title: Phosphate homeostasis, 1,25-dihydroxyvitamm D(3), and hyperparathyroidism in early chronic renal failure.
abstract: In early chronic renal failure, low plasma levels of calcitriol (1,25[OH](2)D(3)) do not seem to be merely the consequence of a reduced mass of functional nephrons. Indeed, this alteration can be considered as a compensatory mechanism, as analyzed according to a new concept of inorganic phosphate (P(i)) homeostasis that integrates both 1,25(OH)(2)D(3) production and renal P(i) reabsorption as essential regulating elements. Accordingly, the observed reduction in the renal production of 1,25(OH)(2)D(3) that occurs concomitantly with a decrease in tubular P(i) reabsorptive capacity (TmP(i)/GFR) may well represent a secondary adaptive response to a primary alteration in P(i) homeostasis. This crucial alteration in P(i) homeostasis would consist of an overload of a putative regulated intracellular P(i) pool, the localization of which remains to be determined. The observed hypophosphatemia, hypocalcemia, and PTH hypersecretion would represent alterations secondary to a low TmP(i)/GFR and to reduced 1,25(OH)(2)D(3) production. According to this pathophysiologic sequence, 1,25(OH)(2)D(3), rather than PTH as proposed in a former theory, would be "traded off" to preserve P(i) homeostasis in early chronic renal failure. Both theories predict that dietary P(i) restriction represents a logical preventive therapy at least until the nature of the primary defect in P(i) homeostasis is understood. However, assuming that low 1,25(OH)(2)D(3) levels in early chronic renal failure represent a compensatory phenomenon, this new theory suggests that calcitriol should be only administered at a later stage of the disease, when the production of 1,25(OH)(2)D(3) becomes inappropriately low to maintain mineral homeostasis.
authors.affiliation: Division of Clinical Pathophysiology, Department of Medicine, University Hospital of Geneva, Geneva 14, Switzerland.
authors.forename: J P
authors.initials: JP
authors.lastname: Bonjour
authors.forename: J
authors.initials: J
authors.lastname: Caverzasio
authors.forename: R
authors.initials: R
authors.lastname: Rizzoli