Anémie de l'insuffisance rénale chronique

Atherosclerotic cardiovascular disease and malnutrition are widely recognized as leading causes of the increased morbidity and mortality observed in uremic patients. C-reactive protein (CRP), an acute-phase protein, is a predictor of cardiovascular mortality in nonrenal patient populations. In chronic renal failure (CRF), the prevalence of an acute-phase response has been associated with an increased mortality. One hundred and nine predialysis patients (age 52 +/- 1 years) with terminal CRF (glomerular filtration rate 7 +/- 1 ml/min) were studied. By using noninvasive B-mode ultrasonography, the cross-sectional carotid intima-media area was calculated, and the presence or absence of carotid plaques was determined. Nutritional status was assessed by subjective global assessment (SGA), dual-energy x-ray absorptiometry (DXA), serum albumin, serum creatinine, serum urea, and 24-hour urine urea excretion. The presence of an inflammatory reaction was assessed by CRP, fibrinogen (N = 46), and tumor necrosis factor-alpha (TNF-alpha; N = 87). Lipid parameters, including Lp(a) and apo(a)-isoforms, as well as markers of oxidative stress (autoantibodies against oxidized low-density lipoprotein and vitamin E), were also determined. Compared with healthy controls, CRF patients had an increased mean carotid intima-media area (18.3 +/- 0.6 vs. 13.2 +/- 0.7 mm2, P or = 10 mg/liter). Malnourished patients had higher CRP levels (23 +/- 3 vs. 13 +/- 2 mg/liter, P < 0.01), elevated calculated intima-media area (20.2 +/- 0.8 vs. 16.9 +/- 0.7 mm2, P < 0.01) and a higher prevalence of carotid plaques (90 vs. 60%, P < 0.0001) compared with well-nourished patients. During stepwise multivariate analysis adjusting for age and gender, vitamin E (P < 0.05) and CRP (P < 0.05) remained associated with an increased intima-media area. The presence of carotid plaques was significantly associated with age (P < 0.001), log oxidized low-density lipoprotein (oxLDL; P < 0.01), and small apo(a) isoform size (P < 0.05) in a multivariate logistic regression model. These results indicate that the rapidly developing atherosclerosis in advanced CRF appears to be caused by a synergism of different mechanisms, such as malnutrition, inflammation, oxidative stress, and genetic components. Apart from classic risk factors, low vitamin E levels and elevated CRP levels are associated with an increased intima-media area, whereas small molecular weight apo(a) isoforms and increased levels of oxLDL are associated with the presence of carotid plaques.

The human erythropoietin gene has been isolated from a genomic phage library by using mixed 20-mer and 17-mer oligonucleotide probes. The entire coding region of the gene is contained in a 5.4-kilobase HindIII-BamHI fragment. The gene contains four intervening sequences (1562 base pairs) and five exons (582 base pairs). It encodes a 27-amino acid signal peptide and a 166-amino acid mature protein with a calculated Mr of 18,399. The erythropoietin gene, when introduced into Chinese hamster ovary cells, produces erythropoietin that is biologically active in vitro and in vivo.

Anemia is common in patients with chronic renal insufficiency and secondary hyperparathyroidism. Erythropoietin therapy is effective, but the dose required varies greatly. One possible determinant of the efficacy of erythropoietin therapy is the extent of marrow fibrosis caused by hyperparathyroidism. We examined the relation between the erythropoietic response to erythropoietin and hyperparathyroidism in a cross-sectional study of 18 patients undergoing hemodialysis who had received erythropoietin therapy for one to three years. In 7 patients (the poor-response group), the dose of intravenous erythropoietin needed to maintain a mean (+/- SD) target hematocrit of 35 +/- 3 percent was > 100 units per kilogram of body weight three times a week, and in 11 patients (the good-response group) it was < or = 100 units per kilogram. In all patients, indexes of the adequacy of dialysis and the extent of hyperparathyroidism and aluminum toxicity were determined monthly, and bone histomorphometry was performed. The mean (+/- SD) dose of erythropoietin required to maintain the target hematocrit was 174 +/- 33 units per kilogram three times a week in the poor-response group and 56 +/- 18 units per kilogram in the good-response group. The mean ages, duration and adequacy of dialysis, increment in hematocrit, iron requirements, and serum concentrations of calcium, phosphate, and aluminum were similar in the two groups. The percentages of osteoid volume and surface, the osteoid thickness, and the stainable aluminum content of bone were similar in the two groups. In contrast, the mean serum parathyroid hormone concentration, the percentages of osteoclastic and eroded bone surfaces, and the degree of marrow fibrosis were greater in the poor-response group than in the good-response group (P = 0.03, P = 0.04, P = 0.009, and P = 0.009, respectively). In patients with uremia, the dose of erythropoietin needed to achieve an adequate hematocrit response may depend on the severity of secondary hyperparathyroidism and the extent of bone marrow fibrosis.