eGFRdiff

Large negative discordance: eGFRcys is substantially lower than eGFRcr.

• Low creatinine production: low muscle mass, sarcopenia, frailty, inactivity, malnutrition, amputation, or chronic illness.
• High cystatin C production: obesity/adiposity, glucocorticoid use, metabolic/inflammatory disease.
• Shrunken pore syndrome: reduced glomerular pore diameter making cystatin C harder to filter, while smaller creatinine passes more easily.

In meta analysis by Liu et al. 2025, people with eGFRcys - eGFRcr < –15 had a 58% higher mortality risk and a 32% higher cardiovascular event risk, compared with people whose eGFRcys and eGFRcr were within ±15.

For kidney outcomes, this pattern was associated with a 63% higher risk of diabetic kidney disease incidence and, when modeled as a time-updated covariate, an 83% higher risk of ESKD.

Creatinine and cystatin C based eGFR are broadly concordant (similar). This increases confidence that the estimated kidney function is not being strongly distorted by major non-GFR determinants of either marker.

Large positive discordance: eGFRcys is substantially higher than eGFRcr.

• High creatinine production: high muscle mass, long distance running, strength training.
• High creatinine intake: creatine supplementation, high meat intake.
• Reduced tubular creatinine secretion: drugs such as trimethoprim, cimetidine, cobicistat, dolutegravir, rilpivirine, ranolazine, or pyrimethamine can raise serum creatinine (lower eGFRcr) without lowering measured GFR.
• Lower cystatin C production: hypothyroidism can lower cystatin C and make eGFRcys look higher.

In Liu et al. 2025, people with eGFRcys - eGFRcr ≥ +15 had a 39% lower mortality risk and a 29% lower cardiovascular event risk , compared with people whose eGFRcys and eGFRcr were within ±15 .

For kidney outcomes, this pattern was associated with a 61% lower risk of diabetic kidney disease incidence and, when modeled as a time-updated covariate, a 50% lower risk of ESKD.