Effects of simvastatin on cytokines secretion from mononuclear cells from critically ill patients with acute kidney injury

Purpose: To assess the in vitro effects of simvastatin on IL-10 and TNF-alpha secretion from peripheral blood mononuclear cells (PBMC) of critically ill patients with and without acute kidney injury (AKI).Methods: PBMC were collected from 63 patients admitted to the intensive care unit (ICU) and from 20 healthy controls. Patients were divided in 3 subgroups: with AKI, with sepsis and without AKI and with AKI and sepsis. After isolation by ficoll-gradient centrifugation cells were incubated in vitro with LPS 1 ng/mL, simvastatin (10(-8)M) and with LPS plus simvastatin for 24 h. TNF-alpha and IL-10 concentrations on cells surnatant were determined by ELISA.Results: Cells isolated from critically ill patients showed a decreased spontaneous production of TNF-alpha and IL-10 compared to healthy controls (6.7(0.2-12) vs 103(64-257) pg/mL and (20 (13-58) vs 315(105-510) pg/mL, respectively, p < 0.05). Under LPS-stimulus, IL-10 production remains lower in patients compared to healthy control (451 (176-850) vs 1150(874-1521) pg/mL,p < 0.05) but TNF-alpha production was higher (641 (609-841) vs 406 (201-841) pg/mL, p < 0.05). the simultaneous incubation with LPS and simvastatin caused decreased IL-10 production in cells from patients compared to control (337 (135-626) vs 540 (345-871) pg/mL, p < 0.05) and increased TNF-alpha release (711 (619-832) vs 324 (155-355) pg/mL, p < 0.05). Comparison between subgroups showed that the results observed in TNF-alpha and IL-10 production by PBMC from critically ill patients was independent of AKI occurrence.Conclusions: the PBMC treatment with simvastatin resulted in attenuation on pro-inflammatory cytokine spontaneous production that was no longer observed when these cells were submitted to a second inflammatory stimulus. Our study shows an imbalance between pro and anti-inflammatory cytokine production in PBMC from critically ill patients regardless the presence of AKI. (C) 2011 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Instituto de Ensino e Pesquisa do Hospital Israelita Albert EinsteinUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilIAEH IEP Hosp Israelita Albert Einstein Inst Ensi, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilWeb of Scienc

Remoção de mediadores inflamatórios por hemofiltração em pacientes com lesão renal aguda

Introdução: Os pacientes graves com lesão renal aguda (LRA) apresentam altas taxas de mortalidade. A magnitude da resposta inflamatória pode determinar o prognóstico desses doentes. A terapia de substituição renal contínua (CRRT) pode desempenhar um papel na remoção de mediadores inflamatórios em pacientes com LRA. Objetivo: Investigar se a magnitude da remoção do mediador inflamatório está associada com a mortalidade entre os pacientes criticamente enfermos em CVVHDF, uma modalidade de CRRT. Métodos: Este estudo consistiu de 64 pacientes criticamente enfermos que necessitavam de CVVHDF. Os níveis plasmáticos de C3a, TNF-?, IL-10, IL-6, IL-1?, sTNFRI e sTNFRII foram determinados por ensaio imunoenzimático (ELISA), no início de CVVHDF e após 24 horas. A quantidade estimada de citocinas durante as primeiras 24 horas de CVVHDF foi calculada. Os dados clínicos e laboratoriais foram adquiridos a partir de registros de dados do paciente. Resultados: A média de idade dos pacientes que necessitam CVVHDF foi de 63 anos, 67,2% eram homens e 87,3% eram brancos. Trinta e cinco (35) pacientes (54,7%) foram a óbito. Comparando não sobreviventes com o grupo de sobreviventes, observamos maior incidência de sepse (68,6 versus 37,9%, p 2,93)) verificou-se que os pacientes com maior remoção TNF-? por CRRT (3º tercil) tiveram um melhor sobrevida. A análise multivariada mostrou que a menor quantidade removida de TNF-? permaneceu independentemente associada com a alta mortalidade mesmo após o ajuste para fatores como sexo, idade, uso de drogas vasoativas, escore de APACHE II, sepse, creatinina e lactato antes da CVVHDF (HR: 0,179, IC 95%: 0,049-0,661 , p <0,01). Conclusão: A atenuação da resposta inflamatória pode estar relacionada com a menor mortalidade observada em pacientes com maior quantidade removida de TNF-? por CVVHDF.Dados abertos - Sucupira - Teses e dissertações (2013 a 2016

A new spectrophotometric method to detect residual amounts of peroxide after reprocessing hemodialysis filters

ABSTRACT Objective: Reuse of hemodialysis filters is a standard practice and the sterilizing chemical most often employed is peracetic acid. Before starting the dialysis session, filters and lines are checked for residual levels of peracetic acid by means of a non-quantitative colorimetric test that is visually interpreted. The objective of this study was to investigate a new quantitative spectrophotometric test for detection of peracetic acid residues. Methods: Peracetic acid solutions were prepared in concentrations ranging from 0.01 to 10 ppm. A reagent (potassium-titanium oxide + sulfuric acid) was added to each sample in proportions varying from 0.08 to 2.00 drops/mL of solution. Optical densities were determined in a spectrophotometer using a 405-nm filter and subjected to visual qualitative test by different observers. Results: A relation between peroxide concentrations and respective optical densities was observed and it was linear with R2 > 0.90 for all reagent/substrate proportions. The peak optical densities were obtained with the reagent/substrate ratio of 0.33 drops/mL, which was later standardized for all further experiments. Both qualitative and quantitative tests yielded a specificity of 100%. The quantitative test was more sensitive than the qualitative test and resulted in higher positive and negative predictive values. There was a difference between observers in the qualitative test and some samples with significant amounts of peroxide were not detected. Conclusion: A quantitative spectrophotometric test may improve detection of residues of peracetic acid when compared to the standard visual qualitative test. This innovation may contribute to the development of safer standards for reuse of hemodialysis filters

Index of coexisting disease and old age as predictors of survival in hemodialysis patients

Objective: To identify the factors that may influence survival inpatients on chronic hemodialysis at a private hospital in Brazil.Methods: In this study, 99 patients in the CDE (Hemodialysis Unitof Hospital Albert Einstein) undergoing chronic hemodialysis for atleast 3 months were evaluated retrospectively over the period fromFebruary 2000 to October 2006. The following patient characteristicswere evaluated as possibly having an influence on survival: cause ofchronic renal failure (with and without diabetes mellitus), sex, age,albumin levels, C-reactive protein (CRP), hemoglobin levels and ICED(Index of Coexisting Disease), an instrument to assess the presence andseverity of comorbidities). Statistical analysis: Survival curves werecalculated by the Kaplan-Meyer method and the differences betweenthe curves were evaluated by a log-rank test. Results: The mean ageof patients was 63.14 ± 16.18 years, 34% of them were female and40% of them presented diabetes mellitus as the cause of chronic renalfailure. Mean albumin and hemoglobin levels on admission were 3.44± 0.58 g/dl and 10.55 ± 1.51 g/dl, respectively, and median CRP levelwas 9.55 g/dl. The distribution of patients by ICED was mild (25%),moderate (36%) and severe (38%). Thirty-three (33%) patients died,24 (24%) underwent renal transplantation, 5 (5%) were transferredto another dialysis unit, 36 (36%) continued dialysis treatment and1 (1%) recovered renal function. One-year survival was 80% and themedian survival period was 42.34 months (95% CI: 28.06-54.84).In univariate analysis, the following variables were associated withsurvival of patients: CRP levels on admission (RR: 1.39; 95% CI: 1.04-1.85; p = 0.026), age (RR: 1.049; 95% CI: 1.017-1.082; p = 0.028)and the level of ICED 3 compared with the level of ICED 1 (RR: 9.25;95% CI: 1.23-69.48; p = 0.03). In multivariate analysis, the followingvariables were associated with survival of patients: age (p = 0.0025)and severe ICED compared with mild ICED (p = 0.0341). Conclusion:The factors associated with survival of patients were advanced ageand severity of comorbidities. The utilization of ICED enables stratifyingthe dialysis patients according to severity of their comorbidities andit is useful to identify the patients with a greater risk of death andhospitalization, as well as to aid in the forecast of and optimization ofresources necessary for their treatment