PMID- 14633150
OWN - NLM
STAT- MEDLINE
DCOM- 20040716
LR  - 20141120
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 64
IP  - 6
DP  - 2003 Dec
TI  - ACE inhibition limits chronic injury of kidney transplant even with treatment 
      started when lesions are established.
PG  - 2253-61
AB  - BACKGROUND: Inhibition of the renin-angiotensin system (RAS) prevents development 
      of chronic allograft dysfunction in experimental animals. Whether this 
      therapeutic approach is effective even if started when signs of allograft 
      nephropathy are already manifested has not been investigated. METHODS: To address 
      this issue, we studied the effect of a late treatment with the 
      angiotensin-convertine enzyme (ACE) inhibitor trandolapril in the Fisher 344 to 
      Lewis rat kidney transplant model. Seven months after transplant a renal biopsy 
      was done for graft histology examination. Thereafter rats received either no 
      treatment (allograft-none) or trandolapril until sacrifice at month 13. RESULTS: 
      All animals were alive at the end of the study with the exception of a rat in the 
      untreated group that died of renal insufficiency at day 292. Despite the fact 
      that the grafts had already signs of structural injury and function impairment at 
      the time treatment was stated, trandolapril completely restored renal function to 
      baseline pretransplant values. Trandolapril also halted the progression of 
      glomerular damage and suppressed intragraft T-lymphocyte infiltration and reduced 
      the expression of the chemokine monocyte chemoattractant protein-1 (MCP-1). 
      However, trandolapril had no direct effect on T cell function, since in vivo 
      treatment did not modify recipient T-cell alloreactivity against donor antigens. 
      CONCLUSION: These findings provide the basis for a novel treatment intervention 
      with RAS blockade that, together with pharmacologic inhibition of the immune 
      response, could interrupt progression of chronic allograft dysfunction and 
      injury.
FAU - Noris, Marina
AU  - Noris M
AD  - Department of Medicine and Transplantation, Ospedali Riuniti Bergamo-Mario Negri 
      Institute for Pharmacological Research, Bergamo, Italy. noris@marionegri.it
FAU - Mister, Marilena
AU  - Mister M
FAU - Pezzotta, Anna
AU  - Pezzotta A
FAU - Azzollini, Nadia
AU  - Azzollini N
FAU - Cassis, Paola
AU  - Cassis P
FAU - Benigni, Ariela
AU  - Benigni A
FAU - Gagliardini, Elena
AU  - Gagliardini E
FAU - Perico, Norberto
AU  - Perico N
FAU - Remuzzi, Giuseppe
AU  - Remuzzi G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Indoles)
RN  - 1T0N3G9CRC (trandolapril)
SB  - IM
MH  - Angiotensin-Converting Enzyme Inhibitors/*pharmacology
MH  - Animals
MH  - Antibody Formation/drug effects
MH  - Chemokine CCL2/antagonists & inhibitors
MH  - Indoles/*pharmacology
MH  - Kidney/pathology/*physiopathology
MH  - Kidney Diseases/*drug therapy/etiology/pathology/*physiopathology
MH  - Kidney Transplantation/*adverse effects
MH  - Lymphocyte Culture Test, Mixed
MH  - Rats
MH  - Rats, Inbred F344
MH  - Rats, Inbred Lew
MH  - Recovery of Function
MH  - T-Lymphocytes/immunology
EDAT- 2003/11/25 05:00
MHDA- 2004/07/17 05:00
CRDT- 2003/11/25 05:00
PHST- 2003/11/25 05:00 [pubmed]
PHST- 2004/07/17 05:00 [medline]
PHST- 2003/11/25 05:00 [entrez]
AID - S0085-2538(15)49596-1 [pii]
AID - 10.1046/j.1523-1755.2003.00318.x [doi]
PST - ppublish
SO  - Kidney Int. 2003 Dec;64(6):2253-61. doi: 10.1046/j.1523-1755.2003.00318.x.