1. Long-Term Prognostic Value for Patients with Chronic Heart Failure of Estimated Glomerular Filtration Rate Calculated with the New CKD-EPI Equations Containing Cystatin C E. Zamora, J. Lupón, M. de Antonio, J. Vila, J. Peñafiel, A. Galán, A. Urrutia, M. Domingo, and A. Bayes-Genis March 2014 www.clinchem.org/content/60/3/481.full © Copyright 2014 by the American Association for Clinical Chemistry

2. © Copyright 2009 by the American Association for Clinical Chemistry Introduction  Background  Correct estimation of renal function is crucial in assessing prognosis of patients with heart failure (HF).  Recently, two new equations have been proposed to calculate estimated glomerular filtration rate (eGFR) with cystatin C alone or both creatinine and cystatin C:  CKD-EPI-cystatin C  CKD-EPI-creatinine-cystatin C  Aims  To assess the prognostic value of eGFR estimated by these new equations in outpatients with HF.

3. © Copyright 2009 by the American Association for Clinical Chemistry Measurements of performance  Discrimination  The area under the ROC curve (AUC) summarized the diagnostic discrimination.  We used the index of rank correlation, Somers D, which incorporates information from censored data.  AUCs between models were compared with 10,000 bootstrapping replicates.  Calibration  The D’Agostino–Nam version of the Hosmer–Lemeshow calibration test was used to calculate 2 values.  In addition, the Bayesian information criterion (BIC), the Akaike information criterion (AIC), and the Brier score were calculated for each model.  Reclassification  Two main statistics were used to assess reclassification. The integrated discrimination improvement (IDI) and the net reclassification improvement (NRI).

4. © Copyright 2009 by the American Association for Clinical Chemistry QUESTION  Is it important to assess in heart failure the prognostic value of eGFR calculated with the newer equations?

5. © Copyright 2009 by the American Association for Clinical Chemistry Table 1. Patient demographics, baseline clinical data, and treatments. Data are n (%) or median (25th, 75th percentile) unless noted otherwise

6. © Copyright 2009 by the American Association for Clinical Chemistry Figure 1. Long-term Kaplan–Meier survival curves according to National Kidney Foundation eGFR categories for all equations. (A) MDRD-4-IDMS. (B) CKD-EPI. (C) CKD-EPI-cystatin C. (D) CKD-EPI-creatinine- cystatin C.

7. © Copyright 2009 by the American Association for Clinical Chemistry Table 2. Multivariable Cox regression analysis for risk of death based on eGFR National Kidney Foundation categories a from all equations. a Categories IV and V of the National Kidney Foundation have been merged into 1 category for reasons of sample size. b I–II vs III–IV.

8. © Copyright 2009 by the American Association for Clinical Chemistry Figure 2. Hazard ratios for death from any cause according to eGFR as calculated with each of the 4 equations. The graphs show associations by plotting the hazard ratio versus a reference eGFR, which is indicated by diamond at 95 mL·min -1 ·(1.73 m 2 ) -1. Coefficients per 1-mL·min -1 ·(1.73 m 2 ) -1 eGFR increment have been calculated in each eGFR interval (i.e., 30, 30 to 60, 60 to 90, 90+), and then a coefficient resulting from the addition of these coefficients has been created for all eGFR values.

9. © Copyright 2009 by the American Association for Clinical Chemistry QUESTION  What is the likely explanation for the large differences in HR (prognostic implication) found in the different equations to estimate a given eGFR?

10. © Copyright 2009 by the American Association for Clinical Chemistry Table 3. Performance for risk of death prediction at 4 years of CKD-EPI-cystatin C and CKD-EPI-creatinine-cystatin C compared to MDRD-4-IDMS equation. a P < 0.001; b P =0.51; c P =0.11; d P =0.76; e P =0.045 Table 3

11. © Copyright 2009 by the American Association for Clinical Chemistry Table 4. Performance for risk of death prediction at 4 years of CKD-EPI-cystatin C and CKD-EPI-creatinine-cystatin C compared to CKD-EPI equation. a P < 0.001; b P =0.68; c P =0.11; d P =0.76; e P =0.003; f P =0.360 Table 4

12. © Copyright 2009 by the American Association for Clinical Chemistry Figure 3. AUC for risk of death prediction at 4 years according to eGFR calculated with the 4 equations. The best AUC was obtained with CKD-EPI-cystatin C equation.

13. © Copyright 2009 by the American Association for Clinical Chemistry QUESTION  Why do you think CKD-EPI-cystatin C was the best-performing prognostically, despite prior studies that found it is not the more accurate equation for estimating real eGFR (compared with isotopic GFR)?

14. © Copyright 2009 by the American Association for Clinical Chemistry Conclusions  The two new CKD-EPI equations containing cystatin C are useful for HF risk stratification and show better prognostic performance than creatinine-only based eGFR equations, mostly in patients with intermediate eGFR.  These equations seem appropriate for assessing prognosis of HF patients with moderate renal insufficiency.

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