Early RAS activation and Coll III upregulation in allograft protocol renal biopsies.
D. Del Prete, R. Graziotto, F.Anglani, M. Ceol, 1ML. Valente, N. Baldan, F. Marchini, L. Bonfante, P. Rigotti, A. D’Angelo, G. Gambaro.
Department of Medical and Surgical Sciences, 1Institute of Anatomical Pathology, University of Padua, Italy
In kidney transplants the Renin-Angiotensin System (RAS) might be involved in systemic and local modifications that could induce fibrosis and chronic allograft nephropathy (CAN) . Aim: to evaluate in serial allograft biopsies the gene expression of TGF beta1, Coll III and RAS. mRNA levels of Angiotensinogen (AG), renin (R), Angiotensin Converting Enzyme (ACE), type 1 (AT1) and type 2 (AT2) angiotensin II receptors, TGF beta 1 and Coll III were analyzed by Real-Time RT/PCR. We have collected 43 donor biopsies before reperfusion (T0), 18 biopsies for diagnostic purpose (Td), and 25 protocol biopsies performed two months after transplantation in patients with normal renal function (Tp). Histological analysis was performed according to Banff '97 criteria. Patients received FK, or CyA or RAD. Results:1) in T0 AG mRNA level was higher than in Td (p< 0.05); 2) in T0 there was a direct correlation between ACE and AT1R (r=0,66 p=2,26E-06), ACE and AT2R (r=0,44 p=0,031) and between AT1R and Coll III (r=0,33 p=0,028); 3) in Tp there was a direct correlation between AG and ACE (r=0,72 p=7,65E-05), ACE and AT1R (r=0,39 p=0,05), ACE and AT2R (r=0,52 p=0,008), AT1R and AT2R (r=0,40 p=0,04) and between R and Coll III (r=0,76 p=1,45E-05); 4) in Td there was a direct correlation between AT1R and AT2R (r=0,48 p=0,04); 5) no difference in mRNA levels between patients with acute and no rejection was observed; 6) in 17 patients with sequential T0 and Tp, a higher level of AT1R and Coll III transcripts was found in Tp ( p<0,03 and p<0,02 respectively); 7)the Coll III and TGF beta 1 mRNA levels were not influenced by therapy. Conclusions: activation of RAS in Tp, the relationship between RAS and fibrogenic cascade, and the increased Coll III expression demonstrate the very early activation of processes leading to CAN.