Molecular and clinical response to angiotensin II receptor antagonist in kidney transplant patients with chronic allograft nephropathy.
Chronic allograft nephropathy (CAN) represents an important cause of graft loss after kidney transplantation. TGF-beta1 is a key factor in fibrogenesis, and the angiotensin II receptor antagonist losartan may decrease the intra-graft synthesis of TGF-beta1. The aim of this study was to determine the clinical and molecular effect of losartan in kidney transplant patients (KTPs) with CAN. We studied nine KTPs, after the first year of transplantation, with proteinuria (more than 500 mg/24 h), stable renal function, and histological signs of CAN. Immunosuppression was cyclosporine, azathioprine, and corticoids. Kidney biopsy was performed in all patients at the beginning of the study and 12 weeks after treatment with 50 mg/day of losartan. Quantitation of intra-graft expression of TGF-beta1 was performed in all biopsies, by real-time PCR. After losartan treatment there were no differences in patients' BP and blood creatinine level. The proteinuria significantly dropped to 414.2+/-377 mg/24 h, P=0.001. Intra-graft expression of TGF-beta1 was decreased after treatment. In conclusion, losartan significantly decreases the intra-graft expression of TGF-beta1 and proteinuria in KTPs with CAN.
Mas
Valeria R
VR
Department of Pathology and Surgery, Virginia Commonwealth University, MCV Campus, West Hospital, Ninth Floor, South Wing, P.O Box 980057, 23298-0057, Richmond, VA, USA. vrmas@hsc.vcu.edu
Alvarellos
Teresita
T
Maluf
Daniel G
DG
Ferreira-Gonzalez
Andrea
A
Oliveros
Liliana
L
Maldonado
Rafael A
RA
de Boccardo
Graciela
G
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000652:urine; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000652:urine; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
D047228:Angiotensin II Type 1 Receptor Blockers; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019808:Losartan