IMMUNOHISTOCHEMICAL STUDY OF HUMAN ADVANCED GLYCATION END-PRODUCTS (AGE) AND GROWTH-FACTORS IN CARDIAC TISSUES OF PATIENTS ON MAINTENANCE DIALYSIS AND WITH KIDNEY-TRANSPLANTATION

Cardiovascular disease is one of the most common complications of dial ysis and renal transplant patients, and high levels of AGE are present in end-stage renal failure, To address the potential involvement of A GE and growth factors in the pathophysiology of cardiovascular complic ations, we performed immunostaining using cardiac tissues from autopsy cases of patients on maintenance dialysis (10 cases), long-term survi ving renal transplant patients with functioning grafts (8 cases), cont rol subjects with normal renal function (7 cases) and non diabetic sub jects with mild renal insufficiency (8 cases). We used two types of AG E-antibodies, 6D12 [monoclonal anti-AGE antibody, recognizing N-epsilo n-(carboxymethyl) lysine(CML)-modified AGE] (oxidative AGE) and non-CM L-PA [polyclonal, not recognizing CML], and antibodies against PDGFs, PDGF receptors and TGF beta, Positive 6D12 staining was observed in th e coronary arterial walls and in macrophages. The accumulation of 6D12 -reactive AGE in the coronary arterial walls of maintenance dialysis p atients was significantly greater than that of control subjects (p <0. 05). Renal transplantation significantly reduced this accumulation (p <0.05). On the other hand non-CML-PA mainly detected AGE in intracardi ac arterioles and neural tissues. There was little difference in the a ccumulation of non-CML-AGE among the four groups. PDGFs and PDGF recep tors were mainly detected in vascular endothelial cells and infiltrati ng: cells of cardiac tissues of renal transplant patients, but not of maintenance dialysis patients, TGF beta was not detected in cardiovasc ular tissue of transplant patients. Our results indicated that the acc umulation of oxidative AGE (CML-AGE) in the cardiac vascular tissue is one of the factors for cardiovascular complications of maintenance di alysis patients, and also that renal transplantation has a reducing ef fect on CML-AGE accumulation. PDGFs may be involved in the cardiovascu lar complications after renal transplantation.