NDT Advance Access originally published online on November 28, 2006
Nephrology Dialysis Transplantation 2007 22(3):956-957; doi:10.1093/ndt/gfl692
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Impact of calcium and vitamin D therapy on arterial and cardiac disease in young adults with childhood-onset end stage renal disease
Email: Fournier.Albert{at}chu-aminus.frSir,
In the discussion of their well-documented study on cardiovascular disease in young adults with childhood-onset of end-stage renal disease (ESRD), the Berlin paediatricians Briese et al. [1] pointed out interesting differences with a quite similar study reported 4 years ago by their colleagues of Heidelberg [2]: the prevalence of coronary calcifications (10 vs 92%) and of cardiac valve calcifications (0 vs 32%) was quite lower in the Berlin study than in the Heidelberg one, while the technique of evaluation was comparable (Table 1). This difference was all the more remarkable in that the population characteristics were quite similar regarding the proportion of transplanted patients. However, the age was slightly younger (23 vs 27 years) while time on dialysis was shorter (2.9 vs 5 years) and that of transplantation longer (9.2 vs 7.8 years). In spite of these differences, at the time of cardiovascular evaluation, the classical cardiovascular risks [body mass index (BMI), smoking, low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol] were comparable (with the exception of mean blood pressure which was 11 mmHg lower), as well as the non-classic risk factors such as albumin and homocysteine, with the exception of CRP that was 11 mg/l higher in the Berlin study. Regarding the serum mineral parameters, although their evaluation in the Berlin study was only punctual and not time-integrated as in the Heidelberg one, it is remarkable to note that the Ca x PO4 product was similar while the serum parathyroid harmone (PTH) levels were twice lower in Berlin, despite the fact that the cumulative doses of both calcium oral phosphate binder (Ca-OPB) and ‘active’ vitamin D (alfacalcidol or calcitriol) were much lower (respectively by 7- and 35- folds). Since the Berlin authors did not comment on such differences in calcium and vitamin D therapy and clinical results, we would like to propose the following comments.
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We have noted that in contrast to the Heidelberg group, the Berlin group mentioned the use of cholecalciferol i.e. plain vitamin D at a dose of 2.1–106 IU per year i.e. 5.750 IU (or 143 µg) per day i.e. a dose that would certainly secure a serum 25 OH vitamin D level well above the recommended thresholds of 30–40 ng/ml [3]. Even though the 3 year difference in age and the 2 years less time on dialysis may have contributed to the 2-fold difference in PTH suppression, we think that a causal relationship between lower PTH levels and lower prevalence of cardiovascular calcifications with cholecalciferol use cannot be excluded. Indeed, there is a rational to relate this better PTH suppression to cholecalciferol use since the Slatopolsky group [4] recently evidenced in bovine parathyroid cell cultures that at a concentration of 40 ng/ml 25 OH vitamin OH D was as efficient as calcitriol at a maximally PTH suppressive dose (40–80 ng/ml), for suppressing PTH. The reason for this efficiency is not only that the concentration of 25 OH vitamin D is about 103 higher, but that provided calcidiol concentration is sufficient, it can be taken up by the LR2-megalin receptor present in the parathyroid cells and presented to their mitochondrial 25 OH vitamin D-1
hydroxylase, in order to synthesize 1.25(OH)2 vitamin D [5]. This in situ synthesized calcitriol can then suppress the transcription of the prepro PTH gene and therefore, the synthesis of PTH. Regarding the link between lower PTH levels and lower prevalence of cardiovascular calcifications it is suggested not only by comparison of the two paediatric studies, but also by a direct correlation reported in the Heidelberg study, between PTH levels and extension of calcifications; a correlation which was even tighter than that between this latter with the Ca.PO4 product. The contrast between the association of lower calcification extension with lower PTH in the Berlin Study and the reverse association in the Heidelberg study, is all the more remarkable in that it was not confounded by a three-times higher CRP level in the Berlin Study, since inflammation is a factor favouring vascular calcification [6]. This contrast can be explained by the fact that 25 OH vitamin D3 compared with 1,25(OH);D3, given at doses inducing the same PTH suppression and the same Ca.Pi product, was found to better mineralize the osteoid tissue [7].
We would hope that these remarks will lead paediatricians to document the serum 25 OH vitamin D concentration of their uraemic children and to correct any vitamin D deficiency and even insufficiency (S 25 OH vitamin >30 ng/ml), not only in pre-dialysis chronic kidney disease patients but also in dialysis children, even though this recommendation is not made in the American NKF-K/DOQI guidelines [3].
Conflict of interest statement. None declared.
References
- Briese S, Wiesner S, Will JC, et al. (2006) Arterial and cardiac disease in young adults with childhood-onset end-stage renal disease-impact of calcium and vitamin D therapy. Nephrol Dial Transplant 21:1906–1914.
[Abstract/Free Full Text] - Oh J, Wunsch R, Turzer M, et al. (2002) Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure. Circulation 106:100–105.
- KDOQI. (2003) National Kidney Foundation KDOQI (Kidney Disease Outcomes Quality Initiative): clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42:[suppl 13], S1–S201.[Medline]
- Ritter CS, Armbrecht HJ, Slatopolsky E, Brown AJ. (2005) 25 hydroxyvitamin D3 suppresses PTH synthesis and secretion by cultured bovine parathyroid cells: potential role for intracrine1.25(OH)2 D3. JASN 16:Poster SA PO 889.
- Segersten U, Correa P, Hewison M, et al. (2002) 25-hydroxyvitamin D(3)-1alpha-hydroxylase expression in normal and pathological parathyroid glands. J Clin Endocrinol Metab 87:2967–2972.
[Abstract/Free Full Text] - Jung HH, Kim SW, Han H. (2006) Inflammation, mineral metabolism and progressive coronary artery calcification in patients on haemodialysis. Nephrol Dial Transplant 21:1915–1920.
[Abstract/Free Full Text] - Fournier A, Bordier P, de Luca H, et al. (1979) Comparison of 1 alpha (OH)2 vitamin D3 and 25 OH vitamin D3 in the treatment of renal osteodystrophy: greater effect of 25 OH vitamin D3 on bone mineralization. Kidney Int 15:196–204.[Web of Science][Medline]
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