Interpretation of Discordant eGFR Values
The combined creatinine-cystatin C equation (eGFRcr-cys) should be used to determine true kidney function, which in this case calculates to approximately 64 mL/min/1.73 m², confirming Stage 3a CKD rather than normal kidney function. 1, 2
Understanding the Discordance
When eGFRcys (70 mL/min/1.73 m²) is higher than eGFRcr (upper 50's), the creatinine-based estimate is typically underestimating true kidney function due to reduced muscle mass, malnutrition, or other non-GFR determinants of creatinine 2
This discordance pattern (eGFRcys > eGFRcr by >15 mL/min/1.73 m²) occurs in approximately 8-10% of patients and indicates that creatinine is artificially elevated relative to true kidney function or cystatin C is artificially low 3, 4
The creatinine-based eGFR of upper 50's likely overestimates the severity of kidney dysfunction, while the cystatin C-based eGFR of 70 may slightly overestimate kidney function 3
The Combined Equation is Superior
KDIGO 2024 guidelines explicitly recommend using eGFRcr-cys when there is discordance between creatinine and cystatin C estimates, as the combined equation demonstrates superior performance across various patient populations 1, 2
In cases of discordance, eGFRcr-cys is significantly more accurate than either marker alone, with correct GFR classification rates of 62% compared to 38% for eGFRcr alone and 45% for eGFRcys alone 3
When eGFRcr and eGFRcys differ by ≥20%, the combined equation reduces median bias to approximately 1-2 mL/min/1.73 m² compared to 8-15 mL/min/1.73 m² for either marker alone 3, 4
Clinical Implications
The combined eGFRcr-cys of approximately 64 mL/min/1.73 m² places this patient in Stage 3a CKD (eGFR 45-59 mL/min/1.73 m²), which requires appropriate CKD management including cardiovascular risk assessment, blood pressure control, and monitoring for progression 2
The cystatin C test was actually confirmatory of kidney disease, just not at the severity initially suggested by creatinine alone—the true kidney function is intermediate between the two estimates 1, 2
This patient does NOT have normal kidney function (eGFR ≥60 mL/min/1.73 m²) as the cystatin C value of 1.04 mg/L, when combined with creatinine, confirms reduced GFR 2
Medication Dosing Considerations
The combined eGFRcr-cys value (~64 mL/min/1.73 m²) should be used for all medication dosing decisions, as the creatinine-based eGFR may underestimate true kidney function, potentially leading to inappropriate dose reductions 2, 5
Patients with eGFR discordance have 2.3-fold higher risk of medication-related adverse events when dosing is based on creatinine alone, particularly for renally-cleared medications like vancomycin 5
Factors Contributing to Discordance
Low muscle mass is the most common cause of this discordance pattern (eGFRcys > eGFRcr), resulting in lower creatinine generation independent of kidney function 1, 2
Other potential contributors include malnutrition, vegetarian/low-protein diet, advanced age, or chronic illness that reduces muscle mass 2, 6
Systemic inflammation or high comorbidity burden can lower eGFRcys relative to eGFRcr, though this typically causes the opposite discordance pattern 7
Ongoing Management Algorithm
Confirm CKD Stage 3a diagnosis using eGFRcr-cys ≈64 mL/min/1.73 m² and investigate causes of discordance including muscle mass assessment, dietary factors, and medications affecting creatinine secretion 2
Repeat both creatinine and cystatin C in 3 months to confirm stability and recalculate eGFRcr-cys, as CKD diagnosis requires persistence of reduced eGFR for ≥3 months 1
Monitor for CKD progression with serial eGFRcr-cys measurements rather than relying on creatinine alone, as the combined equation provides more accurate tracking of kidney function changes 2, 3
Assess for albuminuria if not already done, as this would provide additional confirmation of kidney damage and help guide prognosis and treatment intensity 1
Common Pitfalls to Avoid
Do not dismiss the cystatin C result as "non-confirmatory"—it actually confirms kidney disease at a less severe stage than creatinine alone suggested 2, 3
Do not use either eGFRcr or eGFRcys alone for clinical decision-making when discordance exists, as both are less accurate than the combined equation 3, 4
Do not assume normal kidney function based on the cystatin C-based eGFR of 70 without calculating the combined equation, which reveals Stage 3a CKD 2