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Purpose: To study the use of the self-expanding Covera covered stent for the treatment of stenotic lesions at the venous anastomosis of hemodialysis arteriovenous grafts (AVGs)., Materials and Methods: A total of 110 patients with AVG venous anastomotic stenosis of ≥50% and access dysfunction were treated at 14 centers in the United States using percutaneous transluminal angioplasty followed by covered stent placement. The primary end points were 30-day safety and 6-month target lesion primary patency (TLPP). The secondary measures included access circuit primary patency, circuit cumulative patency, and the number of reinterventions through 24 months., Results: Freedom from a primary safety event at 30 days was 96.4% while the 6-month TLPP rate was 70.3%. Seventy-five patients completed 24-month follow-up (68.2%). The TLPP rates were 54.2% at 365 days and 36.9% at 730 days while the access circuit primary patency rates were 16.7% at 365 days and 7.8% at 730 days (Kaplan-Meier analysis). The access circuit cumulative patency rates were 85.4% at 12 months and 73.6% at 24 months. The number of reinterventions to maintain the patency of the access circuit was 3.6 ± 3.1 at 24 months (1.6 ± 1.9 at the target lesion)., Conclusions: Use of the Covera covered stent for hemodialysis graft-vein anastomotic stenosis provided a safe treatment option with a TLPP rate of 70.3% at 6 months and TLPP and cumulative access circuit patency rates of 36.9% and 73.6% at 2 years., (Copyright © 2022 SIR. Published by Elsevier Inc. All rights reserved.)

Claudin-7 knockout (CLDN7 -/- ) mice display renal salt wasting and dehydration phenotypes. To address the role of CLDN7 in kidneys, we established collecting duct (CD) cell lines from CLDN7 +/+ and CLDN7 -/- mouse kidneys. We found that deletion of CLDN7 increased the transepithelial resistance (TER) and decreased the paracellular permeability for Cl - and Na + in CLDN7 -/- CD cells. Inhibition of transcellular Cl - and Na + channels has no significant effect on TER or dilution potentials. Current-voltage curves were linear in both CLDN7 +/+ and CLDN7 -/- CD cells, indicating that the ion flux was through the paracellular pathway. The impairment of Cl - and Na + permeability phenotype can be rescued by CLDN7 re-expression. We also found that WNK4 (its mutations lead to hypertension) expression, but not WNK1, was significantly increased in CLDN7 -/- CD cell lines as well as in primary CLDN7 -/- CD cells, suggesting that the expression of WNK4 was modulated by CLDN7. In addition, deletion of CLDN7 upregulated the expression level of the apical epithelial sodium channel (ENaC), indicating a potential cross-talk between paracellular and transcellular transport systems. This study demonstrates that CLDN7 plays an important role in salt balance in renal CD cells and modulating WNK4 and ENaC expression levels that are vital in controlling salt-sensitive hypertension.

Claudins are a family of tight junction (TJ) integral membrane proteins that play a crucial role in maintaining cell polarity, adhesion, and paracellular permeability. Changes in expression levels of claudin proteins have been associated with human lung cancer. Previously, we have reported that claudin-7 expression is significantly downregulated in human lung carcinomas. To investigate the role of claudin-7 in lung cancer cells after anti-cancer drug treatments, we transfected claudin-7 cDNA into human NCI-H522 lung cancer cells, which have no detectable expression of claudin-7 protein. Flow cytometry analysis demonstrated that cells transfected with claudin-7 had a significantly higher percentage of cell apoptosis when compared to that of vector transfected cell population. The cell viability assayed by MTT and Annexin V was significantly decreased and cell apoptosis was dramatically increased in claudin-7 transfected cells compared to that of vector transfected cells after cisplatin treatment. Cisplatin is an anti-cancer drug clinically used to treat tumors in several tissues including lung tumors. Most importantly, after cisplatin treatment, the expression levels of cleaved caspase-3, -8, and poly adenosine 5'-diphosphate ribose polymerase (PARP) were much higher in claudin-7 transfected cells than in control cells. Furthermore, using the site-directed mutagenesis approach, we identified that claudin-7 was phosphorylated at serine 204 by protein kinase C. Non-phosphorylated claudin-7 mutant showed increased cell viability, suggesting that phosphorylation increases chemosensitivity to cisplatin treatment. We concluded that claudin-7 expression in H522 lung cancer cells increases chemosensitivity to cisplatin through the increased activation of caspase pathway., (© 2013 Japanese Cancer Association.)

Cardiovascular implantable electronic devices (CIEDs) are frequently utilized for management of cardiac dysrhythmias in patients with chronic kidney disease or end-stage renal disease receiving hemodialysis. The survival benefit from use of implantable cardioverter defibrillators in patients with CKD or ESRD is not as clear as in the general population, particularly when used for primary prevention of sudden cardiac death. Transvenous CIED leads are associated with central vein stenosis resulting in significant adverse consequences for existing or future arteriovenous access. Venous hypertension from CIED lead-related central vein stenosis is a challenging clinical problem and may require repeated percutaneous interventions, replacement of the CIED, or creation of alternative arteriovenous access. Infections associated with transvenous CIED leads are more frequent and associated with worse outcomes in patients with renal disease. Epicardial CIED leads or other nontransvenous devices may reduce complications of both central venous stenosis and endovascular infection in these vulnerable patients. Consensus recommendations are offered for avoidance and management of complications arising from the use of CIEDs and arteriovenous hemodialysis access., (© 2012 Wiley Periodicals, Inc.)

Tight junctions are the most apical component of the junctional complex critical for epithelial cell barrier and polarity functions. Although its disruption is well documented during cancer progression such as epithelial-mesenchymal transition, molecular mechanisms by which tight junction integral membrane protein claudins affect this process remain largely unknown. In this report, we found that claudin-7 was normally expressed in bronchial epithelial cells of human lungs but was either downregulated or disrupted in its distribution pattern in lung cancer. To investigate the function of claudin-7 in lung cancer cells, we transfected claudin-7 cDNA into NCI-H1299, a human lung carcinoma cell line that has no detectable claudin-7 expression. We found that claudin-7 expressing cells showed a reduced response to hepatocyte growth factor (HGF) treatment, were less motile, and formed fewer foot processes than the control cells did. In addition, cells transfected with claudin-7 dramatically decreased their invasive ability after HGF treatment. These effects were mediated through the MAPK signaling pathway since the phosphorylation level of ERK1/2 was significantly lower in claudin-7 transfected cells than in control cells. PD98059, a selective inhibitor of ERK/MAPK pathway, was able to block the motile effect. Claudin-7 formed stable complexes with claudin-1 and -3 and was able to recruit them to the cell-cell junction area in claudin-7 transfected cells. When control and claudin-7 transfected cells were inoculated into nude mice, claudin-7 expressing cells produced smaller tumors than the control cells. Taken together, our study demonstrates that claudin-7 inhibits cell migration and invasion through ERK/MAPK signaling pathway in response to growth factor stimulation in human lung cancer cells., (Copyright © 2011 Elsevier Inc. All rights reserved.)

At the time of hemodialysis vascular access evaluation, many chronic kidney disease patients already have iatrogenic injury to their veins which impedes the surgical construction of an arteriovenous fistula (AVF). Achieving the important goal of a greater prevalence of arteriovenous fistulae in the US hemodialysis population will require identification of those patients prior to reaching end-stage renal disease and an educational and procedural system for preserving their veins.

A procedure-related complication is an unanticipated adverse event that requires therapy. In order to analyze frequency and severity of complications in the process of quality assurance, it is useful to have a classification of complications, indicating the type and severity. The Clinical Practice Committee of American Society of Diagnostic and Interventional Nephrology has developed a Classification of Complications relating to Hemodialysis Vascular Access Procedures, based on the system first proposed by Beathard in 2006. In this system, the "type" refers to the procedure being performed or vessel entered, and the "grade" is based on the intensity of medical care needed to address the complication. This publication describes 10 Types and 4 Grades of complications.

Objective: To determine patient preference for once-weekly Epoetin alfa versus once-monthly (QM) darbepoetin alfa in patients with chronic kidney disease (CKD) not receiving dialysis., Methods: AMPS (Aranesp Monthly Preference Study) consisted of two studies of similar design, each with a 2-week screening/baseline period, a 20-week QM darbepoetin alfa dosing period, and an 8-week follow-up period. Patients aged > or = 18 years had a nephrologist-reported diagnosis of CKD but were not receiving dialysis, and were required to have at least two hemoglobin levels within 10-12 g/dL and to have been receiving a stable dose (< 25% change) of once-weekly or once-every-other-weekly Epoetin alfa for at least 8 weeks. At week 21, patients could continue on QM darbepoetin alfa or revert back to their previous Epoetin alfa regimen. The primary analysis assessed patient preference at week 21 for QM darbepoetin alfa versus previous once-weekly Epoetin alfa., Results: AMPS enrolled 442 patients: 54% were female, 67% were Caucasian, and mean (SD) age was 68.3 (13.5) years. At week 21, 346 patients remained on study. Of the patients converted from once-weekly Epoetin alfa, 86% (138/161) preferred darbepoetin alfa QM, and of all patients who expressed a preference, regardless of previous Epoetin alfa dosing frequency, 96% (305/319) preferred QM darbepoetin alfa. Mean (SD) hemoglobin at week 29 of the study was similar to mean hemoglobin at baseline (for those who completed the study and were receiving QM darbepoetin alfa at week 29: 11.2 [1.1] g/dL at week 29 versus 11.4 [0.7] g/dL at baseline). QM darbepoetin alfa was well tolerated., Conclusion: These data show that the majority of study patients preferred QM darbepoetin alfa to more frequent Epoetin alfa, and that QM darbepoetin alfa maintained hemoglobin levels at week 29 and was well tolerated over the study period. The single-item questionnaire could be a potential limitation of this study and further investigation with a multi-question instrument may be helpful in confirming these results.