RESUMO
AIM: To determine place of vitamin D in prevention and treatment of cardiorenal syndrome (CRS) and chronic allograft nephropathy (CAN) in the aspect of myocardial and renal reparation. METHODS AND MATERIAL: In Russia and the Netherlands we included in a randomized placebo controlled study 120 vitamin D deficient [25(OH) vitamin D<40 mol/l] recipients of asystolic and cadaveric donors. Patients were divided in 4 groups: paricalcitol (2-4 g/day) group (n=28), calcitriol (1-6 g/day orally) group (n=28), diet (1200-1800 IU/day of vitamin D with multivitamins and from foodstuffs) group (n=26), placebo with diet control group (n=27). RESULTS: After 180 days degree of CAN according to the Banff classification was 1.24 and 1.22 in paricalcitol and calcitriol groups, respectively, compared with 1.43 and 1.68 in diet and placebo groups, respectively (p<0.05). Glomerular filtration rate (GFR) changed from 46.7 to 84.4, 81.4, 76.8, and 54.5 ml/min/1.73 m3 in paricalcitol, calcitriol, diet and placebo groups, respectively. Fluorescence activated cell scanning (FACS) analysis allowed to detect quantitative induction of SP+ cells amounting 7.4, 2.9 and 1.2%; 7.2, 2.7; and 1.1%; 6.1, 2.9 and 1.2%; 9.3, 1.3 and 0.7% of peripheral blood progenitors, renal epithelial cells, and cardiomyocytes in paricalcitol, calcitriol, diet and placebo groups, respectively. Levels of CD133, CD34, CD73, and CD105 were significantly elevated in patients of paricalcitol (median 161, range 0-834 copies), calcitriol (163, 0-721), and diet (119, 0-401) groups, compared with the placebo group (0,0-41), p<0.01. Level of nuclear vitamin D receptor (VDR) protein in renal tissue homogenizate and myocardium achieved 584, 599, 478, and 333 mole VRD/mg and 801, 715, 654, and 389 Φmole VRD/mg of protein in paricalcitol, calcitriol, diet and placebo groups, respectively (p<0.01). Circulating progenitor stem cells demonstrated comparatively high level of VDR expression--529, 526, 401, and 211 mole VRD/mg in CD133, CD34 cells; 432, 414, 303, and 290 mole VRD/mg in CD73, CD105 cells; 549, 558, 442, and 302 φmole VRD/mg in SP+ cells in paricalcitol, calcitriol, diet and placebo groups, respectively (p<0.05). Hypercalcemia was detected in 4(14%) patients in calcitriol group (p<0.001). Under influence of antihypertensive therapy arterial pressure decreased after transplantation from 180/101 to 143/87, 141/94, 147,102, and 165/101 mm Hg in paricalcitol, calcitriol, diet and placebo groups, respectively (p<0.01). NYHA heart failure functional class changed from 2.3 to 1.8, 1.9, 1.9, and 2.5 in paricalcitol, calcitriol, diet and placebo groups, respectively (p<0.01). In 6 months after transplantation average CCS scores were 533 (0-998), 611 (0-1712), 524 (122-1278) and 990 (120-1800) cells in paricalcitol, calcitriol, diet and placebo groups, respectively (p<0.05). CONCLUSIONS: Vitamin D is an effective mean of prevention and treatment of CRS and CAN, stimulator of reparation of renal and myocardial tissues. Optimal for wide clinical practice is the use of active vitamin D analog paricalcitol (2-4 g/day) as well as special diet with multivitamins (up to 1800 IU of cholecalciferol).