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 dialysis and renal transplant patients, and high levels of AGE are present in end-stage renal failure. To address the potential involvement of AGE and growth factors in the pathophysiology of cardiovascular complications, we performed immunostaining using cardiac tissues from autopsy cases of patients on maintenance dialysis (10 cases), long-term surviving renal transplant patients with functioning grafts (8 cases), control subjects with normal renal function (7 cases) and non diabetic subjects with mild renal insufficiency (8 cases). We used two types of AGE-antibodies, 6D12 [monoclonal anti-AGE antibody, recognizing N e -(carboxymethyl) lysine(CML)-modified AGE] (oxidative AGE) and non-CML-PA [polyclonal, not recognizing CML], and antibodies against PDGFs, PDGF receptors and TGFβ. Positive 6D12 staining was observed in the coronary arterial walls and in macrophages. The accumulation of 6D12-reactive AGE in the coronary arterial walls of maintenance dialysis patients 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 intracardiac arterioles and neural tissues. There was little difference in the accumulation of non-CML-AGE among the four groups. PDGFs and PDGF receptors were mainly detected in vascular endothelial cells and infiltrating cells of cardiac tissues of renal transplant patients, but not of maintenance dialysis patients. TGFβ was not detected in cardiovascular tissue of transplant patients. Our results indicated that the accumulation of oxidative AGE (CML-AGE) in the cardiac vascular tissue is one of the factors for cardiovascular complications of maintenance dialysis patients, and also that renal transplantation has a reducing effect on CML-AGE accumulation. PDGFs may be involved in the cardiovascular complications after renal transplantation.