Addressing Kidney Transplant Shortage: The Potential of Kidney Paired Exchanges in Jordan.

Jordan performed the Middle East's first living-donor kidney transplant in 1972. In 1977, the country became one of the first Arab countries to regulate organ donation and transplantation. Despite these early advances in living donor transplantation, Jordan's organ donation after brain death program remains inactive, making it challenging to meet organ demand and placing many patients on long transplant waiting lists. As of 2020, only 14.2% of the patients with end-stage kidney disease have access to a living donor. The scarcity of compatible living donors exacerbates Jordan's organ shortage, leaving patients with extended waits and uncertain transplant prospects. Due to the lack of living donors and the inactive brain death donation program, additional options are needed to meet organ demand. Kidney paired exchange (KPE), emerges as a potential solution to the problem of donor shortage and donor-recipient incompatibility. By allowing living donors to direct their donated organs to different compatible recipients, KPE offers the promise of expanding transplant opportunities for patients without suitable living donors. However, the current Jordanian law restricting living kidney donation to fifth-degree relatives further limits the pool of potential donors, aggravating the organ shortage situation. This article explores the feasibility of implementing KPE in Jordan and proposes an approach to implementing KPE in Jordan, considering ethical and legal aspects to substantially increase kidney transplants.

CD36-mediated activation of endothelial cell apoptosis by an N-terminal recombinant fragment of thrombospondin-2 inhibits breast cancer growth and metastasis in vivo.

Thus far the clinical benefits seen in breast cancer patients treated with drugs targeting the vascular endothelial growth factor (VEGF) pathway are only modest. Consequently, additional antiangiogenic approaches for treatment of breast cancer need to be investigated. Thrombospondin-2 (TSP-2) has been shown to inhibit tumor growth and angiogenesis with a greater potency than the related molecule TSP-1. The systemic effects of TSP-2 on tumor metastasis and the underlying molecular mechanisms of the antiangiogenic activity of TSP-2 have remained poorly understood. We generated a recombinant fusion protein consisting of the N-terminal region of TSP-2 and the IgG-Fc1 fragment (N-TSP2-Fc) and could demonstrate that the antiangiogenic activity of N-TSP2-Fc is dependent on the CD36 receptor. We found that N-TSP2-Fc inhibited VEGF-induced tube formation of human dermal microvascular endothelial cells (HDMEC) on matrigel in vitro and that concurrent incubation of anti-CD36 antibody with N-TSP2-Fc resulted in tube formation that was comparable to untreated control. N-TSP2-Fc potently induced apoptosis of HDMEC in vitro in a CD36-dependent manner. Moreover, we could demonstrate a CD36 receptor-mediated loss of mitochondrial membrane potential and activation of caspase-3 in HDMEC in vitro. Daily intraperitoneal injections of N-TSP2-Fc resulted in a significant inhibition of the growth of human MDA-MB-435 and MDA-MB-231 tumor cells grown in the mammary gland of immunodeficient nude mice and in reduced tumor vascularization. Finally, increased serum concentrations of N-TSP2-Fc significantly inhibited regional metastasis to lymph nodes and distant metastasis to lung as shown by quantitative real-time alu PCR. These results identify N-TSP2-Fc as a potent systemic inhibitor of tumor metastasis and provide strong evidence for an important role of the CD36 receptor in mediating the antiangiogenic activity of TSP-2.

Immune-complex deposits in "pauci-immune" glomerulonephritis: a case report and brief review of recent literature.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis is considered a "pauci-immune" disease, characterized by absent or mild glomerular tuft staining for immunoglobulin and/or complement. We describe a 72-year-old man with progressive renal failure over five months who was found to have P-ANCA associated crescentic glomerulonephritis. Renal biopsy also revealed immunofluorescence staining for Immunoglobulin G and C3. Treatment comprised corticosteroids, cyclophosphamide, and plasmapheresis but unfortunately kidney function did not recover, likely due to substantial interstitial fibrosis at diagnosis. This case illustrates that serologic evaluation for ANCAs should not be discounted when immune deposits are present. Prompt diagnosis is warranted.

Formation of downhill esophageal varices as a rare but serious complication of hemodialysis access: a case report and comprehensive literature review.

BACKGROUND: Proximal or "downhill" esophageal varices are a rare complication of superior vena caval (SVC) obstruction. Few reports describe downhill varices in dialysis patients with catheter-related SVC occlusion. METHODS: We studied a case of downhill esophageal varices in a dialysis patient from our center and reviewed the published literature on presentation, evaluation and treatment in other dialysis patients (MEDLINE database search). RESULTS: Including our current case, we identified eight reports of dialysis patients with downhill varices. All cases were recognized after presentation with gastrointestinal bleeding, in contrast to low reported bleeding rates of downhill varices in non-dialysis patients. Localized edema and superficial venous engorgement (signs of SVC occlusion) were each observed in four of eight patients. The duration of hemodialysis dependence ranged from 2.5 to 23 years, and dialysis access history included multiple central venous catheters when described (seven cases). Central venous imaging by direct, magnetic resonance or computerized tomographic venography documented SVC stenosis in all cases. Management included percutaneous transluminal angioplasty of the SVC with or without stenting in five of eight patients, three of whom developed restenosis during observation. Successful surgical venous bypass was performed in one patient after failed percutaneous venoplasty. Varices were treated with band ligation in four of eight cases without reported complications. CONCLUSIONS: Although rare, downhill esophageal varices should be considered in the differential diagnosis of upper gastrointestinal hemorrhage in dialysis patients exposed to central venous catheters. Diagnosis should prompt radiographic evaluation of SVC patency. Treatment requires timely and coordinated care by specialists in endovascular interventions and gastrointestinal endoscopy.