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BACKGROUND: Oral anticoagulation therapy (OAT) is the choice treatment for thromboembolism prevention in atrial fibrillation (AF), although data about OAT use in haemodialysis (HD) patients with AF are contradictory. METHODS: The effect of OAT on the risk of mortality, stroke and bleeding was prospectively evaluated in a population of HD patients with AF. All the patients of 10 HD Italian centres alive on 31 October 2010 with documented AF episode(s) were recruited and followed-up for 2 years. OAT and antiplatelet intake, age, dialytic age, comorbidities and percentage time in the target international normalized ratio (INR) range (target therapeutic range; TTR) were considered as predictors of hazard of death, thromboembolic and bleeding events. RESULTS: At recruitment, 134 patients out of 290 were taking OAT. During the follow-up, 115 patients died (4 strokes, 3 haemorrhagic and 1 thromboembolic). Antiplatelet therapy, but not OAT, was associated with increased mortality (HR 1.71, CI 1.10-2.64, P = 0.02). The estimated survival of patients always taking OAT tended to be higher than that of patients who stopped taking (68.6 versus 49.6%, P = 0.07). OAT was not correlated to a significant decreased risk of thromboembolic events (HR 0.12, CI 0.00-3.59, P = 0.20), while it was associated with an increased risk of bleeding (HR 3.96, CI 1.15-13.68, P = 0.03). Higher TTR was associated with a reduced bleeding risk (HR 0.09, CI 0.01-0.76, P = 0.03), while previous haemorrhagic events were associated with higher haemorrhagic risk (HR 2.17, CI 1.09-4.35, P = 0.03). CONCLUSIONS: In our population of HD patients with AF, the mortality is very high. OAT is not associated with increased mortality, while antiplatelet drugs are. OAT seems, on the contrary, associated with a better survival; however, it does not decrease the incidence of ischaemic stroke, whereas it increases the incidence of bleeding. Bleeding risk is lower in subjects in whom the INR is kept within the therapeutic range.
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Anticoagulantes/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Hemorragia/etiología , Diálisis Renal , Accidente Cerebrovascular/etiología , Warfarina/efectos adversos , Anciano , Fibrilación Atrial/mortalidad , Femenino , Hemorragia/mortalidad , Humanos , Incidencia , Italia/epidemiología , Masculino , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/mortalidad , Tasa de SupervivenciaRESUMEN
BACKGROUND: Primary or secondary glomerulonephritis has been anecdotally reported in association with atypical haemolytic uraemic syndrome (aHUS). We here report a series of six patients who developed aHUS and glomerulopathy, and review the literature on aHUS and glomerulonephritis. METHODS: Out of all patients diagnosed at our unit with biopsy-proven glomerular diseases between March 2007 and October 2011, selected cases developing aHUS during the follow-up are presented. The following tests were performed in all six patients: serum C3 and C4 levels, ADAMTS13 activity, CFH levels and anti-CFH autoantibodies and genetic screening for CFH, MCP, CFI, C3 and CFHR1-3 mutations and risk haplotypes associated with aHUS. RESULTS: Two hundred and forty-eight patients received a biopsy-proven diagnosis of glomerulopathy and were followed for a median of 31 months (range 2-58). Of these, six developed aHUS, within a median of 15 months (range 1-36) of their initial diagnosis of glomerulopathy. One of these patients had focal segmental glomerulosclerosis (FSGS), two membranoproliferative glomerulonephritis (MPGN) type I, one C3 glomerulonephritis and two systemic small vessel vasculitis [one granulomatosis with polyangiitis (Wegener's), one Henoch-Schoenlein purpura]. Five patients (one of them heterozygous for a CFH mutation) carried, in homo- or heterozygosity, the risk haplotype CFH-H3 (CFH tgtgt), previously described to be associated with aHUS, while another one patient was homozygous for the MCPggaac risk haplotype predisposing to aHUS when present on both alleles. CONCLUSIONS: Different types of glomerulopathies can be complicated by aHUS. Several mechanisms can contribute to this association, such as nephrotic-range proteinuria, mutations or aHUS-risk haplotypes involving genes encoding alternative complement regulatory proteins in some patients and inflammatory triggers associated with systemic immune-mediated diseases.
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Proteínas del Sistema Complemento/genética , Glomerulonefritis/complicaciones , Síndrome Hemolítico-Urémico/etiología , Adolescente , Adulto , Anciano , Síndrome Hemolítico Urémico Atípico , Proteínas del Sistema Complemento/inmunología , Femenino , Estudios de Seguimiento , Síndrome Hemolítico-Urémico/patología , Humanos , Masculino , Persona de Mediana Edad , Literatura de Revisión como Asunto , Adulto JovenRESUMEN
ANCA-associated vasculitides are a group of inflammatory diseases affecting medium and small vessels with a redundant and hence complex pathogenetic mechanism. Since their first identification, their dismal prognosis has forced researchers to find effective therapies. The prognosis has changed since the advent of immunomodulatory drugs like steroids, cyclophosphamide, azathioprine, mycophenolate mofetil and, more recently, biological drugs. Plasmapheresis in association with immune suppressant drugs has shown beneficial effects in some clinical trials, mostly in dialysis-dependent patients. Apheresis should remove, in a nonselective manner, pathogenetic antibodies like ANCA but also immune complexes, cytokines and inflammatory mediators. A recent meta-analysis took into account 28 randomized clinical trials studying therapeutic interventions in adult vasculitis with renal involvement, six of them scheduling plasmapheresis as adjunctive therapy to immune suppressant drugs. This association significantly reduced the need for dialysis at three (1 trial: RR 0.45, 95% CI 0.24-0.84) and twelve (5 trials: RR 0.47, 95% CI 0.3-0.75) months but not the mortality at one year. We can conclude that plasmapheresis is an effective treatment option for vasculitides with severe renal failure. It can also be considered in case of ineffectiveness of or contraindications to standard treatment.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Eliminación de Componentes Sanguíneos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/mortalidad , Ensayos Clínicos como Asunto , Humanos , Inmunosupresores/uso terapéutico , Metaanálisis como Asunto , Plasmaféresis , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Kidney damage caused by immunoglobulin free light chains in the setting of plasma cell dyscrasias is common and may involve all renal compartments, from the glomerulus to the tubulointerstitium, in a wide variety of histomorphological and clinical patterns. The knowledge of how free light chains can promote kidney injury is growing: they can cause functional changes, be processed and deposited, mediate inflammation, apoptosis and fibrosis, and obstruct nephrons. Each clone of the free light chain is unique and its primary structure and post-translation modification can determine the type of renal disease. Measurement of serum free light chain concentrations and calculation of the serum kappa/lambda ratio, together with renal biopsy, represent essential diagnostic tools. An early and correct diagnosis of renal lesions due to plasma cell dyscrasias will allow early initiation of disease-specific treatment strategies. The treatment of free light chain nephropathies is evolving and knowledge of the pathways that promote renal damage should lead to further therapeutic developments.
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Enfermedades Renales/etiología , Paraproteinemias/complicaciones , Humanos , Enfermedades Renales/terapia , Glomérulos Renales , Túbulos RenalesRESUMEN
This article describes the birth and development of the Renal Immunopathology Group of the Italian Society of Nephrology. It collects the stories of nephrologists and pathologists who, since the early Seventies up to the first decade of this century, devoted their professional lives to the study of renal pathology with a strong personal involvement, characterized by enthusiasm, commitment, ability, strong spirit of cooperation, and friendship. All this enabled the Group to: propose the criteria for a standardized histological and immuno-histological examination of renal biopsies and reporting; produce several multicenter studies, whose results were also published in important international journals; to set up a national registry of renal biopsies; to organize a number of courses, some of which were associated with the publication of monographs, on various renal diseases. This article also traces the history of renal pathology in Italy from the second half of the Sixties - when young Italian nephrologists and pathologists from different institutions moved to French laboratories to learn new techniques to apply to renal biopsies - up to the present days. It also shows us how Italian renal pathology has been an essential tool for the development of the nephrological clinical practice and the advancement of scientific research.
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Enfermedades Renales , Nefrología , Humanos , Italia , Riñón , Nefrólogos , Nefrología/historiaRESUMEN
BACKGROUND AND OBJECTIVES: Renin-angiotensin system (RAS) inhibitors reduce cardiovascular morbidity and mortality in patients with CKD. We evaluated the cardioprotective effects of the angiotensin-converting enzyme inhibitor ramipril in patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this phase 3, prospective, randomized, open-label, blinded end point, parallel, multicenter trial, we recruited patients on maintenance hemodialysis with hypertension and/or left ventricular hypertrophy from 28 Italian centers. Between July 2009 and February 2014, 140 participants were randomized to ramipril (1.25-10 mg/d) and 129 participants were allocated to non-RAS inhibition therapy, both titrated up to the maximally tolerated dose to achieve predefined target BP values. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the single components of the primary end point, new-onset or recurrence of atrial fibrillation, hospitalizations for symptomatic fluid overload, thrombosis or stenosis of the arteriovenous fistula, and changes in cardiac mass index. All outcomes were evaluated up to 42 months after randomization. RESULTS: At comparable BP control, 23 participants on ramipril (16%) and 24 on non-RAS inhibitor therapy (19%) reached the primary composite end point (hazard ratio, 0.93; 95% confidence interval, 0.52 to 1.64; P=0.80). Ramipril reduced cardiac mass index at 1 year of follow-up (between-group difference in change from baseline: -16.3 g/m2; 95% confidence interval, -29.4 to -3.1), but did not significantly affect the other secondary outcomes. Hypotensive episodes were more frequent in participants allocated to ramipril than controls (41% versus 12%). Twenty participants on ramipril and nine controls developed cancer, including six gastrointestinal malignancies on ramipril (four were fatal), compared with none in controls. CONCLUSIONS: Ramipril did not reduce the risk of major cardiovascular events in patients on maintenance hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ARCADIA, NCT00985322 and European Union Drug Regulating Authorities Clinical Trials Database number 2008-003529-17.
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Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Ramipril/uso terapéutico , Diálisis Renal , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
In the wide spectrum of therapies for hematological malignancies, hematopoietic stem cell transplantation, whether autologous or allogeneic, is a common procedure. In addition to other transplant-related organ toxicities, renal failure is a common complication following transplantation. This paper discusses the incidence, timing, etiologies, risk factors and prognosis of renal failure associated with three commonly used transplantation procedures: myeloablative autologous, myeloablative allogeneic, and non-myeloablative allogeneic transplantation. The epidemiology and prognosis of renal failure are different after these three procedures. Severe renal failure occurs with all three varieties, but the frequency increases from myeloablative autologous to non-myeloablative allogeneic to myeloablative allogeneic. In all three types of transplantation, the mortality is clearly associated with the severity of renal injury, and it is greater than 80% when dialysis is required. Strategies to improve renal failure following transplantation may have a beneficial impact on these patients. Reduction of acute renal failure will likely reduce the severity of non-renal organ dysfunction, the incidence and severity of chronic kidney disease, and the mortality.
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Trasplante de Médula Ósea/efectos adversos , Trasplante de Riñón , Insuficiencia Renal/etiología , Síndrome de Lisis Tumoral/etiología , Neoplasias Hematológicas/cirugía , HumanosRESUMEN
To investigate associations between gender and myocardial involvement in systemic amyloidosis, we reviewed all patients presenting between 1994 and September 2006 in our institutional network (100 AL and 98 familial transthyretin-related amyloidosis (ATTR) patients, plus 12 elderly men with senile systemic amyloidosis). We focused on echocardiographic descriptors of myocardial involvement (height-indexed mean left ventricular (LV) wall thickness, LV mass index), and baseline LV function. Among familial ATTR patients, female prevalence was lower within the highest tertile of either echocardiographic indicator of myocardial involvement. Gender was independently associated with height-indexed mean LV wall thickness (as were gene mutations). Female prevalence appeared rather similar across the different neurological stages. Within the subgroup of familial ATTR patients with amyloidotic cardiomyopathy, women tended to display a considerably less severe morphological and functional echocardiographic profile. We explored the possible role of female sex hormones by considering menopausal status: women in the highest tertile of mean LV wall thickness index were more often postmenopausal than those in the other two tertiles and had a much higher ( approximately 15 years) mean age; analogous age-related associations were not observable for men. In conclusion, these findings raise the hypothesis that some biological characteristic associated with female gender protects against myocardial involvement in familial ATTR.
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Amiloidosis/complicaciones , Cardiomiopatías/etiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Amiloidosis/diagnóstico por imagen , Amiloidosis/epidemiología , Amiloidosis/metabolismo , Cardiomiopatías/diagnóstico por imagen , Cardiomiopatías/epidemiología , Cardiomiopatías/metabolismo , Ecocardiografía , Femenino , Hormonas Esteroides Gonadales/metabolismo , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Masculino , Menopausia/metabolismo , Persona de Mediana Edad , Estudios Retrospectivos , Factores SexualesRESUMEN
BACKGROUND: Mixed cryoglobulinemia is a multisystem disorder associated strongly with hepatitis C virus (HCV) infection. The kidney frequently is involved, and glomerulonephritis represents the key factor affecting prognosis. METHODS: Clinical, serological, immunogenetic, and morphological data were collected retrospectively from medical records of 146 patients with cryoglobulinemic glomerulonephritis who underwent biopsies in 25 Italian centers and 34 cryoglobulinemic controls without renal involvement. RESULTS: Eighty-seven percent of patients were infected with HCV; genotype 1b was more frequent than genotype 2 (55% versus 43%). Diffuse membranoproliferative glomerulonephritis was the most prevalent histological pattern (83%). Type II cryoglobulin (immunoglobulin Mkappa [IgMkappa]/IgG) was detected in 74.4% of cases. The remainder had type III (polyclonal IgM/IgG) cryoglobulins. A multivariate Cox proportional hazard model showed that age, serum creatinine level, and proteinuria at the onset of renal disease were associated independently with risk for developing severe renal failure at follow-up. Overall survival at 10 years was about 80%. Kaplan-Meier survival curves were worsened by a basal creatinine value greater than 1.5 mg/dL (>133 mumol/L), but were unaffected by sex and HCV infection. Cardiovascular disease was the cause of death in more than 60% of patients. CONCLUSION: Data confirm the close association between mixed cryoglobulinemia and HCV infection and between glomerulonephritis and type II cryoglobulin. Survival profiles are better than previously reported in the literature, probably because of improvement in therapeutic regimens. Causes of death reflect this improvement in survival, with an increased prevalence of cardiovascular events compared with infectious complications and hepatic failure, which were predominant in the past.
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Crioglobulinemia/virología , Glomerulonefritis/virología , Hepatitis C/complicaciones , Adulto , Anciano , Crioglobulinemia/complicaciones , Femenino , Glomerulonefritis/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: The aim of this study was to evaluate, in a cohort of haemodialysis patients with atrial fibrillation (AF), the relationship between oral anticoagulant therapy (OAT) and mortality, thromboembolic events and haemorrhage. METHODS: Two hundred and ninety patients with AF were prospectively followed for 4 years. Warfarin and antiplatelet intake, age, dialytic age, comorbidities, CHA2DS2-VASc and HAS-BLED scores were considered as predictors of risk of death, thromboembolism and bleeding events. In patients taking OAT, the international normalized ratio (INR) was assessed and the percentage time in the target therapeutic range (TTR) was calculated. RESULTS: At recruitment, 134/290 patients were taking warfarin. During follow-up there were 170 deaths, 28 thromboembolic events and 95 bleedings. After balancing for treatment propensity, intention-to-treat analysis on OAT intake at recruitment did not show differences in total mortality, thromboembolic events and bleedings, while the as-treated analysis, accounting for treatment switch, showed that patients taking OAT at recruitment had a significantly lower mortality than those not taking it [hazard ratio, HR 0.53 (95% confidence interval 0.28-0.90), p = 0.04], with a decrease of thromboembolic events [HR 0.36 (0.13-1.05), p = 0.06], and an increase of bleedings [HR 1.79 (0.72-4.39), p = 0.20], both non-significant. Among patients taking OAT at recruitment, those continuing to take warfarin had a significant reduction in the risk of total [HR 0.28 (0.14-0.53), p < 0.001] and cardiovascular [HR 0.21 (0.11-0.40), p < 0.001] mortality compared to patients stopping OAT. CONCLUSIONS: In haemodialysis patients with AF, continuously taking warfarin is associated with a reduction of the risk of total and cardiovascular mortality.
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Anticoagulantes/administración & dosificación , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/mortalidad , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Diálisis Renal/mortalidad , Tromboembolia/mortalidad , Tromboembolia/prevención & control , Warfarina/administración & dosificación , Administración Oral , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Fibrilación Atrial/diagnóstico , Comorbilidad , Femenino , Hemorragia/inducido químicamente , Hemorragia/mortalidad , Humanos , Análisis de Intención de Tratar , Italia , Estimación de Kaplan-Meier , Fallo Renal Crónico/diagnóstico , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores Protectores , Diálisis Renal/efectos adversos , Factores de Riesgo , Tromboembolia/diagnóstico , Factores de Tiempo , Resultado del Tratamiento , Warfarina/efectos adversosRESUMEN
BACKGROUND: We conducted a pilot trial to compare the effectiveness and safety of 2 different treatments in patients with membranous nephropathy and nephrotic syndrome. METHODS: To validate the hypothesis that the 2 treatments were equivalent, patients with biopsy-proven membranous nephropathy and nephrotic syndrome were randomly assigned to methylprednisolone alternated with a cytotoxic drug every other month for 6 months (group A) or to intramuscular synthetic adrenocorticotropic hormone administered twice a week for 1 year (group B). RESULTS: The primary outcome measure is cumulative number of remissions as a first event. Fifteen of 16 patients in group A and 14 of 16 patients in group B entered complete or partial remission as a first event. After a median follow-up of 24 months (interquartile range, 15 to 25 months), there were 4 complete remissions and 8 partial remissions in group A versus 8 complete remissions and 6 partial remissions in group B. Median proteinuria decreased from protein of 5.1 g/d (interquartile range, 4.0 to 7.3 g/d) to 2.1 g/d (interquartile range, 0.4 to 3.8 g/d; P = 0.004) in group A and 6.0 g/d (interquartile range, 4.4 to 8.5 g/d) to 0.3 g/d (interquartile range, 0.2 to 1.9 g/d; P = 0.049) in group B. Two patients from each group interrupted treatment because of side effects or inefficacy. CONCLUSION: Most nephrotic patients with membranous nephropathy responded to either treatment. Proteinuria was significantly decreased with both methylprednisolone and cytotoxic agents or prolonged administration of synthetic adrenocorticotropic hormone, without significant differences between these 2 therapies.
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Hormona Adrenocorticotrópica/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Clorambucilo/administración & dosificación , Ciclofosfamida/administración & dosificación , Glomerulonefritis Membranosa/tratamiento farmacológico , Hormonas/administración & dosificación , Metilprednisolona/administración & dosificación , Síndrome Nefrótico/tratamiento farmacológico , Adulto , Anciano , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios ProspectivosRESUMEN
Medium- and large-vessel vasculitides (MVV and LVV, respectively) comprise a heterogeneous group of disorders whose common denominator is the inflammatory involvement of vessels of medium and large size. This disease spectrum includes giant-cell arteritis and Takayasu's arteritis, which typically affect the aorta and its main branches, and Kawasaki's disease and polyarteritis nodosa, which involve medium-sized arteries. Chronic periaortitis, characterized by a perivascular fibro-inflammatory reaction affecting the abdominal aorta and the periaortic tissue, frequently has a systemic distribution, involving other segments of the aorta and its major branches, and could thus be included in this group. Unlike small-vessel vasculitides, MVV and LVV do not cause glomerulonephritis, although glomerular immune-mediated lesions and tubulo-interstitial nephritis occur with varying frequency. However, MVV and LVV can often involve the renal artery and its branches, causing a wide array of lesions that range from renal artery stenosis to intra-renal vasculitis causing renal ischaemia/infarction, microaneurysms and haemorrhage. This review focuses on renal involvement in MVV and LVV and underlines why renal abnormalities in these syndromes should not be overlooked.
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Arteritis de Células Gigantes/complicaciones , Enfermedades Renales/etiología , Síndrome Mucocutáneo Linfonodular/complicaciones , Poliarteritis Nudosa/complicaciones , Fibrosis Retroperitoneal/complicaciones , Arteritis de Takayasu/complicaciones , HumanosRESUMEN
Healthcare is in the middle of a digital revolution. Physicians are adopting mobile apps that make them more effective and patients are taking to ones that give them more control over their healthcare. Mobile technology is changing Medicine. A new movement for free open access medical education (FOAMed) is growing through Social Media. E-learning is increasing access to new and exciting learning opportunities, deeply changing the traditional concept of continuous medical education. What will be the future of Nephrology in the era of Digital Health?
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Aplicaciones Móviles , Nefrología/tendencias , Medios de Comunicación Sociales , Telemedicina , Instrucción por Computador , Predicción , Humanos , Nefrología/educaciónAsunto(s)
Proteínas Sanguíneas/metabolismo , Ergocalciferoles/uso terapéutico , Hiperparatiroidismo Secundario/tratamiento farmacológico , Enfermedades Renales/terapia , Diálisis Renal , Enfermedad Crónica , Humanos , Hiperparatiroidismo Secundario/sangre , Enfermedades Renales/sangre , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba , alfa-2-Glicoproteína-HSRESUMEN
BACKGROUND: Fabry disease is a lysosomal storage disease resulting from deficient alpha-galactosidase A (alpha-Gal A) activity. End-stage renal disease generally occurs around the fourth decade of age, and dialysis therapy is a life-saving procedure. For patients with Fabry disease undergoing dialysis, death usually occurs from cardiac or cerebrovascular complications. Recently, enzyme replacement therapy was introduced for treatment of the disease. METHODS: We report results of several clinical outcomes after 2 years of treatment with alpha-Gal A in patients with Fabry disease undergoing dialysis. Nine dialysis patients underwent a complete clinical, cardiac, and cerebrovascular evaluation at baseline and after 24 months of treatment. Two patients reported a recurrent pain crisis, and 6 patients reported gastrointestinal symptoms. In all patients, enzyme replacement therapy was undertaken because of the presence of Fabry cardiomyopathy. A complete echocardiographic study was performed in 6 patients 12 and 24 months before and 12 and 24 months during enzyme replacement therapy. RESULTS: Enzyme replacement therapy was well tolerated. Pain crises disappeared completely after approximately 6 months of treatment, and patients with gastrointestinal involvement reported improvement in symptoms after 6 to 8 months. At baseline, all patients had left ventricular concentric hypertrophy. Enzyme replacement therapy did not affect heart rate or mean arterial pressure. The mean slope of left ventricular mass index progression decreased from 0.98 +/- 0.01 in the pretreatment period (24 months) to 0.46 +/- 0.960 in the enzyme-replacement-therapy period (P = 0.06). CONCLUSION: Our observation indicates that in dialysis patients, enzyme replacement therapy is safe and effective, improving global quality of life and possibly ameliorating the progression of typical Fabry cardiomyopathy.
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Enfermedad de Fabry/tratamiento farmacológico , Fallo Renal Crónico/etiología , Diálisis Renal , alfa-Galactosidasa/uso terapéutico , Adulto , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Trastornos Cerebrovasculares/etiología , Trastornos Cerebrovasculares/prevención & control , Progresión de la Enfermedad , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/enzimología , Enfermedad de Fabry/patología , Femenino , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/prevención & control , Hemodinámica/efectos de los fármacos , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/patología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Dolor/etiología , Dolor/prevención & control , Estudios Prospectivos , Calidad de Vida , Volumen Sistólico , Encuestas y Cuestionarios , Resultado del Tratamiento , Ultrasonografía , alfa-Galactosidasa/genéticaRESUMEN
BACKGROUND: In myeloma cast nephropathy, fast reduction of serum free light chain (FLC) levels correlates with renal recovery. Recently, extracorporeal treatments using filters with a high-molecular weight cut-off have been successfully used for FLC removal. However, using these new filters, high cost and elevated albumin leakage are common drawbacks. We studied a new and cheaper therapeutic approach with adsorbent resins to evaluate its efficacy. METHODS: We treated four patients, affected by dialysis-dependent acute kidney injury (AKI) due to biopsy proven de novo FLC myeloma cast nephropathy. Each patient underwent bortezomib chemotherapy and extracorporeal treatment with the supra-hemodiafiltration with endogenous reinfusion (HFR) technique (Supra-HFR, Bellco Mirandola, Modena, Italy). Supra-HFR is a kind of hemodiafiltration that utilizes separated convection, diffusion and adsorption. The sorbent cartridge has a high affinity for FLC (both κ and λ) but is able to re-infuse albumin, avoiding the need for albumin perfusions. Supra HFR treatments (4 h each) were carried out for eight consecutive days and then every other day. RESULTS: All patients showed a significant reduction of serum FLC, whereas serum albumin concentration remained unchanged. Renal function recovered in three out of four patients. CONCLUSIONS: FLC removal with adsorbent resins represents an effective therapeutic strategy that does not require replacement with albumin .
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Lesión Renal Aguda/terapia , Hemodiafiltración/métodos , Cadenas Ligeras de Inmunoglobulina/sangre , Mieloma Múltiple/complicaciones , Albúmina Sérica/metabolismo , Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Lesión Renal Aguda/fisiopatología , Anciano , Antineoplásicos/uso terapéutico , Bortezomib/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/tratamiento farmacológicoRESUMEN
BACKGROUND: Light chain deposition disease (LCDD) is characterized by the tissue deposition of monotypical immunoglobulin light chains (LCs). The aim of this study was to investigate its clinical characteristics and prognostic factors. METHODS: Multicenter study of LCDD with renal and patient survival analyses. RESULTS: Sixty-three cases were studied (age: 58 +/- 14.2; males: 63.5%; kappa/lambda deposition: 68/32%; underlying disorders: multiple myeloma [MM] 65%, lymphoproliferative disorders 3%, idiopathic 32%). Ninety-six percent presented with renal insufficiency (acute, 52%; chronic, 44%), and 84% with proteinuria >1 g/d. During the follow-up, 36 patients reached uremia (incidence rate: 23.7/100 patient-years) and 37 died (17.5/100 patient-years). The factors independently associated with a worse renal prognosis were age (relative risk [RR], 1.05; 95% confidence interval [CI], 1.009 to 1.086) and serum creatinine at presentation (RR, 1.24; 95% CI, 1.02 to 1.5). Those independently associated with a worse patient survival were age (RR, 1.06; 95% CI, 1.03 to 1.1), MM (RR, 2.75; 95% CI, 1.22 to 6.2), and extrarenal LC deposition (RR, 2.24; 95% CI, 1.15 to 4.35). While kappa-LC deposition was more frequently associated with nodular sclerosing glomerulopathy, histological parameters were not predictors of renal/patient prognosis. The survival of the uremic patients undergoing dialysis was similar to that of patients not reaching uremia. CONCLUSION: LCDD is characterized by renal insufficiency with proteinuria and has a severe prognosis. Apart from age, the prognostic factors identified were degree of renal insufficiency at presentation affecting the renal prognosis, underlying hematologic disorder and extrarenal LC deposition affecting the patient prognosis. Dialysis is worth performing in uremic LCDD patients.
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Cadenas Ligeras de Inmunoglobulina/metabolismo , Enfermedades Renales/epidemiología , Paraproteinemias/epidemiología , Corticoesteroides/uso terapéutico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Alquilantes/uso terapéutico , Creatinina/sangre , Femenino , Humanos , Cadenas kappa de Inmunoglobulina/metabolismo , Cadenas lambda de Inmunoglobulina/metabolismo , Inmunosupresores/uso terapéutico , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/mortalidad , Tablas de Vida , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/epidemiología , Mieloma Múltiple/metabolismo , Mieloma Múltiple/patología , Paraproteinemias/complicaciones , Paraproteinemias/metabolismo , Paraproteinemias/patología , Paraproteinemias/terapia , Plasmaféresis , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Riesgo , Análisis de Supervivencia , Uremia/etiología , Uremia/mortalidadRESUMEN
BACKGROUND: The prevalence of atrial fibrillation (AF) is high in hemodialysis (HD) patients. It was suggested that oral anticoagulant therapy (OAT), the choice treatment for reducing the thromboembolic risk in AF patients, increases the incidence of both ischemic and hemorrhagic strokes in the HD population. Moreover, the therapy-related bleeding risk is particularly high in these patients. For these reasons there is no agreement on the use of OAT in HD patients with AF. The aim of this study was to evaluate the criteria adopted by nephrologists in prescribing OAT in HD patients with AF. METHODS: All the patients presenting AF (paroxysmal, persistent or permanent) at 31/10/2010 (n = 290) were recruited from 1529 HD patients from ten Italian HD centres. To detect factors related to OAT administration the main clinical features, CHADS2 and HASBLED scores were evaluated in logistic regression models. RESULTS: The presence of permanent AF (OR = 4.28, p < 0.0001) was the only clinical factor directly associated to OAT administration, while previous bleedings (OR = 0.35, p = 0.004) were inversely related. The CHADS2 score was not associated with OAT prescription (OR = 0.85, p = 0.08), while an inverse relation was found with the hemorrhagic risk score (OR = 0.74, p = 0.03). CONCLUSION: A high AF prevalence was observed in our HD population, but less than 50 % of these patients received OAT. Patients with permanent AF were more frequently treated with warfarin, while OAT administration was uncommon in those with previous bleedings. The thromboembolic risk score was not associated with warfarin prescription, while there was an inverse relation with the hemorrhagic risk score.
Asunto(s)
Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Nefrología , Selección de Paciente , Pautas de la Práctica en Medicina , Diálisis Renal , Tromboembolia/prevención & control , Administración Oral , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Isquemia Encefálica/complicaciones , Femenino , Humanos , Hemorragias Intracraneales/complicaciones , Masculino , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Accidente Cerebrovascular/complicaciones , Tromboembolia/etiologíaRESUMEN
Myeloma kidney is a tubulointerstitial pathology that accounts for approximately 80-90% of severe acute kidney injury in patients with multiple myeloma. Unless there is rapid intervention, progressive irreversible damage from interstitial fibrosis and tubular atrophy occurs. Work over the past decade has demonstrated that an early sustained reduction in serum concentrations of pathogenic monoclonal free light chains (FLCs) leads to improved renal recovery rates. In turn, an early improvement in renal function is associated with improved patient survival. An early reduction in FLC levels should therefore become standard of care, although the optimum mechanisms to achieve this depletion of FLCs remain to be determined. To provide a coordinated, cross-disciplinary approach to research in this disease, the International Kidney and Monoclonal Gammopathy Research Group was formed. In this Review, we address the current state of knowledge in the management of myeloma kidney.