Cardiovascular event prediction in kidney transplant recipients: a new risk score derivation and internal validation

Background: Kidney transplant recipients (KTRs) have a cardiovascular (CV) risk 3 to 5-fold higher than that of the general population. CV disease represents the main cause of death in KTRs, both due to the presence of traditional risk factors and factors strictly related to transplant. The main CV risk calculators proved to be poorly predictive in the KTR population. We, therefore, aimed to compare the performance of CV risk scores already in use and to develop and validate a CV risk score in our KTRs population. Methods Our analysis included 371 adult KTRs in follow-up at the outpatient clinic from 1 January 2015 to 31 December 2016. The composite outcome was the occurrence of MACE. We compared the performance of two main CV risk calculators (Framingham Risk Score -FRS- and Patient Outcomes in Renal Transplantation-PORT-risk score). Thereafter, we built a predictive model selecting study variables by backward stepwise Cox regression. The risk score for each variable was weighted according to the hazard ratio (HR) of the final multivariable model. Internal and external validation of the prediction score and its discriminative capacity was assessed via area under the curve (AUC), and the calibration via the Hosmer–Lemeshow test. Results After a mean follow-up of 68 months, CV events occurred in 71 (19%) KTRs. FRS and PORT were demonstrated to have low predictive power in our population. The accuracy did not improve after adjustment for immunological and adjuntive transplant-related variables. Therefore, we derived a model including significative variables at multivariate analysis: age, dialysis vintage, systolic blood pressure, eGFR and 24-hour proteinuria. The model discrimination was good (Harrel’s c: 0.73, AIC 713). According to the HR, 3 points were attributed to age higher than 60 years and 24 h proteinuria higher than 1 g/d, 2 points to dialysis vintage longer than 5 years, systolic blood pressure higher than 140 mmHg and eGFR less than 30 ml/min/1.73m2. The new score demonstrated good discrimination (AUC 0.70) and acceptable calibration (Hosmer-Lemeshow test χ211.34, P=0.12). The new score was internally validated by 10-fold cross-validation (mean AUC 0.70, 95% CI 0.60-0.77). For each point of the new score, the risk of the event increased by 40% and a score higher than three was associated with a 4-fold increased risk of composite endpoint.