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1.
Medicine (Baltimore) ; 100(18): e25857, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33951000

RESUMO

RATIONALE: Focal segmental glomerulosclerosis (FSGS) is one of the most common glomerular diseases, leading to end-stage renal disease. Among the 5 variants of FSGS, the collapsing variant is rare and has the worst prognosis. Solid and hematologic malignancies are associated with glomerular diseases, such as membranous nephropathy, minimal change disease, and FSGS. However, squamous cell carcinoma of the oral cavity is rarely associated with nephrotic syndrome, especially FSGS. PATIENT CONCERNS: A 55-year-old woman diagnosed with oral cavity cancer presented with generalized edema with heavy proteinuria and renal dysfunction after neoadjuvant chemotherapy and wide surgical excision. DIAGNOSIS: Renal biopsy shows segmental or global collapse of glomerular capillaries with marked hyperplasia and swelling of overlying epithelial cells, suggesting a collapsing variant of FSGS. INTERVENTIONS: After the renal biopsy, we prescribed oral prednisolone at a dose of 1 mg/kg/day. Despite immunosuppressive treatment, renal function deteriorated, and hemodialysis was started. OUTCOMES: After 23 sessions of hemodialysis and high-dose oral glucocorticoid treatment, renal function gradually improved, and oral glucocorticoid therapy was discontinued after 8 months. Currently, this patient is in a cancer-free state and has normal renal function without proteinuria. LESSONS: Unusual collapsing FSGS might be associated with neoadjuvant chemotherapy and wide surgical excision in patients with oral cavity cancer. Proper diagnostic workup, such as renal biopsy and high-dose glucocorticoid therapy, might have helped recover from nephrotic syndrome and acute renal injury in cancer patients.


Assuntos
Glomerulosclerose Segmentar e Focal/diagnóstico , Neoplasias Bucais/complicações , Síndrome Nefrótica/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicações , Biópsia , Quimioterapia Adjuvante , Relação Dose-Resposta a Droga , Feminino , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Glomérulos Renais/patologia , Pessoa de Meia-Idade , Neoplasias Bucais/terapia , Terapia Neoadjuvante/métodos , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/patologia , Síndrome Nefrótica/terapia , Prednisolona/administração & dosagem , Diálise Renal , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Resultado do Tratamento
2.
Kidney Blood Press Res ; 46(1): 114-120, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33326976

RESUMO

INTRODUCTION: Onconephrology is an emerging medical subspecialization that focuses on the numberless interrelations between cancer and kidney diseases. Tumor cells evade immune surveillance through activation of immune checkpoint pathways that suppress antitumor immune responses. By blocking checkpoints, new anticancer agents disrupt immune homeostasis but potentially induce immune-mediated diseases. Nephrologists and nephroimmunologists should be able to treat the nephrotoxic sequelae of cancer therapy and ensure continuation of the life-saving treatment. METHODS: Thirty-seven renal biopsies have been carried out over 42 months in oncologic patients, that is, 5.2% of the total native renal biopsies were carried out in the same period. The commonest diagnoses (>6 cases) were interstitial tubular nephritis, membranous glomerulopathy, IgA nephropathy, vasculitis, and focal and segmental glomerulosclerosis. CASE PRESENTATION: Three example cases, including focusing on key questions which could involve the nephrologists are reported in detail. They include a cancer-related Goodpasture Syndrome, the peculiar toxic effects of pemetrexed on tubular cells, and the intriguing relationship between bevacizumab and cryoglobulinemic glomerulonephritis. CONCLUSION: As shown by these 3 example cases, nephrologists need to be open-minded with regard to kidney biopsy in order to get a timely diagnosis. Nephrologists also need to improve their knowledge of cancer biology and therapy in order to prevent kidney problems, manage therapy-related immune-mediated disorders, and improve patient life expectancy.


Assuntos
Rim/patologia , Neoplasias/complicações , Nefrite/complicações , Idoso , Gerenciamento Clínico , Feminino , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/terapia , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/terapia , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Nefrite/patologia , Nefrite/terapia , Vasculite/complicações , Vasculite/patologia , Vasculite/terapia
3.
CuidArte, Enferm ; 14(2): 265-269, jul.-dez.2020.
Artigo em Português | BDENF - Enfermagem | ID: biblio-1148134

RESUMO

Introdução: Glomeruloesclerose focal e segmentar é uma doença que afeta crianças e adultos e se caracteriza pelo aparecimento de esclerose com colapso capilar em 50% dos glomérulos renais (lesão focal) e em partes das alças de cada glomérulo acometido (lesão segmentar). Objetivo: Realizar uma revisão bibliográfica e descrever os diagnósticos laboratoriais aplicados até o momento, os diferentes tipos de tratamento utilizados e qual a função dos corticosteroides e imunossupressores na glomeruloesclerose focal e segmentar. Método: O trabalho foi baseado na revisão da literatura nas seguintes bases de dados, Medline, LILACS, SciELO, Bireme, PubMed e Biblioteca Virtual de Saúde. Resultado: O prognóstico dos pacientes não tratados é reservado, uma vez que a doença é normalmente progressiva. A maior parte dos pacientes com GESF são córtico-resistentes, menos frequentemente córtico-dependentes e raramente córtico-sensíveis com recidivas frequentes. Por isso, diversos outros imunossupressores têm sido tentados no controle desta doença. Conclusão: Na literatura existem poucos dados sobre os resultados das estratégias medicamentosas. Futuramente, o uso de drogas mais eficientes e com menos efeitos colaterais poderá ampliar as possibilidades de tratamento específico.(AU)


Introduction: Focal and segmental glomerulosclerosis is a disease that affects children and adults and is characterized by the appearance of sclerosis with capillary collapse in 50% of the renal glomeruli (focal lesion) and in parts of the loops of each affected glomerulis (segmental lesion). Objective: To carry out a bibliographic review and describe the laboratory diagnoses applied so far, the different types of treatment used and the function of corticosteroids and immunosuppressants in focal and segmental glomerulosclerosis. Method: The study was based on the literature review in the following databases, Medline, LILACS, Scielo, Bireme, Pubmed and Virtual Health Library. Result: The prognosis of untreated patients is reserved, since the disease is usually progressive. Most patients with GESF are corticalresistant, less frequently corticic-dependent and rarely cortical-sensitive with frequent recurrences. Therefore, several other immunosuppressants have been tried in the control of this disease. Conclusion: In the literature there is little data on the results of drug strategies. In the future, the use of more efficient drugs with fewer side effects may increase the possibilities of specific treatment.(AU)


Introducción: Glomeruloesclerosis focal y segmentaria es una enfermedad que afecta a niños y adultos, y se caracteriza por la aparición de esclerosis con colapso capilar en el 50% de los glomérulos renales (lesión focal) y en partes de las asas de cada glomérulo acometido (lesión segmentaria). Objetivo: Realizar una revisión de la literatura y describir los diagnósticos de laboratorio aplicados hasta el momento, los diferentes tipos de tratamiento utilizados y cuál es el papel de los corticosteroides y los inmunosupresores en la glomeruloesclerosis focal y segmentaria. Método: El estudio se basó en la revisión de la literatura en las siguientes bases de datos, Medline, LILACS, SciELO, Bireme, PubMed y Biblioteca Virtual em Salud. Resultado: El pronóstico de los pacientes no tratados es reservado, ya que la enfermedad es normalmente progresiva. La mayoría de los pacientes con GESF son córtico-resistentes, menos frecuentemente córtico-dependientes y raramente córtico-sensibles con recidivas frecuentes. Por eso, varios otros inmunosupresores han sido tentados en el control de esta enfermedad. Conclusión: En la literatura existen pocos datos sobre los resultados de las estrategias medicamentosas. En el futuro, el uso de drogas más eficientes y con menos efectos colaterales podrá ampliar las posibilidades de tratamiento específico.(AU)


Assuntos
Humanos , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/terapia , Prognóstico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Plasmaferese , Ciclosporina/uso terapêutico , Corticosteroides/uso terapêutico , Técnicas e Procedimentos Diagnósticos , Taxa de Filtração Glomerular , Imunossupressores/uso terapêutico
4.
Am J Kidney Dis ; 75(6): 955-964, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32331832

RESUMO

Podocyte injury is the initiating step in the pathway toward clinically evident forms of nephrotic syndrome known as podocytopathies, represented as either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). There are hallmark differences in the histologic appearances of MCD and FSGS, which in turn represent distinct pathogenic models after initial podocyte injury (eg, no change in podocyte number in MCD vs podocyte detachment and death in FSGS). However, MCD and FSGS also share a number of common causes, supporting the theory that these diseases lie along a shared podocytopathy spectrum. In this installment of AJKD's Core Curriculum in Nephrology, we demonstrate how the podocytopathies can be classified according to pathogenesis and treatment response as an alternative to histologic description. Using case examples, we show how these alternative classification schemes can assist not only diagnosis, but also long-term management of podocytopathies.


Assuntos
Glomerulosclerose Segmentar e Focal , Nefrose Lipoide , Síndrome Nefrótica , Podócitos/patologia , Adulto , Gerenciamento Clínico , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Nefrose Lipoide/etiologia , Nefrose Lipoide/patologia , Nefrose Lipoide/terapia , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/patologia , Síndrome Nefrótica/terapia
5.
Transplant Proc ; 52(3): 843-849, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32199645

RESUMO

BACKGROUND: Idiopathic focal segmental glomerulosclerosis (FSGS) commonly recurs in the early post-transplant period. The treatment protocols and results are conflictive in recurrent FSGS. We aimed to present the results of our treatment protocol and basic approach to the disease recurrences. METHODS: This prospective, single-center study was conducted between the years 2015 and 2018. Twelve patients who fit completely the diagnosis of idiopathic FSGS by clinical, laboratory, and biopsy findings were included. A specific treatment protocol which consists of plasma exchange and high dose intravenous cyclosporine was delivered to the patients independently of induction protocols. Twenty-four months of outcomes of graft functions were evaluated. RESULTS: Nine patients completed the treatment protocol and were documented for evaluation. All patients achieved a complete or partial remission in an average 24 months of follow-up period. CONCLUSION: Idiopathic FSGS is more commonly recurrent than thought to be. The early detection of proteinuria is crucial because the administration of a plasma exchange-based treatment protocol can reverse proteinuria. We think our treatment protocol is a well-established, efficient, and safe choice for post-transplant recurrent FSGS in adults.


Assuntos
Ciclosporina/administração & dosagem , Glomerulosclerose Segmentar e Focal/terapia , Transplante de Rim/efeitos adversos , Troca Plasmática/métodos , Complicações Pós-Operatórias/terapia , Administração Intravenosa , Adulto , Terapia Combinada , Feminino , Glomerulosclerose Segmentar e Focal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Proteinúria/etiologia , Recidiva , Resultado do Tratamento
6.
Biochem Biophys Res Commun ; 522(3): 618-625, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-31787235

RESUMO

Focal segmental glomerulosclerosis (FSGS) is the most common cause of adult nephrotic syndrome in USA. Its mechanisms remain unclear and the effective treatment lacks. We previously reported that upregulation of microRNA (miR)-150 in human podocytes increases profibrotic proteins and decreases anti-fibrotic suppressor of cytokine signaling 1 (SOCS1). We aimed to clarify whether miR-150 inhibitor can ameliorate glomerular injury and to identify its corresponding mechanisms in adriamycin-induced FSGS mice. We found that renal miR-150 increased in adriamycin-induced FSGS mice and FAM-labeled locked nucleic acid-anti-miR-150 (LNA-anti-miR-150) was absorbed by the animal kidneys 6 h after subcutaneous injection. The administration of LNA-anti-miR-150 (2 mg/kg BW twice weekly for 6 w) inhibited renal miR-150 levels without systemic toxicity. With renal miR-150 inhibition, proteinuria, hypoalbuminemia, and hyperlipemia were ameliorated in FSGS mice compared to the scrambled LNA. Meanwhile, the elevated profibrotic proteins and proinflammatory cytokines, decreased antifibrotic SOCS1, and the filtration of T cells in FSGS mice were reverted by LNA-anti-miR-150. Finally, we found that miR-150 most located on podocytes in renal biopsies of FSGS patients. We conclude that LNA-anti-miR-150 might be a novel promising therapeutic agent for FSGS. The renal protective mechanisms might be mediated by anti-fibrosis and anti-inflammation as well as reducing infiltration of T cells in the kidney.


Assuntos
Glomerulosclerose Segmentar e Focal/terapia , MicroRNAs/antagonistas & inibidores , Oligonucleotídeos/uso terapêutico , Animais , Doxorrubicina/efeitos adversos , Fibrose , Terapia Genética , Glomerulosclerose Segmentar e Focal/induzido quimicamente , Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Rim/metabolismo , Rim/patologia , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética
7.
BMC Nephrol ; 20(1): 435, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31771524

RESUMO

BACKGROUND: Experimental studies have demonstrated that hypersecretion of growth hormone (GH) is associated with development of glomerular sclerosis. However, clinical case of such condition is very rare. Here we presented a case of focal segmental glomerulosclerosis (FSGS) associated with acromegaly. CASE PRESENTATION: A 63-year-old man was diagnosed as nephrotic syndrome with minimal change disease for 2 years. Prednisone 1 mg/kg/day for 9 months led to no response. After admission, the second kidney biopsy indicated FSGS (NOS variant). On admission, his acromegalic features were noticed and he complained with a 20-year history of soft tissue swelling of hands and feet. Serum GH and insulin-like growth factor 1 (IGF-1) concentrations were both elevated significantly. An oral glucose tolerance test showed inadequate suppression of serum GH. The presence of a pituitary macroadenoma with a diameter of 1.4 cm by MRI confirmed the diagnosis of acromegaly. Then, the tumor was subtotally removed by trans-sphenoidal surgery. Partial remission of proteinuria was achieved 3 months after surgery and maintained during follow-up, with gradual reduce of corticosteroid. CONCLUSIONS: This rare case suggested that the hypersecretion of GH may participate, at least in part, in FSGS development and progression. Early diagnosis and treatment of acromegaly is beneficial.


Assuntos
Acromegalia , Adenoma , Glomerulosclerose Segmentar e Focal , Hormônio do Crescimento Humano/análise , Fator de Crescimento Insulin-Like I/análise , Rim/patologia , Neoplasias Hipofisárias , Acromegalia/sangue , Acromegalia/diagnóstico , Acromegalia/etiologia , Adenoma/sangue , Adenoma/patologia , Adenoma/cirurgia , Diagnóstico Diferencial , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/terapia , Teste de Tolerância a Glucose , Humanos , Hipofisectomia/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Hipófise/diagnóstico por imagem , Neoplasias Hipofisárias/sangue , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Resultado do Tratamento
8.
Am J Case Rep ; 20: 1576-1580, 2019 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-31655844

RESUMO

BACKGROUND Malaria adversely affects the kidney in a variety of ways. The most common kidney injury is acute tubular necrosis, although various glomerular lesions are also described. Of these, collapsing focal segmental glomerulosclerosis (cFSGS) is the most rarely seen. Thus, the natural history of this lesion and response to treatment are not clear. Herein, we present a case of cFSGS complicated by acute interstitial nephritis caused by Plasmodium falciparum (P. falciparum) unresponsive to prednisone. CASE REPORT A 64-year-old Nigerian man with chronic kidney disease due to hypertensive nephropathy was admitted to the hospital, diagnosed with active P. falciparum malaria infection after returning from Nigeria. He developed acute kidney injury and nephrotic range proteinuria. Renal biopsy showed acute interstitial nephritis and cFSGS. Despite corticosteroid therapy, his kidney function worsened, requiring initiation of renal replacement therapy. This is the fifth case report of cFSGS due to malaria P. falciparum but the first to report the presence of acute interstitial nephritis in association with cFSGS due to malaria. CONCLUSIONS cFSGS is rarely seen as a manifestation of P. falciparum infection. When associated with acute interstitial nephritis, the prognosis seems to be worse. It appears that age and co-morbidities are the risk factors for unresponsiveness to corticosteroids, and treatment of the renal disease should focus on rapidly eradicating the parasitemia and providing supportive care. Our case report is the first to describe a combination of cFSGS and interstitial nephritis caused by P. falciparum unresponsive to corticosteroids.


Assuntos
Resistência a Medicamentos , Glomerulosclerose Segmentar e Focal/parasitologia , Malária Falciparum/complicações , Nefrite Intersticial/parasitologia , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/terapia , Nigéria/epidemiologia , Plasmodium falciparum , Prednisona/administração & dosagem , Terapia de Substituição Renal
9.
J Med Case Rep ; 13(1): 298, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31540583

RESUMO

BACKGROUND: Focal segmental glomerulosclerosis is characterized by partial (segmental) sclerotic lesions in some glomeruli (focal). Primary focal segmental glomerulosclerosis is generally considered resistant to steroid therapy. However, acromegaly is a disease that causes peculiar facial features, body types, and metabolic abnormalities due to the excessive secretion of growth hormone by a pituitary adenoma. Growth hormone has been reported to be involved in glomerular cell growth, mesangial proliferation, and glomerulosclerosis in the kidney. CASE PRESENTATION: We report a case of a Japanese patient with focal segmental glomerulosclerosis in whom decreased urinary protein was observed after surgical treatment for acromegaly. CONCLUSION: The patient's urinary protein improved as the concentration of growth hormone/insulin-like growth factor 1 decreased.


Assuntos
Acromegalia/cirurgia , Glomerulosclerose Segmentar e Focal/terapia , Proteinúria/terapia , Acromegalia/etiologia , Adenoma/complicações , Adenoma/cirurgia , Hormônio do Crescimento/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgia
10.
Pediatr Transplant ; 23(6): e13538, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31271240

RESUMO

Focal segmental glomerulosclerosis (FSGS) occurring in association with cytomegalovirus (CMV) infection in a renal transplant patient with no previous history of FSGS has rarely been reported. We present a case of a 16-year-old renal transplant recipient who developed acute hepatitis, leukopenia, nephrotic syndrome, and progressive renal dysfunction in the setting of acute infection with CMV. The cytomegalovirus infection was successfully treated with IV ganciclovir followed by oral valganciclovir but renal function deterioration and massive proteinuria continued. Features of FSGS were found on two renal allograft biopsies. Plasmapheresis and cyclophosphamide treatment was instituted with no clear effect on disease progress.


Assuntos
Infecções por Citomegalovirus/complicações , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/terapia , Transplante de Rim/efeitos adversos , Adolescente , Aloenxertos , Biópsia , Ciclofosfamida/uso terapêutico , Progressão da Doença , Humanos , Rim/fisiopatologia , Masculino , Síndrome Nefrótica/terapia , Diálise Peritoneal , Plasmaferese , Proteinúria/terapia , Transplantados
11.
Kidney Int ; 96(3): 597-611, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31200942

RESUMO

Podocytes are differentiated post-mitotic cells that cannot replace themselves after injury. Glomerular parietal epithelial cells are proposed to be podocyte progenitors. To test whether a subset of parietal epithelial cells transdifferentiate to a podocyte fate, dual reporter PEC-rtTA|LC1|tdTomato|Nphs1-FLPo|FRT-EGFP mice, named PEC-PODO, were generated. Doxycycline administration permanently labeled parietal epithelial cells with tdTomato reporter (red), and upon doxycycline removal, the parietal epithelial cells (PECs) cannot label further. Despite the presence or absence of doxycycline, podocytes cannot label with tdTomato, but are constitutively labeled with an enhanced green fluorescent protein (EGFP) reporter (green). Only activation of the Nphs1-FLPo transgene by labeled parietal epithelial cells can generate a yellow color. At day 28 of experimental focal segmental glomerulosclerosis, podocyte density was 20% lower in 20% of glomeruli. At day 56 of experimental focal segmental glomerulosclerosis, podocyte density was 18% lower in 17% of glomeruli. TdTomato+ parietal epithelial cells were restricted to Bowman's capsule in healthy mice. However, by days 28 and 56 of experimental disease, two-thirds of tdTomato+ parietal epithelial cells within glomerular tufts were yellow in color. These cells co-expressed the podocyte markers podocin, nephrin, p57 and VEGF164, but not markers of endothelial (ERG) or mesangial (Perlecan) cells. Expansion microscopy showed primary, secondary and minor processes in tdTomato+EGFP+ cells in glomerular tufts. Thus, our studies provide strong evidence that parietal epithelial cells serve as a source of new podocytes in adult mice.


Assuntos
Transdiferenciação Celular , Células Epiteliais/fisiologia , Glomerulosclerose Segmentar e Focal/patologia , Podócitos/fisiologia , Animais , Modelos Animais de Doenças , Genes Reporter/genética , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Microscopia Intravital , Proteínas Luminescentes/química , Proteínas Luminescentes/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Transgênicos , Microscopia de Fluorescência
12.
Pediatr Nephrol ; 34(11): 2343-2350, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31250206

RESUMO

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) in pediatric patients is typically difficult to treat and will progress to end-stage renal disease (ESRD) in about 10% of cases. Following kidney transplantation, FSGS can recur in up to 56% of renal allografts-with a near 100% recurrence in subsequent transplants. METHODS: Four different pediatric centers across the USA and the UK employed a protocol using LDL-apheresis (LDL-A) and pulse solumedrol to treat recurrent FSGS after transplantation in seven patients. All the patients included in this series demonstrated immediate, or early, recurrence of FSGS, which clinically presented as nephrotic-range proteinuria within hours to days after implantation of the kidney. RESULTS: All patients experienced reductions in urinary protein to creatinine ratios resulting in partial or complete remission. All patients demonstrated improvements in their estimated GFRs at their most recent follow-up since LDL-A discontinuation. CONCLUSIONS: This case series describes the successful treatment, across four different pediatric centers, of seven pediatric patients with recurrent post-transplant FSGS using the Liposorber® LA-15 in combination with pulse solumedrol.


Assuntos
Remoção de Componentes Sanguíneos/métodos , Glomerulosclerose Segmentar e Focal/terapia , Transplante de Rim , Lipoproteínas LDL/sangue , Hemissuccinato de Metilprednisolona/administração & dosagem , Proteinúria/terapia , Aloenxertos/patologia , Criança , Pré-Escolar , Terapia Combinada/métodos , Creatinina/urina , Progressão da Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular , Glomerulosclerose Segmentar e Focal/sangue , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Lactente , Falência Renal Crônica/cirurgia , Glomérulos Renais/patologia , Masculino , Proteinúria/sangue , Proteinúria/diagnóstico , Proteinúria/patologia , Pulsoterapia , Recidiva , Indução de Remissão/métodos , Estudos Retrospectivos , Resultado do Tratamento
13.
J Prim Care Community Health ; 10: 2150132719843437, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31064291

RESUMO

A 19-year-old male presented to the clinic and was found to be prehypertensive and have proteinuria on urine testing. He was subsequently diagnosed with focal segmental glomerulosclerosis (FSGS). Initial workup for pediatric hypertension includes urinalysis, chemistry panel, lipid panel, and renal ultrasound. Abnormalities on urinalysis, including proteinuria, hypercholesterolemia, and low serum albumin in children are characteristic of nephrotic disease. FSGS is a type of kidney pathology that often contributes to nephrotic disease and results from a variety of causes. For the primary care provider, being aware of the guidelines for pediatric hypertension screening and evaluation is important as 20% of children with hypertensive disease are due to kidney disease. FSGS is the third leading cause of end-stage renal disease in children aged 12 to 19 years, and its incidence was found to be rising in a study of Olmsted County, MN residents. Treatment to complete or partial remission of the proteinuria can slow the progression of renal disease. In this case report, we will discuss the evaluation of pediatric hypertension workup with proteinuria, specifically due to FSGS, and review current management strategies.


Assuntos
Glomerulosclerose Segmentar e Focal/diagnóstico , Hipertensão/diagnóstico , Proteinúria/diagnóstico , Anti-Hipertensivos/uso terapêutico , Tratamento Conservador , Dieta com Restrição de Proteínas , Dieta Hipossódica , Feminino , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Hipertensão/etiologia , Hipertensão/terapia , Losartan/uso terapêutico , Nefrite Hereditária , Proteinúria/etiologia , Proteinúria/terapia , Adulto Jovem
14.
CRISPR J ; 2: 108-120, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30998089

RESUMO

Focal segmental glomerulosclerosis (FSGS) is defined by focal (involving few glomeruli) and segmental sclerosis of the glomerular tuft that manifests with nephrotic syndrome. Mutations in genes involved in the maintenance of structure and function of podocytes have been found in a minority of these patients. A family with adult-onset autosomal dominant FSGS was recently found to carry a new germline missense heterozygous mutation (p.G189R) in the octapeptide domain of the transcription factor PAX2. Here, we efficiently corrected this point mutation in patient-derived induced pluripotent stem cells (iPSCs) by means of CRISPR-Cas9-based homology-directed repair. The iPSC lines were differentiated into podocytes, which were tested for their motility. Editing the PAX2 p.G189R mutation restored podocyte motility, which was altered in podocytes derived from patient iPSCs.


Assuntos
Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/terapia , Fator de Transcrição PAX2/genética , Adulto , Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas/genética , Diferenciação Celular , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Engenharia Genética/métodos , Mutação em Linhagem Germinativa/genética , Glomerulosclerose Segmentar e Focal/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/fisiologia , Glomérulos Renais/metabolismo , Mutação/genética , Fator de Transcrição PAX2/análise , Podócitos/química , Podócitos/metabolismo , Podócitos/fisiologia , Polimorfismo de Nucleotídeo Único/genética
15.
Nephrology (Carlton) ; 24(11): 1179-1188, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30891898

RESUMO

AIM: Focal segmental glomerulosclerosis recurs in up to 30% and up to 80% of adult and pediatric kidney transplant recipients, respectively. There is no standard of care treatment. The purpose of this study was to evaluate clinical characteristics, treatments and outcomes of patients with focal segmental glomerulosclerosis recurrence (FSGSr). METHODS: This was a retrospective single-center cohort study including FSGSr patients treated with plasmapheresis (PP) and combinations of high dose steroids, cyclosporine and rituximab. RESULTS: Among 61 patients included in this analysis the median time to diagnosis was 19 days. The incidence of first biopsy-confirmed FSGSr was 18% reaching 52.4% with follow-up biopsies. During PP treatment 54% of the patients developed infectious complications. PP was discontinued in 37% of patients due to treatment failure (no remission or graft loss) and in 26% due to an adverse event. All patients who discontinued PP due to adverse event did not show clinical response or lost the allograft. The incidence of acute rejection was 34.4%. The incidences of partial and complete remissions were 16.4% and 27.8%, respectively. Overall 6-years patient and graft survivals were 90.7% and 64.5%, respectively. CONCLUSION: This analysis confirms the low, variable and unpredictable rate of FSGSr remission, inconsistencies among available therapeutic options and its high rate of adverse events, and the negative impact on graft survival.


Assuntos
Glomerulosclerose Segmentar e Focal/epidemiologia , Transplante de Rim , Adolescente , Adulto , Criança , Feminino , Glomerulosclerose Segmentar e Focal/terapia , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Plasmaferese/efeitos adversos , Recidiva , Estudos Retrospectivos , Adulto Jovem
16.
BMC Nephrol ; 20(1): 45, 2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30732569

RESUMO

BACKGROUND: Nephrotic syndrome (NS) is one of the most frequent occurring chronic kidney diseases in childhood, despite its rarely occurrence in the general population. Detailed information about clinical data of NS (e.g. average length of stay, complications) as well as of secondary nephrotic syndrome (SNS) is not well known. METHODS: A nationwide ESPED follow-up study presenting the clinical course and management of children with NS in Germany. RESULTS: In course of 2 years, 347 children developed the first onset of NS, hereof 326 patients (93.9%) had a primary NS, and 19 patients had a SNS (missing data in 2 cases), the majority due to a Henoch-Schönlein Purpura. Patients with steroid-resistant NS (SRNS) stayed significantly longer in hospital than children with steroid-sensitive NS (25.2 vs. 13.3 d, p <  0.001). Patients with bacterial/viral infections stayed longer in hospital (24.9 d/19.5d) than children without an infection (14.2 d/14.9 d; p <  0.001; p = 0.016). Additionally, children with urinary tract infections (UTI) (p < 0,001), arterial hypertension (AH) (p < 0.001) and acute renal failure (ARF) (p < 0,001) stayed significantly longer in hospital. Patients with SRNS had frequent complications (p = 0.004), such as bacterial infections (p = 0.013), AH (p < 0.001), UTI (p < 0.001) and ARF (p = 0.007). Children with a focal segmental glomerulosclerosis (FSGS) had significantly more complications (p = 0.04); specifically bacterial infections (p = 0.01), UTI (p = 0.003) and AH (p < 0,001). Steroid-resistance was more common in patients with UTI (p < 0.001) and in patients with ARF (p = 0.007). Furthermore, steroid-resistance (p < 0.001) and FSGS (p < 0.001) were more common in patients with AH. CONCLUSIONS: This nationwide, largest German study presents results on the clinical course of children with NS considering a diverse range of complications that can occur with NS. The establishment of a region-wide and international pediatric NS register would be useful to conduct further diagnostic and therapy studies with the aim to reduce the complication rate and to improve the prognosis of NS, and to compare the data with international cohorts.


Assuntos
Síndrome Nefrótica/terapia , Adolescente , Corticosteroides/uso terapêutico , Fatores Etários , Criança , Criança Hospitalizada/estatística & dados numéricos , Pré-Escolar , Comorbidade , Resistência a Medicamentos , Feminino , Seguimentos , Alemanha/epidemiologia , Glomerulosclerose Segmentar e Focal/epidemiologia , Glomerulosclerose Segmentar e Focal/terapia , Inquéritos Epidemiológicos , Humanos , Hipertensão/epidemiologia , Lactente , Recém-Nascido , Infecções/epidemiologia , Tempo de Internação/estatística & dados numéricos , Masculino , Síndrome Nefrótica/epidemiologia , Turquia/etnologia
17.
Pediatr Nephrol ; 34(10): 1655-1669, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30218191

RESUMO

Low-density lipoprotein (LDL) apheresis has been used increasingly in clinical practice for the treatment of renal diseases with nephrotic syndrome (NS), specifically focal segmental glomerulosclerosis (FSGS). Persistent hyperlipidemia for prolonged periods is nephrotoxic and leads to chronic progressive glomerular and tubulointerstitial injury. Effective management of hyperlipidemia with HMG-CoA reductase inhibitors or LDL apheresis in drug-resistant NS patients may prevent the progression of renal disease and, in some patients, resolution of NS symptoms. Available literature reveals beneficial effects of LDL apheresis for NS refractory to drug therapy. Here we update on the current understanding of lipid nephrotoxicity and application of LDL apheresis to prevent progression of renal diseases.


Assuntos
Remoção de Componentes Sanguíneos/métodos , Glomerulosclerose Segmentar e Focal/terapia , Hiperlipidemias/terapia , Lipoproteínas LDL/metabolismo , Síndrome Nefrótica/terapia , Animais , Criança , Modelos Animais de Doenças , Progressão da Doença , Glomerulosclerose Segmentar e Focal/sangue , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/fisiopatologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Glomérulos Renais/metabolismo , Glomérulos Renais/fisiopatologia , Metabolismo dos Lipídeos , Lipoproteínas LDL/sangue , Síndrome Nefrótica/sangue , Síndrome Nefrótica/etiologia , Eliminação Renal/fisiologia , Resultado do Tratamento
18.
Transplantation ; 103(1): 202-209, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29894413

RESUMO

BACKGROUND: Treatment of focal segmental glomerular sclerosis (FSGS) after kidney transplantation is challenging with unpredictable outcomes. The objective was to investigate the use of adrenocorticotropic hormone (ACTH) analogue gel in kidney transplant recipients with de novo or recurrent FSGS resistant to therapeutic plasma exchange (TPE) and/or rituximab. METHODS: We performed a retrospective review of cases of de novo or recurrent resistant FSGS at 2 large US transplant centers between April 2012 and December 2016. Proteinuria was measured by urine protein to creatinine ratio. RESULTS: We identified 20 cases of posttransplant recurrent and de novo FSGS resistant to conventional therapy with TPE and rituximab. Mean ± SD age was 49 ± 15.5 years, 14 (70%) were male, 13 (65%) were whites, and 8 (38%) had previous kidney transplants. Median (interquartile range) of recurrent and de novo FSGS was 3 (0.75-7.5) months posttransplant. The majority of patients, 15 (75%), received TPE as a treatment at the time of diagnosis and 10 (50%) received rituximab, which was started before the use of ACTH gel. There was a significant improvement of urine protein to creatinine ratio from a mean ± SD of 8.6 ± 7.6 g/g before ACTH gel to 3.3 ± 2.3 g/g after the use of ACTH gel (P = 0.004). Ten (50%) patients achieved complete or partial remission. CONCLUSIONS: Although, the response varied among the recipients, ACTH gel might be an effective therapy for posttransplant resistant FSGS cases that fail to respond to TPE and rituximab.


Assuntos
Hormônio Adrenocorticotrópico/uso terapêutico , Glomerulosclerose Segmentar e Focal/terapia , Transplante de Rim , Hormônio Adrenocorticotrópico/efeitos adversos , Hormônio Adrenocorticotrópico/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Baltimore , Feminino , Géis , Glomerulosclerose Segmentar e Focal/diagnóstico , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Missouri , Troca Plasmática , Recidiva , Indução de Remissão , Estudos Retrospectivos , Rituximab/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
19.
Med Clin (Barc) ; 152(9): 361-367, 2019 05 03.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30554809

RESUMO

Collapsing glomerulopathy (CG) is a rare entity as a glomerular disease. Although it has been considered as a variant of focal segmental glomerulosclerosis, the fact is that the podocyte lesions show different features with respect to the typical focal segmental glomerulosclerosis, an aspect that has been attributed to a type of podocytopathy. In CG, the podocyte lesion is typically characterised by a dysregulated podocyte phenotype, reflected by the loss of expression of mature podocyte markers. CG can be a primary disease or it can be associated with several causal factors that develop a common histopathological entity. The clinical expressiveness of CG is often characterised by the presence of a nephrotic syndrome and a rapid deterioration of the renal function than other variants of the focal segmental glomerulosclerosis. The prognosis of these patients is a rapid progression towards end-stage renal disease with poor response to treatment.


Assuntos
Glomerulonefrite , Diagnóstico Diferencial , Glomerulonefrite/diagnóstico , Glomerulonefrite/etiologia , Glomerulonefrite/fisiopatologia , Glomerulonefrite/terapia , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/fisiopatologia , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/fisiopatologia , Síndrome Nefrótica/terapia , Prognóstico , Fatores de Risco
20.
Exp Clin Transplant ; 17(4): 461-469, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30570457

RESUMO

OBJECTIVES: High recurrence and inferior graft survival rates have been reported for kidney transplant recipients with primary focal segmental glomerulosclerosis. Plasmapheresis is widely used to treat posttransplant relapsing focal segmental glomerulosclerosis, but the effectiveness of prophylactic plasmapheresis remains controversial. MATERIALS AND METHODS: In this single-center retrospective study, 21 adult deceased-donor kidney transplant recipients who received prophylactic plasmapheresis were analyzed. Of these, 10 received posttransplant prophylactic plasmapheresis only (less-intensive regimen) and 11 received pre- and posttransplant prophylactic plasmapheresis (more-intensive regimen). Patients with recurrence were treated with steroids and plasmapheresis. Median follow-up was 45 months (interquartile range, 30-107 mo). RESULTS: At last visit, 20/21 patients (95%) were alive and 17/21 (81%) had functioning grafts. Cumulative focal segmental glomerulosclerosis recurrence rate was 38% (8/21): 30% (3/10) in the less-intensive and 45% (5/11) in the more-intensive group (P = .6594). Four of 8 patients (50%) with relapse eventually had graft loss due to recurrence: 100% (3/3) in the less-intensive and 20% (1/5) in the more-intensive group (P = .1429). Complete remission was observed in 25% (2/8) of recipients with recurrence: 0% (0/3) in the less-intensive and 40% (2/5) in the more-intensive group (P = .4643). Two of 8 patients (25%) remained plasmapheresis dependant: 0% (0/3) in the less-intensive and 40% (2/5) in the more-intensive group (P = .4643). Response rate (complete/partial) was higher in the more-intensive group (80% [4/5] vs 0% [0/3]; P = .1429); however, overall, the 2 regimens did not show significantly different outcomes. Comparison between this series and a historical control group of 52 patients with primary focal segmental glomerulosclerosis transplanted at our center and not receiving plasmapheresis prophylaxis did not demonstrate any advantages. CONCLUSIONS: No benefits from prophylactic plasmapheresis in deceased-donor kidney transplant recipients with primary focal segmental glomerulosclerosis were shown. Prospective randomized studies comparing alternative preemptive strategies are warranted.


Assuntos
Glomerulosclerose Segmentar e Focal/terapia , Transplante de Rim , Plasmaferese , Adolescente , Adulto , Feminino , Glomerulosclerose Segmentar e Focal/sangue , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/imunologia , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Masculino , Plasmaferese/efeitos adversos , Recidiva , Retratamento , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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