Hyperhomocysteinemia is associated with atherosclerotic occlusive arterial accidents in predialysis chronic renal failure patients.

Hyperhomocysteinemia has been shown to constitute an independent risk factor for premature occlusive arterial disease. Moderate hyperhomocysteinemia is present in chronic uremic patients, who often develop premature atherosclerosis, but no direct evidence of an association between the occurrence of atherosclerotic cardiovascular accidents (CVAs) and hyperhomocysteinemia has yet been reported in such patients. We serially determined total plasma homocysteine (Hcy) levels in a cohort of 93 consecutive chronic renal failure, undialyzed patients (57 males, 36 females) with creatinine clearance (Ccr) < 50 ml/min.1.73 m2 and age > or = 50 years at start of follow-up, together with serial assessment of Ccr and blood lipid parameters. From January 1989 to December 1995, 24 patients (group 1) experienced myocardial infarction (18 cases, 13 males) or cerebral infarction (6 cases, 3 males) while the remaining 69 (group 2) remained free of CVAs. Patients in groups 1 and 2 did not differ with respect to age (66 +/- 1.8 vs. 65 +/- 1.1 years, mean +/- Se) or serum creatinine (227 +/- 24 vs. 251 +/- 36 mumol/l) at onset of a CVA (group 1) or at the end of follow-up (group 2). The mean Hcy level was significantly higher in group 1 (20.7 +/- 1.6 vs. 12.8 +/- 0.5 mumol/l, p < 0.0001), as was the proportion of patients with Hcy in excess of 14 mumol/l, the upper limit in healthy controls (83 vs. 30%, p < 0.0001). Logistic regression analysis identified Hcy as an independent risk factor for CVA, with an odds ratio of 11.4 (95% confidence interval 3.5-37.7), which remained significant after adjustment on other variables. We conclude that an elevated Hcy level is associated with a risk of occlusive arterial accidents in patients with chronic renal failure and that hyperhomocysteinemia contributes to the accelerated atherosclerosis complicating chronic uremia.

Specificity and sensitivity of gp210 autoantibodies detected using an enzyme-linked immunosorbent assay and a synthetic polypeptide in the diagnosis of primary biliary cirrhosis.

Between 10% and 42% of patients with primary biliary cirrhosis (PBC) have been reported to have autoantibodies directed against a restricted epitope of gp210, a glycoprotein of the nuclear pore membrane. The prevalence and specificity of these antibodies was studied in a French series of 285 patients with PBC and 497 control individuals affected with other liver or autoimmune diseases. Sera were analyzed by an enzyme-linked immunosorbent assay (ELISA) that used a synthetic polypeptide containing the predominant autoepitope of gp210, in parallel to immunoblotting of gp210 protein and immunofluorescence microscopy. Autoantibodies to the gp210 epitope detected by ELISA were 25.5% sensitive and 99.5% specific for the diagnosis of PBC. These results were in agreement with a 99.4% specificity with immunoblotting analysis and a 96.6% specificity with immunofluorescence. In a subset of PBC patients without detectable antimitochondrial autoantibodies (AMA), gp210 autoantibodies were found in 7 of 15 patients (47%). Therefore, gp210 autoantibodies are highly specific for PBC and may be of particular utility in assessing patients without AMA or with other atypical presentations.