vitamin-d-2 and Cardio-Renal-Syndrome

The ubiquitous distribution of vitamin D receptors in the human body is responsible for the pleiotropic effects of vitamin D-receptor activation. We discuss the possible beneficial effects of a selective activator of vitamin D receptor, paricalcitol, on the cardiovascular system in chronic heart failure patients and chronic kidney patients, in light of new trials. Paricalcitol should provide additional clinical benefits over the standard treatment for chronic kidney and heart failure, especially in cases of cardiorenal syndrome.

Topics: Aging; Animals; Bone Density Conservation Agents; Cardio-Renal Syndrome; Cardiovascular System; Chronic Disease; Ergocalciferols; Heart Failure; Humans; Randomized Controlled Trials as Topic; Receptors, Calcitriol; Renal Insufficiency, Chronic

The involvement of vitamin D deficiency in cardiovascular morbidity and mortality is attracting great interest. In patients with chronic kidney disease this association is stronger because vitamin D levels decrease as a result of renal progressive impairment. In chronic kidney disease secondary hyperparathyroidism commonly occurs in response to persistent hypocalcemia and hyperphosphatemia; moreover, parathyroid gland volume increases, vascular calcification is accelerated, and structural and functional modifications of the left ventricle are observed. These alterations entail both cardiac and renal involvement, resulting in cardio-renal syndrome. Recent studies concluded that vitamin D administration seems to have cardioprotective and renoprotective effects and improve peripheral vascular disease, vascular calcification, cardiac outcome, and blood pressure control. In clinical practice, therefore, the use of this hormone may play an important role in cardio-renal syndrome prevention.

Topics: Cardio-Renal Syndrome; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Hyperphosphatemia; Hypocalcemia; Kidney; Parathyroid Glands; Parathyroid Hormone; Receptors, Calcitriol; Renal Insufficiency, Chronic; Vascular Calcification; Vitamin D; Vitamin D Deficiency

In uremic animals, vitamin D receptor (VDR) agonists like paricalcitol (Pc) attenuate cardiac hypertrophy, but this effect has not been replicated consistently in humans with chronic kidney disease. Elevated fibroblast growth factor 23 (FGF23) levels cause cardiac hypertrophy with activation of the myocardial calcineurin/nuclear factor of activated T cell (NFAT) axis and may antagonize the cardioprotective effects of VDR agonist therapy. We hypothesized that the effectiveness of Pc may depend on the prevailing circulating levels of FGF23 and could be potentiated by the combined administration of a pan-FGF23 receptor (FGFR) blocker agent (PD173074).. In rats with 5/6 nephrectomy treated with Pc or PD173074 or both agents concurrently, myocardial mRNA expression of renin-angiotensin system, VDR, FGFR4, and calcineurin/NFAT target genes was determined. In adolescents on hemodialysis, we analyzed sequential echocardiograms, blood pressures and serial FGF23 measurements, and their relations to the cumulative administered dose of parenteral Pc.. The ratio of Pc dose/plasma levels of FGF23 correlated inversely (P < 0.005) with the cardiac mass in uremic rats and in hemodialysis patients, independently of hypertension. Despite persistently elevated FGF23 levels and myocardial FGFR4 activation, Pc suppressed upregulated myocardial calcineurin/NFAT target genes, and the effects were amplified by coadministration of PD173074.. The beneficial effects of Pc on uremic cardiac hypertrophy are counterbalanced by the increased FGF23 levels. Blockade of FGF23-mediated signaling increased the Pc-induced suppression of the myocardial calcineurin/NFAT system. Higher doses of Pc should be considered in the treatment of patients with uremic cardiomyopathy.

Topics: Adolescent; Animals; Cardio-Renal Syndrome; Cardiomyopathies; Child; Disease Models, Animal; Drug Therapy, Combination; Ergocalciferols; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Heart Ventricles; Humans; Kidney Failure, Chronic; Male; Pyrimidines; Rats, Sprague-Dawley; Receptor, Fibroblast Growth Factor, Type 4; Receptors, Calcitriol; Retrospective Studies; Signal Transduction; Uremia; Ventricular Function, Left; Ventricular Remodeling

Vitamin D has been shown to induce beneficial effects on cardiovascular and renal morbidity by regulating inflammation and tissue fibrosis.. To evaluate the effect of vitamin D analogues on cardiac function and fibrosis in an animal model of cardiorenal syndrome.. Unilateral nephrectomy was performed and myocardial infarction induced in rats. The rats were treated with vitamin D receptor activator (VDRA, paricalcitol, 40 ng/250 g x 3/week) versus a vehicle. A third group of animals, which served as the control, underwent sham surgery and received no treatment. After 4 weeks of treatment, cardiac function and fibrosis were assessed by trans-thoracic echo and histology, respectively. As a parameter of systemic inflammation, previously shown to be altered in acute coronary syndrome, T regulatory (Treg) cell levels were measured by flow cytometry. Renal dysfunction was documented by standard laboratory tests.. After 4 weeks of treatment, no significant improvement in cardiac function parameters was noted following VDRA administration. VDRA treatment did not significantly alter Treg cell systemic levels. Consistently, despite a trend toward less extent of myocardial fibrosis, we found no clear beneficial effects of VDRA on myocardial tissue inflammation and remodeling.. Vitamin D treatment showed no beneficial effects on cardiac function parameters and fibrosis in an animal model of cardiorenal syndrome.

Topics: Animals; Cardio-Renal Syndrome; Disease Models, Animal; Ergocalciferols; Fibrosis; Flow Cytometry; Inflammation; Male; Rats; Rats, Inbred Lew; T-Lymphocytes, Regulatory; Treatment Outcome