Regulation of the renal sodium-dependent phosphate cotransporter NaPi2 (Npt2) in acute renal failure due to ischemia and reperfusion.
BACKGROUND
Acute renal failure (ARF) is associated with hyperphosphatemia and decreased urinary phosphate excretion. The present study was undertaken to characterize the effects of ARF due to ischemia and reperfusion on renal phosphate transport and on gene and protein expression of type IIa NaPi cotransporter (Npt2) the physiologically most relevant renal sodium-dependent phosphate cotransporter.


METHODS
The following groups of rats with intact parathyroid glands were studied: (1) sham operated (sham); (2) after 1 h ischemia by bilateral renal artery clamping (I), and after 1 h ischemia and reperfusion of 1 h (I + R 1 h); (3) 24 h (I + R 24 h); (4) 48 h (I + R 48 h), and (5) 72 h (I + R 72 h) duration. The effect of ARF on Npt2 mRNA and protein expression was also examined after parathyroidectomy (PTX) of 2 and 4 days' duration.


RESULTS
Ischemia and reperfusion were associated with increases in plasma creatinine, hyperphosphatemia, and with decreased tubular phosphate reabsorption. Npt2 mRNA was significantly downregulated in the cortex, maximal at 24 and 48 h of reperfusion. The degree of Npt2 mRNA downregulation was not affected by PTX of 2-4 days' duration. The abundance of Npt2 protein in proximal tubular apical brush border membrane was markedly decreased after reperfusion. Npt2 protein, however, was more abundant in PTX animals than in those with intact parathyroids and a similar degree of renal insufficiency. The immunohistochemical analysis of proximal tubular apical brush border membrane showed a progressive decrease of Npt2 protein labeling after ischemia and reperfusion, with progressive regeneration after 72 h.


CONCLUSIONS
These results suggest that downregulation of Npt2 protein may contribute to the decreased tubular reabsorption of phosphate in acute ischemic renal failure and hyperphosphatemia.
Rubinger
Dvora
D
Hadassah University Hospital, Jerusalem, Israel. rdvora@hadassah.org.il
Wald
Hanna
H
Gimelreich
Dimitri
D
Halaihel
Nabil
N
Rogers
Thomas
T
Levi
Moshe
M
Popovtzer
Mordecai M
MM
D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D005786:Gene Expression Regulation; D008297:Male; D016105:Parathyroidectomy; D010710:Phosphates / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism*; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D010710:Phosphates; D012333:RNA, Messenger; C493556:Slc34a1 protein, rat; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa