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BACKGROUND: Lymphopaenia is commonly observed in autoimmune diseases, where it has been associated with disease activity or prognosis. However, in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) only a few small-scale studies have been targeted towards this issue. Research has not yet focused on AAV with renal involvement (AAV-RI). Thus the aim of this study was to analyse the association between lymphocyte counts and outcomes in a large cohort of AAV-RI patients. METHODS: We used the Maine-Anjou AAV registry that retrospectively gathers data on consecutive patients affected by AAV in four French nephrology centres, recorded since January 2000. We analysed clinical, biological and histological data at diagnosis of AAV-RI. Risk factors for end-stage kidney disease (ESKD) were analysed. Event-free survival was also assessed. RESULTS: Among the 145 patients included in the study, those with lymphopaenia at diagnosis had a lower renal function at baseline [estimated glomerular filtration rate (eGFR) 13 versus 26 mL/min; P = 0.002] and were more likely to require kidney replacement therapy (51% versus 25%; P = 0.003). Lymphopaenia was correlated with histological lesions and especially with the percentage of sclerotic glomeruli (P = 0.0027). ESKD-free survival was lower in lymphopaenic patients (P < 0.0001). In multivariate Cox analysis, lymphopaenia was an independent risk factor for ESKD [hazard ratio 4.47 (95% confidence interval 2.06-9.72), P < 0.001]. CONCLUSIONS: Lymphopaenia correlates with the severity of AAV glomerulonephritis at diagnosis and predicts poor renal outcome. In this view, lymphopaenia could be used as a simple and cost-effective biomarker to assess renal prognosis at AAV-RI diagnosis.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Falência Renal Crônica , Linfopenia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/análise , Humanos , Rim/patologia , Rim/fisiologia , Falência Renal Crônica/complicações , Linfopenia/diagnóstico , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: Therapeutic plasma exchange (TPE) can be proposed in the treatment of chronic dysimmune peripheral neuropathies (CDPN). Actual guidelines are however based on few studies, and indications and protocols still remain to be clarified. We conducted a 10-year retrospective study in order to assess the effectiveness and tolerance of TPE in CDPN. METHODS: All patients treated for CDPN with TPE from October 2006 to March 2016 in the university hospital of Angers were included. Patients were considered responders when they presented a clinical improvement substantial enough to continue the treatment. The Hughes functional grading score was also determined for each patient before and after TPE initiation. RESULTS: Among the 206 patients who received TPE during the study period, 30 (14.6%) met the diagnostic criteria of CDPN. Four of the five paraprotein neuropathies (PPN) patients (80%) and 8 of the 11 chronic inflammatory demyelinating polyneuropathies (CIDP) patients (72.7%) were responders, with a significant improvement of the Hughes score for the latter (P = 0.013). None of the three Lewis-Sumner and the two POEMS patients showed substantial improvement. Six of the nine anti-MAG neuropathy patients (66.7%) responded to treatment, with a trend towards improvement of the Hughes score (P = 0.072). CONCLUSION: TPE appears to be effective in CIDP and PPN, and ineffective in Lewis-Sumner and POEMS syndromes. Interestingly, anti-MAG neuropathy patients showed a good rate of response to TPE. Regarding these preliminary results, a randomized trial would be very worthwhile in this disease for which there is no evidence based treatment to date.
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Troca Plasmática/métodos , Polineuropatias/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome POEMS/terapia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a devastating form of renal thrombotic microangiopathy. Despite plasma exchange, the standard treatment of aHUS for decades, the renal prognosis for patients with aHUS has remained poor. We assessed the off-trial use of eculizumab in adult patients with aHUS affecting the native kidneys. STUDY DESIGN: A retrospective study was conducted. aHUS was defined as the presence of 3 or more of the following: acute kidney injury (serum creatinine >1.4 mg/dL [120 µmol/L]), mechanical hemolytic anemia, thrombocytopenia, and the presence of thrombotic microangiopathy features in a kidney biopsy specimen. Patients who had received 4 or more weekly 900-mg infusions of eculizumab were included. SETTING & PARTICIPANTS: 19 patients were identified through a query sent to all French nephrology centers. OUTCOMES & MEASUREMENTS: Evolution of kidney function, hemolysis, and thrombocytopenia after the initiation of eculizumab therapy. RESULTS: All patients had acute kidney injury (serum creatinine range, 2.2-17.0 mg/dL) and 12 required hemodialysis. Thirteen patients carried a mutation in 1 complement gene and 1 had anti-factor H antibodies. For first-line therapy, 16 patients underwent plasma exchange and 3 patients received eculizumab. Median time between aHUS onset and eculizumab therapy initiation was 6 (range, 1-60) days and median time to platelet count normalization after eculizumab therapy initiation was 6 (range, 2-42) days. At the 3-month follow-up, 4 patients still required dialysis, 8 had non-dialysis-dependent chronic kidney disease, and 7 had normalized kidney function. At last follow-up (range, 4-22 months), 3 patients remained dialysis dependent, 7 had non-dialysis-dependent chronic kidney disease (estimated glomerular filtration rate, 17-55 mL/min/1.73 m(2)), and 9 had normal kidney function. Risks of reaching end-stage renal disease within 3 months and 1 year of aHUS onset were reduced by half in eculizumab-treated patients compared with recent historical controls. LIMITATIONS: Retrospective study and use of historical controls. CONCLUSIONS: Our data indicate that eculizumab improves kidney disease outcome in patients with aHUS.
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Injúria Renal Aguda , Anticorpos Monoclonais Humanizados , Síndrome Hemolítico-Urêmica , Falência Renal Crônica , Rim , Injúria Renal Aguda/patologia , Injúria Renal Aguda/fisiopatologia , Adulto , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Síndrome Hemolítico-Urêmica Atípica , Biópsia/métodos , Biópsia/estatística & dados numéricos , Creatinina/sangue , Monitoramento de Medicamentos/métodos , Feminino , França , Síndrome Hemolítico-Urêmica/complicações , Síndrome Hemolítico-Urêmica/diagnóstico , Síndrome Hemolítico-Urêmica/tratamento farmacológico , Síndrome Hemolítico-Urêmica/epidemiologia , Síndrome Hemolítico-Urêmica/fisiopatologia , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Rim/patologia , Rim/fisiopatologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Testes de Função Renal/métodos , Masculino , Contagem de Plaquetas/métodos , Diálise Renal/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Adult Henoch-Schönlein purpura (HSP) has been associated with poor outcome and end-stage renal disease in >20% of cases. Although the benefit of adding another immunosuppressant to steroids in severe adult HSP has not been shown, the benefit of plasma exchange (PE) therapy has been poorly evaluated. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 11 consecutive patients with severe and newly diagnosed HSP since 1988 who were treated with steroids and PE. OUTCOME & MEASUREMENT: Patients' characteristics and outcome were analyzed. Birmingham Vasculitis Activity Score (BVAS), estimated glomerular filtration rate (eGFR), and proteinuria were measured at baseline, at the end of PE treatment, at months 6 and 12, and at the last visit. Side effects of corticoid treatment and PE were recorded. RESULTS: 11 patients were identified in 1988-2010. Patients received intravenous corticoid pulses in 64% of cases, followed by oral prednisone for a median of 6.6 months. They received a median of 12 PE sessions. BVAS, eGFR, and proteinuria improved significantly between baseline and the last PE at a median of 2 months. PE sessions were well tolerated, except in one patient who developed central catheter-associated septicemia. One patient required dialysis therapy 15 days after HSP diagnosis and did not recover kidney function. At the last medical evaluation at a mean follow-up of 6 years, median eGFR and proteinuria were 83 ± 22 mL/min/1.73 m(2) and protein excretion of 140 ± 10 mg/d, respectively. 3 women had pregnancy without complications. LIMITATIONS: This case series did not have a control group. CONCLUSIONS: The combination of PE and corticoid therapy in severe forms of HSP was associated with fast improvement and good long-term outcome.
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Glucocorticoides/uso terapêutico , Vasculite por IgA/terapia , Troca Plasmática , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Humanos , Vasculite por IgA/fisiopatologia , Masculino , Pessoa de Meia-Idade , Proteinúria/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Introduction: The "Renal Risk Score" (RRS) and the histopathological classification have been proposed to predict the risk of end-stage kidney disease (ESKD) in ANCA-associated glomerulonephritis (ANCA-GN). Besides, factors associated with kidney function recovery after ANCA-GN onset remain to be more extensively studied. In the present study, we analyzed the value of the RRS and of the histopathological classification for ESKD prediction. Next, we analyzed factors associated with eGFR change within the first 2 years following ANCA-GN diagnosis. Materials and Methods: We included patients from the Maine-Anjou ANCA-associated vasculitis registry with at least 6 months of follow-up. The values of ANCA-GN, histopathological classification, and RRS, and the factors associated with eGFR variations between ANCA-GN diagnosis and 2 years of follow-up were assessed. Results: The predictive values of the histopathological classification and RRS were analyzed in 123 patients. After a median follow-up of 42 months, 33.3% patients developed ESKD. The predictive value of RRS for ESKD was greater than that of the histopathological classification. Determinants of eGFR variation were assessed in 80/123 patients with complete eGFR measurement. The median eGFR increased from ANCA-GN diagnosis to month 6 and stabilized thereafter. The only factor associated with eGFR variation in our study was eGFR at ANCA-GN diagnosis, with higher eGFR at diagnosis being associated with eGFR loss (p<0.001). Conclusion: The RRS has a better predictive value for ESKD than the histopathological classification. The main determinant of eGFR variation at 2 years was eGFR at ANCA-GN diagnosis. Thus, this study suggests that eGFR recovery is poorly predicted by histological damage at ANCA-GN diagnosis.
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Glomerulonefrite , Falência Renal Crônica , Anticorpos Anticitoplasma de Neutrófilos/análise , Biópsia , Glomerulonefrite/patologia , Humanos , Rim/patologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Falência Renal Crônica/patologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
Background: Thrombotic microangiopathies (TMAs) are highly suspected in patients showing mechanical hemolytic anemia, thrombocytopenia, and haptoglobin consumption. Primary [thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome] and secondary TMA are considered. Even if ADAMTS13 measurements and alternative complement pathway explorations have greatly improved the ability to identify primary TMA, their diagnosis remains difficult, and their frequency relative to that of secondary TMA is undetermined. The objectives of the present study were, therefore, to describe the etiologies, management, and the outcomes of patients presenting with TMA in real-life clinical practice. Methods: We conducted a retrospective study between 01/01/2008 and 31/12/2018 that included all consecutive patients presenting with biological TMA syndrome at admission or developing during hospitalization. Patients were identified from the laboratory databases, and their medical files were reviewed to confirm TMA diagnosis, to determine etiology, and to analyze their therapeutic management and outcomes. Results: During this period, 239 patients with a full TMA biological syndrome were identified, and the TMA diagnosis was finally confirmed in 216 (90.4%) after the cases were reviewed. Primary TMAs (thrombotic thrombocytopenic purpura or atypical hemolytic uremic syndrome) were diagnosed in 20 of 216 patients (9.3%). Typical HUS was diagnosed in eight patients (3.7%), and the most frequent secondary TMAs were HELLP syndrome (79/216, 36.6%) and active malignancies (30/219, 13.9%). ADAMTS13 measurements and alternative complement pathway analyses were performed in a minority of patients. Multiple factors identified as TMA triggers were present in most patients, in 55% of patients with primary TMA, vs. 44.7% of patients with secondary TMA (p = 0.377). Death occurred in 57 patients (23.4%) during follow-up, and dialysis was required in 51 patients (23.6%). Active malignancies [odds ratio (OR) 13.7], transplantation (OR 4.43), male sex (OR 2.89), and older age (OR 1.07) were significantly associated with death. Conclusion: Secondary TMAs represent many TMA causes in patients presenting a full TMA biological syndrome during routine clinical practice. Multiple factors favoring TMA are present in about half of primary or secondary TMA. ADAMTS13 and complement pathway were poorly explored in our cohort. The risk of death is particularly high in patients with malignancies as compared with patients with other TMA.
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PURPOSE: Data regarding the long-term outcome of very elderly (VE) patients undergoing renal biopsy (RB) are lacking. The objective of this study was to analyse the outcome of VE patients undergoing RB. METHODS: All patients over 65 years that underwent native RB between 2004 and 2016 in our center were included. Among the 206 included patients, those over 80 years (VE, 46 patients) were analysed and compared to those aged 65-80 years (160 patients). The outcomes of the VE group were analysed. RESULTS: Baseline characteristics, renal presentation, safety of RB and RB-related diagnosis were not different between VE patients and 65-80-year-old patients. Survival of VE patients was 73.1, 50.6 and 21.8% at 2, 4 and 6 years after RB, significantly poorer than those of 65-80-year-old group. Early death (< 1 year) occurred in 10 VE patients, was associated with a higher proteinuria-to-creatininuria ratio and tended to be associated with a more frequent dialysis need at RB. Of the 46 VE patients, 31 (67.4%) were diagnosed with a potentially reversible kidney disease, of whom 17 (40%) were started on immunosuppressive regimens. Survival of patients with a reversible kidney disease tended to be better than those with other diseases. CONCLUSION: RB appears as a safe and valuable procedure to assess diagnosis of kidney disease in VE patients. Our data suggest that RB is critical for the identification and treatment decision of patients with potentially reversible diseases and may translate in clinical improvement.
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Biópsia , Nefropatias/diagnóstico , Rim/patologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Creatinina/urina , Feminino , Humanos , Imunossupressores/uso terapêutico , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Masculino , Proteinúria/urina , Diálise Renal , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
(1) Introduction: The incidence of venous thromboembolisms (VTE) has not been extensively analyzed in patients with antineutrophil cytoplasmic antibody (ANCA)-glomerulonephritis (ANCA-GN). Thus, the aim of the present study was to assess the frequency and the risk factors of VTE in patients with ANCA-GN. (2) Methods: Patients from the Maine-Anjou ANCA-associated vasculitis (AAV) registry with a biopsy showing pauci-immune glomerulonephritis were included. VTE events, site, and interval from AAV diagnosis were analyzed. (3) Results: 133 patients fulfilled the inclusion criteria of the study and were analyzed. VTE episodes were diagnosed in 23/133 (17.3%) patients at a median delay of 3 months from ANCA-GN diagnosis. Patients with VTE had lower serum albumin (p = 0.040), were less frequently on statin therapy (p = 0.009) and had less frequently proteinase-3 (PR3)-ANCAs (p = 0.078). Univariate analysis identified higher age (p = 0.022), lower serum albumin (p = 0.030), lack of statin therapy (p = 0.009), and rituximab treatment (p = 0.018) as significant risk factors of VTE. In multivariate analysis, only lack of statin therapy (HR 4.873; p = 0.042) was significantly associated with VTE. (4) Conclusion: Patients with ANCA-GN are at high risk of VTE, especially within the first months following AAV diagnosis. Our results suggest that statin therapy is associated with a lower risk of VTE in ANCA-GN patients.
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BACKGROUND: Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. METHODS: Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. RESULTS: Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of > 4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. CONCLUSIONS: Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.
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Glomerulonefrite por IGA/microbiologia , Glomerulonefrite por IGA/patologia , Infecções Estafilocócicas/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/complicações , Criança , Pré-Escolar , Feminino , França , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) is a rare and severe drug-induced hypersensitivity syndrome characterized by haematological abnormalities (hypereosinophilia and/or mononucleosis) and multiorgan involvement. Renal failure has been rarely described. We report the case of a 77-year-old female with sulphasalazine-induced DRESS syndrome who improved rapidly on corticosteroid treatment. After prednisone withdrawal, the patient developed renal failure that necessitated a session of haemodialysis. A kidney biopsy showed acute tubulointerstitial nephritis with an intense lymphocytic infiltrate and tubular necrosis. Kidney function normalized after a further 2 weeks of corticosteroid treatment. This is the first histologically proven case of acute tubulointerstitial nephritis in the setting of sulphasalazine-induced DRESS syndrome.
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Anti-Inflamatórios não Esteroides/efeitos adversos , Toxidermias/etiologia , Eosinofilia/induzido quimicamente , Nefrite Intersticial/induzido quimicamente , Sulfassalazina/efeitos adversos , Doença Aguda , Corticosteroides/uso terapêutico , Idoso , Toxidermias/tratamento farmacológico , Toxidermias/patologia , Eosinofilia/tratamento farmacológico , Feminino , Herpesvirus Humano 6 , Humanos , Nefrite Intersticial/tratamento farmacológico , Nefrite Intersticial/patologia , Prednisona/uso terapêutico , Infecções por Roseolovirus/complicações , Síndrome , Fatores de TempoRESUMO
UNLABELLED: This study was carried out to evaluate dialysis initiation of failed transplant patient and the short-term outcome of these patients on dialysis. PATIENTS AND METHOD: We conducted a retrospective study of transplanted patients from one centre returning in dialysis after allograft failure. Those patients were transplanted between 31st October 1986 and 3rd March 2004. Patients who experienced allograft failure after 6 months on transplantation were included in the study. RESULTS: Among 600 transplanted patients, 92 patients restarted dialysis after allograft failure. Of the 92 failed transplant patients, 69 had a graft survival of more than 6 months. The mean glomerular filtration rate at dialysis initiation was 13+/-5mL per minute. At time of dialysis initiation, patients had mean haemoglobin level at 80.7+/-10.7g/L, and mean serum albumin level at 34+/-6g/L. Urgent dialysis was needed for 39 over 57 patients. Fourteen over 58 patients had no vascular access or peritoneal catheter at dialysis initiation. Fifty-six over 69 patients were treated by haemodialysis. Of the 13 patients treated by peritoneal dialysis 7 were on PD before transplantation whereas 49 over 57 haemodialysis patients were treated by haemodialysis before transplant failure (p<0.05). Immunosuppressive therapy was stopped during the first year following transplantation failure in 52 over 69 patients and 36 over 69 patients underwent transplantectomy. Thirteen over 56 patients presented a least one cardiovascular events after transplantation failure. CONCLUSION: Unplanned dialysis initiation is frequent in failed transplant patients, in whom an early dialysis start is probably mandatory.
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Transplante de Rim , Diálise Renal , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Falha de Tratamento , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: The overlap between antineutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (ANCA-GN) and connective tissue diseases (CTD) has been reported mainly as case series in the literature. Frequency of this association, as well as presentation and outcomes are unknown. MATERIALS AND METHODS: Patients from the Maine-Anjou ANCA-associated vasculitides (AAV) registry with ANCA-GN diagnosed between 01/01/2000 and 01/01/2018, ANCA positivity, and at least six months of follow-up, were included. RESULTS: 106 out of 142 patients fulfilled the inclusion criteria and were analyzed. CTD was present at ANCA-GN diagnosis in 16 (15.1%) patients. The most common CTD were rheumatoid arthritis, Sjogren syndrome and systemic sclerosis. Compared to the control group, females were more represented in the CTD group (75%, p = 0.001). Renal presentation was comparable between groups, including the pathological analysis of renal biopsies. Patients of CTD group presented a higher rate of non-renal relapse (25% versus 7.7%, p = 0.037), and experienced more frequently a venous thrombotic event (31.2% versus 10%, p = 0.021). No difference between groups was observed according to major outcomes. CONCLUSION: Association between CTD and ANCA-GN is not a rare condition and predominantly affects females. While AAV presentation is not significantly different, CTD patients experience more frequently non-renal relapse and venous thrombotic events.
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The glucose side-effects, the main osmotic agent in conventional peritoneal dialysis (PD) solutions, are structural and functional changes of the peritoneal membrane, especially diabetic alterations in the microvasculature. Therefore, hyperpermeability with high small solutes transport and less ultrafiltration necessitates more and more high glucose concentration solutions. Glucose degradation products (PDF) and advanced glycation end-products (AGE) are formed and may induce peritoneal membrane alterations. More biocompatible solutions have to be used with less PDF and physiological pH. Icodextrin containing PD solutions have beneficial effect on sustained ultrafiltration for long dwells in PD, limitating fluid overload common in PD patients above all during peritonitis episodes. Amino acid-based PD solutions contribute to the prevention of malnutrition often observed in the diabetic PD population.
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Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/terapia , Soluções para Diálise , Diálise Peritoneal , Humanos , Diálise Peritoneal/métodosAssuntos
Dor Abdominal/etiologia , Injúria Renal Aguda/etiologia , Ascite/diagnóstico por imagem , Edema/diagnóstico por imagem , Jejuno/patologia , Lúpus Eritematoso Sistêmico/complicações , Metilprednisolona/administração & dosagem , Ácido Micofenólico/administração & dosagem , Prednisona/administração & dosagem , Abdome/diagnóstico por imagem , Dor Abdominal/diagnóstico por imagem , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/imunologia , Administração Intravenosa , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Ascite/etiologia , Astenia/etiologia , Meios de Contraste , Creatinina/sangue , Progressão da Doença , Edema/complicações , Edema/etiologia , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Jejuno/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Metilprednisolona/uso terapêutico , Ácido Micofenólico/uso terapêutico , Prednisona/uso terapêutico , Tomografia Computadorizada por Raios X , Ultrassonografia , Vômito/etiologiaRESUMO
Angiotensin II is a potent growth factor involved in arterial wall homeostasis. In resistance arteries, chronic increases in blood flow induce a rise in diameter associated with arterial wall hypertrophy. Nevertheless, the role of angiotensin II in this remodeling is unknown. We investigated the effect of blocking angiotensin II production or receptor activation on flow-induced remodeling of mesenteric resistance arteries. Arteries were ligated in vivo to generate high-flow arteries compared with normal flow (control) vessels located at a distance. Arteries were isolated after 1 week for in vitro analysis. Arterial diameter, media surface, endothelial NO synthase expression, superoxide production, and extracellular signal-regulated kinase 1/2 phosphorylation were higher in high-flow than in control arteries. Angiotensin-converting enzyme inhibition (perindopril) and angiotensin II type 1 receptor blockade (candesartan) prevented arterial wall hypertrophy without affecting diameter enlargement. The nonselective vasodilator hydralazine had no effect on remodeling. Although perindopril and candesartan increased endothelial NO synthase expression in high-flow arteries, hypertrophy remained in rats treated with N(G)-nitro-l-arginine methyl ester and mice lacking endothelial NO synthase. Perindopril and candesartan reduced oxidative stress in high-flow arteries, but superoxide scavenging did not prevent hypertrophy. Both Tempol and the absence of endothelial NO synthase prevented the rise in diameter in high-flow vessels. Extracellular signal-regulated kinase 1/2 activation in high-flow arteries was prevented by perindopril and candesartan and not by hydralazine. Extracellular signal-regulated kinase 1/2 inhibition in vivo (U0126) prevented hypertrophy in high-flow arteries. Thus, a chronic rise in blood flow in resistance arteries induces a diameter enlargement involving NO and superoxide, whereas hypertrophy was associated with extracellular signal-regulated kinase 1/2 activation by angiotensin II.
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Angiotensina II/fisiologia , Artérias Mesentéricas/fisiopatologia , Resistência Vascular/fisiologia , Angiotensina II/metabolismo , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Antioxidantes/farmacologia , Benzimidazóis/farmacologia , Compostos de Bifenilo , Velocidade do Fluxo Sanguíneo , Western Blotting , Butadienos/farmacologia , Óxidos N-Cíclicos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hidralazina/farmacologia , Masculino , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/patologia , Camundongos , Camundongos Knockout , Microscopia Confocal , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Nitrilas/farmacologia , Perindopril/farmacologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Marcadores de Spin , Tetrazóis/farmacologia , Resistência Vascular/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
Blood flow reduction induces inward remodeling of resistance arteries (RAs). This remodeling occurs in ischemic diseases, diabetes and hypertension. Nonetheless, the effect of flow reduction per se, independent of the effect of pressure or metabolic influences, is not well understood in RA. As angiotensin II is involved in the response to flow in RA, we hypothesized that angiotensin II may also be involved in the remodeling induced by a chronic flow reduction. We analyzed the effect of angiotensin I-converting enzyme inhibition (perindopril) and angiotensin II type 1 receptor blockade (candesartan) on inward remodeling induced by blood flow reduction in vivo in rat mesenteric RAs (low flow (LF) arteries). After 1 week, diameter reduction in LF arteries was associated with reduced endothelium-dependent relaxation and lower levels of eNOS expression. Superoxide production and extracellular signal-regulated kinases 1/2 (ERK1/2 phosphorylation were higher in LF than in normal flow arteries. Nevertheless, the absence of eNOS or superoxide level reduction (tempol or apocynin) did not prevent LF remodeling. Perindopril and candesartan prevented inward remodeling in LF arteries. Contractility to angiotensin II was reduced in LF vessels by perindopril, candesartan and the ERK1/2 blocker PD98059. ERK1/2 activation (ratio phospho-ERK/ERK) was higher in LF arteries, and this activation was prevented by perindopril and candesartan. ERK1/2 inhibition in vivo (U0126) prevented LF-induced diameter reduction. Thus, inward remodeling because of blood flow reduction in mesenteric RA depends on unopposed angiotensin II-induced contraction and ERK1/2 activation, independent of superoxide production. These findings might be of importance in the treatment of vascular disorders.