Putative atherogenic factors in patients with chronic renal failure.

HIS review analyzes several factors which may initiate and sustain atherosclerosis in patients with chronic renal failure. These factors are examined within the framework of the “injury” theory of atherogenesis, which postulates that repeated cycles of endothelial cell injury, platelet deposition, and smooth muscle cell proliferation lead to the formation of typical atherosclerotic plaques. Thus, in the patient with chronic renal failure, endothelial cell damage may be due to hypertension, immunologic injury, or cigarette smoking. Platelet adherence to the damaged vessel wall may be facilitated by the increased levels of the factor VIII/van Willebrand factor found in these patients. Platelets activated during hemodialysis can release growth factors which stimulate vascular smooth muscle cell proliferation. Discrete areas of proliferating smooth muscle cells may preferentially incorporate cholesterol, which then accumulates in the tissues because the transfer of tissue cholesterol to plasma is impaired as a result of reduced or abnormal plasma high density lipoprotein. Ultimately, intimal thickening may occlude the vessel lumen, producing end-organ damage. As the treatment of chronic renal failure enters upon another decade of continued progress and the life span of affected patients lengthens, atherosclerosis and its complications are emerging as significant problems in these patients. In 1974, Lindner et al’ reported a mortality rate of 56 percent in a group of 39 patients with chronic renal failure treated by maintenance hemodialysis. These patients had a mean age of 37 years and were initially free of vascular or other systemic disease. Careful follow-up over a 13-year period disclosed that 14 (16 percent) of the deaths were due to complications of atherosclerosis; coronary heart disease was confirmed by necropsy in most cases. The mortality rates for this group were five times those seen in age matched subjects with hypertension, and were similar to those noted in familial hypercholesterolemia.’ The data suggest that atherosclerosis develops often and progresses with great rapidity in these individuals. Studies of larger numbers of patients have confirmed the high rate of complications due to cardiovascular disease.3*4 There is disagreement, however, as to whether this “accelerated atherosclerosis” is due to dialysis per se or is explainable by the high prevalence of major risk factors in these patients. 5-g Nicholls et al” presented evidence that the disease is already established in these patients when they come to dialysis. They observed that the morbidity and mortality due to atherosclerosis was most prominent in newly recognized patients with chronic renal failure, and that the incidence of new atheromatous disease did not increase during dialysis. Nevertheless, 9 of their 32 patients who died and were autopsied had severe occlusive arterial disease, and the average age of these patients was only 47 years. In another series,’ the de novo incidence of ischemic heart disease in 382 patients on chronic hemodialysis was 10.2%. In this review, we will examine several factors