Sodium-glucose cotranspor ter 2 (SGLT2) inhibitors in nephrolithiasis: should we "gliflozin" patients with kidney stone disease? / Inibidores de cotransportadores sódio-glicose-2 (SGLT2) na nefrolitíase - devemos "gliflozinar" os litiásicos?

ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also "gliflozin" our patients with kidney stone disease?

RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também "gliflozinar" os litiásicos?

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.

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.

Tratamento da nefrolitíase: onde está a evidência dos ensaios clínicos? / Therapy of nephrolithiasis: where is the evidence from clinical trials?

Resumo A prevalência da nefrolitíase está aumentando em todo o mundo e resulta em ônus significativo para o sistema de saúde. Novos estudos revelam que a formação de cálculos urinários está associada a várias morbidades graves. No entanto, poucos estudos observacionais ou ensaios clínicos randomizados de qualidade demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. Portanto, nesta revisão são analisadas as evidências disponíveis da terapia médica expulsiva para cálculos ureterais; avaliam-se os dados da terapêutica não farmacológica, incluindo modificações dietéticas e terapia à base de sucos cítricos; e discute-se a eficácia dos diuréticos tiazídicos no tratamento da hipercalciúria associada à nefrolitíase recorrente.

Abstract The prevalence of kidney stone disease is increasing worldwide with significant health and economic burden. Newer research is finding that stones are associated with several serious morbidities. Yet, few randomized clinical trials or high quality observational studies have assessed whether clinical interventions decrease the recurrence of kidney stones. Therefore, in this review we analyze the available evidence on medical expulsive therapy for ureteral stones; describe the evidence about non-pharmacological stone therapy including dietary modifications and citrus juice-based therapy; and discuss the efficacy of thiazide diuretics for the treatment of hypercalciuria in recurrent nephrolithiasis.

Association of primary hyperparathyroidism and humoral hypercalcemia of malignancy in a patient with clear cell renal carcinoma.

Hypercalcemia is found frequently in patients with cancer. Besides the etiology related to the malignancy, other causes should be considered in the differential diagnostic, as primary hyperparathyroidism, granulomatous diseases and the use of thiazide diuretics. We present a case report of a severe hypercalcemia due to a rare association and review the relevant literature. A female patient, 57 years old, sent to the Endocrinology Service of Hospital das Clínicas da Universidade do Paraná (SEMPR) in order to investigate severe hypercalcemia with frequent need of hospitalization. The patient was in chemotherapy treatment for recurrence of clear cell renal cancer. During the investigation she presented high level of parathyroid hormone (PTH) and parathyroid scintigraphy suggestive of hyperplasia/ adenoma of parathyroid, histopathological diagnosis was confirmed after parathyroidectomy. After surgery the patient presented undetectable levels of PTH. However, she continued with progressive increase of serum calcium, with no signs of bone metastases or change in vitamin D metabolism. The investigation showed high levels of PTH-related protein (PTHrP), leading us to the diagnosis of hypercalcemia of malignancy. The patient presented severe hypercalcemia due to the rare association of primary hyperparathyroidism and humoral hypercalcemia of malignancy due to secretion of PTHrP by tumor cells. The presence of isolated primary hyperparathyroidism, as a cause of hypercalcemia in cancer patients, has been described in approximately 5-10% of the patients. However, the association of primary hyperparathyroidism and humoral hypercalcemia of malignancy (which means with concomitant elevation of PTH and PTHrP) is rare, only three cases have been described in the literature.

Association of primary hyperparathyroidism and humoral hypercalcemia of malignancy in a patient with clear cell renal carcinoma

Hypercalcemia is found frequently in patients with cancer. Besides the etiology related to the malignancy, other causes should be considered in the differential diagnostic, as primary hyperparathyroidism, granulomatous diseases and the use of thiazide diuretics. We present a case report of a severe hypercalcemia due to a rare association and review the relevant literature. A female patient, 57 years old, sent to the Endocrinology Service of Hospital das Clínicas da Universidade do Paraná (SEMPR) in order to investigate severe hypercalcemia with frequent need of hospitalization. The patient was in chemotherapy treatment for recurrence of clear cell renal cancer. During the investigation she presented high level of parathyroid hormone (PTH) and parathyroid scintigraphy suggestive of hyperplasia/ adenoma of parathyroid, histopathological diagnosis was confirmed after parathyroidectomy. After surgery the patient presented undetectable levels of PTH. However, she continued with progressive increase of serum calcium, with no signs of bone metastases or change in vitamin D metabolism. The investigation showed high levels of PTH-related protein (PTHrP), leading us to the diagnosis of hypercalcemia of malignancy. The patient presented severe hypercalcemia due to the rare association of primary hyperparathyroidism and humoral hypercalcemia of malignancy due to secretion of PTHrP by tumor cells. The presence of isolated primary hyperparathyroidism, as a cause of hypercalcemia in cancer patients, has been described in approximately 5-10% of the patients. However, the association of primary hyperparathyroidism and humoral hypercalcemia of malignancy (which means with concomitant elevation of PTH and PTHrP) is rare, only three cases have been described in the literature. Arch Endocrinol Metab. 2015;59(1):84-8.

Emphysematous and xanthogranulomatous pyelonephritis: rare diagnosis.

Pyelonephritis is a pyogenic infection of renal parenchyma that involves the renal pelvis. It is generally of easy diagnosis. The present case report aims to describe two different manifestations of this infection: xanthogranulomatous pyelonephritis and emphysematous pyelonephritis, which have poor prognosis and require a more effective treatment. The two cases were women in the fiftieth and sixtieth decade of life, with diabetes mellitus and history of weight loss. The diagnosis of the renal infection was established through computed tomography and the treatment was based in surgical procedure, with favorable outcome.

Emphysematous and xanthogranulomatous pyelonephritis: rare diagnosis

Pyelonephritis is a pyogenic infection of renal parenchyma that involves the renal pelvis. It is generally of easy diagnosis. The present case report aims to describe two different manifestations of this infection: xanthogranulomatous pyelonephritis and emphysematous pyelonephritis, which have poor prognosis and require a more effective treatment. The two cases were women in the fiftieth and sixtieth decade of life, with diabetes mellitus and history of weight loss. The diagnosis of the renal infection was established through computed tomography and the treatment was based in surgical procedure, with favorable outcome.

Hemibalismo-hemicoreia em estado hiperglicêmico não cetótico: distúrbio do movimento associado ao diabetes melito / Hemiballism-hemichorea with non-ketotic hyperglycemia: movement disorder related to diabetes mellitus

O diabetes melito, especialmente quando descompensado, pode culminar em várias complicações neurológicas, sendo o desenvolvimento de movimentos involuntários uma das formas mais raras. O estado hiperglicêmico não cetótico em pacientes idosos, que se apresentam com movimentos tipo balismo-coreia associados a alterações nos exames de imagem cerebral (tomografia computadorizada e/ou ressonância magnética), constitui uma síndrome de caracterização recente e de poucos relatos na literatura. Apresentamos o caso de um paciente admitido com história de movimentos involuntários do tipo hemibalismo-hemicoreia à esquerda associado a estado hiperglicêmico com hemoglobina glicada de 14,4 por cento. O exame tomográfico de crânio revelou área hiperdensa em topografia de gânglios da base à direita. Após controle glicêmico adequado, houve melhora progressiva e recuperação do quadro neurológico, com desaparecimento completo da lesão hiperdensa inicial.

Diabetes mellitus, especially when not under control, can lead to several neurological complications being the development of involuntary movements one of the rarest presentations. Nonketotic hyperglycemia in aged patients who present with ballismus-chorea movements and cerebral image alterations in computerized tomography (CT) and magnetic resonance constitute a syndrome of recent characterization and few cases in literature. We present a case of a 75 year-old male patient admitted with history of hemiballismus-hemichorea movements, hyperglycemia, glycated hemoglobin of 14.4 percent and CT with a hyperdense area in the topography of the right basal ganglia. After glycemic control, the neurological signs resolved completely and the initial hyperdense lesion disappeared.

[Antineutrophil cytoplasmic antibody (Anca)-associated autoimmune disease induced by propylthiouracil]. / Auto-imunidade ANCA (Anticorpo Anti-Citoplasma de Neutrófilos) positiva induzida por propiltiouracil: relato de caso e revisão da literatura.

Antithyroid drugs sometimes cause severe complications. Propylthiouracil (PTU) can be associated to ANCA positive vasculitis, most often related to myeloperoxidase subtype (ANCA-MPO). Our objective is to describe a female patient with Graves' disease, who developed PTU induced-autoimmune disease, with cutaneous, pulmonary, and renal lesions, associated with ANCA. Histopathological examination revealed diffuse pulmonary hemorrhage, and focal segmental glomerulosclerosis at the kidney biopsy. She was treated with systemic corticosteroid therapy and cyclophosphamide, with clinical improvement. This case highlights the need for greater awareness of this relatively rare adverse effect of propylthiouracil.

Auto-imunidade ANCA (Anticorpo Anti-Citoplasma de Neutrófilos) positiva induzida por propiltiouracil: relato de caso e revisão da literatura / Antineutrophil Cytoplasmic Antibody (Anca)-Associated autoimmune disease induced by propylthiouracil

A terapêutica com drogas antitireoidianas pode ser acompanhada de efeitos colaterais. Propiltiouracil (PTU) pode induzir vasculites anticorpo anti-citoplasma de neutrófilos (ANCA) positivas, na maioria das vezes relacionadas ao subtipo mieloperoxidase (ANCA-MPO). O nosso objetivo é relatar o caso de uma paciente com doença de Graves que desenvolveu auto-imunidade induzida por PTU, com manifestações cutâneas, pulmonares e renais, associadas à positividade do ANCA. O exame anátomo-patológico pulmonar revelou hemorragia difusa e a biópsia renal demonstrou glomeruloesclerose segmentar e focal. Foi tratada com pulsoterapia com corticóides e ciclofosfamida, com boa evolução clínica. Este caso enfatiza a necessidade de detecção e tratamento precoce deste efeito adverso relativamente raro do PTU.

Antithyroid drugs sometimes cause severe complications. Propylthiouracil (PTU) can be associated to ANCA positive vasculitis, most often related to myeloperoxidase subtype (ANCA-MPO). Our objective is to describe a female patient with Graves' disease, who developed PTU induced-autoimmune disease, with cutaneous, pulmonary, and renal lesions, associated with ANCA. Histopathological examination revealed diffuse pulmonary hemorrhage, and focal segmental glomerulosclerosis at the kidney biopsy. She was treated with systemic corticosteroid therapy and cyclophosphamide, with clinical improvement. This case highlights the need for greater awareness of this relatively rare adverse effect of propylthiouracil.

Associaçäo de espondilite anquilosante com síndrome de Ehlers Danlos / Association of ankylosing spondylitis with Ehlers Danlos syndrome

Relata-se caso de paciente de 17 anos de idade, com início há seis meses de quadro espondilite anquilosante (artrite de tornozelos, lombalgia inflamatória, restriçäo a movimentaçäo lombar, sacroiliíte bilateral) e que, conconcomitantemente, estava acometido de síndrome de Ehlers-Danlos. A apresentaçäo se justifica pela condiçäo inusitada e interessante, pois no mesmo doente coexistem duas doenças antagônicas (uma que confere rigidez e outra hipermobilidade), bem como pelo fato de na literatura pesquisada näo haver relato anterior dessa associaçäo. Discutem-se as formas de apresentaçäo de Ehlers-Danlos em que este paciente se enquadra