Publications by authors named "Annarita Di Nunzio"

The triad composed by α-Klotho, fibroblast growth factor-23, and its receptor are involved in the pathogenesis of chronic kidney disease-mineral and bone disorder. A disintegrin and metalloproteinase 17 (ADAM17) is a metalloproteinase causing the proteolytic shedding of α-Klotho from the cell membrane, and its role in chronic kidney disease-mineral and bone disorder is not yet known. We studied the circulating levels of the above-mentioned mediators in patients with secondary hyperparathyroidism due to uremia, compared to control subjects, as well as in patients with primary hyperparathyroidism.

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Dialysis patients display a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity. Among uremic toxins, homocysteine and cysteine are both substrates of cystathionine β-synthase and cystathionine γ-lyase in hydrogen sulfide biosynthesis, leading to the formation of two sulfur metabolites, lanthionine and homolanthionine, considered stable indirect biomarkers of its production. Hydrogen sulfide is involved in the modulation of multiple pathophysiological responses.

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Human mesenchymal stem cells (hMSCs), the precursors of osteoblasts during osteogenesis, play a role in the balance of bone formation and resorption, but their functioning in uremia has not been well defined. To study the effects of the uremic milieu on osteogenic properties, we applied an in vitro assay culturing hMSCs in osteogenic medium supplemented with serum from healthy donors and from uremic patients on hemodialysis. Compared to control, serum from uremic patients induces, in hMSC cultures, a modification of several key regulators of bone remodeling, in particular a reduction of the ratio Receptor Activator of Nuclear factor Kappa B Receptor (RANKL) over osteoprotegerin, indicating an adaptive response of the system to favor osteogenesis over osteoclastosis.

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Hydrogen sulfide, (H2S), is an endogenous gas which exerts a protective function in several biological processes, including those involved in inflammation, blood pressure regulation, and energy metabolism. The enzymes involved in H2S production are cysthationine -synthetase, cysthationine -lyase and 3-mercaptopyruvate sulfurtransferase. Low plasma H2S levels have been found in chronic renal failure (CRF) in both humans and animal models.

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