RESUMO
BACKGROUND: Previous studies have reported that polymicrobial peritonitis in peritoneal dialysis (PD) is associated with poor outcomes, but recent data from European cohorts are scarce. METHODS: We included from the French Language Peritoneal Dialysis Registry all patients ≥18 years of age who started PD between January 2014 and November 2020. We compared microbiology and patient characteristics associated with mono- and polymicrobial peritonitis. We assessed patient outcomes after a first polymicrobial peritonitis using survival analysis with competing events. We differentiated microorganisms isolated from dialysis effluent as enteric or non-enteric pathogens. RESULTS: A total of 8848 patients contributed 13 023 patient-years of follow-up and 3348 culture-positive peritonitis episodes, including 251 polymicrobial ones. This corresponded to rates of 0.32 and 0.02 episodes/patient-year, respectively. For most patients (72%) who experienced polymicrobial peritonitis, this was their first peritonitis episode. Enteric pathogens were more frequently isolated in polymicrobial than in monomicrobial peritonitis (57 versus 44%; P < .001). In both cases of peritonitis with and without enteric pathogens, the polymicrobial versus monomicrobial character of the peritonitis was not associated with mortality in patients who did not switch to haemodialysis {adjusted cause-specific hazard ratio [acsHR] 1.2 [95% confidence interval (CI) 0.3-5.0], P = .78 and 1.1 [95% CI 0.7-1.8], P = .73, respectively}. However, the risks of death and switch to haemodialysis were higher for monomicrobial peritonitis with enteric pathogens compared with those without [acsHR 1.3 (95% CI 1.1-1.7), P = .02 and 1.9 (95% CI 1.5-2.4), P < .0001, respectively]. CONCLUSION: Isolation of enteric pathogens, rather than the polymicrobial character of the peritonitis, is associated with poorer outcomes.
Assuntos
Falência Renal Crônica , Diálise Peritoneal , Peritonite , Humanos , Estudos de Coortes , Diálise Renal , Estudos Retrospectivos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Diálise Peritoneal/efeitos adversos , Peritonite/epidemiologia , Peritonite/etiologia , Sistema de Registros , Idioma , Fatores de RiscoRESUMO
BACKGROUND: Data from the PEXIVAS trial challenged the role of plasma exchange (PLEX) in ANCA-associated vasculitides (AAV). We aimed to describe kidney biopsy from patients with AAV treated with PLEX, evaluate whether histopathologic findings could predict kidney function, and identify which patients would most benefit from PLEX. METHODS: We performed a multicenter, retrospective study on 188 patients with AAV and AKI treated with PLEX and 237 not treated with PLEX. The primary outcome was mortality or KRT at 12 months (M12). RESULTS: No significant benefit of PLEX for the primary outcome was found. To identify patients benefitting from PLEX, we developed a model predicting the average treatment effect of PLEX for an individual depending on covariables. Using the prediction model, 223 patients had a better predicted outcome with PLEX than without PLEX, and 177 of them had >5% increased predicted probability with PLEX compared with without PLEX of being alive and free from KRT at M12, which defined the PLEX-recommended group. Risk difference for death or KRT at M12 was significantly lower with PLEX in the PLEX-recommended group (-15.9%; 95% CI, -29.4 to -2.5) compared with the PLEX not recommended group (-4.8%; 95% CI, 14.9 to 5.3). Microscopic polyangiitis, MPO-ANCA, higher serum creatinine, crescentic and sclerotic classes, and higher Brix score were more frequent in the PLEX-recommended group. An easy to use score identified patients who would benefit from PLEX. The average treatment effect of PLEX for those with recommended treatment corresponded to an absolute risk reduction for death or KRT at M12 of 24.6%. CONCLUSIONS: PLEX was not associated with a better primary outcome in the whole study population, but we identified a subset of patients who could benefit from PLEX. However, these findings must be validated before utilized in clinical decision making.
Assuntos
Injúria Renal Aguda , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Injúria Renal Aguda/complicações , Injúria Renal Aguda/terapia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Anticorpos Anticitoplasma de Neutrófilos , Feminino , Humanos , Rim/patologia , Masculino , Troca Plasmática/efeitos adversos , Estudos RetrospectivosRESUMO
OBJECTIVE: The optimal induction therapy for severe glomerulonephritis of ANCA-associated vasculitis (AAV) is debated. We compared the efficacy of glucocorticoid and rituximab (RTX) or CYC induction therapy for severe AAV-related glomerulonephritis and evaluated the potential benefit of plasma exchange (PE) as adjunct therapy to CYC. METHODS: This retrospective, multicentre study included AAV patients with severe renal active disease (serum creatinine level ≥350 µmol/l and/or estimated glomerular filtration ratio ≤15 ml/min/1.73 m2). Propensity-score analysis was used to adjust for potential confounders. RESULTS: Between 2005 and 2017, 153 patients with AAV-related glomerulonephritis were studied (96 [60%] men; mean [s.d.] age 63 [13.1] years): 19 (12%) were treated with RTX and 134 (88%) with CYC. Remission rates did not differ between RTX- and CYC-treated groups. Although more patients with RTX than CYC were dialysis-free at month (M) 12 (79% vs 68%), the difference was not significant after adjustment. Among 134 patients with CYC-treated glomerulonephritis, 76 (57%) also had PE. M3 and M6 remission rates were comparable for weighted CYC groups with or without PE. For weighted groups, the dialysis-free survival rate with CYC was higher with than without PE at M6 (72% vs 64%; odds ratio 2.58) and M12 (74% vs 60%; odds ratio 2.78) reaching statistical significance at M12. CONCLUSION: We could not find any difference between RTX and CYC as induction therapy for patients with severe AAV-related glomerulonephritis. In patients receiving CYC induction regimen, the addition of PE conferred short-term benefits with higher dialysis-free rate at M12.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Creatinina , Ciclofosfamida , Feminino , Glomerulonefrite/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Troca Plasmática , Indução de Remissão , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do TratamentoRESUMO
Recurrence of primary focal and segmental glomerulosclerosis following kidney transplantation (rFSGS) is a frequent and severe disease. We studied the time to recurrence of FSGS and its impact on the response to plasma exchange (PE) and graft survival. Between 1990 and 2013, 2730 kidney transplants were performed, including 52 patients with a primary diagnosis of FSGS. Of these patients with primary FSGS, 34 (67%) developed rFSGS. We retrospectively divided these patients into two groups depending on the time to recurrence: early (up to three months after transplantation, n = 26) or late (more than three months after transplantation, n = 8). Survival did not significantly differ between the two groups. In cases of late recurrence, PE was started later and was performed less frequently, and remission was achieved after more PE sessions and longer PE treatment than for the early group (P = 0.01). In early recurrence, resistance to PE at 40 days was associated with no long-term response to PE. PE should be performed as soon as possible after rFSGS. Patients with late rFSGS need to be offered the same treatment regime as those with early rFSGS.
Assuntos
Glomerulosclerose Segmentar e Focal , Glomerulosclerose Segmentar e Focal/terapia , Sobrevivência de Enxerto , Humanos , Troca Plasmática , Recidiva , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Obesity has become an important issue in patients with end-stage renal disease (ESRD). Since it is considered a relative contraindication for renal transplantation, bariatric surgery has been advocated to treat morbid obesity in transplant candidates, and laparoscopic sleeve gastrectomy (LSG) is the most reported procedure. However, comparative data regarding outcomes of LSG in patients with or without ESRD are scarce. Consecutive patients with ESRD (n = 29) undergoing LSG were compared with matched patients with normal renal function undergoing LSG in a 1:3 ratio using propensity score adjustment. Data were collected from a prospective database. Eligibility for transplantation was also studied. A lower weight loss (20 kg (16-30)) was observed in patients with ESRD within the first year as compared to matched patients (28 kg (21-34)) (P < 0.05). After a median follow-up of 30 (19-50) months in the ESRD group, contraindication due to morbid obesity was lifted in 20 patients. Twelve patients underwent transplantation. In patients with ESRD potentially eligible for transplantation, LSG allows similar weight loss in comparison with matched patients with normal renal function, enabling lifting contraindication for transplantation due to morbid obesity in the majority of patients within the first postoperative year.
Assuntos
Transplante de Rim , Laparoscopia , Obesidade Mórbida , Índice de Massa Corporal , Estudos de Casos e Controles , Gastrectomia , Humanos , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The optimal management of anticoagulation in hemodialyzed patients with a high risk of bleeding is controversial. METHODS: We compared premature termination of dialysis caused by clotting events between AN69ST membranes (G1) and 0.8 mmol/L citrate-enriched dialysate (G2). The number of sessions that had increased venous pressure (VP) and variations in urea-reduction ratio (URR) were analyzed. RESULTS: Six hundred and two sessions were analyzed in 259 patients: 22.4% had sessions that ended prematurely (25% in G1 and 19.1% in G2, p = ns, OR 0.60 [0.34-1.08], p = 0.08). The increase in VP was lower in G2 (23 vs. 70, p < 0.001). URR was higher in G2 (0.56 vs. 0.60, p < 0.001). CONCLUSION: Clotting events that led to the termination of dialysis were comparable in the 2 groups. However, UUR was better in G2, and the number of patients with increased VP in the sessions was lower in G2. SHORT SUMMARY: Our study compared the effects of the AN69ST membrane and citrate-enriched dialysate on clotting events during the dialysis of 259 patients with a high risk of bleeding. URR was significantly better and fewer cases of increased VP occurred in the citrate group compared to the AN69 ST group. No significant difference was observed regarding the need to prematurely terminate a dialysis session.
Assuntos
Ácido Cítrico/farmacologia , Soluções para Diálise/farmacologia , Membranas Artificiais , Diálise Renal/métodos , Adulto , Coagulação Sanguínea , Pressão Sanguínea , Soluções para Diálise/química , Feminino , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Ureia/análiseRESUMO
FSGS is a common glomerular disorder that has a high propensity for recurrence after kidney transplant. The pathophysiology of FSGS is unknown, but podocytes seem to be the target of one or several circulating factors that lead to cytoskeleton reorganization and proteinuria. Research on podocytes has identified B7-1 as an important factor in podocyte biology and a new therapeutic target in renal disease. Indeed, in four patients with recurrent FSGS after transplant, treatment with the B7-1 blocker abatacept was associated with proteinuria remission. Here, we prospectively treated nine patients with recurrent FSGS after transplant using either abatacept or belatacept, a B7-1 blocker with higher affinity, and did not induce proteinuria remission. Furthermore, we did not detect B7-1 expression by immunofluorescence in podocytes of biopsy specimens from these or other kidney grafts or podocytes of native kidney biopsy specimens. In conclusion, B7-1 blockade did not induce FSGS remission after transplant in our study.
Assuntos
Abatacepte/farmacologia , Abatacepte/uso terapêutico , Antígeno B7-1/antagonistas & inibidores , Glomerulosclerose Segmentar e Focal/complicações , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Transplante de Rim , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/prevenção & controle , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Falha de Tratamento , Adulto JovemRESUMO
Chronic kidney disease, secondary to renal fibrogenesis, is a burden on public health. There is a need to explore new therapeutic pathways to reduce renal fibrogenesis. To study this, we used unilateral ureteral obstruction (UUO) in mice as an experimental model of renal fibrosis and microarray analysis to compare gene expression in fibrotic and normal kidneys. The cannabinoid receptor 1 (CB1) was among the most upregulated genes in mice, and the main endogenous CB1 ligand (2-arachidonoylglycerol) was significantly increased in the fibrotic kidney. Interestingly, CB1 expression was highly increased in kidney biopsies of patients with IgA nephropathy, diabetes, and acute interstitial nephritis. Both genetic and pharmacological knockout of CB1 induced a profound reduction in renal fibrosis during UUO. While CB2 is also involved in renal fibrogenesis, it did not potentiate the role of CB1. CB1 expression was significantly increased in myofibroblasts, the main effector cells in renal fibrogenesis, upon TGF-ß1 stimulation. The decrease in renal fibrosis during CB1 blockade could be explained by a direct action on myofibroblasts. CB1 blockade reduced collagen expression in vitro. Rimonabant, a selective CB1 endocannabinoid receptor antagonist, modulated the macrophage infiltrate responsible for renal fibrosis in UUO through a decrease in monocyte chemoattractant protein-1 synthesis. Thus, CB1 has a major role in the activation of myofibroblasts and may be a new target for treating chronic kidney disease.
Assuntos
Fibrose/genética , Rim/patologia , Miofibroblastos/metabolismo , RNA Mensageiro/metabolismo , Receptor CB1 de Canabinoide/genética , Doença Aguda , Animais , Ácidos Araquidônicos , Células Cultivadas , Quimiocina CCL2/metabolismo , Colágeno/metabolismo , Diabetes Mellitus/metabolismo , Modelos Animais de Doenças , Endocanabinoides , Fibrose/metabolismo , Fibrose/patologia , Perfilação da Expressão Gênica , Glomerulonefrite por IGA/metabolismo , Glicerídeos , Humanos , Ligantes , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Knockout , Miofibroblastos/efeitos dos fármacos , Nefrite Intersticial/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Piperidinas/farmacologia , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/análise , Receptor CB2 de Canabinoide/análise , Receptor CB2 de Canabinoide/genética , Rimonabanto , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima , Obstrução Ureteral/complicações , Obstrução Ureteral/metabolismoRESUMO
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a serious disease, the pathogenesis of which is unknown. Its recurrence after transplantation (Tx) and its partial remission after treatment with immunoadsorption (IA) on a protein A column indicate the existence of a circulating factor responsible for the disease that is able to bind to a protein A column. Recently, the soluble receptor of urokinase (suPAR) was described as the factor responsible for FSGS. We tested the capacity of suPAR to bind to protein A and to be eliminated by IA. METHODS: We measured suPAR in eluates of protein A columns from seven patients with recurrent FSGS after Tx (rFSGS) treated with IA, and in the serum of 13 patients with rFSGS and 11 healthy donors (HDs). Additionally, the plasma of these patients was immunoadsorbed in vitro on a protein A Sepharose column, and we quantified suPAR in the eluates and in pre- and post-column samples. RESULTS: The concentration of suPAR was higher in the plasma of patients with rFSGS than that of HD patients. However, the concentration of suPAR was similar before and after IA on protein A for the rFSGS and HD samples. The suPAR concentration was very low in the eluates from protein A columns incubated with plasma from HD or rFSGS patients. However, 85% of rFSGS patients showed a decrease in immunoglobulin G and proteinuria. CONCLUSIONS: Thus, suPAR does not significantly bind to protein A in vitro or in vivo.
Assuntos
Glomerulosclerose Segmentar e Focal/terapia , Técnicas de Imunoadsorção , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Proteína Estafilocócica A , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Glomerulosclerose Segmentar e Focal/sangue , Glomerulosclerose Segmentar e Focal/imunologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Transplante de Rim , Masculino , Recidiva , Estudos RetrospectivosAssuntos
Colchicina/uso terapêutico , Ciclosporina/uso terapêutico , Interações Medicamentosas , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/métodos , Complicações Pós-Operatórias/prevenção & controle , Tacrolimo/uso terapêutico , Quimioterapia Combinada , Rejeição de Enxerto/diagnóstico , Humanos , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Complicações Pós-Operatórias/diagnóstico , Prognóstico , Transplante HomólogoRESUMO
Chronic renalfailure (CRF), one of several disorders involving progressive loss of function of a vital organ, is a paradigm for medical/paramedical coordination networks, especially in view of the explosion of the geriatric CRF/dialysis population. An efficient network is crucial in this setting, given the very high incidence of CRF, its cost, its impact on employment, quality of life and quality of care; and the progression from medical treatment to replacement therapy (peritoneal or hemodialysis) and, eventually, organ transplantation from a living or deceased donor. There is a constant flow of patients entering and exiting care pathways between community practices (public or private), hospitals (general or teaching), medical laboratories, pharmacies (commuity and hospital) and a large number of allied health professions (nurses, social workers, dieticians, physiotherapists, secretaries, etc.). In the predialytic stage of CRF the goal of the network is to establish the diagnosis, slow disease progression, prevent or treat the many potentially complications, inform patients and their families, and postpone the need for dialysis and transplantation. When renal replacement therapy becomes necessary, the choice between peritoneal dialysis and hemodialysis follows strict rules and requires a more technical approach, with predominant involvement of the nephrologist. Finally, transplantation is highly hospital-centered, but patient monitoring in the community requires an approach very similar to that of the predialytic stage, with the involvement of specialists in internal medicine/general practitioners, as the potential complications cover a very broad field of disciplines (infectious, cardiovascular, metabolic, cancer). CRF is a major public health problem that requires a network-based approach involving multiple specialties and skills, the most difficult problem being its coordination. A similar approach can probably be extrapolated to other patients with chronically failing major organs (liver, lungs, heart).
Assuntos
Falência Renal Crônica/terapia , Qualidade da Assistência à Saúde/organização & administração , Humanos , Falência Renal Crônica/epidemiologia , Transplante de Rim/normas , Organização e Administração , Saúde Pública/métodos , Saúde Pública/normas , Diálise Renal/métodos , Diálise Renal/normasRESUMO
The diabetes and renal phenotype of patients with maturity-onset diabetes of the young (MODY) on a transplantation waiting list is not known; neither is their outcome after pancreas (PT) and/or kidney transplantation (KT). Between 2002 and 2009, we screened 50 of 150 patients referred for kidney and pancreas transplantation to the Kremlin-Bicêtre center for HNF1B and HNF1A mutations if one or more of the following criteria was present (i) an atypical history of diabetes (ii) diabetes with at least one affected parent or two affected relatives, (iii) an absence of auto-antibodies at diagnosis (iv) a persistent secretion of fasting C peptide (v) a personal or a family history of renal cysts or dysplasia. Their phenotype and their outcome were analyzed. Four HNF1A (MODY3) and eight HNF1B mutations [renal cysts and diabetes (RCAD)] were identified. All MODY3 patients had diabetic nephropathy, but only 50% of RCAD patients. Four patients underwent a kidney and pancreas transplantation and two a kidney transplant alone. After 4.1 ± 1.1 years of follow-up, 83% of patients still have a functioning kidney and 75% a functioning pancreas. PT can be proposed with good results for MODY3 and RCAD patients.
Assuntos
Doenças do Sistema Nervoso Central/cirurgia , Diabetes Mellitus Tipo 2/cirurgia , Transplante das Ilhotas Pancreáticas , Doenças Renais Císticas/cirurgia , Transplante de Rim , Adulto , Doenças do Sistema Nervoso Central/genética , Estudos de Coortes , Esmalte Dentário/anormalidades , Esmalte Dentário/cirurgia , Diabetes Mellitus Tipo 2/genética , Feminino , Seguimentos , Sobrevivência de Enxerto , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-beta Nuclear de Hepatócito/genética , Humanos , Transplante das Ilhotas Pancreáticas/fisiologia , Doenças Renais Císticas/genética , Transplante de Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Mutação , Análise de SobrevidaRESUMO
BACKGROUND: The current Coronavirus disease 2019 (COVID-19) outbreak is associated with significant mortality, especially in patients suffering from end stage renal disease (ESRD) and hemodialysis patients. Several previous studies reported an over-risk of arterial and venous thrombosis, in particular pulmonary embolism and venous thrombosis of catheter in COVID19 patients in intensive care unit. However, arteriovenous fistula (AVF) thrombosis has rarely been reported yet in these patients. AVF thrombosis is a serious complication that impacts significantly patients outcome. Here, we aim to describe characteristics and prognosis of a cohort of COVID-19 hemodialysis (HD) patients presenting with AVF thrombosis. METHODS: In the Ile de France region (Paris area) during the March 11th-April 30th 2020 period, fistula thrombosis cases were collected among COVID-19 hemodialysis patients in seven dialysis units and in interventional vascular departments. These patients' characteristics were analyzed through a review of the patient's medical records. RESULTS: Seventeen patients were included in our study (median age 69 years). Ten patients (59%) were men. Ten patients (59%) were diabetic and 88% had a high blood pressure. The mortality rate in these patients was 47%. All thrombosis treated with a declotting procedures (64%) were successfully cleared, but with early relapse in 36%. CONCLUSION: Our study highlights AVF thrombosis as a severe complication in COVID-19 hemodialysis patients that contributed to the severity and accelerated death.
Assuntos
Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , COVID-19 , Falência Renal Crônica , Trombose , Idoso , Fístula Arteriovenosa/etiologia , Derivação Arteriovenosa Cirúrgica/efeitos adversos , COVID-19/complicações , COVID-19/terapia , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Trombose/etiologiaRESUMO
BACKGROUND: The (H1N)1v influenza virus infection emerged in 2009 as a serious disease in targeted populations. Herein, we report on the tolerability and efficacy of (anti-H1N1)v vaccination in dialysis and transplant patients. METHODS: 18 renal-transplant recipients (RTR) and 19 dialysis patients (DP) [12 patients treated with peritoneal dialysis (PDP), 7 patients treated with haemodialysis (HDP)] were enrolled. DPs received one monovalent H1N1 adjuvanted-vaccine injection, and RTRs received two unadjuvanted vaccine injections within a 21-day period. Serologic response was defined as a haemagglutination inhibition titre of > 40 (seroprotection) and/or at least a four-fold increase in antibody titre from baseline (seroconversion). RESULTS: Seroprotection rate after vaccination was greater in DPs than RTRs (p = 0.007), as was seroconversion (p = 0.001). Serologic response was similar in PDPs and HDPs. CONCLUSIONS: Serologic response was satisfactory in DPs, whichever dialysis mode (DPD or HDP). It was low in RTRs as compared to DPs.
Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Transplante de Rim , Diálise Renal , Adjuvantes Imunológicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Masculino , Pessoa de Meia-Idade , VacinaçãoRESUMO
Major medical progress has been made in the field of renal transplantation over the last 40 years, thanks to advances in areas such as metabolism, immunology, therapeutics, and pathology. This progress has been accompanied by important changes in French legislation that governs organ harvest and transplantation, as well as the institutions that regulate organ allocation. Patient and graft survival have both increased markedly, although long-term improvements have been somewhat offset by complications, including adverse effects of immunosuppression. On average recipients are older than in the past and some recipients are now dying from age-related comorbidities despite having functional grafts.
Assuntos
Transplante de Rim/história , França , História do Século XX , História do Século XXI , Hospitais Universitários , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/mortalidade , Transplante de Rim/tendênciasRESUMO
Medium- and long-term renal graft survival depends on 4 main factors: the quality of the harvested graft, ischemia-reperfusion injury during harvesting and re-implantation, rejection, and the nephrotoxicity of certain drugs (especially immunosuppressants) used in this setting. The most nephrotoxic immunosuppressive drugs are the anticalcineurins (cyclosporine A and tacrolimus), a class discovered in the late 1970s and currently representing a basic component of all immunosuppressive protocols for solid organ graft recipients. The renal tubular and vascular toxicity of anticalcineurins is due to their immunosuppressive mechanism: they block the calcineurin pathway and thereby prevent transmission of the first signal from the T cell receptor to the nucleus, which normally triggers cytokine synthesis, New non-nephrotoxic immunosuppressants are therefore needed, especially for grafts of poor quality or subject to severe ischemia-reperfusion injury. Attention is turning to "old " molecules such as anti-thymocyte globulins, but exciting new immunosuppressants are now appearing. Alefacept is a fusion protein that binds to the immunological synapse-associated molecule CD2, which normally interacts with LFA-3. Belatacept, another fusion protein, blocks the T cell second signal CD 28-B7.1/B7.2. Finally, new chemical agents are being developed, such as sautrasporine, a tyrosine kinase inhibitor, and tofacitinib, a Jak inhibitor.
Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Rim , Sobrevivência de Enxerto , Humanos , Traumatismo por Reperfusão/prevenção & controle , Imunologia de TransplantesRESUMO
PURPOSE OF REVIEW: The nonimmune effects of currently used immunosuppressive drugs result in a high incidence of late graft loss due to nephrotoxicity and death. As an immune-specific alternative to conventional immunosuppressants, new biotechnology tools can be used to block the costimulation signal of T-cell activation. RECENT FINDINGS: Many experimental studies, particularly preclinical studies in nonhuman primates, have focused on blocking 'classical' B7/CD28 and CD40/CD40L pathways, which are critical in primary T-cell activation, but also on new B7/CD28 and TNF/TNF-R pathways families of costimulatory molecules that can deliver positive or negative costimulation signals to regulate the alloimmune response. SUMMARY: Belatacept is a new fusion protein derived from CTLA4-Ig that can be used to prevent acute rejection in renal transplantation instead of calcineurin inhibitors. Belatacept can also prevent acute rejection efficiently in humans and, more interestingly, can improve renal function and cardiovascular risk factors in this population.
Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Terapia de Imunossupressão , Transplante de Rim/imunologia , Ativação Linfocitária , Transdução de Sinais , Linfócitos T/imunologia , Abatacepte , Animais , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunoconjugados/uso terapêutico , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Resultado do TratamentoRESUMO
Introduction: Focal and segmental glomerulosclerosis (FSGS) is a frequent form of glomerulonephritis that may be caused by a soluble permeability factor and regulated by the immune system. We previously described a soluble form of calcium/calmodulin-dependent serine/threonine kinase (CASK) acting as a permeability factor in patients with recurrent FSGS (rFSGS). Here, we aimed to identify the immune cells associated with CASK secretion in patients with rFSGS. Methods: FACS, western blotting and immunoprecipitation were performed to detect CASK in peripheral blood mononuclear cells, including CD3+, CD20+, and CD14+subsets, from patients with rFSGS, healthy donors, transplant patients and patients with nephrotic syndrome due to diabetes mellitus, and in KHM2 cells. Results: CASK was produced mostly by monocytes in patients with rFSGS but not by T or B lymphocytes. It was not detectein cells from control patients. CASK was also produced and secreted by M2 polarized macrophages and KMH2 cells, but not by M1 polarized macrophages. CASK secretion was not not inhibited by brefeldin A, suggesting an absence of classical secretion pathway involvement. Within cells, CASK was partly colocalized with ALIX, a molecule involved in exosome development, and these two molecules were coprecipitated from M2 macrophages. Moreover, exosomes derived from M2 macrophages induced podocyte cytoskeleton alterations and increased podocyte motility. Conclusion: These results suggest that the soluble permeability factor CASK is secreted by monocytes and M2 macrophages, via exosomes, to alter the glomerular filtration barrier in rFSGS.
Assuntos
Glomerulosclerose Segmentar e Focal/imunologia , Guanilato Quinases/imunologia , Macrófagos/metabolismo , Adulto , Idoso , Animais , Transporte Biológico , Exossomos , Feminino , Glomerulosclerose Segmentar e Focal/sangue , Guanilato Quinases/metabolismo , Humanos , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
INTRODUCTION: Coronavirus disease 2019 (COVID-19) represents a serious threat to patients on maintenance dialysis. The clinical setting, mortality rate, and prognostic factors in these patients have not been well established. METHODS: We included all dialyzed patients with COVID-19 referred to our dialysis center between March 11 and April 11, 2020. Data were obtained through the review of the medical records and were censored at the time of data cutoff, on May 11, 2020. RESULTS: Forty-four patients on maintenance dialysis with COVID-19 were referred to our dialysis unit during the COVID-19 epidemic. Median age was 61 years (interquartile range [IQR]: 51.5-72.5); 65.9% were men. Comorbidities included hypertension (97.7%), diabetes mellitus (50%), and chronic cardiac (38.6%) and respiratory (27.3%) diseases. Initial symptoms were fever (79.5%), shortness of breath (29.5%), cough (43.2%), and diarrhea (13.6%). Three profiles of severity were distinguished based on the World Health Organization (WHO) progression scale. Forty-one (93.2%) were hospitalized and only 3 were maintained on outpatient hemodialysis. Thirty-three (75%) patients required oxygen therapy, including 15 (45.5%) who were referred to the intensive care unit. Overall, 27.3% of patients died, and 58.5% were discharged from hospital, including only 2 (13.3%) of those admitted to the intensive care unit. By multivariate analysis, cough, thrombopenia <120 g/l, lactate dehydrogenase (LDH) level greater than 2 times the upper limit of normal, and blood C-reactive protein (CRP) >175 mg/l were significantly associated with death. CONCLUSION: A major outbreak of COVID-19 occurred in the Paris region, and spread among dialyzed patients. Our study underscores the severity of COVID-19 in these patients and identified prognostic markers.
RESUMO
BACKGROUND: The number of obese patients who are candidates for renal transplantation has considerably increased, but obesity can be a barrier to kidney transplantation. Weight loss is often difficult through diet alone. We studied the efficacy and tolerance of the intra-gastric balloon (IGB) procedure in obese patients who were undergoing dialysis and were candidates for a renal transplantation. PATIENTS AND METHODS: Obese patients (BMI > 30 kg/m2) who were candidates for renal transplantation were prospectively included in the study between 2010 and 2012. The balloon was inserted and removed during a gastric endoscopy under general anesthesia. The treatment lasted 6 months. The end point was a decrease in BMI after 6 months. Body impedance spectrometry (BIS) and nutritional statute were evaluated initially and then after IGB removal. RESULTS: Seventeen patients (nine females and eight males) with a mean age of 53.4 years [19.4-69.4] were included. The decrease in body mass index (BMI) during the 6-month placement was 3 kg/m2 (from 37.7 to 34.4 kg/m2). The mean weight loss was 7 kg. The mean percentage of excess weight loss after 6 months was 20.2 (± 11.4). The tolerance was good without any complications. Eleven patients underwent kidney transplantation. CONCLUSION: IGB in obese dialyzed patients who are candidates for renal transplantation is safe and effective. However, the amount of weight loss can vary.