CKD-EPI Cr-Cys eGFR 2021 (eGFRcr-cys)

Low creatinine usually reflects low muscle mass — sarcopenia, frailty, disuse atrophy.

Other causes: low protein intake or malnutrition, pregnancy (increased GFR and plasma volume expansion), and advanced liver disease (impaired hepatic creatine synthesis).

High creatinine usually reflects impaired kidney clearance — acute or chronic kidney disease, diabetic nephropathy, urinary obstruction, or reduced renal perfusion (dehydration, shock, congestive heart failure, renal artery atherosclerosis).

Increased production: rhabdomyolysis or muscle trauma, intense exercise (i.e. long distance running, bodybuilding), myocardial infarction, acromegaly, high cooked red meat intake and creatine supplementation.

Low Cystatin C is rarely clinically significant in isolation.

Common reasons: Kidney hyperfiltration, Hypothyroidism, Bladder cancer.

Low Cystatin C is associated with cognitive dysfunction and Alzheimer’s disease.

The dominant cause is reduced glomerular filtration — chronic kidney disease, acute kidney injury, or any condition impairing renal clearance.

Several non-renal factors also raise Cystatin C independently of GFR: hyperthyroidism, obesity, chronic inflammation, corticosteroid (and other immunosuppressant) therapy, current smoking, alcohol, older age.

Because of these confounders, Cystatin C is considered unreliable in patients with untreated thyroid disease or on chronic steroids.