Arterial disease in chronic renal failure--an experimental study in the rabbit

Epidemiological studies have indicated an increased incidence of cardiovascular events among patients with chronic renal failure. An acceleration of the atherosclerotic disease process in uremia has been proposed and a few studies have even suggested the existence of a specific pathological entity, uremic arterial disease, characterized by medial degeneration and calcification rather than by accumulation of cholesterol. As an experimental model of arterial disease in uremia, rabbits with chronic renal failure (CRF rabbits) induced by renal cauterization and contralateral nephrectomy were studied. Serum levels of creatinine were increased 2-3 times and the glomerular filtration rate reduced to 1/3-1/4 of the normal value. The CRF rabbits had lower body weights, hematocrit values and serum albumin concentrations than corresponding control animals. The arterial blood pressure was normal in all rabbits studied. The serum calcium concentration was significantly increased as was the serum phosphate. The gastrointestinal absorption of calcium of the CRF rabbits was decreased in contrast to an increased absorption of phosphate. The possible regulatory mechanisms responsible for the peculiar aspects of the mineral metabolism in normal and CRF rabbits are discussed but have not been clarified in detail. As regards the serum lipids, increased triglyceride levels were the most constant finding whereas serum cholesterol was only increased in rabbits with rather severe renal insufficiency. The earliest morphological changes were observed in the media of the aorta following seven weeks of CRF. Increased amounts of alcianophilic intercellular substance and a wavy pattern of the elastic membranes were seen. After three months of CRF, medial focal proliferations of smooth muscle cells accompanied by degenerative changes and calcifications were seen, frequently associated with increased thickness of the overlying intima due to accumulation of smooth muscle cells. After eight months of CRF the aorta was often transformed into a stiff, calcified tube and similar changes were observed in all major systemic arteries, including the coronary arteries. No evidence of lipid accumulation was found. Chemical analysis confirmed that accumulation of calcium, phosphate and magnesium was a prominent feature of the arterial changes, whereas the aortic content of cholesterol was not increased. Restriction of dietary calcium and phosphate decreased the mineral accumulation as well as the severity of the morphological changes. Increased amounts of calcium and phosphate in the diet increased the mineral accumulation of the aorta.(ABSTRACT TRUNCATED AT 400 WORDS)