Vitamin D receptor activators inhibit vascular smooth muscle cell mineralization induced by phosphate and TNF-α.

BACKGROUND: Vascular calcification is a highly regulated process. Tumor necrosis factor-α (TNF-α) has been shown to accelerate the highly regulated osteogenic process in vascular smooth muscle cells (VSMCs). Vitamin D receptor activators (VDRAs) have been associated with beneficial cardiovascular outcomes in patients with chronic kidney disease. We examined whether maxacalcitol, a vitamin D(3) analog, exhibits a suppressive effect on VSMC mineralization induced by phosphate and TNF-α. METHODS: Human VSMCs were treated with either vehicle, maxacalcitol (10(-9) to 10(-7) M), or calcitriol (10(-9) to 10(-7) M) in 2.5 mM of phosphate media with TNF-α (1 ng/mL) for 9 days. VSMC mineralization was determined and expression of genes associated with the osteogenic process was examined by real-time reverse transcription-polymerase chain reaction. Expression of matrix metalloproteinase-2 (MMP-2) messenger RNA (mRNA) in VSMCs and MMP-2 protein in media was also analyzed. RESULTS: Vehicle-treated VSMCs exhibited massive mineralization, which was inhibited by maxacalcitol in a concentration-dependent manner. Calcitriol also inhibited the mineralization. While vehicle-treated VSMCs exhibited increased mRNA expression of genes associated with the osteogenic process (Cbfa1/Runx2 and osteocalcin) compared with VSMCs grown in normal media without TNF-α (control), maxacalcitol and calcitriol suppressed the increase in mRNA species. Furthermore, vehicle-treated VSMCs exhibited increased MMP-2 mRNA and protein in the media that were suppressed notably by maxacalcitol. CONCLUSIONS: Both the VDRAs abrogated the acceleration of the osteogenic process induced by phosphate and TNF-α in VSMCs, which was linked to inhibition of mineralization in VSMCs. MMP-2 blockade by VDRAs may contribute to an inhibitory effect on vascular calcification.

Olmesartan medoxomil is associated with decreased plasma AGEs, pentosidine, and N-(epsilon)-carboxymethyl-lysine levels in hemodialysis patients.

BACKGROUND: Advanced glycation end products (AGEs) are associated with comorbidity and death among patients on hemodialysis (HD). Angiotensin II type 1 receptor blockers (ARBs) can decrease the formation of AGEs in vitro. This study examines the ability of various ARBs to decrease plasma AGE levels in hypertensive patients on HD. METHODS: This preliminary randomized prospective study included 24 hypertensive patients on HD who were treated with candesartan (8 mg/day). The patients were randomly assigned to an olmesartan (20 mg/day, n = 12) or a telmisartan (40 mg/day, n = 12) group and followed up 24 weeks. Blood pressure was monitored before each HD session, and plasma pentosidine, N-(epsilon)-carboxymethyl-lysine (CML), serum malondialdehyde-low-density lipoprotein (LDL), high-sensitive CRP, and serum total free radical (TFR) were measured at baseline, and at 4, 12, and 24 weeks. RESULTS: Olmesartan was significantly associated with decreased systolic blood pressure compared with telmisartan. After 24 weeks of treatment, plasma pentosidine and CML levels were significantly decreased and serum TFR levels tended to be decreased in the olmesartan group, but remained unchanged in the telmisartan group. CONCLUSIONS: These results suggest that olmesartan can help to decrease plasma AGE levels in patients on HD.

[CKD-MBD (chronic kidney disease-mineral and bone disorder). CKD-MBD: chronic kidney disease-mineral and bone disorder].

Disturbances in bone and mineral metabolism in patients with chronic kidney disease (CKD) affect not only the bone diseases but also other organ disorders in the whole body and deteriorate the survival of these patients. The term CKD-Mineral and Bone Disorder (CKD-MBD) has been established describing a broader clinical syndrome that develops as a systemic disorder of mineral and bone metabolism due to CKD. Vascular calcification and secondary hyperparathyroidism are major diseases in CKD-MBD.

Membranous nephropathy that first presented in pregnancy.

A 37-year-old woman at 17 weeks of gestation who was first noted to have proteinuria and microscopic hematuria at 13 weeks of gestation was admitted to our hospital with proteinuria that progressed to nephrotic syndrome (NS). Despite the treatment with prednisolone, including methylprednisolone pulse therapy, the NS worsened. The patient underwent an elective abortion at 21 weeks of gestation, and the NS then went into partial remission. A renal biopsy revealed membranous nephropathy (MN). There was no evidence of secondary MN. This is the first reported case of subclinical idiopathic MN that first developed in pregnancy.

A case of tuberculous peritonitis in a hemodialysis patient with high serum soluble interleukin-2 receptor and CA-125 levels.

A hemodialysis patient with tuberculous peritonitis with hypercalcemia and high serum soluble interleukin-2 receptor (sIL-2R) and CA-125 levels is reported. An 82-year-old woman who had been on hemodialysis therapy for 6 years was admitted to our hospital for evaluation and treatment of hypercalcemia. Laboratory examination and radiologic studies revealed markedly increased serum sIL-2R and CA-125 levels and exudative ascites, with high levels of adenosine deaminase (ADA) and CA-125, which was suggestive of malignancy or tuberculosis. She was finally diagnosed as having tuberculous peritonitis based on positivity for Mycobacterium tuberculosis in ascitic fluid. The ascites subsided with normalization of hypercalcemia and a marked decrease in serum sIL-2R and CA-125 levels in response to anti-tuberculosis treatment. This case indicates that serum sIL-2R and CA-125 levels can rise to levels suggestive of malignancy in tuberculous peritonitis, and that they can be used to monitor the response to anti-tuberculosis treatment.