Rapidly progressive severe vascular calcification sparing the kidney allograft following warfarin initiation.

We describe a case of rapid onset of vascular calcification coincident with the initiation of warfarin therapy in a kidney transplant recipient. Calcification developed within the media of the blood vessel wall, with relative intimal sparing. Medium and small arteries were affected; however, the aorta was mostly free of calcifications, suggesting a differential response to warfarin between the intima and media and between different vascular beds. In addition, unlike the highly calcified native kidney's vessels, the kidney allograft was not calcified, suggesting local genetically determined mechanisms in preventing vascular calcification. Distal subcutaneous necrosis ultimately led to the patient's death.

Impact of ergocalciferol treatment of vitamin D deficiency on serum parathyroid hormone concentrations in chronic kidney disease.

BACKGROUND: Vitamin D deficiency is highly prevalent and associated with secondary hyperparathyroidism in patients with chronic kidney disease (CKD). The Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines recommend treatment of vitamin D deficiency starting with CKD stage 3, though no data are available showing an impact on serum parathyroid hormone (PTH) concentrations. The goal of this analysis, therefore, was to determine the effect of ergocalciferol treatment on plasma PTH concentrations in vitamin D-deficient patients with stage 3 and stage 4 CKD. METHODS: A prospective, nonrandomized observational analysis was conducted in an academic community hospital CKD clinic. Fifty-two patients with stage 3 or stage 4 CKD with vitamin D deficiency and elevated PTH concentrations received ergocalciferol dosed per a modified K/DOQI guidelines protocol and adjusted every 3 months. Serum PTH, 25-vitamin D, 1,25-vitamin D, calcium, phosphorus, and albumin levels were drawn at initiation of therapy and repeated every 3 months. RESULTS: The mean 25-vitamin D levels normalized in patients with stage 3 and 4 CKD, with values of 31.6 +/- 2.2 ng/ml (78.8 +/- 5.49 nmol/l) and 35.4 +/- 1.9 ng/ml (88.4 +/- 4.74 nmol/l), respectively (p < 0.0001). A median decrease in PTH concentrations of 13.1 and 2.0% was noted in patients with stage 3 and stage 4 CKD, respectively (p = 0.041, p = nonsignificant). CONCLUSIONS: Ergocalciferol therapy is a reasonable initial therapy for vitamin D deficiency associated with elevated PTH levels in stage 3 CKD. It does not appear to have equivalent benefits in stage 4 CKD.

The Caenorhabditis elegans heterochronic regulator LIN-14 is a novel transcription factor that controls the developmental timing of transcription from the insulin/insulin-like growth factor gene ins-33 by direct DNA binding.

A temporal gradient of the novel nuclear protein LIN-14 specifies the timing and sequence of stage-specific developmental events in Caenorhabditis elegans. The profound effects of lin-14 mutations on worm development suggest that LIN-14 directly or indirectly regulates stage-specific gene expression. We show that LIN-14 can associate with chromatin in vivo and has in vitro DNA binding activity. A bacterially expressed C-terminal domain of LIN-14 was used to select DNA sequences that contain a putative consensus binding site from a pool of randomized double-stranded oligonucleotides. To identify candidates for genes directly regulated by lin-14, we employed DNA microarray hybridization to compare the mRNA abundance of C. elegans genes in wild-type animals to that in mutants with reduced or elevated lin-14 activity. Five of the candidate LIN-14 target genes identified by microarrays, including the insulin/insulin-like growth factor family gene ins-33, contain putative LIN-14 consensus sites in their upstream DNA sequences. Genetic analysis indicates that the developmental regulation of ins-33 mRNA involves the stage-specific repression of ins-33 transcription by LIN-14 via sequence-specific DNA binding. These results reinforce the conclusion that lin-14 encodes a novel class of transcription factor.