Dataset Information

The Kidney Failure Risk Equation for Prediction of Allograft Loss in Kidney Transplant Recipients.

ABSTRACT:

Rationale & objective

The 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 design

Validation study of the KFRE as a post hoc analysis of the Folic Acid for Vascular Outcomes Reduction in Transplantation (FAVORIT) Trial.

Setting & participants

Adult 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.

Predictor

2- and 5-year kidney failure risk predicted by the KFRE using variables at study entry.

Outcome

Graft loss, defined by initiation of dialysis.

Analytical approach

Discrimination of the KFRE was assessed using C statistics; calibration was assessed by plotting predicted risk against observed cumulative incidence of graft loss.

Results

2,889 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.

Limitations

Unavailable cause of graft loss.

Conclusions

The 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.

SUBMITTER: Chu CD

PROVIDER: S-EPMC7729246 | biostudies-literature | 2020 Nov-Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Kidney Failure Risk Equation for Prediction of Allograft Loss in Kidney Transplant Recipients.

Chu Chi D CD Ku Elaine E Fallahzadeh Mohammad Kazem MK McCulloch Charles E CE Tuot Delphine S DS

Kidney medicine 20201028 6

<h4>Rationale & objective</h4>The 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.<h4>Study design</h4>Validation study of the KFRE as a post hoc analysis of the Folic Acid for Vascular Outcomes Reduction in Transplantation (FAVORIT) Trial.<h4>Setting & ...[more]

PMID: 33319199

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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: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:BackgroundKidney tubulointerstitial fibrosis marks risk for allograft failure in kidney transplant recipients, but is poorly captured by estimated glomerular filtration rate (eGFR) or urine albumin-creatinine ratio (ACR). Whether urinary markers of tubulointerstitial fibrosis can noninvasively identify risk for allograft failure above and beyond eGFR and ACR is unknown.Study designCase-cohort study.Setting & participantsThe FAVORIT (Folic Acid for Vascular Outcome Reduction in Transplantation) Trial was a randomized double-blind trial testing vitamin therapy to lower homocysteine levels in stable kidney transplant recipients. We selected a subset of participants at random (n=491) and all individuals with allograft failure during follow-up (cases; n=257).PredictorUsing spot urine specimens from the baseline visit, we measured 4 urinary proteins known to correlate with tubulointerstitial fibrosis on biopsy (urine α1-microglobulin [A1M], monocyte chemoattractant protein 1 [MCP-1], and procollagen type III and type I amino-terminal amino pro-peptide).OutcomeDeath-censored allograft failure.ResultsIn models adjusted for demographics, chronic kidney disease risk factors, eGFR, and ACR, higher concentrations of urine A1M (HR per doubling, 1.73; 95% CI, 1.43-2.08) and MCP-1 (HR per doubling, 1.60; 95% CI, 1.32-1.93) were strongly associated with allograft failure. When additionally adjusted for concentrations of other urine fibrosis and several urine injury markers, urine A1M (HR per doubling, 1.76; 95% CI, 1.27-2.44]) and MCP-1 levels (HR per doubling, 1.49; 95% CI, 1.17-1.89) remained associated with allograft failure. Urine procollagen type III and type I levels were not associated with allograft failure.LimitationsWe lack kidney biopsy data, BK titers, and HLA antibody status.ConclusionsUrine measurement of tubulointerstitial fibrosis may provide a noninvasive method to identify kidney transplant recipients at higher risk for future allograft failure, above and beyond eGFR and urine ACR.

Project description:BackgroundIn chronic kidney disease, intensive systolic blood pressure (SBP) control reduces mortality at a cost of greater acute kidney injury risk. Kidney transplantation involves implantation of denervated kidneys and immunosuppressive medications that increase acute kidney injury risk. The optimal blood pressure (BP) target in kidney transplant recipients (KTRs) is uncertain. Prior observational studies from the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial demonstrate associations of lower SBP levels and reduced mortality risk, but the relationship of BP with kidney allograft function remains unknown. Thus, in FAVORIT, we investigated the relationship of SBP and diastolic blood pressure (DBP) with risk of kidney allograft failure and estimated glomerular filtration rate (eGFR) slope among stable KTRs.MethodsCox proportional hazards and multivariable linear regression models adjusted for demographics, transplant characteristics, comorbidities, baseline eGFR, and urine albumin-to-creatinine ratio were used to determine associations of SBP and DBP with time to a composite kidney outcome of ≥50% eGFR decline or dialysis dependence, and with annualized eGFR change, respectively. Multivariable restricted cubic spline plots were developed to evaluate the functional form of the relationships.ResultsAmong 3,598 KTRs, mean age was 52 ± 9 years, SBP was 136 ± 20 mm Hg, DBP was 79 ± 12 mm Hg, and eGFR was 49 ± 18 ml/minute/1.73 m2. There were 369 events of ≥50% eGFR decline or dialysis dependence during a mean follow-up of 4.0 ± 1.5 years. There was no association of either SBP (compared with SBP 120 to <130 mm Hg, hazard ratio (HR) for the SBP < 110 was 1.01 (95% confidence interval (CI) 0.60 to 1.70) and 130 to <140 was 0.89 (0.64 to 1.24)) or DBP (compared with DBP 70 to <80 mm Hg, HR for the DBP 60 to <70 was 1.00 (95% CI 0.74 to 1.34) and 80 to <90 was 0.90 (0.68 to 1.18)) with the kidney failure outcome or annualized eGFR slope, and, when examined using restricted cubic splines, there was no evidence of "J"- or "U"-shaped relationships.ConclusionsIn a large sample of stable KTRs, we found no evidence of thresholds at which lower BPs were related to higher risk of allograft failure or eGFR decline. In light of prior findings of mortality benefit at low SBP, these observational findings suggest lower BP may be beneficial in KTRs. This important question requires confirmation in future randomized trials in KTRs.

Project description:BACKGROUND:Pediatric patients with focal segmental glomerulosclerosis (FSGS) have high rates of disease recurrence and allograft failure after kidney transplantation, but there are few data for long-term survival posttransplantation. STUDY DESIGN:Retrospective cohort study. SETTING & PARTICIPANTS:12,303 pediatric patients (aged <18 years), including 1,408 (11%) patients with FSGS, who received a first kidney transplant in 1990 through 2009 and were followed up through June 2015 were identified from the US Renal Data System database. PREDICTORS:Primary cause of end-stage renal disease, FSGS or other. OUTCOMES:All-cause patient mortality and allograft loss. RESULTS:All-cause mortality significantly improved for patients with FSGS who underwent transplantation in the 2000s versus the 1990s (6.72 vs 12.24 deaths/1,000 patient-years; HR, 0.55; 95% CI, 0.39-0.78; P<0.001). Reductions in allograft loss were less dramatic (75.91 vs 89.05 events/1,000 patient-years; HR, 0.85; 95% CI, 0.74-0.98; P=0.02). After adjusting for baseline characteristics at the time of transplantation, patients with FSGS had similar rates of death compared with patients without FSGS (HRs of 0.81 [P=0.6] and 1.06 [P=0.2] among those who underwent transplantation in the 2000s and 1990s, respectively) despite higher rates of allograft loss (HRs of 1.17 [P=0.03] and 1.27 [P<0.001], respectively). Among patients who underwent transplantation in the 2000s, further adjustment for allograft failure as a time-varying covariate demonstrated a lower rate of death among patients with FSGS compared with those without FSGS (HR, 0.70; P=0.02). LIMITATIONS:Lack of information about certain risk factors for mortality, including duration of chronic kidney disease; missing data; and potential primary disease misclassification. CONCLUSIONS:Survival of pediatric kidney transplant recipients with FSGS improved between the 1990s and 2000s and was similar to that of recipients without FSGS. Interestingly, adjustment for allograft failure showed greater survival for pediatric patients with FSGS who underwent transplantation in the 2000s as compared with others, suggesting that effective interventions to decrease allograft loss due to disease recurrence may improve patient survival.

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

The Kidney Failure Risk Equation for Prediction of Allograft Loss in Kidney Transplant Recipients.

Rationale & objective

Study design

Setting & participants

Predictor

Outcome

Analytical approach

Results

Limitations

Conclusions

Publications

The Kidney Failure Risk Equation for Prediction of Allograft Loss in Kidney Transplant Recipients.

Similar Datasets

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