Acute kidney injury: effect of hemodialysis membrane on Hgf and recovery of renal function.

OBJECTIVES: Acute kidney injury (AKI) is associated with a high mortality and morbidity rate. In this study we investigated whether dialysis membranes influence the recovery of renal function, through the regulation of hepatocyte growth factor (HGF). DESIGN AND METHODS: 21 patients were enrolled and assigned to hemodialysis (HD) with cellulose (CE, N=11) versus polymethylacrylate (PMMA, N=10) membranes in alternating order. HGF and IL-1 were measured in serum and in peripheral blood mononuclear cells (PBMC) supernatants collected immediately before the first HD session (T0), at 15 minutes (T15), at 240 minutes (T240) and after the last HD, when renal recovery occurred. Eight healthy volunteers were the controls (CON). RESULTS: Time to renal function recovery was lower in CE than in PMMA patients. Serum HGF in HD patients was significantly higher than in CON. HGF levels were higher in CE than in PMMA patients at T15 (13.4±2.7 vs 8.9±3.0 ng/mL, P=0.004) and T240. At recovery, HGF levels decreased. IL-1 serum levels showed a similar trend (at T15 CE: 20.5±2.9 vs PMMA: 16.9±3.2 pg/mL, P=0.005). HGF release significantly increased in the course of HD, resulting in higher levels in CE than that in PMMA patients. Considering all the patients, basal HGF release negatively correlated with time to renal recovery (r2=0.42, P<0.01). CONCLUSIONS: Here we demonstrated that dialysis membranes influence the cytokine profile in AKI patients, HGF release being higher in patients treated with the CE membrane, in comparison to PMMA. Our results suggest that treatment with CE might improve clinical outcomes, possibly through increased release of HGF.

Effects of different peritoneal dialysis fluids on the TH1/TH2 balance.

BACKGROUND: Peritoneal dialysis (PD) is associated with a depression of T cell function, as suggested by the impaired production of cytokines by Th cells collected from PD patients. Although treatment biocompatibility could be implicated in this immune dysfunction, it has been poorly investigated, thus far. Therefore, we undertook a study aiming to analyze the effects of different peritoneal dialysis fluids on the Th1/Th2 balance in PD patients. METHODS: Twenty three patients on continuous ambulatory peritoneal dialysis (CAPD) were evaluated. Seven patients were on CAPD with icodextrin solution (ICO-PD), seven with glucose and lactate/bicarbonate-buffered solution (LAC/BIC-PD), and nine with glucose and lactate-buffered solution (LAC-PD). The Th1/Th2 balance was evaluated by measuring IFN-γ (Th1 subset) and IL-4 (Th2 subset), both in circulating and peritoneum-derived Th lymphocytes unstimulated or stimulated by phytohemoagglutinin (PHA). Moreover inflammatory, nutritional and dialysis-related parameters were recorded. Eight normal subjects comprised the control group (CON). RESULTS: Circulating T cells: IFN-γ was significantly lower in the LAC-PD group (p<0.05) compared to the ICO-PD and LAC/BIC-PD groups. The IFN-γ/IL-4-producing cell ratio was significantly lower in PD patients than in CON. Peritoneal T cells: after 24-h PHA stimulation, IFN-γ increased in all patients, but the rise was less pronounced in the LAC-PD group (p<0.05) than in the other two PD groups. The Th1/Th2 ratio was significantly lower in the LAC-PD group when compared both to LAC/BIC-PD and ICO-PD groups. In addition, the LAC-PD group presented a significantly higher rate of peritoneal infections compared to the other PD groups. CONCLUSIONS: CAPD with lactate-buffered peritoneal fluid has deleterious effects on the Th1 cell subset, while the use of more biocompatible fluids, bicarbonate-buffered and icodextrin, is associated with a more physiologically representative Th1/Th2 balance and a reduced peritonitis rate.

Adalimumab (Humira™): a promising monoclonal anti-tumor necrosis factor alpha in ophthalmology.

Tumor necrosis factor alpha (TNF-α) is a key soluble mediator involved in the inflammatory cascade of many disorders including uveitis. Among the anti-TNF-α agents, one of the most used in immune-mediated diseases, such as inflammatory arthropathies, is adalimumab (Humira™, Abbott Pharmaceutical Inc.), a fully humanized antibody. The purpose of this review is to analyze the main pharmacological and clinical aspects of adalimumab and its efficacy both in systemic and ocular inflammatory disorders. Adalimumab was effective in treating several autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. In recent years, adalimumab has been used successfully in refractory cases of intraocular inflammation. Moreover, this biological agent showed good safety and efficacy profiles in ocular use including childhood uveitis. Switching from other anti-TNF-α agents to adalimumab may offer several advantages, such as easier administration, better patient compliance, and lower rate of adverse events. Adalimumab is a promising drug for the therapy of uveitis, although further studies are needed on its application in uveitis.

Adalimumab (humira™) in ophthalmology: a review of the literature.

Tumor Necrosis Factor alpha (TNF-α) is a pleiotropic cytokine which plays a primary role in the induction of inflammation in autoimmune diseases. The newest anti-TNF-α agent is adalimumab (Humira, Abbott Pharmaceutical Inc.), a human-derived antibody. This review summarizes the characteristics of adalimumab, highlighting its clinical use in systemic and ocular inflammatory disorders, and the possible therapeutic strategies. Adalimumab has been successfully used for the treatment of rheumatoid arthritis, ankylosing spondylitis, and psoriasis arthritis. More recently, adalimumab has shown promising qualities in controlling intraocular inflammations, even though this has been used prevalently as a rescue therapy for unresponsive cases. This biologic agent was also used in pediatric cases, showing a good safety and efficacy profile. Albeit no direct comparison with other biologics has been done, and adalimumab seems to be equivalent to the other anti-TNF-α, the switching to adalimumab can offer a better uveitic control. Adalimumab is a promising drug for the treatment of uveitis, even though further studies are needed on its application as a primary therapy in uveitis.

Echo-color-Doppler balance in dialysis patient.

Ultrasonography is a non-invasive,well-controlled, quickly and easily available diagnostic procedure for the patient, is repeatable and not using ionizing radiation. For all these features plays an important role in the clinical management of patients undergoing dialysis. A census of the National Renal Ultrasound Study Group from Italian Society of Nephrology revealed that the 73.04% of Italian Departments of Nephrology and Dialysis are equipped with the ultrasound scanning and this one is commonly used in normal working routine. The main fields of application of this methodology in dialysis patient are: vascular pathology (damages due to systemic atherosclerosis, study and monitoring of arteriovenous fistula), muscle-tendon pathology (caused by hyperparathyroidism and amyloidosis), hyperparathyroidism (parathyroid assessment) and neoplastic disease.

Intermittent haemodiafiltration in refractory congestive heart failure: BNP and balance of inflammatory cytokines.

BACKGROUND: Elevated plasma levels of cytokines have been associated with an increased risk of congestive heart failure (CHF) even in people without history of myocardial infarction. Here we have tested the hypothesis that effective removal of pro-inflammatory cytokines in patients with advanced CHF unresponsive to diuretic treatment is associated with diuresis restoration and with a significant reduction of B-type natriuretic peptide (BNP) circulating levels. METHODS: We prospectively enrolled 10 patients with decompensated CHF (NYHA classes III-IV). Five patients unresponsive to diuretic treatment underwent a short course of intermittent haemodiafiltration (iHDF), whereas five patients responsive to diuretics were treated with intravenous boluses of furosemide. Renal function was similar between the two groups. RESULTS: Excess body fluids were removed in both groups always resulting in a reduction of pulmonary congestion and peripheral oedema. NYHA class improved in all patients, but one treated by intravenous boluses of furosemide. Only patients treated with iHDF showed a significant reduction of circulating interleukin-8 and monocyte chemoattractant protein-1. After the end of iHDF treatment, patients showed consistent restoration of diuretic responsiveness to significantly lower doses of oral furosemide up to one month of follow-up. Plasma levels of BNP before treatment were significantly higher in the iHDF group, lowering significantly in both groups after treatment. CONCLUSIONS: Our results suggest that HDF is an effective treatment for patients with advanced CHF when cytokines have to be cleared and diuretic responsiveness needs to be restored. In our experience, iHDF is a cost-effective option when compared with continuous ultrafiltration methods because it can be performed in a routine dialysis unit without adjunctive costs for machinery or personnel training.

Vitamin E-loaded dialyzer resets PBMC-operated cytokine network in dialysis patients.

BACKGROUND: In hemodialysis patients the activity of stimulated Th1 lymphocytes is depressed, while Th2 cells are constitutively primed. Such phenomena may depend on monocyte activation and altered release of interleukin (IL)-12 and IL-18, which regulate Th cell differentiation. Reactive oxygen species (ROS) activate monocytes; therefore, a hemodialyzer with antioxidant activity would contrast ROS, prevent monocyte activation, reset IL-12 and IL-18 release, and restore Th1/Th2 balance. METHODS: Ten patients on regular dialysis treatment (RDT) with cellulosic membrane (CM) were shifted to vitamin E-coated dialyzer (VE). During treatment with CM and after 3, 6, and 12 months of treatment with VE, peripheral blood mononuclear cells (PBMC) and purified CD4+ cells were isolated, and cultured, resting, mitogen-stimulated, and interferon gamma (IFNgamma), IL-4, IL-10, IL-12, and IL-18 release was measured. Vitamin E and A plasma levels and the effects of a single dialysis session on peripheral blood NO levels were assayed. RESULTS: The constitutive release of IL-4 and IL-10 by CD4+ cells was abated significantly by treatment with VE (nadir -77.8% and -55.3%, respectively, at 12 months). INFgamma release by mitogen-stimulated CD4+ recovered with VE (zenith +501% at 12 months). PBMC constitutive production of IL-12 and IL-18 was significantly reduced by VE (nadir at 12 months -64.7% and -51.3%, respectively). VE increased plasma levels of vitamins E and A. NO plasma levels fell after a single dialysis treatment with VE (-17%, P < 0.05) in contrast with CU (+27.1%, P < 0.05). CONCLUSION: The network of cytokines released by monocytes and Th cells is reset toward normality by treatment with vitamin E-coated dialyzer.