External Validation of Proposed American Heart Association Algorithm for Cardiovascular Screening Before Kidney Transplantation.

BACKGROUND: Screening for cardiovascular disease is currently recommended before kidney transplantation. The present study aimed to validate the proposed algorithm by the American Heart Association (AHA-2022) considering cardiovascular findings and outcomes in kidney transplant candidates, and to compare AHA-2022 with the previous recommendation (AHA-2012). METHODS AND RESULTS: We applied the 2 screening algorithms to an observational cohort of kidney transplant candidates (n=529) who were already extensively screened for coronary heart disease by referral to cardiac computed tomography between 2014 and 2019. The cohort was divided into 3 groups as per the AHA-2022 algorithm, or into 2 groups as per AHA-2012. Outcomes were degree of coronary heart disease, revascularization rate following screening, major adverse cardiovascular events, and all-cause death. Using the AHA-2022 algorithm, 69 (13%) patients were recommended for cardiology referral, 315 (60%) for cardiac screening, and 145 (27%) no further screening. More patients were recommended cardiology referral or screening compared with the AHA-2012 (73% versus 53%; P<0.0001). Patients recommended cardiology referral or cardiac screening had a higher risk of major adverse cardiovascular events (hazard ratio [HR], 5.5 [95% CI, 2.8-10.8]; and HR, 2.1 [95% CI, 1.2-3.9]) and all-cause death (HR, 12.0 [95% [CI, 4.6-31.4]; and HR, 5.3 [95% CI, 2.1-13.3]) compared with patients recommended no further screening, and were more often revascularized following initial screening (20% versus 7% versus 0.7%; P<0.001). CONCLUSIONS: The AHA-2022 algorithm allocates more patients for cardiac referral and screening compared with AHA-2012. Furthermore, the AHA-2022 algorithm effectively discriminates between kidney transplant candidates at high, intermediate, and low risk with respect to major adverse cardiovascular events and all-cause death.

ß-Trace Protein and ß2-Microglobulin do not Improve Estimation of Glomerular Filtration Rate in Kidney Transplant Recipients Compared With Creatinine and Cystatin C.

BACKGROUND: Reliable estimates of glomerular filtration rate (eGFR) are important for detecting changes in graft function in kidney transplant recipients. Current eGFR equations are based on plasma creatinine and/or cystatin C; however, these are associated with significant bias. This study investigated if equations based on ß-trace protein (BTP) and ß2-microglobulin (B2M) performed better than the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on creatinine and cystatin C among kidney transplant recipients. METHODS: We included samples and data from the clinical trial CONTEXT. Glomerular filtration rate (GFR) was measured by plasma clearance of an exogenous marker. The eGFR was calculated using the CKD-EPI equations for estimating GFR from BTP and/or B2M and the 2021 CKD-EPI creatinine and creatinine-cystatin C equations. The GFR estimates were evaluated 3 (n = 82) and 12 (n = 64) months after transplant using mean bias, precision, and accuracy. Furthermore, we analyzed the ability of the equations to correctly classify the direction of changes in measured GFR from 3 to 12 months. RESULTS: Among the BTP- and B2M-based equations, the combined eGFR-BTP-B2M performed best with respect to precision (SD = 7.64 mL/min/1.73 m2) and accuracy (±10% from measured GFR = 36%). The eGFR-BTP-B2M and the eGFR-creatinine-cystatin C (2021) performed similarly when comparing precision, accuracy, and residuals (P = .481). The BTP- and/or B2M-based equations did not perform better than the eGFR-creatinine-cystatin C (2021) in correctly classifying the direction of changes in measured GFR from 3 to 12 months. CONCLUSIONS: ß-trace protein and/or B2M do not improve the estimation of GFR when compared with creatinine- and cystatin C-based 2021 CKD-EPI equations.

In a real-life setting, risk factors, coronary artery calcium score, and coronary stenosis at computed tomography angiography are associated with major adverse cardiovascular events and all-cause mortality among kidney transplant candidates.

Kidney failure is associated with an increased risk of cardiovascular disease and death. This single-center, a retrospective study evaluated the association between risk factors, coronary artery calcium score (CACS), coronary computed tomography angiography (CTA), major adverse cardiovascular events (MACEs), and all-cause mortality in kidney transplant candidates. Data on clinical risk factors, MACE, and all-cause mortality were collected from patient records. A total of 529 kidney transplant candidates were included (median follow-up of 4.7 years). CACS was evaluated in 437 patients and CTA in 411. Both the presence of ≥3 risk factors, CACS of ≥400, as well as multiple-vessel stenoses or left main artery disease predicted MACE (hazard ratio, 2.09; [95% confidence interval, 1.35-3.23]; 4.65 [2.20-9.82]; 3.70 [1.81-7.57]; 4.90 [2.40-10.01]) and all-cause mortality (harad ratio, 4.44; [95% confidence interval, 2.54-7.76]; 4.47 [2.22-9.02]; 2.82 [1.34-5.94]; 5.41 [2.81-10.41]) in univariate analyses. Among patients eligible for CACS and CTA (n = 376), only CACS and CTA were associated with both MACE and all-cause mortality. In conclusion, risk factors, CACS, and CTA provide information on the risk of MACE and mortality in kidney transplant candidates. An additional value of CACS and CTA compared with risk factors was observed for the prediction of MACE in a subpopulation undergoing both CACS and CTA.

Race-free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study.

OBJECTIVE: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients. DESIGN: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials). PARTICIPANTS: 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021. MAIN OUTCOME MEASURE: The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. RESULTS: The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient's creatinine level, age, and sex (https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/). CONCLUSION: A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys. TRIAL REGISTRATION: ClinicalTrials.gov NCT05229939.

Endotrophin Levels Are Associated with Allograft Outcomes in Kidney Transplant Recipients.

Early prediction of kidney graft function may assist clinical management, and for this, reliable non-invasive biomarkers are needed. We evaluated endotrophin (ETP), a novel non-invasive biomarker of collagen type VI formation, as a prognostic marker in kidney transplant recipients. ETP levels were measured with the PRO-C6 ELISA in the plasma (P-ETP) of 218 and urine (U-ETP/Cr) of 172 kidney transplant recipients, one (D1) and five (D5) days, as well as three (M3) and twelve (M12) months, after transplantation. P-ETP and U-ETP/Cr at D1 (P-ETP AUC = 0.86, p < 0.0001; U-ETP/Cr AUC = 0.70, p = 0.0002) were independent markers of delayed graft function (DGF) and P-ETP at D1 had an odds ratio of 6.3 (p < 0.0001) for DGF when adjusted for plasma creatinine. The results for P-ETP at D1 were confirmed in a validation cohort of 146 transplant recipients (AUC = 0.92, p < 0.0001). U-ETP/Cr at M3 was negatively associated with kidney graft function at M12 (p = 0.007). This study suggests that ETP at D1 can identify patients at risk of delayed graft function and that U-ETP/Cr at M3 can predict the future status of the allograft. Thus, measuring collagen type VI formation could aid in predicting graft function in kidney transplant recipients.

A comparison of four established GFR formulas to estimate measured GFR and changes in GFR in adult kidney transplant recipients.

The accurate assessment of glomerular filtration rate (GFR) is important in the follow-up of kidney transplant recipients in order to identify graft dysfunction. A number of formulas have been proposed to calculate GFR from endogenous plasma markers such as creatinine or cystatin C since measuring GFR using exogenous markers is troublesome. This study compares and evaluates the ability of four different GFR formulas to estimate kidney graft function and to detect changes in GFR in kidney transplant recipients. The study included patients from the prospective, multicenter CONTEXT trial in kidney transplant recipients. GFR was measured using plasma clearance of 51Cr-EDTA and estimated using the MDRD, CKD-EPI Creatinine, CKD-EPI Cystatin C and CKD-EPI Cystatin C + Creatinine equations at three (n = 83) and twelve (n = 65) months post-transplantation. For each formula mean bias, precision, and accuracy were evaluated. The MDRD equation had the lowest mean bias (0.2 ml/min/1.73 m2), whereas the CKD-EPI Cystatin C + Creatinine equation had the highest precision (8 ml/min/1.73 m2). Accuracy at three months were similar for all equations (P30 > 80%) except for the CKD-EPI Cystatin C equation, which performed poorer (P30 = 55%). None of the formulas evaluated avoided misclassification of changes in GFR. The most optimal combination of precision and accuracy suggests the use of CKD-EPI Creatinine + Cystatin C equation in kidney transplant recipients.