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INTRODUCTION: The spectrum of clinical presentation of Fabry disease (FD) in women is broad and challenging. The aim is to evaluate the effectiveness of an alternative screening method for FD in women. METHODS: A collaborative multicenter cross-sectional study to evaluate the sensitivity and specificity of the combination of two tests (α-GAL enzyme activity assay and lyso-GL3 assay) for the diagnosis of FD in women. We included women with chronic kidney disease (CKD) stages 3 to 5, receiving conservative treatment or on dialysis programs, from different nephrology services in Brazil. RESULTS: We evaluated 1874 patients that underwent blood collection for α-GAL and lyso-GL3 assays. Isolated decreased α-GAL enzyme activity was found in 64 patients (3.5%), while isolated increased lyso-GL3 levels were found in 67 patients (3.6%), with one patient presenting alterations in both tests. All cases with low α-GAL enzyme activity and/or increased lyso-GL3 levels underwent genetic analysis for FD variants (132 performed GLA genetic test). Low α-GAL enzyme activity had higher sensitivity and specificity to detect FD compared to the other measures (elevated lyso-GL3 alone or both altered). The negative predictive value (NPV) of α-GAL activity was 99%, and the positive predictive value (PPV) was 9.2%. For lyso-GL3 assay, the specificity was 99.7% and the PPV was 2.9%, therefore considered inferior to α-GAL assay. Both assays altered, had higher PPV (100%) and higher NPV (99.7%) considered the best method. We found 7 cases of GLA gene variants found, resulting in an initial prevalence of 0.37% for FD in this sample female population. CONCLUSION: This study contributes to the diagnostic value of the biomarkers α-GAL and lyso-GL3 in the context of FD in women with CKD. The combination of these biomarkers was an effective approach for the diagnosis of the disease, with high PPV and NPV.
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Introduction and objectives: To minimize our peritoneal dialysis (PD) population exposure to coronavirus disease (COVID-19), in April 2020 we developed and implemented a telemedicine program. In this investigation, we aimed to compare the hospitalization rates and metabolic disorders in patients undergoing PD 6 months before and after the COVID-19 pandemic and telemedicine implementation. Materials and methods: This single-center retrospective analysis included all active prevalent patients undergoing PD from April 2020. Dialysis records were reviewed to obtain clinical, demographic, laboratory, appointment, and hospitalization data. We compared hospitalization rates (total, non-PD-related, and PD-related), hospitalization-associated factors, and metabolic disorders (hemoglobin, serum potassium, and serum phosphate) 6 months before and after the pandemic. Results: Our sample comprised 103 participants. During the pre-pandemic and post-pandemic periods, there were 13 and 27 hospital admissions, respectively. The total hospitalization incident rate ratio (IRR) was 2.48 (95% confidence interval [CI], 1.29-4.75). PD-related hospitalizations increased from 3 to 15 episodes (IRR = 7.25 [95% CI, 2.11-24.78]). In the pre-pandemic period, the educational level was lower in participants hospitalised due to PD-related issues than in participants not hospitalised. In the post-pandemic period, only sex distribution differed between patients not hospitalised and those hospitalised due to non-PD-related issues. Only serum potassium levels changed significantly in the post-pandemic period (4.79 ± 0.48 vs. 4.93 ± 0.54 mg/dL; P < 0.01). Conclusion: This study showed a significant increase in hospitalization rates after the COVID-19 pandemic period and telemedicine implementation, mainly due to PD-related infectious causes. Strategies to improve distance monitoring assistance are needed for the PD population.
Introducción y objetivos: Para minimizar la exposición de nuestra población de diálisis peritoneal (DP) a la enfermedad por coronavirus (COVID-19), en abril del 2020 desarrollamos e implementamos un programa de telemedicina. En esta investigación, nuestro objetivo fue comparar las tasas de hospitalización y los trastornos metabólicos en pacientes sometidos a DP 6 meses antes y después de la pandemia de COVID-19 y la implementación de la telemedicina. Materiales y métodos: Este análisis retrospectivo de un solo centro incluyó a todos los pacientes prevalentes activos sometidos a DP desde abril del 2020. Se revisaron los registros de diálisis para obtener datos clínicos, demográficos, de laboratorio, de citas y de hospitalización. Comparamos las tasas de hospitalización (total, no relacionada con la DP y relacionada con la DP), los factores asociados a la hospitalización y los trastornos metabólicos (hemoglobina, potasio sérico y fosfato sérico) 6 meses antes y después de la pandemia. Resultados: Nuestra muestra fue compuesta por 103 participantes. Durante los períodos prepandémico y pospandémico, hubo 13 y 27 ingresos hospitalarios, respectivamente. La razón de la tasa de incidentes de hospitalización (TIR) total fue de 2,48 (intervalo de confianza [IC] del 95%, 1,29-4,75). Las hospitalizaciones relacionadas con la DP aumentaron de 3 a 15 episodios (TIR = 7,25 [IC del 95%, 2,11-24,78]). En el período prepandémico, el nivel educativo fue más bajo en los participantes hospitalizados debido a problemas relacionados con la DP que en los participantes no hospitalizados. En el período posterior a la pandemia, solo la distribución por sexo difirió entre los pacientes no hospitalizados y los hospitalizados debido a problemas no relacionados con la DP. Solo los niveles de potasio sérico cambiaron significativamente en el período pospandémico (4.79 ± 0.48 frente a 4.93 ± 0.54 mg/dL; P < 0.01). Conclusión: Este estudio mostró un aumento significativo en las tasas de hospitalización después del período pandémico de COVID-19 y la implementación de la telemedicina, principalmente debido a causas infecciosas relacionadas con la DP. Se necesitan estrategias para mejorar la asistencia de monitoreo a distancia para la población con DP.
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INTRODUCTION AND OBJECTIVES: To minimize our peritoneal dialysis (PD) population exposure to coronavirus disease (COVID-19), in April 2020 we developed and implemented a telemedicine program. In this investigation, we aimed to compare the hospitalization rates and metabolic disorders in patients undergoing PD 6 months before and after the COVID-19 pandemic and telemedicine implementation. MATERIALS AND METHODS: This single-center retrospective analysis included all active prevalent patients undergoing PD from April 2020. Dialysis records were reviewed to obtain clinical, demographic, laboratory, appointment, and hospitalization data. We compared hospitalization rates (total, non-PD-related, and PD-related), hospitalization-associated factors, and metabolic disorders (hemoglobin, serum potassium, and serum phosphate) 6 months before and after the pandemic. RESULTS: Our sample comprised 103 participants. During the pre-pandemic and post-pandemic periods, there were 13 and 27 hospital admissions, respectively. The total hospitalization incident rate ratio (IRR) was 2.48 (95% confidence interval [CI], 1.29-4.75). PD-related hospitalizations increased from 3 to 15 episodes (IRR=7.25 [95% CI, 2.11-24.78]). In the pre-pandemic period, the educational level was lower in participants hospitalised due to PD-related issues than in participants not hospitalised. In the post-pandemic period, only sex distribution differed between patients not hospitalised and those hospitalised due to non-PD-related issues. Only serum potassium levels changed significantly in the post-pandemic period (4.79±0.48 vs. 4.93±0.54mg/dL; P<0.01). CONCLUSION: This study showed a significant increase in hospitalization rates after the COVID-19 pandemic period and telemedicine implementation, mainly due to PD-related infectious causes. Strategies to improve distance monitoring assistance are needed for the PD population.
RESUMEN
INTRODUCTION: Urgent-start peritoneal dialysis (US-PD) has been proposed as a safe modality of renal replacement therapy (RRT) for end-stage renal disease (ESRD) patients with an indication for emergency dialysis initiation. We aimed to compare the characteristics, 30-day complications, and clinical outcomes of US-PD and planned peritoneal dialysis (Plan-PD) patients over the first year of therapy. METHODS: This was a single-center retrospective study that included incident adult patients followed for up to one year. US-PD was considered when incident patients started therapy within 7 days after Tenckhoff catheter implantation. Plan-PD group consisted of patients who started therapy after the breaking period (15 days). Mechanical and infectious complications were compared 30 days from PD initiation. Hospitalization and technique failure during the first 12 months on PD were assessed by Kaplan-Meier curves and the determinants were calculated by Cox regression models. RESULTS: All patients starting PD between October/2016 and November/2019 who fulfilled the inclusion criteria were analyzed. We evaluated 137 patients (70 in the US-PD x 67 Plan-PD). The main complications in the first 30 days were catheter tip migration (7.5% Plan-PD x 4.3% US-PD - p= 0.49) and leakage (4.5% Plan-PD x 5.7% US-PD - p=0.74). Most catheters were placed using the Seldinger technique. The main cause of dropout was death in US-PD patients (15.7%) and transfer to HD in Plan-PD patients (13.4%). The occurrence of complications in the first 30 days was the only risk factor for dropout (OR = 2.9; 95% CI 1.1-7.5, p = 0.03). Hospitalization rates and technique survival were similar in both groups. CONCLUSION: The lack of significant differences in patients' outcomes between groups reinforces that PD is a safe and applicable dialysis method in patients who need immediate dialysis.
Asunto(s)
Fallo Renal Crónico , Diálisis Peritoneal , Adulto , Humanos , Diálisis Renal/efectos adversos , Estudios Retrospectivos , Factores de Tiempo , Diálisis Peritoneal/métodos , Fallo Renal Crónico/terapia , Fallo Renal Crónico/etiologíaRESUMEN
There are more than 150 different rare genetic kidney diseases. They can be classified according to diagnostic findings as (i) disorders of growth and structure, (ii) glomerular diseases, (iii) tubular, and (iv) metabolic diseases. In recent years, there has been a shift of paradigm in this field. Molecular testing has become more accessible, our understanding of the underlying pathophysiologic mechanisms of these diseases has evolved, and new therapeutic strategies have become more available. Therefore, the role of nephrologists has progressively shifted from a mere spectator to an active player, part of a multidisciplinary team in the diagnosis and treatment of these disorders. This article provides an overview of the recent advances in rare hereditary kidney disorders by discussing the genetic aspects, clinical manifestations, diagnostic, and therapeutic approaches of some of these disorders, named familial focal and segmental glomerulosclerosis, tuberous sclerosis complex, Fabry nephropathy, and MYH-9 related disorder.
Asunto(s)
Enfermedades Genéticas Congénitas/genética , Enfermedades Renales/congénito , Enfermedades Renales/diagnóstico , Riñón/fisiopatología , Adulto , Niño , Preescolar , Enfermedad de Fabry/diagnóstico , Enfermedad de Fabry/genética , Enfermedad de Fabry/terapia , Femenino , Enfermedades Genéticas Congénitas/diagnóstico , Pruebas Genéticas/métodos , Tasa de Filtración Glomerular/fisiología , Glomeruloesclerosis Focal y Segmentaria/diagnóstico , Glomeruloesclerosis Focal y Segmentaria/genética , Glomeruloesclerosis Focal y Segmentaria/terapia , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/terapia , Humanos , Lactante , Comunicación Interdisciplinaria , Enfermedades Renales/fisiopatología , Enfermedades Renales/terapia , Glomérulos Renales/patología , Túbulos Renales/patología , Masculino , Enfermedades Metabólicas/patología , Nefrología/normas , Trombocitopenia/congénito , Trombocitopenia/diagnóstico , Trombocitopenia/genética , Trombocitopenia/terapia , Esclerosis Tuberosa/diagnóstico , Esclerosis Tuberosa/genética , Esclerosis Tuberosa/terapiaRESUMEN
INTRODUCTION: Anemia is a frequent multifactorial complication of CKD seen in patients on dialysis derived mainly from impaired erythropoietin (EPO) production. A less common cause of anemia in individuals with CKD is pure red cell aplasia (PRCA) secondary to the production of anti-EPO antibodies. OBJECTIVE: This paper aimed two describe two cases of PRCA secondary to the production of anti-EPO antibodies including choice of treatment, patient progression, and a literature review. MATERIALS: This study included the cases of two patients with CKD on hemodialysis with severe anemia in need of specific investigation and management. RESULTS: Patient 1 with CKD secondary to hypertension treated with EPO for 7 months showed persistent decreases in hemoglobin (Hb) levels despite the subcutaneous administration of increasing doses of EPO; the patient required recurring blood transfusions. Workup and imaging tests were negative for the main causes of anemia in individuals with CKD on dialysis. Patient 2 with CKD secondary to adult polycystic kidney disease had been taking EPO for 2 years. The patient developed severe abrupt anemia the month he was started on HD, and required recurring transfusions to treat the symptoms of anemia. Workup and imaging findings were inconclusive. Specific laboratory tests confirmed the patients had anti-EPO antibodies. After six months of immunosuppressant therapy (corticosteroids + cyclosporine) the patients were stable with Hb > 9.0 g/dl. CONCLUSION: PRCA is a rare condition among patients on dialysis treated with rhEPO and should be considered as a possible cause of refractory anemia. Treating patients with PRCA may be challenging, since the specific management and diagnostic procedures needed in this condition are not always readily available.
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Anticuerpos Neutralizantes/sangre , Eritropoyetina/inmunología , Eritropoyetina/uso terapéutico , Fallo Renal Crónico/tratamiento farmacológico , Proteínas Recombinantes/uso terapéutico , Aplasia Pura de Células Rojas/etiología , Diálisis Renal/efectos adversos , Anciano , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Ciclosporina/administración & dosificación , Ciclosporina/uso terapéutico , Eritropoyetina/efectos adversos , Eritropoyetina/síntesis química , Femenino , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Masculino , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Proteínas Recombinantes/efectos adversos , Aplasia Pura de Células Rojas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
INTRODUCTION: Pseudoporphyria is a rare photodermatosis with characteristics similar to those of porphyria cutanea tarda, without, however, presenting abnormalities in porphyrin metabolism. Its etiology is related to chronic kidney disease, ultraviolet radiation and certain medications. The aim of the present study is to describe a case of furosemide-related pseudoporphyria in a patient with chronic kidney disease. CASE DESCRIPTION: A 76-year-old male patient with stage 4 chronic kidney disease and in continuous use of furosemide presented ulcerated lesions with peripheral erythema and central hematic crust in the legs. On a skin infection suspicion, treatment with quinolone and neomycin sulfate was initiated, without improvement. A biopsy of the lesion was performed, with histopathological examination demonstrating findings compatible with porphyria, although the patient did not present high porphyrin levels. The diagnosis of furosemide-induced pseudoporphyria was then established, with medication suspension, and there was a significant improvement of the lesions. DISCUSSION: There are few cases of pseudoporphyria described, but it is believed that this condition is underdiagnosed, especially in patients with chronic kidney disease. Both clinical and histopathological findings closely resemble porphyria, differentiating it from normal levels of porphyrin in plasma, urine, or feces. CONCLUSIONS: Although the lesions are mostly benign, they may increase the morbidity and mortality of these patients, so a proper diagnosis and early treatment are extremely important.
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Diuréticos/efectos adversos , Furosemida/efectos adversos , Porfiria Cutánea Tardía/inducido químicamente , Anciano , Diuréticos/uso terapéutico , Furosemida/uso terapéutico , Humanos , Masculino , Insuficiencia Renal Crónica/tratamiento farmacológicoRESUMEN
Introduction and objectives: To minimize our peritoneal dialysis (PD) population exposure to coronavirus disease (COVID-19), in April 2020 we developed and implemented a telemedicine program. In this investigation, we aimed to compare the hospitalization rates and metabolic disorders in patients undergoing PD 6 months before and after the COVID-19 pandemic and telemedicine implementation. Materials and methods: This single-center retrospective analysis included all active prevalent patients undergoing PD from April 2020. Dialysis records were reviewed to obtain clinical, demographic, laboratory, appointment, and hospitalization data. We compared hospitalization rates (total, non-PD-related, and PD-related), hospitalization-associated factors, and metabolic disorders (hemoglobin, serum potassium, and serum phosphate) 6 months before and after the pandemic. Results: Our sample comprised 103 participants. During the pre-pandemic and post-pandemic periods, there were 13 and 27 hospital admissions, respectively. The total hospitalization incident rate ratio (IRR) was 2.48 (95% confidence interval [CI], 1.294.75). PD-related hospitalizations increased from 3 to 15 episodes (IRR=7.25 [95% CI, 2.1124.78]). In the pre-pandemic period, the educational level was lower in participants hospitalised due to PD-related issues than in participants not hospitalised. In the post-pandemic period, only sex distribution differed between patients not hospitalised and those hospitalised due to non-PD-related issues. Only serum potassium levels changed significantly in the post-pandemic period (4.79±0.48 vs. 4.93±0.54mg/dL; P<0.01). (AU)
Introducción y objetivos: Para minimizar la exposición de nuestra población de diálisis peritoneal (DP) a la enfermedad por coronavirus (COVID-19), en abril del 2020 desarrollamos e implementamos un programa de telemedicina. En esta investigación, nuestro objetivo fue comparar las tasas de hospitalización y los trastornos metabólicos en pacientes sometidos a DP 6 meses antes y después de la pandemia de COVID-19 y la implementación de la telemedicina. Materiales y métodos: Este análisis retrospectivo de un solo centro incluyó a todos los pacientes prevalentes activos sometidos a DP desde abril del 2020. Se revisaron los registros de diálisis para obtener datos clínicos, demográficos, de laboratorio, de citas y de hospitalización. Comparamos las tasas de hospitalización (total, no relacionada con la DP y relacionada con la DP), los factores asociados a la hospitalización y los trastornos metabólicos (hemoglobina, potasio sérico y fosfato sérico) 6 meses antes y después de la pandemia. Resultados: Nuestra muestra fue compuesta por 103 participantes. Durante los períodos prepandémico y pospandémico, hubo 13 y 27 ingresos hospitalarios, respectivamente. La razón de la tasa de incidentes de hospitalización (TIR) total fue de 2,48 (intervalo de confianza [IC] del 95%, 1,29-4,75). Las hospitalizaciones relacionadas con la DP aumentaron de 3 a 15 episodios (TIR=7,25 [IC del 95%, 2,11-24,78]). En el período prepandémico, el nivel educativo fue más bajo en los participantes hospitalizados debido a problemas relacionados con la DP que en los participantes no hospitalizados. En el período posterior a la pandemia, solo la distribución por sexo difirió entre los pacientes no hospitalizados y los hospitalizados debido a problemas no relacionados con la DP. Solo los niveles de potasio sérico cambiaron significativamente en el período pospandémico (4.79±0.48 frente a 4.93±0.54 mg/dL; P<0.01). (AU)
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pandemias , Infecciones por Coronavirus/epidemiología , Diálisis Peritoneal , Telemedicina , Estudios Retrospectivos , Brasil , HospitalizaciónRESUMEN
MYH9-related disease is an autosomal dominant disorder caused by mutations of the MYH9 gene, which encodes the non-muscle myosin heavy chain IIA on chromosome 22q12. It is characterized by congenital macrothrombocytopenia, bleeding tendency, hearing loss, and cataracts. Nephropathy occurs in approximately 30% of MYH9-related disease in a male patient carrier of a de novo missense mutation in exon 1 of the MYH9 gene [c.287C > T; p.Ser(TCG)96(TTG)Leu]. He presented all phenotypic manifestations of the disease, but cataracts. Renal alterations were microhematuria, nephrotic-range proteinuria (up to 7.5 g/24h), and rapid loss of renal function. The decline per year of the glomerular filtration rate was 20 mL/min/1.73m2 for five years. Blockade of the renin-angiotensin system, the only recommended therapy for slowing the progression of this nephropathy, was prescribed. Although MYH9-related disease is a rare cause of glomerulopathy and end-stage renal disease, awareness of rare genetic kidney disorders is essential to ensure accurate diagnosis and proper management of orphan disease patients.
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Pérdida Auditiva Sensorineural/complicaciones , Síndrome Nefrótico/etiología , Trombocitopenia/congénito , Pérdida Auditiva Sensorineural/diagnóstico , Humanos , Masculino , Síndrome Nefrótico/diagnóstico , Trombocitopenia/complicaciones , Trombocitopenia/diagnóstico , Adulto JovenRESUMEN
Abstract Introduction: Urgent-start peritoneal dialysis (US-PD) has been proposed as a safe modality of renal replacement therapy (RRT) for end-stage renal disease (ESRD) patients with an indication for emergency dialysis initiation. We aimed to compare the characteristics, 30-day complications, and clinical outcomes of US-PD and planned peritoneal dialysis (Plan-PD) patients over the first year of therapy. Methods: This was a single-center retrospective study that included incident adult patients followed for up to one year. US-PD was considered when incident patients started therapy within 7 days after Tenckhoff catheter implantation. Plan-PD group consisted of patients who started therapy after the breaking period (15 days). Mechanical and infectious complications were compared 30 days from PD initiation. Hospitalization and technique failure during the first 12 months on PD were assessed by Kaplan-Meier curves and the determinants were calculated by Cox regression models. Results: All patients starting PD between October/2016 and November/2019 who fulfilled the inclusion criteria were analyzed. We evaluated 137 patients (70 in the US-PD x 67 Plan-PD). The main complications in the first 30 days were catheter tip migration (7.5% Plan-PD x 4.3% US-PD - p= 0.49) and leakage (4.5% Plan-PD x 5.7% US-PD - p=0.74). Most catheters were placed using the Seldinger technique. The main cause of dropout was death in US-PD patients (15.7%) and transfer to HD in Plan-PD patients (13.4%). The occurrence of complications in the first 30 days was the only risk factor for dropout (OR = 2.9; 95% CI 1.1-7.5, p = 0.03). Hospitalization rates and technique survival were similar in both groups. Conclusion: The lack of significant differences in patients' outcomes between groups reinforces that PD is a safe and applicable dialysis method in patients who need immediate dialysis.
Resumo Introdução: A diálise peritoneal de início urgente (US-PD) foi proposta como modalidade segura de terapia renal substitutiva (TRS) para pacientes com doença renal em estágio 5 (DRC-5) com indicação de início de diálise de emergência. Buscamos comparar características, complicações em 30 dias e desfechos clínicos de pacientes em US-PD e diálise peritoneal planejada (DP-plan) no primeiro ano de terapia. Métodos: Estudo retrospectivo de centro único, que incluiu pacientes adultos incidentes em DP acompanhados por até um ano. Considerou-se US-PD quando os pacientes iniciaram terapia até 7 dias após implante do cateter Tenckhoff. O grupo DP-plan consistiu de pacientes iniciando terapia após período break-in (15 dias). Compararam-se complicações mecânicas e infecciosas 30 dias após o início da DP. Hospitalização e falha da técnica durante os primeiros 12 meses em terapia foram avaliados por curvas Kaplan-Meier e os seus determinantes foram analisados por modelos de regressão de Cox. Resultados: Analisaram-se todos os pacientes iniciando DP entre Outubro/2016-Novembro/2019 que preencheram os critérios de inclusão. Avaliamos 137 pacientes (70 US-PD x 67 DP-plan). As principais complicações nos primeiros 30 dias foram migração da ponta do cateter (7,5% DP-plan x 4,3% US-PD - p= 0,49) e extravasamento (4,5% DP-plan x 5,7% US-PD - p=0,74). A maioria dos cateteres foi implantada pela técnica de Seldinger. A principal causa de saída da terapia foi óbito em pacientes em US-PD (15,7%) e transferência para HD em pacientes em DP-plan (13,4%). A ocorrência de complicações nos primeiros 30 dias foi o único fator de risco para saída da terapia (OR = 2,9; IC 95% 1,1-7,5, p = 0,03). Taxas de hospitalização e sobrevida da técnica foram similares em ambos os grupos. Conclusão: A ausência de diferenças significativas nos desfechos dos pacientes entre os grupos reforça que DP é um método de diálise seguro e aplicável em pacientes que necessitam diálise imediata.
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Abstract There are more than 150 different rare genetic kidney diseases. They can be classified according to diagnostic findings as (i) disorders of growth and structure, (ii) glomerular diseases, (iii) tubular, and (iv) metabolic diseases. In recent years, there has been a shift of paradigm in this field. Molecular testing has become more accessible, our understanding of the underlying pathophysiologic mechanisms of these diseases has evolved, and new therapeutic strategies have become more available. Therefore, the role of nephrologists has progressively shifted from a mere spectator to an active player, part of a multidisciplinary team in the diagnosis and treatment of these disorders. This article provides an overview of the recent advances in rare hereditary kidney disorders by discussing the genetic aspects, clinical manifestations, diagnostic, and therapeutic approaches of some of these disorders, named familial focal and segmental glomerulosclerosis, tuberous sclerosis complex, Fabry nephropathy, and MYH-9 related disorder.
Resumo As doenças renais genéticas raras compreendem mais de 150 desordens. Elas podem ser classificadas segundo achados diagnósticos como (i) distúrbios do crescimento e estrutura, (ii) doenças glomerulares, (iii) tubulares e (iv) metabólicas. Nos últimos anos, houve uma mudança de paradigma nesse campo. Os testes moleculares tornaram-se mais acessíveis, nossa compreensão sobre os mecanismos fisiopatológicos subjacentes a essas doenças evoluiu e novas estratégias terapêuticas foram propostas. Portanto, o papel do nefrologista mudou progressivamente de mero espectador a participante ativo, parte de uma equipe multidisciplinar, no diagnóstico e tratamento desses distúrbios. O presente artigo oferece um panorama geral dos recentes avanços a respeito dos distúrbios renais hereditários raros, discutindo aspectos genéticos, manifestações clínicas e abordagens diagnósticas e terapêuticas de alguns desses distúrbios, mais especificamente a glomeruloesclerose segmentar e focal familiar, complexo da esclerose tuberosa, nefropatia de Fabry e doença relacionada ao MYH9.
Asunto(s)
Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adulto , Enfermedades Genéticas Congénitas/genética , Riñón/fisiopatología , Enfermedades Renales/congénito , Enfermedades Renales/diagnóstico , Trombocitopenia/congénito , Trombocitopenia/diagnóstico , Trombocitopenia/terapia , Esclerosis Tuberosa/terapia , Pruebas Genéticas/métodos , Enfermedad de Fabry/diagnóstico , Enfermedad de Fabry/genética , Enfermedad de Fabry/terapia , Comunicación Interdisciplinaria , Tasa de Filtración Glomerular/fisiología , Pérdida Auditiva Sensorineural/diagnóstico , Enfermedades Genéticas Congénitas/diagnóstico , Túbulos Renales/patología , Enfermedades Metabólicas/patología , Nefrología/normasRESUMEN
ABSTRACT Introduction: Anemia is a frequent multifactorial complication of CKD seen in patients on dialysis derived mainly from impaired erythropoietin (EPO) production. A less common cause of anemia in individuals with CKD is pure red cell aplasia (PRCA) secondary to the production of anti-EPO antibodies. Objective: This paper aimed two describe two cases of PRCA secondary to the production of anti-EPO antibodies including choice of treatment, patient progression, and a literature review. Materials: This study included the cases of two patients with CKD on hemodialysis with severe anemia in need of specific investigation and management. Results: Patient 1 with CKD secondary to hypertension treated with EPO for 7 months showed persistent decreases in hemoglobin (Hb) levels despite the subcutaneous administration of increasing doses of EPO; the patient required recurring blood transfusions. Workup and imaging tests were negative for the main causes of anemia in individuals with CKD on dialysis. Patient 2 with CKD secondary to adult polycystic kidney disease had been taking EPO for 2 years. The patient developed severe abrupt anemia the month he was started on HD, and required recurring transfusions to treat the symptoms of anemia. Workup and imaging findings were inconclusive. Specific laboratory tests confirmed the patients had anti-EPO antibodies. After six months of immunosuppressant therapy (corticosteroids + cyclosporine) the patients were stable with Hb > 9.0 g/dl. Conclusion: PRCA is a rare condition among patients on dialysis treated with rhEPO and should be considered as a possible cause of refractory anemia. Treating patients with PRCA may be challenging, since the specific management and diagnostic procedures needed in this condition are not always readily available.
RESUMO Introdução: Anemia é complicação frequente da Doença Renal Crônica (DRC) em pacientes dialíticos. Apresenta caráter multifatorial principalmente pela insuficiente produção de eritropoietina (EPO). Situação rara causadora de anemia na DRC é Aplasia Pura de Células Vermelhas (APCV), em decorrência da produção de anticorpos anti-EPO. Objetivo: Descrever 2 casos de APCV com formação de anticorpos anti-EPO, sua abordagem clínica, evolução e revisão de literatura. Métodos: Dois pacientes em hemodiálise que desenvolveram anemia grave, necessitando investigação e manejo específico. Resultados: Paciente nº 1: feminina, 75 anos, DRC secundária à hipertensão arterial. Após 7 meses com EPO desenvolveu queda persistente em valores de hemoglobina (Hb) mesmo com incremento em doses EPO SC, necessitando transfusões de sangue recorrentes. Extensa investigação laboratorial e de imagem resultou negativa para principais causas de anemia. Paciente nº 2: masculino, 66 anos, DRC secundária à DRPA, há 2 anos em uso de EPO. No mês de entrada em HD desenvolveu anemia severa, também exigindo transfusões recorrentes para tratamento da anemia sintomática. Extensa investigação laboratorial e por imagem, sem chegar a uma conclusão definitiva. Em ambos os casos a presença de anticorpos anti-EPO foi confirmada por exames laboratoriais específicos. Terapia imunossupressora resultou em estabilização do quadro e Hb > 9,0 g/dl em ambos os pacientes, 6 meses após início do tratamento. Conclusão: APCV é condição rara entre pacientes dialíticos que recebem EPOHuR e deve ser lembrada como causa de anemia refratária. Seu manejo específico e diagnóstico laboratorial nem sempre acessível, tornando desafiadora a condução dos casos para o nefrologista.
Asunto(s)
Humanos , Masculino , Femenino , Anciano , Proteínas Recombinantes/uso terapéutico , Eritropoyetina/inmunología , Eritropoyetina/uso terapéutico , Diálisis Renal/efectos adversos , Aplasia Pura de Células Rojas/etiología , Anticuerpos Neutralizantes/sangre , Fallo Renal Crónico/tratamiento farmacológico , Proteínas Recombinantes/efectos adversos , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Eritropoyetina/biosíntesis , Eritropoyetina/efectos adversos , Trasplante de Riñón , Resultado del Tratamiento , Ciclosporina/administración & dosificación , Ciclosporina/uso terapéutico , Aplasia Pura de Células Rojas/tratamiento farmacológico , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéuticoRESUMEN
INTRODUCTION: Influenza A (H1N1) virus was first reported on April 2009 and, since then, several studies have reported the characteristics concerning the clinical presentation and pulmonary involvement. However, accurate information about the acute kidney injury (AKI) and kidney histopathological findings in these patients remain scarce. OBJECTIVE: To describe the kidney histopathological findings of 6 patients with H1N1 who developed AKI and underwent kidney biopsy, correlating them with clinical features. METHODS: We studied six patients admitted to Hospital de Clínicas UFPR with a PCR-confirmed diagnosis of H1N1who developed ARF and underwent kidney biopsy. We reviewed their medical file and the microscopy findings of the biopsy. RESULTS: Clinical and/or laboratory evidence of AKI was present in all cases, and only one did not present oliguria. Kidney tissues revealed glomerular lesions in two patients: one patient, with systemic lupus erythematosus, showed changes consistent with lupus nephritis class III A-C according to the ISN/RPS 2003 and focal thrombotic microangiopathy; the other one had intercapillary nodular glomerulosclerosis, but without clinical or laboratory evidence of diabetes. Vacuolar degenerative tubular changes were present in all cases, with focus of oxalosis in two cases. Mild to moderate atherosclerosis was found in two patients. CONCLUSION: In this study, varying degrees of vacuolar degenerative tubular changes were present in all patients, but there were no signs of acute tubular necrosis. It seems that in the present study a prerenal cause of acute renal failure was the main involved mechanim to explain the cause of renal failure in these patients.
Asunto(s)
Lesión Renal Aguda/patología , Lesión Renal Aguda/virología , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/complicaciones , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
ABSTRACT MYH9-related disease is an autosomal dominant disorder caused by mutations of the MYH9 gene, which encodes the non-muscle myosin heavy chain IIA on chromosome 22q12. It is characterized by congenital macrothrombocytopenia, bleeding tendency, hearing loss, and cataracts. Nephropathy occurs in approximately 30% of MYH9-related disease in a male patient carrier of a de novo missense mutation in exon 1 of the MYH9 gene [c.287C > T; p.Ser(TCG)96(TTG)Leu]. He presented all phenotypic manifestations of the disease, but cataracts. Renal alterations were microhematuria, nephrotic-range proteinuria (up to 7.5 g/24h), and rapid loss of renal function. The decline per year of the glomerular filtration rate was 20 mL/min/1.73m2 for five years. Blockade of the renin-angiotensin system, the only recommended therapy for slowing the progression of this nephropathy, was prescribed. Although MYH9-related disease is a rare cause of glomerulopathy and end-stage renal disease, awareness of rare genetic kidney disorders is essential to ensure accurate diagnosis and proper management of orphan disease patients.
RESUMO A doença relacionada ao MYH9 é um distúrbio autossômico dominante causado por mutações no gene MYH9 que codifica a cadeia pesada da miosina não muscular IIA no cromossomo 22q12. Ela é caracterizada por macrotrombocitopenia congênita, tendência a sangramento, perda auditiva e catarata. A nefropatia ocorre em aproximadamente 30% dos pacientes. O presente artigo relata o caso de um paciente com doença relacionada ao MYH9 portador de mutação missense de novo no exon 1 do gene MYH9 [c.287C > T; p.Ser(TCG)96(TTG)Leu]. Com a exceção de catarata, o paciente apresentou todas as manifestações fenotípicas da doença. As alterações renais incluíram micro-hematúria, proteinúria nefrótica (até 7,5 g/24h) e perda rápida da função renal. O declínio anual da taxa de filtração glomerular foi de 20 mL/min/1,73 m2 durante cinco anos. Foi receitado bloqueio do sistema renina-angiotensina, a única terapia recomendada para retardar a progressão dessa nefropatia. Embora a doença relacionada ao MYH9 seja uma causa rara de glomerulopatia e doença renal terminal, a conscientização sobre distúrbios genéticos renais raros é essencial para garantir o diagnóstico preciso e o manejo adequado dos pacientes com tal doença órfã.
Asunto(s)
Humanos , Masculino , Adulto Joven , Trombocitopenia/congénito , Pérdida Auditiva Sensorineural/complicaciones , Síndrome Nefrótico/etiología , Trombocitopenia/complicaciones , Trombocitopenia/diagnóstico , Pérdida Auditiva Sensorineural/diagnóstico , Síndrome Nefrótico/diagnósticoRESUMEN
ABSTRACT Introduction: Pseudoporphyria is a rare photodermatosis with characteristics similar to those of porphyria cutanea tarda, without, however, presenting abnormalities in porphyrin metabolism. Its etiology is related to chronic kidney disease, ultraviolet radiation and certain medications. The aim of the present study is to describe a case of furosemide-related pseudoporphyria in a patient with chronic kidney disease. Case description: A 76-year-old male patient with stage 4 chronic kidney disease and in continuous use of furosemide presented ulcerated lesions with peripheral erythema and central hematic crust in the legs. On a skin infection suspicion, treatment with quinolone and neomycin sulfate was initiated, without improvement. A biopsy of the lesion was performed, with histopathological examination demonstrating findings compatible with porphyria, although the patient did not present high porphyrin levels. The diagnosis of furosemide-induced pseudoporphyria was then established, with medication suspension, and there was a significant improvement of the lesions. Discussion: There are few cases of pseudoporphyria described, but it is believed that this condition is underdiagnosed, especially in patients with chronic kidney disease. Both clinical and histopathological findings closely resemble porphyria, differentiating it from normal levels of porphyrin in plasma, urine, or feces. Conclusions: Although the lesions are mostly benign, they may increase the morbidity and mortality of these patients, so a proper diagnosis and early treatment are extremely important.
RESUMO Introdução: A pseudoporfiria é uma fotodermatose rara com características semelhantes às da porfiria cutânea tardia, sem, no entanto, apresentar anormalidades no metabolismo da porfirina. Sua etiologia está relacionada a doença renal crônica, radiação ultravioleta e determinados medicamentos. O objetivo do presente trabalho é descrever um caso de pseudoporfiria relacionada a furosemida em paciente portador de doença renal crônica. Descrição do caso: Paciente masculino, 76 anos, com doença renal crônica estágio 4 e em uso contínuo de furosemida, apresentou lesões ulceradas com eritema periférico e crosta hemática central nas pernas. Por suspeita de infecção de pele, foi iniciado tratamento com quinolona e sulfato de neomicina, sem melhora. Foi realizada então biópsia da lesão, com exame histopatológico demonstrando achados compatíveis com porfiria, sem, no entanto, o paciente apresentar níveis elevados de porfirinas. Foi então estabelecido o diagnóstico de pseudoporfiria induzida por furosemida, com suspensão de medicação , e houve melhora significativa das lesões. Discussão: Há poucos casos de pseudoporfiria descritos, mas acredita-se que essa condição seja subdiagnosticada, principalmente em pacientes com doença renal crônica. Tanto achados clínicos quanto histopatológicos se assemelham muito à porfiria, diferenciando desta por níveis normais de porfirina no plasma, na urina ou nas fezes. Conclusões: Embora as lesões sejam majoritariamente benignas, podem aumentar a morbimortalidade desses pacientes, por isso um diagnóstico adequado e tratamento precoce são de extrema importância.
Asunto(s)
Humanos , Masculino , Anciano , Porfiria Cutánea Tardía/inducido químicamente , Diuréticos/efectos adversos , Furosemida/efectos adversos , Diuréticos/uso terapéutico , Insuficiencia Renal Crónica/tratamiento farmacológico , Furosemida/uso terapéuticoRESUMEN
INTRODUÇÃO: O vírus Influenza A (H1N1) foi primeiramente descrito em abril de 2009 e, desde então, diversos estudos relataram as características pertinentes à apresentação clínica e ao acometimento pulmonar da doença. Contudo, informações precisas referentes à insuficiência renal aguda (IRA) e às alterações histopatológicas renais nesses pacientes ainda são escassas. OBJETIVO: O objetivo deste estudo é descrever os achados histopatológicos renais de seis pacientes comprovadamente infectados pelo H1N1, que desenvolveram IRA e realizaram biópsia renal, correlacionando-os com os aspectos clínicos. MÉTODOS: Avaliamos seis pacientes do Hospital de Clínicas da UFPR com diagnóstico de H1N1 por PCR viral em 2009 que evoluíram com IRA e que foram submetidos à biópsia renal. Foram revisados os seus prontuários e das lâminas da biópsia renal. RESULTADOS: Todos os casos estudados apresentaram dados clínicos e/ou laboratoriais de IRA, sendo que somente um não apresentou oligúria. À biópsia renal, dois pacientes apresentaram alterações glomerulares: um deles, portador de lupus eritematoso sistêmico, apresentou lesões compatíveis com nefrite lúpica classe III A-C da ISN/RPS 2003 e microangiopatia trombótica focal; outro paciente apresentou glomerulosclerose nodular intercapilar, porém, sem comemorativos clínicos ou laboratoriais de diabetes. Todos os pacientes mostraram graus variáveis de alterações degenerativas vacuolares dos túbulos, com focos de oxalose em dois casos. Dois pacientes possuíam arteriosclerose em grau discreto a moderado. CONCLUSÃO: Em nosso estudo, todos os pacientes apresentarem graus variáveis de alteração degenerativa vacuolar, contudo, não foram encontrados sinais evidentes de necrose tubular aguda, parecendo existir um componente pré-renal como a causa principal de IRA nestes pacientes.
INTRODUCTION: Influenza A (H1N1) virus was first reported on April 2009 and, since then, several studies have reported the characteristics concerning the clinical presentation and pulmonary involvement. However, accurate information about the acute kidney injury (AKI) and kidney histopathological findings in these patients remain scarce. OBJECTIVE: To describe the kidney histopathological findings of 6 patients with H1N1 who developed AKI and underwent kidney biopsy, correlating them with clinical features. METHODS: We studied six patients admitted to Hospital de Clínicas UFPR with a PCR-confirmed diagnosis of H1N1who developed ARF and underwent kidney biopsy. We reviewed their medical file and the microscopy findings of the biopsy. RESULTS: Clinical and/or laboratory evidence of AKI was present in all cases, and only one did not present oliguria. Kidney tissues revealed glomerular lesions in two patients: one patient, with systemic lupus erythematosus, showed changes consistent with lupus nephritis class III A-C according to the ISN/RPS 2003 and focal thrombotic microangiopathy; the other one had intercapillary nodular glomerulosclerosis, but without clinical or laboratory evidence of diabetes. Vacuolar degenerative tubular changes were present in all cases, with focus of oxalosis in two cases. Mild to moderate atherosclerosis was found in two patients. CONCLUSION: In this study, varying degrees of vacuolar degenerative tubular changes were present in all patients, but there were no signs of acute tubular necrosis. It seems that in the present study a prerenal cause of acute renal failure was the main involved mechanim to explain the cause of renal failure in these patients.