#5059 EXTERNAL VALIDATION OF THE KFRE AND GRAMS PREDICTION MODELS FOR DEATH AND KRT IN A SPANISH POPULATION WITH ADVANCED CHRONIC KIDNEY DISEASE
Authors: Valcarce Eduardo Gallego , Shabaka Amir , Ribera Ana María Tato , Landaluce-Triska Eugenia , León-Póo Mariana , Roldan Deborah , Gruss Enrique 
Published: June 2023

Abstract

Background and Aims
The Kidney Failure Risk Equation (KFRE) is used to predict the risk of kidney replacement therapy (KRT) initiation in the following 2 and 5 years, in patients with chronic kidney disease (CKD) stages G3-G5. The Grams model is applied exclusively to stage G4-G5 patients who have a higher risk of dying or requiring KRT. This model predicts both events, KRT and death, at 2 and 4 years, but unlike the KFRE, it considers the patient's death as a competing event with respect to the start of RRT. It has been suggested that the Grams model makes a more accurate prediction of the onset of KRT in the long term, since by including mortality as a competing event it does not overestimate the risk of KRT. However, there are few external validations of the Grams model to predict mortality in patients with CKD G4+. We performed an external validation of both models with respect to the start of KRT and mortality in a Spanish population with CKD G4+, followed up prospectively during 4-9 years.

Method
We conducted a prospective cohort analysis of incident patients followed in the Advanced Chronic Kidney Disease clinic of the Hospital Universitario Fundación Alcorcón, Spain between 1-1-2014 and 31-12-2018 who had CKD G4-G5. Clinical data was registered prospectively in a database at each visit to the clinic. Follow-up ended on 31-12-2022. For each patient, the follow-up time ranged from 4 to 9 years. The outcomes were: observed incidence of KRT (haemodialysis, peritoneal dialysis, or pre-emptive kidney transplantation) by 2, 4 and 5 years and death at 2 and 4 years before starting KRT. The predictors used in the study were calculated at the time of initial clinic referral and included the 2-year and 4-year Grams’ calculator risk scores (Grams-2 and Grams-4, respectively) for KRT and death and the 2-year and 5-year 4-variable KFRE scores for KRT (KFRE-2 and KFRE-5 respectively). We performed calibration and discrimination analyses to evaluate the performance of both predictive models. Discrimination was assessed by calculating the area under the ROC curve (C-statistic with 95% confidence interval). Calibration was assessed by using the Hosmer-Lemeshow test, through calculation of the slope and intercept, and visually by generating a calibration plot, evaluating the level of agreement between predicted probabilities versus observed outcomes. Overall model performance was evaluated using the Brier score as a composite measure of both model discrimination and calibration.

Results
We studied 347 patients, 31.1% were women, with a mean age of 72.1 ± 12.7 years, 52.4% with cardiovascular disease and 58.8% diabetics. At the start, the mean eGFR was 20.7 ± 5.0 ml/min and the median urine albumin-creatinine ratio was 327 (IQR 52-1118) mg/g. At 2, 4 and 5 years the percentage of patients who required KRT was 20.2%, 38.3% and 45.7% respectively, while 12.7% and 23.6% died at 2 and 4 years respectively, before starting KRT. For KTR both models had an excellent discrimination. For KFRE-2 and Grams-2 the AUC was 0.896 (95% CI 0.858-0.933) and 0.904 (95% CI 0.866-0.941) respectively, for Grams-4 the AUC was 0.842 (95% CI 0.801-0.884), and for KFRE-5 the AUC was 0.805 (95% CI 0.751-0.859). For death before KTR the Grams model demonstrated an acceptable discrimination, with an AUC of 0.726 (95% CI 0.646-0.806) and 0.749 (95% CI 0.690-0.809) for Grams-2 and Grams-4 respectively. There was excellent calibration for KRT for both models, the Hosmer-Lemeshow test presented a p&gt;0.05 in all cases, the Brier score was less than 0.20. The adjustment was very precise and only in the event of estimated risks greater than 70% at 2 and 4 years is the observed risk overestimated. The calibration of the Grams model to estimate mortality before starting KTR was also excellent, although for estimated risks greater than 50% at 4 years the observed risk is underestimated.

Conclusion
In a Spanish cohort of patients with CKD G4+, the Grams and KFRE models adequately estimate the risk of KRT. The Grams model provides an acceptable estimate of the risk of death before starting KRT at both 2 and 4 years. It can be considered for treatment planning and information for patients with CKD G4+.