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1.
Clin Genet ; 92(5): 517-527, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28632965

RESUMO

Familial microscopic hematuria (FMH) is associated with a genetically heterogeneous group of conditions including the collagen-IV nephropathies, the heritable C3/CFHR5 nephropathy and the glomerulopathy with fibronectin deposits. The clinical course varies widely, ranging from isolated benign familial hematuria to end-stage renal disease (ESRD) later in life. We investigated 24 families using next generation sequencing (NGS) for 5 genes: COL4A3, COL4A4, COL4A5, CFHR5 and FN1. In 17 families (71%), we found 15 pathogenic mutations in COL4A3/A4/A5, 9 of them novel. In 5 families patients inherited classical AS with hemizygous X-linked COL4A5 mutations. Even more patients developed later-onset Alport-related nephropathy having inherited heterozygous COL4A3/A4 mutations that cause thin basement membranes. Amongst 62 heterozygous or hemizygous patients, 8 (13%) reached ESRD, while 25% of patients with heterozygous COL4A3/A4 mutations, aged >50-years, reached ESRD. In conclusion, COL4A mutations comprise a frequent cause of FMH. Heterozygous COL4A3/A4 mutations predispose to renal function impairment, supporting that thin basement membrane nephropathy is not always benign. The molecular diagnosis is essential for differentiating the X-linked from the autosomal recessive and dominant inheritance. Finally, NGS technology is established as the gold standard for the diagnosis of FMH and associated collagen-IV glomerulopathies, frequently averting the need for invasive renal biopsies.


Assuntos
Colágeno Tipo IV/genética , Glomerulosclerose Segmentar e Focal/genética , Hematúria/genética , Mutação/genética , Nefrite Hereditária/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Família , Feminino , Membrana Basal Glomerular/patologia , Membrana Basal Glomerular/ultraestrutura , Glomerulosclerose Segmentar e Focal/complicações , Hematúria/complicações , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite Hereditária/complicações , Linhagem , Penetrância , Adulto Jovem
2.
Transpl Infect Dis ; 15(4): 393-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23773581

RESUMO

PURPOSE: The purpose of this study was to present a fatal case of fulminant hepatitis B (FHB) that developed in a renal transplant recipient, immunized against hepatitis B, 1 year post transplantation. METHODS: Polymerase chain reaction amplification and full genome sequencing were performed to investigate whether specific mutations were associated with hepatitis B virus (HBV) transmission and FHB. RESULTS: Molecular analysis revealed multiple mutations in various open reading frames of HBV, the most important being the G145R escape mutation and a frameshift mutation-insertion (1838insA) within the pre-C/C reading frame. CONCLUSIONS: Our results highlight the possibility of developing FHB, despite previous immunization against HBV or administration of hyperimmune gammaglobulin, because of the selection of escape virus mutants. The current literature and guidelines regarding renal transplantation from hepatitis B surface antigen (HBsAg)-positive to HBsAg-negative patients were also reviewed.


Assuntos
Antígenos de Superfície da Hepatite B/sangue , Hepatite B/virologia , Transplante de Rim/efeitos adversos , Falência Hepática Aguda/virologia , Mutação , Doadores de Tecidos , Evolução Fatal , Hepatite B/diagnóstico , Hepatite B/imunologia , Hepatite B/transmissão , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/genética , Humanos , Falência Hepática Aguda/diagnóstico , Falência Hepática Aguda/imunologia , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA
3.
Lupus ; 20(14): 1484-93, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21976398

RESUMO

Mycophenolic acid, in combination with glucocorticoids, has been shown in a series of trials to be safe and effective for treatment of lupus nephritis. Regimens that permit glucocorticoid dose reduction without loss of efficacy would be advantageous. MyLupus was a 24-week, multicentre, open-label, study in patients with active proliferative lupus nephritis treated with enteric-coated mycophenolate sodium (EC-MPS), randomized to standard-dose (n = 42) or reduced-dose (n = 39) glucocorticoids. Complete response at week 24, the primary endpoint, was achieved in 19.8% (16/81) of patients (19.0% standard-dose, 20.5% reduced-dose; lower limit of 97.5% CI for the difference -15.9%, p = 0.098, i.e. non-inferiority was not shown). Partial response occurred in 42.0% of patients (34/81). From baseline to week 24, the mean global British Isles Lupus Assessment Group (BILAG) score decreased from 14.0 ± 5.4 to 5.0 ± 3.8 (p < 0.001). The incidence of adverse events was 80.2% (65/81), most frequently gastrointestinal complications (31/81, 38.3%). Infections were reported in 57.1% and 35.9% of standard- and reduced-dose glucocorticoid patients, respectively (p = 0.056), with herpes zoster in 16.7% and 0% (p = 0.012). Three patients discontinued study medication due to adverse events. This exploratory study suggests that EC-MPS may facilitate glucocorticoid reduction without loss of efficacy in patients with active lupus nephritis, but results require confirmation in a controlled, longer-term study versus the current standard of care.


Assuntos
Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/análogos & derivados , Adulto , Quimioterapia Combinada , Feminino , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Comprimidos com Revestimento Entérico , Adulto Jovem
6.
Transplant Proc ; 47(6): 1662-74, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26293031

RESUMO

BACKGROUND: Serum creatinine (S-Cr) is the most commonly used marker for the assessment of renal function in kidney transplantation (KTx). Cystatin-C (Cys-C) has been proposed as an alternative marker of renal function for the estimated glomerular filtration rate (eGFR), which seems to be more accurate than S-Cr. The aim of this study was to investigate the relationship between changes in S-Cr, Cys-C, and eGFR measurements in KT patients during the early post-transplantation (post-Tx) period. METHODS: Fifty consecutive patients, aged 15 to 70 years, were subjected to KT. Blood samples were collected at stable time-points on pre-Tx and post-Tx days 2, 6, and 14 and in the third month. Cys-C and S-Cr levels were measured, and GFR was estimated at all time-points using the Cockcroft-Gault and Le Bricon equations. RESULTS: S-Cr and Cys-C levels decreased significantly post-Tx in all time-point determinations compared with pre-Tx levels. Both markers showed a parallel decrease, reaching normal levels in the third month. Estimated GFR post-Tx by S-Cr and Cys-C exhibited a parallel progressive increase without significant difference between the calculations. Correlation between S-Cr and Cys-C in all time-point determinations was positive and of high significance using Pearson's correlation (r = 0.969, P < .01; r = 0.951, P < .01; r = 0.969, P < .01; r = 0.701, P < .01). Also, the correlation between the eGFR by Cys-C and S-Cr was positive and of high significance in all post-Tx calculations (r = 0.896, P < .01; r = 0.935, P < .01; r = 0.929, P < .01; r = 0.861, P < .01). Ten recipients had acute rejection and were treated successfully with antirejection therapy. Their S-Cr, cys-C, and eGFR results were analyzed separately and showed a significant difference from no-rejection patients, with Cys-C being more sensitive to earlier eGFR changes. CONCLUSION: Cystatin-C is an alternative and accurate marker of renal function in KT patients showing similar diagnostic characteristics to S-Cr. However, Cys-C appears superior to S-Cr in reflecting early GFR temporary changes, which is critical for the early detection of acute rejection.


Assuntos
Creatinina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular/fisiologia , Transplante de Rim , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/fisiopatologia , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Perit Dial Int ; 9(1): 65-7, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2488185

RESUMO

A randomised trial, comparing Tenckhoff catheter replacement as a one-stage procedure and i.p. urokinase, was undertaken in the management of recurrent continuous ambulatory peritoneal dialysis (CAPD) peritonitis. In addition to appropriate i.p. antibiotic treatment, 17 patients received i.p. urokinase (5000 i.u.) on the second and fourth days of antibiotic treatment, and 14 patients underwent CAPD catheter replacement. An additional six patients also underwent catheter replacement following the recurrence of peritonitis after urokinase treatment. The subsequent recurrence rate of peritonitis following CAPD catheter replacement (5%) was significantly less than after urokinase (41%) (p less than 0.001). Fourteen patients remained free of peritonitis for at least three months after catheter replacement, and five patients were peritonitis-free following urokinase for this period.


Assuntos
Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Peritonite/terapia , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Cateteres de Demora , Feminino , Gentamicinas/uso terapêutico , Humanos , Infusões Parenterais , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Peritonite/etiologia , Recidiva , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Vancomicina/uso terapêutico
8.
Transplant Proc ; 46(9): 3199-202, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25420858

RESUMO

OBJECTIVE: One of the most common malignancies in kidney transplant recipients is Kaposi sarcoma. The incidence of Kaposi sarcoma, which develops after renal transplantation, is 400-500 times higher than that in the general population. The aims of this study were to review the experience with Kaposi sarcoma in the highest-volume transplantation Unit in Greece and to analyze clinical characteristics and response to treatment, with respect to both the patients' survival and the renal graft function. MATERIALS AND METHODS: The records of 2008 renal graft recipients between March 1983 and December 2012 were retrospectively reviewed. Kaposi sarcoma was diagnosed based on clinical, laboratory, radiological, endoscopic, and histopathologic examinations. The disease was staged according to the classification of Al-Khader et al. RESULTS: The prevalence of Kaposi sarcoma was 1.2% in our renal transplant population. Of these, 1006 recipients underwent living-donor renal transplantation, whereas 1002 received their graft from deceased donors. Post-transplantation malignancy developed in 153 patients, among which, Kaposi sarcoma has been found in 24 cases. Of the 24 cases of Kaposi sarcoma, lesions were mainly cutaneous in 14 cases, visceral and cutaneous in 8, and concomitant visceral and lymph node involvement was observed in 2 patients. With regard to the final outcome, 20 patients (83.3%) showed remission of the disease, whereas 4 patients with visceral involvement (16.6%) did not respond to chemotherapy and discontinuation of immunosuppression and died. Moreover, 8 deaths occurred due to apparently unrelated causes. CONCLUSIONS: Kaposi sarcoma is an important part (15.7%) of all post-transplantation neoplasias in our series. Furthermore, our findings confirmed the previously described close association between human herpesvirus-8 and post-transplantation Kaposi sarcoma. Reduction of immunosuppression or discontinuation of calcineurin inhibitors results in remission of the disease in most of the cases. Prognosis in patients with Kaposi sarcoma limited to the skin is favorable, whereas visceral involvement is associated with high mortality.


Assuntos
Terapia de Imunossupressão/métodos , Transplante de Rim , Sarcoma de Kaposi/epidemiologia , Neoplasias Cutâneas/epidemiologia , Transplantados , Adulto , Idoso , Feminino , Grécia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Sarcoma de Kaposi/terapia , Neoplasias Cutâneas/terapia , Adulto Jovem
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