RESUMO
BACKGROUND: Epstein-Barr virus (EBV) is a herpesvirus linked to nine different human tumors and lymphoproliferative disorders. Immunosuppression promotes EBV-driven malignancies. The most frequent EBV-induced malignancies are lymphomas and nasopharyngeal carcinoma. By promoting smooth muscle proliferation, EBV can induce EBV-associated smooth muscle tumors (EBV-SMT). EBV-SMT is a rare oncological entity for which no current guideline for diagnosis or management exists. Data on posttransplant EBV-SMT (PT-SMT) are scarce in kidney transplant recipients. METHODS: We conducted a national multicentric retrospective study and collected cases among transplantation centers in France. Kidney transplant recipients experiencing histologically proven PT-SMT were included. We collected data on demographic characteristics of patient, history of kidney transplantation, history of PT-SMT, evolution of graft function, and patient survival. RESULTS: Eight patients were included. The median age at PT-SMT diagnosis was 31 years (range 6.5-40). PT-SMT occurred after a median delay of 37.8 months after transplantation (range 6-175). PT-SMT management consisted in immunosuppressive regimen minimization in all patients. Introduction of mTOR inhibitors was performed in two patients. Four patients (50%) needed chemotherapy. Surgical resection was performed in four patients. At last follow-up after PT-SMT diagnosis (median 33 months (range 17-132)), five patients were considered in complete remission, and two patients had died. Two patients experienced graft rejection; two resumed dialysis (25%). All patients with available data presented with impaired graft function at last follow-up. CONCLUSION: PT-SMT is a subacute and progressive disease during kidney transplantation. Even if the risk of developing PT-SMT is low in kidney transplant recipients (0.07% in our cohort), PT-SMT is associated with significant graft loss, possibly due to reduced immunosuppression. Developing guidelines could help transplantation teams better manage these patients.
Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Transplante de Rim , Complicações Pós-Operatórias , Tumor de Músculo Liso , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Masculino , Feminino , Tumor de Músculo Liso/virologia , Tumor de Músculo Liso/etiologia , Tumor de Músculo Liso/patologia , Tumor de Músculo Liso/diagnóstico , Adulto , Seguimentos , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/isolamento & purificação , Prognóstico , França/epidemiologia , Adolescente , Adulto Jovem , Criança , Complicações Pós-Operatórias/diagnóstico , Rejeição de Enxerto/etiologia , Falência Renal Crônica/cirurgia , Sobrevivência de Enxerto , Fatores de Risco , Testes de Função Renal , Taxa de Filtração Glomerular , Taxa de SobrevidaRESUMO
Chronic kidney disease (CKD) is a major cause of death worldwide and is associated with a high risk for cardiovascular and all-cause mortality. In CKD, endothelial dysfunction occurs and uremic toxins accumulate in the blood. miR-126 is a regulator of endothelial dysfunction and its blood level is decreased in CKD patients. In order to obtain a better understanding of the physiopathology of the disease, we correlated the levels of miR-126 with several markers of endothelial dysfunction, as well as the representative uremic toxins, in a large cohort of CKD patients at all stages of the disease. Using a univariate analysis, we found a correlation between eGFR and most markers of endothelial dysfunction markers evaluated in this study. An association of miR-126 with all the evaluated uremic toxins was also found, while uremic toxins were not associated with the internal control, specifically cel-miR-39. The correlation between the expression of endothelial dysfunction biomarker Syndecan-1, free indoxyl sulfate, and total p-cresyl glucuronide on one side, and miR-126 on the other side was confirmed using multivariate analysis. As CKD is associated with reduced endothelial glycocalyx (eGC), our results justify further evaluation of the role of correlated parameters in the pathophysiology of CKD.
Assuntos
Biomarcadores/metabolismo , Indicã/metabolismo , MicroRNAs/genética , Insuficiência Renal Crônica/genética , Sindecana-1/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Glicocálix/metabolismo , Humanos , Indicã/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/metabolismo , Toxinas Biológicas/metabolismo , Uremia/metabolismoRESUMO
MicroRNAs (miRNAs) are short single-stranded RNAs that control gene expression through base pairing with regions within the 3'-untranslated region of target mRNAs. These small non-coding RNAs are now increasingly known to be involved in kidney physiopathology. In this review we will describe how miRNAs were in recent years implicated in cellular and animal models of kidney disease but also in chronic kidney disease, haemodialysed and grafted patients, acute kidney injury patients and so on. At the moment miRNAs are considered as potential biomarkers in nephrology, but larger cohorts as well as the standardization of methods of measurement will be needed to confirm their usefulness. It will further be of the utmost importance to select specific tissues and biofluids to make miRNAs appropriate in day-to-day clinical practice. In addition, up- or down-regulating miRNAs that were described as deregulated in kidney diseases may represent innovative therapeutic methods to cure these disorders. We will enumerate in this review the most recent methods that can be used to deliver miRNAs in a specific and suitable way in kidney and other organs damaged by kidney failure, such as the cardiovascular system.
Assuntos
Injúria Renal Aguda/genética , Biomarcadores/análise , Regulação da Expressão Gênica , MicroRNAs/genética , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/terapia , Animais , HumanosAssuntos
Regulação da Expressão Gênica/fisiologia , Macrófagos/metabolismo , MicroRNAs/metabolismo , Monócitos/metabolismo , Animais , Proteínas de Transporte/biossíntese , Proteínas de Drosophila/biossíntese , Genômica , Macrófagos/citologia , Camundongos , Monócitos/citologia , Proteína-Arginina N-Metiltransferases/biossíntese , Células RAW 264.7 , Enzimas de Conjugação de Ubiquitina/biossínteseRESUMO
INTRODUCTION: Kidney transplant recipients (KTRs) produce a weak humoral response to coronavirus disease 2019 (COVID-19) vaccines. However, the factors associated with the quality of the serological response to three doses of COVID-19 vaccine have not been unambiguously identified. METHODS: We included KTRs followed in the Nephrology Department at Amiens University Hospital (Amiens, France) between June and December 2021 who had received three doses of a COVID-19 mRNA vaccine (or two doses plus an episode of polymerase chain reaction-confirmed COVID-19). The lack of a humoral response was defined as an antibody titer below 7.1 binding antibody units (BAU)/mL, and an optimal response was defined as an antibody titer above 264 BAU/mL. RESULTS: Of the 371 patients included, 246 (66.3%) were seropositive, and 97 (26.1%) had an optimal response. In a multivariate analysis, the only factor associated with seropositivity was a history of COVID-19 [odds ratio (OR) 87.2; 95% confidence interval (CI) (7.88-965.0); p < 0.0001], while the main factors associated with non-response were female sex [OR 0.28; 95%CI (0.15-0.51); p < 0.0001], less than 36 months between kidney transplantation and vaccination [OR 0.26; 95%CI (0.13-0.52); p < 0.0001], a higher creatinine level [OR 0.33; 95%CI (0.19-0.56); p < 0.0001], the use of tacrolimus [OR 0.23; 95%CI (0.12-0.45); p < 0.0001], the use of belatacept [OR 0.01; 95%CI (0.001-0.20); p = 0.002] and three-drug immunosuppression [OR 0.39; 95%CI (0.19-0.78); p = 0.015]. A history of COVID-19 was associated with an optimal response [OR 4.03; 95%CI (2.09-7.79); p < 0.0001], while an older age at vaccination [OR 0.97; 95%CI (0.95-0.99); p = 0.002], less than 36 months between kidney transplantation and vaccination [OR 0.35; 95%CI (0.18-0.69); p = 0.002], a higher creatinine level [OR 0.60; 95%CI (0.38-0.93); p = 0.02], three-drug immunosuppression [OR 0.45; 95%CI (0.27-0.76); p = 0.003] were associated with a poorer response. CONCLUSION: We identified factors associated with a humoral response to a COVID-19 mRNA vaccine in KTRs. These findings might help physicians to optimize vaccination in KTRs.
Assuntos
COVID-19 , Transplante de Rim , Humanos , Feminino , Masculino , Vacinas contra COVID-19/uso terapêutico , COVID-19/prevenção & controle , Creatinina , Vacinas de mRNARESUMO
Background: Glomerulonephritis (GN) with non-Randall-type, non-cryoglobulinaemic monoclonal immunoglobulin G deposits encompasses rare diseases [proliferative GN with non-organized deposits (PGNMID) and immunotactoid GN] that cannot be distinguished without ultrastructural analysis by electron microscopy (EM). Methods: Here, we report and analyse the prognosis of 41 EM-proven (PGNMID for 39/41) and 22 non-EM-proven/DNAJB9-negative cases, diagnosed between 2001 and 2019 in 12 French nephrology centres. Results: Median (interquartile range) serum creatinine (SCr) at presentation was 150 (92-256) µmol/L. The predominant histological pattern was membranoproliferative GN (79%), with IgG3 (74%) kappa (78%) deposits the most frequently observed. Disease presentation and patient management were similar between EM-proven and non-EM-proven cases. A serum monoclonal spike was detected for 21 patients and 10 had an underlying haematological malignancy. First-line therapy was mixed between clone-targeted therapy (n = 33), corticosteroids (n = 9) and RAAS inhibitors (n = 19). After 6 months, nine patients achieved complete and 23 partial renal recovery. In univariate analysis, renal recovery was associated with baseline SCr (odds ratio 0.70, P = 0.07). After a median follow-up of 52 (35-74) months, 38% of patients had progressed to end-stage kidney disease independently associated with baseline SCr [hazard ratio (HR) 1.41, P = 0.003] and glomerular crescentic proliferation (HR 4.38, P = 0.004). Conclusions: Our results confirm that non-cryoglobulinaemic and non-Randall GN with monoclonal IgG deposits are rarely associated with haematological malignancy. The prognosis is uncertain but may be improved by early introduction of a specific therapy.
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Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurological symptom were independently associated with CM (p < 0.001). Positive serum cryptococcal antigen at diagnosis was also significantly associated with CM (p < 0.001). On magnetic resonance imaging (MRI), three patterns of brain injury were identified: parenchymal, meningeal, and vascular lesions. Although CM does not affect graft function directly, it entails a grim prognosis.
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Several microRNAs (miRNAs) have been linked to chronic kidney disease (CKD) mortality, cardiovascular (CV) complications and kidney disease progression. However, their association with clinical outcomes remains poorly evaluated. We used real-time qPCR to measure serum levels of miR-126 and miR-223 in a large cohort of 601 CKD patients (CKD stage G1 to G5 patients or on renal replacement therapy - CKD G5D) from Ghent University Hospital and 31 healthy controls. All-cause mortality and cardiovascular and renal events were registered as endpoints over a 6 year follow-up period. miR-126 levels were significantly lower from CKD stage G2 on, compared to controls. The serum levels of miR-223 were significantly lower from CKD stage G3B on. When considering overall mortality, patients with levels of either miR-126 or miR-223 below the median had a lower survival rate. Similar results were observed for CV and renal events. The observed link between the two miRNAs' seric levels and mortality, cardiovascular events or renal events in CKD appears to depend on eGFR. However, this does not preclude their potential role in the pathophysiology of CKD. In conclusion, CKD is associated with a decrease in circulating miR-223 and miR-126 levels.