Cellular mechanisms of the age-related decrease in renal phosphate reabsorption

Kidney Int. 1996 Sep;50(3):855-63. doi: 10.1038/ki.1996.385.

Abstract

The aging process in humans and in the rat is associated with an impairment in renal tubular reabsorption of Pi and renal tubular adaptation to a low Pi diet. The purposes of the present study were to determine whether changes in the abundance of type II Na-Pi contransporter (NaPi-2) protein and/or mRNA play a role in the age-related decrease in Na-Pi cotransport activity, and to further determine the cellular mechanisms of impaired adaptation to a low Pi diet. In studies performed in 3- to 4-month-old young adult rats and 32-to 16-month-old aged rats we found that there was an age-related twofold decrease in proximal tubular apical brush border membrane (BBM) Na-Pi cotransport activity, which was associated with similar decreases in BBM NaPi-2 protein abundance and renal cortical NaPi-2 mRNA level. Immunohisto-chemistry showed lower NaPi-2 protein expression in the BBM of proximal tubules of superficial, midcortical, and juxtamedullary nephrons. We also found that in response to chronic (7 days) and/or acute (4 hr) feeding of a low Pi diet there were similar adaptive increases in BBM Na-Pi cotransport activity and BBM NaPi-2 protein abundance in both young and aged rats. However, BBM Na-Pi cotransport activity and BBM NaPi-2 protein abundance were still significantly lower in aged rats, in spite of a significantly lower serum Pi concentration in aged rats. The results indicate that impaired expression of the type II renal Na-Pi cotransporter protein at the level of the apical BBM plays an important role in the age-related impairment in renal tubular reabsorption of Pi and renal tubular adaptation to a low Pi diet.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Physiological / physiology
  • Aging / physiology*
  • Animals
  • Blotting, Northern
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Immunohistochemistry
  • Kidney / metabolism*
  • Kidney / ultrastructure
  • Kidney Tubules, Proximal / metabolism
  • Male
  • Phosphates / metabolism*
  • Phosphorus, Dietary / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Phosphate Cotransporter Proteins
  • Sodium-Phosphate Cotransporter Proteins, Type II
  • Symporters*

Substances

  • Carrier Proteins
  • Phosphates
  • Phosphorus, Dietary
  • RNA, Messenger
  • Sodium-Phosphate Cotransporter Proteins
  • Sodium-Phosphate Cotransporter Proteins, Type II
  • Symporters