How does prednisone affect cystatin C (Cystatin C) estimated glomerular filtration rate (eGFR)?

How Prednisone Affects Cystatin C eGFR

Direct Answer

Prednisone artificially elevates serum cystatin C levels without impairing actual kidney function, causing cystatin C-based eGFR (eGFRcys) to falsely underestimate true glomerular filtration rate. 1

Mechanism of Effect

Cystatin C Elevation Without Renal Impairment

• Prednisone significantly increases serum cystatin C concentrations by approximately 30% (from 1.24 mg/L to 1.61 mg/L) after just 2 weeks of treatment, independent of any change in actual kidney function. 1

• This elevation occurs through non-renal mechanisms, likely related to increased cystatin C production or altered metabolism from corticosteroid effects on cellular function. 1

• Paradoxically, prednisone actually improves measured GFR slightly while simultaneously raising cystatin C levels, creating a false impression of worsening kidney function when using eGFRcys. 1, 2

Dose-Dependent Relationship

• The effect is dose-dependent, with prednisolone doses ≥0.170 mg/kg/day causing clinically significant divergence between eGFRcys and creatinine-based eGFR (eGFRcr). 3

• At this threshold dose, the eGFRcys/eGFRcr ratio falls below 0.79 with 62.4% sensitivity and 84.7% specificity, indicating substantial underestimation of GFR by cystatin C. 3

• The correlation between prednisolone dose and eGFRcys/eGFRcreat divergence becomes markedly stronger (rs = -0.434) at doses above this threshold. 3

Clinical Implications from Guidelines

When to Avoid Cystatin C

• The KDIGO 2024 guidelines explicitly identify exogenous steroid use as a source of error in eGFRcr-cys, recommending against relying on cystatin C-based estimates in patients receiving corticosteroids. 4

• In steroid-treated patients, eGFRcr (creatinine-based) is more reliable than eGFRcys for assessing kidney function, despite creatinine's own limitations. 4

Preferred Approach in Steroid Users

• For patients on corticosteroids requiring accurate GFR assessment, use creatinine-based eGFR or measured GFR using exogenous filtration markers rather than cystatin C-based estimates. 4, 5

• The combined eGFRcr-cys equation should be avoided in steroid-treated patients, as the cystatin C component will artificially lower the estimate. 4, 5

Comparative Effects on Different Markers

Creatinine vs. Cystatin C Response

• Prednisone has opposite effects on the two markers: it increases serum creatinine (from 89.66 to 76.55 μmol/L) through catabolic effects and increased creatinine production, while simultaneously elevating cystatin C levels. 1, 2

• Despite raising plasma creatinine concentration, prednisone actually increases true GFR (from 93 to 102 mL/min/1.73 m²) and urinary creatinine excretion, demonstrating improved kidney function. 2

• Glucocorticoids have less impact on the diagnostic accuracy of cystatin C compared to beta-trace protein (another GFR marker), but cystatin C is still significantly affected. 6

Practical Recommendations

Monitoring Kidney Function in Steroid-Treated Patients

• Use creatinine-based eGFR as the primary method for monitoring kidney function in patients receiving prednisone or other corticosteroids. 4, 5

• If more accurate GFR assessment is needed for critical decisions (drug dosing, CKD staging), measure GFR directly using plasma or urinary clearance of exogenous filtration markers rather than relying on cystatin C. 4

• Avoid ordering cystatin C tests in patients on corticosteroids unless you are prepared to interpret falsely elevated values that do not reflect true kidney function. 1, 3

Interpreting Pre-Existing Cystatin C Values

• If cystatin C was measured before steroid initiation and shows elevation after starting prednisone, do not interpret this as worsening kidney function—it is an expected pharmacologic effect of the corticosteroid. 1

• Consider the timing: significant cystatin C elevation can occur within 2 weeks of starting prednisone therapy. 1

Common Pitfalls to Avoid

• Do not use eGFRcys or eGFRcr-cys for drug dosing decisions in patients receiving corticosteroids, as this will lead to underdosing of renally eliminated medications. 4, 7

• Do not assume kidney function has declined based solely on rising cystatin C levels in steroid-treated patients without corroborating evidence from creatinine-based estimates or measured GFR. 1

• Be aware that even "low-dose" prednisone (≥0.170 mg/kg/day, approximately 10-12 mg daily in a 70 kg adult) can cause clinically significant cystatin C elevation. 3