Modulation of inflammatory response by selective inhibition of cyclooxygenase-1 and cyclooxygenase-2 in acute kidney injury

This work explored the role of inhibition of cyclooxygenases (COXs) in modulating the inflammatory response triggered by acute kidney injury.C57Bl/6 mice were used.Animals were treated or not with indomethacin (IMT) prior to injury (days -1 and 0).Animals were subjected to 45 min of renal pedicle occlusion and sacrificed at 24 h after reperfusion. Serum creatinine and blood urea nitrogen, reactive oxygen species (ROS), kidney myeloperoxidase (MPO) activity, and prostaglandin E2 (PGE(2)) levels were analyzed. Tumor necrosis factor (TNF)-alpha, t-bet, interleukin (IL)-10, IL-1 beta, heme oxygenase (HO)-1, and prostaglandin E synthase (PGES) messenger RNA (mRNA) were studied. Cytokines were quantified in serum.IMT-treated animals presented better renal function with less acute tubular necrosis and reduced ROS and MPO production. Moreover, the treatment was associated with lower expression of TNF-alpha, PGE(2), PGES, and t-bet and upregulation of HO-1 and IL-10. This profile was mirrored in serum, where inhibition of COXs significantly decreased interferon (IFN)-gamma, TNF-alpha, and IL-12 p70 and upregulated IL-10.COXs seem to play an important role in renal ischemia and reperfusion injury, involving the secretion of pro-inflammatory cytokines, activation of neutrophils, and ROS production. Inhibition of COX pathway is intrinsically involved with cytoprotection.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ São Paulo, Inst Biomed Sci, Dept Immunol, Transplantat Immunobiol Lab, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Expt & Clin Immunol Lab, São Paulo, BrazilUniv Fed Juiz de Fora, Div Nephrol, Juiz de Fora, MG, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, São Paulo, BrazilHosp Israelita Albert Einstein, Inst Ensino & Pesquisa, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Expt & Clin Immunol Lab, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biol Sci, São Paulo, BrazilFAPESP: 04/08311-4FAPESP: 07/07139-3 e 06/03982-5Web of Scienc

Physical Activity in Hemodialysis Patients Measured by Triaxial Accelerometer

Different factors can contribute to a sedentary lifestyle among hemodialysis (HD) patients, including the period they spend on dialysis. The aim of this study was to evaluate characteristics of physical activities in daily life in this population by using an accurate triaxial accelerometer and to correlate these characteristics with physiological variables. Nineteen HD patients were evaluated using the DynaPort accelerometer and compared to nineteen control individuals, regarding the time spent in different activities and positions of daily life and the number of steps taken. HD patients were more sedentary than control individuals, spending less time walking or standing and spending more time lying down. The sedentary behavior was more pronounced on dialysis days. According to the number of steps taken per day, 47.4% of hemodialysis patients were classified as sedentary against 10.5% in control group. Hemoglobin level, lower extremity muscle strength, and physical functioning of SF-36 questionnaire correlated significantly with the walking time and active time. Looking accurately at the patterns of activity in daily life, HDs patients are more sedentary, especially on dialysis days. These patients should be motivated to enhance the physical activity

Clinical variables add incremental value to fasting blood glucose in predicting a positive glucose tolerance test in established renal transplant recipients

Lamivudine treatment for patients with chronic hepatitis B virus (HBV) infection may improve clinical state and suppress viral replication before liver transplantation (LTx). Emergence of lamivudine-resistant YMDD mutant is common and may be regarded as a contraindication for transplantation. We report the results of LTx in 16 patients with pre-transplant YMDD mutants after receiving lamivudine for a median of 738 days (400 to 1799 days). Adefovir dipivoxil (10 mg daily) was added-on to lamivudine for a median duration of 20 (8 to 271) days before (n=11) or at (n=5) LTx and the combination was continued indefinitely thereafter. Eight patients received additional intravenous hepatitis B immune globulin (HBIG) for a median of 24 months. Fifteen patients with known pre-adefovir serum HBVDNA level had a median titer of 14,200 x 103 (2.2 x 103 to 4,690,000 x 103) copies/ml and 14 had HBVDNA >105 copies/ml. All except one patient remained positive for HBVDNA (by qPCR) at the time of LTx and the titer was >105 copies/ml in 8 patients. The median follow-up after LTx was 21.1 (4.4 to 68.9) months. One patient died of an unrelated cause at 12.2 months post-transplant and 15 (94%) patients were alive with the original graft. All patients cleared HBVDNA and had no detectable HBVDNA by qPCR at the latest follow-up. Fourteen patients had HBsAg seroconversion but 2 patients who received only adefovir dipivoxil and lamivudine without HBIG had not cleared HBsAg after 7.7 and 9.5 months. Serum HBVDNA, however was negative and there was no biochemical or histologic evidence of recurrence. Adefovir dipivoxil was well-tolerated with no significant renal toxicity. In conclusion, combination of add-on adefovir dipivoxil to lamivudine therapy provides effective prophylaxis in patients with pre-transplant YMDD mutant that may be actively replicating. The cost effectiveness of additional passive immunoprophylaxis remains to be defined.link_to_OA_fulltex