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BACKGROUND: High-quality patient-reported outcome (PRO) measures for dialysis patients with chronic pruritus are urgently needed. However, no known, well-validated multidimensional tools have been investigated to measure pruritus symptoms in dialysis patients. OBJECTIVES: To examine the psychometric properties of a multidimensional tool of chronic pruritus, the Uraemic Pruritus in Dialysis patients (UP-Dial) 14-item scale, by comparing haemodialysis and peritoneal dialysis modality. METHODS: This validation study used data from the Thai Renal Outcomes Research-Uraemic Pruritus, a prospective, multicentre, longitudinal study. Data for this study were collected from 1 February 2019 to 31 May 2022. The adult sample of 226 haemodialysis and 327 peritoneal dialysis patients fulfilled the criteria of chronic pruritus based on the International Forum for the Study of Itch. Psychometric properties of the UP-Dial included validity and reliability, as measured across haemodialysis and peritoneal dialysis patients. Patients completed a set of anchor-based measurement tools, including global itching, Dermatology Life Quality Index (DLQI), EuroQoL-5 dimension-5 level (EQ-5D-5L), Kidney Disease Quality of Life-36 (KDQOL-36), Pittsburgh Sleep Quality Index (PSQI), global fatigue, Somatic Symptom Scale-8 (SSS-8) and Patient Health Questionnaire-9 (PHQ-9). RESULTS: From the patient's perspective, face validity was satisfactory for both dialysis samples. Psychometric analyses of the UP-Dial for each dialysis sample had good convergent validity. Spearman rho correlations indicate a positively strong correlation (0.73-0.74) with global itching, a positively moderate correlation (0.33-0.58) with DLQI, PSQI, global fatigue, SSS-8 and PHQ-9, and a negatively moderate correlation (-0.39 to -0.58) with EQ-5D-5L and KDQOL-36. The discriminant validity was satisfactory with a group of moderate and severe burden of pruritus for both dialysis samples. For scale reliability, the UP-Dial revealed excellent internal consistency (Cronbach's α = 0.89 and McDonald's ω = 0.90) and reproducibility (intraclass correlation 0.84-0.85) for both dialysis samples. Regarding psychometric properties, no statistically significant differences between dialysis samples were observed (all P > 0.05). CONCLUSIONS: The findings reaffirm good measurement properties of the UP-Dial 14-item scale in haemodialysis and peritoneal dialysis patients with chronic pruritus. These suggest a transferability of the UP-Dial as a PRO measure in clinical trial and practice settings.
Itch is a common symptom in chronic kidney disease, especially for people experiencing end-stage kidney disease and receiving dialysis. Itching among dialysis patients can present and affect any part of the body. Although there has been improvement in dialysis treatment over time, chronic itching (itching lasting more than 6 weeks) remains under-recognized in dialysis patients. In recent years, a specific clinical tool called the Uraemic Pruritus in Dialysis patients (UP-Dial) has been developed to assess the severity and burden of itching in dialysis patients. However, a comprehensive tool for evaluating itching symptoms has yet to be tested in a large dialysis population (haemodialysis and peritoneal dialysis). We examined and validated the measurement properties of the UP-Dial scale in an adult sample of 226 haemodialysis and 327 peritoneal dialysis patients with chronic itching. Our study found that the UP-Dial had good measurement properties for evaluating the burden of itching symptoms among haemodialysis and peritoneal dialysis patients with chronic itching. Our findings support the use of UP-Dial to compare treatments for chronic itching clinical trials and track treatment responses in daily practice.
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Medidas de Resultados Relatados pelo Paciente , Diálise Peritoneal , Prurido , Psicometria , Qualidade de Vida , Diálise Renal , Humanos , Prurido/etiologia , Prurido/diagnóstico , Prurido/psicologia , Prurido/terapia , Feminino , Masculino , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/psicologia , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Estudos Prospectivos , Reprodutibilidade dos Testes , Estudos Longitudinais , Adulto , Idoso , Uremia/terapia , Uremia/complicações , Uremia/diagnóstico , Doença Crônica , Índice de Gravidade de Doença , Tailândia , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Falência Renal Crônica/psicologiaRESUMO
BACKGROUND AND HYPOTHESIS: Identifying meaningful estimated glomerular filtration rate (eGFR) reductions in younger adults (<65 years) could guide prevention efforts. To aid in interpretation and identification of young adults at risk, we examined the association of population-level eGFR percentiles relative to the median by age and clinical outcomes. METHODS: We conducted a retrospective cohort study of 8.7 million adults from Ontario, Canada from age 18 to 65 from 2008 to 2021 with an eGFR measure (both single outpatient value and repeat measures). We calculated median eGFR values by age and examined the association of reduced eGFR percentiles (≤10th, 5th, 2.5th and 1st) with outcomes using time to event models. Outcomes were a composite of all-cause mortality, major adverse cardiac outcomes (MACE) with/without heart failure (MACE+) and kidney failure as well as each component individually. RESULTS: From age 18 to 65, the median eGFR declined with age (range 128 to 90) and across percentiles [eGFR ranges 102 to 68 for ≤10th, 96 to 63 for ≤5th, 90 to 58 for ≤2.5th and 83 to 54 for 1st]. The adjusted rate for any adverse outcome was elevated at ≤ 10th percentile (HR 1.14 95%CI 1.10-1.18) and was consistent for all-cause mortality, MACE, MACE+ and predominant for kidney failure (HR 5.57 95%CI 3.79-8.19) compared to the median eGFR for age. Young adults with an eGFR in the lower percentiles were less likely to be referred to a specialist, have a repeat eGFR or albumin to creatinine ratio measure. CONCLUSIONS: eGFR values at the 10th percentile or lower based on a population-level distribution are associated with adverse clinical outcomes and in younger adults (18 to 39) this corresponds to a higher level of eGFR that may be underrecognized. Application of population-based eGFR percentiles may aid interpretation and improve identification of younger adults at risk.
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RATIONALE & OBJECTIVE: Race-free estimated glomerular filtration rate (eGFR) equations incorporating creatinine with and without cystatin C were recently developed and recommended for routine use. However, the performance of these equations among kidney transplant recipients (KTRs) remains unknown. STUDY DESIGN: Cross-sectional study to validate the 2021 race-free Chronic Kidney Disease (CKD) Epidemiology Collaboration (CKD-EPI) eGFR equation based on creatinine alone (eGFRcr) or based on creatinine and cystatin C (eGFRcr-cys) among KTRs. SETTING & PARTICIPANTS: KTRs in stable condition (N = 415) from Canada and New Zealand with same-day measurements of creatinine, cystatin C, and glomerular filtration rate (GFR) using radiolabeled diethylenetriaminepentaacetic acid. TESTS COMPARED: The 2009 CKD-EPI eGFRcr, 2021 CKD-EPI eGFRcr, 2012 CKD-EPI eGFRcr-cys, 2021 CKD-EPI eGFRcr-cys, 2012 CKD-EPI eGFRcys, and Modification of Diet in Renal Disease (MDRD) Study eGFR equations were compared with measured GFR. OUTCOMES: Bias, precision, accuracy, and correct classification by CKD stage. Bias was defined as the difference between estimated and measured GFR. Precision was represented by the interquartile range. Accuracy was defined as the percentages of participants with eGFRs within 10%/20%/30% (P10/P20/P30) of measured GFR, root mean square error, and mean absolute error. RESULTS: 87% of patients studied were White, 3% Black, and 10% other races. Mean measured GFR was 53 ± 19 (SD) mL/min/1.73 m2. The 2009 and 2021 CKD-EPI eGFRcr equations demonstrated similar median bias (-2.3 vs -0.2 mL/min/1.73 m2, respectively), precision (14.5 vs 14.9 mL/min/1.73 m2), and accuracy (P10/P20/P30, 32%/65%/84% vs 33%/63%/84%). The 2012 and 2021 CKD-EPI eGFRcr-cys equations also demonstrated similar median bias (-3.6 vs 0.3 mL/min/1.73 m2, respectively), precision (13.3 vs 14.3 mL/min/1.73 m2), and accuracy (P10/P20/P30, 32%/63%/80% vs 32%/67%/83%). No clear difference in performance was detected between the 2021 CKD-EPI eGFRcr and eGFRcr-cys equations among KTRs. The proportion of correct classification by CKD stage was similar across all eGFR equations. LIMITATIONS: Moderate sample size, few patients had a GFR <30 mL/min/1.73 m2, and the large majority of patients were White. CONCLUSIONS: Among KTRs, the 2021 race-free CKD-EPI eGFR equations perform similarly to the previous CKD-EPI equations that included race correction terms. No significant difference in performance was observed between the 2021 CKD-EPI eGFRcr and eGFRcr-cys equations in the kidney transplant population.
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Transplante de Rim , Insuficiência Renal Crônica , Creatinina , Estudos Transversais , Cistatina C , Taxa de Filtração Glomerular , Humanos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/cirurgiaRESUMO
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
Urinary inulin clearance is considered the gold standard of glomerular filtration rate (GFR) measurement but plasma clearance of less expensive and more accessible tracers is more commonly performed. Many plasma sampling protocols exist but little is known about their accuracy. Here, the study objectives were to compare plasma iohexol and 99mTc-DTPA GFR with varying sampling strategies to the GFR measured by urinary inulin and to identify protocols with the greatest accuracy according to clinical characteristics. GFR was measured simultaneously using urinary inulin, plasma iohexol, and plasma 99mTc DTPA clearance. Blood was sampled from 2 to 10 hours after injection. For each method, bias, precision, and accuracy (P30 and mean absolute error) were calculated for the entire cohort and for eGFR-EPI creatinine subgroups (<30, 30-59, and ≥60 ml/min/1.73m2) and the edema stage using urinary inulin clearance as the gold standard. The mean inulin GFR of the 77 participants was 33 ml/min/1.73m2. Delay of both the initial and the final samples in plasma iohexol protocols yielded the highest accuracy in the setting of low GFR (<30 ml/min/1.73m2). Early initial and final samples yielded the highest accuracy in the setting of high GFRs (≥60 ml/min/1.73m2). No sampling strategy was accurate in edematous patients. Thus, our study demonstrates that customization of GFR protocols according to the anticipated level of GFR are required to optimize protocol accuracy.
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Iohexol , Pentetato de Tecnécio Tc 99m , Taxa de Filtração Glomerular , Humanos , Inulina , Testes de Função RenalRESUMO
RATIONALE & OBJECTIVES: Alpha-blockers (ABs) are commonly prescribed for control of resistant or refractory hypertension in patients with and without chronic kidney disease (CKD). The association between AB use and kidney, cardiac, mortality, and safety-related outcomes in CKD remains unknown. STUDY DESIGN: Population-based retrospective cohort study. SETTINGS & PARTICIPANTS: Ontario (Canada) residents 66 years and older treated for hypertension in 2007 to 2015 without a prior prescription for an AB. EXPOSURES: New use of an AB versus new use of a non-AB blood pressure (BP)-lowering medication. OUTCOMES: 30% or greater estimated glomerular filtration rate (eGFR) decline; dialysis initiation or kidney transplantation (kidney replacement therapy); composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation; safety (hypotension, syncope, falls, and fractures) events; and mortality. ANALYTICAL APPROACH: New users of ABs (doxazosin, terazosin, and prazosin) were matched to new users of non-ABs by a high dimensional propensity score. Cox proportional hazards and Fine and Gray models were used to examine the association of AB use with kidney, cardiac, mortality, and safety outcomes. Interactions by eGFR categories (≥90, 60-89, 30-59, and<30mL/min/1.73m2) were explored. RESULTS: Among 381,120 eligible individuals, 16,088 were dispensed ABs and matched 1:1 to non-AB users. AB use was associated with higher risk for≥30% eGFR decline (HR, 1.14; 95% CI, 1.08-1.21) and need for kidney replacement therapy (HR, 1.28; 95% CI, 1.13-1.44). eGFR level did not modify these associations, P interaction=0.3and 0.3, respectively. Conversely, AB use was associated with lower risk for cardiac events, which was also consistent across eGFR categories (HR, 0.92; 95% CI, 0.89-0.95; P interaction=0.1). AB use was also associated with lower mortality risk, but only among those with eGFR<60mL/min/1.73m2 (P interaction<0.001): HRs were 0.85 (95% CI, 0.78-0.93) and 0.71 (95% CI, 0.64-0.80) for eGFR of 30 to 59 and<30mL/min/1.73m2, respectively. LIMITATIONS: Observational design, BP measurement data unavailable. CONCLUSIONS: AB use in CKD is associated with higher risk for kidney disease progression but lower risk for cardiac events and mortality compared with alternative BP-lowering medications.
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Antagonistas Adrenérgicos alfa/uso terapêutico , Fibrilação Atrial/epidemiologia , Insuficiência Cardíaca/epidemiologia , Hipertensão/tratamento farmacológico , Falência Renal Crônica/epidemiologia , Infarto do Miocárdio/epidemiologia , Insuficiência Renal Crônica/metabolismo , Terapia de Substituição Renal/estatística & dados numéricos , Acidentes por Quedas/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Estudos de Coortes , Progressão da Doença , Doxazossina/uso terapêutico , Feminino , Fraturas Ósseas/epidemiologia , Taxa de Filtração Glomerular , Humanos , Hipertensão/complicações , Hipotensão/induzido quimicamente , Falência Renal Crônica/terapia , Masculino , Mortalidade , Revascularização Miocárdica/estatística & dados numéricos , Ontário/epidemiologia , Prazosina/análogos & derivados , Prazosina/uso terapêutico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Síncope/induzido quimicamenteRESUMO
Polyvalent immunoglobulin is commonly used for desensitization and treatment of antibody-mediated rejection in kidney transplantation but its impact on other outcomes is not known. This systematic review investigated the impact of immunoglobulin prophylaxis on infection, rejection, graft loss, and death following kidney transplantation. A comprehensive literature search located 18 studies (n = 8 randomized controlled trials). None examined the effect of immunoglobulin prophylaxis in transplant recipients with hypogammaglobulinemia. Quality of included studies was variable with high to very high risk of bias. In the randomized trials, immunoglobulin use did not reduce cytomegalovirus infection (OR 0.68 [0.39, 1.21]; 6 studies, n = 295), rejection (OR 0.96 [0.50, 1.82]; 4 studies, n = 187), or graft loss (OR 1.03 [0.46, 2.30]; 6 studies, n = 265). In non-randomized studies, immunoglobulin did not reduce cytomegalovirus infection (OR 0.63 [0.20, 1.94]; 6 studies, n = 361) or death (OR 1.32 [0.05, 38.79]; 3 studies, n = 222) but reduce rejection (OR 0.47 [0.24, 0.94]; 4 studies, n = 268) and graft loss (OR 0.15 [0.05, 0.43]; 2 studies, n = 118). Data were scarce and sample size of current evidence was small. Adequately powered randomized trials are needed to determine if immunoglobulin is an effective intervention to reduce infection, rejection, graft loss, or death following kidney transplantation with and without hypogammaglobulinemia.
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Agamaglobulinemia/tratamento farmacológico , Rejeição de Enxerto/tratamento farmacológico , Imunoglobulinas/uso terapêutico , Infecções/tratamento farmacológico , Transplante de Órgãos/efeitos adversos , Agamaglobulinemia/etiologia , Rejeição de Enxerto/etiologia , Humanos , Infecções/etiologia , Prognóstico , TransplantadosRESUMO
Immunoglobulin (IG) is commonly used to desensitize and treat antibody-mediated rejection in solid organ transplant (SOT) recipients. The impact of IG on other outcomes such as infection, all-cause mortality, graft rejection, and graft loss is not clear. We conducted a similar systematic review and meta-analysis to our previously reported Part I excluding kidney transplant. A comprehensive literature review found 16 studies involving the following organ types: heart (6), lung (4), liver (4), and multiple organs (2). Meta-analysis could only be performed on mortality outcome in heart and lung studies due to inadequate data on other outcomes. There was a significant reduction in mortality (OR 0.34 [0.17-0.69]; 4 studies, n = 455) in heart transplant with hypogammaglobulinemia receiving IVIG vs no IVIG. Mortality in lung transplant recipients with hypogammaglobulinemia receiving IVIG was comparable to those of no hypogammaglobulinemia (OR 1.05 [0.49, 2.26]; 2 studies, n = 887). In summary, IVIG targeted prophylaxis may decrease mortality in heart transplant recipients as compared to those with hypogammaglobulinemia not receiving IVIG, or improve mortality to the equivalent level with those without hypogammaglobulinemia in lung transplant recipients, but there is a lack of data to support physicians in making decisions around using immunoglobulins in all SOT recipients for infection prophylaxis.
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Agamaglobulinemia/tratamento farmacológico , Rejeição de Enxerto/tratamento farmacológico , Imunoglobulinas Intravenosas/administração & dosagem , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Agamaglobulinemia/etiologia , Rejeição de Enxerto/etiologia , Humanos , Complicações Pós-Operatórias/etiologia , Prognóstico , Fatores de Risco , TransplantadosRESUMO
BACKGROUND: Young women wishing to become living kidney donors frequently ask whether nephrectomy will affect their future pregnancies. METHODS: We conducted a retrospective cohort study of living kidney donors involving 85 women (131 pregnancies after cohort entry) who were matched in a 1:6 ratio with 510 healthy nondonors from the general population (788 pregnancies after cohort entry). Kidney donations occurred between 1992 and 2009 in Ontario, Canada, with follow-up through linked health care databases until March 2013. Donors and nondonors were matched with respect to age, year of cohort entry, residency (urban or rural), income, number of pregnancies before cohort entry, and the time to the first pregnancy after cohort entry. The primary outcome was a hospital diagnosis of gestational hypertension or preeclampsia. Secondary outcomes were each component of the primary outcome examined separately and other maternal and fetal outcomes. RESULTS: Gestational hypertension or preeclampsia was more common among living kidney donors than among nondonors (occurring in 15 of 131 pregnancies [11%] vs. 38 of 788 pregnancies [5%]; odds ratio for donors, 2.4; 95% confidence interval, 1.2 to 5.0; P=0.01). Each component of the primary outcome was also more common among donors (odds ratio, 2.5 for gestational hypertension and 2.4 for preeclampsia). There were no significant differences between donors and nondonors with respect to rates of preterm birth (8% and 7%, respectively) or low birth weight (6% and 4%, respectively). There were no reports of maternal death, stillbirth, or neonatal death among the donors. Most women had uncomplicated pregnancies after donation. CONCLUSIONS: Gestational hypertension or preeclampsia was more likely to be diagnosed in kidney donors than in matched nondonors with similar indicators of baseline health. (Funded by the Canadian Institutes of Health Research and others.).
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Hipertensão Induzida pela Gravidez/epidemiologia , Transplante de Rim , Doadores Vivos , Pré-Eclâmpsia/epidemiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Nefrectomia , Razão de Chances , Ontário/epidemiologia , Hemorragia Pós-Parto/epidemiologia , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: A prolonged living kidney donor evaluation may result in worse outcomes for transplant recipients. Better knowledge of the duration of this process may help inform future donors and identify opportunities for improvement. STUDY DESIGN: 1 prospective and 1 retrospective cohort study. SETTING & PARTICIPANTS: At 16 Canadian and Australian transplantation centers (prospective cohort) and 5 Ontario transplantation centers (retrospective cohort), we assessed the duration of living kidney donor evaluation and explored donor, recipient, and transplantation factors associated with longer evaluation times. Data were obtained from 2 sources: donor medical records using chart abstraction and health care administrative databases. PREDICTORS: Donor and recipient demographics, direct versus paired donation, center-level variables. OUTCOMES: Duration of living donor evaluation. RESULTS: The median total duration of transplantation evaluation (time from when the candidate started the evaluation until donation) was 10.3 (IQR, 6.5-16.7) months. The median duration from evaluation start until approval to donate was 7.9 (IQR, 4.6-14.1) months, and from approval until donation was 0.7 (IQR, 0.3-2.4) months, respectively. The median time between the first and last consultation among donors who completed a nephrology, surgery, and psychosocial assessment in the prospective cohort was 3.0 (IQR, 1.0-6.3) months, and between computed tomography angiography and donation was 4.8 (IQR, 2.6-9.2) months. After adjustment, the total duration of transplantation evaluation was longer if the donor participated in paired donation (6.6 [95% CI, 1.6-9.7] months) and if the recipient was referred later relative to the donor's evaluation start date (0.9 [95% CI, 0.8-1.0] months [per month of delayed referral]). Results depended on whether the recipient was receiving dialysis. LIMITATIONS: Living donor candidates who did not donate were not included and proxy measures were used for some dates in the donor evaluation process. CONCLUSIONS: The duration of kidney transplant donor evaluation is variable and can be lengthy. Better understanding of the reasons for a prolonged evaluation may inform quality improvement initiatives to reduce unnecessary delays.
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Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Doadores Vivos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/normas , Transplantados/estatística & dados numéricos , Adulto , Fatores Etários , Austrália , Canadá , Intervalos de Confiança , Feminino , Seguimentos , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Internacionalidade , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nefrectomia/métodos , Ontário , Seleção de Pacientes , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Obtenção de Tecidos e Órgãos/tendências , Resultado do TratamentoRESUMO
BACKGROUND: Prophylactic immunoglobulin has been used with varying efficacy to reduce complications in hematopoietic stem cell transplant recipients. STUDY DESIGN AND METHODS: A systematic review and meta-analysis was conducted of randomized controlled trials that assessed clinical outcomes (overall survival, transplant-related mortality, graft-versus-host disease [GVHD], veno-occlusive disease [VOD], interstitial pneumonitis, disease relapse, cytomegalovirus [CMV] infection and disease, non-CMV infection) of immunoglobulin prophylaxis versus placebo in hematopoietic stem cell transplant recipients. MEDLINE, EMBASE, EBM Reviews, and the Cochrane Central Register of Controlled Trials were searched up to June 2017. Quality of included studies and outcomes were evaluated via Risk of Bias assessment and Grading of Recommendations, Assessment, Development and Evaluation criteria, respectively. RESULTS: Of 899 citations screened, 27 studies (n = 3934) were included. Immunoglobulin prophylaxis had no impact on survival (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.88-1.01; 11 studies, n = 1962) but decreased risk of acute GVHD (RR, 0.78; 95% CI, 0.65-0.94; eight studies, n = 1097) and CMV disease (RR, 0.52; 95% CI, 0.28-0.97; two studies, n = 167). Meta-analysis revealed increased risk of VOD (RR, 3.04; 95% CI, 1.10-8.41; three studies, n = 384) and disease relapse (RR, 1.26; 95% CI, 1.07-1.49; seven studies, n = 1647). Other outcomes were small in sample size or nonsignificant. Results should be interpreted cautiously given the low quality of studies and evidence of outcomes. CONCLUSION: Immunoglobulin prophylaxis did not have a significant effect on survival. Positive clinical effects were shown for acute GVHD and CMV disease and negative effects against VOD and disease relapse. No studies examined the effect of immunoglobulin treatment in hypogammaglobulinemic patients despite current guidelines, warranting further studies in this population.
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Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Imunoglobulinas/uso terapêutico , Pré-Medicação/métodos , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/prevenção & controle , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de SobrevidaRESUMO
BACKGROUND: Beta Trace Protein (BTP) is a promising marker of glomerular filtration rate (GFR). Equations to estimate GFR using BTP have been proposed. Very little is known about BTP's production and metabolism. It has been hypothesized that the liver metabolizes certain BTP isoforms. As such, hepatic dysfunction may influence serum levels independently of GFR. This would impact on the accuracy and precision of GFR estimates using BTP. The purpose of this study was to assess the impact of cirrhosis on serum BTP concentrations. METHODS: BTP, cystatin C (cysC) and creatinine (Cr) were measured in 99 cirrhotic subjects and in matched controls. BTP/cysC and Cr/cysC ratios were compared between cases and controls. This was repeated after stratification by Child Pugh category. Comparisons of ratios between Child Pugh category A and combined B and C case subjects were also performed. RESULTS: There were no differences in BTP/cysC ratios between cases and controls for the entire cohort (0.80 vs 0.79) or for any of the Child Pugh categories (p > 0.10). There were significant differences between cases (1.09) and controls (0.73) for the BTP/Cr ratios (p < 0.001). The BTP/Cr ratio was higher in those with more advanced cirrhosis as compared to those with less severe cirrhosis (1.20 vs 1.03, p < 0.01). There were no differences in BTP/cysC ratios between those with less severe and more advanced cirrhosis (p = 0.25). CONCLUSIONS: This study suggests that hepatic dysfunction does not influence serum BTP levels and argues against a significant role for the liver in BTP metabolism. Confirmation in a larger group of patients with advanced cirrhosis is required.
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Taxa de Filtração Glomerular , Oxirredutases Intramoleculares/sangue , Lipocalinas/sangue , Cirrose Hepática/enzimologia , Cirrose Hepática/fisiopatologia , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Creatinina/sangue , Cistatina C/sangue , Feminino , Humanos , Fígado/metabolismo , Fígado/fisiopatologia , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Renin-angiotensin system [RAS] blockade has been established as the cornerstone of therapy in the general population, and especially in chronic kidney disease. However, its efficacy in the kidney transplant population remains unknown. STUDY DESIGN: We conducted a systematic review and meta-analysis using MEDLINE (1966 to November 2015), Embase (1980 to November 2015), and the Cochrane Library (third quarter 2015), as well as a PubMed search for recent nonindexed citations. SETTINGS & POPULATION: Adult kidney transplant recipients. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials, with follow-up of 1 year or longer and reporting clinical outcomes of interest. INTERVENTION: RAS blockade (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) versus placebo, active comparator, or standard of care. OUTCOMES: All-cause mortality, all-cause transplant failure, and doubling of serum creatinine level. RESULTS: 8 trials (1,502 participants) were included in the systematic review. RAS blockade did not significantly alter all-cause mortality (risk ratio [RR], 0.96; 95% CI, 0.62-1.51), transplant failure (RR, 0.76; 95% CI, 0.49-1.18), or creatinine level doubling (RR, 0.84; 95% CI, 0.51-1.39) compared to the control group. This result was robust across the subgroups of interest (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker intervention, follow up ≥ 1 year, and baseline proteinuria as an inclusion criterion). There was significantly higher risk for hyperkalemia with RAS blockade (RR, 2.44; 95% CI, 1.53-3.90). There was no statistical heterogeneity in any of these pooled analyses. LIMITATIONS: Relatively smaller number of events (overall, 71 deaths and 72 transplant failures among 8 trials) and relatively short follow-up (only 2 trials > 5 years). CONCLUSIONS: This analysis neither supports nor refutes the hypothesis that RAS blockade improves clinical outcomes in kidney transplant recipients. A trial with more than 10,000 patients would be needed to definitively answer whether RAS blockade reduces transplant loss in this population. In the meantime, clinicians should weigh the risks and benefits of using these medications with their patients on a case-by-case basis.
Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Transplante de Rim , Complicações Pós-Operatórias/prevenção & controle , Sistema Renina-Angiotensina/efeitos dos fármacos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The implications of venous thromboembolism (VTE) for morbidity and mortality in kidney transplant recipients are not well described. METHODS: We conducted a retrospective study using linked healthcare databases in Ontario, Canada to determine the risk and complications of VTE in kidney transplant recipients from 2003 to 2013. We compared the incidence rate of VTE in recipients (n = 4,343) and a matched (1:4) sample of the general population (n = 17,372). For recipients with evidence of a VTE posttransplant, we compared adverse clinical outcomes (death, graft loss) to matched (1:2) recipients without evidence of a VTE posttransplant. RESULTS: During a median follow-up of 5.2 years, 388 (8.9%) recipients developed a VTE compared to 254 (1.5%) in the matched general population (16.3 vs. 2.4 events per 1,000 person-years; hazard ratio [HR] 7.1, 95% CI 6.0-8.4; p < 0.0001). Recipients who experienced a posttransplant VTE had a higher risk of death (28.5 vs. 11.2%; HR 4.1, 95% CI 2.9-5.8; p < 0.0001) and death-censored graft loss (13.1 vs. 7.5%; HR 2.3, 95% CI 1.4-3.6; p = 0.0006) compared to matched recipients who did not experience a posttransplant VTE. CONCLUSIONS: Kidney transplant recipients have a sevenfold higher risk of VTE compared to the general population with VTE conferring an increased risk of death and graft loss.
Assuntos
Rejeição de Enxerto/epidemiologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Tromboembolia Venosa/epidemiologia , Adulto , Idoso , Feminino , Rejeição de Enxerto/etiologia , Humanos , Incidência , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Complicações Pós-Operatórias/etiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND: Major hemorrhagic events are associated with significant morbidity and mortality. We examined the three-year cumulative incidence of hospitalization with major nontraumatic hemorrhage after kidney transplantation. METHODS: We performed a retrospective cohort study using healthcare administrative data of all adult-incident kidney-only transplantation recipients in Ontario, Canada from 1994 to 2009. We calculated the three-year cumulative incidence, event rate, and incident rate ratio of hospitalization with major hemorrhage, its subtypes and those undergoing a hemorrhage-related procedure. RESULTS were stratified by patient age and donor type and compared to a random and propensity-score matched sample from the general population. RESULTS: Among 4,958 kidney transplant recipients, the three-year cumulative incidence of hospitalization with nontraumatic major hemorrhage was 3.5% (95% confidence interval [CI] 3.0-4.1%, 12.7 events per 1,000 patient-years) compared to 0.4% (95% CI 0.4-0.5%) in the general population (RR = 8.2, 95% CI 6.9-9.7). The crude risk of hemorrhage was 3-9-fold higher in all subtypes (upper/lower gastrointestinal, intra-cranial) and 15-fold higher for gastrointestinal endoscopic procedures compared to the random sample from the general population. After propensity score matching, the relative risk for major hemorrhage and its subtypes attenuated but remained elevated. The cumulative incidence of hemorrhage was higher for older individuals and those with a deceased donor kidney. CONCLUSION: Kidney transplantation recipients have a higher risk of hospitalization with hemorrhage compared to the general population, with about 1 in 30 recipients experiencing a major hemorrhage in the three years following transplant.
Assuntos
Hemorragia Gastrointestinal/epidemiologia , Transplante de Rim/estatística & dados numéricos , Hemorragia Pós-Operatória/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Hemorragia Cerebral/epidemiologia , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Ontário/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/epidemiologiaRESUMO
BACKGROUND: Quantification of proteinuria (albuminuria) in renal transplant recipients is important for diagnostic and prognostic purposes. Recent guidelines have recommended quantification of proteinuria by spot protein-to-creatinine ratio (PCR) or spot albumin-to-creatinine ratio (ACR). Validity of spot measurements remains unclear in renal transplant recipients. METHODS: Systematic review of adult kidney transplant recipients. Studies that reported the diagnostic accuracy of PCR or ACR as compared with 24-h urine protein or albumin excretion in renal transplant recipients were included. RESULTS: The search identified 8 studies involving 1871 renal transplant recipients. The correlation of the PCR to 24-h protein ranged from 0.772 to 0.998 with a median value of 0.92. PCR sensitivity ranged from 63 to 99 (50% of sensitivities were >90%); PCR specificity varied from 73 to 99 (50% of specificities were >90%). Only one study reported the bias; percent bias ranged from 12 to 21% and accuracy (within 30% of 24 h urine protein) ranged from 47 to 56% depending on the degree of proteinuria. For the ACR, percent bias ranged from 9 to 21%, and the accuracy (within 30%) ranged from 38 to 80%. CONCLUSIONS: The data regarding diagnostic accuracy of PCR and ACR is limited. Only one report studied the absolute measures of agreement (bias and accuracy). We recommend verifying PCR and ACR measurements with a 24-h protein before making any major diagnostic (e.g. biopsy) or therapeutic (e.g. change in immunosuppressive agents) decisions in this population.
Assuntos
Creatinina/urina , Rejeição de Enxerto/diagnóstico , Transplante de Rim , Proteinúria/diagnóstico , Adulto , Feminino , Rejeição de Enxerto/complicações , Rejeição de Enxerto/urina , Humanos , Proteinúria/etiologia , Proteinúria/urina , Reprodutibilidade dos Testes , UrináliseRESUMO
IMPORTANCE: BK virus infection is a significant complication of modern immunosuppression used in kidney transplantation. Viral reactivation occurs first in the urine (BK viruria) and is associated with a high risk of transplant failure. There are currently no therapies to prevent or treat BK virus infection. Quinolone antibiotics have antiviral properties against BK virus but efficacy at preventing this infection has not been shown in prospective controlled studies. OBJECTIVE: To determine if levofloxacin can prevent BK viruria in kidney transplant recipients. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled randomized trial involving 154 patients who received a living or deceased donor kidney-only transplant in 7 Canadian transplant centers between December 2011 and June 2013. INTERVENTIONS: Participants were randomly assigned to receive a 3-month course of levofloxacin (500 mg/d; n = 76) or placebo (n = 78) starting within 5 days after transplantation. MAIN OUTCOMES AND MEASURES: The primary outcome was time to occurrence of BK viruria (detected using quantitative real-time polymerase chain reaction) within the first year after transplantation. Secondary outcomes included BK viremia, peak viral load, rejection, and patient and allograft survival. RESULTS: The mean follow-up time was 46.5 weeks in the levofloxacin group and 46.3 weeks in the placebo group (27 patients had follow-up terminated before the end of the planned follow-up period or development of viruria because the trial was stopped early owing to lack of funding). BK viruria occurred in 22 patients (29%) in the levofloxacin group and in 26 patients (33.3%) in the placebo group (hazard ratio, 0.91; 95% CI, 0.51-1.63; P = .58). There was no significant difference between the 2 groups in regard to any of the secondary end points. There was an increased risk of resistant infection among isolates usually sensitive to quinolones in the levofloxacin group vs placebo (14/24 [58.3%] vs 15/45 [33.3%], respectively; risk ratio, 1.75; 95% CI, 1.01-2.98) as well as a nonsignificant increased risk of suspected tendinitis (6/76 [7.9%] vs 1/78 [1.3%]; risk ratio, 6.16; 95% CI, 0.76-49.95). CONCLUSIONS AND RELEVANCE: Among kidney transplant recipients, a 3-month course of levofloxacin initiated early following transplantation did not prevent BK viruria. Levofloxacin was associated with an increased risk of adverse events such as bacterial resistance. These findings do not support the use of levofloxacin to prevent posttransplant BK virus infection. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01353339.
Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Vírus BK/isolamento & purificação , Terapia de Imunossupressão/efeitos adversos , Transplante de Rim , Levofloxacino/uso terapêutico , Infecções por Polyomavirus/prevenção & controle , Infecções Tumorais por Vírus/prevenção & controle , Adulto , Vírus BK/genética , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Urina/virologia , Carga Viral , ViremiaRESUMO
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.