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RATIONALE & OBJECTIVE: Females have a higher prevalence of chronic kidney disease (CKD) than males, but are less likely to be treated with kidney replacement therapy (KRT). We studied the interaction between sex and the association of cardiometabolic risk factors for the decline in kidney function over time. STUDY DESIGN: A population-based cohort study. SETTING & PARTICIPANTS: 1,127,731 adults living in Wales, UK, within the Secure Anonymised Information Linkage Databank. EXPOSURES: Sex and risk factors including age, estimated glomerular filtration rate (eGFR), cardiometabolic conditions, smoking, and socioeconomic deprivation. These risk factors were defined using primary care records. OUTCOMES: The yearly declines in eGFR and the risk of incident kidney failure defined as long-term KRT and/or sustained eGFR<15mL/min/1.73m2. ANALYTICAL APPROACH: Linear mixed effects models and Cox proportional hazards analysis. RESULTS: The average decline in eGFR age ≤73 was equal in males and females. After age 73, eGFR decline was faster in males than females, particularly for males with heart failure (males -1.22 mL/min/1.73m2 per year: 95% confidence interval (CI) -1.25 to -1.20 versus females -0.87mL/min/1.73m2: CI -0.89 to -0.85) and current smokers (males -1.58 mL/min/1.73m2 per year: CI -1.60 to -1.55 versus females -1.27 mL/min/1.73m2: CI -1.29 to -1.25). Socioeconomic deprivation was one of the most impactful risk factors on eGFR decline among females age >73, whereas cardiometabolic risk factors were more important among males. Older females at baseline were less likely to develop incident kidney failure than older males (p-value for age<0.001). LIMITATIONS: Study of people who were almost exclusively White and who had blood laboratory test data. Reliance on creatinine-based eGFR. Albuminuria and body mass index data were incomplete. CONCLUSIONS: eGFR decline was faster in males than in females especially in the setting of heart failure and smoking. Socioeconomic deprivation was an important risk factor associated with eGFR decline, particularly for females. While further work is required to explore less well-recognised risk factors these findings may inform clinical management strategies of CKD overall and within sex-specific groups.
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BACKGROUND AND HYPOTHESIS: People with chronic kidney disease (CKD) have increased incidence and mortality from most cancer types. We hypothesised that odds of presenting with advanced cancer may vary according to differences in eGFR, that this could contribute to increased all-cause mortality and that sex differences may exist. METHODS: Data were from Secure Anonymised Information Linkage Databank, including people with de-novo cancer diagnosis (2011-2017) and two kidney function tests within two years prior to diagnosis to determine baseline eGFR (mL/min/1.73m2). Logistic regression models determined odds of presenting with advanced cancer by baseline eGFR. Cox proportional hazards models tested associations between baseline eGFRcr and all-cause mortality. RESULTS: eGFR < 30 was associated with higher odds of presenting with advanced cancer of prostate, breast and female genital organs, but not other cancer sites. Compared to eGFR > 75-90, eGFR < 30 was associated with greater hazards of all-cause mortality in both sexes, but the association was stronger in females (female: HR 1.71, 95%CI 1.56-1.88; male versus female comparison HR 0.88, 95%CI 0.78-0.90). CONCLUSIONS: Lower or higher eGFR was not associated with substantially higher odds of presenting with advanced cancer across most cancer sites, but was associated with reduced survival. A stronger assocation with all-cause mortality in females compared to males with eGFR < 30 is concerning and warrants further scrutiny.
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SIGNIFICANCE STATEMENT: In children with kidney failure, little is known about their treatment trajectories or the effects of kidney failure on lifetime survival and years of life lost, which are arguably more relevant measures for children. In this population-based cohort study of 2013 children who developed kidney failure in Australia and New Zealand, most children were either transplanted after initiating dialysis (74%) or had a preemptive kidney transplant (14%). Life expectancy increased with older age at kidney failure, but more life years were spent on dialysis than with a functioning transplant. The expected (compared with the general population) number of life years lost ranged from 16 to 32 years, with female patients and those who developed kidney failure at a younger age experiencing the greatest loss of life years. BACKGROUND: Of the consequences of kidney failure in childhood, those rated as most important by children and their caregivers are its effects on long-term survival. From a life course perspective, little is known about the experience of kidney failure treatment or long-term survival. METHODS: To determine expected years of life lost (YLL) and treatment trajectory for kidney failure in childhood, we conducted a population-based cohort study of all children aged 18 years or younger with treated kidney failure in Australia (1980-2019) and New Zealand (1988-2019).We used patient data from the CELESTIAL study, which linked the Australian and New Zealand Dialysis and Transplant registry with national death registers. We estimated standardized mortality ratios and used multistate modeling to understand treatment transitions and life expectancy. RESULTS: A total of 394 (20%) of 2013 individuals died over 30,082 person-years of follow-up (median follow-up, 13.1 years). Most children (74%) were transplanted after initiating dialysis; 14% (18% of male patients and 10% of female patients) underwent preemptive kidney transplantation. Excess deaths (compared with the general population) decreased dramatically from 1980 to 1999 (from 41 to 22 times expected) and declined more modestly (to 17 times expected) by 2019. Life expectancy increased with older age at kidney failure, but more life years were spent on dialysis than with a functioning transplant. The number of YLL ranged from 16 to 32 years, with the greatest loss among female patients and those who developed kidney failure at a younger age. CONCLUSIONS: Children with kidney failure lose a substantial number of their potential life years. Female patients and those who develop kidney failure at younger ages experience the greatest burden.
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Fallo Renal Crónico , Insuficiencia Renal , Humanos , Masculino , Niño , Femenino , Estudios de Cohortes , Australia/epidemiología , Esperanza de Vida , Insuficiencia Renal/terapia , Probabilidad , Sistema de Registros , Fallo Renal Crónico/epidemiologíaRESUMEN
BACKGROUND: Quality-of-life is an essential outcome for clinical care. Both chronic kidney disease (CKD) and diabetes have been associated with poorer quality-of-life. The combined impact of having both diseases is less well understood. As diabetes is the most common cause of CKD, it is imperative that we deepen our understanding of their joint impact. METHODS: This was a prospective, longitudinal cohort study of community-based Australians aged ≥25 years who participated in the Australian Diabetes, Obesity and Lifestyle study. Quality-of-life was measured by physical component summary (PCS) and mental component summary sub-scores of the Short Form (36) Health Survey. Univariate and multivariate linear mixed effect regressions were performed. RESULTS: Of the 11 081 participants with quality-of-life measurements at baseline, 1112 had CKD, 1001 had diabetes and of these 271 had both. Of the 1112 with CKD 421 had Stage 1, 314 had Stage 2, 346 had Stage 3 and 31 had Stages 4/5. Adjusted linear mixed effect models showed baseline PCS was lower for those with both CKD and diabetes compared with either disease alone (P < 0.001). Longitudinal analysis demonstrated a more rapid decline in PCS in those with both diseases. CONCLUSIONS: The combination of CKD and diabetes has a powerful adverse impact on quality-of-life, and participants with both diseases had significantly poorer quality-of-life than those with one condition.
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Diabetes Mellitus , Insuficiencia Renal Crónica , Australia/epidemiología , Diabetes Mellitus/epidemiología , Humanos , Estudios Prospectivos , Calidad de Vida , Insuficiencia Renal Crónica/epidemiologíaRESUMEN
Evidence on cancer transmission from organ transplantation is poor. We sought to identify cases of cancer transmission or non-transmission from transplantation in an Australian cohort of donors and recipients. We included NSW solid organ deceased donors 2000-2012 and living donors 2004-2012 in a retrospective cohort using linked data from the NSW Biovigilance Register (SAFEBOD). Central Cancer Registry (CCR) data 1972-2013 provided a minimum one-year post-transplant follow-up. We identified cancers in donors and recipients. For each donor-recipient pair, the transmission was judged likely, possible, unlikely, or excluded using categorization from international guidelines. In our analysis, transmissions included those judged likely, while those judged possible, unlikely, or excluded were non-transmissions. In our cohort, there were 2502 recipients and 1431 donors (715 deceased, 716 living). There were 2544 transplant procedures, including 1828 (72%) deceased and 716 (28%) living donor transplants. Among 1431 donors, 38 (3%) had past or current cancer and they donated to 68 recipients (median 6.7-year follow-up). There were 64 (94%) non-transmissions, and 4 (6%) transmissions from two living and two deceased donors (all kidney cancers discovered during organ recovery). Donor transmitted cancers are rare, and selected donors with a past or current cancer may be safe for transplantation.
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Neoplasias Renales , Trasplante de Órganos , Obtención de Tejidos y Órganos , Australia , Supervivencia de Injerto , Humanos , Donadores Vivos , Estudios Retrospectivos , Donantes de TejidosRESUMEN
Chronic kidney disease (CKD) is a sustained reduction in estimated glomerular filtration rate (eGFR), and/or presence of albuminuria. People with CKD have adverse cardiovascular outcomes including stroke. CKD and stroke share several risk factors, most notably older age, diabetes and hypertension, but CKD is also an independent risk factor for stroke. Relative burden of increased risk is worse for younger people and women, with <40 years with end stage CKD having more than 11 times the risk of their age-matched peers. Risk also varies by CKD treatment, with a risk peak for those starting dialysis, but dropping after the first month of treatment. Proposed mechanisms for increased risk are uraemia, cerebral blood flow dysregulation, vascular calcification, arterial stiffness, chronic inflammation, vascular access impacts, and for those on haemodialysis the use of anticoagulation to maintain dialysis circuits. Outcomes for people with CKD and stroke are poorer; functional outcomes may be impacted by reduced access to specialised stroke care. Stroke mortality is higher for those with CKD; with standardised mortality ratio more than three times higher than expected, but for some groups higher still (young women <40 years with a kidney transplant have 19 times the risk of stroke mortality than women without a transplant). Interventions to prevent and treat stroke lack the evidence base in CKD patients that is present for the general population.
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Insuficiencia Renal Crónica/epidemiología , Accidente Cerebrovascular/epidemiología , Albuminuria/epidemiología , Tasa de Filtración Glomerular , Humanos , Incidencia , Riñón/fisiopatología , Pronóstico , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/terapia , Terapia de Reemplazo Renal , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/terapiaRESUMEN
PURPOSE: Quality-of-life is poor in end-stage kidney disease; however, the relationships between earlier stages of chronic kidney disease (CKD) and are poorly understood. This study explored longitudinal quality-of-life changes in a community-based CKD cohort and assessed associations between CKD and quality-of-life over time, and between baseline quality-of-life and CKD outcomes. METHODS: We used the Australian diabetes, obesity and lifestyle study-a nationally representative, prospective cohort with data collected at baseline, year 5 and year 12-to examine the relationships between CKD stage, quality-of-life and outcomes. Linear mixed regression, cox proportional hazards, Kaplan-Meier and competing risks analyses were used. RESULTS: Of 1112 participants with CKD and baseline quality-of-life data, the physical component summary (PCS) score was significantly lower than for the general population (p = 0.01 age and sex adjusted), while the mental component summary (MCS) score was no different (p = 0.9 age and sex adjusted). In our unadjusted mixed effects model, more advanced kidney disease was associated with lower PCS and higher MCS at baseline (p < 0.001 and p < 0.01, respectively); however, this effect was no longer significant after adjustment for demographic and clinical variables. The rate of decline in PCS over the period of follow-up was greatest for those with more advanced kidney disease (p < 0.001 in unadjusted model, p = 0.007 in adjusted model). There was no association between change in MCS over the period of follow-up and severity of kidney disease in either the unadjusted or adjusted model (p = 0.7 and p = 0.1, respectively). Lower PCS, but not MCS, was associated with increased cardiovascular and increased all-cause mortality even after adjustment for key demographic and clinical variables (p < 0.001). CONCLUSIONS: Physical, but not mental, quality-of-life is significantly impaired in CKD, and continues to decline with disease progression.
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Estado de Salud , Fallo Renal Crónico/psicología , Calidad de Vida/psicología , Insuficiencia Renal Crónica/psicología , Adulto , Anciano , Australia , Estudios de Cohortes , Diabetes Mellitus/patología , Progresión de la Enfermedad , Femenino , Humanos , Fallo Renal Crónico/terapia , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Renal Crónica/terapiaRESUMEN
AIM: Assessing the impact of interventions on the patient experience requires measures that are plausibly responsive to change. In a community cohort of people with and without chronic kidney disease (CKD) markers at baseline, we aimed to evaluate change in commonly used measures of quality of life (QOL) over the passage of 5 years. METHODS: Included were 6400 participants in the Australian Diabetes, Obesity and Lifestyle (AusDiab) surveys with baseline and 5-year CKD and QOL measures. Changes in SF-6D utility, and the Medical Outcomes Study 36-Item Short Form (SF-36) physical (PCS) and mental (MCS) component summary scores, were evaluated with regression analyses according to the baseline presence of reduced estimated glomerular filtration rate (eGFR) (CKD-Epidemiology Collaboration eGFR ≤60 m/min per 1.73 m2 ) or albuminuria (urine albumin:creatinine ratio ≥3.4 mg/mmol). RESULTS: At baseline, eGFR was reduced in 2.4% of participants and 5.1% had albuminuria. Participants with reduced eGFR had a lower SF-6D and PCS, and those with albuminuria a lower PCS, compared with those without, but the differences were explained by known confounders. MCS scores were not affected by the presence of reduced eGFR or albuminuria. Over 5 years all groups exhibited stable SF-6D and MCS scores but declining unadjusted PCS scores. PCS decline was greater for those with reduced eGFR, and remained significant after adjustment (-2.7 (-4.1 to -1.3) vs. -0.8 (-1.1 to -0.6, P < 0.01). Analyses according to CKD stages were essentially unchanged. CONCLUSION: Utility and mental QOL appears stable over 5 years, unaffected by time or markers of CKD health. Physical QOL appeared to deteriorate with time, especially for those with CKD, making it a more likely candidate assessment measure for intervention and health service evaluations.
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Albuminuria/diagnóstico , Tasa de Filtración Glomerular , Riñón/fisiopatología , Salud Mental , Calidad de Vida , Insuficiencia Renal Crónica/diagnóstico , Encuestas y Cuestionarios , Anciano , Albuminuria/fisiopatología , Albuminuria/psicología , Albuminuria/terapia , Australia , Biomarcadores/orina , Creatinina/orina , Progresión de la Enfermedad , Femenino , Estado de Salud , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/psicología , Insuficiencia Renal Crónica/terapia , Reproducibilidad de los Resultados , Factores de TiempoAsunto(s)
Hiperparatiroidismo , Neoplasias de las Paratiroides , Compresión de la Médula Espinal , Humanos , Hiperparatiroidismo/complicaciones , Hiperparatiroidismo/diagnóstico , Compresión de la Médula Espinal/diagnóstico por imagen , Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/cirugíaRESUMEN
BACKGROUND: The disparity between the demand for and supply of kidney transplants has resulted in prolonged waiting times for patients with kidney failure. A potential approach to address this shortage is to consider kidneys from donors with a history of common cancers, such as breast, prostate, and colorectal cancers. METHODS: We used a patient-level Markov model to evaluate the outcomes of accepting kidneys from deceased donors with a perceived history of breast, prostate, or colorectal cancer characterized by minimal to intermediate transmission risk. Data from the Australian transplant registry were used in this analysis. The study compared the costs and quality-adjusted life years (QALYs) from the perspective of the Australian healthcare system between the proposed practice of accepting these donors and the conservative practice of declining them. The model simulated outcomes for 1500 individuals waitlisted for a deceased donor kidney transplant for a 25-y horizon. RESULTS: Under the proposed practice, when an additional 15 donors with minimal to intermediate cancer transmission risk were accepted, QALY gains ranged from 7.32 to 20.12. This translates to an approximate increase of 7 to 20 additional years of perfect health. The shift in practice also led to substantial cost savings, ranging between $1.06 and $2.3 million. CONCLUSIONS: The proposed practice of accepting kidneys from deceased donors with a history of common cancers with minimal to intermediate transmission risk offers a promising solution to bridge the gap between demand and supply. This approach likely results in QALY gains for recipients and significant cost savings for the health system.
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Análisis Costo-Beneficio , Trasplante de Riñón , Cadenas de Markov , Años de Vida Ajustados por Calidad de Vida , Donantes de Tejidos , Humanos , Trasplante de Riñón/economía , Masculino , Femenino , Donantes de Tejidos/provisión & distribución , Australia , Persona de Mediana Edad , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/economía , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/economía , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/economía , Adulto , Sistema de Registros , Selección de Donante/economía , Factores de Riesgo , Listas de Espera , Modelos Económicos , Factores de TiempoRESUMEN
BACKGROUND: Optimal treatment of atrial fibrillation (AF) in the haemodialysis population is uncertain due to the exclusion of this group from randomized trials. The risk-benefit profile for anticoagulation and anti-platelet therapy in haemodialysis differs from the general population due to platelet dysfunction from uraemia, altered pharmacokinetics and increased falls risk. METHODS: This decision analysis used a Markov-state transition model that took a patient perspective over a 5 year timeframe. The Markov model compared life-years gained and quality-adjusted life-years gained (QALY) for three AF treatment strategies: warfarin, aspirin and no treatment. The base case was a 70-year-old man on haemodialysis with non-valvular AF. RESULTS: In the base case, the total health outcomes in life-years and QALY were 2.37 and 1.47 respectively for warfarin, 2.38 and 1.61 respectively for aspirin, and 2.39 and 1.61 respectively for no treatment. Thus, warfarin led to 0.14 fewer QALY or 1.7 fewer months of life lived in full health, compared with either aspirin or no therapy. The finding that warfarin generated the lowest expected QALY was robust to one-way, two-way and probabilistic sensitivity analyses. CONCLUSIONS: Our results suggest that warfarin should not be the default choice for older haemodialysis patients with non-valvular AF as it provides the fewest QALY compared with aspirin or no therapy.
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Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Diálisis Renal , Anciano , Anticoagulantes/efectos adversos , Técnicas de Apoyo para la Decisión , Humanos , Masculino , Cadenas de Markov , Inhibidores de Agregación Plaquetaria/efectos adversos , Probabilidad , Años de Vida Ajustados por Calidad de VidaRESUMEN
Background: Women are more likely than men to be living kidney donors. We summarized the evidence concerning the reasons behind sex and gender disparities in living kidney donation (LKD). Methods: A scoping review of quantitative and qualitative evidence on reasons for sex and gender disparities in LKD was conducted from inception to March 2023. Results: Of 1123 studies screened, 45 were eligible for inclusion. Most studies were from North America, Europe, and Central Asia (n = 33, 73%). A predominance of women as living donors (55%-65%) was observed in 15 out of 18 (83%) studies. Reasons for sex and gender disparities in LKD included socioeconomic, biological, and cognitive or emotional factors. A gendered division of roles within the families was observed in most studies, with men being the primary income earner and women being the main caregiver. Fear of loss of income was a barrier to male donation. Human leukocyte antigen sensitization through pregnancy in female recipients precluded male partner donation, whereas female donation was supported by altruism and a positive attitude toward LKD. Conclusions: Sex imbalance in LKD is prevalent, with a predominance of women as living donors. Such disparities are driven by societal and cultural perceptions of gender roles, pregnancy-induced sensitization, and attitudes toward donation and at least some of these factors are modifiable. Donor compensation to support predonation assessments and income loss, implementation of innovative desensitization treatments, promotion of paired kidney exchange program, and targeted educational initiatives to promote equitable living donation may help to close the gender gap in LKD.
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Background: Females account for 60% of all living kidney donors worldwide. We defined the proportion of female to male donors for living donor kidney transplantation stratified by recipient gender, and explored the factors associated with female kidney donation. Methods: Data from the ANZDATA (Australian and New Zealand Dialysis and Transplantation) and ANZOD (Australian and New Zealand Organ Donor) registries (2002-2019) were used to identify the sociodemographic characteristics and their interactions associated with living donation from female donors. We derived the predicted probabilities from adjusted logistic models using marginal means. Results: Of 3523 living donor pairs, 2203 (63%) recipients were male, and 2012 (57%) donors were female. Male recipients were more likely to receive kidneys from female donors than male donors. Donor and recipient sex association was modified by donor-recipient relationship (P < 0.01), with sensitivity analysis suggesting that spousal donor-recipient pairs drive this interaction. Older recipients residing in regional or remote areas were more likely to receive kidneys from female donors compared with those from major cities (aged ≥60 years: 0.67 [0.63-0.71] vs. aged <60 years: 0.57 [0.53-0.60]). Conclusions: Factors associated with female donation include recipient sex, with spousal donors contributing to the interaction between recipient gender and donor-recipient relationship. Recipient age and location of residence have interactive effects on the likelihood of living donor transplantation from female donors.
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BACKGROUND: Demand for donor kidneys outstrips supply. Using kidneys from selected donors with an increased risk of blood-borne virus (BBV) transmission (hepatitis B virus and hepatitis C virus [HCV], human immunodeficiency virus) may expand the donor pool, but cost-effectiveness of this strategy is uncertain. METHODS: A Markov model was developed using real-world evidence to compare healthcare costs and quality-adjusted life years (QALYs) of accepting kidneys from deceased donors with potential increased risk of BBV transmission, because of increased risk behaviors and/or history of HCV, versus declining these kidneys. Model simulations were run over a 20-y time horizon. Parameter uncertainty was assessed through deterministic and probabilistic sensitivity analyses. RESULTS: Accepting kidneys from donors at increased risk of BBVs (2% from donors with increased-risk behaviors and 5% from donors with active or past HCV infection) incurred total costs of 311 303 Australian dollars with a gain of 8.53 QALYs. Foregoing kidneys from these donors incurred total costs of $330 517 and a gain of 8.44 QALYs. A cost-saving of $19 214 and additional 0.09 QALYs (~33 d in full health) per person would be generated compared with declining these donors. Increasing the availability of kidneys with increased risk by 15% led to further cost-savings of $57 425 and additional 0.23 QALY gains (~84 d in full health). Probabilistic sensitivity analysis using 10 000 iterations showed accepting kidneys from donors at increased risk led to lower costs and higher QALY gains. CONCLUSIONS: Shifting clinical practice to accept increased BBV risk donors would likely produce lower costs and higher QALYs for health systems.
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Hepatitis C , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Análisis Costo-Beneficio , Australia , Donantes de Tejidos , Hepacivirus , Años de Vida Ajustados por Calidad de VidaRESUMEN
Kidneys from potential deceased donors with brain cancer are often foregone due to concerns of cancer transmission risk to recipients. There may be uncertainty around donors' medical history and their absolute transmission risk or risk-averse decision-making among clinicians. However, brain cancer transmissions are rare, and prolonging waiting time for recipients is harmful. Methods: We assessed the cost-effectiveness of increasing utilization of potential deceased donors with brain cancer using a Markov model simulation of 1500 patients waitlisted for a kidney transplant, based on linked transplant registry data and with a payer perspective (Australian government). We estimated costs and quality-adjusted life-years (QALYs) for three interventions: decision support for clinicians in assessing donor risk, improved cancer classification accuracy with real-time data-linkage to hospital records and cancer registries, and increased risk tolerance to allow intermediate-risk donors (up to 6.4% potential transmission risk). Results: Compared with current practice, decision support provided 0.3% more donors with an average transmission risk of 2%. Real-time data-linkage provided 0.6% more donors (1.1% average transmission risk) and increasing risk tolerance (accepting intermediate-risk 6.4%) provided 2.1% more donors (4.9% average transmission risk). Interventions were dominant (improved QALYs and saved costs) in 78%, 80%, and 87% of simulations, respectively. The largest benefit was from increasing risk tolerance (mean +18.6 QALYs and AU$2.2 million [US$1.6 million] cost-savings). Conclusions: Despite the additional risk of cancer transmission, accepting intermediate-risk donors with brain cancer is likely to increase the number of donor kidneys available for transplant, improve patient outcomes, and reduce overall healthcare expenditure.
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PURPOSE: We sought to explore whether adding kidney function biomarkers based on creatinine (eGFRCr), cystatin C (eGFRCys) or a combination of the two (eGFRCr-Cys) could improve risk stratification for stroke and major bleeding, and whether there were sex differences in any additive value of kidney function biomarkers. METHOD: We included participants from the UK Biobank who had not had a previous ischaemic or haemorrhagic stroke or major bleeding episode, and who had kidney function measures available at baseline. Cause-specific Cox proportional hazards models tested associations between eGFRCr, eGFRCys and eGFRCr-Cys (mL/min/1.73 m2) with ischaemic and haemorrhagic stroke, major bleeding (gastrointestinal or intracranial, including haemorrhagic stroke) and all-cause mortality. FINDINGS: Among 452,879 eligible participants, 246,244 (54.4%) were women. Over 11.5 (IQR 10.8-12.2) years, there were 3706 ischaemic strokes, 795 haemorrhagic strokes, 26,025 major bleeding events and 28,851 deaths. eGFRCys was more strongly associated with ischaemic stroke than eGFRCr: an effect that was more pronounced in women (men - HR: 1.16, 95% CI: 1.12-1.19; female to male comparison - HR: 1.11, 95% CI: 1.05-1.16, per 10 mL/min/1.73 m2 decline in eGFRCys). This interaction effect was also demonstrated for eGFRCr-Cys, but not eGFRCr. eGFRCys and eGFRCr-Cys were more strongly associated with major bleeding and all-cause mortality than eGFRCr in both men and women. Event numbers were small for haemorrhagic stroke. DISCUSSION: To a greater degree than is seen in men, eGFRCr underestimates risk of ischaemic stroke and major bleeding in women compared to eGFRCys. The difference between measures is likely explained by non-GFR biology of creatinine and cystatin C. CONCLUSION: Enhanced measurement of cystatin C may improve risk stratification for ischaemic stroke and major bleeding and clinical treatment decisions in a general population setting, particularly for women.
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Isquemia Encefálica , Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Femenino , Humanos , Masculino , Accidente Cerebrovascular/diagnóstico , Creatinina , Cistatina C , Caracteres Sexuales , Hemorragia , RiñónRESUMEN
BACKGROUND: Chronic kidney disease (CKD) is a common and costly condition to treat. Economic evaluations of health care often incorporate patient preferences for health outcomes using utilities. The objective of this study was to determine pooled utility-based quality of life (the numerical value attached to the strength of an individual's preference for a specific health outcome) by CKD treatment modality. METHODS AND FINDINGS: We conducted a systematic review, meta-analysis, and meta-regression of peer-reviewed published articles and of PhD dissertations published through 1 December 2010 that reported utility-based quality of life (utility) for adults with late-stage CKD. Studies reporting utilities by proxy (e.g., reported by a patient's doctor or family member) were excluded. In total, 190 studies reporting 326 utilities from over 56,000 patients were analysed. There were 25 utilities from pre-treatment CKD patients, 226 from dialysis patients (haemodialysis, nâ=â163; peritoneal dialysis, nâ=â44), 66 from kidney transplant patients, and three from patients treated with non-dialytic conservative care. Using time tradeoff as a referent instrument, kidney transplant recipients had a mean utility of 0.82 (95% CI: 0.74, 0.90). The mean utility was comparable in pre-treatment CKD patients (difference â= â-0.02; 95% CI: -0.09, 0.04), 0.11 lower in dialysis patients (95% CI: -0.15, -0.08), and 0.2 lower in conservative care patients (95% CI: -0.38, -0.01). Patients treated with automated peritoneal dialysis had a significantly higher mean utility (0.80) than those on continuous ambulatory peritoneal dialysis (0.72; pâ=â0.02). The mean utility of transplant patients increased over time, from 0.66 in the 1980s to 0.85 in the 2000s, an increase of 0.19 (95% CI: 0.11, 0.26). Utility varied by elicitation instrument, with standard gamble producing the highest estimates, and the SF-6D by Brazier et al., University of Sheffield, producing the lowest estimates. The main limitations of this study were that treatment assignments were not random, that only transplant had longitudinal data available, and that we calculated EuroQol Group EQ-5D scores from SF-36 and SF-12 health survey data, and therefore the algorithms may not reflect EQ-5D scores measured directly. CONCLUSIONS: For patients with late-stage CKD, treatment with dialysis is associated with a significant decrement in quality of life compared to treatment with kidney transplantation. These findings provide evidence-based utility estimates to inform economic evaluations of kidney therapies, useful for policy makers and in individual treatment discussions with CKD patients.
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Calidad de Vida , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/terapia , Humanos , Trasplante de Riñón , Diálisis RenalRESUMEN
Polyomavirus BK virus (BKPyV) infection is an important complication of kidney transplantation and allograft failure. The prevalence of viremia is 10%-15%, compared with BK-associated nephropathy (BKPyVAN) at 3%-5%. Given that there are no effective antiviral prophylaxis or treatment strategies for BKPyVAN, active screening to detect BKPyV viremia is recommended, particularly during the early posttransplant period. Immunosuppression reduction to allow viral clearance may avoid progression to severe and irreversible allograft damage. The frequency and duration of screening are highly variable between transplant centers because the evidence is reliant largely on observational data. While the primary treatment goals center on achieving viral clearance through immunosuppression reduction, prevention of subsequent acute rejection, premature graft loss, and return to dialysis remain as major challenges. Treatment strategies for BKPyV infection should be individualized to the recipient's underlying immunological risk and severity of the allograft infection. Efficacy data for adjuvant therapies including intravenous immunoglobulin and cidofovir are sparse. Future well-powered and high-quality randomized controlled trials are needed to inform evidence-based clinical practice for the management of BKPy infection.
Asunto(s)
Virus BK , Trasplante de Riñón , Infecciones por Polyomavirus , Poliomavirus , Infecciones Tumorales por Virus , Humanos , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/tratamiento farmacológico , Infecciones por Polyomavirus/epidemiología , Receptores de Trasplantes , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/tratamiento farmacológico , Infecciones Tumorales por Virus/epidemiologíaRESUMEN
BACKGROUND: Kidney transplantation is considered the ideal treatment for most people with kidney failure, conferring both survival and quality of life advantages, and is more cost effective than dialysis. Yet, current health systems may serve some people better than others, creating inequities in access to kidney failure treatments and health outcomes. AcceSS and Equity in Transplantation (ASSET) investigators aim to create a linked data platform to facilitate research enquiry into equity of health service delivery for people with kidney failure in New Zealand. METHODS: The New Zealand Ministry of Health will use patients' National Health Index (NHI) numbers to deterministically link individual records held in existing registry and administrative health databases in New Zealand to create the data platform. The initial data linkage will include a study population of incident patients captured in the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), New Zealand Blood Service Database and the Australia and New Zealand Living Kidney Donor Registry (ANZLKD) from 2006 to 2019 and their linked health data. Health data sources will include National Non-Admitted Patient Collection Data, National Minimum Dataset, Cancer Registry, Programme for the Integration of Mental Health Data (PRIMHD), Pharmaceutical Claims Database and Mortality Collection Database. Initial exemplar studies include 1) kidney waitlist dynamics and pathway to transplantation; 2) impact of mental illness on accessing kidney waitlist and transplantation; 3) health service use of living donors following donation. CONCLUSION: The AcceSS and Equity in Transplantation (ASSET) linked data platform will provide opportunity for population-based health services research to examine equity in health care delivery and health outcomes in New Zealand. It also offers potential to inform future service planning by identifying where improvements can be made in the current health system to promote equity in access to health services for those in New Zealand.