Vascular endothelial function in cyclosporine and tacrolimus treated renal transplant recipients.

BACKGROUND: Endothelial dysfunction is an early key event in the development of arteriosclerotic cardiovascular disease (ASCVD), thus an early marker of subclinical ASCVD. Endothelial function is impaired in renal transplant recipients (RTR) treated with cyclosporine (CyA). Tacrolimus is associated with less hyperlipidemia and hypertension than CyA, however, there are no data on endothelial function in tacrolimus-treated RTR. METHODS: High-resolution brachial ultrasonography was used to assess endothelium-dependent dilatation (EDD), and endothelium-independent dilatation (EID) in 20 stable RTR and a control group of 10 healthy subjects without clinical evidence of ASCVD. The RTR group included patients receiving CyA (n=10) and tacrolimus (n=10). EDD and EID were measured as percent increase in brachial artery diameter in response to reactive hyperemia and nitroglycerin, respectively. RESULTS AND CONCLUSIONS: EDD was significantly lower in RTR versus controls (1.7+/-0.7 vs. 7.3+/-0.7%, P<0.0001), whereas EID was similar in the two groups. No significant differences were found in EDD or in EID between CyA- and tacrolimus-treated RTR. Glomerular filtration rate, plasma homocysteine, blood pressure, and lipid profiles were similar in CyA- and tacrolimus-treated RTR.

Familial calcium stone disease: TaqI polymorphism and the vitamin D receptor.

BACKGROUND AND OBJECTIVE: Calcium nephrolithiasis has a strong familial component. However, to date, no specific genetic abnormality has been identified. Allelic variation in the vitamin D receptor (VDR) gene has been suggested as a partial explanation of differential calcium absorption or excretion in these patients. Polymorphism of this gene has been associated with altered vitamin D activity and has been implicated in osteoporosis and prostate cancer. We propose that a similar association may be found between familial hypercalciuric stone disease and the VDR. SUBJECTS AND METHODS: Genomic DNA was isolated from 37 controls and 19 patients with hypercalciuria (> 250 mg/24 hours) and a family history of nephrolithiasis. A 740-basepair segment of the VDR gene was amplified by polymerase chain reaction, digested with TaqI endonuclease, and resolved by gel electrophoresis. Alleles were classified as "T" if only one TaqI site was present and "t" if two were present. A simplified strength of family history score (FHS) was computed by adding 2 and 1 points, respectively, for each first- and second-degree relative affected by stone disease. RESULTS: No difference in allelic or genotypic frequencies between the study and control groups was present. In the stone group, a significant association was found between the strength of the family history and the TT genotype. Patients with this genotype had an average FHS of 4.0, whereas the mean FHS for the Tt and tt genotypes was 2.0 and 1.8, respectively (P < 0.05). Nonsignificant trends of the TT genotype toward a higher number of stone episodes (19 v 13 and 3) and higher 24-hour urine calcium excretion (408 v 297 and 353 mg) were also noted in the study group. CONCLUSION: The results suggest that the TT genotype is associated with more aggressive stone disease, both within families and with respect to recurrence. Quantifying the risk of calcium stone disease through DNA markers has potential application in determining the risk of a patient's family members for nephrolithiasis or a patient's risk of recurrence. This information may have therapeutic implications with regard to the rigor of medical therapy and frequency of follow-up.