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The aim of the present study was to extend the creatinine-based Lund-Malmö GFR equation for use with rescaled cystatin C (r-LMR Cys ) and validate it against measured GFR (mGFR) in the EKFC cystatin C cohort of children ( n  = 2,293) and adults ( n  = 7,727). Rescaling was obtained by dividing each biomarker by a Q-value, representing the population-specific median biomarker level among healthy individuals. Validation included median bias/precision/accuracy (percent estimates within ±30% of mGFR, P 30 ). Performance was compared with the EKFC-equation (EKFC Cys ), the CAPA cystatin C equation, the corresponding equations based on rescaled creatinine (r-LMR Cr and EKFC Cr ) and the arithmetic mean of r-LMR Cr and CAPA (r-LMR Cr +CAPA), r-LMR Cr and r-LMR Cys (r-LMR Mean ), and EKFC Cr and EKFC Cys (EKFC Mean ). The overall P 30 of r-LMR Cys in adults was 86.2% (95% CI 85.4%-86.9%), which was 6.6 percentage points (pp; 95% CI 5.8-7.4 pp) higher than for CAPA and similar to r-LMR Cr (P 30 87.4%, 95% CI 86.6%-88.1%). r-LMR Cys and EKFC Cys exhibited similar performance both overall and across subgroups of age, sex, GFR and BMI and in children. All three arithmetic mean equations had similar P 30 -accuracy and generally performed better than the corresponding single-marker equations. Our results show that the Lund-Malmö GFR equation can be adapted for use with rescaled cystatin C with performance that is similar to the best-performing equations based on rescaled creatinine. The generality of the applied biomarker rescaling principle implies that the future demand for population- and biomarker-specific GFR estimating equations can be expected to decrease substantially.

Background: A new cystatin C based European Kidney Function Consortium (EKFC CysC ) equation was recently developed for adults, using the same mathematical form as the previously published full age spectrum creatinine based EKFC-equation (EKFC Crea ). In the present study the cystatin C based EKFC-equation is extended to children, by defining the appropriate cystatin C rescaling factor Q CysC ., Methods: Rescaling factor Q CysC for cystatin C was defined as: a) 0.83 mg/L, exactly as it was defined for young adults in the adult equation, and b) a more complex Q CysC -age relationship based on 4 th degree cystatin C-age polynomials after evaluation of data from Uppsala, Stockholm and Canada and aggregated data from Germany. The EKFC CysC equation was then validated in an independent dataset in European children (n = 2,293) with measured GFR, creatinine, cystatin C, age, height and sex available., Results: The EKFC CysC with the simple Q CysC -value of 0.83 had a bias of -7.6 [95%CI -8.4;-6.5] mL/min/1.73 m 2 and a P30-value of 85.8% [95%CI 84.4;87.3] equal to the EKFC CysC with the more complex 4 th degree Q CysC -value. The arithmetic mean of the EKFC Crea and EKFC CysC with the simple Q CysC of 0.83 had a bias of -4.0 [95%CI -4.5;-3.1] mL/min/1.73 m 2 and P30 of 90.4% [95%CI 89.2;91.6] similar to using the more complex 4 th degree Q CysC -polynomial., Conclusion: Using exactly the same Q CysC of 0.83 mg/L, the adult EKFC CysC can easily be extended to children, with some bias but acceptable P30-values. The arithmetic mean of EKFC Crea and EKFC CysC results in bias closer to zero and P30 slightly over 90%., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)