Changes in renal phosphate reabsorption in the aged rat.
Depletion of inorganic phosphate (Pi) reserves occurs frequently in aged animals and can result in diminished bone mineralization and osteoporosis. This altered Pi balance results from a reduction in intestinal Pi absorption and an elevation in renal Pi excretion. Since the kidney plays a central role in maintaining Pi homeostasis, we tested whether the increased phosphaturia seen with aging is a consequence of changes in the intrinsic tubular capacity to reabsorb Pi (TmPi). Male Wistar rats (12-, 18-, and 24-months-old) were acutely thyroparathyroidectomized (TPTX) and prepared for renal clearance studies in the presence and absence of fixed levels of parathyroid hormone (synthetic PTH-(1-34), 1 U/kg/min). The maximum capacity for Pi transport (TmPi) was assessed by infusion of Pi at progressively higher rates (0-6 micromol/min) to increase the filtered load of Pi and facilitate the determination of the TmPi. TmPi declined significantly with age (3.51 +/- 0.12 vs 3.04 +/- 0.19 vs 2.30 +/- 0.18 micromol/ml, for 12-, 18-, and 24-month-old rats, respectively, P < 0.05) in TPTX rats. Administration of PTH markedly reduced the TmPi in all age groups. Although the TmPi attained was similar among the age groups (1.15 +/- 0.13 vs 1.15 +/- 0.06 vs 1.03 +/- 0.09 micromol/ml, for 12-, 18-, and 24-month-old rats, respectively), the magnitude of the reduction in the presence of PTH declined from 67% in 12-month-old rats to 62% and 55% in 18- and 24-month-old rats, respectively. These results demonstrate that aging is associated with a PTH-independent decrease in the intrinsic capacity of the kidney to reabsorb phosphate. Further, the kidney of the aged rat can respond to a pharmacological dose of PTH with appropriate reductions in the TmPi although the magnitude of the response declines with age.
Mulroney
S E
SE
Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, DC 20007, USA.
Woda
C
C
Haramati
A
A
D000042:Absorption; D000375:Aging / Q000502:physiology*; D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000097:blood; D016105:Parathyroidectomy; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013965:Thyroidectomy
D010281:Parathyroid Hormone; D010710:Phosphates