RESUMO
BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A2 receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P = 0.06). CONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).
Assuntos
Ciclosporina/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclosporina/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/efeitos adversos , Infusões Intravenosas , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proteinúria/tratamento farmacológico , Indução de Remissão , Rituximab/efeitos adversos , Falha de Tratamento , Adulto JovemRESUMO
RATIONALE & OBJECTIVE: Interpersonal communication skills and professionalism competencies are difficult to assess among nephrology trainees. We developed a formative "Breaking Bad News" simulation and implemented a study in which nephrology fellows were assessed with regard to their skills in providing counseling to simulated patients confronting the need for kidney replacement therapy (KRT) or kidney biopsy. STUDY DESIGN: Observational study of communication competency in the setting of preparing for KRT for kidney failure, for KRT for acute kidney injury (AKI), or for kidney biopsy. SETTING & PARTICIPANTS: 58 first- and second-year nephrology fellows assessed during 71 clinical evaluation sessions at 8 training programs who participated in an objective structured clinical examination of simulated patients in 2017 and 2018. PREDICTORS: Fellowship training year and clinical scenario. OUTCOME: Primary outcome was the composite score for the "overall rating" item on the Essential Elements of Communication-Global Rating Scale 2005 (EEC-GRS), as assessed by simulated patients. Secondary outcomes were the score for EEC-GRS "overall rating" item for each scenario, score < 3 for any EEC-GRS item, Mini-Clinical Examination Exercise (Mini-CEX) score < 3 on at least 1 item (as assessed by faculty), and faculty and fellow satisfaction with simulation exercise (via a survey they completed). ANALYTICAL APPROACH: Nonparametric tests of hypothesis comparing performance by fellowship year (primary goal) and scenario. RESULTS: Composite scores for EEC-GRS overall rating item were not significantly different between fellowship years (P = 0.2). Only 4 of 71 fellow evaluations had an unsatisfactory score for the EEC-GRS overall rating item on any scenario. On Mini-CEX, 17% scored < 3 on at least 1 item in the kidney failure scenario; 37% and 53% scored < 3 on at least 1 item in the AKI and kidney biopsy scenarios, respectively. In the survey, 96% of fellows and 100% of faculty reported the learning objectives were met and rated the experience good or better in 3 survey rating questions. LIMITATIONS: Relatively brief time for interactions; limited familiarity with and training of simulated patients in use of EEC-GRS. CONCLUSIONS: The fellows scored highly on the EEC-GRS regardless of their training year, suggesting interpersonal communication competency is achieved early in training. The fellows did better with the kidney failure scenario than with the AKI and kidney biopsy scenarios. Structured simulated clinical examinations may be useful to inform curricular choices and may be a valuable assessment tool for communication and professionalism.
Assuntos
Competência Clínica/normas , Simulação por Computador/normas , Internato e Residência/normas , Nefrologia/normas , Relações Médico-Paciente , Terapia de Substituição Renal/normas , Adulto , Comunicação , Bolsas de Estudo/normas , Feminino , Humanos , Nefropatias/psicologia , Nefropatias/terapia , Masculino , Nefrologia/educação , Estudos Prospectivos , Terapia de Substituição Renal/psicologiaRESUMO
BACKGROUND: In 2022, the Accreditation Council for Graduate Medical Education reduced minimum program director protected time for program administration from 10 to 8 h/wk, with no core faculty requirement. We surveyed program leaders regarding the effect of these changes. METHODS: This is an anonymous, online survey of all US adult nephrology program directors (March 2023), who forwarded core faculty/associate program director (APD) surveys. The questions included protected time in 2022-2023 and 2021-2022, whether it was sufficient, estimated time needed, and two validated single-item burnout measures (emotional exhaustion and depersonalization). The analysis was descriptive. RESULTS: Program directors: Their response was 62% (92/149), with geographic distribution/approved fellow positions similar to those nationally. Overall, protected time slightly increased from 2021 to 2022, largely in >6-fellow programs, but 42% (13/31) of these were still not meeting minimum requirements. Only 37% (30/81) agreed that they had sufficient protected time. Those with ≤6 fellows estimated needing 11±4 h/wk (15±4 h/wk with >6 fellows). Twenty-five percent (20/81) reported high levels of emotional exhaustion. Core faculty: 57 of 149 program directors (38%) forwarded the link to 454 faculty. Ninety-four percent of APDs (49/52) responded, reported 3±3 h/wk protected time (42% had none), and estimated needing 6±3 h/wk, regardless of program size. Sixty-seven of 402 core faculty (17%) responded, reported 2±3 h/wk (50% had none), and estimated needing 5±3 h/wk, regardless of program size. ≥85% of APDs and core faculty precepted clinical rotations, gave lectures, evaluated fellows, mentored scholarly work, and participated in recruitment. The majority assisted in fellow remediation. Thirty-four percent (15/44) of APDs and 21% (13/61) of core faculty reported high levels of emotional exhaustion. CONCLUSIONS: Program leaders estimated minimum necessary program administration times (on the basis of program size) that exceeded the Accreditation Council for Graduate Medical Education requirements. APDs/core faculty contributed substantially to nonclinical training. Thirty-four percent of APDs and 25% of program directors had a high likelihood of burnout.
Assuntos
Esgotamento Profissional , Educação de Pós-Graduação em Medicina , Liderança , Nefrologia , Humanos , Nefrologia/educação , Estados Unidos , Esgotamento Profissional/prevenção & controle , Esgotamento Profissional/epidemiologia , Fatores de Tempo , Masculino , Feminino , Docentes de Medicina , Inquéritos e Questionários , Adulto , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND OBJECTIVES: The Accreditation Council for Graduate Medical Education (ACGME) required that program directors receive 10-20 h/wk of protected time for program administration (including didactic teaching). In July 2022, this was reduced for all internal medicine subspecialties on the basis of program size, with 8 h/wk required for programs with fewer than seven fellows, the majority of nephrology programs. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We surveyed all 151 US adult nephrology program directors (ACGME Public List of Programs 2021-2022) to determine how much protected time they receive, how much they think is necessary, and the division of their professional time. The anonymous 20-question online survey was administered from March 31 to April 30, 2022. The analysis was descriptive. RESULTS: Response rate was 66% (99 of 151). Geographic distribution and approved fellow positions were similar to programs nationally; 59% had fewer than seven approved positions. Median protected time was 10 h/wk (interquartile range, 5-10), with 8 h/wk (interquartile range, 5-10) for those with fewer than seven positions. Program directors estimated needing 12 h/wk (interquartile range, 10-16) to effectively administer programs, including those with fewer than seven positions, a median 5 h/wk (interquartile range, 0-7) more than received. Of program directors reporting <10 h/wk for program administration, 62% provided >20 hours of direct patient care. Thirty-nine percent had no protected time for core faculty. Fellow recruitment (68%) was the most time-consuming task, and didactic teaching (80%) was the most professionally rewarding. CONCLUSIONS: Approximately half of the nephrology programs surveyed were not in compliance with the ACGME-stipulated 10-h/wk minimum protected time for the 2021-2022 training year. Program directors estimated a median of 12 h/wk are needed to effectively manage programs.
Assuntos
Nefrologia , Adulto , Humanos , Estados Unidos , Nefrologia/educação , Educação de Pós-Graduação em Medicina , Inquéritos e Questionários , Bolsas de EstudoRESUMO
One of the most common manifestations of the development of portal hypertension in the patient with cirrhosis is the appearance of ascites. Once ascites develops, the prognosis worsens and the patient becomes susceptible to complications such as bacterial peritonitis, hepatic hydrothorax, hyponatremia, and complications of diuretic therapy. As the liver disease progresses, the ascites becomes more difficult to treat and many patients develop renal failure. Most patients can be managed by diuretics which, when used correctly, will control the ascites. Spontaneous bacterial peritonitis can be treated effectively, but portends a worse prognosis. Once the ascites becomes refractory to diuretics, liver transplantation is the best option, although use of transjugular intrahepatic portosystemic shunts will control the ascites in many patients. Lastly, the development of hepatorenal syndrome indicates the patient's liver disease is advanced, and transplantation again is the best option. However, use of vasoconstrictors may improve renal function in some patients, helping in their management while they await a liver transplant.
Assuntos
Ascite/terapia , Síndrome Hepatorrenal/terapia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Ascite/complicações , Ascite/fisiopatologia , Diagnóstico Diferencial , Diuréticos/uso terapêutico , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/prevenção & controle , Humanos , Hidrotórax/etiologia , Hidrotórax/terapia , Hipertensão Portal/fisiopatologia , Hiponatremia/etiologia , Hiponatremia/terapia , Cirrose Hepática/fisiopatologia , Transplante de Fígado , Infecções Oportunistas/complicações , Peritonite/complicações , Peritonite/tratamento farmacológico , Derivação Portossistêmica Transjugular Intra-Hepática , Prognóstico , Terapia de Substituição Renal , Vasoconstritores/uso terapêuticoRESUMO
Podocytopenia characterizes many forms of glomerular disease, preceding the development of glomerulosclerosis. While detachment of viable podocytes from the underlying glomerular basement membrane is an important mechanism of podocyte loss, the underlying factors involved remain unclear. Secreted protein acidic and rich in cysteine (SPARC), a matricellular protein with counteradhesive properties, is normally expressed at low levels by the podocyte but is markedly increased following podocyte injury. Accordingly, we elucidate the role of SPARC in mediating experimental crescentic glomerulonephritis by inducing passive nephrotoxic nephritis in SPARC(+/+) and SPARC(-/-) mice. By days 4, 7, and 21 following disease induction, podocyte number is better preserved, glomerulosclerosis is ameliorated, and proteinuria is reduced in SPARC(-/-) mice as compared with SPARC(+/+) littermates. Moreover, the preserved podocyte number in SPARC(-/-) mice correlates with reduced urinary levels of both nephrin and podocin. To establish a causal role for SPARC in mediating detachment, cultured SPARC(+/+) and SPARC(-/-) podocytes were subjected to mechanical strain as well as trypsin digestion, and detachment assays were performed. While podocytes lacking SPARC were more resistant to stretch-induced detachment, stable re-expression of SPARC restored detachment rates to levels comparable with SPARC(+/+) podocytes. Taken together, this study proves that SPARC plays a causal role in mediating podocyte detachment and accelerating glomerulosclerosis in experimental crescentic glomerulonephritis.
Assuntos
Modelos Animais de Doenças , Glomerulonefrite/fisiopatologia , Osteonectina/fisiologia , Animais , Células Cultivadas , Progressão da Doença , Immunoblotting , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Podócitos/metabolismo , Podócitos/patologiaRESUMO
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy used in the management of cardiopulmonary failure. Continuous renal replacement therapy (CRRT) is often added to the treatment for the correction of fluid and electrolyte imbalance in patients with acute kidney injury. Most of the literature on the use of combined ECMO and CRRT has been on pediatric patients. There are limited outcome data on the use of these combined modalities in adult patients. METHODS: This is a retrospective analysis of all the patients above the age of 18 years who underwent combined ECMO and CRRT at a tertiary care medical center during the period January 2007 to January 2012. The primary outcomes measured were mortality at one year and renal recovery or dialysis dependence at one month. RESULTS: A total of 40 patients who were treated concurrently with ECMO and CRRT were identified. The mean age was 47.01 ± 18.29 years. The most common indications for initiation of CRRT were combined fluid overload and electrolyte imbalance. Mortality at one month was (32/40) 80%. Among the 8 survivors (20%), 3 patients required continuation of hemodialysis and 5 patients were independent of dialysis at 30 days. CONCLUSIONS: Mortality of patients treated with combined ECMO and CRRT is high. Initiation of CRRT in these patients is simply an indicator of severity of illness and fatality. Younger age, higher arterial pH, left ventricular dysfunction and use of VA ECMO are associated with improved survival in these patients.
Assuntos
Oxigenação por Membrana Extracorpórea , Diálise Renal , Adulto , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Desequilíbrio Hidroeletrolítico/terapiaRESUMO
BACKGROUND: Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria. METHODS AND DESIGN: Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with i.v. rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study. DISCUSSION: This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic membranous nephropathy.
Assuntos
Ciclosporina/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Pressão Sanguínea/efeitos dos fármacos , Ciclosporina/efeitos adversos , Determinação de Ponto Final , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Proteinúria/tratamento farmacológico , Rituximab/efeitos adversos , Resultado do Tratamento , Adulto JovemRESUMO
Chronic hemodialysis is associated with significant thrombophilia. Of interest, hemodialysis patients have increased carboxyhemoglobin (COHb) and exhaled carbon monoxide (CO), signs of upregulated heme oxygenase (Hmox) activity. Given that CO enhances plasmatic coagulation, we determined whether patients requiring chronic hemodialysis had an increase in endogenous CO, plasmatic hypercoagulability and decreased fibrinolytic vulnerability. Carbon monoxide was determined by noninvasive pulse oximetry measurement of COHb. Blood samples were obtained just before hemodialysis. Thrombelastographic methods to assess plasma coagulation kinetics, fibrinolytic kinetics, and formation of carboxyhemefibrinogen (COHF) were used. Hemodialysis patients (n = 45) had abnormally increased COHb concentrations of 2.2 ± 1.9%, indicative of Hmox upregulation. Coagulation and fibrinolytic parameter normal values were determined with normal individual (n = 30) plasma. Thirty-seven patients of the hemodialysis cohort had COHF formation (82.2%, [67.9%-92.0%]; mean, [95% confidence interval]), and many of this group of patients had abnormally great velocity of clot growth (73.3%, [58.1%-85.4%]) and strength (75.6%, [60.5%-87.1%]). Furthermore, over half of COHF positive patients had a hypofibrinolytic state, evidenced by an abnormally prolonged time to maximum rate of lysis (53.3%, [37.9%-68.6%]) and clot lysis time (64.4%, [48.8%-78.1%]). Carbon monoxide enhanced coagulation and diminished fibrinolytic vulnerability in hemodialysis patients. Future investigation of hemodialysis, CO-related thrombophilia is warranted.
Assuntos
Monóxido de Carbono/sangue , Fibrinólise , Diálise Renal/efeitos adversos , Trombofilia/sangue , Trombofilia/etiologia , Adulto , Idoso , Coagulação Sanguínea , Carboxihemoglobina/metabolismo , Feminino , Fibrinogênio/análogos & derivados , Fibrinogênio/metabolismo , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Cinética , Masculino , Pessoa de Meia-Idade , Tromboelastografia , Adulto JovemRESUMO
We describe a rare case of a 46-year-old woman with history of refractory nephrotic syndrome and hypertension who presented with worsening proteinuria and kidney function. Work-up for both autoimmune and infectious diseases and hematologic malignancies including multiple myeloma were negative. Kidney biopsy demonstrated glomerular sclerotic change with lambda light chain deposits in the subendothelial space, which is consistent with proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID). The patient was treated with bortezomib and dexamethasone without clinical improvement and eventually became hemodialysis dependent.
RESUMO
Membranous nephropathy is a common cause of nephrotic syndrome in adults. It usually occurs secondary to underlying disease processes such as autoimmune disorders, malignancy, infection, and drugs. The presentation of nephrotic syndrome with concomitant precipitous decline in renal function warrants investigation of a coexistent disorder.We report the case of a 30-year-old male who presented with symptoms and signs of hypothyroidism.A diagnosis of Hashimoto's thyroiditis was contemplated based on the presence of high serum levels of antithyroglobulin and antithyroid peroxidase antibodies. Upon initiation of treatment with levothyroxine, patient symptomatology improved; however, the laboratory studies demonstrated continued elevated creatinine, hematuria, and proteinuria, which had not been addressed. Two months following treatment initiation, he had progressive deterioration in renal function and proteinuria. A renal biopsy revealed coexistent necrotizing and crescentic glomerulonephritis and membranous nephropathy.The final diagnosis was necrotizing, crescentic glomerulonephritis with superimposed membranous nephropathy likely secondary to Hashimoto's thyrodiitis.Induction treatment with oral cyclophosphamide and prednisone was started.At the end of 6 months of treatment, there was improvement in renal function and proteinuria and maintenance treatment with azathioprine and low-dose prednisone was initiated. This case highlights the importance of precise and detailed evaluation of patients with autoimmune diseases such as Hashimoto's thyroiditis particularly in the presence of active urine sediment. Proper evaluation and diagnosis of such patients has implications on the prognosis and response to treatment.