Project description:BackgroundPredicting allograft failure in kidney transplant recipients can help plan renal replacement therapy and guide patient-provider communication. The kidney failure risk equation (KFRE) accurately predicts the need for dialysis in patients with chronic kidney disease (CKD), but has not been validated in kidney transplant recipients.ObjectiveWe sought to validate the 4-variable KFRE (age, sex, estimated glomerular filtration rate [eGFR], and urine albumin-to-creatinine ratio [ACR]) for prediction of 2- and 5-year death-censored allograft failure.DesignRetrospective cohort study.SettingFour independent North American Cohorts from Ontario, Canada; Alberta, Canada; Manitoba, Canada; and Wisconsin, United States, between January 1999 and December 2017.PatientsAdult kidney transplant patients at 1-year posttransplantation.MeasurementsKidney failure risk as measured by the KFRE (eGFR, urine ACR, age, and sex).MethodsWe included all adult patients who had at least 1 serum creatinine and at least 1 urine ACR measurement approximately 1 year following kidney transplantation. The performance of the KFRE was evaluated using the area under the receiver operating characteristic curve (C-statistic). C-statistics from the 4 cohorts were meta-analyzed using random-effects models.ResultsA total of 3659 patients were included. Pooled C-statistics were good in the entire population, at 0.81 (95% confidence interval: 0.72-0.91) for the 2-year KFRE and 0.73 (0.67-0.80) for the 5-year KFRE. Discrimination improved among patients with poorer kidney function (eGFR < 45 mL/min/1.73 m2), with a C-statistic of 0.88 (0.78-0.98) for the 2-year KFRE and 0.83 (0.74-0.91) for the 5-year KFRE.LimitationsThe KFRE does not predict episodes of acute rejection and there was heterogeneity between cohorts.ConclusionsThe KFRE accurately predicts kidney failure in kidney transplant recipients at 1-year posttransplantation. Further validation in larger cohorts with longer follow-up times can strengthen the case for clinical implementation.

Project description:Rationale & objectiveThe Kidney Failure Risk Equation (KFRE) is a simple widely validated prediction model using age, sex, estimated glomerular filtration rate, and urinary albumin-creatinine ratio to predict the risk for end-stage kidney disease. Data are limited for its applicability to kidney transplant recipients.Study designValidation study of the KFRE as a post hoc analysis of the Folic Acid for Vascular Outcomes Reduction in Transplantation (FAVORIT) Trial.Setting & participantsAdult kidney transplant recipients with functioning kidney allografts at least 6 months posttransplantation from 30 centers in the United States, Canada, and Brazil. Participants with estimated glomerular filtration rates < 60 mL/min/1.73 m2 at study entry were included.Predictor2- and 5-year kidney failure risk predicted by the KFRE using variables at study entry.OutcomeGraft loss, defined by initiation of dialysis.Analytical approachDiscrimination of the KFRE was assessed using C statistics; calibration was assessed by plotting predicted risk against observed cumulative incidence of graft loss.Results2,889 participants were included. Within 2 years, 98 participants developed graft loss, 107 participants died with a functioning graft, and 129 participants were lost to follow-up, and by 5 years, 252 had developed graft loss, 265 died with a functioning graft, and 1,543 were lost to follow-up. The KFRE demonstrated accurate calibration and discrimination (C statistic, 0.85 [95% CI, 0.81-0.88] at 2 years and 0.81 [95% CI, 0.78-0.84] at 5 years); performance was similar regardless of donor type (living vs deceased) and graft vintage, with the noted exception of poorer calibration for graft vintage less than 2 years.LimitationsUnavailable cause of graft loss.ConclusionsThe KFRE accurately predicted the risk for graft loss among adult kidney transplant recipients with graft vintage longer than 2 years and may be a useful prognostic tool for nephrologists caring for kidney transplant recipients.

Project description:BackgroundThere is emerging evidence that the 4-variable Kidney Failure Risk Equation (KFRE) can be used for risk prediction of graft failure in transplant recipients. However, geographical validation of the 4-variable KFRE in transplant patients is lacking, as is whether the more extensive 8-variable KFRE improves predictive accuracy. This study aimed to validate the 4- and 8-variable KFRE predictions of the 5-year death-censored risk of graft failure in patients in the United Kingdom.MethodsA retrospective cohort study involved 415 transplant recipients who had their first renal transplant between 2003 and 2015 and were under follow-up at Salford Royal NHS Foundation Trust. The KFRE risk scores were calculated on variables taken 1-year post-transplant. The area under the receiver operating characteristic curves (AUC) and calibration plots were evaluated to determine discrimination and calibration of the 4- and 8-variable KFREs in the whole cohort as well as in a subgroup analysis of living and deceased donor recipients and in patients with an eGFR< 45 ml/min/1.73m2.ResultsThere were 16 graft failure events (4%) in the whole cohort. The 4- and 8-variable KFREs showed good discrimination with AUC of 0.743 (95% confidence interval [CI] 0.610-0.876) and 0.751 (95% CI 0.629-0.872) respectively. In patients with an eGFR< 45 ml/min/1.73m2, the 8-variable KFRE had good discrimination with an AUC of 0.785 (95% CI 0.558-0.982) but the 4-variable provided excellent discrimination in this group with an AUC of 0.817 (0.646-0.988). Calibration plots however showed poor calibration with risk scores tending to underestimate risk of graft failure in low-risk patients and overestimate risk in high-risk patients, which was seen in the primary and subgroup analyses.ConclusionsDespite adequate discrimination, the 4- and 8-variable KFREs are imprecise in predicting graft failure in transplant recipients using data 1-year post-transplant. Larger, international studies involving diverse patient populations should be considered to corroborate these findings.

Project description:BackgroundGraft loss is a major health concern for kidney transplant (KTx) recipients. It is of clinical interest to develop a prognostic model for both graft function, quantified by estimated glomerular filtration rate (eGFR), and the risk of graft failure. Additionally, the model should be dynamic in the sense that it adapts to accumulating longitudinal information, including time-varying at-risk population, predictor-outcome association, and clinical history. Finally, the model should also properly account for the competing risk by death with a functioning graft. A model with the features above is not yet available in the literature and is the focus of this research.MethodsWe built and internally validated a prediction model on 3,893 patients from the Wisconsin Allograft Recipient Database (WisARD) who had a functioning graft 6 months after kidney transplantation. The landmark analysis approach was used to build a proof-of-concept dynamic prediction model to address the aforementioned methodological issues: the prediction of graft failure, accounted for competing risk of death, as well as the future eGFR value, are updated at each post-transplant time. We used 21 predictors including recipient characteristics, donor characteristics, transplant-related and post-transplant factors, longitudinal eGFR, hospitalization, and rejection history. A sensitivity analysis explored a less conservative variable selection rule that resulted in a more parsimonious model with reduced predictors.ResultsFor prediction up to the next 1 to 5 years, the model achieved high accuracy in predicting graft failure, with the AUC between 0.80 and 0.95, and moderately high accuracy in predicting eGFR, with the root mean squared error between 10 and 18 mL/min/1.73m2 and 70%-90% of predicted eGFR falling within 30% of the observed eGFR. The model demonstrated substantial accuracy improvement compared to a conventional prediction model that used only baseline predictors.ConclusionThe model outperformed conventional prediction model that used only baseline predictors. It is a useful tool for patient counseling and clinical management of KTx and is currently available as a web app.

Project description:BackgroundIt is unknown whether meat intake is beneficial for long-term patient and graft survival in kidney transplant recipients (KTR).ObjectivesWe first investigated the association of the previously described meat intake biomarkers 1-methylhistidine and 3-methylhistidine with intake of white and red meat as estimated from a validated food frequency questionnaire (FFQ). Second, we investigated the association of the meat intake biomarkers with long-term outcomes in KTR.MethodsWe measured 24-h urinary excretion of 1-methylhistidine and 3-methylhistidine by validated assays in a cohort of 678 clinically stable KTR. Cross-sectional associations were assessed by linear regression. We used Cox regression analyses to prospectively study associations of log2-transformed biomarkers with mortality and graft failure.ResultsUrinary 1-methylhistidine and 3-methylhistidine excretion values were median: 282; interquartile range (IQR): 132-598 µmol/24 h and median: 231; IQR: 175-306 µmol/24 h, respectively. Urinary 1-methylhistidine was associated with white meat intake [standardized β (st β): 0.20; 95% CI: 0.12, 0.28; P < 0.001], whereas urinary 3-methylhistidine was associated with red meat intake (st β: 0.30; 95% CI: 0.23, 0.38; P < 0.001). During median follow-up for 5.4 (IQR: 4.9-6.1) y, 145 (21%) died and 83 (12%) developed graft failure. Urinary 3-methylhistidine was inversely associated with mortality independently of potential confounders (HR per doubling: 0.55; 95% CI: 0.42, 0.72; P < 0.001). Both urinary 1-methylhistidine and urinary 3-methylhistidine were inversely associated with graft failure independent of potential confounders (HR per doubling: 0.84; 95% CI: 0.73, 0.96; P = 0.01; and 0.59; 95% CI: 0.41, 0.85; P = 0.004, respectively).ConclusionsHigh urinary 3-methylhistidine, reflecting higher red meat intake, is independently associated with lower risk of mortality. High urinary concentrations of both 1- and 3-methylhistidine, of which the former reflects higher white meat intake, are independently associated with lower risk of graft failure in KTR. Future intervention studies are warranted to study the effect of high meat intake on mortality and graft failure in KTR, using these biomarkers.

Dataset Information

Accuracy of Kidney Failure Risk Equation in Transplant Recipients.

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Accuracy of Kidney Failure Risk Equation in Transplant Recipients.

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