Cystatin C-based equations: Enhancing accuracy in kidney function tests for type 2 diabetes

Table 1 Comparison of estimated glomerular filtration rate equations based on creatinine and/or cystatin C, highlighting biomarkers, clinical variables, advantages, and limitations

Equation	Biomarkers used	Variables used	Year/version	Advantages	Limitations	Main features
Cockcroft and Gault	Creatinine	Age, weight, sex	1976	Simple, used for drug dosing	Underestimates GFR in slim and overestimates GFR in obese older patients, not accurate for CKD staging, not validated in older population	Estimates creatinine clearance; less precise for eGFR. It has not been expressed using standardized creatinine values. It can overestimate kidney function
4-parameters MDRD	Creatinine	Age, sex, BSA	2002	Standardized, widely used in older studies	Less accurate for high eGFR values	Abstract version of the 1999 expanded formula with 6 variables. The equation has not been validated in patients over 70 years of age, though it is still applied in these subjects
CKD-EPI 2009	Creatinine	Age, sex, race	2009	Improved accuracy over MDRD, widely used	Still affected by muscle mass, not always optimal	Dominant equation; initially included ethnicity
BIS1	Creatinine	Age, sex	2012	Designed for older adults, more accurate	Limited external validation	Developed for elderly populations (BIS)
BIS2	Creatinine + cystatin C	Age, sex	2021	Improved accuracy in elderly, accounts for muscle mass loss	Limited validation outside European cohorts, higher cost	BIS equation combining creatinine and cystatin C; optimized for geriatric populations
FASCr	Creatinine	Age	2017	Applicable to all ages, better performance	Limited validation in elderly with CKD	FAS equation; better for diverse ages/clinical conditions
FASCr-Cys	Creatinine + cystatin C	Age	2017	Optimized for all ages, reliable in CKD	More expensive, not always available	Combined FAS version; versatile across populations
EKFC (creatinine)	Creatinine	Age, sex	2020	Ethnicity-independent, validated in healthy populations	Less accurate in acute kidney injury or extremes of BMI	Ethnicity- and sex-independent; based on mean creatinine in healthy individuals
CKD-EPICr-Cys	Creatinine + cystatin C	Age, sex	2021	Most accurate among different populations	Higher cost, requires additional testing	Combined CKD-EPI equation; recommended for elderly with impaired renal function
CKD-EPI 2021 (creatinine)	Creatinine	Age, sex	2021	Removes race coefficient, more equitable	Slight underestimation in Black individuals	Removed ethnicity factor; improved for multiethnic populations
CKD-EPI 2021 (cystatin C)	Cystatin C	Age, sex	2021	Unaffected by muscle mass, reliable in sarcopenia	Costly, influenced by inflammation/thyroid disorders	Cystatin C-specific CKD-EPI equation; alternative to creatinine
CKD-EPI 2021 (creatinine-cys)	Creatinine + cystatin C	Age, sex	2021	Most accurate among different populations	Higher cost, requires additional testing	Combined equation; recommended by KDIGO 2024 for accuracy
EKFC (cystatin C)	Cystatin C	Age, sex	2023	Ethnicity-independent, validated in multiple regions	Limited data in non-European populations	Cystatin C-specific EKFC equation; validated in Europe, United States, and Africa

GFR: Glomerular filtration rate; eGFR: Estimated glomerular filtration rate; CKD: Chronic kidney disease; MDRD: Modification of Diet in Renal Disease; EPI: Epidemiology collaboration; BMI: Body mass index; BIS: Berlin Initiative Study; FASCr: Full age spectrum from creatinine; BSA: Body surface area; Cys: Cystatin equation; FAS: Full age spectrum; EKFC: European Kidney Function Consortium; EPICr: Epidemiology collaboration equation from creatinine; KDIGO: Kidney disease: Improving global outcomes.