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1.
Ren Fail ; 43(1): 1049-1059, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34187290

RESUMEN

Background. Identifying trajectories of kidney disease progression in chronic kidney disease (CKD) patients may help to deliver better care. We aimed to identify and characterize trajectories of renal function decline in CKD patients and to investigate their association with mortality after dialysis.Methods. This retrospective cohort study included 378 CKD patients who initiated dialysis (aged 65 years and over) between 2009 and 2016. Were considered mixed models using linear quadratic and cubic models to define the trajectories, and we used probabilistic clustering procedures. Patient characteristics and care practices at and before dialysis were examined by multivariable multinomial logistic regression. The association of these trajectories with mortality after dialysis was examined using Cox models.Results. Four distinct groups of eGFR trajectories decline before dialysis were identified: slower decline (18.3%), gradual decline (18.3%), early rapid decline (41.2%), and rapid decline (22.2%). Patients with rapid eGFR decline were more likely to have diabetes, more cognitive impairment, to have been hospitalized before dialysis, and were less likely to have received pre-dialysis care compared to the patients with a slower decline. They had a higher risk of death within the first and fourth year after dialysis initiation, and after being more than 4 years in dialysis.Conclusions. There are different patterns of eGFR trajectories before dialysis initiation in the elderly, that may help to identify those who are more likely to experience an accelerated decline in kidney function, with impact on pre ESKD care and in the mortality risk after dialysis.


Asunto(s)
Progresión de la Enfermedad , Riñón/fisiopatología , Diálisis Renal , Insuficiencia Renal Crónica/fisiopatología , Anciano , Anciano de 80 o más Años , Femenino , Tasa de Filtración Glomerular/fisiología , Humanos , Masculino , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/terapia , Tasa de Supervivencia , Factores de Tiempo
2.
Kidney Blood Press Res ; 45(1): 38-50, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31825925

RESUMEN

AIM: Mortality in end-stage renal disease (ESRD) remains high, particularly among elderly, who represents the most rapidly growing segment of the ESRD population in wealthier countries. We developed and validated a risk score in elderly patients to predict 6-month mortality after dialysis initiation. METHODS: We used data from a cohort of 421 patients, aged 65 years and over who started dialysis between 2009 and 2016, in our Nephrology department. The predictive score was developed using a multivariable logistic regression analysis. A bootstrapping technique was used for internal validation. RESULTS: The overall mortality within 6 months was 14.0%. Five independent predictors were identified, and a points system was constructed: age 75 years or older (2 points), coronary artery disease (2), cerebrovascular disease with hemiplegia (2), time of nephrology care before dialysis (<3.0 months [2]; ≥3 to <12 months [1]), and serum albumin levels (3.0-3.49 g/dL [1]; <3.0 g/dL [2]). A score of 6 identified patients with a 70% risk of 6-month mortality. Model performance was good in both discrimination (area under the curve of 0.793; [95% CI 0.73-0.86]) and validation (concordance statistics of 0.791 [95% CI 0.73-0.85]). CONCLUSIONS: We developed a simple prediction score based on readily available clinical and laboratory data that can be a practical and useful tool to assess short-term prognosis in elderly patients starting dialysis. It may help to inform patients and their families about ESRD treatment options and provide a more patient-centered overall approach to care.


Asunto(s)
Diálisis/estadística & datos numéricos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Factores de Edad , Anciano , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Mortalidad , Portugal/epidemiología , Pronóstico , Estudios Retrospectivos , Riesgo
3.
Am J Kidney Dis ; 70(2): 235-243, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28359658

RESUMEN

BACKGROUND: Fibrinogen A α-chain (AFib) amyloidosis results from autosomal-dominant mutations in the gene encoding AFib (FGA). Patients with this disorder typically present with proteinuria. Isolated cases of AFib amyloidosis, carrying the FGA p.Glu545Val variant, were identified in the district of Braga, in northwest Portugal. This observation led us to hypothesize that this disorder might be an unrecognized cause of kidney disease in that region and prompted us to carry out targeted genetic testing for the p.Glu545Val variant in the local hemodialysis population and family members of identified cases. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 3 groups of participants: (1) kidney biopsy registry, n=4; (2) hemodialysis facility, n=122 of 267 patients; and (3) genetically at-risk individuals; n=69 of 167 family members. OUTCOMES: Kidney disease, kidney disease progression, and survival. RESULTS: The p.Glu545Val variant was identified in all 4 patients of the biopsy registry, 12 of 122 (9.8%) hemodialysis patients tested, and 34 of 69 (49%) relatives tested. These 50 cases belonged to 13 unrelated families with kidney disease or amyloidosis identified in 61% of probands. 35 individuals presented with hypertension at a mean of 51.0±10.4 years. Of these, 30 developed kidney disease at a mean of 56.7±12.0 years, and 21 initiated dialysis therapy at a mean of 61.4±11.3 years. Heart, liver, spleen, colon, and ileum were involved along the progression of the disease. Kidney disease was formerly attributed to hypertension in 25% of patients with AFib amyloidosis undergoing hemodialysis. LIMITATIONS: Retrospective data collection for patients with amyloidosis previously diagnosed. CONCLUSIONS: AFib amyloidosis appears to be an under-recognized disorder in Braga, Portugal, where we found a high frequency of the FGA p.Glu545Val variant. Due to the nonspecific nature of its major clinical features, the diagnosis of AFib amyloidosis should have a high index of suspicion, particularly in populations in which hypertension is prevalent.


Asunto(s)
Amiloidosis/diagnóstico , Amiloidosis/genética , Fibrinógeno/genética , Enfermedades Renales/diagnóstico , Enfermedades Renales/genética , Mutación , Anciano , Femenino , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
4.
Eur J Case Rep Intern Med ; 8(4): 002448, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33987124

RESUMEN

Granulomatosis with polyangiitis (GPA) is the most common antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We describe the case of a 38-year-old woman with relapsing GPA who presented with intracranial hypertension, followed by the appearance of cavitated lung nodules despite treatment with azathioprine. Clinical improvement and ANCA titre reduction were observed after rituximab treatment. We report a rare form of GPA relapse and highlight the challenge of following-up patients with GPA, in whom can be hard to distinguish relapse from the consequences of long-term immunosuppression. LEARNING POINTS: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare inflammatory disease with pauci-immune focal necrotising lesions that affect small and medium vessels. It has a wide clinical presentation, affecting mainly the upper and lower respiratory tract and kidneys.Granulomatosis with polyangiitis (GPA) is frequently associated with PR3-ANCA and is risk factor for relapse.Follow-up of ANCA titres, which may rise before the development of symptoms, is crucial for recurrence diagnosis. Titres can also be used to distinguish recurrence from the consequences of long-term immunosuppression.

5.
J Bras Nefrol ; 43(2): 165-172, 2021.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-33258463

RESUMEN

INTRODUCTION: Estimated glomerular filtration rate (eGFR) based on serum cystatin-C (sCys) seems as accurate as when based on serum creatinine (sCr), but sCys seems a better predictor of adverse outcomes. We aimed to study whether sCys could be a reliable tool for the prediction of adverse outcomes in elderly patients with severe chronic kidney disease (CKD). METHODS: A group of 348 elderly patients with non-end-stage CKD (stages 1-4, according to eGFR-EPI sCr and/or sCys), referred to our consultation unit during 2016, was retrospectively studied and divided into four exclusive categories: CKD_stage4_neither (eGFR-sCr≥30mL/min; eGFR-sCys≥30mL/min), CKD_stage4_sCr_only (eGFR-sCr<30mL/min), CKD_stage4_sCys_only (eGFR-sCys<30mL/min) and CKD_stage4_combined (eGFRsCr<30mL/min; eGFR-sCys<30mL/min). Baseline characteristics, predictors of death, and clinical events (cardiovascular events and admissions for cardiovascular, acute kidney injury or infectious events) were explored until December 2018. RESULTS: A 77±7.4 year-old cohort, with a modified Charlson Comorbidty Index (mCCI) of 3 (IQR:1-4), was followed-up during 29 (IQR: 26-33) months. There were no significant differences between the characteristics of the stage 4 groups. Survival analysis was stratified by follow-up at 12 months, and in the first year, survival curves of CKD_stage4_sCys_only and CKD_stage4_combined groups were significantly lower than the other groups (p=0.028). Adjusting for age, sex, and mCCI, CKD_stage4_sCys_only, conversely to CKD_stage4_sCr_only, had higher rates of clinical events (p<0.05) than CKD_stage4_neither group. CONCLUSION: In elderly patients with discordant CKD staging, sCys-based eGFR seems to be a better predictor of adverse outcomes than sCr-based eGFR. Patients with stage 4 CKD defined by sCr alone seem to behave similar to those with less severe CKD.


Asunto(s)
Lesión Renal Aguda , Insuficiencia Renal Crónica , Anciano , Niño , Creatinina , Tasa de Filtración Glomerular , Humanos , Insuficiencia Renal Crónica/complicaciones , Estudios Retrospectivos
7.
Curr Gerontol Geriatr Res ; 2017: 8067094, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29317867

RESUMEN

Mortality in chronic kidney disease remains high, particularly among the elderly, who represent the most rapidly growing segment of the end-stage renal disease population in wealthier countries. The management of older adults with chronic kidney disease has become a clinical challenge, and care for those patients expected to progress to end-stage renal disease should focus on evaluating the overall benefit of offering renal replacement therapy to them. Predictive mortality models may help to inform shared decision-making in the trajectory of the elderly with chronic kidney disease. This review discusses current literature on the available predictive models for predicting survival in elderly chronic kidney disease patients and reflects the author's own interpretation and experience.

8.
World J Nephrol ; 6(2): 72-78, 2017 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-28316940

RESUMEN

The clinical spectrum of diseases associated with monoclonal gammopathies is wide and they are most commonly the consequence of renal deposition of monoclonal immunoglobulin or its components. The differential diagnosis is difficult and renal biopsy is essential. To distinguish many of these pathologies is necessary to use techniques that are not always available, even in tertiary central hospitals. This review will discuss the clinical presentation, pathologic features, treatment, prognosis and common diagnostic difficulties of these entities.

9.
J Investig Med ; 65(7): 1041-1048, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28729248

RESUMEN

Chronic kidney disease (CKD) is higher in elderly, but mortality outweighs the risk of end-stage renal disease (ESRD). Our aim was to identify prognostic markers for ESRD or death in elderly CKD, within a competing-risk analysis. This is a longitudinal study of consecutive newly referred patients with CKD ages 65 years, followed until the time of the first event (ESRD or death), using a competing-risk analysis. A modified Charlson Comorbidity Index (mCCI) was subdivided into subgroups (0-2, 3-4, ≥5). Patients were followed for hospitalizations that occurred prior to the outcomes. Among 416 patients, age 76±8 years, 52% male, median estimated glomerular filtration rate of 32 mL/min per 1.73 m2, 50% had diabetes, and 67% cardiovascular disease. Over a median follow-up of 3.6 years, 36 patients progressed to ESRD (8.7%) and 103 died (24.8%). Older age (subdistribution HR (sHR)=1. 06; p<0.001), creatinine≥1.6 mg/dL (sHR=2.03, p=0.004), hemoglobin <11 g/dL (sHR=1.91, p=0.003), mCCI score≥5 (sHR=3.01, p<0.001) and having one or more hospitalizations (sHR=1.73, p<0.001) were associated with death before ESRD. The independent predictors for ESRD with competing risk of death were: lower age (sHR=0.94; p=0.009), creatinine≥1.6 mg/dL (sHR=3.26, p=0.006), hemoglobin <11 g/dL (sHR=2.15, p=0.027), peripheral vascular disease (sHR=3.45, p=0.001) and having one or more hospitalizations (sHR=1.56, p=0.031). Elderly referred patients with CKD are near threefold more likely to die than progress to ESRD. A competing-risk framework based on available clinical and laboratory data may discriminate between those outcomes and could be used as a decision-making tool.


Asunto(s)
Fallo Renal Crónico/patología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Determinación de Punto Final , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Incidencia , Masculino , Portugal , Modelos de Riesgos Proporcionales , Factores de Riesgo
11.
Rev Assoc Med Bras (1992) ; 62(5): 434-40, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27656853

RESUMEN

INTRODUCTION: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disease that can affect multiple organs, the kidney being one of the most affected. Apart from the diagnostics value of ANCA, they have also been advocated as biomarkers of the disease activity. Recently, the genetic changes found in polyangiitis associated with serine-protease proteinase 3 (PR3)-ANCA or myeloperoxidase (MPO)-ANCA raised the possibility of immune-pathogenic and therapeutic differences. OBJECTIVE: To identify differences in the number of relapses, inflammatory markers, outcomes and renal histology related to the types of ANCA. To analyze the implications of ANCA titers in prognosis. METHOD: A retrospective observational study in a Portuguese tertiary hospital. RESULTS: There were no differences in the progression of renal function, histological pattern and initial treatment with regard to ANCA subtypes. As for the evaluated parameters, there were no significant differences according to the types of ANCA, except for mean CRP values within the normal range, which was 6.3±1.3 mg/L for MPO-ANCA and 12.4±10.14 mg/L for PR3-ANCA (p=0.04). We found that 66.7% of the MPO-ANCA-positive showed no relapses versus 40% in the case of PR3-ANCA-positive. There was no correlation between the ANCA titers at presentation, during remission, and in the last evaluation, and the number of relapses. CONCLUSION: PR3-ANCA patients have a mean CRP value within the normal range significantly higher than that of MPO-ANCA patients (p=0.04), which seems to reveal greater inflammatory activity in the first.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/sangre , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/patología , Anticuerpos Anticitoplasma de Neutrófilos/sangre , Adulto , Anciano , Anciano de 80 o más Años , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Biomarcadores , Biopsia , Proteína C-Reactiva/análisis , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Riñón/patología , Enfermedades Renales/etiología , Enfermedades Renales/patología , Masculino , Persona de Mediana Edad , Mieloblastina/sangre , Peroxidasa/sangre , Pronóstico , Proteinuria , Recurrencia , Valores de Referencia , Estudios Retrospectivos , Estadísticas no Paramétricas
12.
J. bras. nefrol ; 43(2): 165-172, Apr.-June 2021. tab
Artículo en Inglés | LILACS | ID: biblio-1286926

RESUMEN

ABSTRACT Introduction: Estimated glomerular filtration rate (eGFR) based on serum cystatin-C (sCys) seems as accurate as when based on serum creatinine (sCr), but sCys seems a better predictor of adverse outcomes. We aimed to study whether sCys could be a reliable tool for the prediction of adverse outcomes in elderly patients with severe chronic kidney disease (CKD). Methods: A group of 348 elderly patients with non-end-stage CKD (stages 1-4, according to eGFR-EPI sCr and/or sCys), referred to our consultation unit during 2016, was retrospectively studied and divided into four exclusive categories: CKD_stage4_neither (eGFR-sCr≥30mL/min; eGFR-sCys≥30mL/min), CKD_stage4_sCr_only (eGFR-sCr<30mL/min), CKD_stage4_sCys_only (eGFR-sCys<30mL/min) and CKD_stage4_combined (eGFRsCr<30mL/min; eGFR-sCys<30mL/min). Baseline characteristics, predictors of death, and clinical events (cardiovascular events and admissions for cardiovascular, acute kidney injury or infectious events) were explored until December 2018. Results: A 77±7.4 year-old cohort, with a modified Charlson Comorbidty Index (mCCI) of 3 (IQR:1-4), was followed-up during 29 (IQR: 26-33) months. There were no significant differences between the characteristics of the stage 4 groups. Survival analysis was stratified by follow-up at 12 months, and in the first year, survival curves of CKD_stage4_sCys_only and CKD_stage4_combined groups were significantly lower than the other groups (p=0.028). Adjusting for age, sex, and mCCI, CKD_stage4_sCys_only, conversely to CKD_stage4_sCr_only, had higher rates of clinical events (p<0.05) than CKD_stage4_neither group. Conclusion: In elderly patients with discordant CKD staging, sCys-based eGFR seems to be a better predictor of adverse outcomes than sCr-based eGFR. Patients with stage 4 CKD defined by sCr alone seem to behave similar to those with less severe CKD.


RESUMO Introdução: A taxa estimada de filtração glomerular (TFGe) com base na cistatina-C sérica (Cis-C) parece ser tão precisa quanto aquela baseada na creatinina sérica (Cr), mas cis-C parece ser um melhor preditor de resultados adversos. Nosso objetivo foi avaliar se a cis-C poderia ser uma ferramenta confiável para a previsão de desfechos adversos em pacientes idosos com doença renal crônica grave (DRC). Métodos: Um grupo de 348 pacientes idosos com DRC em estágio não terminal (estágios 1-4, de acordo com TFGe-EPI Cr e/ou Cis-C), encaminhados para nossa unidade de consulta durante 2016, foi estudado retrospectivamente e dividido em quatro categorias exclusivas: DRC_estágio 4 nenhum (TFGe-Cr≥30mL/min; TFGe -Cis-C≥30mL/min), DRC_estágio 4_Cr apenas (TFGe-Cr <30mL/min), DRC_estágio 4 _Cis-C_apenas (TFGe-Cis-C <30 mL/min), DRC_estágio4_combinado (TFGe-Cis-C <30mL/min. TFGe-Cr <30mL/min). Características basais, preditores de óbito e eventos clínicos (eventos cardiovasculares e internações por doenças cardiovasculares, lesão renal aguda ou eventos infecciosos) foram explorados até dezembro de 2018. Resultados: Uma coorte de 77 ± 7,4 anos, com índice de comorbidade de Charlson modificado (mCCI) de 3 (IQR: 1-4), foi acompanhada durante 29 (IQR: 26-33) meses. Não houve diferenças significativas entre as características dos grupos no estágio 4. A análise de sobrevida foi estratificada pelo acompanhamento aos 12 meses, sendo que no primeiro ano, as curvas de sobrevida dos grupos DRC_estágio4_Cis-C_apenas e DRC_estágio4_ combinado foram significativamente inferiores quando comparadas com os restantes grupos (p = 0,028). Ajustando para idade, sexo e mCCI, DRC_estágio4_Cis-C_apenas, ao contrário do grupo DRC_estágio4_Cr_apenas, teve maiores taxas de eventos clínicos (p <0,05) do que o grupo DRC_estágio4_nenhum. Conclusão: Em pacientes idosos com estadiamento discordante da DRC, a TFGe baseada na Cis-C parece ser um melhor preditor de resultados adversos do que a TFGe baseada na Cr. Pacientes com DRC em estágio 4, definida apenas por Cr, parecem se comportar de forma semelhante àqueles com DRC menos grave.


Asunto(s)
Humanos , Niño , Anciano , Insuficiencia Renal Crónica/complicaciones , Lesión Renal Aguda , Estudios Retrospectivos , Creatinina , Tasa de Filtración Glomerular
14.
Int J Artif Organs ; 38(4): 173-7, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25907533

RESUMEN

INTRODUCTION: Patients undergoing chronic hemodialysis using tunneled cuffed catheters (TCCs) are at increased risk of metastatic infections, namely endocarditis and spondydodiscitis, and mortality is high in this group. The aim of this study was to determine the clinical features, causative organisms, its susceptibility and outcomes in patients hospitalized with these infections from a single center. METHODS: All consecutive patients with TCC and endocarditis and/or spondylodiscitis treated at the authors' institution between 2005 and 2011 were selected retrospectively. RESULTS: A total of 7 cases of endocarditis and 7 cases of spondylodiscitis were diagnosed. Concurrent infection was present in 1 patient. The mean age was 63.4 years, 53.8% were male, 23% had diabetes and 31% had previous immunosuppression. The average time on hemodialysis was 24 months. Those patients with endocarditis presented with fever, and 43% had previous valvular disease; mitral valve involvement was the most common. Early surgery was performed in 2 patients.Concerning spondylodiscitis, the median time from first symptom to diagnosis was 48 days. The first manifestation was back pain in 86% percent of patients, and 71% had an epidural or paraspinous abscess demonstrated by neuroimaging. One patient underwent surgical drainage of the abscess. Regarding both infections, staphylococcus aureus was the most common causative agent with a lower rate of negative blood cultures. All patients received intravenous antibiotics for a mean duration of six weeks. The mortality rate was 46%. CONCLUSIONS: A high index of suspicion is critical in the early recognition and management of both of these infections.


Asunto(s)
Antibacterianos , Infecciones Relacionadas con Catéteres , Discitis , Endocarditis , Diálisis Renal/efectos adversos , Staphylococcus aureus/aislamiento & purificación , Administración Intravenosa , Anciano , Antibacterianos/administración & dosificación , Antibacterianos/clasificación , Infecciones Relacionadas con Catéteres/diagnóstico , Infecciones Relacionadas con Catéteres/microbiología , Infecciones Relacionadas con Catéteres/mortalidad , Infecciones Relacionadas con Catéteres/terapia , Catéteres de Permanencia/efectos adversos , Catéteres de Permanencia/microbiología , Discitis/diagnóstico , Discitis/etiología , Discitis/microbiología , Discitis/mortalidad , Discitis/terapia , Manejo de la Enfermedad , Endocarditis/diagnóstico , Endocarditis/etiología , Endocarditis/microbiología , Endocarditis/mortalidad , Endocarditis/terapia , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Huésped Inmunocomprometido , Fallo Renal Crónico/terapia , Masculino , Evaluación de Resultado en la Atención de Salud , Portugal/epidemiología , Diálisis Renal/instrumentación , Diálisis Renal/métodos , Factores de Riesgo , Sepsis/diagnóstico , Sepsis/etiología , Sepsis/microbiología , Sepsis/mortalidad , Sepsis/terapia , Tiempo de Tratamiento
15.
World J Nephrol ; 4(3): 345-53, 2015 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-26167457

RESUMEN

Kidney transplantation is the treatment of choice for end-stage renal disease. The evaluation of graft function is mandatory in the management of renal transplant recipients. Glomerular filtration rate (GFR), is generally considered the best index of graft function and also a predictor of graft and patient survival. However GFR measurement using inulin clearance, the gold standard for its measurement and exogenous markers such as radiolabeled isotopes ((51)Cr EDTA, (99m)Tc DTPA or (125)I Iothalamate) and non-radioactive contrast agents (Iothalamate or Iohexol), is laborious as well as expensive, being rarely used in clinical practice. Therefore, endogenous markers, such as serum creatinine or cystatin C, are used to estimate kidney function, and equations using these markers adjusted to other variables, mainly demographic, are an attempt to improve accuracy in estimation of GFR (eGFR). Nevertheless, there is some concern about the inability of the available eGFR equations to accurately identify changes in GFR, in kidney transplant recipients. This article will review and discuss the performance and limitations of these endogenous markers and their equations as estimators of GFR in the kidney transplant recipients, and their ability in predicting significant clinical outcomes.

16.
Case Rep Nephrol ; 2015: 919763, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26199771

RESUMEN

Systemic hereditary amyloidoses are autosomal dominant diseases associated with mutations in genes encoding ten different proteins. The clinical phenotype has implications on therapeutic approach, but it is commonly variable and largely dependent on the type of mutation. Except for rare cases involving gelsolin or transthyretin, patients are heterozygous for the amyloidogenic variants. Here we describe the first patient identified worldwide as homozygous for a nephropathic amyloidosis, involving the fibrinogen variant associated with the fibrinogen alpha-chain E526V (p.Glu545Val) mutation. In 1989, a 44-year-old woman presented with hypertension, hepatosplenomegaly, nephrotic syndrome, and renal failure. She started hemodialysis in 1990 and 6 years later underwent isolated kidney transplantation from a deceased donor. Graft function and clinical status were unremarkable for 16 years, despite progressively increased left ventricular mass on echocardiography. In 2012, 4 months before death, she deteriorated rapidly with severe heart failure, precipitated by Clostridium difficile colitis and urosepsis. Affected family members developed nephropathy, on average, nearly three decades later, which may be explained by the gene dosage effects on the phenotype of E526V (p.Glu545Val) fibrinogen A alpha-chain amyloidosis.

17.
Metabolism ; 64(2): 202-7, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25458832

RESUMEN

CONTEXT AND OBJECTIVE: Based on evidence that leptin and adiponectin are removed from circulation primarily by the kidney, we designed a study to examine the longitudinal changes of these adipokines during the first week after kidney transplantation (KTx) and to test the hypothesis that higher levels of leptin and/or adiponectin could be early biomarkers of delayed graft function (DGF=dialysis requirement during the first post-transplant week) and acute rejection. STUDY DESIGN: Repeated-measures prospective study. MATERIAL AND METHODS: Forty consecutive adult patients with end-stage renal disease who were undergoing KTx. Leptin and adiponectin were measured in blood samples that were collected before (day-0) and after KTx (days-1, 2, 4 and 7). Linear mixed-models, receiver operating characteristic and area under curve (AUC-ROC) were used. RESULTS: At post-transplant day-1, leptinemia and adiponectinemia declined 43% and 47%, respectively. At all times studied after KTx, the median leptin levels were significantly higher in patients developing DGF (n=18), but not adiponectin levels. Shortly after KTx (day-1), leptin values were significantly higher in DGF recipients in contrast to patients with promptly functioning kidneys, approximately two times higher when controlling for gender and BMI. The leptin reduction rate between pre-tranplant and one-day after KTx moderately predicted DGF (AUC=0.73). On day-1, serum leptin predicted DGF (AUC-ROC=0.76) with a performance slightly better than serum creatinine (AUC-ROC=0.72), even after correcting for BMI (AUC-ROC=0.73). Separating this analysis by gender showed that the performance of leptin in predicting DGF for male gender (AUC-ROC=0.86) improved. CONCLUSIONS: Kidney graft function is an independent determinant of leptin levels, but not of adiponectin. Leptin levels at day-1 slightly outperformed serum creatinine in predicting the occurrence of DGF, and more accurately in male gender. No significant association was detected with acute rejection.


Asunto(s)
Adiponectina/sangre , Funcionamiento Retardado del Injerto/diagnóstico , Fallo Renal Crónico/terapia , Trasplante de Riñón/efectos adversos , Riñón/fisiopatología , Leptina/sangre , Regulación hacia Arriba , Adulto , Biomarcadores/sangre , Estudios de Cohortes , Funcionamiento Retardado del Injerto/sangre , Funcionamiento Retardado del Injerto/fisiopatología , Diagnóstico Precoz , Femenino , Hospitales Urbanos , Humanos , Masculino , Portugal , Periodo Posoperatorio , Estudios Prospectivos , Sensibilidad y Especificidad
18.
Clin Biochem ; 48(16-17): 1033-8, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26162495

RESUMEN

INTRODUCTION: Serum creatinine (SCr) alone does not allow for the early diagnosis of delayed graft function (DGF) following kidney transplantation (KTx). OBJECTIVE, DESIGN AND METHODS: The diagnostic utility of urinary neutrophil gelatinase-associated lipocalin (uNGAL), serum leptin, malondialdehyde (MD.A), and cystatin C (CysC) for the early detection of DGF was previously evaluated by our group in a prospective cohort study of 40 consecutive adults undergoing KTx. Because no single biomarker achieved adequate sensitivity or specificity for practical purposes, this study was designed to evaluate the combined use of new markers with SCr. Urine and blood samples were collected 8-to-12h after KTx (day-1). Logistic regression was used to combine the biomarkers, and receiver operating characteristic curves and areas under the curve (AUC-ROC) were generated. RESULTS: Eighteen recipients developed DGF (dialysis requirement during the first post-transplant week). On day-1, the AUC for SCr to predict DGF was 0.73, 0.88 for uNGAL, 0.90 for MDA, 0.76 for leptin, and 0.91 for CysC. Adding new biomarkers to SCr enhanced the performance of DGF prediction, and the best combination was achieved with SCr, MDA, and CysC (AUC=0.96, sensitivity=100%; specificity=86%). CONCLUSION: A combination of graft damage biomarkers outperformed SCr in the early diagnosis of DGF, and the best performance was achieved by a triple-marker approach, using SCr, MDA, and CysC.


Asunto(s)
Biomarcadores/sangre , Funcionamiento Retardado del Injerto/sangre , Proteínas de Fase Aguda/orina , Adulto , Área Bajo la Curva , Creatinina/sangre , Cistatina C/sangre , Diagnóstico Precoz , Femenino , Humanos , Riñón/fisiopatología , Riñón/cirugía , Pruebas de Función Renal/métodos , Trasplante de Riñón/métodos , Leptina/sangre , Lipocalina 2 , Lipocalinas/orina , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Proto-Oncogénicas/orina , Curva ROC , Diálisis Renal/métodos , Sensibilidad y Especificidad
20.
Transplantation ; 97(10): 1058-65, 2014 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-24406454

RESUMEN

BACKGROUND: Oxidative stress is one of the most important components of the ischemia-reperfusion process after kidney transplantation (KTx) and increases with graft dysfunction. METHODS: This prospective study was conducted on 40 consecutive KTx recipients to evaluate time-dependent changes in oxidative stress-related parameters within the first week after KTx and to assess their performance in predicting delayed graft function (DGF=dialysis requirement during initial posttransplant week) and graft function at 1 year. Blood samples were collected before (day 0) and after KTx (days 1, 2, 4, and 7). Total antioxidant capacity, plasma levels of malondialdehyde (MDA), and activities of glutathione peroxidase, glutathione reductase and superoxide dismutase were measured. Multivariable linear mixed and linear regression models, receiver-operating characteristic (ROC), and areas under ROC curves (AUC-ROC) were used. RESULTS: At all time points after KTx, mean MDA levels were significantly higher in patients developing DGF (n=18). Shortly after KTx (8-12 hr), MDA values were higher in DGF recipients (on average, +0.16 µmol/L) and increased further on following day, contrasting with prompt functioning recipients. Day 1 MDA levels accurately predicted DGF (AUC-ROC=0.90), with a performance higher than SCr (AUC-ROC=0.73) and similar to cystatin C (AUC-ROC=0.91). Multivariable analysis revealed that MDA levels on day 7 represented an independent predictor of 1-year graft function. Antioxidant enzyme activities were not significantly changed during the study period and were not predictors of 1-year graft function. CONCLUSIONS: Increased MDA levels on day 1 after KTx might be an early prognostic indicator of DGF, and levels on day 7 might represent a useful predictor of 1-year graft function.


Asunto(s)
Funcionamiento Retardado del Injerto/sangre , Supervivencia de Injerto/fisiología , Trasplante de Riñón , Malondialdehído/sangre , Estrés Oxidativo/fisiología , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Factores de Tiempo
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