Beneficial effect of atorvastatin on erythropoietin responsiveness in maintenance haemodialysis patients

Aim: To evaluate the effect of atorvastatin on erythropoietin responsiveness and whether this effect is mediated by C‐reactive protein (CRP) reduction in prevalent dyslipidemic, haemodialysis patients. Methods: We studied prospectively 33 stable, iron‐repleted haemodialysis patients with low‐density lipoprotein cholesterol (LDL) ≥2.58 mmol/L, who received 20 mg atorvastatin aiming to achieve the target of LDL <2.58 mmol/L, over a period of 9 months. Twenty‐five patients completed the study, 15 men, with mean age 66.1 ± 8.2 years. The duration of haemodialysis was 56.6 ± 63.1 months and 5/25 patients were diabetics. Total serum cholesterol, triglycerides, high‐density lipoprotein cholesterol, LDL, haemoglobin, albumin, intact parathyroid hormone, serum iron, ferritin, total iron binding capacity, CRP and weekly dose of erythropoietin/body weight/haemoglobin were analysed. Results: Twenty of the 25 patients (80%) achieved the goal of LDL <2.58 mmol/L. There was a significant decrease in total cholesterol (5.77 ± 0.88 to 4.16 ± 0.96 mmol/L, P < 0.001) and LDL (3.59 ± 0.77 to 1.94 ± 0.77 mmol/L, P < 0.001). Haemoglobin increased from 121 ± 11 to 126 ± 7 g/L (P < 0.05), while weekly dose of erythropoietin/body weight/haemoglobin decreased significantly from 8.34 ± 3.70 to 7.87 ± 3.11 IU/kg per haemoglobin (P < 0.05). CRP decreased not significantly from 7.0 ± 6.1 to 4.5 ± 2.2 mg/L. Conclusion: Dyslipidemia of haemodialysis patients was treated safely and effectively with atorvastatin, but a fifth of the patients failed to achieve the therapeutic target. Statin therapy resulted in a significant increase of haemoglobin levels and improvement of erythropoietin responsiveness without a significant reduction in CRP levels, suggesting that the beneficial effect of statins on erythropoietin responsiveness may be driven by a mechanism other than CRP reduction.     

IMMUNOHISTOCHEMISTRY IN HISTOID LEPROSY

Background. Histoid leprosy is a rare form of multibacillary leprosy as the result of secondary or even primary resistance to dapsone. The etiopathogenesis has not been clarified up to now. Methods. An immunohistochemical study was carried out for the expression of various markers on epidermal and dermal cell populations using sections of frozen skin specimens from 5 patients with histoid leprosy as compared to specimens from 7 tuberculoid and 7 lepromatous patients. Results. Dendritic epidermal cells, identified by monoclonal antibodies against CD1, hla-dr , CD45, and CD36, were found reduced in histoid leprosy as compared to both tuberculoid and lepromatous groups. A gradual reduction of keratinocytic hla-dr expression from tuberculoid to lepromatous to histoid leprosy was observed. The pattern of CD36, CD4, and CD8 expression of lymphomonocytic cells in the dermis of histoid lesions was similar to that of tuberculoid leprosy, but without the formation of an organized granuloma. CD45+ cells as well as activated lymphocytic cells, expressed by the activation immunophenotype (CD1, hla-dr , CD25, CD71, egf-r ) were found frequently in all groups. Conclusions. The in situ immunohistochemical findings support a modified hypersensitivity reaction of the cellular type that results in an inhibition of the lesional expansion, but not in the destruction of the bacilli within the histoid lesion.     

Antiplatelet effects of prasugrel vs. double clopidogrel in patients on hemodialysis and with high on‐treatment platelet reactivity

Summary. Background: High on‐treatment platelet reactivity (HTPR) is frequent in patients on hemodialysis (HD) receiving clopidrogel. Objectives: The primary aim of this study was to determine the antiplatelet effects of prasugrel vs. high‐dose clopidogrel in patients on HD with HTPR. Patients/Methods: We performed a prospective, single‐center, single‐blind, investigator‐initiated, randomized, crossover study to compare platelet inhibition by prasugrel 10 mg day^?1 with that by high‐dose 150 mg day^?1 clopidogrel in 21 patients on chronic HD with HTPR. Platelet function was assessed with the VerifyNow assay, and genotyping was performed for CYP2C19*2 carriage. Results: The primary endpoint of platelet reactivity (PR, measured in P2Y12 reaction units [PRU]) was lower in patients receiving prasugrel (least squares [LS] estimate 156.6, 95% confidence interval [CI] 132.2–181.1) than in those receiving high‐dose clopidogrel (LS 279.9, 95% CI 255.4–304.3), P < 0.001). The LS mean differences between the two treatments were ? 113.4 PRU (95% CI ? 152.9 to ? 73.8, P < 0.001) and ? 163.8 PRU (95% CI ? 218.1 to ? 109.2, P < 0.001) in non‐carriers and carriers of at least one CYP2C19*2 allele, respectively. HTPR rates were lower for prasugrel than clopidogrel, in all patients (19% vs. 85.7%, P < 0.001) and in non‐carriers (25.7% vs. 80%, P = 0.003). All carriers continued to show HTPR while receiving high‐dose clopidogrel, but none showed it while receiving prasugrel. Conclusions: In HD patients exhibiting HTPR following standard clopidogrel treatment, prasugrel 10 mg day^–1 is significantly more efficient than doubling the clopidogrel dosage in achieving adequate platelet inhibition. Neither effect seems to be influenced by carriage of the loss‐of‐function CYP2C19*2 allele.