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1.
Transplantation ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587920

RESUMO

Renal ischemia/reperfusion (I/R) injury is a common clinical challenge faced by clinicians in kidney transplantation. I/R is the leading cause of acute kidney injury, and it occurs when blood flow to the kidney is interrupted and subsequently restored. I/R impairs renal function in both short and long terms. Renal ischemic preconditioning refers to all maneuvers intended to prevent or attenuate ischemic damage. In this context, the present review focuses on the dual-specificity phosphatase 3 (DUSP3), also known as vaccinia H1-related phosphatase, an uncommon regulator of mitogen-activated protein kinase (MAPK) phosphorylation. DUSP3 has different biological functions: (1) it acts as a tumor modulator and (2) it is involved in the regulation of immune response, thrombosis, hemostasis, angiogenesis, and genomic stability. These functions occur either through MAPK-dependent or MAPK-independent mechanisms. DUSP3 genetic deletion dampens kidney damage and inflammation caused by I/R in mice, suggesting DUSP3 as a potential target for preventing renal I/R injury. Here, we discuss the putative role of DUSP3 in ischemic preconditioning and the potential mechanisms of such an attenuated inflammatory response via improved kidney perfusion and adequate innate immune response.

2.
Nat Rev Nephrol ; 20(6): 402-420, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38443710

RESUMO

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the presence of proliferative lesions throughout the body. Management of TSC is challenging because patients have a multifaceted systemic illness with prominent neurological and developmental impact as well as potentially severe kidney, heart and lung phenotypes; however, every organ system can be involved. Adequate care for patients with TSC requires a coordinated effort involving a multidisciplinary team of clinicians and support staff. This clinical practice recommendation was developed by nephrologists, urologists, paediatric radiologists, interventional radiologists, geneticists, pathologists, and patient and family group representatives, with a focus on TSC-associated kidney manifestations. Careful monitoring of kidney function and assessment of kidney structural lesions by imaging enable early interventions that can preserve kidney function through targeted approaches. Here, we summarize the current evidence and present recommendations for the multidisciplinary management of kidney involvement in TSC.


Assuntos
Esclerose Tuberosa , Esclerose Tuberosa/genética , Esclerose Tuberosa/terapia , Esclerose Tuberosa/complicações , Humanos , Consenso , Angiomiolipoma/genética , Angiomiolipoma/etiologia , Guias de Prática Clínica como Assunto
4.
Clin Kidney J ; 16(12): 2542-2548, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38046039

RESUMO

Background: Autosomal dominant polycystic kidney disease (ADPKD) is prone to multiple complications, including cyst infection (CyI). 2-Deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography ([18F]-FDG PET/CT) imaging has proved useful in the diagnosis of renal and hepatic CyI. A 4-point scale comparing the uptake of [18F]-FDG in the suspected infected cyst versus the hepatic physiological background has been recently proposed. We performed an independent validation of this semi-quantitative scoring system. Methods: All ADPKD patients hospitalized between January 2009 and November 2019 who underwent an [18F]-FDG PET/CT for suspected CyI were retrospectively identified using computer-based databases. Medical files were reviewed. CyI was conventionally defined by the combination of fever (≥38°C), abdominal pain, increased plasma C-reactive protein levels (≥70 mg/L), absence of any other cause of inflammation and favourable outcome after ≥21 days of antibiotics. [18F]-FDG uptake of the suspected CyI was evaluated using a 4-point scale comparing the uptake of [18F]-FDG around the infected cysts with the uptake in the hepatic parenchyma. Statistics were performed using SAS version 9.4. Results: Fifty-one [18F]-FDG PET/CT scans in 51 patients were included, of which 11 were cases of CyI. The agreement between the 4-point scale and the gold-standard criteria of CyI was significant [odds ratio of 6.03 for CyI in case of a score ≥3 (P = .014)]. The corresponding sensitivity, specificity, and positive and negative predictive values of [18F]-FDG PET/CT using the 4-point scale were 64% [Clopper-Pearson 95% confidence interval (CI) 30%-89%], 78% (95% CI 62%-89%), 44% (95% CI 20%-70%) and 89% (95% CI 73%-97%), respectively. Conclusions: Our independent validation cohort confirms the use of a semi-quantitative 4-point scoring system of [18F]-FDG PET/CT imaging in the diagnosis of CyI in patients with ADPKD. Considering its performance metrics with high specificity and negative predictive value, the scoring system is particularly useful to distinguish other causes of clinical inflammation than CyI and as such avoid unnecessarily long antibiotic treatment.

5.
Rev Med Liege ; 78(12): 710-714, 2023 Dec.
Artigo em Francês | MEDLINE | ID: mdl-38095035

RESUMO

Syphilis is an acquired or congenital systemic pathology, currently on the rise in Europe. The clinical manifestations of syphilis are not very specific and variable over time. In this case report, we describe two renal presentations of syphilis in patients followed in a Pre-Exposure Prophylaxis (PrEP) program for the prevention of HIV infection. The specificity of the renal involvement of syphilis, the diagnostic and the therapeutic management will be discussed in this article.


La syphilis est une pathologie systémique acquise ou congénitale, actuellement en recrudescence en Europe. Les manifestations cliniques de la syphilis sont souvent peu spécifiques et variables au cours du temps. Nous décrivons ici deux présentations rénales de la syphilis survenues chez des patients suivis dans un programme de Pre-Exposure Prophylaxis (PrEP) de prévention contre l'infection VIH. La spécificité de l'atteinte rénale de la syphilis, la mise au point diagnostique et la prise en charge thérapeutique seront discutées dans cet article.


Assuntos
Infecções por HIV , Sífilis , Humanos , Sífilis/complicações , Sífilis/diagnóstico , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Rim , Europa (Continente)
6.
Rev Med Liege ; 78(11): 665-673, 2023 Nov.
Artigo em Francês | MEDLINE | ID: mdl-37955298

RESUMO

Streptococcus pneumoniae infections cause community-acquired pneumonia and invasive pneumococcal disease such as sepsis and acute meningitis. In the adult population, the risk of severe infections, which can be lethal, is particularly high among people aged above 65 years and subgroups with comorbidities. Pneumococcal vaccines underwent progressive improvement and a new conjugated vaccine targeting 20 serotypes (PCV20) is now available. The Belgian Superior Health Council has recently reiterated the importance of vaccinating at-risk individuals against S. pneumoniae and now recommends vaccination with PCV20 (Apexxnar®) as the preferred primary vaccination regimen in all at-risk adults. The present article reminds the risk of severe pneumococcal infections among patients with comorbidities, by targeting five of them, chronic respiratory diseases, heart failure, chronic kidney disease, diabetes mellitus and cirrhosis. It emphasizes the too low rate of pneumococcal vaccination in these at-risk subgroups and summarizes the last guidelines of the Belgian Superior Health Council in favor of pneumococcal vaccination in at-risk patients with comorbidities. Finally, it describes the Belgian reimbursement criteria recently granted to people aged 65-85 years with comorbidities.


Les infections par le Streptococcus pneumoniae sont responsables de pneumonies communautaires et de maladies invasives à pneumocoques telles que sepsis et méningites aiguës. Dans la population adulte, le risque d'infections graves, potentiellement léthales, est particulièrement élevé chez les personnes âgées de plus de 65 ans et parmi des sous-groupes avec comorbidités. Les vaccins antipneumococciques ont été progressivement améliorés et un nouveau vaccin conjugué ciblant 20 sérotypes (PCV20) est désormais disponible. Le Conseil Supérieur de la Santé (CSS) belge a rappelé, en 2022, l'importance de vacciner contre S. pneumoniae les personnes à risque et privilégie le PCV20 (Apexxnar®) pour la primo-vaccination chez les personnes adultes dans tous les groupes à risque. Cet article rappelle le risque d'infections pneumococciques graves chez les patients avec comorbidités, en ciblant plus particulièrement quatre d'entre elles, les maladies respiratoires chroniques, l'insuffisance cardiaque, la maladie rénale chronique, le diabète sucré et la cirrhose. Il insiste sur le trop faible taux de vaccination antipneumococcique dans ces populations à risque et résume les dernières recommandations du CSS en faveur de la vaccination antipneumococcique des groupes à risque en fonction de la présence de comorbidités. Enfin, il fait état des conditions de remboursement récemment accordées à la vaccination antipneumococcique dans les groupes à risque chez les personnes âgées de 65 à 85 ans.


Assuntos
Infecções Pneumocócicas , Adulto , Humanos , Bélgica/epidemiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Streptococcus pneumoniae , Vacinação , Vacinas Pneumocócicas , Vacinas Conjugadas
7.
Rev Med Liege ; 78(9): 529-532, 2023 Sep.
Artigo em Francês | MEDLINE | ID: mdl-37712164

RESUMO

Rhabdomyolysis is a clinical syndrome related to the damage of skeletal muscle. The symptomatology is often poor, but it classically includes muscle weakness, myalgia and red-brown urine. The causes may be multiple but are most frequently traumatic : the so-called "crush syndrome". The diagnosis is based on the increase in serum creatine kinase, which is sometimes associated with myoglobinuria. Rhabdomyolysis may cause severe complications, such as ionic disorders or acute kidney injury which can lead to the death of the patient.


La rhabdomyolyse est un syndrome clinique lié à la destruction du muscle squelettique. La symptomatologie est souvent pauvre et associe classiquement une faiblesse musculaire, des myalgies et des urines noirâtres. Les causes peuvent être multiples, mais sont le plus fréquemment traumatiques et regroupées sous le terme anglophone de «crush syndrome¼. Le diagnostic repose sur la majoration sérique de la créatine kinase, à laquelle s'associe parfois une myoglobinurie. Rarement bénigne, la rhabdomyolyse peut engendrer des complications sévères, telles que des troubles ioniques ou une insuffisance rénale pouvant mener au décès du patient.


Assuntos
Injúria Renal Aguda , Rabdomiólise , Humanos , Rabdomiólise/diagnóstico , Rabdomiólise/etiologia , Debilidade Muscular , Síndrome
8.
Cell Death Dis ; 14(8): 562, 2023 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-37626062

RESUMO

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Glomerular hyperfiltration and albuminuria subject the proximal tubule (PT) to a subsequent elevation of workload, growth, and hypoxia. Hypoxia plays an ambiguous role in the development and progression of DKD and shall be clarified in our study. PT-von-Hippel-Lindau (Vhl)-deleted mouse model in combination with streptozotocin (STZ)-induced type I diabetes mellitus (DM) was phenotyped. In contrary to PT-Vhl-deleted STZ-induced type 1 DM mice, proteinuria and glomerular hyperfiltration occurred in diabetic control mice the latter due to higher nitric oxide synthase 1 and sodium and glucose transporter expression. PT Vhl deletion and DKD share common alterations in gene expression profiles, including glomerular and tubular morphology, and tubular transport and metabolism. Compared to diabetic control mice, the most significantly altered in PT Vhl-deleted STZ-induced type 1 DM mice were Ldc-1, regulating cellular oxygen consumption rate, and Zbtb16, inhibiting autophagy. Alignment of altered genes in heat maps uncovered that Vhl deletion prior to STZ-induced DM preconditioned the kidney against DKD. HIF-1α stabilization leading to histone modification and chromatin remodeling resets most genes altered upon DKD towards the control level. These data demonstrate that PT HIF-1α stabilization is a hallmark of early DKD and that targeting hypoxia prior to the onset of type 1 DM normalizes renal cell homeostasis and prevents DKD development.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas , Animais , Camundongos , Nefropatias Diabéticas/genética , Rim , Túbulos Renais Proximais , Glomérulos Renais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética
10.
Rev Med Liege ; 78(3): 165-172, 2023 Mar.
Artigo em Francês | MEDLINE | ID: mdl-36924155

RESUMO

Tuberculosis is one of the deadliest infectious disease. Its annual incidence was 10 million cases in 2019. We report the case of a 40 years old immunocompetent patient presenting with two large subcutaneous masses in his back. The diagnosis work-up will reveal multifocal tuberculosis with pulmmonary, vertebral, muscular and lymph node lesions. This case is unusual due to its presentation in an immunocompetent patient. Several laboratories have conducted experiments to isolate characteristics of the host that would allow the infection to spread despite the absence of an immunosuppressive medical condition. We also analyze the role of the PET scanner in the initial assessment and its interest in the monitoring of extra-pulmonary disease under anti-tuberculosis treatment. Multifocal tuberculosis cases are no longer the preserve of the immunocompromised and can be found in our industrialized countries. We must enonciate this diagnosis in front of unusual presentations. The delay in consultation, but also the delay of treatment, allows more widespread infections.


La tuberculose est une des maladies infectieuses les plus mortelles. Son incidence annuelle était de 10 millions de cas en 2019. Nous rapportons le cas d'un patient immunocompétent de 40 ans qui se présente avec deux volumineuses masses sous-cutanées au niveau du dos. La mise au point révélera une tuberculose multifocale avec une atteinte pulmonaire, vertébrale, ganglionnaire et des collections abcédées musculaires plurifocales. Ce cas est atypique de par sa présentation chez un patient immunocompétent. Plusieurs laboratoires ont essayé d'isoler des caractéristiques de l'hôte qui permettraient à l'infection une extension disséminée malgré l'absence de condition médicale immunodépressive. Nous analysons également le rôle du PET scanner dans le bilan initial et son intérêt dans le suivi des foyers extra-pulmonaires sous traitement anti-tuberculeux. Les cas de tuberculose multifocale ne sont plus l'apanage des patients immunodéprimés et peuvent se rencontrer dans les pays industrialisés. Le diagnostic doit pouvoir être évoqué devant des présentations atypiques. Le retard du diagnostic et de la prise en charge thérapeutique favorise des infections plus étendues.


Assuntos
Tuberculose , Humanos , Adulto , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Imunocompetência
11.
Rev Med Liege ; 78(2): 107-113, 2023 Feb.
Artigo em Francês | MEDLINE | ID: mdl-36799328

RESUMO

Delayed Graft Function (DGF) is defined as the need for dialysis during the first week after transplantation. DGF is frequent and mostly derived from the ischemia/reperfusion cascade to which the graft is subjected throughout the transplantation process. A graft biopsy is recommended after 7 days of DGF to exclude an episode of acute rejection. Note that DGF per se is associated with an increased risk of acute graft rejection, as well as with a shorter long-term graft survival. Several strategies are being studied to mitigate the ischaemic damage, thereby improving graft quality. Among these, cellular therapy using mesenchymal stromal cells (MSC) is promising, in particular via the administration of MSC in the machine perfusion during the preservation of the graft. We will discuss here the different definitions of DGF and the main predictive factors of DGF, as well as the impact on the graft outcomes. The current strategies to prevent DGF will be briefly reviewed.


La reprise retardée de fonction du greffon rénal (DGF en anglais pour Delayed Graft Function), définie notamment par la nécessité de dialyse durant la 1ère semaine après transplantation, reste un événement fréquent. La DGF résulte principalement des phénomènes d'ischémie/reperfusion auxquels le greffon est soumis tout au long du processus de transplantation. Néanmoins, une biopsie du greffon est préconisée après 7 jours de DGF afin d'exclure une cause non ischémique telle qu'un rejet aigu. La DGF est per se associée à un risque accru de rejet du greffon, ainsi qu'à une moins bonne survie du greffon rénal au long cours. Plusieurs stratégies sont étudiées afin d'atténuer les dommages ischémiques et améliorer la qualité du greffon. Parmi celles-ci, la thérapie cellulaire par cellules stromales mésenchymateuses est prometteuse, notamment via l'administration de celles-ci dans la machine de perfusion lors de la préservation du greffon. Nous aborderons les différentes définitions de la DGF ainsi que ses principaux facteurs prédictifs, l'impact sur le devenir du greffon et, brièvement, les stratégies actuelles dans le cadre de la prévention de la DGF.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Rim , Função Retardada do Enxerto/prevenção & controle , Função Retardada do Enxerto/etiologia , Sobrevivência de Enxerto , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/patologia , Isquemia , Fatores de Risco , Resultado do Tratamento
12.
Hypertension ; 80(4): 719-729, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36606502

RESUMO

The nondipping blood pressure (BP) pattern corresponds to a disruption in the circadian BP rhythm with an insufficient decrease in BP levels during nighttime sleep as observed using 24-hour ambulatory BP monitoring. Patients with nondipping BP pattern have poorer renal and cardiovascular outcomes, independent of their average 24-hour BP levels. The pathophysiology of nondipping BP is complex and involves numerous mechanisms: perturbations of (1) the circadian rhythm, (2) the autonomic nervous system, and (3) water and sodium regulation. This review provides an outline of the pathways potentially involved in the nondipping BP profile in different conditions. A recent hypothesis is also discussed involving the role of gut microbiota in the dipping/nondipping patterns, via the fecal diet-derived short chain fatty acids.


Assuntos
Sistema Cardiovascular , Hipertensão , Humanos , Pressão Sanguínea/fisiologia , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano/fisiologia
13.
Bioengineering (Basel) ; 10(1)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36671640

RESUMO

Ionizing irradiation is widely applied as a fundamental therapeutic treatment in several diseases. Acute kidney injury (AKI) represents a global public health problem with major morbidity and mortality. Renal ischemia/reperfusion (I/R) is the main cause of AKI. I/R injury occurs when blood flow to the kidney is transiently interrupted and then restored. Such an ischemic insult significantly impairs renal function in the short and long terms. Renal ischemic preconditioning (IPC) corresponds to the maneuvers intended to prevent or attenuate the ischemic damage. In murine models, irradiation-induced preconditioning (IP) renders the renal parenchyma resistant to subsequent damage by activating defense pathways involved in oxidative stress, angiogenesis, and inflammation. Before envisioning translational applications in patients, safe irradiation modalities, including timing, dosage, and fractionation, need to be defined.

14.
Acta Clin Belg ; 78(3): 200-205, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35938938

RESUMO

BACKGROUND: The impact of immunosuppression on the occurrence of Coronavirus Disease 2019 (COVID-19) remains unclear. METHODS: We conducted a prospective screening of anti-S1/S2 IgGs against SARS-CoV-2 Spike protein from March, 1 2020 to May, 15 2021 (prior to the vaccination campaign) in a cohort of 713 kidney transplant recipients (KTRs). In a first phase, the factual incidence and seroprevalence of COVID-19 was established in this cohort: cases diagnosed by serology were added to RT-PCR-based diagnoses to obtain the overall incidence of COVID-19 in both symptomatic and asymptomatic KTRs. In the second phase, the kinetics of the post-COVID-19 humoral response were studied, taking into account the severity of the disease defined by the need for oxygen therapy (group S, "severe") or not (group nS, "not severe"). RESULTS: The combined diagnostic approaches identified 138 COVID-19 cases (19.2%), with 37 diagnoses by serology (26.8%). The rate of asymptomatic KTRs reached 20.3% (28/138). Thirteen patients (9.4%) died from COVID-19. The seroconversion rate was 91.7% (99/108). The peak anti-S1/S2 IgG level was 85 [30-150] AU/ml and was similar between the S and nS groups (117 [38; 186] AU/ml versus 73 [23; 140] AU/ml). A high probability of persistence of anti-S1/S2 IgG post-COVID-19 was observed, with only 10.1% (7/69) of the patients having negated their serology during the 9-month follow-up. CONCLUSION: Our pragmatic serological screening combined with RT-PCR tests provides a better estimation of the real incidence of COVID-19 in KTRs. A significant proportion of KTRs develop humoral immunity post COVID-19, which most often persists beyond 9 months.


Assuntos
COVID-19 , Transplante de Rim , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , Incidência , Estudos Prospectivos , SARS-CoV-2 , Estudos Soroepidemiológicos , Imunoglobulina G
15.
Antivir Ther ; 27(4): 13596535221094898, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-36000318

RESUMO

BACKGROUND: Data on low bone mineral density (BMD) in people living with HIV (PLWH) are mainly derived from younger adults; little is known about how antiretroviral therapy (ART) and alterations in the renal-bone axis relate to BMD in older PLWH. METHODS: Cross-sectional study of men > 50 years and post-menopausal women with HIV. Antiretroviral therapy exposure was stratified into four groups based on use of tenofovir disoproxil fumarate (TDF) and protease inhibitors (PI): non-TDF/non-PI, non-TDF/PI, TDF/non-PI, and TDF/PI. Bone mineral density was measured by dual X-ray absorptiometry (DXA). Bone turnover/regulatory markers and renal tubular function were analysed in stored plasma and urine samples. The association of ART exposure and bone/renal biomarkers on BMD was explored using logistic regression models. RESULTS: 247 individuals (median [IQR] age 57 [53, 65] years; 47% female; 13% of Black ethnicity; CD4 count 643 [473, 811] cells/mm3; and 98% with HIV RNA < 200 copies/mL) were included. Bone turnover and renal tubular function differed significantly by ART exposure. In analyses adjusted for demographic and traditional renal/bone risk factors, exposure to TDF and PI was associated with a fourfold greater risk of low BMD at the femoral neck and exposure to TDF and/or PI with a threefold greater risk of low BMD at the lumbar spine. The relationship between ART and low BMD was not altered by further adjustment for bone turnover or renal tubular function markers. CONCLUSIONS: The associations between low BMD and ART exposure (TDF vs. non-TDF and boosted vs. unboosted third agents) were minimally affected by adjustments for bone and kidney biomarkers.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adulto , Idoso , Fármacos Anti-HIV/efeitos adversos , Antirretrovirais/efeitos adversos , Biomarcadores , Densidade Óssea , Estudos Transversais , Feminino , Infecções por HIV/complicações , Humanos , Rim , Masculino , Pessoa de Meia-Idade , Tenofovir/efeitos adversos
16.
Am J Physiol Renal Physiol ; 323(2): F198-F211, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35796462

RESUMO

Renal ischemia-reperfusion (I/R) causes acute kidney injury (AKI). Ischemic preconditioning (IPC) attenuates I/R-associated AKI. Whole body irradiation induces renal IPC in mice. Still, the mechanisms remain largely unknown. Furthermore, the impact of kidney-centered irradiation on renal resistance against I/R has not been studied. Renal irradiation (8.5 Gy) was done in male 8- to 12-wk-old C57bl/6 mice using a small animal radiation therapy device. Left renal I/R was performed by clamping the renal pedicles for 30 min, with simultaneous right nephrectomy, at 7, 14, and 28 days postirradiation. The renal reperfusion lasted 48 h. Following I/R, blood urea nitrogen (BUN) and serum creatinine (SCr) levels were lower in preirradiated mice compared with controls; so was the histological Jablonski score of AKI. The metabolomics signature of renal I/R was attenuated in preirradiated mice. The numbers of proliferating cell nuclear antigen (PCNA)-, cluster of differentiation molecule 11b (CD11b)-, and cell surface glycoprotein F4/80-positive cells in the renal parenchyma post-I/R were reduced in preirradiated versus control groups. Such IPC was significantly observed as early as day 14 postirradiation. RNA sequencing showed an upregulation of angiogenesis- and stress response-related signaling pathways in irradiated nonischemic kidneys on day 28. Qualitative RT-PCR confirmed the increased expression of vascular endothelial growth factor (VEGF), activin receptor-like kinase 5 (ALK5), heme oxygenase-1 (HO1), platelet endothelial cell adhesion molecule-1 (PECAM1), NADPH oxidase 2 (NOX2), and heat shock proteins 70 and 27 (HSP70 and HSP27, respectively) in irradiated kidneys compared with controls. In addition, irradiated kidneys showed an increased CD31-positive vascular area compared with controls. A 14-day gavage of irradiated mice with the antiangiogenic drug sunitinib before I/R abrogated the irradiation-induced IPC at both functional and structural levels. Our observations suggest that kidney-centered irradiation activates proangiogenic pathways and induces IPC, with preserved renal function and attenuated inflammation post-I/R.NEW & NOTEWORTHY This study based on a mouse model of renal ischemia-reperfusion (I/R) aimed to 1) test whether and how irradiation strictly centered on the kidney protects against the I/R injury and 2) determine the shortest efficient delay of kidney irradiation to achieve such nephroprotection. Kidney irradiation increased the vascular surface in the renal parenchyma and conferred resistance against renal I/R damage, which highlights novel putative strategies in the field of ischemic acute kidney injury.


Assuntos
Injúria Renal Aguda , Precondicionamento Isquêmico , Traumatismo por Reperfusão , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Injúria Renal Aguda/prevenção & controle , Animais , Isquemia/metabolismo , Rim/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Front Immunol ; 13: 877953, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35757737

RESUMO

Introduction: Mesenchymal stromal cells (MSCs) have particular properties that are of interest in organ transplantation, including the expansion of regulatory T cells (Tregs), a key factor in transplant tolerance induction. However, the most effective immunosuppressive drug to associate with MSCs has yet to be defined. Additionally, the impact of the association of everolimus with MSCs on Treg expansion, and on the induction of liver graft tolerance, has never been studied. The aim of this study was to evaluate the effects of MSCs in combination, or not, with everolimus on Treg expansion and in a model of rejection after liver transplantation (LT) in the rat. Methods: Firstly, 24 Lewis rats were assigned to 4 groups (n=6 in each group) receiving intravenous MSCs or saline injection at day (D)9 with/without subcutaneous everolimus from D0 to D14. Analysis of circulating Tregs was performed at D0, D14 and D28. In a second set of experiment, 30 Lewis rats were randomized in 3 groups 48hours after LT with a Dark Agouti rat liver: everolimus (subcutaneous for 14 days), MSCs (intravenous injection at post-operative day 2 and 9), or both everolimus and MSCs. Rejection of the liver graft was assessed by liver tests, histology and survival. Results: Individually, MSC infusion and everolimus promoted Treg expansion in rats, and everolimus had no negative impact on Treg expansion in combination with MSCs. However, in the LT model, injections of MSCs two and nine days following LT were not effective at preventing acute rejection, and the combination of MSCs with everolimus failed to show any synergistic effect when compared to everolimus alone. Conclusion: Everolimus may be used in association with MSCs. However, in our model of LT in the rat, post-transplant MSC injections did not prevent acute rejection, and the association of MSCs with everolimus did not show any synergistic effect.


Assuntos
Transplante de Fígado , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Everolimo/farmacologia , Rejeição de Enxerto/patologia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias , Ratos , Ratos Endogâmicos Lew , Linfócitos T Reguladores
19.
Clin Chem Lab Med ; 60(7): 1064-1072, 2022 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-35508416

RESUMO

OBJECTIVES: Severity of chronic kidney disease is defined by glomerular filtration rate (GFR) and albuminuria (ACR) by the KDIGO and are related to cardiovascular outcomes and end-stage-kidney-failure. However, proteinuria (PCR) is more often available than ACR in records. Recently, equations were developed to estimate ACR from PCR. We investigated their performances in our population. METHODS: In the academic medical hospital of Liège, we retrospectively analysed same day measurement of ACR and PCR and staged them according to the KDIGO A1-A2-A3 categories. Analyser Roche Cobas (R) gathered 2,633 urinalysis (May 2018-May 2019) and analyser Abbott Alinity (A) 2,386 urinalysis (May 2019-March 2020). We compared the KDIGO staging of mACR and eACR obtained from Weaver's and Sumida's equations. RESULTS: Median age was 63 [52;71]/64 [53;72] years old, 43/42% were female; 78/74% had diabetes; proportion of mACR-A1 was 65.6%/64.2%, A2 was 25.5%/25.5% and A3 was 8.8%/10.3% (Method R/A, respectively). Both equations gave similar distribution of KDIGO staging of eACR. Overall agreements were higher than 88% regardless of the analyser or of the equation. Performances in between equations were equivalent according to the multi-level AUC (multinomial logistic regression model). CONCLUSIONS: Good concordance was observed between mACR and eACR regardless of the equation or of the analyser. No patient with an A3-measured ACR was estimated within the KDIGO A1 category. Though ACR should be measured when clinically needed, it may be reasonably estimated from the PCR through these equations, for epidemiologic retrospective studies or research purposes.


Assuntos
Insuficiência Renal Crônica , Urinálise , Idoso , Albuminas/análise , Albuminúria/diagnóstico , Albuminúria/urina , Creatinina/urina , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas , Insuficiência Renal Crônica/urina , Estudos Retrospectivos , Urinálise/métodos
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