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Comment on Calcium-Regulated Renal Calcium Handling in Healthy Men

University of Arkansas for Medical Sciences Little Rock, Arkansas 72205

Dr. Fuleihan and her colleagues (1) found that the relationship between urinary calcium excretion and plasma calcium during a PTH clamp was broadly similar to that previously observed without the clamp. This is an important new finding, indicating that acute changes in PTH secretion have little effect on tubular reabsorption of calcium and that unclamped calcium infusions can give useful information.

However, the authors’ fascination with sigmoid curves has misled them about basic renal physiology (2). When the amount of ion per unit of glomerular filtrate (GFR) is plotted against plasma level then, absent a change in GFR, the amount filtered is given by a straight line through the origin of slope unity. For tubular maximum limited substances such as glucose, the amount excreted is given by a line that is curvilinear at the lower end (the splay segment) and parallel to the line of filtration at the upper end. The plasma level dividing these segments is the saturation threshold, so-called because, above that level, the amount reabsorbed (filtered minus excreted) is constant, reflecting saturation of a tubular transport process.

If, as is implied by a sigmoid curve, the amount of calcium excreted reaches a plateau, than absent a change in GFR, the amount reabsorbed will increase without limit as plasma calcium rises, the opposite to what is predicted by the authors’ model in Fig. 7. We suggest three possible explanations for this paradox. First, in Fig. 3, the inference of a sigmoid relationship, rather than a linear relationship above the splay segment, rests on only two points. Second, if creatinine clearance, which was not reported, fell during the infusion, then calcium reabsorption may not have increased. Third, the natriuretic effect of calcium may have induced sufficient sodium deficiency during the infusion to have increased both sodium and calcium reabsorption. We believe the third explanation is the most likely.

Footnotes

Address correspondence to: A.M. Parfitt, M.D., Professor of Medicine, University of Arkansas for Medical Sciences 4301 W. Markham St. Slot 587, Little Rock, Arkansas 72205-7199.

Received October 23, 1998.

References

1. Fuleihan GE, Seifter J, Scott J, Brown EM. 1998 Calcium-regulated renal calcium handling in healthy men: relationship to sodium handling. J Clin Endocrinol Metab. 83:2366–2372.[Abstract/Free Full Text]
2. Parfitt AM, Kleerekoper M. 1980 The divalent ion homeostatic system: Physiology and metabolism of calcium, phosphorus, magnesium and bone. In: Maxwell M, Kleeman CR, eds. Clinical Disorders of Fluid and Electrolyte Metabolism, 3rd ed. New York: McGraw Hill; 269–398.

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