TY - JOUR
T1 - Molecular and clinical response to angiotensin II receptor antagonist in kidney transplant patients with chronic allograft nephropathy
AU - Mas, Valeria R.
AU - Alvarellos, Teresita
AU - Maluf, Daniel G.
AU - Ferreira-Gonzalez, Andrea
AU - Oliveros, Liliana
AU - Maldonado, Rafael A.
AU - De Boccardo, Graciela
PY - 2004/10
Y1 - 2004/10
N2 - Chronic allograft nephropathy (CAN) represents an important cause of graft loss after kidney transplantation. TGF-β1 is a key factor in fibrogenesis, and the angiotensin II receptor antagonist losartan may decrease the intra-graft synthesis of TGF-β1. 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-β1 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-β1 was decreased after treatment. In conclusion, losartan significantly decreases the intra-graft expression of TGF-β1 and proteinuria in KTPs with CAN.
AB - Chronic allograft nephropathy (CAN) represents an important cause of graft loss after kidney transplantation. TGF-β1 is a key factor in fibrogenesis, and the angiotensin II receptor antagonist losartan may decrease the intra-graft synthesis of TGF-β1. 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-β1 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-β1 was decreased after treatment. In conclusion, losartan significantly decreases the intra-graft expression of TGF-β1 and proteinuria in KTPs with CAN.
KW - Angiotensin II
KW - Angiotensin II receptor antagonist
KW - Chronic allograft nephropathy
KW - Kidney transplantation
KW - Losartan
KW - TGF-β1
UR - http://www.scopus.com/inward/record.url?scp=9944224312&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=9944224312&partnerID=8YFLogxK
U2 - 10.1007/s00147-004-0740-5
DO - 10.1007/s00147-004-0740-5
M3 - Article
C2 - 15349718
AN - SCOPUS:9944224312
SN - 0934-0874
VL - 17
SP - 540
EP - 544
JO - Transplant International
JF - Transplant International
IS - 9
ER -