. Although every organ system is affected by the disease, kidney involvement is a leading cause of death in adults with TSC. Over the past decade, significant progress has been made in understanding the renal disease.

Identification of an Electrogenic 2Cl/H Exchanger, ClC5, as a Chloride-Secreting Transporter Candidate in Kidney Cyst Epithelium in Tuberous Sclerosis.

Kidney cyst expansion in tuberous sclerosis complex (TSC) or polycystic kidney disease (PKD) requires active secretion of chloride (Cl) into the cyst lumen. In PKD, Cl secretion is primarily mediated via the cystic fibrosis transmembrane conductance regulator (CFTR) in principal cells. Kidney cystogenesis in TSC is predominantly composed of type A intercalated cells, which do not exhibit noticeable expression of CFTR.

Single Gene Mutations in or Alter Extracellular Vesicle Production and Trafficking.

Patients with autosomal dominant polycystic kidney disease (ADPKD) and tuberous sclerosis complex (TSC) are born with normal or near-normal kidneys that later develop cysts and prematurely lose function. Both renal cystic diseases appear to be mediated, at least in part, by disease-promoting extracellular vesicles (EVs) that induce genetically intact cells to participate in the renal disease process. We used centrifugation and size exclusion chromatography to isolate the EVs for study.

Acute kidney injury in pediatric hematopoietic cell transplantation: critical appraisal and consensus.

Hematopoietic cell transplantation (HCT) is a common therapy for the treatment of neoplastic and metabolic disorders, hematological diseases, and fatal immunological deficiencies. HCT can be subcategorized as autologous or allogeneic, with each modality being associated with their own benefits, risks, and post-transplant complications. One of the most common complications includes acute kidney injury (AKI).

mutation induces renal tubular cell nonautonomous disease.

TSC renal cystic disease is poorly understood and has no approved treatment. In a new principal cell-targeted murine model of cystic disease, the renal cystic epithelium is mostly composed of type A intercalated cells with an intact gene confirmed by sequencing, although these cells exhibit a -mutant disease phenotype. We used a newly derived targeted murine model in lineage tracing and extracellular vesicle (EV) characterization experiments and a cell culture model in EV characterization and cellular induction experiments to understand TSC cystogenesis.

Leptin receptor defect with diabetes causes skeletal muscle atrophy in female obese Zucker rats where peculiar depots networked with mitochondrial damages.

Tibialis anterior muscles of 45-week-old female obese Zucker rats with defective leptin receptor and non-insulin dependent diabetes mellitus (NIDDM) showed a significative atrophy compared to lean muscles, based on histochemical-stained section's measurements in the sequence: oxidative slow twitch (SO, type I) < oxidative fast twitch (FOG, type IIa) < fast glycolytic (FG, type IIb). Both oxidative fiber's outskirts resembled 'ragged' fibers and, in these zones, ultrastructure revealed small clusters of endoplasm-like reticulum filled with unidentified electron contrasted compounds, contiguous and continuous with adjacent mitochondria envelope. The linings appeared crenated stabbed by circular patterns resembling those found of ceramides.

Indocyanine green-guided nephron-sparing surgery for pediatric renal tumors.

Background: Indocyanine green (ICG), a water-soluble tricarbocyanine fluorophore, is being increasingly used for tumor localization based on its passive intra-tumoral accumulation due to enhanced permeability and retention in tumor tissue. Therefore, we hypothesized that ICG can provide contrast to facilitate accurate, real-time recognition of renal tumors at the time of nephron-sparing surgery in children.

Methods: This retrospective study examined the feasibility of ICG in guiding nephron-sparing surgery for pediatric renal tumors.

Racial Health Disparity and COVID-19.

The infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and resultant coronavirus diseases-19 (COVID-19) disproportionally affects minorities, especially African Americans (AA) compared to the Caucasian population. The AA population is disproportionally affected by COVID-19, in part, because they have high prevalence of underlying conditions such as obesity, diabetes, and hypertension, which are known to exacerbate not only kidney diseases, but also COVID-19. Further, a decreased adherence to COVID-19 guidelines among tobacco smokers could result in increased infection, inflammation, reduced immune response, and lungs damage, leading to more severe form of COVID-19.

Renal cystic disease in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is associated with or gene mutations resulting in hyperactivation of the mTORC1 pathway. This mTORC1 activation is associated with abnormal tissue development and proliferation such that in the kidney there are both solid tumors and cystic lesions. This review summarizes recent advances in tuberous sclerosis complex nephrology and focuses on the genetics and cell biology of tuberous sclerosis complex renal disease, highlighting a role of extracellular vesicles and the innate immune system in disease pathogenesis.

Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations.

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations.

Gene Locus Disruption and Differences in Renal Epithelial Extracellular Vesicles.

In tuberous sclerosis complex (TSC), mutations are associated with more severe disease manifestations than mutations and the role of extracellular vesicles (EVs) in this context is not yet studied. We report a comparative analysis of EVs derived from isogenic renal cells except for or gene status and hypothesized that in spite of having similar physical characteristics, EVs modulate signaling pathways differently, thus leading to TSC heterogenicity. We used mouse inner medullary collecting duct (mIMCD3) cells with the (T1G cells) or (T2J cells) gene disrupted by CRISPR/CAS9.

Continuous Renal Replacement Therapy: A Review of Use and Application in Pediatric Hematopoietic Stem Cell Transplant Recipients.

Hematopoietic stem cell transplant (HSCT) is a curative therapy for malignant and non-malignant conditions. However, complications post-HSCT contribute to significant morbidity and mortality in this population. Acute kidney injury (AKI) is common in the post-allogeneic transplant phase and contributes to morbidity in this population.

Kidney intercalated cells and the transcription factor FOXi1 drive cystogenesis in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is caused by mutations in either TSC1 or TSC2 genes and affects multiple organs, including kidney, lung, and brain. In the kidney, TSC presents with the enlargement of benign tumors (angiomyolipomata) and cysts, which eventually leads to kidney failure. The factors promoting cyst formation and tumor growth in TSC are incompletely understood.

Tuberous Sclerosis Complex Axis Controls Renal Extracellular Vesicle Production and Protein Content.

The tuberous sclerosis complex (Tsc) proteins regulate the conserved mTORC1 growth regulation pathway. We identified that loss of the gene in mouse inner medullary collecting duct (mIMCD) cells induced a greater than two-fold increase in extracellular vesicle (EV) production compared to the same cells having an intact axis. We optimized EV isolation using a well-established size exclusion chromatography method to produce high purity EVs.