Changes in Renal Phosphate Reabsorption in the Aged Rat

Abstract

Abstract

Depletion of inorganic phosphate (P_i) reserves occurs frequently in aged animals and can result in diminished bone mineralization and osteoporosis. This altered P_i balance results from a reduction in intestinal P_i absorption and an elevation in renal P_i excretion. Since the kidney plays a central role in maintaining P_i homeostasis, we tested whether the increased phosphaturia seen with aging is a consequence of changes in the intrinsic tubular capacity to reabsorb P_i (TmP_i). 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), 1U/kg/min). The maximum capacity for P_i transport (TmP_i) was assessed by infusion of P_i at progressively higher rates (0–6 μmol/min) to increase the filtered load of P_i and facilitate the determination of the TmP_i. TmP_i declined significantly with age (3.51 ± 0.12 vs 3.04 ± 0.19 vs 2.30 ± 0.18 μmol/ml, for 12-, 18-, and 24-month-old rats, respectively, P < 0.05) in TPTX rats. Administration of PTH markedly reduced the TmP, in all age groups. Although the TmP, attained was similar among the age groups (1.15 ± 0.13 vs 1.15 ± 0.06 vs 1.03 ± 0.09 μmol/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 TmP, although the magnitude of the response declines with age.