Rare inherited kidney diseases: an evolving field in Nephrology / Doenças renais hereditárias raras: um campo em evolução na Nefrologia

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.

Rare inherited kidney diseases: an evolving field in Nephrology.

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.

Burnout syndrome: are stroke neurologists at a higher risk? / Síndrome de Burnout: neurologistas vasculares apresentam maior risco?

ABSTRACT Background: Burnout syndrome is a work-related psychological response, characterized by emotional exhaustion, depersonalization and low professional accomplishment. Objective: The study aimed to evaluate the prevalence of burnout syndrome in neurologists in the State of Paraná, Brazil, dividing them into stroke neurologists and non-stroke neurologists. Methods: We performed a crosssectional observational study, with a quantitative approach, based on the online Maslach Burnout Inventory - Human Services Survey questionnaire. Results: A total of 74 neurologists were evaluated, 44.6% of whom had burnout syndrome, predominantly among females and stroke neurologists. Both the stroke neurologist and non-stroke neurologist groups had medium degrees of emotional exhaustion and depersonalization; however, while stroke neurologists had high professional accomplishment, non-stroke neurologists had mean-to-low scores of professional accomplishment. There was a proportional relationship between age and emotional exhaustion. Female neurologists also reported lower professional accomplishment levels. Conclusion: Burnout is prevalent among the neurologists of Paraná, corroborating the results previously reported in other studies. There seems to be no significant difference between those neurologists who work in the emergency stroke care setting compared with those who don't.

RESUMO Introdução: A síndrome de burnout é uma resposta psicológica relacionada à profissão, caracterizada por exaustão emocional, despersonalização e redução da realização pessoal. Objetivos: Objetivamos avaliar a prevalência da síndrome de burnout em neurologistas do Paraná, distribuindo a atuação entre neurologistas vasculares e não-vasculares. Métodos: Estudo observacional, transversal, com abordagem quantitativa, realizado a partir do questionário online autoaplicável Maslach Burnout Inventory - Human Services Survey. Resultados: 74 neurologistas foram avaliados, desses 44.6% apresentaram critérios para síndrome de burnout, predominando entre mulheres e stroke neurologists. Ambos os grupos apresentaram médios graus de exaustão emocional e despersonalização. Enquanto os neurologistas vasculares apresentaram alto grau de realização pessoal, os não-vasculares apresentaram médio grau. Houve relação proporcional entre idade e exaustão emocional. Neurologistas do gênero feminino mostraram menores níveis de realização pessoal. Conclusão: A síndrome de burnout é frequente nos neurologistas do Paraná, compatível com a literatura que sugere a especialidade como uma das mais susceptíveis. Não obtivemos contudo, diferenças entre os neurologistas que lidam ou não com a emergência vascular.

Furosemide-induced pseudoporphyria in a patient with chronic kidney disease: case report / Pseudoporfiria induzida por furosemida em paciente com doença renal crônica: relato de caso

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.

Furosemide-induced pseudoporphyria in a patient with chronic kidney disease: case report.

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.

Macrothrombocytopenia, renal dysfunction and nephrotic syndrome in a young male patient: a case report of MYH9-related disease / Macrotrombocitopenia, disfunção renal e síndrome nefrótica em paciente jovem do sexo masculino: relato de caso de doença relacionada ao MYH9

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.