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Angiotensin type 1 and type 2 receptor blockade in chronic allograft nephropathy

J Lutz1, K Risch, S Liu

  • 1Department of Nephrology, Klinikum rechts der Isar, Technische Universität München, München, Germany.

Kidney International
|July 20, 2006
PubMed

Insights

Long-term blockade of Angiotensin-II (Ang-II) type 1 (AT(1)) receptors effectively delays chronic allograft nephropathy (CAN) progression in rats. This treatment reduces apoptosis and p53 mRNA levels, suggesting a key role for AT(1) blockade in managing CAN.

Area of Science:

  • Nephrology
  • Immunology
  • Pharmacology

Background:

  • Chronic allograft nephropathy (CAN) is a major cause of kidney transplant failure.
  • Angiotensin-II (Ang-II) type 1 (AT(1)) receptor blockers show potential in delaying CAN progression.
  • The optimal timing for AT(1) receptor blockade and the role of Ang-II type 2 (AT(2)) receptors in CAN remain unclear.

Purpose of the Study:

  • To determine the optimal initiation time for AT(1) receptor blockade to delay CAN.
  • To investigate the role of AT(2) receptors during AT(1) receptor blockade in CAN.
  • To examine the effects of angiotensin receptor blockade on apoptosis and p53 expression in a rat model of CAN.

Main Methods:

  • A rat kidney transplantation model (Fisher F344 into Lewis rats) was utilized.
  • Animals received AT(1) (candesartan) and/or AT(2) (PD123319) receptor antagonists, a calcium channel blocker, or vehicle.
  • Treatment groups included long-term (pre-transplant to 24 weeks), late (12-24 weeks), and early (pre-transplant to 5 days) initiation periods.

Main Results:

  • Long-term AT(1) receptor blockade significantly reduced proteinuria, CAN grade, and apoptotic cell counts.
  • Combined AT(1)/AT(2) blockade showed similar efficacy to AT(1) blockade alone.
  • Apoptotic cells and p53 mRNA levels were significantly lower in long-term AT(1) blocker-treated rats.

Conclusions:

  • Long-term AT(1) receptor blockade is effective in delaying the progression of chronic allograft nephropathy.
  • Reduced apoptosis, potentially mediated by decreased p53 expression, may underlie the beneficial effects of AT(1) blockade.
  • The AT(2) receptor does not appear to play a significant role in the development or treatment of CAN in this model.

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