Analyse der Korrelation von 1,25-Dihydroxycholecalciferol Plasmaspiegel und Intima-Media-Dicke bei niereninsuffizienten und nierentransplantierten Kindern und Jugendlichen

Chronic renal insufficiency represents a cardiovascular high-risk constellation. Children and adolescents in late stages of chronic kidney disease (CKD) are almost all affected by a disturbance of the calcium-phosphate balance, which is not least due to a deficiency of the active vitamin D metabolite. If renal function decreases, not only is the excretory function insufficient, but incremental performance also decreases, and consequently also the 1-alpha-hydroxylation of 25-hydroxycholecalciferol (25(OH)D) in the proximal tubule cells of the kidney. The absence of 1,25-dihydroxycholecalciferol (1,25(OH)₂D), which is the active form of vitamin D, leads to a decrease in serum calcium, a regulatory increase in parathyroid hormone secretion and following to hypercalcemia and hyperphosphatemia. The consequences are premature arterial vascular damage and subsequently increased cardiovascular mortality. In order to reduce this risk factor, it is necessary to find out how to establish and maintain normal metabolic conditions in childhood CKD patients. We are therefore investigating the influence of 1,25(OH)₂D levels and other parameters of calcium-phosphate metabolism on arterial calcification. Since the intima-media-thickness (IMT) increases with progressive CKD and is an important parameter for the development of cardiovascular disease, it serves as a surrogate parameter for vascular changes. The study included 35 patients aged 6-18 years (median 13.7), who are in CKD stages 3-5D or have already received a kidney transplant (n=22). The underlying diseases of the children and adolescents that led to the advanced renal insufficiency are manifold. To obtain reliable results for this inhomogeneous patient group, age- and sex-adjusted intima-media-thickness standard deviation scores (IMT-SDS) were used and correlated with the individual serum levels of further parameters, such as 25(OH)D, 1,25(OH)₂D, parathyroid hormone, alkaline phosphatase, Calcium, phosphate, ionised calcium, and CRP. With the exception of a few patients, the IMT-SDS of all children and adolescents (n=32/35) were above their age-related average. The patients without kidney transplant had higher IMT-SDS values than the transplanted ones. The changes described above with increasing renal insufficiency were able to be reproduced in this study. Thus a decrease in 1,25(OH)₂D serum levels were observed in the presence of increasing CKD stage and increasing parathyroid hormone serum levels with decreasing 1,25(OH)₂D. These correlations were statistically significant. Although the results showed no significant correlation of 1,25(OH)₂D with IMT-SDS, a positive correlation of IMT-SDS with parathyroid hormone, ionized calcium and phosphate was shown in the transplanted patients. High average values of these parameters seem to promote the increase in IMT. Consequently, parathyroid hormone appears to be a link between 1,25(OH)₂D and IMT. It increases with a decrease in 1,25(OH)₂D and as a consequence contributes to an increase in IMT. These seem to be relevant factors for vascular damage, the normalization of which should be given even more weight in clinical work.