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1.
Kidney Int ; 105(5): 1100-1112, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38431217

RESUMO

Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 µmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represents a very high proportion of patients with TMA and results from virtually all known causes of TMA and includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Microangiopatias Trombóticas , Adulto , Humanos , Rim/patologia , Microangiopatias Trombóticas/epidemiologia , Microangiopatias Trombóticas/terapia , Microangiopatias Trombóticas/patologia , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Síndrome Hemolítico-Urêmica Atípica/epidemiologia , Proteínas do Sistema Complemento , Testes de Função Renal
2.
Nephrol Dial Transplant ; 38(4): 913-921, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35791491

RESUMO

BACKGROUND: Cancer-associated thrombotic microangiopathy (TMA) is a rare disease, with a poor prognosis. The classical treatment is urgent chemotherapy. Few data are available on the efficacy of plasma exchange (PE) and eculizumab in these patients. METHODS: Cases of cancer-related TMA treated between January 2008 and December 2019 in 12 French treatment centres were retrospectively analysed, excluding cases associated with chemotherapy and stem cell transplantation. Patients were divided into four groups depending on the treatment received: none, PE therapy alone, chemotherapy, with or without PE therapy, or eculizumab, with or without chemotherapy and PE therapy. RESULTS: The data of 59 patients with cancer-associated TMA were analysed. Twenty of these cases were related to a cancer recurrence. The cancer was metastatic in 90% of cases (53/59). Bone marrow invasion was observed in 20/41 biopsies. Some laboratory results, including disseminated intravascular coagulation high ferritin and C-reactive protein, were suggestive of cancer. None of the 16 patients whose alternative complement pathway was assessed had abnormal levels of protein expression or activity. The median survival time was 27 days. Chemotherapy was significantly associated with improved survival, with a 30-day survival rate of 85% (17/20) among patients who received PE and chemotherapy, versus 20% (3/15) among patients who received PE alone. Patients treated with eculizumab in addition to chemotherapy and PE therapy did not have longer overall survival or higher haematological remission rates than those treated with chemotherapy and PE therapy alone. Renal remission rates were non-significantly higher, and times to remission non-significantly shorter, in the eculizumab group. CONCLUSIONS: Nephrologists and oncologists should make themselves aware of cancer diagnoses in patients with TMA and bone marrow biopsies should be performed systematically in these cases. All 59 patients had poor survival outcomes, but patients treated with urgent initiation of chemotherapy survived significantly longer than those who were not.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasias , Microangiopatias Trombóticas , Humanos , Estudos Retrospectivos , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/terapia , Rim , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias/complicações , Neoplasias/terapia
3.
Clin Nephrol ; 93(5): 227-233, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32213281

RESUMO

BACKGROUND: The use of a catheter for hemodialysis is associated with a 5-fold increased risk of septicemia. Early detection of catheter-related bloodstrean infection (CRBSI) may decrease morbidity and mortality, but the benefits of systematic blood cultures have not been demonstrated. MATERIALS AND METHODS: We retrospectively studied the blood culture results of patients who had been dialyzed with a tunneled jugular catheter for more than 1 month in a dialysis unit from January to December 2015. Systematic monthly catheter blood cultures were taken from the heparin lock solutions in the arterial and venous branches, at the beginning or end of the session. CRBSI was assessed using patient symptoms (fever, chills, hemodynamic instability) and positive catheter blood cultures. RESULTS: 75 patients were included. We analyzed the results of 577 systematic catheter blood cultures. 27 (5%) were positive, including 23 from patients who did not develop CRBSI in the following month. For the latter, there was a predominance of coagulase-negative staphylococci. Only four patients with positive catheter blood cultures went on to develop CRBSI in the following month. The sensitivity and specificity of these monthly blood cultures to detect CRBSI in the following month were 0.44 and 0.95, respectively. The positive and negative predictive values of the test were 0.14 and 0.99, respectively. CONCLUSION: In this study, systematic catheter blood cultures did not predict the occurrence of CRBSI. The sensitivity of these tests could be improved by increasing the sampling frequency. A cost-benefit analysis of such measures should be performed.


Assuntos
Bacteriemia/diagnóstico , Hemocultura/métodos , Infecções Relacionadas a Cateter/diagnóstico , Diálise Renal/efeitos adversos , Idoso , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
4.
Hum Mutat ; 36(8): 743-52, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25907713

RESUMO

Dent disease is a rare X-linked tubulopathy characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis and/or nephrolithiasis, progressive renal failure, and variable manifestations of other proximal tubule dysfunctions. It often progresses over a few decades to chronic renal insufficiency, and therefore molecular characterization is important to allow appropriate genetic counseling. Two genetic subtypes have been described to date: Dent disease 1 is caused by mutations of the CLCN5 gene, coding for the chloride/proton exchanger ClC-5; and Dent disease 2 by mutations of the OCRL gene, coding for the inositol polyphosphate 5-phosphatase OCRL-1. Herein, we review previously reported mutations (n = 192) and their associated phenotype in 377 male patients with Dent disease 1 and describe phenotype and novel (n = 42) and recurrent mutations (n = 24) in a large cohort of 117 Dent disease 1 patients belonging to 90 families. The novel missense and in-frame mutations described were mapped onto a three-dimensional homology model of the ClC-5 protein. This analysis suggests that these mutations affect the dimerization process, helix stability, or transport. The phenotype of our cohort patients supports and extends the phenotype that has been reported in smaller studies.


Assuntos
Canais de Cloreto/genética , Doença de Dent/genética , Mutação , Animais , Canais de Cloreto/química , Canais de Cloreto/metabolismo , Estudos de Coortes , Doença de Dent/metabolismo , Estudos de Associação Genética , Humanos , Masculino , Camundongos , Camundongos Knockout , Linhagem
5.
Nephrol Ther ; 20(3): 1-9, 2024 06 14.
Artigo em Francês | MEDLINE | ID: mdl-38874419

RESUMO

Introduction: Difelikefalin is to date the first and only specific treatment to be approved for the treatment of moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP) in adult patients on hemodialysis. Patients and methods: This was a retrospective, single-center, real-life study in hemodialysis patients with CKD-aP treated with difelikefalin. The primary objective was to evaluate the evolution of the intensity of pruritus during treatment with difelikefalin using the Worst Itch Intensity-Numerical Rating Scale (WI-NRS). Adult patients were included if they had been on hemodialysis for at least 3 months and were suffering from moderate to severe CKD-aP (objectified by the WI-NRS score) for which difelikefalin had been prescribed. Results: 11 patients (7 men and 4 women; mean age, 63.8 years) with a mean (SD) weekly dialysis time of 13 h (2.4) were included. The mean hemodialysis duration was 5 (3.6) years and the mean pruritus duration was 4.3 (3.2) years. At inclusion, on-going treatments of CKD-aP were emollients in all patients and antihistamines in 9 patients. The mean WI-NRS score was 7.4 (1.1) at initiation of difelikefalin. At last assessment after a median follow-up of 9.0 months, the mean change of WI-NRS score was -5.1 (2.9) and 82% of patients had a decrease ≥ 3 points. Mild to moderate adverse reactions to difelikefalin were reported in 4 patients, all of whom recovered without sequelae. Conclusion: These results show that difelikefalin, prescribed according to its therapeutic indication, is effective in the treatment of CKD-aP under real-life conditions, outside the controlled conditions of a clinical trial.


Introduction: La difélikéfaline est à ce jour le premier et le seul traitement spécifique approuvé pour le traitement du prurit d'intensité modérée à sévère associé à la maladie rénale chronique (Pa-MRC) chez les patients adultes hémodialysés. Patients et méthodes: Il s'agit d'une étude rétrospective, monocentrique, en vie réelle, chez des patients hémodialysés souffrant de Pa-MRC et traités par difélikéfaline. L'objectif principal était d'évaluer l'évolution de l'intensité du prurit au cours du suivi à l'aide de l'échelle WI-NRS (Worst Itch Intensity-Numerical Rating Scale). Les patients adultes ont été inclus s'ils étaient hémodialysés depuis au moins trois mois et souffraient d'un Pa-MRC modéré à sévère (objectivé par le score WI-NRS) pour lequel la difélikéfaline avait été prescrite. Résultats: Onze patients (7 hommes et 4 femmes ; âge moyen : 63,8 ans) avec un temps de dialyse hebdomadaire moyen (SD) de 13 h (2,4) ont été inclus. La durée moyenne d'hémodialyse était de 5 ans (3,6) et la durée moyenne de prurit de 4,3 ans (3,2). À l'inclusion, les traitements du prurit en cours étaient des émollients pour tous les patients et des antihistaminiques pour 9 d'entre eux. Le score WI-NRS moyen était de 7,4 (1,1) au début du traitement par la difélikéfaline. À la dernière évaluation, après un suivi médian de 9 mois, la variation moyenne du score WI-NRS était de -5,1 (2,9) et 82 % des patients avaient une diminution ≥ 3 points. Des effets indésirables d'intensité légère à modérée liés à la difélikéfaline ont été rapportés chez 4 patients, tous rétablis sans séquelles. Conclusion: Ces résultats montrent que la difélikéfaline, prescrite conformément à son indication thérapeutique, est efficace en vie réelle dans le traitement du Pa-MRC, en dehors des conditions contrôlées d'un essai clinique.

6.
Nephrol Ther ; 20(1): 61-80, 2024 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-38379375

RESUMO

Kidney Biopsy (KB) is a crucial diagnostic tool in the field of renal diseases and is routinely performed in nephrology departments. A previous survey conducted by the Société Francophone de Néphrologie Dialyse Transplantation (SFNDT) revealed significant disparities in clinical practices, sometimes conflicting with the existing literature and recently published recommendations. In response, the SFNDT wished to promote the development of best practice guidelines, under the auspices of the French National Authority for Health (HAS), to establish a standardized framework for performing kidney biopsies in France.


La biopsie rénale (BR) est un outil diagnostique crucial dans le domaine des maladies rénales et est pratiquée en routine dans les services de néphrologie. Une précédente enquête menée par la Société francophone de néphrologie, dialyse et transplantation (SFNDT) a révélé d'importantes disparités dans les pratiques cliniques, parfois en contradiction avec la littérature existante et les recommandations récemment publiées. En réponse, la SFNDT a souhaité promouvoir l'élaboration de recommandations de bonnes pratiques, sous l'égide de la Haute Autorité de santé (HAS), afin d'établir un cadre standardisé pour la réalisation des biopsies rénales en France.


Assuntos
Nefropatias , Nefrologia , Humanos , Nefropatias/diagnóstico , Nefropatias/terapia , Nefropatias/patologia , França , Rim/patologia , Biópsia
7.
Clin J Am Soc Nephrol ; 18(8): 1031-1040, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37283461

RESUMO

BACKGROUND: IgG4-related kidney disease is a major manifestation of IgG4-related disease, a systemic fibroinflammatory disorder. However, the clinical and prognostic kidney-related factors in patients with IgG4-related kidney disease are insufficiently defined. METHODS: We conducted an observational cohort study using data from 35 sites in two European countries. Clinical, biologic, imaging, and histopathologic data; treatment modalities; and outcomes were collected from medical records. Logistic regression was performed to identify the possible factors related to an eGFR ≤30 ml/min per 1.73 m 2 at the last follow-up. Cox proportional hazards model was performed to assess the factors associated with the risk of relapse. RESULTS: We studied 101 adult patients with IgG4-related disease with a median follow-up of 24 (11-58) months. Of these, 87 (86%) patients were male, and the median age was 68 (57-76) years. Eighty-three (82%) patients had IgG4-related kidney disease confirmed by kidney biopsy, with all biopsies showing tubulointerstitial involvement and 16 showing glomerular lesions. Ninety (89%) patients were treated with corticosteroids, and 18 (18%) patients received rituximab as first-line therapy. At the last follow-up, the eGFR was below 30 ml/min per 1.73 m 2 in 32% of patients; 34 (34%) patients experienced a relapse, while 12 (13%) patients had died. By Cox survival analysis, the number of organs involved (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.01 to 1.55) and low C3 and C4 concentrations (HR, 2.31; 95% CI, 1.10 to 4.85) were independently associated with a higher risk of relapse, whereas first-line therapy with rituximab was protective (HR, 0.22; 95% CI, 0.06 to 0.78). At their last follow-up, 19 (19%) patients had an eGFR ≤30 ml/min per 1.73 m 2 . Age (odd ratio [OR], 1.11; 95% CI, 1.03 to 1.20), peak serum creatinine (OR, 2.74; 95% CI, 1.71 to 5.47), and serum IgG4 level ≥5 g/L (OR, 4.46; 95% CI, 1.23 to 19.40) were independently predictive for severe CKD. CONCLUSIONS: IgG4-related kidney disease predominantly affected middle-aged men and manifested as tubulointerstitial nephritis with potential glomerular involvement. Complement consumption and the number of organs involved were associated with a higher relapse rate, whereas first-line therapy with rituximab was associated with lower relapse rate. Patients with high serum IgG4 concentrations (≥5 g/L) had more severe kidney disease.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Nefrite Intersticial , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Idoso , Feminino , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Rituximab/efeitos adversos , Estudos de Coortes , Prognóstico , Rim/patologia , Nefrite Intersticial/patologia , Imunoglobulina G , Recidiva , Estudos Retrospectivos
8.
Ann Vasc Surg ; 25(2): 266.e9 - 16, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20926247

RESUMO

We report a case of a 75-year-old man who had been complaining of fever and pelvic pain for 3 weeks. First angio-computed tomography (CT) characteristics and blood culture led to suspicion of a pneumococcal-infected aortic aneurysm, which however was not confirmed by the surgeon. The abdominal infectious aortitis caused by Streptococcus pneumoniae was affirmed by a second angio-CT performed 7 days later. Without further delay, the patient underwent surgery for resection of mycotic aneurysm and in situ reconstruction with aortobiiliac homograft, in association with antibiotics. He died 10 days after the surgery as a result of severe sepsis in a polyvalent intensive care unit. This case report highlights the severity of this pathology. We reviewed the relevant literature related to Streptococcal pneumoniae mycotic aneurysm located in the abdominal aorta, including 29 more cases. Various microorganisms have already been associated with mycotic aneurysms, including S pneumoniae. Infectious aortitis remains a rare disease. It is extremely important to establish an early diagnosis but it may be delayed because clinical manifestations are usually nonspecific. However, if left untreated it is always lethal. Antibiotic in combination with complete surgical excision of the infected aorta is the treatment of reference. This therapeutic association dramatically improved patient survival.


Assuntos
Aneurisma Infectado/microbiologia , Aneurisma da Aorta Abdominal/microbiologia , Aortite/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Idoso , Aneurisma Infectado/diagnóstico por imagem , Aneurisma Infectado/cirurgia , Antibacterianos/uso terapêutico , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Aortite/diagnóstico por imagem , Aortite/cirurgia , Aortografia/métodos , Implante de Prótese Vascular , Evolução Fatal , Humanos , Masculino , Infecções Estreptocócicas/diagnóstico por imagem , Infecções Estreptocócicas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
9.
Ann Intensive Care ; 10(1): 27, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32124091

RESUMO

BACKGROUND: Rhabdomyolysis is a life-threatening disease that can lead to severe hyperkalemia, acute kidney injury (AKI) and hypovolemic shock. The predictive factors of AKI and acute to chronic kidney disease (CKD) transition remain poorly described. METHODS: This multicenter retrospective study enrolled 387 patients with severe rhabdomyolysis (CPK > 5000 U/L). Primary end-point was the development of severe AKI, defined as stage 2 or 3 of KDIGO classification. Secondary end-points included the incidence of AKI to CKD transition. RESULTS: Among the 387 patients, 315 (81.4%) developed AKI, including 171 (44.1%) with stage 3 AKI and 103 (26.6%) requiring RRT. Stage 2-3 AKI was strongly correlated with serum phosphate, potassium and bicarbonate at admission, as well as myoglobin over 8000 U/L and the need for mechanical ventilation. 42 patients (10.8%) died before day 28. In the 80 patients with available eGFR values both before and 3 months after the rhabdomyolysis, the decrease in eGFR (greater than 20 mL/min/1.73 m2 in 23 patients; 28.8%) was correlated to the severity of the AKI and serum myoglobin levels > 8000 U/L at admission. CONCLUSIONS: Severe rhabdomyolysis leads to AKI in most patients admitted to an ICU. Mechanical ventilation and severity of the rhabdomyolysis, including myoglobin level, are associated with the risk of stage 2-3 AKI. The long-term renal decline is correlated to serum myoglobin at admission.

10.
Joint Bone Spine ; 84(1): 51-57, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27118022

RESUMO

OBJECTIVES: ANCA-associated vasculitis are severe autoimmune pathologies that are characterized by inflammation and necrosis of the small vessels. The physiopathological mechanisms are complex and have yet to be totally elucidated. Several environmental factors have been described as being associated: medications, infectious agents… and rarely, neoplasms. METHODS: We performed a retrospective multicenter study over a period of 12 years with a view to describing the association of ANCA-associated vasculitis and malignant hemopathies, excluding hemopathies secondary to vasculitis treatment. RESULTS: Sixteen patients with ANCA-associated vasculitis with an hemopathy were identified. The gender ratio was 7 and the mean age was 65 years. The frequency of this association is estimated at 1%. The ANCA-associated vasculitis were micropolyangiitis (n=7), followed by granulomatous polyangiitis (n=4), vasculitis limited to the kidney (n=3), and eosinophilic granulomatous polyangiitis (n=2). The associated malignant hemopathies were mainly non-Hodgkin's lymphoma in seven cases and myelodysplasia in five cases. The other hemopathies were: Hodgkin's disease, hypereosinophilic syndrome, and Waldenström's macroglobulinemia. Hemopathy treatment was associated with vasculitis treatment in seven cases. CONCLUSION: The association of ANCA-associated vasculitis and malignant hemopathy is rare but must nevertheless be recognized because: (i) the clinical signs of both pathologies are not specific, (ii) the survival scores that are used for ANCA-associated vasculitis do not appear to be applicable, (iii) both pathologies must be taken into account in order to implement an effective therapeutic strategy that limits the inherent risks.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Glomerulonefrite Membranosa/epidemiologia , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/patologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Biópsia por Agulha , Comorbidade , Feminino , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/terapia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Humanos , Imuno-Histoquímica , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Estudos de Amostragem , Índice de Gravidade de Doença , Distribuição por Sexo , Taxa de Sobrevida , Adulto Jovem
11.
Transplantation ; 100(9): 1970-8, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26555949

RESUMO

BACKGROUND: Patients with HNF1B mutations develop progressive chronic renal failure, diabetes mellitus (40-50%), and liver tests abnormalities (40-70%). In HNF1B patients who reach end-stage renal disease, single kidney transplantation (SKT) or combined kidney-pancreas transplantation can be considered. METHODS: A retrospective multicenter study including 18 HNF1B patients receiving SKT or kidney-pancreas transplantation, and in vitro experiments including the characterization of the HNF1B expression after calcineurin inhibitor (CNI) exposure. RESULTS: After SKT, 50% of the HNF1B patients develop early posttransplantation diabetes mellitus, whereas 40% experience new-onset or severe worsening of preexisting abnormalities of liver tests, including severe cholestasis. In liver biopsies, disorders of the cholangiocytes primary cilium and various degrees of bile duct paucity and dysplasia were identified. In vitro studies combining CNI exposure and siRNA-mediated inhibition of NFATc revealed that calcineurin inhibition decreases HNF1B expression in epithelial cells but independent of NFATc. CONCLUSIONS: Because HNF1B-related disease is a heterozygous condition, CNIs used to prevent rejection may induce reduced expression of the nonmutated allele of HNF1B leading to a superimposed defect of HNF-1ß transcriptional activity. Taking into account the specific risk of posttransplantation diabetes mellitus and liver disorders in HNF1B patients, these findings advocate for in-depth characterization of pathways that regulate HNF1B and plead for considering individually tailored graft management that may include a CNI-free immunosuppressive regimen. Interventional studies will have to confirm this individualized approach.


Assuntos
Inibidores de Calcineurina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Diabetes Mellitus/induzido quimicamente , Fator 1-beta Nuclear de Hepatócito/metabolismo , Imunossupressores/efeitos adversos , Falência Renal Crônica/cirurgia , Transplante de Rim , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Adolescente , Adulto , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Criança , Pré-Escolar , Estudos Transversais , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo , França , Predisposição Genética para Doença , Células Hep G2 , Fator 1-beta Nuclear de Hepatócito/genética , Humanos , Lactente , Recém-Nascido , Rim/metabolismo , Rim/patologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/genética , Falência Renal Crônica/metabolismo , Transplante de Rim/efeitos adversos , Fígado/metabolismo , Fígado/patologia , Mutação , Fatores de Transcrição NFATC/genética , Fatores de Transcrição NFATC/metabolismo , Transplante de Pâncreas , Fenótipo , Interferência de RNA , Estudos Retrospectivos , Fatores de Tempo , Transfecção , Resultado do Tratamento
12.
PLoS One ; 9(8): e105422, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25144742

RESUMO

Clinicians are well aware of existing pharmacologically-induced immune deficient status in kidney-transplanted patients that will favor their susceptibility to bacterial or viral infections. Previous studies indicated that advanced Stage 4-5 Chronic Kidney Disease might also be regarded as an immune deficiency-like status as well, even though the mechanisms are not fully understood. Here, we analyzed the ex vivo frequency and the functional properties of both conventional and innate-like T (ILT) lymphocyte subsets in the peripheral blood of 35 patients on hemodialysis, 29 kidney transplanted patients and 38 healthy donors. We found that peripheral blood cell count of ILT cells, as iNKT (invariant Natural Killer T) and MAIT (mucosal-associated invariant T), were significantly decreased in hemodialyzed patients compared to healthy controls. This deficiency was also observed regarding conventional T cells, including the IL-17-producing CD4(+) Th17 cells. Pertaining to regulatory T cells, we also noticed major modifications in the global frequency of CD4(+)CD25(+)Foxp3(+) T lymphocytes, including the resting suppressive CD45RA(+)Foxp3lo and activated suppressive CD45RA-Foxp3hi T cell subpopulations. We found no significant differences between the immune status of hemodialyzed and kidney-transplanted subjects. In conclusion, we demonstrated that both ILT and conventional T cell numbers are equally impaired in hemodialyzed and kidney-transplanted patients.


Assuntos
Imunidade Inata , Transplante de Rim , Diálise Renal , Subpopulações de Linfócitos T/imunologia , Adulto , Citocinas/metabolismo , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunofenotipagem , Falência Renal Crônica/etiologia , Falência Renal Crônica/imunologia , Falência Renal Crônica/terapia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Fenótipo , Subpopulações de Linfócitos T/metabolismo , Adulto Jovem
13.
Exp Clin Transplant ; 11(3): 239-44, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23530925

RESUMO

OBJECTIVES: Scarce data exist regarding the effect of acute graft pyelonephritis on kidney histology after a kidney transplant. This study sought to assess the kidney histology at 1 month, and kidney function at 1 year, after acute graft pyelonephritis in kidney transplant patients. MATERIALS AND METHODS: All kidney transplant patients with acute graft pyelonephritis between October 2006, and December 2008, underwent a kidney biopsy 1 month later (n=28). Histologic findings were compared with those observed in a control group (n=28) who underwent a protocol kidney biopsy at 1 year posttransplant and did not present with acute graft pyelonephritis. Patients were matched according to age, sex, and immunosuppressive regimen. RESULTS: Kidney function was impaired by the acute graft pyelonephritis episodes at the time of biopsy. In 40% of patients, the estimated glomerular filtration rate did not return to baseline by 1 month after acute graft pyelonephritis and remained impaired thereafter. Three patients had features of acute rejection. Tubulitis was seen more frequently in the acute graft pyelonephritis group, especially in patients in whom estimated glomerular filtration rate did not completely recover by 1 month after acute graft pyelonephritis. Patients with acute graft pyelonephritis who had inflammatory infiltrate of > 20% 1 month after acute graft pyelonephritis had worse kidney function 1 year later. CONCLUSIONS: After transplant, when kidney function remains impaired 1 month after acute graft pyelonephritis, kidney biopsies allowed graft rejection diagnosis and predicted kidney function recovery.


Assuntos
Transplante de Rim/efeitos adversos , Rim/patologia , Pielonefrite/diagnóstico , Doença Aguda , Adulto , Idoso , Biópsia , Estudos de Casos e Controles , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Pielonefrite/etiologia , Pielonefrite/patologia , Pielonefrite/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Tempo , Adulto Jovem
14.
PLoS One ; 8(5): e63585, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23704921

RESUMO

Epithelial repair following acute kidney injury (AKI) requires epithelial-mesenchyme-epithelial cycling associated with transient re-expression of genes normally expressed during kidney development as well as activation of growth factors and cytokine-induced signaling. In normal kidney, the Hnf-1ß transcription factor drives nephrogenesis, tubulogenesis and epithelial homeostasis through the regulation of epithelial planar cell polarity and expression of developmental or tubular segment-specific genes. In a mouse model of ischemic AKI induced by a 2-hours hemorrhagic shock, we show that expression of this factor is tightly regulated in the early phase of renal repair with a biphasic expression profile (early down-regulation followed by transient over-expression). These changes are associated to tubular epithelial differentiation as assessed by KSP-cadherin and megalin-cubilin endocytic complex expression analysis. In addition, early decrease in Hnf1b expression is associated with the transient over-expression of one of its main target genes, the suppressor of cytokine signaling Socs3, which has been shown essential for renal repair. In vitro, hypoxia induced early up-regulation of Hnf-1ß from 1 to 24 hours, independently of the hypoxia-inducible factor Hif-1α. When prolonged, hypoxia induced Hnf-1ß down-regulation while normoxia led to Hnf-1ß normalization. Last, Hnf-1ß down-regulation using RNA interference in HK-2 cells led to phenotype switch from an epithelial to a mesenchyme state. Taken together, we showed that Hnf-1ß may drive recovery from ischemic AKI by regulating both the expression of genes important for homeostasis control during organ repair and the state of epithelial cell differentiation.


Assuntos
Células Epiteliais/metabolismo , Células Epiteliais/patologia , Fator 1-beta Nuclear de Hepatócito/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Rim/metabolismo , Rim/patologia , Injúria Renal Aguda/genética , Injúria Renal Aguda/patologia , Injúria Renal Aguda/fisiopatologia , Animais , Biomarcadores/metabolismo , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/genética , Linhagem Celular , Modelos Animais de Doenças , Endocitose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Fator 1-beta Nuclear de Hepatócito/antagonistas & inibidores , Fator 1-beta Nuclear de Hepatócito/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Rim/efeitos dos fármacos , Rim/fisiopatologia , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Túbulos Renais Proximais/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Inibidores de Prolil-Hidrolase/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Choque Hemorrágico/complicações , Choque Hemorrágico/patologia , Choque Hemorrágico/fisiopatologia , Cicatrização/efeitos dos fármacos
16.
Clin J Am Soc Nephrol ; 6(8): 1895-902, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21737848

RESUMO

BACKGROUND AND OBJECTIVES: Enteric overabsorption of oxalate may lead to hyperoxaluria and subsequent acute oxalate nephritis (AON). AON related to chronic pancreatitis is a rare and poorly described condition precluding early recognition and treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We collected the clinical characteristics, treatment, and renal outcome of 12 patients with chronic pancreatitis-associated AON followed in four French renal units. RESULTS: Before AON, mild to moderate chronic kidney disease was present in all patients, diabetes mellitus in eight (insulin [n = 6]; oral antidiabetic drugs [n = 2]), and known chronic pancreatitis in only eight. At presentation, pancreas imaging showed gland atrophy/heterogeneity, Wirsung duct dilation, calcification, or pseudocyst. Renal findings consisted of rapidly progressive renal failure with tubulointerstitial profile. Acute modification of glomerular filtration preceded the AON (i.e., diarrhea and diuretics). Increase in urinary oxalate excretion was found in all tested patients and hypocalcemia in nine (<1.5 mmol/L in four patients). Renal biopsy showed diffuse crystal deposits, highly suggestive of oxalate crystals, with tubular necrosis and interstitial inflammatory cell infiltrates. Treatment consisted of pancreatic enzyme supplementation, oral calcium intake, and an oxalate-free diet in all patients and renal replacement therapy in five patients. After a median follow-up of 7 months, three of 12 patients reached end-stage renal disease. CONCLUSION: AON is an under-recognized severe crystal-induced renal disease with features of tubulointerstitial nephritis that may occur in patients with a long history of chronic pancreatitis or reveal the pancreatic disease. Extrinsic triggering factors should be prevented.


Assuntos
Oxalato de Cálcio/metabolismo , Hiperoxalúria/etiologia , Falência Renal Crônica/etiologia , Rim/metabolismo , Nefrite Intersticial/etiologia , Pancreatite Crônica/complicações , Insuficiência Renal/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , França , Taxa de Filtração Glomerular , Humanos , Hiperoxalúria/metabolismo , Hiperoxalúria/patologia , Hiperoxalúria/fisiopatologia , Hiperoxalúria/terapia , Rim/fisiopatologia , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/metabolismo , Nefrite Intersticial/patologia , Nefrite Intersticial/fisiopatologia , Nefrite Intersticial/terapia , Pancreatite Crônica/metabolismo , Pancreatite Crônica/patologia , Pancreatite Crônica/fisiopatologia , Pancreatite Crônica/terapia , Insuficiência Renal/metabolismo , Insuficiência Renal/patologia , Insuficiência Renal/fisiopatologia , Insuficiência Renal/terapia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
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