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1.
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
2.
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 , Tempo de Internação/estatística & dados numéricos , Masculino , Síndrome Nefrótica/epidemiologia , Turquia/etnologia
3.
Am J Kidney Dis ; 73(2): 218-229, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30420158

RESUMO

RATIONALE & OBJECTIVES: Glomerular diseases, including minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A (IgA) nephropathy, share clinical presentations, yet result from multiple biological mechanisms. Challenges to identifying underlying mechanisms, biomarkers, and new therapies include the rarity of each diagnosis and slow progression, often requiring decades to measure the effectiveness of interventions to prevent end-stage kidney disease (ESKD) or death. STUDY DESIGN: Multicenter prospective cohort study. SETTING & PARTICIPANTS: Cure Glomerulonephropathy (CureGN) will enroll 2,400 children and adults with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (including IgA vasculitis) and a first diagnostic kidney biopsy within 5 years. Patients with ESKD and those with secondary causes of glomerular disease are excluded. EXPOSURES: Clinical data, including medical history, medications, family history, and patient-reported outcomes, are obtained, along with a digital archive of kidney biopsy images and blood and urine specimens at study visits aligned with clinical care 1 to 4 times per year. OUTCOMES: Patients are followed up for changes in estimated glomerular filtration rate, disease activity, ESKD, and death and for nonrenal complications of disease and treatment, including infection, malignancy, cardiovascular, and thromboembolic events. ANALYTICAL APPROACH: The study design supports multiple longitudinal analyses leveraging the diverse data domains of CureGN and its ancillary program. At 2,400 patients and an average of 2 years' initial follow-up, CureGN has 80% power to detect an HR of 1.4 to 1.9 for proteinuria remission and a mean difference of 2.1 to 3.0mL/min/1.73m2 in estimated glomerular filtration rate per year. LIMITATIONS: Current follow-up can only detect large differences in ESKD and death outcomes. CONCLUSIONS: Study infrastructure will support a broad range of scientific approaches to identify mechanistically distinct subgroups, identify accurate biomarkers of disease activity and progression, delineate disease-specific treatment targets, and inform future therapeutic trials. CureGN is expected to be among the largest prospective studies of children and adults with glomerular disease, with a broad goal to lessen disease burden and improve outcomes.


Assuntos
Glomerulonefrite por IGA/patologia , Glomerulonefrite Membranosa/patologia , Glomerulosclerose Segmentar e Focal/patologia , Falência Renal Crônica/prevenção & controle , Nefrose Lipoide/patologia , Centros Médicos Acadêmicos , Adolescente , Adulto , Fatores Etários , Biópsia por Agulha , Criança , Diagnóstico Diferencial , Progressão da Doença , Feminino , Glomerulonefrite/mortalidade , Glomerulonefrite/patologia , Glomerulonefrite/terapia , Glomerulonefrite por IGA/mortalidade , Glomerulonefrite por IGA/terapia , Glomerulonefrite Membranosa/mortalidade , Glomerulonefrite Membranosa/terapia , Glomerulosclerose Segmentar e Focal/mortalidade , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Imuno-Histoquímica , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nefrose Lipoide/mortalidade , Nefrose Lipoide/terapia , Prognóstico , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Análise de Sobrevida , Adulto Jovem
4.
Exp Anim ; 68(1): 103-111, 2019 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-30369533

RESUMO

Multicentric carpotarsal osteolysis (MCTO) is a condition involving progressive osteolysis of the carpal and tarsal bones that is associated with glomerular sclerosis and renal failure (MCTO nephropathy). Previous work identified an autosomal dominant missense mutation in the transactivation domain of the transcription factor MAFB as the cause of MCTO. Several methods are currently used for MCTO nephropathy treatment, but these methods are invasive and lead to severe side effects, limiting their use. Therefore, the development of alternative treatments for MCTO nephropathy is required; however, the pathogenesis of MCTO in vivo is unclear without access to a mouse model. Here, we report the generation of an MCTO mouse model using the CRISPR/Cas9 system. These mice exhibit nephropathy symptoms that are similar to those observed in MCTO patients. MafbMCTO/MCTO mice show developmental defects in body weight from postnatal day 0, which persist as they age. They also exhibit high urine albumin creatinine levels from a young age, mimicking the nephropathic symptoms of MCTO patients. Characteristics of glomerular sclerosis reported in human patients are also observed, such as histological evidence of focal segmental glomerulosclerosis (FSGS), podocyte foot process microvillus transformation and podocyte foot process effacement. Therefore, this study contributes to the development of an alternative treatment for MCTO nephropathy by providing a viable mouse model.


Assuntos
Modelos Animais de Doenças , Glomerulosclerose Segmentar e Focal/genética , Fator de Transcrição MafB/genética , Mutação de Sentido Incorreto/genética , Osteólise/genética , Insuficiência Renal/genética , Albuminúria , Animais , Peso Corporal/genética , Proteína 9 Associada à CRISPR , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Creatinina/urina , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Mutantes , Osteólise/terapia , Insuficiência Renal/terapia , Ativação Transcricional/genética
5.
Transplant Proc ; 51(1): 223-225, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30580884

RESUMO

BACKGROUND: Recurrence of focal segmental glomerulosclerosis (FSGS) in renal allograft recipients after first transplant occurs in the second graft in virtually all patients. There is little evidence regarding optimal treatment. CASE PRESENTATION: A 55-year-old man with primary FSGS and disease recurrence in both the first and the second kidney grafts is presented. In 1999, the patient developed FSGS 3 years after transplant, which was treated with plasmapheresis and cyclophosphamide. Hemodialysis was started at 8 years from the onset of relapse. In February 2014, the patient received a second kidney transplant, and after 2 weeks laboratory analysis showed nephrotic proteinuria (5.9 g/d) with increased serum creatinine. Biopsy results revealed recurrence of FSGS. At that time, he was treated with steroids and plasmapheresis with partial efficacy, achieving a serum creatinine level of 1.1 mg/dL with decreased proteinuria (1 g/d). After 4 months, creatinine worsened (1.6 mg/dL) with new evidence of proteinuria. Second biopsy results showed evidence of FSGS progression. The patient then received plasmapheresis and 2 doses of rituximab. Follow-up was characterized by progressive remission up to complete resolution. The patient is currently free from relapses after 3 years with good renal function and almost no proteinuria. CONCLUSIONS: More evidence and prospective studies are needed to better understand the role of rituximab in FSGS in order to obtain an optimized therapeutic protocol for recurrence of FSGS in renal transplant recipients.


Assuntos
Glomerulosclerose Segmentar e Focal/terapia , Fatores Imunológicos/uso terapêutico , Transplante de Rim , Plasmaferese/métodos , Ciclofosfamida/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Rituximab/uso terapêutico
6.
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
7.
BMC Nephrol ; 19(1): 361, 2018 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-30558559

RESUMO

BACKGROUND: Therapeutic plasma exchange (TPE) is an important therapy for recurrent focal segmental glomerulosclerosis (rFSGS) post kidney transplant. suPAR has been causally implicated in rFSGS, and shown to be a unique biomarker for the occurrence and progression of chronic kidney disease. This study was targeted to evaluate the application of monitoring suPAR in TPE treated rFSGS. METHODS: A retrospective (n = 19) and a prospective (n = 15) cohort of post transplant FSGS patients treated with TPE and rituximab were enrolled. We measured serum suPAR levels before and after the combined therapies, and assessed the role of suPAR changes on proteinuria reduction and podocyte ß3- integrin activity. RESULTS: Treatment with TPE and rituximab resulted in significant decrease in proteinuria and suPAR levels. Among the variables including baseline suPAR, serum creatinine, proteinuria, eGFR, age at diagnosis, age at transplantation, transplantation numbers, time to recurrence, and TPE course numbers, only the reduction in suPAR levels and baseline proteinuria significantly correlated with the changes in proteinuria after treatment, with the former performed better in predicting proteinuria alteration. Additionally, the mean podocyte ß3 integrin activity significantly decreased after TPE and rituximab treatment (1.10 ± 0.08) as compared to before treatment (1.34 ± 0.08), p < 0.05. Only the reduction in suPAR predicted the response to therapies with an odds ratio of 1.43, 95% CI (1.02, 2.00), p < 0.05. CONCLUSIONS: Serum suPAR levels reduced significantly after TPE and rituximab treatment in post transplant FSGS patients. The reduction in suPAR levels may be utilized to assess the changes in proteinuria and monitor the response to the therapies. Larger, multi-centered prospective studies monitoring serum suPAR levels in TPE managed post transplant FSGS are warranted.


Assuntos
Glomerulosclerose Segmentar e Focal/sangue , Glomerulosclerose Segmentar e Focal/terapia , Troca Plasmática , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Adulto , Biomarcadores/sangue , Feminino , Glomerulosclerose Segmentar e Focal/complicações , Humanos , Fatores Imunológicos/uso terapêutico , Integrina beta3/metabolismo , Falência Renal Crônica/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Podócitos/metabolismo , Estudos Prospectivos , Proteinúria/etiologia , Recidiva , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento
8.
Medicine (Baltimore) ; 97(49): e13304, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30544390

RESUMO

RATIONALE: Inflammatory demyelinating neuropathies such as Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and focal segmental glomerulosclerosis (FSGS) are autoimmune disorders that may have a common pathogenesis. Here, we describe 2 unique cases of FSGS, 1 with GBS and the other with CIPD. We believe that reviewing these multisystemic diseases will help in better understanding of FSGS pathogenesis. PATIENT CONCERNS: The 1st patient, a 66-year-old woman, complained of tingling and numbness in the limbs and within 2 days, she developed progressive muscle weakness. The 2nd patient was a 63-year-old man with a complaint of lower-limb edema, lower-limb weakness, and numbness. DIAGNOSIS: In the 1st patient, a diagnosis of GBS was confirmed with the nerve conduction velocity test as well as CSF studies. A renal biopsy revealed FSGS. The 2nd patient was diagnosed with CIDP and a subsequent renal biopsy revealed FSGS. INTERVENTIONS: Large dose of steroid with calcineurin inhibitor, intravenous immunoglobulin, and supportive treatment. OUTCOMES: Neurologic symptoms disappeared, urine protein was maintained at low levels, and no further recurrences were noted in 2 cases. INF2 gene mutation was not found in either case. LESSONS: Co-occurrence of inflammatory demyelinating polyneuropathy, GBS, CIDP, and FSGS suggests synergistic cellular and humoral autoimmune mechanisms related to either cross-reactivity within antigenic targets or mimicry epitopes. Further follow-up and intensive study for the pathogenesis are necessary.


Assuntos
Glomerulosclerose Segmentar e Focal/complicações , Síndrome de Guillain-Barré/complicações , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/complicações , Idoso , Feminino , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/terapia , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/patologia , Síndrome de Guillain-Barré/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia
9.
BMC Nephrol ; 19(1): 335, 2018 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-30466397

RESUMO

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is the most common glomerular etiology of end-stage kidney disease (ESKD). Increasing evidence has indicated the reparative potential of mesenchymal stem cells (MSCs) in damaged diseased kidneys. However, the effect of bone marrow mesenchymal stem cells (BMSCs) on the FSGS progression remains unclear. This study aimed to investigate the protective effects of BMSCs on FSGS progression. METHODS: A rat model of FSGS was generated via unilateral nephrectomy plus adriamycin injection. Rat BMSCs were isolated and characterized on the basis of their differentiative potential towards adipocytes and osteoblasts and via flow cytometry analysis. Thereafter, rat BMSCs were transplanted into FSGS recipients through the caudal vein. After 8 weeks, 24-h proteinuria, serum creatinine, and urea nitrogen levels were determined. Renal morphology was assessed using a light and transmission electron microscope. MMP9 and TIMP-1 positive cells were detected via immunohistochemical analysis. Expression levels of proinflammatory cytokines IL-6 and TNF-α were examined via RT-PCR. RESULTS: The isolated adherent cells from the bone marrow of rats were phenotypically and functionally equivalent to typical MSCs. Clinical examination revealed that BMSC transplantation reduced the 24-h urinary protein excretion, and serum creatinine and urea nitrogen levels. Renal morphology was ameliorated in BMSCs-transplanted rats. Mechanistically, BMSC transplantation significantly downregulated TIMP-1 and upregulated MMP9, thereby increasing the renal MMP9/TIMP-1 ratio. Moreover, BMSC transplantation also downregulated IL-6 and TNF-α. CONCLUSIONS: BMSC transplantation can attenuate FSGS progression in a rat model of FSGS, thereby providing a theoretical foundation for the application of autologous BMSCs in clinical FSGS therapy.


Assuntos
Modelos Animais de Doenças , Progressão da Doença , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Animais , Diferenciação Celular/fisiologia , Células Cultivadas , Doxorrubicina/efeitos adversos , Glomerulosclerose Segmentar e Focal/etiologia , Masculino , Células-Tronco Mesenquimais/fisiologia , Nefrectomia/efeitos adversos , Ratos , Ratos Sprague-Dawley
11.
Nurs Clin North Am ; 53(4): 551-567, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30388981

RESUMO

Progressive glomerular damage can occur as a result of various etiologic factors including infections, medications, diseases, and autoimmune disorders. This article discusses the clinical management of the leading conditions associated with glomerular disease, including glomerulosclerosis, diabetic nephropathy, focal segmental glomerulosclerosis, and membranous nephropathy. Glomerular damage and disease progression may lead to end stage renal disease. Clinical management is individualized, as based on causative factors and clinical manifestations, with the overall goal of limiting glomerular damage. Collaborative and comprehensive care is imperative to improving patient outcomes.


Assuntos
Nefropatias Diabéticas/terapia , Glomerulosclerose Segmentar e Focal/terapia , Falência Renal Crônica/terapia , Nefropatias Diabéticas/enfermagem , Glomerulosclerose Segmentar e Focal/enfermagem , Humanos , Falência Renal Crônica/enfermagem
12.
Saudi J Kidney Dis Transpl ; 29(4): 816-821, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30152417

RESUMO

Our objective is to study the demographical data, clinical course and outcome of children with primary focal segmental glomerulosclerosis (FSGS) in Jordan. A retrospective chart review of patients with a diagnosis of FSGS at a tertiary care hospital from the period July 2010 to July 2016 was conducted. A total of 99 patients were analyzed. The mean age of presentation was 3.71 ± 2.59 years, 66% were male. At presentation, 66.6% of patients were steroid-resistant, 10% had a steroid dependant course and 20.2% had familial FSGS. Cyclosporine was used in 66.6% of children with a response rate of 46.9%. Long-term follow-up showed complete remission in 29.3%, partial remission in 31.3%, end-stage renal disease in 22.2%, and death in 11.1%. There is a high prevalence of familial FSGS in our Jordanian cohort with a high rate of progression to end-stage kidney disease.


Assuntos
Glomerulosclerose Segmentar e Focal , Criança , Pré-Escolar , Progressão da Doença , Feminino , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/epidemiologia , Glomerulosclerose Segmentar e Focal/mortalidade , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Lactente , Jordânia/epidemiologia , Masculino , Estudos Retrospectivos , Centros de Atenção Terciária
13.
Stem Cell Res Ther ; 9(1): 220, 2018 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-30107860

RESUMO

BACKGROUND: Mesenchymal stromal cell (MSC)-based therapy is a promising strategy for preventing the progression of chronic kidney disease (CKD), with the potential to induce tissue regeneration. In search of the best cellular source we compared, in the rat model of adriamycin (ADR) nephropathy, the regenerative potential of human stromal cells of non-renal origin, such as bone marrow (bm) MSCs and umbilical cord (uc) MSCs, with that of newly discovered stromal cells of renal origin, the kidney perivascular cells (kPSCs) known to exhibit tissue-specific properties. METHODS: The therapeutic effect of repeated infusions of human bmMSCs, ucMSCs, kPSCs (1.5 × 106 cells/rats) or conditioned medium from ucMSCs was studied in athymic rats with ADR-induced nephropathy (7.9 mg/kg). The ability of the three stromal cell populations to engraft the damaged kidney was evaluated by detecting the presence of human nuclear antigenpos cells. Glomerular podocyte loss and endothelial damage, sclerotic lesions and inflammation were assessed at 14 and 28 days. In-vitro experiments with a transwell system were performed to investigate the effects of different stromal cell populations on parietal epithelial cells (PECs) activated or not with albumin or angiotensin II for 24 h. RESULTS: Infusions of non-renal and renal stromal cells resulted in a comparable engraftment into the kidney, in the peritubular areas and around the glomerular structures. All three cell populations limited podocyte loss and glomerular endothelial cell injury, and attenuated the formation of podocyte and PEC bridges. This translated into a reduction of glomerulosclerosis and fibrosis. Human ucMSCs had an anti-inflammatory effect superior to that of the other stromal cells, reducing macrophage infiltration and inducing polarisation towards the M2 macrophage phenotype. Conditioned medium from ucMSCs shared the same renoprotective effects of the cells. Consistent with in-vivo data, bmMSCs and kPSCs, but even more so ucMSCs, limited proliferation, migratory potential and extracellular matrix production of activated PECs, when cultured in a transwell system. CONCLUSIONS: Our data indicate that either non-renal or renal stromal cells induce renal tissue repair, highlighting ucMSCs and their conditioned medium as the most reliable clinical therapeutic tool for CKD patients.


Assuntos
Glomerulosclerose Segmentar e Focal/terapia , Sobrevivência de Enxerto , Transplante de Células-Tronco Mesenquimais , Insuficiência Renal Crônica/terapia , Cordão Umbilical/citologia , Animais , Antígenos Nucleares/genética , Antígenos Nucleares/metabolismo , Biomarcadores/metabolismo , Células da Medula Óssea/citologia , Células da Medula Óssea/imunologia , Proliferação de Células , Técnicas de Cocultura , Meios de Cultivo Condicionados/farmacologia , Modelos Animais de Doenças , Doxorrubicina/administração & dosagem , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/patologia , Glomerulosclerose Segmentar e Focal/induzido quimicamente , Glomerulosclerose Segmentar e Focal/imunologia , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/imunologia , Podócitos/efeitos dos fármacos , Podócitos/imunologia , Podócitos/patologia , Ratos , Ratos Nus , Regeneração , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/imunologia , Insuficiência Renal Crônica/patologia , Transplante Heterólogo , Cordão Umbilical/imunologia , Cordão Umbilical/transplante
14.
G Ital Nefrol ; 35(3)2018 May.
Artigo em Italiano | MEDLINE | ID: mdl-29786187

RESUMO

A 39-year man with primary steroid resistant focal segmental glomerulosclerosis (FSGS) was treated with mycophenolate mofetil and ACE-inhibitors. After six months a different therapeutics approach was mandatory due to the worsening of renal function and the relapse of proteinuria at the nephrotic range. The combination of cascade plasmafiltration and single dose of rituximab (375 mg/m²) achieved clinical remission and improved renal function in six months follow up. Cascade plasmafiltration in association with rituximab can be considered as a salvage method for primary steroid-resistant FSGS. Clinical trials should be carried out for protocol approval.


Assuntos
Glomerulosclerose Segmentar e Focal/terapia , Imunossupressores/uso terapêutico , Plasmaferese , Rituximab/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Atorvastatina/uso terapêutico , Terapia Combinada , Diuréticos/uso terapêutico , Resistência a Medicamentos , Quimioterapia Combinada , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/patologia , Humanos , Masculino , Ácido Micofenólico/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Terapia de Salvação
15.
Blood Purif ; 46(2): 90-93, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29672314

RESUMO

BACKGROUND/AIMS: We present a case of a male patient with severe recurrence of focal and segmental glomerulosclerosis (FSGS) after transplant. METHODS: Before the transplant he was treated with plasma exchange. Massive proteinuria was detected post-transplantation and plasma exchanges were performed without response. We administered 5 doses of Rituximab (375 mg/m2) and partial remission was achieved. Proteinuria relapse occurred 1 year post-transplant, so Immunoadsorption (IA) was started instead of plasma exchange with reduction of proteinuria. Later, 2 new episodes of proteinuria relapse were detected and treated by increasing the number of IA sessions and administering new cycles of Rituximab. After achieving partial remission, IA was reduced to one session every 7-10 days as maintenance therapy. RESULTS: Despite the fact of the severe recurrence, renal function and proteinuria remain stable over 8 years after the transplantation was performed. CONCLUSION: Combination of maintenance IA and cycles of Rituximab is an effective treatment for aggressive forms of FSGS recurrence after renal transplantation.


Assuntos
Glomerulosclerose Segmentar e Focal/terapia , Técnicas de Imunoadsorção , Transplante de Rim/efeitos adversos , Rituximab/uso terapêutico , Glomerulosclerose Segmentar e Focal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Troca Plasmática , Proteinúria/patologia , Proteinúria/terapia , Recidiva , Indução de Remissão/métodos , Resultado do Tratamento
16.
Pediatr Transplant ; 22(5): e13185, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29676031

RESUMO

Disease recurrence affects around a third of renal transplants for children with FSGS and is associated with poor graft outcomes. Unfortunately, there are no large trials guiding treatment for recurrent FSGS. We aimed to describe current therapies and treatment response for recurrent FSGS in 4 centres in Australia and New Zealand. Data were collected on children (age <18 years) with recurrent FSGS (1990-2015). We reviewed patient charts to obtain clinical information. Ethics approval was obtained from the relevant boards. Complete records were available on 24 patients (62% female, 54% Caucasian). Median time to first recurrence was 4 days (IQR 2-5 days). There were 14 separate treatment regimens, involving an average of 2 agents. The most common therapies were plasma exchange (20/24 patients, 83%), cyclosporin (15/24, 63%), and methylprednisolone (9/24, 38%). Full remission was achieved in 15 (63%), partial remission in 2 (8%), and no remission in 7 (29%) patients. Of the patients with no remission, 5 lost their graft to recurrent disease and 1 to concurrent acute vascular rejection. The plethora of different treatment regimens reflects the poor evidence guiding management for recurrent FSGS. More research is needed to improve outcomes.


Assuntos
Ciclosporina/uso terapêutico , Glomerulosclerose Segmentar e Focal/terapia , Imunossupressores/uso terapêutico , Transplante de Rim , Metilprednisolona/uso terapêutico , Troca Plasmática , Adolescente , Austrália , Criança , Pré-Escolar , Feminino , Humanos , Estudos Longitudinais , Masculino , Nova Zelândia , Recidiva , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
17.
Saudi J Kidney Dis Transpl ; 29(1): 185-188, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29456227

RESUMO

Various adverse reactions may occur after intravesical bacillus Calmette-Guérin (BCG) therapy. Although the virulence of attenuated BCG is low, serious complications such as bacterial cystitis, bladder contractures, granulomatous prostatitis, epididymitis, orchitis, and systemic reactions such as fever and malaise have been described. Disseminated granulomatosis such as hepatitis and pneumonitis have also been described, but are rare. We report here the case of a 67-year-old patient who presented with renal granulomatosis with polyangiitis following intravesical BCG therapy for superficial bladder tumor. The biological evaluation revealed the presence of perinuclear anti-neutrophil cytoplasmic antibodies with specificity for antimyeloperoxidase. Renal biopsy specimen revealed pauci-immune crescentic glomerulonephritis with segmental glomerular necrosis, presence of granulomas and no evidence of any caseating necrosis. He received antituberculosis drugs in addition to corticosteroids and cyclophosphamide without any improvement of the renal function.


Assuntos
Antineoplásicos/efeitos adversos , Vacina BCG/efeitos adversos , Glomerulosclerose Segmentar e Focal/induzido quimicamente , Granulomatose com Poliangiite/induzido quimicamente , Rim/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Corticosteroides/uso terapêutico , Idoso , Anticorpos Anticitoplasma de Neutrófilos/análise , Antineoplásicos/administração & dosagem , Antituberculosos/uso terapêutico , Vacina BCG/administração & dosagem , Biópsia , Glomerulosclerose Segmentar e Focal/imunologia , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/terapia , Granulomatose com Poliangiite/imunologia , Granulomatose com Poliangiite/patologia , Granulomatose com Poliangiite/terapia , Humanos , Imunossupressores/uso terapêutico , Rim/imunologia , Rim/patologia , Masculino , Peroxidase/imunologia , Diálise Renal , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
18.
Pediatr Transplant ; 22(3): e13154, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29388290

RESUMO

Many pediatric centers utilize a variety of protocols including preemptive plasmapheresis to prevent the recurrence of FSGS post-transplant. But the effectiveness of this expensive, time-consuming process of plasmapheresis in the prevention of FSGS recurrence is still unclear. We retrospectively reviewed all pediatric cases of FSGS in our center that received a kidney transplant and compared the transplant and patient outcomes of those transplanted after 2006 who received pretransplant plasmapheresis to those prior to 2006 who did not. Of the 57 children with FSGS, 31 and 26 were transplanted before and after 2006, respectively. The cohorts differed significantly in keeping with the center immunosuppression protocol changes, and prior to 2006, the recipients were significantly younger. All children with FSGS transplanted after 2006 underwent three and one sessions of 1.0 plasma volume/exchange plasmapheresis with fresh frozen plasma replacement prior to the transplant in living and deceased donors, respectively, in addition to five sessions of every other day post-transplant pheresis. The incidence (27% vs 26%, P = 1.0) and time to recurrence of FSGS in the kidney allograft (P = .22) were not significantly different in patients that did and did not undergo prophylactic plasmapheresis. We need to re-evaluate the role of preemptive plasmapheresis in the prevention of FSGS recurrence in a prospective multicenter study.


Assuntos
Glomerulosclerose Segmentar e Focal/terapia , Transplante de Rim , Assistência Perioperatória/métodos , Plasmaferese/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
19.
Nephrol Dial Transplant ; 33(6): 954-963, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28992235

RESUMO

Background: Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation (KTx) in children. This can lead to delayed graft loss. As the management of children with recurrent FSGS is not well established, apheresis strategies could be a cornerstone to control the disease. Immunoadsorption (IA) is a recent apheresis therapy. There have been few studies examining IA in this setting. We report the results of IA for management of recurrent FSGS after KTx in children in France. Methods: We included all children treated with IA for early FSGS recurrence after KTx between January 2011 and June 2014 in France. We excluded genetic forms of FSGS. Patients' characteristics and technical data on IA were retrospectively collected. Recurrence was defined as nephrotic proteinuria during the post-transplantation period. Partial and complete remissions were defined when urine protein:creatinine ratios were less than 0.2 and 0.05 g/mmol, respectively. Results: Twelve patients, from six paediatric KTx units, presenting with FSGS recurrence between 0 and 21 days after KTx were treated with IA. Ten of 12 children were responders: 2 achieved partial remission and 8 complete remission. The decrease of proteinuria rapidly occurred within the first 10 sessions after initiating IA. After 3 months of IA, two patients maintained remission without IA and eight became IA dependent. No severe side effects were reported. Conclusions: Our study reports on the efficacy of IA in the recurrence of FSGS after KTx in children. Further prospective controlled studies are required to confirm these results and to optimize the management of FSGS recurrence after paediatric KTx.


Assuntos
Glomerulosclerose Segmentar e Focal/terapia , Transplante de Rim/efeitos adversos , Plasmaferese/métodos , Proteinúria/terapia , Adolescente , Criança , Pré-Escolar , Feminino , França , Glomerulosclerose Segmentar e Focal/etiologia , Humanos , Masculino , Proteinúria/etiologia , Recidiva , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
20.
Clin Exp Nephrol ; 22(3): 491-500, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28752288

RESUMO

A broad range of genetic and non-genetic factors can lead to kidney injury that manifests as focal segmental glomerulosclerosis (FSGS), which can be classified into primary (idiopathic) and secondary forms. Previous genetic approaches to familial or sporadic cases of FSGS or steroid-resistant nephrotic syndrome identified causal mutations in a subset of genes. Recently, next-generation sequencing (NGS) approaches are becoming a part of a standard assessment in medical genetics. Current knowledge of the comprehensive genomic information is changing the way we think about FSGS and draws attention not only to identification of novel causal genes, but also to potential roles for combinations of mutations in multiple genes, mutations with complex inheritance, and susceptibility genes with variable penetrance carrying relatively minor but significant effects. This review provides an update on recent advances in the genetic analysis of FSGS and highlights the potential as well as the new challenges of NGS for diagnosis and mechanism-based treatment of FSGS.


Assuntos
Glomerulosclerose Segmentar e Focal/genética , Síndrome Nefrótica/congênito , Análise de Sequência de DNA , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/genética , Síndrome Nefrótica/terapia , Penetrância
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