Immunogenicity and safety of a booster dose of the hepatitis B vaccine HepB-CpG (HEPLISAV-B®) compared with HepB-Eng (Engerix-B®) and HepB-AS04 (Fendrix®) in adults receiving hemodialysis who previously received hepatitis B vaccination and are not seroprotected: Results of a randomized, multicenter phase 3 study.

This study compared the immunogenicity and safety of a booster dose of HepB-CpG (HEPLISAV-B® vaccine) with HepB-Eng (Engerix-B®) and HepB-AS04 (Fendrix®) in patients receiving chronic hemodialysis. This was a multicenter, randomized, open-label, phase 3 study of adults receiving hemodialysis with antibodies to HBsAg (anti-HBs) <10 mIU/mL at study entry. The objective was to compare the seroprotection rate (SPR) induced by HepB-CpG with HepB-Eng or HepB-AS04. The SPR was defined as the percentage of patients with anti-HBs ≥10 mIU/mL post-vaccination. At 20 sites in Germany, 155 participants were randomized: HepB-CpG = 54; HepB-Eng = 50; and HepB-AS04 = 51. Of the 149 participants in the modified intention-to-treat population, 76.5% had not previously responded to at least one series of hepatitis B vaccine. Based on a post hoc analysis, the SPR in HepB-CpG recipients (52.8%; 95% confidence interval [CI]: 38.6%, 66.7%) was significantly higher than in HepB-Eng recipients (32.6%; 95% CI: 19.5%, 48.0%), and non-inferior to that in HepB-AS04 recipients (43.1%; 95% CI: 29.3%, 57.8%). Local post-injection reactions occurred in significantly fewer HepB-CpG (9.3%) than HepB-AS04 recipients (31.4%; p = .007) and at a similar rate to HepB-Eng recipients (8.2%). Systemic post-injection reactions in HepB-CpG recipients (18.5%) were similar to the HepB-AS04 group (19.6%) and higher than in the HepB-Eng group (12.2%). In this difficult-to-immunize population, a booster dose of HepB-CpG induced significantly higher levels of seroprotection than HepB-Eng with a similar safety profile. The higher levels of immunogenicity were not accompanied by higher levels of local post-injection reactions compared with HepB-AS04.

Initial use of once-monthly administration of C.E.R.A. is effective and safe in correcting renal anemia in non-dialysis patients: the MERCUR trial.

BACKGROUND: Continuous erythropoietin receptor activator (C.E.R.A.) is routinely given once every 2 weeks to correct hemoglobin (Hb) level, but monthly use is recommended in the maintenance phase. PATIENTS AND METHODS: In an open-label, single- arm, multicenter trial, 184 ESA-naïve non-dialysis patients with renal anemia (Hb ≤ 10.5 g/dl) received C.E.R.A. monthly from the start of therapy. The trial comprised a titration phase (Months 2 - 7) and an evaluation phase (Months 8 - 9). Mean Hb increased from 9.8 ± 0.7 g/dl at baseline to 11.5 ± 1.1 g/ dl during the evaluation phase (mean change 1.6 ± 1.1 g/dl; 95% CI 1.4 - 1.8 g/dl). Among patients with two Hb values available during the evaluation phase, 18.1% (19/105) were maintained at 11.0 - 12.0 g/dl and 49.5% (52/105) at 11.0 - 13.0 g/dl. 20 patients started dialysis and received C.E.R.A during the titration phase. RESULTS: Their mean Hb increased from 10.6 ± 1.6 g/dl (last pre-dialysis value) to 11.3 ± 1.6 g/dl. Nine patients (4.9%) experienced one adverse event with a suspected relation to C.E.R.A.; 5 were graded serious. 54 patients (29.3%) discontinued the study (22 for adverse events). CONCLUSION: Although no control arm was included, such that robust comparisons cannot be drawn, these results suggest that C.E.R.A. therapy can be initiated once a month in non-dialysis CKD patients with renal anemia without appearing to compromise the rate or degree of Hb correction.

Correlation of renal tubular epithelial cell-derived interleukin-18 up-regulation with disease activity in MRL-Faslpr mice with autoimmune lupus nephritis.

OBJECTIVE: MRL-Fas(lpr) mice spontaneously develop an autoimmune disease that mimics systemic lupus erythematosus in humans. Infiltrating T cells expressing interferon-gamma (IFNgamma) are responsible for the autoimmune kidney destruction in MRL-Fas(lpr) mice, and interleukin-18 (IL-18) released by mononuclear phagocytes stimulates T cells to produce the IFNgamma. Since MRL-Fas(lpr) T cells are characterized by an overexpression of the IL-18 receptor accessory chain, we sought to determine the impact of IL-18 on the progression of lupus nephritis in MRL-Fas(lpr) mice. METHODS: IL-18 expression in sera and kidney tissues from MRL-Fas(lpr) mice was determined by enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and Western blotting. IL-18 production by primary cultured tubular epithelial cells (TECs) from MRL-Fas(lpr) and BALB/c mice were examined by RT-PCR, ELISA, and Western blotting. The interactions of TEC-derived IL-18 and MRL-Fas(lpr) T cells were studied in coculture assays. IL-18-related effects on TEC viability and adhesion molecule expression were determined by fluorescence-activated cell sorting and cell proliferation assays. RESULTS: Up-regulation of mature IL-18 was restricted to nephritic MRL-Fas(lpr) kidneys and increased in parallel with the severity of lupus nephritis. IL-18 expression was not confined to infiltrating monocytes but was primarily detected in TECs. Similarly, interleukin-1beta-converting enzyme expression, which is required for the processing of precursor IL-18, was localized in TECs. De novo synthesis of IL-18 by MRL-Fas(lpr) TECs was confirmed by RT-PCR and Western blotting. Functional assays revealed that activated TECs induced IFNgamma production in MRL-Fas(lpr) T cells through IL-18. IL-18, in turn, increased apoptotic TEC death and up-regulation of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1. CONCLUSION: Taken together, our findings suggest that IL-18-producing TECs may directly be involved in the pathogenesis of lupus nephritis.