RESUMO
Recent studies suggest that chronic inflammation plays a role in the pathogenesis of cardiovascular disease. Cytokines released from jeopardized tissues stimulate the liver to synthesize acute phase proteins, including C-reactive protein (CRP). Baseline levels of CRP in apparently healthy persons or in persons with unstable angina constitute an independent risk factor for cardiovascular events. More recently, it has been suggested that CRP is useful not only as a marker of the acute phase response, but is also involved in the pathogenesis of the disease. CRP may, in fact, directly interact with the atherosclerotic vessels or ischemic myocardium by activation of the complement system, thereby promoting inflammation and thrombosis. Several studies in uremic patients have implicated CRP as a marker of malnutrition, resistance to erythropoietin, and chronic stimulation in hemodialysis. An increased cytokine production secondary to blood interaction with bioincompatible dialysis components has been reported by several studies; interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and mainly IL-6 are the three proinflammatory cytokines involved in the pathogenesis of hemodialysis-related disease. We have provided evidence for the occurrence of high CRP and IL-6 levels in chronic dialytic patients exposed to contaminate dialysate and suggest that backfiltration may induce a chronic, slowly developing inflammatory state that may be abrogated by avoiding backfiltration of contaminate dialysate. Therefore, CRP is implicated as a marker linking bioincompatibility associated with backfiltration and increased cytokine production with a clinical state of chronic inflammation.
Assuntos
Citocinas/biossíntese , Falência Renal Crônica , Diálise Renal/efeitos adversos , Reação de Fase Aguda/imunologia , Materiais Biocompatíveis/efeitos adversos , Humanos , Falência Renal Crônica/imunologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapiaRESUMO
Secondary hyperparathyroidism is a common feature of chronic renal failure and vitamin D deficiency plays an important role in the development of this abnormality. Several therapeutical calcitriol schedules have been used in treating uremic hyperparathyroidism but recently oral boluses have been proposed as more effective. In this study we compare the efficacy of three different oral calcitriol regimens in suppressing iPTH secretion in predialytic chronic renal failure. Sixteen (16) patients (mean age 51 +/- 16 years; creatinine clearance 22.9 +/- 9.8 ml; range 8-32 ml/min) were treated in a cross-over randomized design with oral daily calcitriol 0.5 micrograms/die (Treatment A), three oral boluses of 2 micrograms of calcitriol a week (Treatment B) and a single oral bolus of 2 micrograms of calcitriol a week (Treatment C). All treatment periods lasted three months and were followed by a wash-out period of one month. Serum iPTH (Allegro Nichols), 1-25 vitamin D (IRMA-MAB), total and ionized calcium (Nova 8 Pabish), serum phosphate, alkaline phosphatase and creatinine clearance were measured every two weeks. Serum iPTH was also determined in a control group of fifteen (15) patients (mean age 47 +/- 12 years, creatinine clearances of 21 +/-12 ml/min) observed for three months without calcitriol treatment. Daily oral intake of 0.5 micrograms of calcitriol prevents an increase of iPTH without causing hypercalcemia, but only oral boluses (B and C) decreased iPTH: from 270 +/- 169 pg/ml to 135 +/- 76 pg/ml (p < 0.01; B) and to 165 +/- 121 pg/ml (p < 0.05; C). Serum iPTH increased from 293 +/- 121 to 323 +/- 129 pg/ml (p = n.s.). No significant differences in renal function were observed during the different study periods. Our results confirm the good efficacy of multiple calcitriol oral boluses but also suggest for the first time a single weekly bolus as a reliable approach to the treatment of secondary hyperparathyroidism in pre-dialytic renal failure.
Assuntos
Calcitriol/administração & dosagem , Hiperparatireoidismo Secundário/prevenção & controle , Falência Renal Crônica , Hormônio Paratireóideo/sangue , Administração Oral , Calcitriol/uso terapêutico , Estudos Cross-Over , Esquema de Medicação , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/metabolismoRESUMO
In previous trials we proved how propionyl carnitine, an acyl carnitine characterized by its intense mitochondrial metabolic, and cardio and vasoprotective activity, could prevent the cyclosporine-induced nephrotoxicity. Subsequently we also noted how propionyl carnitine could prevent the increase in renal intracellular calcium, which is the base of many cyclosporine-induced toxic phenomena. In our trials, we used the isolated and perfused rat kidney technique to examine if with the variations of the concentration of intracellular calcium, the adenosine 5'-triphosphate concentrations also varied, and if this decrease could be corrected by administrating propionyl carnitine. The results we obtained in these experiments indicated that when propionyl carnitine was administered preventively, the concentrations of renal intracellular adenosine 5'-triphosphate which were decreased by the cyclosporine returned to their normal values and, at the same time, a decrease in the increased vascular resistance of the kidney was noted. Therefore, propionyl carnitine corrected one of the biochemical alterations which explained the pathogenesis of the renal damage induced by cyclosporine.
Assuntos
Trifosfato de Adenosina/metabolismo , Cardiotônicos/uso terapêutico , Carnitina/análogos & derivados , Ciclosporina/antagonistas & inibidores , Imunossupressores/antagonistas & inibidores , Córtex Renal/efeitos dos fármacos , Animais , Carnitina/uso terapêutico , Ciclosporina/toxicidade , Imunossupressores/toxicidade , Técnicas In Vitro , Córtex Renal/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
INTRODUCTION: Postdilution hemofiltration with a polyamide membrane is a renal replacement technique widely used, but very little information is available regarding the biocompatibility of this treatment. In this paper we report the results of an acute study of the biocompatibility of polyamide hemofiltration. PATIENTS AND METHODS: Complement activation such as C3a and C5a Des Arg (RIA), granulocyte degranulation like alpha 1 elastase intradialytic increase (ELISA) and the expression of high affinity membrane receptors for IL-2 (anti-TAC) were determined. Beta 2-microglobulin (RIA) intradialytic decrease, as well as its convective removal, was evaluated. The nature of protein layer adsorbed onto the polyamide membrane, at the end of the dialytic session was investigated with a new immunohistochemical technique. Cell-associated cytokine concentration (like IL-1 beta and IL-1Ra - ELISA) was determined on mononuclear cell lysates. RESULTS: A low degree of complement activation was detected with the polyamide membrane when data were adjusted for hemoconcentration and for 1 m2 of membrane surface area. An important convective removal not only of Beta 2-microglobulin (258+/-20 mg/session), but also of the activated anaphylatoxins (225+/-76 ng/ml for C3a and 22.5+/-4 ng/ml for C5a) was revealed. A marked deposition of all coagulation factors with no detectable amount of immunoglobulins and complement factors was revealed on the polyamide membrane at the end of the dialytic session. No intradialytic (for IL-1beta) (from 14. 1+/-3.0 to 13.5+/-2.9 pg/2.5 x 10(6) cell) and interdialytic (for IL-1Ra) (from 4572+/-1076 to 5408+/-615 pg/2.5 x 10(6) cell) cell-associated cytokine expression was induced by hemofiltration. DISCUSSION AND CONCLUSION: Polyamide hemofiltration is a highly biocompatible technique due to the use of a synthetic membrane with a sterile reinfusion fluid and the convective removal of the activated anaphylatoxins and Beta 2-microglobulin.
Assuntos
Materiais Biocompatíveis , Hemofiltração/instrumentação , Membranas Artificiais , Nylons , Adulto , Idoso , Anafilatoxinas/análise , Anafilatoxinas/isolamento & purificação , Ativação do Complemento , Complemento C3a/análise , Complemento C5a des-Arginina/análise , Citocinas/análise , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Proteínas/análise , Receptores de Interleucina-2/análise , Microglobulina beta-2/análise , Microglobulina beta-2/isolamento & purificaçãoRESUMO
In order to investigate the nature of the protein layer deposited on hemodialysis membranes we developed a direct immunohistochemical technique using fluoresceinated antibodies to plasma membranes. Fifteen patients on regular dialytic treatment were dialyzed with CU, HE, PAN, PS and PMMA and the dialyzers analyzed at the end of a standard dialytic session. Snap frozen sections of hollow fiber devices were treated with flourescein-isothiocyante conjugated antibodies for IgG, IgA, IgM C3c, fibrinogen, factor VIII, factor XIIIa-s, antithrombin III, fibrinogen degradation products (PDF) and plasminogen. Protein deposits were evaluated by a quantitative criteria, which evaluates the intensity of fluorescence and the area of the capillary wall occupied by this fluorescence by using an image analysis software. The coagulation cascade is activated by all membranes and similar deposits of these proteins were revealed, whereas important differences in C3c deposition were found.
Assuntos
Proteínas Sanguíneas/análise , Membranas Artificiais , Diálise Renal , Adsorção , Fatores de Coagulação Sanguínea/análise , Técnica Direta de Fluorescência para Anticorpo , Humanos , Imuno-Histoquímica , Falência Renal Crônica/sangue , Falência Renal Crônica/terapiaRESUMO
UNLABELLED: BACKGROUND. Anti-neutrophil cytoplasmic autoantibodies (ANCA) have been described in patients suffering from systemic vasculitis such as Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and other pathological conditions. In this paper we report a greater incidence of ANCA in hemodialysis patients as compared to peritoneal dialysis patients, pre-dialytic uremic patients and non-renal patients; a possible role for dialysis bioincompatibility in ANCA generation was also investigated. METHODS: A total of 335 uremics in substitutive treatment (176 in hemodialytic treatment and 159 in peritoneal dialysis) were examined for ANCA positivity. A total of 189 patients with advanced renal failure in conservative treatment and 100 healthy subjects were used as control. The dialysis techniques were standard hemodialysis (n = 119), low volume hemodiafiltration (n = 26) and hemofiltration (n = 31). ANCA positivity was examined by immunofluorescence (IF): diffuse finely granular staining was considered as classical positive reaction (C-ANCA) and P-ANCA was diagnosed if a perinuclear staining was observed. EIA for proteinase-3 (anti PR-3) and myeloperoxidase-antibodies (anti-MPO) were also performed. RESULTS: In non-renal patients and in patients with pre-dialytic renal insufficiency none were found ANCA positive. In peritoneal dialysis patients all but one were ANCA negative with IF, with all EIA test resulting negative. In hemodialytic patients, a positive IF test was found in 26 (14.7%) for P-ANCA and in 5 (2.8%) for C-ANCA; using the EIA test 23 (13%) patients were positive for MPO and 12 (6.8%) for PR-3. CONCLUSIONS: No correlation with age, primary renal diseases, dialytic age, dialysis membrane materials was found; regarding the different extracorporeal dialytic techniques a higher incidence (p < 0.02) was detected in patients undergoing HDF Backfiltration of contaminated dialysate may induce ANCA via an increased cytokine generation.
Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Diálise Peritoneal , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Técnicas Imunoenzimáticas , Falência Renal Crônica/imunologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Uremia/imunologia , Uremia/terapiaRESUMO
The renal haemodynamic effects and renin-angiotensin II response to calcitonin gene-related peptide (CGRP) infusion were assessed in 16 patients with moderate hypertension and renal insufficiency. CGRP lowered the systemic mean blood pressure by 13% and increased the heart rate by 25%; the glomerular filtration rate rose from 56 +/- 11 ml/min to 71 +/- 8 ml/min (p < 0.005), the renal plasma flow decreased from 369 +/- 19 ml/min to 342 +/- 25 ml/min (p < 0.002) and the filtration fraction increased from 15 +/- 0.2% to 20 +/- 0.2%. Plasma renin activity rose stepwise during the CGRP infusion from 1.28 +/- 0.5 ng/ml/h to 1.66 +/- 0.4 and 1.89 +/- 0.4 ng/ml/h (p < 0.001). Angiotensin II showed a marked increase after 10 min of infusion (91.6 +/- 47.00 pg/ml) (control value 6.01 +/- 3.09 pg/ml) and at the end (28.63 +/- 16.00 pg/ml) (p < 0.001). CGRP exerts an apparently favourable effect on renal function of patients with renal insufficiency, but the observed increase of glomerular filtration rate is obtained by an increase of intraglomerular pressure secondary to angiotensin II production.
Assuntos
Angiotensina II/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Hemodinâmica/efeitos dos fármacos , Circulação Renal/efeitos dos fármacos , Insuficiência Renal/tratamento farmacológico , Renina/metabolismo , Adulto , Idoso , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/complicações , Insuficiência Renal/fisiopatologia , Fatores de TempoAssuntos
Trifosfato de Adenosina/metabolismo , Anti-Inflamatórios não Esteroides/farmacologia , Carnitina/análogos & derivados , Ciclosporina/farmacologia , Rim/efeitos dos fármacos , Análise de Variância , Animais , Carnitina/farmacologia , Técnicas In Vitro , Rim/metabolismo , Masculino , Perfusão , Ratos , Ratos WistarAssuntos
Anti-Inflamatórios não Esteroides/farmacologia , Cálcio/metabolismo , Carnitina/análogos & derivados , Ciclosporina/toxicidade , Imunossupressores/toxicidade , Túbulos Renais/enzimologia , Rim/patologia , Acetilglucosaminidase/metabolismo , Análise de Variância , Animais , Carnitina/farmacologia , Ciclosporina/antagonistas & inibidores , Relação Dose-Resposta a Droga , Imunossupressores/antagonistas & inibidores , Técnicas In Vitro , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Perfusão , Ratos , Ratos WistarAssuntos
Calcitriol/farmacologia , Cálcio/fisiologia , Citocinas/biossíntese , Lipopolissacarídeos/farmacologia , Linfócitos/imunologia , Células Cultivadas , Citocinas/sangue , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Humanos , Interleucina-1/biossíntese , Interleucina-1/sangue , Interleucina-10/biossíntese , Interleucina-10/sangue , Interleucina-6/biossíntese , Interleucina-6/sangue , Lipopolissacarídeos/antagonistas & inibidores , Linfócitos/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossínteseAssuntos
Ciclosporina/toxicidade , Hipertensão/induzido quimicamente , Hipertensão/prevenção & controle , Rim/efeitos dos fármacos , Receptores de Endotelina/biossíntese , Verapamil/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Membrana Celular/metabolismo , Endotelina-1/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Radioisótopos do Iodo , Rim/metabolismo , Masculino , Ensaio Radioligante , Ratos , Ratos Wistar , Receptor de Endotelina A , Receptores de Endotelina/genéticaRESUMO
This is a clinical case concerning an uremic female patient who presented with an important oedema in the omolateral left arm, after the creation of an AV fistula. All the diagnostic procedures including the ultrasound color-Doppler were irrelevant. The patient was positive for a subclavian venous stenosis which was completely unexpected. This clinical case questions how useful it is in indirectly evaluating flow meters by ultrasound color-Doppler in the work-up of central venous steno-occlusions.
Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Veia Subclávia , Ultrassonografia Doppler em Cores , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/etiologia , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/etiologia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
In recent years, acute phase reactants have been reevaluated as not merely biochemical markers of inflammation but also as active modulators of the inflammatory response. C-reactive protein - which is normally present in serum in only trace amounts, but whose concentration may rise markedly with inflammatory stimuli - was the first human acute phase protein discovered. It is now clear that cytokines are the major mediators of acute phase protein induction: interleukin-6 currently is felt to be the principal cytokine influencing C-reactive protein acute changes. Several studies have provided convincing evidence that among normal men, base-line serum levels of C-reactive protein are predictive of future myocardial infarction and ischemic stroke. The relevance of acute phase reactants in morbidity and mortality of haemodialysis patients has not been fully elucidated until now: in fact a few studies have implicated C-reactive protein in malnutrition, EPO-resistance, as a cardiovascular risk factor and as a marker of chronic stimulation in haemodialysis. The authors suggest the hypothesis of the occurrence of long-term complications in patients exposed to contaminated dialysate and suggest that back-filtration may induce a chronic, slowly developing inflammatory state that may be abrogated by avoiding backfiltration of contaminated dialysate.
Assuntos
Proteína C-Reativa , Diálise Renal , Feminino , Humanos , MasculinoRESUMO
Hemofiltration (HF) induces a significant reduction in parathormone (PTH). This effect is related not only to the convective removal of PTH molecules but also to the biological suppression of parathyroid glands by plasma-ionized calcium (iCa) increase. The acute inhibitory effect on parathyroid gland activity, ionized calcium mass balance, phosphate kinetics and intact PTH (PTHi) dialytic removal during post-dilution polyamide HF were studied in 31 chronic uremic patients. HF ensures good phosphate removal (from 2.54 +/- 1.19 to 1.27 +/- 0.35 mEq/l; p < 0.01), a positive iCa mass balance (8 +/- 4 mmol/session) with a iCa plasma increase and negligible convective PTHi removal (9 +/- 2 pg/ml). Study of the PTHi profile during HF characterized two different parathyroid responses: 26/31 patients showed a physiological parathyroid gland response to the iCa increase (from 1.17 +/- 0.09 to 1.42 +/- 0.07 mmol/l; p = 0.002) with a significant PTHi decrease (from 123 +/- 111 to 35 +/- 28 pg/ml; p = 0.01) and a maximal PTH inhibition of 88%. In 5 patients, with more severe hyperparathyroidism, in spite of a comparable increase in iCa (from 1.28 +/- 0.12 to 1.46 +/- 0.08 mmol/l; p = 0.02), this physiological calcium-PTHi feedback was lost, revealing an autonomization of the gland (maximal inhibition of 45%). In our experience, study of the PTHi profile during a single HF session may represent a clinical test for the functional exploration of parathyroid glands, suggesting future (medical or surgical) clinical strategy.
Assuntos
Cálcio/sangue , Hemofiltração/efeitos adversos , Hipoparatireoidismo/etiologia , Fosfatos/sangue , Doença Aguda , Adulto , Idoso , Fosfatase Alcalina/sangue , Calcitriol/sangue , Humanos , Hipoparatireoidismo/sangue , Cinética , Pessoa de Meia-Idade , Osteocalcina/sangue , Pró-Colágeno/sangue , Diálise Renal/efeitos adversosRESUMO
Calcitriol modulates in vivoand in vitro cytokine production: A role for intracellular calcium. Background. Several immunomodulatory properties of calcitriol are currently known, however, only little information is available regarding the in vivo and in vitro effects of calcitriol on cytokine production in chronic renal failure. Methods. To study the in vitro effect of calcitriol on lipopolysaccharide (LPS)-induced cytokine production, peripheral blood mononuclear cells (PBMC, 2.5 ml/ml) from 12 chronic dialytic (HD), 15 undialyzed chronic renal failure (CRF) patients and 10 normal subjects (N) were incubated at 37 degrees for 12 hours with 100 ng of LPS (E. coli and P. maltofilia). Increasing doses of calcitriol from 10-10 to 10-9 M were added and cell associated TNF-alpha and IL-1beta were determined by immunoreactive tests after three freeze-thaw cycles. The intradialytic TNF-alpha and IL-1beta production were evaluated in vivo in 12 HD patients before and after three months of intravenous calcitriol treatment (6 microgram/week). Intracellular calcium [Ca++]i was determined on PBMC with a cytofluorimetric assay using FLUO-3 AM as the indicator. Results. In vitro, TNF-alpha increased from 3.6 +/- 1.9 pg/cell to 1797 +/- 337 in N, from 4.5 +/- 1.7 to 1724 +/- 232 in CRF and from 3.4 +/- 2.3 to 1244 +/- 553 in HD after the LPS stimulus. The production of TNF-alpha was inhibited by calcitriol in a dose-dependent manner [LPS + Vit.D3 100 ng, 2.9 +/- 2.1 in N, 3.7 +/- 1.9 in CRF and 3.4 +/- 1.7 in HD; LPS + Vit.D3 50 ng, 263 +/- 296 (N), 6.73 +/- 11 (CRF), 38 +/- 28 (HD); LPS + Vit.D3 25 ng = 873 +/- 583 (N), 325 +/- 483 (CRF), 588 +/- 507 (HD); LPS + Vit.D3 12.5 ng, 954 +/- 483 (N), 912 +/- 510 (CRF), 875 +/- 527 (HD)]. Comparable data were observed on IL-1beta production. In vivo, the intradialytic TNF-alpha increase (from 8.5 +/- 2.3 to 19 +/- 5.6 pg/2.5 x 106 cell) during hemodialysis was markedly reduced after calcitriol therapy (from 6.6 +/- 3.1 to 11 +/- 4.7). [Ca++]i decreased from 105 +/- 25 to 72 +/- 18 nM (P < 0.05) and a positive correlation between cytokine levels and [Ca++]i was found (r = 0.79; P < 0.001). Conclusions. The in vitro increase of cell-associated cytokine after LPS challenge was inhibited by calcitriol in a dose-dependent manner. These data suggest a possible in vivo modulatory effect of calcitriol therapy on cytokine production in hemodialysis.
Assuntos
Calcitriol/farmacologia , Cálcio/fisiologia , Interleucina-1/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Adulto , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Falência Renal Crônica/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Recombinant human erythropoietin (rHuEpo) is the treatment of choice in anemia associated with end-stage renal disease. Its major side effect is hypertension, which occurs in 8-30% of uremic patients. The exact mechanism of rHuEpo-induced hypertension has not been fully elucidated, and several possibilities have been proposed, such as a direct vascular effect of the drug with a shift in the balance of constrictor and relaxing endothelial factors (endothelins and nitric oxide (NO)). Recent papers suggested an enhanced rather than reduced activity of endogenous NO system in rats with normal renal function and rHuEpo-induced hypertension. Our study was designed to verify whether, in spite of enhanced activity of the renal NO system, rHuEpo may affect endothelium-dependent (acetylcholine-induced) and/or endothelium-independent (sodium nitroprusside-induced) vasorelaxation and to evaluate basal NO release by the infusion of NG-nitro-L-arginine methyl ester (L-NAME) in an isolated and perfused rat kidney model. METHODS: To investigate this hypothesis, we have determined systemic and renal NO activity in Wistar rats treated with a hypertensive dose of rHuEpo (150 IU/kg b.w. every other day for 2 weeks) by measuring stable NO metabolites (NO2+NO3) in the urine and have also evaluated variations in renal vascular resistance after the injection of Ach, SNP and the infusion of L-NAME. RESULTS: Hematocrit, hemoglobin concentration and arterial blood pressure were significantly increased in the treated group as compared with the controls. Urinary excretion of NO2+NO3 was significantly higher in treated than in the controls (438+/-66 vs. 294+/-36 nM/ml/min, p<0.01, respectively). There were no significant differences in the dose-response curves to Ach and SNP between the two groups. The renal vasoconstriction following the infusion of L-NAME was also similar in the two groups. CONCLUSIONS: The analysis of our results seems to indicate that the endogenous NO system activity was enhanced in rHuEpo-induced hypertension in rats with normal renal function and a resistance to NO was not developed in renal circulation. Further studies seem to be necessary to better clarify the exact mechanisms underlying the development of rHuEpo-induced hypertension.
Assuntos
Eritropoetina/farmacologia , Hipertensão/fisiopatologia , Óxido Nítrico/fisiologia , Circulação Renal/fisiologia , Vasodilatação/fisiologia , Animais , Creatinina/sangue , Inibidores Enzimáticos/farmacologia , Humanos , Hipertensão/induzido quimicamente , Masculino , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/sangue , Óxido Nítrico/urina , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III , Nitroprussiato/farmacologia , Perfusão , Ratos , Ratos Wistar , Proteínas Recombinantes , Circulação Renal/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
Base-line serum levels of plasma C-reactive protein (CRP) are predictive of future myocardial infarction and sudden cardiac death in apparently healthy subjects, suggesting the hypothesis that chronic inflammation might be important in the pathogenesis of atherothrombosis. CRP production is mediated by several inflammatory mediators: interleukin 6 (IL-6) is currently felt to be the major cytokine influencing the acute phase response. CRP and other acute phase proteins are elevated in dialysis patients and cardiovascular diseases represent the single largest cause of mortality in chronic renal failure patients. Little information is available, however regarding CRP and IL-6 plasma levels in pre-dialysis renal failure. Plasma CRP was determined by a modification of the laser nephelometry technique; IL-6 by immunoassay (RD System); and fibrinogen, serum albumin, cholesterol, triglycerides, hematocrit, white blood cell count, erythrocytic sedimentation rate (ESR) and urinary protein levels by standard laboratory techniques. Results were obtained in 102 chronic pre-dialysis patients whose mean age was 53+/-5.8 years with a mean creatinine clearance (C(Cr)) of 52+/-37 mL/min). CRP was greater than 5 mg/L in 25% of the global population. CRP and IL-6 were 4.0+/-4.6 mg/L and 5.8+/-5.6 pg/mL, respectively and were not significantly correlated (r=0.11, p=n.s.). CRP and IL-6 were however related with renal function (CRP versus C(Cr) r=-0.40 p <0.001; IL- 6 versus C(Cr) r=-0.45; p <0.001). When patients were divided in two groups according to renal function, CRP resulted 7.4+/-6.3 mg/L in the group of patients with a C(Cr) lower than 20 mL/min (n=32) and 2.76+/-4.35 in the group of patients with a C(Cr) higher than 20 mL/min (n = 70) (p <0.0001). CRP and IL-6 were positively related with ESR (r=0.32 and 0.46 respectively). Serum albumin levels were not significantly different in the two groups of patients (3.2+/-0.4 versus 3.0+/-0.5 g/dL). CRP and serum albumin were not significantly related (r=0.17). CRP and IL-6 correlated positively with ESR (r=0.32 and 0.46 respectively). In pre-dialysis patients we have demonstrated an increase in both CRP and IL-6 that occurs as renal function decreases. These data provided evidence of the activation - even in the predialysis phase of renal failure - of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome.
Assuntos
Proteína C-Reativa/metabolismo , Falência Renal Crônica/sangue , Creatinina/sangue , Morte Súbita Cardíaca , Feminino , Humanos , Inflamação/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Valor Preditivo dos TestesRESUMO
Cardiovascular complications caused by an accelerated atherosclerotic disease represent the largest single cause of mortality in chronic renal failure patients. The rapidly developing atherosclerosis of the uremic syndrome appears to be caused by a synergism of different mechanisms, such as malnutrition, oxidative stress and genetic factors. Recent studies provide evidence that chronic inflammation plays an important role in the pathogenesis of cardiovascular diseases. Elevated serum levels of plasma C-reactive protein (CRP) are associated with an increased risk of experiencing myocardial infarction and sudden cardiac death in apparently healthy subjects. Several recently published papers have confirmed this strong association between CRP and the extent and severity of the atherosclerotic processes. In patients affected by predialytic renal failure, increased levels of CRP and interleukin (IL)-6 were recorded in 25% of our population; CRP and IL-6 were inversely related with renal function. These data suggest the activation - even in the predialytic phase of renal failure - of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome. In recent years we have investigated the hypothesis that the chronic inflammatory state of the uremic patient could at least in part be due to the dialytic technique. We provide evidence suggesting that the increase of CRP in stable dialytic patients may be due to the stimulation of monocyte/macrophage by backfiltration of dialysate contaminants.
Assuntos
Proteína C-Reativa/metabolismo , Inflamação/sangue , Uremia/metabolismo , Arteriosclerose/sangue , Arteriosclerose/etiologia , Biomarcadores/sangue , Doença Crônica , Hemodiafiltração/efeitos adversos , Humanos , Inflamação/etiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapiaRESUMO
BACKGROUND: Bacterial contamination of dialysate may enhance cytokine production in haemodialysis. We tested the hypothesis that intracellular cytokines could be enhanced in a large group of patients exposed to backfiltration of dialysate over a long period of observation. METHODS: The intracellular cytokine (interleukin-1 receptor antagonist and interleukin-1beta) concentrations in chronic uraemic patients undergoing haemodiafiltration, which is known to be associated with backfiltration (Group II, 12 patients), were compared to those found in patients treated with a modified haemodiafiltration modality without backfiltration (Group I, 16 patients), in patients shifted from one modality to the other (Group III, 27 patients) and in 10 patients on haemodialysis (Group IV) in a 1-year multicentre study. Group V comprised 10 healthy volunteers. All dialysis monitors were equipped with dialysate ultrafiltration systems. Dialysate contamination was studied by the LAL and the peripheral mononuclear cell/interleukin-1beta assays in the presence or absence of polymyxin B. RESULTS: Intracellular interleukin-1 receptor antagonist and interleukin-1beta both increased significantly (P < 0.002) but slowly (after 8 months) in Groups II vs I, and during the 4-month period in haemodiafiltration with backfiltration in Group III. The incidence of post/predialysis concentration ratio (over 1.5) increased two- to threefold in patients treated with haemodiafiltration with backfiltration with respect to haemodiafiltration without backfiltration. Results on the assays for LAL (< 0.5 E/ml) and interleukin-1beta (range 80.1-90.2 pg/5 x 10(6) cells; 70.2-81.3 pg/5 x 10(6) cells with polymyxin B) showed a moderate-to-low degree of dialysate contamination. CONCLUSIONS: Backfiltration of dialysate with moderate-to-low degree of contamination may enhance cytokine synthesis in the long term. Thus, the relevance for dialytic strategies aiming at improving dialysate quality and/or at reducing backfiltration is highlighted.
Assuntos
Citocinas/biossíntese , Hemodiafiltração/efeitos adversos , Adulto , Idoso , Citocinas/sangue , Bactérias Gram-Negativas/patogenicidade , Hemodiafiltração/métodos , Soluções para Hemodiálise/efeitos adversos , Humanos , Inflamação/etiologia , Inflamação/prevenção & controle , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/biossíntese , Interleucina-1/sangue , Pessoa de Meia-Idade , Pirogênios/toxicidade , Receptores de Interleucina-1/antagonistas & inibidores , Sialoglicoproteínas/biossíntese , Sialoglicoproteínas/sangue , Fatores de TempoRESUMO
BACKGROUND: The aim of this study was to investigate videodensitometric parameters of the myocardium, in dialysis patients, who represent a complex pathophysiological model of pressure volume overload, and in essential hypertensive patients with the same level of left ventricular mass. METHODS: We compared a group of male dialysis patients (D) with two groups: hypertensive patients (H) with comparable left ventricular mass and normotensive healthy subjects as controls (C). The groups (n=15 each) were age- (53 +/- 9 years) and gender-matched. Quantitative analysis of echocardiographic digitalized imaging was performed to calculate the mean grey level (MGL) and cyclic variation index (CVI). RESULTS: The haemodialysis patients had a significantly lower CVI compared with hypertensives and controls both for septum (D): -2.5 +/- 17.4% vs (H); 11.8 +/- 17% vs (C); 43.2 +/- 15.4% (P<0.001) and for posterior wall (D): -10.1 +/- 261% vs (H); 14.2 +/- 14.7% vs (C); 46.6 +/- 17.2% (P<0.001). A significant inverse relationship was found between intact parathyroid hormone (iPTH) and CVI. CONCLUSION: Abnormalities of two-dimensional echocardiographic grey level distribution are present in both haemodialysis patients and hypertensive patients, but seem unrelated to the degree of echocardiographic hypertrophy. These videodensitometric myocardial alterations are significantly higher in dialysis patients than in hypertensive patients with the same extent of left ventricular hypertrophy. The iPTH level may play a role in the development of the ultrasonic myocardial alterations, which probably represent an early stage of uraemic cardiomyopathy.