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RATIONALE & OBJECTIVE: Kidney transplant patients with glomerulonephritis (GN) as their native disease commonly have received pretransplant immunosuppression (PTI). This may contribute to the immunosuppression burden potentially increasing the risk for infections after transplantation. STUDY DESIGN: Single-center, retrospective cohort study. SETTING & PARTICIPANTS: Recipients of a kidney transplant from January 2005 until May 2020 at a tertiary care university teaching hospital. EXPOSURE: Patients with GN as their native kidney disease who received PTI for treatment of GN (n=184) were compared with nondiabetic recipients of kidney transplants who did not receive PTI (n = 579). OUTCOME: First occurrence after transplantation of an infection outcome, either viral (BK or cytomegalovirus [CMV] infection) or bacterial. ANALYTICAL APPROACH: Cox regression analysis adjusted for age at transplant, sex, race, donor type, year of transplant surgery, dialysis vintage, receipt of T-cell depleting induction, and CMV transplant status. RESULTS: Over a median follow-up period of 5.7 years, patients with GN PTI were not at an increased risk for developing any first viral infection compared with controls (adjusted HR [AHR] 0.69 [95% CI, 0.52-0.91]) nor at increased risk for specific viral infections: BK infection 19.6% vs 26.3% (AHR 0.72 [95% CI, 0.50-1.05]) or CMV infection, 24.5% vs 29.0% (AHR, 0.76 [95% CI, 0.54-1.07]), respectively. There was also no increased risk of developing a first bacterial infection: 54.5% vs 57.5% (AHR, 0.90 [95% CI, 0.71-1.13]). These findings of no increased risk for infection were independent of the type of PTI used (cyclophosphamide, rituximab, mycophenolate mofetil, or calcineurin inhibitor) or the type of T-cell depleting induction therapy (alemtuzumab or antithymocyte globulin) administered. LIMITATIONS: Single-center study, no data on methylprednisone use for PTI, unmeasured confounding. CONCLUSIONS: Use of PTI for the treatment of GN was not associated with an increased risk of viral (BK or CMV) or bacterial infection after transplantation. Additional surveillance for infection after transplantation for patients who received PTI may not be necessary. PLAIN-LANGUAGE SUMMARY: Many kidney transplant patients have glomerular disease as the cause of kidney failure. These patients may be exposed to immunosuppression before transplantation, which could increase the risk for infections after receipt of a transplanted kidney. We identified kidney transplant recipients at a university teaching hospital who received immunosuppression before transplant for the treatment of glomerular kidney disease. We examined their risk for infection after transplantation by comparing it with the risk among transplant patients who were not exposed to immunosuppression before transplant. We observed no increased risk for infection after exposure to prior immunosuppression. Therefore, patients exposed to significant amounts of immunosuppression before transplantation may not require special surveillance or medication adjustment for fear of infection after their receipt of a kidney transplant.
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Glomerulonefrite , Imunossupressores , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Masculino , Feminino , Glomerulonefrite/epidemiologia , Glomerulonefrite/etiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Adulto , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/imunologia , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/métodos , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
OBJECTIVE: In 2020, the Canadian Vasculitis Research Network (CanVasc) published their updated recommendations for the management of ANCA-associated vasculitides (AAV). The current addendum provides further recommendations regarding the use of avacopan in AAV based on a review of newly available evidence. METHODS: An updated systematic literature review on avacopan (formerly, CCX168) using Medline, Embase, and the Cochrane Library was performed for publications up to September 2022. New recommendations were developed and categorized according to the EULAR grading levels, as done for previous CanVasc recommendations. A modified Delphi procedure and videoconferences were used to reach ≥80% consensus on the inclusion, wording and grading of each recommendation. RESULTS: Three new recommendations were developed. They focus on avacopan therapy indication and duration, as well as timely glucocorticoid tapering. CONCLUSION: These 2022 addended recommendations provide rheumatologists, nephrologists and other specialists caring for patients with AAV with guidance for the use of avacopan, based on current evidence and consensus from Canadian experts.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Humanos , Consenso , Canadá , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Citoplasma , Anticorpos Anticitoplasma de NeutrófilosRESUMO
BACKGROUND: Kidney transplant patients with glomerulonephritis (GN) as their native disease may receive significant amounts of pre-transplant immunosuppression (PTI), which could increase the risk for development of malignancy post-transplant. METHODS: We conducted a single-center, retrospective study of kidney transplant recipients from January 2005 until May 2020. Patients with GN as their native kidney disease who received PTI for treatment of GN (n = 184) were compared with a control cohort (n = 579) of non-diabetic, non-PTI-receiving kidney transplant patients. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for outcomes of first occurrence of solid or hematologic malignancy, non-melanoma skin cancer (NMSC) and post-transplant lymphoproliferative disorder (PTLD). RESULTS: Over a median follow-up of 5.7 years, PTI for GN was associated with significantly increased risk for malignancy compared with controls [13.0% vs 9.7%, respectively; adjusted HR 1.82 (95% CI 1.10-3.00)], but not for NMSC [10.3% vs 11.4%, respectively; adjusted HR 1.09 (95% CI 0.64-1.83)] or PTLD [3.3% vs 3.1%, respectively; adjusted HR 1.02 (95% CI 0.40-2.61)]. The risk for malignancy was significantly increased in those who received cyclophosphamide [HR 2.59 (95% CI 1.48-4.55)] or rituximab [HR 3.82 (95% CI 1.69-8.65)] pre-transplant, and particularly in those who received both cyclophosphamide and rituximab, but not for calcineurin inhibitors or mycophenolate. CONCLUSION: The use of PTI for treatment of GN, especially cyclophosphamide or even with rituximab, is associated with increased risk for development of solid or hematologic malignancy post-transplant. These data highlight potential risks with treatment of GN and underscore the importance of post-transplant malignancy surveillance in this patient population.
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Glomerulonefrite , Neoplasias Hematológicas , Transplante de Rim , Transtornos Linfoproliferativos , Neoplasias , Humanos , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Rituximab/efeitos adversos , Terapia de Imunossupressão/efeitos adversos , Glomerulonefrite/etiologia , Ciclofosfamida , Neoplasias/etiologia , Neoplasias/complicações , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/etiologia , Transplantados , Fatores de RiscoRESUMO
Chronic kidney disease (CKD) confers a high risk of thrombosis and bleeding. However, little evidence exists regarding the optimal choice of postoperative thromboprophylaxis in these patients. We conducted a population-based, retrospective cohort study among adults ≥66 years old with CKD undergoing hip or knee arthroplasty who had filled an outpatient prophylactic anticoagulant prescription between 2010 and 2020 in Ontario, Canada. The primary outcomes of venous thrombosis (VTE) and hemorrhage were identified by validated algorithms using relevant diagnoses and billing codes. Overlap-weighted cause-specific Cox proportional hazard models were used to examine the association of direct oral anticoagulants (DOAC) on the 90-day risk of VTE and hemorrhage compared with low-molecular-weight heparin (LMWH). A total of 27 645 patients were prescribed DOAC (N = 22 943) or LMWH (N = 4702) after arthroplasty. Rivaroxaban was the predominant DOAC (94.5%), while LMWH mainly included enoxaparin (67%) and dalteparin (31.5%). DOAC users had higher eGFRs, fewer co-morbidities, and surgery in more recent years compared to LMWH users. After weighing, DOAC (compared with LMWH) was associated with a lower risk of VTE (DOAC: 1.5% vs. LMWH: 2.1%, weighted hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.59-0.94) and a higher risk of hemorrhage (DOAC: 1.3% vs. LMWH: 1.0%, weighted HR 1.44, 95% CI 1.04-1.99). Additional analyses including a more stringent VTE defining algorithm, different eGFR cut-offs, and limiting to rivaroxaban and enoxaparin showed consistent findings. Among elderly adults with CKD, DOAC was associated with a lower VTE risk and a higher hemorrhage risk compared to LMWH following hip or knee arthroplasty.
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Artroplastia do Joelho , Insuficiência Renal Crônica , Tromboembolia Venosa , Adulto , Humanos , Idoso , Anticoagulantes/efeitos adversos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Heparina de Baixo Peso Molecular/efeitos adversos , Enoxaparina/uso terapêutico , Rivaroxabana/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Estudos Retrospectivos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Ontário/epidemiologiaRESUMO
Evaluation of hematuria and microscopic examination of urine sediment are commonly used tools by nephrologists in their assessment of glomerular diseases. Certain morphological aspects of urine red blood cells (RBCs) seen by microscopy may help in identifying the source of hematuria as glomerular or not. Recognized signs of glomerular injury are RBC casts or dysmorphic RBCs, in particular acanthocytes (ring-shaped RBCs with protruding blebs). Despite being a highly operator-dependent test, urine sediment examination revealing these signs of glomerular hematuria has demonstrated specificities and positive predictive values ranging between 90%-100% for diagnosing glomerular disease, although sensitivity can be quite variable. Hematuria is a commonly used tool for diagnosing patients with proliferative glomerulonephritis such as IgA nephropathy, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and lupus nephritis, sometimes even as a surrogate for kidney involvement. Studies examining the role for hematuria in monitoring and predicting adverse outcomes in these diseases have shown inconsistent results, possibly due to inconsistent definitions that often fail to consider specific markers of glomerular hematuria such as dysmorphic RBCs, acanthocytes, or RBC casts. A consensus definition of what constitutes glomerular hematuria would help standardize use in future studies and likely improve the diagnostic and prognostic value of hematuria as a marker of glomerulonephritis.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite por IGA , Glomerulonefrite , Biomarcadores , Glomerulonefrite/complicações , Glomerulonefrite/diagnóstico , Hematúria/diagnóstico , Hematúria/etiologia , Humanos , Glomérulos Renais , MicroscopiaRESUMO
BACKGROUND: Red blood cell transfusion (RBCT) is common after kidney transplantation and could have pro-thrombotic effects predisposing to venous thromboembolism (VTE). The risks for developing of VTE after RBCT in kidney transplant patients are unknown. STUDY DESIGN AND METHODS: This was a retrospective cohort study of adult kidney transplant recipients from 2002 to 2018. The exposure of interest was receipt of RBCT after transplant. Cox proportional hazards models were used to calculate hazard ratios (HR) for the outcomes of venous thromboembolism [VTE] (deep venous thrombosis [DVT] or pulmonary embolism [PE]) using RBCT as a time-varying, cumulative exposure. RESULTS: Out of 1258 kidney transplants recipients, 468 (37%) were transfused during the study period. Seventy-nine study participants (6.3%) developed VTE, 72 DVT (5.7%), and 22 PE (1.8%). For the receipt of 1, 2, 3-5, and >5 RBCT, compared to individuals never transfused, the number of events and adjusted HR (95%CI) for VTE were 6 (6.2%) HR 1.57 (0.69-3.58), 9 (7.6%) HR 2.54 (1.30-4.96), 15 (11.9%) HR 2.73 (1.38-5.41), and 23 (18.1%) HR 5.77 (2.99-11.14) respectively; for DVT, it was 6 (6.2%) HR 1.94 (0.84-4.48), 9 (7.6%) HR 2.92 (1.44-5.94), 14 (11.1%) HR 3.29 (1.63-6.65), and 21 (16.5%) HR 6.97 (3.53-13.76), respectively. For PE, among transfused individuals, there were 14 events (3.0%) and the HR was 2.40 (1.02-5.61). CONCLUSION: The risks for developing VTE, DVT, and PE were significantly increased in kidney transplant patients receiving RBCT after transplant. Receipt of RBCT should prompt considerations for judicious monitoring and assessment for thrombosis.
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Transplante de Rim , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Transfusão de SangueRESUMO
INTRODUCTION: Lupus nephritis (LN) may present with thrombotic microangiopathy (TMA) on kidney biopsy, the impact of which on outcomes is unclear. This study examined the prognostic importance of LN with TMA on kidney biopsy, including response to therapy and long-term outcomes. METHODS: We conducted a single-center, retrospective study of all cases of LN with concomitant TMA on kidney biopsy in the Glomerular Disease Collaborative Network database. Controls were individuals with LN without TMA matched to cases based on demographic and clinical variables. Outcomes were remission at 6- and 12-months, end-stage kidney disease (ESKD) and death. Logistic regression and Cox proportional hazards models were used to ascertain the risks for outcomes, with adjustment for serum creatinine and proteinuria. RESULTS: There were 17 cases and 28 controls. Cases had higher creatinine, higher proteinuria and greater chronicity on biopsy at baseline compared to controls. The rates of remission at 6-months and 12-months were similar between cases and controls (6-months 53.9% vs 46.4%, adjusted OR 2.54, 95% CI 0.48, 13.37; 12-months 53.9% vs 50.0%, adjusted OR 2.95, 95% CI 0.44, 19.78). Cases were at greater risk for ESKD in univariate analysis (HR 3.77; 95% CI 1.24, 11.41) but not when adjusting for serum creatinine and proteinuria (HR 2.20; 95% CI 0.63, 7.71). There was no significant difference in the risk of death between cases and controls. CONCLUSION: Lupus nephritis with renal TMA likely responds to therapy similarly to those without TMA; risk for ESKD is not significantly increased, although the influence of renal function and proteinuria in larger samples is needed.
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Falência Renal Crônica , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Microangiopatias Trombóticas , Biópsia , Creatinina , Humanos , Rim/patologia , Falência Renal Crônica/complicações , Falência Renal Crônica/etiologia , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/complicações , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia , Prognóstico , Proteinúria/complicações , Estudos Retrospectivos , Microangiopatias Trombóticas/complicações , Microangiopatias Trombóticas/etiologiaRESUMO
BACKGROUND: The clinical trajectory for patients with primary membranous nephropathy ranges widely from spontaneous remission to a rapid decline in kidney function. Etiologies for rapid progression with membranous nephropathy include concurrent bilateral renal vein thrombosis, malignant hypertension, and crescentic membranous nephropathy. Given the wide heterogeneity in prognosis, timing of immunosuppressive therapy is often challenging and centers around an individual patient's perceived risk for rapidly progressive disease. CASE PRESENTATION: Herein, we describe the clinical course of a young patient who initially developed a typical presentation of membranous nephropathy with consistent kidney biopsy findings. Given clinical stability, a six month observation period was undertaken prior to initiating immunosuppression. Within this observation window, the patient developed community acquired pneumonia followed several weeks later by a sudden, rapid decline in kidney function requiring dialysis. Repeat kidney biopsy revealed post-infectious glomerulonephritis superimposed upon a background of membranous nephropathy. Immunosuppressive therapy resulted in a favorable long-term outcome with normalization of kidney function and remission of nephrotic syndrome. To our knowledge, this is the first report of the simultaneous occurrence of these two glomerular disease processes. CONCLUSION: This case illustrates the value of repeat kidney biopsy during an atypical course of membranous nephropathy. Superimposed glomerular disease processes should be considered during a course of rapidly progressive membranous nephropathy.
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Glomerulonefrite Membranosa , Glomerulonefrite , Nefropatias , Biópsia , Glomerulonefrite/complicações , Glomerulonefrite/diagnóstico , Glomerulonefrite/patologia , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/patologia , Humanos , Rim/patologia , Nefropatias/patologia , Diálise RenalRESUMO
The novel coronavirus disease 2019 (COVID-19) is associated with increased risk of thromboembolic events, but the extent and duration of this hypercoagulable state remain unknown. We describe the first case report of renal allograft infarction in a 46-year-old kidney-pancreas transplant recipient with no prior history of thromboembolism, who presented 26 days after diagnosis of COVID-19. At the time of renal infarct, he was COVID-19 symptom free and repeat test for SARS-CoV-2 was negative. This case report suggests that a hypercoagulable state may persist even after resolution of COVID-19. Further studies are required to determine thromboprophylaxis indications and duration in solid organ transplant recipients with COVID-19.
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Infarto/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Rim/irrigação sanguínea , Transplante de Pâncreas/efeitos adversos , Transplantados , COVID-19 , Humanos , Infarto/diagnóstico , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
BACKGROUND: The association of atrial fibrillation (AF), estimated glomerular filtration rate (eGFR), and adverse events remains unknown. STUDY DESIGN: Population-based retrospective cohort study from Ontario, Canada. SETTING & PARTICIPANTS: 1,422,978 adult residents with eGFRs < 90mL/min/1.73m2 from April 1, 2006, through March 31, 2015. FACTOR: A diagnosis of AF at hospitalization. OUTCOMES: Congestive heart failure (CHF), myocardial infarction (MI), end-stage kidney disease, all-cause mortality. RESULTS: All adverse events were more frequent in individuals with AF (93,414 propensity score matched) compared to no AF, and this difference was more pronounced within the first 6 months of the index date (CHF: 3.04% [AF] vs 0.28% [no AF], subdistribution HR [sHR] of 11.57 [95% CI, 10.26-13.05]; MI: 0.97% [AF] vs 0.21% [no AF], sHR of 4.76 [95% CI, 4.17-5.43]; end-stage kidney disease: 0.16% [AF] vs 0.03% [no AF], sHR of 5.84 [95% CI, 3.82-8.93]; and all-cause mortality: 6.11% [AF] vs 2.50% [no AF], HR of 2.62 [95% CI, 2.50-2.76]) than in the period more than 6 months after the index date (CHF: 6.87% [AF] vs 2.87% [no AF], sHR of 2.64 [95% CI, 2.55-2.74]; MI: 2.21% [AF] vs 1.81% [no AF], sHR of 1.24 [95% CI, 1.18-1.30]; end-stage kidney disease: 0.52% [AF] vs 0.32% [no AF], sHR of 1.75 [95% CI, 1.57-1.95]; and all-cause mortality: 15.55% [AF] vs 15.10% [no AF], HR of 1.07 [95% CI, 1.04-1.10]). The results accounted for the competing risk for mortality. eGFR level modified the effect of AF on CHF (P for interaction < 0.05). LIMITATIONS: Observational study design does not permit determination of causality; only a single outpatient eGFR measure was used; medication data were not included. CONCLUSIONS: Incident AF is associated with a high risk for adverse outcomes in patients with eGFRs < 90mL/min/1.73m2. Because the risk is exceedingly high within the first 6 months after AF diagnosis, therapeutic interventions and monitoring may improve outcomes.
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Fibrilação Atrial , Insuficiência Cardíaca/mortalidade , Falência Renal Crônica/mortalidade , Infarto do Miocárdio/mortalidade , Insuficiência Renal Crônica , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Canadá/epidemiologia , Estudos de Coortes , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Avaliação das Necessidades , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
Membranous nephropathy (MN) is a common cause of nephrotic syndrome. Rarely, it can present with rapidly-progressive renal failure and hematuria. While this may be due to lupus nephritis, superimposed anti-glomerular basement membrane (GBM) disease, or antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, there have been rare reports of anti-GBM - and ANCA-negative crescentic glomerulonephritis presenting in primary membranous nephropathy (pMN). We present the case of a patient with long-standing pMN who developed acute deterioration of renal function and was found to have a flare of MN along with crescentic glomerulonephritis (GN) despite a negative serum ANCA, anti-GBM, and antinuclear antibody (ANA) work-up. He was started on dialysis and immunosuppressive therapy, and eventually recovered enough renal function to become dialysis-independent. A brief review of available literature suggests that crescentic GN presenting with pMN is a rare but established entity. Much more rarely has it been reported to occur in patients with previously-diagnosed pMN. In these contexts, crescentic GN may be occurring as the most severe manifestation of pMN rather than as a separate entity. Immunosuppressive therapy is often given, however, prognosis is guarded as half of patients will have worsening renal function and a quarter will develop end-stage renal disease.â©.
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Glomerulonefrite Membranoproliferativa/complicações , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranoproliferativa/fisiopatologia , Glomerulonefrite Membranoproliferativa/terapia , Glomerulonefrite Membranosa/fisiopatologia , Glomerulonefrite Membranosa/terapia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Diálise Renal , Fatores de TempoRESUMO
BACKGROUND: The risk for venous thromboembolism (VTE) is elevated with albuminuria or a low estimated glomerular filtration rate (eGFR). However, the VTE risk due to the combined effects of eGFR and albuminuria are unknown. STUDY DESIGN: Population-based cohort study. SETTINGS & PARTICIPANTS: 694,956 adults in Ontario, Canada, from 2002 to 2012. FACTORS: eGFR and albumin-creatinine ratio (ACR). OUTCOME: VTE. RESULTS: 15,180 (2.2%) VTE events occurred during the study period. Both albuminuria and eGFR were independently associated with VTE. The association of albuminuria and VTE differed by level of eGFR (P for ACR × eGFR interaction < 0.001). After considering the competing risk for death, there was a 61% higher rate of VTE in patients with normal eGFRs (eGFRs>90mL/min/1.73m2) and heavy albuminuria (ACR>300mg/g) compared with those with normal eGFRs and no albuminuria (subdistribution HR, 1.61; 95% CI, 1.38-1.89). Among those with reduced kidney function (eGFR, 15-29mL/min/1.73m2), the risk for VTE was only minimally increased, irrespective of albuminuria (subdistribution HRs of 1.23 [95% CI, 1-1.5] and 1.09 [95% CI, 0.82-1.45] for ACR<30 and >300mg/g, respectively). LIMITATIONS: Only single determinations of ACR and eGFR were used. Diagnostic/International Classification of Diseases codes were used to define VTE. CONCLUSIONS: Albuminuria increases the risk for VTE markedly in patients with normal eGFRs compared with those with lower eGFRs.
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Albuminúria/epidemiologia , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/epidemiologia , Tromboembolia Venosa/epidemiologia , Idoso , Albuminúria/urina , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Insuficiência Renal Crônica/metabolismo , Estudos Retrospectivos , RiscoRESUMO
Kidney transplantation is the ideal treatment modality for patients with end-stage kidney disease, with excellent outcomes post-transplant compared with dialysis. However, kidney transplant recipients are at increased risk of infections and cancer because of the need for immunosuppression. Kidney transplant recipients have approximately two to three times greater risk of developing cancer than the general population, and cancer is a major contributor to morbidity and mortality. Most of the increased risk is driven by viral-mediated cancers such as post-transplant lymphoproliferative disorder, anogenital cancers, and Kaposi sarcoma. Nonmelanoma skin cancer is the most frequent type of cancer in kidney transplant recipients, likely due to an interaction between ultraviolet radiation exposure and decreased immune surveillance. Occurrence of the more common types of solid organ cancers seen in the general population, such as breast, prostate, lung, and colorectal cancers, is not, or is only mildly, increased post-transplant. Clinical care and future research should focus on prevention and on improving outcomes for important immunosuppression-related malignancies, and treatment options for other cancers occurring in the transplant setting.
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Transplante de Rim , Neoplasias , Neoplasias Cutâneas , Humanos , Transplante de Rim/efeitos adversos , Neoplasias/epidemiologia , Neoplasias/etiologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/etiologia , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/etiologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/cirurgia , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/etiologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/etiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Fatores de Risco , TransplantadosRESUMO
Rationale & Objective: Research in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has focused on reducing treatment toxicities, notably through reduction of exposure to glucocorticoids. Glucocorticoid-sparing therapies such as avacopan are not widely available in many countries, and patients are exposed to high glucocorticoid doses. There is little data concerning what clinicians should accept as the lowest glucocorticoid dosing that can be used in induction therapy for AAV. Study Design: International, online survey. Setting & Participants: Clinicians in various countries with experience in managing vasculitis. Exposure and Outcomes: Survey questions to gauge interest and preferences in studying an induction of remission regimen for severe AAV using only 2 or 4 weeks of glucocorticoids without avacopan. Data collected included general opinions about standard of care for induction agents, glucocorticoids, and avacopan. Respondents were presented with 3 candidate trial designs, 2 of which proposed a combination of cyclophosphamide and rituximab induction. Analytical Approach: Using a 10-point Likert scale, respondents ranked each candidate trial on its usefulness in demonstrating whether a minimal glucocorticoid regimen would be safe and effective and their willingness to randomize into the trial. Results: There were 210 respondents to the survey. The candidate trials were rated moderate-to-high for usefulness to demonstrate safety and efficacy (scores 6-7/10), and moderate (scores 5-6/10) for willingness to randomize. Four-week glucocorticoid duration was preferred to 2 weeks, and combination cyclophosphamide-rituximab with 4-week glucocorticoids was the most preferred design. Forty-two percent of respondents felt avacopan had to be incorporated into a minimal GC trial design to want to recruit patients. Limitations: Representativeness of survey sample and generalizability of findings. Conclusions: Combination cyclophosphamide-rituximab may be the ideal way of studying minimal glucocorticoid use in severe AAV. Given its increasing uptake, incorporating avacopan into a potential trial design is important.
Research in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has focused on using less glucocorticoids to limit side effects. New drugs that drastically limit glucocorticoid use are not available in many countries. Studies are needed to find other ways of reducing glucocorticoid exposure to treat AAV, but it is unclear how best to achieve this. We administered a survey to doctors with experience in treating AAV and had them grade different combinations of widely available treatments with 2 or 4 weeks of glucocorticoids. We found that a combination of 2 doses cyclophosphamide with 2 doses rituximab and 4 weeks of glucocorticoids was the preferred treatment. The results will guide the development of a trial studying minimal use of glucocorticoids for the treatment of AAV.
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BACKGROUND: Clinicians caring for kidney transplant recipients (KTRs) most commonly use estimated glomerular filtration rate (eGFR) to guide medication dosing as it is the most readily available measure of kidney function. Which eGFR equations provide the most accurate medication dosing guidance for KTRs remains uncertain. METHODS: We studied 415 stable KTRs in Canada and New Zealand. Participants completed same-day measurements of creatinine and cystatin C and measured GFR (diethylenetriaminepentaacetic acid). Chronic Kidney Disease Epidemiology Collaboration, European Kidney Function Consortium, and transplant-specific eGFR equations were compared with both Cockcroft-Gault creatinine clearance (CrCl) and measured GFR. eGFR equations were assessed both indexed to a standardized body surface area (BSA) of 1.73 m2 (milliliter per minute per 1.73 m2, as is conventional reporting from most clinical laboratories) and nonindexed (milliliter per minute) accounting for actual BSA. The primary outcome was the proportion of medication dosing discordance relative to Cockcroft-Gault CrCl or measured GFR for 8 commonly prescribed medications. Stratified analyses were performed on the basis of obesity status. RESULTS: Nonindexed eGFR equations (milliliter per minute) resulted in substantially lower medication dosing discordance compared with indexed eGFR equations (milliliter per minute per 1.73 m2). These findings were most pronounced among KTRs with obesity, in whom underdosing was frequent. When compared with Cockcroft-Gault CrCl, the lowest proportion of discordance was found with the nonindexed 2023 transplant-specific equation. When compared with measured GFR, the lowest proportion of discordance was found with the nonindexed 2021 Chronic Kidney Disease Epidemiology CollaborationCr/CysC equation. CONCLUSIONS: Nonindexed eGFR values accounting for actual BSA should be used by clinicians for medication dosing in KTRs. These findings may inform KT providers about which eGFR equations provide the safest, most accurate medication dosing guidance for KTRs.
Assuntos
Estado Terminal , Hipotensão , Humanos , Prevalência , Diálise Renal , Terapia de Substituição Renal , Fatores de RiscoRESUMO
The last decade has seen tremendous advances in the prevention and treatment of recurrent hyperkalemia. In this narrative review, we aim to highlight contemporary data on key areas in the epidemiology and management of hyperkalemia. Focusing on drug-induced hyperkalemia (the implications of renin-angiotensin-aldosterone system inhibitors [RAASi] discontinuation and the role of mineralocorticoid receptor antagonists), newer concurrent therapies that modify potassium handling (sodium-glucose transporter 2 inhibitors [SGLT2i]), the introduction of new treatment agents (oral potassium binding agents), and the controversial role of dietary potassium restriction, we apply recent research findings and review the evidence in a case-based format.
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Background: With an aging population and growing number of patients with chronic kidney disease (CKD), integrating the latest risk factors when deciding on a treatment plan can result in better patient care. Frailty remains a prevalent syndrome in CKD resulting in adverse health outcomes. However, measures of frailty and functional status remain excluded from clinical decision making. Objective: To examine the degree to which different measures of frailty and functional status are associated with mortality, hospitalization, and other clinical outcomes in patients with advanced CKD. Design: Systematic review. Setting: Observation studies including cohort study, case-control study, or cross-sectional study examining frailty and functional status on clinical outcomes. There were no restrictions on type of setting or country of origin. Patients: Adults with advanced CKD, including both types of dialysis patients. Measurements: Data including demographic information (e.g., sample size, follow-up time, age, country), assessments of frailty or functional status and their domains, and outcomes including mortality, hospitalization, cardiovascular events, kidney function, and composite outcomes were extracted. Methods: A search was conducted using databases Medline, Embase, and Cochrane Central Register for Controlled Trials. Studies were included from inception to March 17, 2021. The eligibility of studies was screened by 2 independent reviewers. Data were presented by instrument and clinical outcome. Point estimates and 95% confidence intervals from the fully adjusted statistical model were reported or calculated from the raw data. Results: A total of 117 unique instruments were found among 140 studies. The median sample size of studies was 319 (interquartile range, 161-893). Most studies focused on incident and chronic dialysis patient populations, with only 15% of studies examining non-dialysis CKD patients. Frailty and lower functional status were associated with an increased risk for adverse clinical outcomes such as mortality and hospitalization. The 5 individual domains of frailty were also found to be associated with poor health outcomes. Limitations: Meta-analysis could not be performed due to significant heterogeneity between studies and methods used to measure frailty and functional status. Many studies had issues with methodological rigor. Selection bias and the validity of data collection could not be ascertained for some studies. Conclusion: Frailty and functional status measures should be integrated to help guide clinical care decision making for a comprehensive assessment of risk for adverse outcomes among patients with advanced CKD. Registration PROSPERO: CRD42016045251.
Contexte: Compte tenu du vieillissement de la population et du nombre croissant de patients atteints d'insuffisance rénale chronique (IRC), l'intégration des plus récents facteurs de risque dans le processus de prise de décision d'un plan de traitement pourrait améliorer les soins aux patients. La fragilité demeure un syndrome prévalant en contexte d'IRC, qui entraîne des effets néfastes sur la santé. Pourtant, les mesures de la fragilité et de l'état fonctionnel demeurent exclues de la prise de décisions cliniques. Objectif: Déterminer à quel point les différentes mesures de la fragilité et de l'état fonctionnel sont associées à la mortalité, à l'hospitalisation et à d'autres résultats cliniques chez les patients atteints d'IRC avancée. Type d'étude: Examen systématique. Sources: Des études d'observation, y compris des études de cohorte, des études cas-témoins ou des études transversales examinant le rôle de la fragilité et de l'état fonctionnel sur les résultats cliniques. Il n'y avait pas de restrictions quant au cadre ou au pays d'origine de l'étude. Sujets: Des adultes atteints d'IRC avancée, y compris les deux types de patients sous dialyse. Mesures: Les données suivantes ont été extraites : les données démographiques (taille de l'échantillon, temps de suivi, âge des patients, pays), les évaluations de la fragilité ou de l'état fonctionnel et de leurs domaines, et les résultats cliniques (mortalité, hospitalisation, événements cardiovasculaires, fonction rénale et résultats composites). Méthodologie: Une recherche a été effectuée dans les bases de données Medline, embase et Cochrane Central Register for Controlled Trials pour répertorier les études de la création jusqu'au 17 mars 2021. L'admissibilité des études a été déterminée par deux examinateurs indépendants. Les données ont été présentées par instrument et par résultat clinique. Des estimations ponctuelles et des intervalles de confiance à 95 % du modèle statistique ajusté ont été rapportés ou calculés à partir des données brutes. Résultats: Parmi les 140 études répertoriées, 117 instruments uniques ont été trouvés. La taille médiane des échantillons était de 319 patients (ÉIQ : 161 à 893). La plupart des études portaient sur des populations de patients incidents et sous dialyse chronique, seulement 15 % des études portaient sur des patients atteints d'IRC non dialysés. La fragilité et un faible état fonctionnel ont été associés à un risque accru de résultats cliniques défavorables comme une hospitalisation ou le décès. Les cinq domaines individuels de la fragilité ont également été associés à de mauvais résultats de santé. Limites: L'hétérogénéité significative entre les études et les méthodes utilisées pour mesurer la fragilité et l'état fonctionnel ne permettait pas de procéder à une méta-analyse. De nombreuses études n'étaient pas rigoureuses sur le plan méthodologique. Les biais de sélection et la validité de la collecte des données n'ont pas pu être vérifiés pour certaines études. Conclusion: Les mesures de la fragilité et de l'état fonctionnel devraient être intégrées au processus de prise de décision afin d'orienter les soins cliniques et de permettre une évaluation complète du risque d'effets indésirables chez les patients atteints d'IRC avancée. Enregistrement PROSPERO: CRD42016045251.