CaCO3 dose and risk of arterial calcification

A. Fournier

Hôpital Sord, Amiens, France

Sir,

We read with interest the cross-sectional study by Guerin et al. [1] pointing out an independent link between the dose of oral CaCO3 and the semi-quantitative score of arterial calcification in four locations. To our knowledge, this is the first time that such a disquieting link is reported in the literature. In 1988, we prospectively analysed the progression of aortic and iliac artery calcification in adult dialysis patients and found it to be independently related to age, male sex, blood pressure, triglyceride, and glucose, but not to the plasma calciumxphosphate product or the dose of CaCO3 [2]. Factors involved in vascular calcification have also been investigated by Goldsmith et al. [3]. In multivariate analysis, only age, blood pressure, and plasma concentrations of phosphate and calcitriol were positively correlated to the progression of the calcification. Interestingly, the progression was negatively correlated to plasma calcium.

Coronary artery calcium density evaluated by electron beam computed tomography in older adult dialysis patients again has been found to be independently correlated to age and blood pressure but not to calciumxphosphate product or PTH levels [4]. Although the dose of CaCO3 was higher in young dialysed adults with presence of coronary calcification than in those without calcification, this link was obviously not independent because the age and duration on dialysis was much greater in those with calcification and no multivariate analysis was performed [5]

Surprisingly in Guerin's study, a negative correlation between PTH and calcification score was found in univariate analysis. Although this correlation was no more significant after adjustment for age, it points nevertheless to the possible role of relative oversuppression of PTH in the occurrence of vascular calcification. This role is further supported by the significantly greater prevalence of hypercalcaemia in the group with the highest calcification score. Indeed, relative hypoparathyroidism may favour adynamic bone disease and hypercalcaemia by decreasing the buffering capacity of the skeleton [6]. It would therefore be interesting to have some information on the bone remodelling status of these patients, be it only by providing values of total alkaline phosphatases if bone alkaline phosphatase is not available. Considering that the dialysis duration was 102 months in the group with the highest calcification score and only 52 months in the group with the lowest score, it would be interesting also to have data on the prescription of Al(OH)3 to all the patients, at least since the beginning of dialysis treatment, as previous aluminium overload is a major determinant of hypercalcaemia in dialysis patients switched to CaCO3, as shown by the work of Hercz et al. [7].

Because low bone turnover potentiates the occurrence of hypercalcaemia and hyperphosphataemia in particular when together with calcitriol use, it is important to recall that compared with calcitriol given with 5 g of CaCO3 and Al(OH)3, higher doses of CaCO3 (l5 g/day) alone have been recently shown to be associated with a lower plasma phosphate, for the same control of plasma calcium and PTH, and with higher bone alkaline phosphatase [8].

Therefore, we think that the observation of Guerin et al. of an independent link between CaCO3 dose and arterial calcifications should make us more cautious about the use of calcitriol rather than about that of CaCO3, the main concern of the nephrologist being to prevent hypercalcaemia and hyperphosphataemia by a continuous adjustment of dialysate calcium, and of CaCO3 dose while maintaining an adequate native vitamin D replete state [1], before using calcitriol.

References

  1. Guerin AP, London GH, Marchais SJ, Metivier P. Arterial stiffening and vascular calcifications in end stage renal disease. Nephrol Dial Transplant2000; 15: 1014–1021[Abstract/Free Full Text]
  2. Renaud H, Atik A, Herve M, et al. Evaluation of vascular calcinosis risk factors in patients on chronic hemodialysis lack of influence of calcium carbonate. Nephron1988; 48: 28–32[ISI][Medline]
  3. Goldsmith D, Covic A, Sambrook P, Ackrill P. Vascular calcification in long term haemodialysis patients in a single unit: a retrospective analysis. Nephron1997; 77: 3743
  4. Braun J, Oldendorf M, Moshage W, Heidler R, Zeitler E, Luft E. Electron beams computed tomography in the evaluation of cardiac calcifications in chronic dialysis patient. Am J Kidney Dis1996; 27: 394–401[ISI][Medline]
  5. Goodman W, Goldin J, Kuizon B, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. New Engl J Med2000; 342: 1478–1483[Abstract/Free Full Text]
  6. Kurz P, Monier Faugere M, Bognar B, Malluche M. Evidence for abnormal calcium homeostasis in patients with adynamic bone disease. Kidney Int1994; 46: 855–861[ISI][Medline]
  7. Hercz G, Pei Y, Greenwood C, et al. Aplastic osteodystrophy without aluminium: the role of suppressed parathyroid function. Kidney Int1993; 44: 860–866[ISI][Medline]
  8. Indridason O, Quarles L, for the Durham renal osteodystrophy group. Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. Kidney Int2000; 57: 282–292[ISI][Medline]

 

Reply

A. P. Guerin and G. M. London

Hôpital F. H. Manhès, Fleury-Mérogis, France

Sir,

We thank Professor Fournier for his remarks concerning the role of aluminium in the occurrence of low bone turnover. We did not analyse bone alkaline phosphate (BAP) as a marker of bone remodelling: (i) because this was not the topic of our study which was aimed at examining the influence of arterial calcifications on arterial stiffness, and (ii) because most of the patients were examined between 1996 and 1998 and at that time we did not perform BAP measurements systematically. Nevertheless, we have recently examined two groups of patients on whom we had sufficient data, namely a group with calcification score 0 and a group with calcification score 4, with 20 patients in each group having had BAP determinations at least twice. The means of the serum BAP measurements were respectively (38.5±29 U/l, n=20) for score 0 and (21±12.6 U/l, n=20) for score 4. The difference was statistically significant (P<0.05). These results, although incomplete, plead in favour of a low bone turnover state in the group with the highest calcification score.

Regarding the issue of a possible link with aluminium prescription and low bone turnover, as stated previously, these patients were examined between 1996 and 1998 and we have stopped aluminium prescription in our haemodialysis unit since 1988.

We then went back to our files and examined a possible relation with serum aluminium levels. In a group of 83 patients, basal serum aluminium before dialysis was 1.33±0.3 µmol/l (control subjects 0.18±0.06 µmol/l) and the increment of serum aluminium after a deferoxamine (DFO) test ({Delta}Al) was 2.2±1.52 µmol/l. If we analyse the relation between age, duration of dialysis, dose of CaCO3 prescribed, serum aluminium, DFO test and calcification score in univariate analysis, the calcification score was not related to serum aluminium, however, it was related to {Delta}Al (t=4.24, r=0.462, P<0.001). In multivariate analysis after adjustment for age, duration of dialysis, and CaCO3 prescribed, the correlation with {Delta}Al was no more significant (t=0.75, r=0.1, P=0.46). In contrast, the link with age, duration of dialysis and CaCO3 prescription persisted.





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