Laboratory Investigation

Kidney International (1982) 21, 471–476; doi:10.1038/ki.1982.48

Parathyroid hormone-independent adaptation of the renal handling of phosphate in response to renal mass reduction

Joseph Caverzasio1, Hans-Jakob Gloor1, Herbert Fleisch1 and Jean-Philippe Bonjour1

1Department of Pathophysiology, University of Berne, Murtenstrasse 35, 3010 Berne, Switzerland

Correspondence: Dr J-P Bonjour, Department of Pathophysiology, University of Berne, Murtenstrasse 35, 3010 Berne, Switzerland

Received 9 October 1980; Revised 9 September 1981.

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Abstract

Parathyroid hormone-independent adaptation of the renal handling of phosphate in response to renal mass reduction. In man as well as in experimental animals progressive renal failure is associated with a decrease in the fractional reabsorption (FR) of inorganic phosphate (Pi). This response has been considered as an adaptation phenomenon and generally attributed to an increase in parathyroid hormone (PTH) secretion. One report indicates that in chronic thyroparathyroidectomized (TPTX) dogs treated with large doses of vitamin D progressive renal failure can also be associated with a fall in FRPi. However, in this latter study the concomittant administration of vitamin D could have accounted for the observed decrease in FRPi. In our study we investigated whether or not chronic reduction in renal mass leads to a similar decrease in maximal net tubular Pi reabsorption per volume of glomerular filtrate (maximal TRPi/ml GF) in the presence and absence of PTH and without pharmacological supplementation in vitamin D. Male rats were either TPTX or sham-operated (intact). One and two weeks later the animals of both groups were either subtotally nephrectomized (NX) in two stages or sham-operated (control). Four weeks after the second renal operation, the glomerular filtration rate (GFR) and the reabsorption of Pi were determined by clearance methodology under acute sodium chloride and Pi infusion, that is, at endogenous and increased plasma Pi concentrations ([Pi]P1.). Thus maximal TRPi/ml GFR could be determined. In rats with intact parathyroid glands GFR was 1.56 plusminus 0.10 (mean plusminus SEM) and 0.54 plusminus 0.10 ml/min in control and NX respectively, whereas maximal TRPi/ml GF was 2.24 plusminus 0.07 in control and 1.57 plusminus 0.18 micromol/ml (P < 0.005) in NX. In TPTX rats GFR was 1.66 plusminus 0.27 and 0.62 plusminus 0.06 ml/min in control and NX respectively, whereas maximal TRPi/ml GF was 3.80 plusminus 0.20 in control and 2.95 plusminus 0.13 micromol/ml (P < 0.005) in NX. The marked decrease in maximal TRPi/ml GF observed in TPTX after subtotal NX could not be ascribed to any consistent change in plasma calcium. Our study provides conclusive evidence that the decrease in maximal TRPi/ml GF in response to renal mass reduction can occur to the same degree in the presence or absence of PTH.

Adaptation indépendente de l'hormone parathyroïdienne du comportement rénal du phosphate en réponse à la réduction de la masse rénale. Chez l'homme de même que chez l'animal d'expérience l'insuffisance rénale progressive est associée à une diminution de la réabsorption fractionnelle (FR) du phosphate inorganique (Pi). Cette réponse a été considérée comme un phénomène d'adaptation et est généralement attribuée à une augmentation de la sécrétion d'hormone parathyroïdienne (PTH). Un travail indique que chez le chien en état de thyroparathyroïdectomie chronique (TPTX) traité par de larges doses de vitamine D, l'insuffisance rénale progressive peut aussi être associée à une diminution de FRPi. Cependant, dans ce dernier travail, l'administration concomitante de vitamine D peut avoir eu pour conséquence la diminution observée de FRPi. Dans le présent travail nous avons recherché si en présence ou en l'absence de PTH et sans supplémentation pharmacologique en vitamine D la réduction chronique de la masse rénale détermine une diminution semblable de la réabsorption maximale nette tubulaire de phosphate par unité de filtrat glomérulaire (max.TRPi/ml GF). Des rats maies ont été soit thyroparathyroïdectomisés soit soumis à un simulacre d'opération. Une puis deux semaines plus tard, les animaux des deux groupes ont été soit soumis à une néphrectomie subtotale (NX) en deux étapes, soit soumis à un simulacre d'intervention (contrôles). Quatre semaines après la deuxième intervention rénale, le débit de filtration glomérulaire (GFR) et la réabsorption de Pi ont été déterminés par la méthode des clearances sous perfusion aiguë de chlorure de sodium et de Pi, c'est-à-dire aux concentrations plasmatiques de Pi endogène et augmentées ([Pi]P1.). Ainsi on a pu déterminer max.TRPi/ml GF. Chez les rats dont les glandes parathyroïdes sont intactes, GFR était de 1,56 plusminus 0,10 (moyenne plusminus SEM) et 0,54 plusminus 0,10 ml/mn chez les contrôles et les NX respectivement alors que max.TRPi/ml GF était de 2,24 plusminus 0,07 chez les contrôles et de 1,57 plusminus 0,18 micromol/ml (P < 0,005) chez NX. Chez les rats TPTX GFR était de 1,66 plusminus 0,27 et 0,62 plusminus 0,06 ml/mn chez les contrôles et NX respectivement, alors que max.TRPi/ml GF était 3,80 plusminus 0,20 chez les contrôles et 2,95 plusminus 0,13 micromol/ml (P < 0,005) chez NX. La diminution importante de max.TRPi/ml GF observée chez TPTX après NX ne peut pas être attribuée à une modification importante du calcium plasmatique. En conclusion, notre travail apporte des preuves importantes de ce que la diminution de max.TRPi/ml GF en réponse à la réduction de la masse rénale peut survenir de la même façon en présence ou en l'absence de PTH.

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