What is the management for a patient with impaired renal function and discrepant eGFR estimates between creatinine (58) and Cystatin C (CysC) (70) with normal uACR?

Management of Discordant eGFR Values

Use the combined creatinine-cystatin C equation (eGFRcr-cys) as your definitive estimate of kidney function, which in this case would average around 64 mL/min/1.73 m², confirming Stage 3a CKD. 1, 2

Understanding the Discordance

Your patient demonstrates a common clinical scenario where eGFRcr (58) and eGFRcys (70) differ by approximately 21%, which constitutes significant discordance (>20% difference). 3, 4

• Discordant eGFR values occur in approximately 55% of patients in real-world practice, making this a frequent clinical challenge rather than an exception. 5
• When eGFRcys is higher than eGFRcr (as in your patient), the creatinine-based estimate is typically underestimating true kidney function, often due to reduced muscle mass, malnutrition, or other non-GFR determinants of creatinine. 1, 4

The Combined Equation is Superior in Discordance

The KDIGO 2024 guidelines explicitly recommend using eGFRcr-cys when there is discordance between creatinine and cystatin C estimates. 1, 2

• In cases of discordance, eGFRcr-cys demonstrates 84% accuracy (P30) compared to only 50% for creatinine alone and 73% for cystatin C alone when validated against measured GFR. 4
• The combined equation had a median bias of only 0.8 mL/min/1.73 m² in discordant cases, compared to 15.0 mL/min/1.73 m² overestimation by creatinine alone. 5
• This superior performance holds true across patients with cardiovascular disease, heart failure, diabetes, liver disease, and cancer—populations traditionally underrepresented in research. 5

Clinical Implications and Risk Stratification

Despite normal uACR, this patient requires careful monitoring because the discordance itself carries prognostic significance:

• Patients with eGFRcys lower than eGFRcr (opposite of your patient) have 2.6-fold higher risk of acute kidney injury, 2.0-fold higher risk of heart failure, and 2.6-fold higher risk of death. 3
• Your patient's pattern (eGFRcys higher than eGFRcr) actually suggests lower cardiovascular risk compared to those with negative discordance. 6, 3
• However, the combined eGFRcr-cys of approximately 64 mL/min/1.73 m² still places this patient in Stage 3a CKD (GFR 45-59 mL/min/1.73 m²), which requires appropriate CKD management even without albuminuria. 1, 2

Medication Dosing Considerations

Use the combined eGFRcr-cys value (approximately 64 mL/min/1.73 m²) for all medication dosing decisions. 1, 7

• Patients with eGFR discordance have 2.30-fold higher odds of supratherapeutic vancomycin levels when dosing is based on creatinine alone. 7
• Discordance increases risk of trimethoprim-sulfamethoxazole-related hyperkalemia (24% vs 12%), baclofen-induced neurotoxicity, and supratherapeutic digoxin levels. 7
• The creatinine-based eGFR of 58 would underestimate this patient's true kidney function, potentially leading to underdosing of renally-cleared medications. 4, 5

Ongoing Management Algorithm

1. Confirm CKD Stage 3a diagnosis using eGFRcr-cys ≈64 mL/min/1.73 m² despite normal uACR. 1, 2

2. Investigate causes of the discordance by assessing:

   • Muscle mass (sarcopenia, malnutrition, muscle wasting diseases) 1, 2
   • Dietary factors (low-protein, ketogenic, or vegetarian diets) 1
   • Medications affecting creatinine secretion 1
   • Inflammatory states or thyroid dysfunction (which affect cystatin C) 2

3. Repeat both creatinine and cystatin C in 3 months to confirm stability and recalculate eGFRcr-cys. 1

4. Monitor for CKD progression with serial eGFRcr-cys measurements rather than relying on creatinine alone. 1, 2

5. Consider measured GFR (iohexol or iothalamate clearance) only if critical decisions depend on precise GFR assessment, such as living kidney donation evaluation or high-risk chemotherapy dosing. 1, 2

Critical Pitfalls to Avoid

• Never rely on creatinine-based eGFR alone when cystatin C data is available—this leads to misclassification in 29-32% of patients. 8
• Do not dismiss the CKD diagnosis simply because uACR is normal; 21% of CKD patients have reduced eGFR without albuminuria. 2
• Avoid using either eGFRcr or eGFRcys individually for clinical decisions when discordance exists—the combined equation is substantially more accurate. 4, 5
• Do not assume the higher eGFR value is correct—in discordant cases, the combined equation often falls between the two values and represents the most accurate estimate. 4, 5