Aryl Hydrocarbon Receptor Pathway Augments Peritoneal Fibrosis in a Murine CKD Model Exposed to Peritoneal Dialysate.

Key Points: CKD and high glucose–containing peritoneal dialysate alter peritoneal membrane contributing to peritoneal dialysis failure, with a poorly understood mechanism. CKD milieu activates the aryl hydrocarbon receptor pathway in the subperitoneal vasculature, increasing the peritoneal fibrosis and collagen deposition in humans and mice. An aryl hydrocarbon receptor inhibitor mitigates CKD and peritoneal dialysis–mediated peritoneal fibrosis, collagen deposition, and vasculogenesis in a mouse model.

Early Kidney Transplantation or Conversion to Peritoneal Dialysis after First-Time Arteriovenous Access Creation.

Background: After autogenous arteriovenous (AV) access creation for end-stage renal disease, a majority of patients will continue on hemodialysis (HD), a minority will receive definitive treatment with kidney transplantation, and a subset of patients will convert to peritoneal dialysis (PD). Our goal was to identify patient factors associated with early transition from HD to either kidney transplantation or PD.

Methods: This is a case-control study of all patients with first-time AV access creation in the Vascular Quality Initiative (2011-2022) who had long-term follow-up.

End Organ Affection in Sickle Cell Disease.

Sickle cell disease is an orphan disease affecting ethnic minorities and characterized by profound systemic manifestations. Although around 100,000 individuals with SCD are living in the US, the exact number of individuals is unknown, and it is considered an orphan disease. This single-gene disorder leads to red blood cell sickling and the deoxygenation of hemoglobin, resulting in hemolysis.

Hydrophilic Coating Microstructure Mediates Acute Drug Transfer in Drug-Coated Balloon Therapy.

Drug-coated balloon (DCB) therapy is a promising endovascular treatment for obstructive arterial disease. The goal of DCB therapy is restoration of lumen patency in a stenotic vessel, whereby balloon deployment both mechanically compresses the offending lesion and locally delivers an antiproliferative drug, most commonly paclitaxel (PTX) or derivative compounds, to the arterial wall. Favorable long-term outcomes of DCB therapy thus require predictable and adequate PTX delivery, a process facilitated by coating excipients that promotes rapid drug transfer during the inflation period.

Alleviating iatrogenic effects of paclitaxel via antiinflammatory treatment.

Background: Paclitaxel (PTX) is touted as an essential medicine due to its extensive use as a chemotherapeutic agent for various cancers and an antiproliferative agent for endovascular applications. Emerging studies in cardio-oncology implicate various vascular complications of chemotherapeutic agents.

Methods: We evaluated the inflammatory response induced by the systemic administration of PTX.

Corrigendum: Integrated metabolomics and proteomics reveal biomarkers associated with hemodialysis in end-stage kidney disease.

[This corrects the article DOI: 10.3389/fphar.2023.

Venous Thrombosis Assay in a Mouse Model of Cancer.

This methodology paper highlights the surgical nuances of a rodent model of venous thrombosis, specifically in the context of cancer-associated thrombosis (CAT). Deep venous thrombosis is a common complication in cancer survivors and can be potentially fatal. The current murine venous thrombosis models typically involve a complete or partial mechanical occlusion of the inferior vena cava (IVC) using a suture.

Characterization of long-term survival in Medicare patients undergoing arteriovenous hemodialysis access.

Background: Patients undergoing arteriovenous (AV) access creation for hemodialysis often have significant comorbidities. Our goal was to quantify the long-term survival and associated risks factors for long-term mortality in these patients to aid in optimization of goals and expectations.

Methods: The Vascular Implant Surveillance and Interventional Outcomes Network Vascular Quality Initiative Medicare linked data was used to assess long-term survival in the HD registry.

Integrated metabolomics and proteomics reveal biomarkers associated with hemodialysis in end-stage kidney disease.

We hypothesize that the poor survival outcomes of end-stage kidney disease (ESKD) patients undergoing hemodialysis are associated with a low filtering efficiency and selectivity. The current gold standard criteria using single or several markers show an inability to predict or disclose the treatment effect and disease progression accurately. We performed an integrated mass spectrometry-based metabolomic and proteomic workflow capable of detecting and quantifying circulating small molecules and proteins in the serum of ESKD patients.

Tryptophan Metabolites Target Transmembrane and Immunoglobulin Domain-Containing 1 Signaling to Augment Renal Tubular Injury.

Chronic kidney disease (CKD) is characterized by the accumulation of uremic toxins and renal tubular damage. Tryptophan-derived uremic toxins [indoxyl sulfate (IS) and kynurenine (Kyn)] are well-characterized tubulotoxins. Emerging evidence suggests that transmembrane and immunoglobulin domain-containing 1 (TMIGD1) protects tubular cells and promotes survival.

Understudied factors in drug-coated balloon design and evaluation: A biophysical perspective.

Drug-coated balloon (DCB) percutaneous interventional therapy allows for durable reopening of the narrowed lumen via physical tissue expansion and local anti-restenosis drug delivery, providing an alternative to traditional uncoated balloons or a permanent indwelling implant such as a conventional metallic drug-eluting stent. While DCB-based treatment of peripheral arterial disease (PAD) has been incorporated into clinical guidelines, DCB use has been recently curtailed due to reports that showed evidence of increased mortality risk in patients treated with paclitaxel (PTX)-coated balloons. Given the United States Food and Drug Administration's 2019 consequent warning regarding PTX-eluting DCBs and the subsequent marked reduction in clinical DCB use, there is now a critical need to better understand the compositional and mechanical factors underlying DCB efficacy and safety.

A Retrograde Implantation Approach for Peritoneal Dialysis Catheter Placement in Mice.

Murine models are employed to probe various aspects of peritoneal dialysis (PD), such as peritoneal inflammation and fibrosis. These events drive peritoneal membrane failure in humans, which remains an area of intense investigation due to its profound clinical implications in managing patients with end-stage kidney disease (ESKD). Despite the clinical importance of PD and its related complications, current experimental murine models suffer from key technical challenges that compromise the models' performance.

Pharmacologic Manipulation of Late SV40 Factor Suppresses Wnt Signaling and Inhibits Growth of Allogeneic and Syngeneic Colon Cancer Xenografts.

Aberrant hyperactivation of Wnt signaling, driven by nuclear β-catenin in the colonic epithelium, represents the seminal event in the initiation and progression of colorectal cancer (CRC). Despite its established role in CRC tumorigenesis, clinical translation of Wnt inhibitors remains unsuccessful. Late SV40 factor (LSF; encoded by TFCP2) is a transcription factor and a potent oncogene.

Janus Kinase Signaling Pathway and Its Role in COVID-19 Inflammatory, Vascular, and Thrombotic Manifestations.

Acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection continues to be a worldwide public health crisis. Among the several severe manifestations of this disease, thrombotic processes drive the catastrophic organ failure and mortality in these patients. In addition to a well-established cytokine storm associated with the disease, perturbations in platelets, endothelial cells, and the coagulation system are key in triggering systemic coagulopathy, involving both the macro- and microvasculatures of different organs.

Determinants of Hemodialysis Performance: Modeling Fluid and Solute Transport in Hollow-Fiber Dialyzers.

Hemodialysis constitutes the lifeline of patients with end stage renal disease, yet the parameters that affect hemodialyzer performance remain incompletely understood. We developed a computational model of mass transfer and solute transport in a hollow-fiber dialyzer to gain greater insight into the determinant factors. The model predicts fluid velocity, pressure, and solute concentration profiles for given geometric characteristics, membrane transport properties, and inlet conditions.

Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease.

Chronic kidney disease (CKD) imposes a strong and independent risk for peripheral artery disease (PAD). While solutes retained in CKD patients (uremic solutes) inflict vascular damage, their role in PAD remains elusive. Here, we show that the dietary tryptophan-derived uremic solutes including indoxyl sulfate (IS) and kynurenine (Kyn) at concentrations corresponding to those in CKD patients suppress β-catenin in several cell types, including microvascular endothelial cells (ECs), inhibiting Wnt activity and proangiogenic Wnt targets in ECs.

Indoleamine 2,3-dioxygenase-1, a Novel Therapeutic Target for Post-Vascular Injury Thrombosis in CKD.

Background: CKD, characterized by retained uremic solutes, is a strong and independent risk factor for thrombosis after vascular procedures . Urem ic solutes such as indoxyl sulfate (IS) and kynurenine (Kyn) mediate prothrombotic effect through tissue factor (TF). IS and Kyn biogenesis depends on multiple enzymes, with therapeutic implications unexplored.

Machine Learning Applications in Nephrology: A Bibliometric Analysis Comparing Kidney Studies to Other Medicine Subspecialities.

Rationale & Objectives: Artificial intelligence driven by machine learning algorithms is being increasingly employed for early detection, disease diagnosis, and clinical management. We explored the use of machine learning-driven advancements in kidney research compared with other organ-specific fields.

Study Design: Cross-sectional bibliometric analysis.

SARS-CoV-2 Disrupts Proximal Elements in the JAK-STAT Pathway.

SARS-CoV-2 can infect multiple organs, including lung, intestine, kidney, heart, liver, and brain. The molecular details of how the virus navigates through diverse cellular environments and establishes replication are poorly defined. Here, we generated a panel of phenotypically diverse, SARS-CoV-2-infectible human cell lines representing different body organs and performed longitudinal survey of cellular proteins and pathways broadly affected by the virus.

Deep-Learning-Driven Quantification of Interstitial Fibrosis in Digitized Kidney Biopsies.

Interstitial fibrosis and tubular atrophy (IFTA) on a renal biopsy are strong indicators of disease chronicity and prognosis. Techniques that are typically used for IFTA grading remain manual, leading to variability among pathologists. Accurate IFTA estimation using computational techniques can reduce this variability and provide quantitative assessment.

Advances in BK Virus Complications in Organ Transplantation and Beyond.

Reactivation of BK virus (BKV) remains a dreaded complication in immunosuppressed states. Conventionally, BKV is known as a cause for BKV-associated nephropathy and allograft dysfunction in kidney transplant recipients. However, emerging studies have shown its negative impact on native kidney function and patient survival in other transplants and its potential role in diseases such as cancer.