GFR estimation based on standardized creatinine and cystatin C: A European multicenter analysis in older adults

Although recommended by the Kidney Disease Improving Global Outcomes, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI_CR) creatinine equation was not targeted to estimate glomerular filtration rate (eGFR) among older adults. The Berlin Initiative Study (BIS1_CR) equation was specifically developed in older adults, and the Lund-Malmö revised (LMR_CR) and the Full Age Spectrum (FAS_CR) equations have shown promising results in older adults. Our aim was to validate these four creatinine equations, including addition of cystatin C in a large multicenter cohort of Europeans ≥70 years. A total of 3226 individuals (2638 with cystatin C) underwent GFR measurement (mGFR; median, 44 mL/min/1.73 m²) using plasma iohexol clearance. Bias, precision (interquartile range [IQR]), accuracy (percent of estimates ±30% of mGFR, P₃₀), eGFR accuracy diagrams and probability diagrams to classify mGFR<45 mL/min/1.73 m² were compared. The overall results of BIS1_CR/CKD-EPI_CR/FAS_CR/LMR_CR were as follows: median bias, 1.7/3.6/0.6/-0.7 mL/min/1.73 m²; IQR, 11.6/12.3/11.1/10.5 mL/min/1.73 m²; and P₃₀, 77.5%/76.4%/80.9%/83.5% (significantly higher for LMR, p<0.001). Substandard P₃₀ (<75%) was noted for all equations at mGFR<30 mL/min/1.73 m², and at body mass index values <20 and ≥35 kg/m². LMR_CR had the most stable performance across mGFR subgroups. Only LMR_CR and FAS_CR had a relatively constant small bias across eGFR levels. Probability diagrams exhibited wide eGFR intervals for all equations where mGFR<45 could not be confidently ruled in or out. Adding cystatin C improved P₃₀ accuracy to 85.7/86.8/85.7/88.7 for BIS2_CR+CYS/CKD-EPI_CR+CYS/FAS_CR+CYS/MEAN_LMR+CAPA. LMR_CR and FAS_CR seem to be attractive alternatives to CKD-EPI_CR in estimating GFR by creatinine-based equations in older Europeans. Addition of cystatin C leads to important improvement in estimation performance.