Adipocyte induced arterial calcification is prevented with sodium thiosulfate.

BACKGROUND: Calcification can occur in fat in multiple clinical conditions including in the dermis, breasts and in the abdomen in calciphylaxis. All of these are more common in patients with advanced kidney disease. Clinically, hyperphosphatemia and obesity are risk factors. Thus we tested the hypothesis that adipocytes can calcify in the presence of elevated phosphorus and/or that adipocytes exposed to phosphorus can induce vascular smooth muscle cell (VSMC) calcification. METHODS: 3T3-L1 preadipocytes were induced into mature adipocytes and then treated with media containing high phosphorus. Calcification was assessed biochemically and PCR performed to determine the expression of genes for osteoblast and adipocyte differentiation. Adipocytes were also co-cultured with bovine VSMC to determine paracrine effects, and the efficacy of sodium thiosulfate was determined. RESULTS: The results demonstrated that high phosphorus induced the calcification of differentiated adipocytes with increased expression of osteopontin, the osteoblast transcription factor Runx2 and decreased expression of adipocyte transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding protein α (CEBPα), indicating that high phosphorus led to a phenotypic switch of adipocytes to an osteoblast like phenotype. Sodium thiosulfate, dose dependently decreased adipocyte calcification and inhibited adipocyte induced increase of VSMC calcification. Co-culture studies demonstrated that adipocytes facilitated VSMC calcification partially mediated by changes of secretion of leptin and vascular endothelial growth factor (VEGF) from adipocytes. CONCLUSION: High phosphorus induced calcification of mature adipocytes, and adipocytes exposed to elevated phosphorus can induce calcification of VSMC in a paracrine manner. Sodium thiosulfate inhibited this calcification and decreased the secretin of leptin and VEGF from adipocytes. These results suggest that adipocyte exposure to elevated phosphorus may be a pathogenic factor in calcification observed in the skin in calciphylaxis and other diseases.

Urinary tract infections and asymptomatic bacteriuria in renal transplant recipients.

Asymptomatic bacteriuria and urinary tract infection are common complications after kidney transplantation. In this population, if urinary tract infection occurred in the first six months post procedure, it carries a grave impact on both graft and patient survival. Renal transplant recipients with urinary tract infection are often clinically asymptomatic as a consequence of immunosuppression. Urinary tract infection, however, may progress to acute pyelonephritis, bacteremia and the full blown picture of urosepsis. PubMed and Cochrane databases were searched. The purpose of this review is to discuss the screening and treatment of urinary tract infection and asymptomatic bacteriuria in renal transplant recipients and to evaluate the guidelines on the basis of a review of published evidence.