The scarcity of transplant allografts for diseased organs has prompted efforts at tissue regeneration using seeded scaffolds, an approach hampered by the enormity of cell types and complex architectures. Our goal was to decellularize intact organs in a manner that retained the matrix signal for differentiating pluripotent cells. We decellularized intact rat kidneys in a manner that preserved the intricate architecture and seeded them with pluripotent murine embryonic stem cells antegrade through the artery or retrograde through the ureter. Primitive precursor cells populated and proliferated within the glomerular, vascular, and tubular structures. Cells lost their embryonic appearance and expressed immunohistochemical markers for differentiation. Cells not in contact with the basement membrane matrix became apoptotic, thereby forming lumens. These observations suggest that the extracellular matrix can direct regeneration of the kidney, and studies using seeded scaffolds may help define differentiation pathways.

With the aggressive algorithm, the construction of native AVF is possible in the overwhelming majority of patients presenting for new hemodialysis access.

Cardiorenal anemia syndrome refers to the simultaneous presence of anemia, heart failure (HF), and chronic kidney disease (CKD) that forms a pathologic triangle with an adverse impact on morbidity and mortality. The reciprocal relationships among these 3 components have been the subject of a number of trials with inconsistent and sometimes paradoxic results. In this paper, the pathophysiologic concepts underlying interactions among these 3 conditions are discussed. Then, the similarities and dissimilarities of the relationships between anemia and either HF or CKD are considered; explanations are provided for differences in the results of the currently available studies. Erythropoietin-stimulating agent protocols are usually based on the results of studies designed for the CKD population, and upper hemoglobin target levels are chosen to avoid cardiovascular complications. It is not yet clear whether those renal guidelines are optimal for patients with HF, especially because those patients may have reversible components of kidney dysfunction, both HF and renal parameters improving with anemia correction. We review these issues and suggest a pragmatic approach to the care of patients with HF until such time that controlled trials establish definitive anemia treatment goals that are dynamic and disease specific, rather than those that adopt a more simplistic hemoglobin-specific approach.

Treatment strategies for calciphylaxis are limited by inadequate understanding of its pathophysiology. Mortality reaches 80%, due to progressive skin ischemia, necrosis and infections. In addition to calcium and parathyroid disorders, hypercoagulability can have a role: primary thrombotic disorders as well as secondary, such as proposed warfarin procoagulant effects. Traditional care addresses the calcium-phosphate-PTH axis: minimizing calcium intake, calcimimetics, cautious vitamin D analogs, strict phosphate control, and surgical parathyroidectomy if necessary. Newer approaches focus on extraosseous mineralization: dissolution of calcium deposits, altering osteoprotegerin and NF-ĸB pathways, and treating macrophage or cytokine-mediated inflammation. Sodium thiosulfate has reported success, and is thought to be due to enhanced calcium solubility and dialysis clearance. Bisphosphonates may have efficacy by lowering bone turnover or a variety of vascular tissue mechanisms. The literature for both agents is very limited, and optimal dosing regimens remain unclear. Patients responsive to a medication will have decreasing pain in days and lesions beginning to heal within approximately 2 weeks. Due to high mortality, early use of combination therapy is advocated, although specific protocols have not been well established. The often dramatic improvements in case-based literature are very encouraging and will hopefully lead to more rigorous studies.

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