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1.
Eur J Pediatr ; 177(11): 1667-1674, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30094644

RESUMO

Shigatoxin Escherichia coli-related hemolytic uremic syndrome (eHUS) is a severe thrombotic microangiopathy (TMA) burdened by life-threatening complications and long-term sequelae. Since hemoconcentration is associated with worse outcome, we tried to develop a reliable and easy-to-calculate index for predicting complications and sequelae based on hemoglobin (Hb) at presentation. The first laboratory examinations with signs of TMA in eHUS patients were analyzed in relation to the outcomes with the receiver operating characteristic curves and their areas under the curve (AUC) for Hb and creatinine (sCr). A total of 197 eHUS patients were identified of whom 24% did not have anemia at presentation. Hb level was the best predictor of a poor outcome (AUC 0.67) but the combination of Hb with sCr, in the formula [(Hb in g/dL + (sCr in mg/dL × 2)], showed an even better AUC of 0.75. The described scoring system was also strongly associated and predictive of all complications and health care needs (8% of patients with scoring > 13 died or entered a permanent vegetative state compared with 0% of those with ≤ 13).Conclusion: The presented score is a simple and early predictor of both short- and long-term outcomes and identifies patients who should undergo rapid volume expansion to counteract hemoconcentration, the spreading of microvascular thrombosis, and the consequent increased organ damage. What is Known: • In eHUS, hemoconcentration is associated with worse short- and long-term outcome. • A prognostic index to identify patients at higher risk for complications at presentation is not available. What is New: • We developed a simple and early prognostic index for eHUS outcome with the combination of Hb and sCr at onset, in the following formula [(Hb in g/dL + (sCr in mg/dL × 2)]. • The proposed HUS Severity Score can promptly identify patients with good outcome and those with high risk of worse short- and long-term outcome.


Assuntos
Infecções por Escherichia coli/complicações , Síndrome Hemolítico-Urêmica/diagnóstico , Toxina Shiga/efeitos adversos , Área Sob a Curva , Criança , Pré-Escolar , Creatinina/sangue , Feminino , Hemoglobinas/análise , Síndrome Hemolítico-Urêmica/complicações , Síndrome Hemolítico-Urêmica/etiologia , Humanos , Lactente , Masculino , Prognóstico , Curva ROC , Índice de Gravidade de Doença , Escherichia coli Shiga Toxigênica
2.
Nephrol Dial Transplant ; 32(10): 1691-1696, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27387472

RESUMO

BACKGROUND: The optimal dosing and the efficacy of rituximab for primary membranous nephropathy (PMN) has not been established. This multicentric prospective study evaluates the efficacy and safety of low-dose rituximab (RTX) therapy in patients with PMN in clinical practice. METHODS: Thirty-four consecutive patients with PMN and nephrotic syndrome were included and received RTX (375 mg/m2) once (18 patients) or twice (16 patients). RTX was the first-line therapy for 19 (56%) and the second line for 15 (44%) patients. All patients were followed for 12 months after RTX and 24 for at least 18 months (mean 23.9 ± 18.6 months). RESULTS: At 12 months, 5 patients (14.7%) achieved complete response, 10 (29.4%) partial and 19 (55.8%) no response. Response occurred ∼6 months after RTX. At 24 months, the clinical situation was unchanged: two non-responders achieved partial response and two responders relapsed. Responders had significantly higher baseline GFR and lower anti-PLA2R antibodies compared with non-responders. Outcome was similar between one or two doses of RTX (non-responders 55.5 versus 56%, respectively) and between patients who had received previous therapy versus those receiving RTX as first-line therapy (non-responders 40 versus 68%, respectively). In the 15 patients already treated, the response to RTX was comparable to that of previous therapies. CONCLUSION: Low-dose RTX obtains remission in <50% of PMN patients. Probably, higher doses and longer treatments are needed to induce and maintain a response. The balance between the costs and benefits should guide the selection of the patient and the optimal dosage.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Síndrome Nefrótica/tratamento farmacológico , Rituximab/uso terapêutico , Adulto , Idoso , Biomarcadores/sangue , Feminino , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/sangue , Síndrome Nefrótica/patologia , Estudos Prospectivos , Receptores da Fosfolipase A2/sangue , Indução de Remissão , Resultado do Tratamento , Adulto Jovem
4.
Blood Purif ; 40 Suppl 1: 24-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26344510

RESUMO

BACKGROUND: Standard low-flux haemodialysis (HD) is not very efficacious, and patient morbidity and mortality rates are still very high. According to the initial study design, the MPO study reported that high-flux HD (hf-HD) showed a significant 37% relative risk reduction of mortality in patients with serum albumin ≤4 g/dl; online haemodiafiltration (HDF) is considered the most efficient technique of using high-flux membranes, as clearances of small solutes, like urea, are higher than in haemofiltration and clearances of middle solutes, like ß2-microglobulin, are higher than in hf-HD. SUMMARY: Three randomized trials have recently been published analysing the effect of online HDF on mortality. Two trials were unable to demonstrate a positive effect of HDF on survival, while 1 showed a significantly better survival in patients randomized to HDF in comparison to those randomized to hf-HD. It is intriguing that post hoc analyses of these 3 studies showed that the patients randomized to online HDF who received the highest convection volumes had a lower risk of mortality and cardiovascular events than those randomized to HD. Four very recently published meta-analyses have shown inconsistent results concerning the effect of convective treatments in improving patient general and cardiovascular survival, while they have consistently shown a significant reduction of the intradialytic symptomatic hypotension in patients treated with convective techniques in comparison with those treated with prevalent diffusive ones. Key Messages: The results of the randomized trials on the effect of HDF in improving patient survival are inconclusive. Moreover, trials specifically designed for testing the effect of increased convection of online HDF on patient survival and morbidity in comparison to patients treated with hf-HD are still awaited.


Assuntos
Soluções para Diálise/uso terapêutico , Hemodiafiltração/métodos , Falência Renal Crônica/terapia , Idoso , Velocidade do Fluxo Sanguíneo , Feminino , Hemodiafiltração/instrumentação , Hemodiafiltração/mortalidade , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/mortalidade , Falência Renal Crônica/patologia , Masculino , Membranas Artificiais , Ensaios Clínicos Controlados Aleatórios como Assunto , Reologia , Fatores de Risco , Análise de Sobrevida , Ureia/sangue , Microglobulina beta-2/sangue
5.
Clin Transplant ; 28(3): 368-76, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24757721

RESUMO

Twenty-yr patient and death-censored graft survival of 348 kidney transplant recipients with primary glomerulonephritis (GN) and of 696 matched controls were 82.2% in GN patients and 75% in controls (p = 0.037) and 49.5% and 54%, respectively (p = 0.013). GN patients had a higher incidence of graft failure than controls even considering death as a competing risk (p = 0.004). In the GN group, graft survival of deceased and of living donor recipients was similar. At multivariate analysis, GN as primary disease (RR: 1.47), delayed graft function recovery (RR: 2.34), acute rejection (RR: 2.36), and any PRA positivity (RR: 1.01) were predictive of graft loss. GN recurred in 85 of 348 grafts (24.4%), and 43 were lost for recurrence. In non-recurrent patients, graft survival at 20 yr was significantly better than in recurrent patients (59.4% vs. 24.4%, p = 0.000), but not different from that of controls (59.4 vs. 54%, p = 0.9). At multivariate analysis, young age at transplantation (RR: 0.97), shorter duration of dialysis (RR: 1.05 per each dialysis year), and graft from living donors (RR: 1.668) were independent predictors of recurrence. Patients with primary GN have reduced graft survival in comparison with controls, and this is mainly due to recurrence of original disease. However, the most frequent recurrence in living recipients does not compromise graft survival.


Assuntos
Glomerulonefrite/complicações , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto/fisiologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Adulto , Aloenxertos , Estudos de Casos e Controles , Feminino , Seguimentos , Taxa de Filtração Glomerular , Glomerulonefrite/cirurgia , Rejeição de Enxerto/etiologia , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Prognóstico , Recidiva , Diálise Renal , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
6.
Nephrol Dial Transplant ; 28(5): 1305-14, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23229925

RESUMO

BACKGROUND: Few data are available on allograft survival at 15 years, the impact and the predictors of recurrence of the original disease in renal transplanted patients with IgA nephropathy (IgAN). METHODS: In this retrospective study, we compared the long-term outcome of renal transplant in 190 patients with IgAN with that of 380 non-diabetic controls and evaluated the impact of recurrence of IgAN on the graft outcome. RESULTS: At 15 years, the patient survival was 88.3% in IgAN patients and 82.6% in controls (P = 0.12), while the death-censored graft survival was 62.6 and 72.4%, respectively (P = 0.038). IgAN had a higher cumulative incidence of graft failures in comparison with controls even considering death as a competing risk (P = 0.025). At multivariate analysis, IgAN [relative risk (RR) = 1.468, P = 0.026], delayed graft function recovery (RR = 2.394, P = 0.000) and acute rejection (RR = 2.51, P = 0.000) were predictive of graft loss. IgAN recurred in 42 grafts (22.1%), of them, 12 were lost for recurrence and in another 6 recurrence was considered a concomitant cause of graft loss. The 15-year death censored graft survival was 68.3% in non-recurrent and 51.2% in recurrent patients (P = 0.069). Pure graft survival of non-recurrent IgAN patients was similar to that of controls (P = 0.406). At Cox analysis, the recurrence of IgAN significantly reduced from 1981 to 2010 (P = 0.0065, RR = 0.936). CONCLUSIONS: IgAN emerged as an independent predictor of worse graft outcome in the long-term. Recurrence of IgAN seems to progressively reduce in transplants performed from 1981 to 2010.


Assuntos
Glomerulonefrite por IGA/complicações , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/efeitos adversos , Adulto , Estudos de Casos e Controles , Feminino , Seguimentos , Glomerulonefrite por IGA/mortalidade , Glomerulonefrite por IGA/terapia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo
7.
Clin Exp Rheumatol ; 31(4 Suppl 78): S75-81, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24129143

RESUMO

OBJECTIVES: Whether and when is it possible to completely stop immunosuppression in patients with lupus nephritis is still poorly defined. METHODS: An attempt to slowly and progressively eliminate steroids and immunosuppressive drugs was tried in 73 of 161 (45.3%) patients with lupus nephritis who achieved a stable clinical remission defined as normal serum creatinine, proteinuria <0.5g/24h, inactive urine sediment, and no clinical signs of extra-renal activity of SLE for at least 12 months. RESULTS: Twenty-one out of the 73 patients (28.7%) who met the criteria for withdrawal of treatment developed flares during the phase of progressive reduction of therapy and their treatment was reinforced. Twenty patients entered remission again; the last patient was lost to follow-up at achievement of partial remission. In the other 52 of the 73 patients (71.2%), it was possible to completely withdraw treatment. Of these, 32 patients (group A) did not resume therapy for the subsequent follow-up (median 101.8 months); the other 20 patients (group B) had at least one flare, in median 37 months after withdrawing therapy, and had to be retreated. At the last observation, after a median follow-up of 286 months, 10 of these 20 patients were off therapy. At the last observation, two patients in group A and two in group B had died, no patient of group A and two of group B had developed renal insufficiency (serum creatinine 2.5 and 3 mg/dl, respectively). Compared to patients in group B, group A patients received longer treatment (98.1 vs. 31.0 months; p=0.01), had longer remission (52.8 vs. 12.0 months; p=0.000) before withdrawal of therapy, and continued chloroquine after stopping therapy (52% vs. 10%; p=0.004). In comparison to patients who never stopped therapy, patients who were able to interrupt treatment had lower risk of chronic renal insufficiency (3.8% vs. 28.4%; p=0.000), end-stage renal disease (0 vs. 12.8%; p=0.01), arterial hypertension (32.7% vs. 66.9%; p=0.000) and cardiovascular events (11.5% vs. 27.5%; p=0.04). CONCLUSIONS: Complete withdrawal of therapy is feasible in selected patients who achieved stable remission after long-term treatment. The reduction of treatment must be done in a very gradual manner, progressively and under strict medical surveillance. The withdrawal of therapy allows the patients to reduce renal and extra-renal damage accrual. Treatment with chloroquine may help to maintain remission in patients who discontinue steroids and immunosuppressive drugs.


Assuntos
Imunossupressores/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Esteroides/administração & dosagem , Adulto , Distribuição de Qui-Quadrado , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/efeitos adversos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/imunologia , Masculino , Seleção de Pacientes , Recidiva , Indução de Remissão , Fatores de Risco , Esteroides/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
G Ital Nefrol ; 40(2)2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37179477

RESUMO

In this article we describe a case of acute kidney injury caused by ethylene glycol intoxication which partially reversed after temporary hemodialysis treatment. The diagnosis was obtained after the patient's clinical history and the finding of ethylene glycol in the blood, numerous intratubular crystals at renal biopsy, and the presence of large amounts of atypical - spindle-like and needle-like - calcium oxalate crystals in the urinary sediment.


Assuntos
Injúria Renal Aguda , Etilenoglicol , Humanos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapia , Injúria Renal Aguda/patologia , Oxalato de Cálcio , Diálise Renal , Rim/patologia
9.
Eur J Nucl Med Mol Imaging ; 39(10): 1635-42, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22801728

RESUMO

PURPOSE: The different stages in idiopathic retroperitoneal fibrosis (IRF) are generally assessed by assay of inflammatory markers and analysis of contrast-enhanced CT images of the retroperitoneal mass. We investigated the potential role of (18)F-FDG PET/CT in this clinical setting. METHODS: (18)F-FDG uptake was assessed visually and semiquantitatively (using maximum standardized uptake values, SUVmax) in images of the abdominal mass in 22 patients prospectively enrolled from June 2008 to December 2010 who underwent a total of 33 PET/CT studies. The accuracy in discriminating active from inactive disease was calculated assuming as reference a biochemical instrumental evaluation of patients with IRF mostly based on the level of inflammatory indices and contrast enhancement (CE) of the mass at the time of each PET study. In particular, the relationship between SUVmax and CE, the latter calculated from the change in radiodensity (Hounsfield units) between the basal and postcontrast venous portal phases, was evaluated on a three-point scale (0 <20 HU, 1 20-30 HU, 2 ≥ 30 HU). SUVmax and CE scores were correlated with the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. The value of PET/CT in assessing the variation of disease activity over time was also investigated by analysing the changes in metabolic volume (MV) of the retroperitoneal lesion between repeat patient studies. RESULTS: PET/CT accurately discriminated (93.9 %) active from inactive disease. Significant agreement (p < 0.01) was observed between visual and semiquantitative analysis of (18)F-FDG uptake, and CE score. A significant correlation (p < 0.01) was found among SUVmax, CRP levels (rho = 0.54) and ESR (rho = 0.55). Corresponding variations in MV and CE score were observed in patients with multiple studies (p < 0.01; rho = 0.68). CONCLUSION: (18)F-FDG PET/CT may be considered an alternative imaging method for the assessment of different stages of IRF.


Assuntos
Fluordesoxiglucose F18 , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Fibrose Retroperitoneal/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Biomarcadores/análise , Sedimentação Sanguínea , Proteína C-Reativa/análise , Feminino , Humanos , Inflamação/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prognóstico
10.
Kidney Int Rep ; 6(6): 1614-1621, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34169201

RESUMO

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is mainly due to complement regulatory gene abnormalities with a dominant pattern but incomplete penetrance. Thus, healthy carriers can be identified in any family of aHUS patients, but it is unpredictable if they will eventually develop aHUS. METHODS: Patients are screened for 10 complement regulatory gene abnormalities and once a genetic alteration is identified, the search is extended to at-risk family members. The present cohort study includes 257 subjects from 71 families: 99 aHUS patients (71 index cases + 28 affected family members) and 158 healthy relatives with a documented complement gene abnormality. RESULTS: Fourteen families (19.7%) experienced multiple cases. Over a cumulative observation period of 7595 person-years, only 28 family members carrying gene mutations experienced aHUS (overall penetrance of 20%), leading to a disease rate of 3.69 events for 1000 person-years. The disease rate was 7.47 per 1000 person-years among siblings, 6.29 among offspring, 2.01 among parents, 1.84 among carriers of variants of uncertain significance, and 4.43 among carriers of causative variants. CONCLUSIONS: The penetrance of aHUS seems a lot lower than previously reported. Moreover, the disease risk is higher in carriers of causative variants and is not equally distributed among generations: siblings and the offspring of patients have a much greater disease risk than parents. However, risk calculation may depend on variant classification that could change over time.

11.
Transplantation ; 103(2): e48-e51, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30365467

RESUMO

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is life-threatening condition particularly when complicating allograft hematopoietic stem cell transplant (HSCT). In the past, the outcome was very poor with the majority of patients reaching end-stage renal disease or dying with little or no chances of kidney transplant (KTx) due to the high risk of relapse. The availability of C5 inhibition has opened up significant therapeutic opportunities and has improved the outcome particularly if complement dysregulation (CD) is the underlying pathogenetic mechanism. METHODS: We describe a peculiar case of a girl with aHUS complicating HSCT and her subsequent successful KTx received from the same donor thus performed without immunosuppression but anti-C5 inhibition. RESULTS: Soon after HSCT performed for acute lymphoblastic leukemia, the patient developed a TMA due to CD and reached end-stage renal disease. After 2 years on dialysis, the patient received a KTx from her father who was already the HSCT donor. Given the full chimerism, no immunosuppressive agent was prescribed except a short (2 days) course of steroids and eculizumab to prevent aHUS relapse. Nine months after the KTx, the patient is well with normal renal function, no immunosuppression and continues eculizumab prevention of aHUS (1 infusion every 21 days). CONCLUSIONS: All patients with transplant-associated thrombotic microangiopathy should be screened for the causes of CD. C5 inhibition with eculizumab is an important therapeutic resource to manage this complication. When KTx is necessary, immunosuppression can be safely withhold in case of same donor for both grafts and documented full chimerism.


Assuntos
Síndrome Hemolítico-Urêmica Atípica/etiologia , Complemento C5/antagonistas & inibidores , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Terapia de Imunossupressão , Transplante de Rim , Doadores de Tecidos , Adulto , Feminino , Humanos , Transplante de Rim/efeitos adversos , Microangiopatias Trombóticas/etiologia
12.
J Nephrol ; 31(1): 137-145, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28012100

RESUMO

BACKGROUND AND AIMS: Encapsulating peritoneal sclerosis (EPS) is an uncommon but severe complication of peritoneal dialysis (PD). A reliable screening tool to identify patients at risk of developing or not EPS is currently not available. We aimed to evaluate whether the reduction in dialysate sodium concentration (sodium sieving) at 60 min (ΔDNa60), during a peritoneal equilibration test with 3.86% glucose concentration (3.86%-PET) was able to early rule out patients who will not develop EPS. METHODS: Prospective controlled longitudinal (20-year) cohort study. All eligible incident PD patients attending the hospital underwent a 3.86%-PET during the first 3 months following start of PD and then once a year. The dip in ΔDNa60 and other factors were correlated with eventual EPS onset. RESULTS: Of 161 incident PD patients, with a median PD duration of 37.8 (24.7-58.3) months and 64.1 (34.5-108.3) months of follow-up, 13 patients (8%) developed EPS at a median PD duration of 72.7 (56.6-109.4) months and 105.0 (76.4-143.2) months of follow-up. ΔDNa60 demonstrated the best sensitivity and specificity values, estimated by conventional receiver operating characteristic (ROC) curve analysis with an area under the curve (AUC) of 0.90, 0.83 and 0.85 at 1, 2 and 3 years before the onset of EPS, respectively. Multifactorial analysis showed that the most useful factors for predicting EPS were age at start of PD, duration of PD, small solutes transport (D/PCreat) and ΔDNa60; the AUC at 1, 2 and 3 years before the onset of EPS was, respectively, 0.97, 0.96 and 0.94, the positive predictive value being 0.48, 0.57 and 0.42, and the negative predictive value 1.0, 1.0 and 1.0. CONCLUSIONS: It is possible to predict the occurrence and, better, the non-occurrence of EPS using simple parameters such as age at PD start, duration of PD, and parameters obtained by 3.86%-PET such as D/PCreat and ΔDNa60.


Assuntos
Soluções para Diálise/metabolismo , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/epidemiologia , Peritônio/metabolismo , Sódio/metabolismo , Adulto , Fatores Etários , Idoso , Área Sob a Curva , Transporte Biológico , Biomarcadores/metabolismo , Soluções para Diálise/administração & dosagem , Soluções para Diálise/efeitos adversos , Feminino , Humanos , Incidência , Itália/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fibrose Peritoneal/diagnóstico , Fibrose Peritoneal/metabolismo , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
15.
Clin Kidney J ; 9(2): 260-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26985378

RESUMO

Anaemia in chronic kidney disease (CKD) is managed primarily with erythropoiesis-stimulating agents (ESAs) and iron therapy. Following concerns around ESA therapy, intravenous (IV) iron is being administered more and more worldwide. However, it is still unclear whether this approach is safe at very high doses or in the presence of very high ferritin levels. Some observational studies have shown a relationship between either high ferritin level or high iron dose and increased risk of death, cardiovascular events, hospitalization or infection. Others have not been able to confirm these findings. However, they suffer from indication biases. On the other hand, the majority of randomized clinical trials have only a very short follow-up (and thus drug exposure) and are inadequate to assess the mortality risk. None of them have tested the role of different iron doses on hard end points. With the lack of clear evidence coming from well-designed and large-scale studies, several data suggest that excessive iron therapy may be toxic in several aspects, ranging from iron overload to tissue damage from labile iron. A number of experimental and clinical data suggest that either excessive iron therapy or iron overload may be a possible culprit of atherogenesis. The process seems to be mediated by oxidative stress. Iron therapy should also be used cautiously in the presence of active infections, since iron is essential for bacterial growth. Recently, the European Medicines Agency officially raised concerns about rare hypersensitivity reactions following IV iron administration. The balance has been in favour of benefits. In several European countries, this has created a lot of confusion and somewhat slowed the run towards excessive use. Altogether, IV iron remains a mainstay of anaemia treatment in CKD patients. However, in our opinion, its excessive use should be avoided, especially in patients with high ferritin levels and when ESA agents are not contraindicated.

17.
PLoS One ; 8(5): e62330, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23690937

RESUMO

OBJECTIVE: Chronic periaortitis (CP) is a rare disease that is characterised by fibro-inflammatory tissue surrounding the abdominal aorta and has both non-aneurysmal (idiopathic retroperitoneal fibrosis [IRF]) and aneurysmal forms (inflammatory abdominal aortic aneurysm [IAAA]). We investigated whether toll-like receptor 4 (TLR-4) and vascular endothelial growth factor (VEGF) polymorphisms were associated with susceptibility to, and the clinical features of CP. METHODS: One hundred and two CP patients and 200 healthy controls were molecularly genotyped for TLR-4 gene polymorphism (+896 A/G) (rs4986790), VEGF mutations +936 C/T (rs3025039) and -634 C/G (rs2010963), and an 18 base pair (bp) insertion/deletion (I/D) polymorphism at -2549 of the VEGF promoter region. The patients were grouped on the basis of the type of CP (IRF or IAAA), and the presence or absence of established atherosclerotic disease (ischemic heart disease, cerebrovascular disease, and peripheral arterial disease). RESULTS: There were no significant differences in the distribution of the studied polymorphisms between the patients and controls. However, carriage of the +936 T allele was significantly more frequent in the patients with IRF than in those with IAAA (26.5% vs 5.3%; p = 0.046; OR 6.49 [95% CI 0.82-51.54]). There were significantly more carriers of the I allele among the patients with ureteral obstruction (83.8% vs 58.8%; p = 0.006; OR 3.63 [95% CI 1.42-9.28]) and those who received conservative treatment (48.5% vs 23.5%; p = 0.015; OR 3.06 [95% CI 1.22-7.721]) than among those without, and II homozygosity was significantly more frequent in the patients with deep vein thrombosis than in those without (30.4% vs 11.7%, p = 0.031; OR 3.31 [95% CI 1.07-10.21]). CONCLUSION: The VEGF +936 C/T polymorphism may be associated with an increased risk of developing the non-aneurysmal IRF form of CP. Carriers of the I allele and II homozygosity are respectively at increased risk of developing ureteral obstruction and deep vein thrombosis.


Assuntos
Polimorfismo Genético/genética , Fibrose Retroperitoneal/genética , Receptor 4 Toll-Like/genética , Fator A de Crescimento do Endotélio Vascular/genética , Alelos , Aterosclerose/complicações , Aterosclerose/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fibrose Retroperitoneal/complicações
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