NDT Advance Access originally published online on July 31, 2008
Nephrology Dialysis Transplantation 2008 23(10):3369-3370; doi:10.1093/ndt/gfn432
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Reply
Nephrol Dial Transplant 2008; doi:10.1093/ndt/gfn428E-mail: juergen_bommer{at}t-online.de
Sir,
In their letter, Dr Drueke and Dr Chanard criticized our assumption that under steady state conditions, urinary calcium excretion corresponds to the calcium load in healthy subjects. We agree that under steady state conditions in adult individuals urinary calcium excretion corresponds more strictly to the net calcium absorption and apologize for the confusion that has been created by the somewhat lax vocabulary. The determination of net calcium absorption under treatment with placebo, sevelamer and calcium carbonate was the primary aim of our study. We calculated the fraction of the dietary intake of calcium excreted in the urine according to Knapp [1]. We defined the ‘calcium load’ as the amount of calcium absorbed in the gut and neither excreted via intestinal, biliary or pancreatic secretion nor stored in the body, for instance in bone, soft tissue, intercellular pool, etc.
The study of Birge [2] does not indicate that a delay of at least 30 days is necessary to achieve steady state conditions as stated in the letter. These authors reported in the paper only that the fractional calcium absorption was identical after 30 days, but they did not study shorter time intervals. The ‘Methods’ section of this paper recommends 10–17 days of constant dietary intake. After a 1-week wash-out period between each treatment period, we determined the calcium excretion in the completely collected daily urine output over 7 days. The procedure was blinded, the protocol included randomization and each person served as its own control. Steady state conditions or at least comparable conditions are suggested during the three treatment periods, since during each of the different treatment periods, the daily calcium excretion was constant for 7 days—an argument against major disturbing influences
In contrast to what had been suggested in the letter, the proportion of 8.7 or 14.8% of oral intake of calcium recovered in the urine is in agreement with the data of Knapp. In this paper, an intake of 15 mg calcium/kg body weight yielded a mean urinary calcium excretion of 18% of the ingested intake; if the dietary calcium intake was increased to 30 mg/kg/day, the mean urinary calcium excretion was 10.4% [1].
We agree with the authors of the letter that balance studies are very time and energy consuming and difficult to perform. We do not deny that double tracer methods are more precise and yield higher values for fractional calcium absorption. Unfortunately in Germany (as in some other countries), studies using radioactive isotopes are no longer allowed. By the way, it is of note that an association has been reported between the dietary calcium load and fractional calcium absorption when isotope methods have been combined with quantitative determination of calcium in diet, faeces and urine [3]. One has to be aware that such acute measurements of fractional calcium absorption rate are influenced not only by age, growth and sex but also by intestinal passage time, solubility of the calcium compound, acidity in the gut, compounds inhibiting calcium absorption such as oxalate or phytate, composition of the diet, action of parathyroid hormone probably via vitamin D metabolites, various diseases like hypothyroidism or hyperthyroidism, intestinal disease, etc. In this context, it is correct that our measurements of PTH do not exclude such small changes of iPTH levels shortly after food intake as reported by Isakowa few weeks ago [4]. This was, however, not the primary aim of the study and does not change our final results.
Conflict of interest statement. None declared.
1 Abtlg Nephrologie und Heimdialyse, Universitaetsklinik Heidelberg 2 Internal Medicine VI 3 Internal Medicine Clinical Pharmacology and Pharmacoepidemiology 4 Clinical Pharmacology and Pharmacoepidemiology 5 Institute for Medical Biometry and Informatics 6 Internal Medicine VI Clinical Pharmacology and Pharmacoepidemiology University of Heidelberg 7 Clinical Pharmacology and Pharmacoepidemiology University Hospital, Heidelberg Germany
References
- Knapp EL. Factors influencing the urinary excretion of calcium: I. Normal persons. J Clin Invest (1947) 26:182–202.[CrossRef][Web of Science][Medline]
- Birge SJ, Peck WA, Berman M, et al. Study of calcium absorption in man: a kinetic analysis and physiologic model. J Clin Invest (1969) 48:1705–1713.[Web of Science][Medline]
- Heaney RP, Saville PD, Recker RR. Calcium absorption as a function of calcium intake. J Lab Clin Med (1975) 85:881–890.[Web of Science][Medline]
- Isakova T, Gutierrez O, Shah A, et al. Postprandial mineral metabolism and secondary hyperparathyroidism in early CKD. J Am Soc Nephrol (2008) 19:615–623.
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