#559 Validation of the Kidney Failure Risk Equation (KFRE) in individuals with chronic kidney disease and multimorbidity
Authors: Walker Heather , Carrero Juan-Jesus , Sullivan Michael , Faucon Anne-Laure , Jani Bhautesh , Gallacher Katie , Mark Patrick 
Published: May 2024

Abstract

Background and Aims
Increasing numbers of individuals with chronic kidney disease (CKD) experience multiple long-term conditions (multimorbidity). Clinical guidance recommends the use of validated risk prediction equations, such as the kidney failure risk equation (KFRE), to guide referral to specialist kidney care services. However, multimorbidity may impact the accuracy of creatinine-based eGFR and bias the prognostic utility of KFRE. Equations with alternative filtration markers, such as Cystatin C eGFR (eGFRcys) or the combined creatinine and Cystatin C eGFR (eGFRcrcys), may improve KFRE's risk stratification and discrimination of future kidney failure risks.
This study aimed to validate the four-variable KFRE in individuals with CKD, with and without multimorbidity in a research-based cohort (UK Biobank) and a population-based cohort (Stockholm Creatinine Measurements project (SCREAM)). The study also assessed the performance of KFRE when using eGFRcr, eGFRcys and eGFRcrcys.

Method
Individuals from both cohorts were included if they had CKD, defined as eGFR&lt;60 mL/min/1.73 m2 by any of the three eGFR equations (eGFRcr, eGFRcys and eGFRcrcys), and had available proteinuria measurement at time of testing or within the previous 12 months. Multimorbidity was defined as the presence of two or more long-term conditions in addition to CKD and was grouped into multimorbidity clusters based on previous research. The outcome was kidney failure, defined as the need for long-term dialysis or kidney transplantation. KFRE performance at 2- and 5-years was assessed using the area under the receiver operating characteristic curve and c-index for discrimination and calibration curves for calibration.

Results
We included 24 489 individuals from UK Biobank and 42 902 individuals from SCREAM (mean age 62.8 (SD 5.6) and 70.1 (SD14.1), 54% and 66% female, respectively). In UK biobank, 14 998 individuals had multimorbidity, of which 5 375 had cardiometabolic multimorbidity. In SCREAM, 30 147 had multimorbidity and 17 854 cardiometabolic multimorbidity.
Overall, there were 252 and 312 kidney failure events and 1 108 and 1 471 death events in UK Biobank and 918 and 1 098 kidney failure events and 8 785 and 10 152 death events in SCREAM within 2- and 5-years respectively.
Model performance was consistent across both cohorts. Discrimination power of KFRE was good in individuals with and without multimorbidity and across the 2-year and 5-year models (Table 1). Calibration plots revealed over-estimation of risk at 2-years in both cohorts and under-estimation of risk at 5-years in patients with multimorbidity in UK Biobank. There was no improvement in model performance when using eGFRcys or eGFRcrcys compared to eGFRCr.
There was a higher cumulative incidence of both kidney failure and death in the multimorbidity group, with a prominent increase in risk of death over time compared to the no multimorbidity group. This was most evident in the SCREAM cohort (Fig. 1).

Conclusion
KFRE adequately predicts kidney failure in individuals with multimorbidity and either creatinine or cystatin C can be used. Given the high rates of mortality amongst people with multimorbidity, exploration of models that account for the competing risk of death is warranted.