What should I do with a patient who has a discrepancy between their estimated Glomerular Filtration Rate (eGFR) with creatinine and cystatin C (43) and their eGFR with creatinine alone (61)?

Managing Discrepancy Between eGFR Measurements

When faced with a discrepancy between eGFR with creatinine and cystatin C (43) and eGFR with creatinine alone (61), you should use the combined creatinine-cystatin C eGFR value (eGFRcr-cys) for clinical decision-making as it provides the most accurate estimate of true kidney function. 1

Understanding the Discrepancy

This significant discrepancy (18 mL/min/1.73m²) between the two measurements requires careful consideration:

• The combined creatinine and cystatin C measurement (eGFRcr-cys of 43) is likely more accurate than the creatinine-only measurement (eGFRcr of 61) 2
• This places your patient in CKD Stage 3b (eGFR 30-44) rather than Stage 3a (eGFR 45-59)
• Large discrepancies between eGFRcr and eGFRcys occur in approximately 30% of patients 2

Clinical Approach

Step 1: Assess reliability of measurements

• Verify both tests were performed using standardized assays
• Consider factors that might affect creatinine or cystatin C independently:
  • Creatinine can be affected by muscle mass, diet, medications 1
  • Cystatin C can be affected by inflammation, steroid use, thyroid disorders 1

Step 2: Clinical decision-making

• Use the combined eGFRcr-cys value (43) for:
  • CKD staging and management decisions
  • Medication dosing adjustments
  • Risk assessment for CKD complications 1

Step 3: Additional evaluation

• Check for albuminuria/proteinuria to complete CKD assessment
• Consider underlying causes for the discrepancy:
  • Low muscle mass (would cause eGFRcr to overestimate true GFR)
  • Inflammatory conditions (may affect cystatin C levels)
  • Medications affecting creatinine secretion 3

Evidence-Based Rationale

Recent evidence strongly supports using the combined measurement:

• The 2024 KDIGO guidelines recommend using eGFRcr-cys when eGFRcr is less accurate and GFR affects clinical decision-making 1
• A 2023 study of 4,050 adults with measured GFR demonstrated that eGFRcr-cys provides the most accurate estimates among persons with discordant eGFRcr and eGFRcys 2
• When eGFRcr and eGFRcys are highly discordant, eGFRcr-cys is consistently more accurate than either alone 4

Clinical Implications

This discrepancy has important implications:

• Medication dosing: Many medications require adjustment at eGFR <45 ml/min/1.73m²
• Risk assessment: Patients with lower eGFRcys than eGFRcr have higher risk of adverse outcomes including:
  • Acute kidney injury (2.6x higher risk)
  • Cardiovascular events (1.4x higher risk)
  • All-cause mortality (2.6x higher risk) 5
• Medication safety: Patients with eGFRcys significantly lower than eGFRcr have increased risk of medication-related adverse events from renally-cleared drugs 6

Common Pitfalls to Avoid

• Don't ignore the discrepancy: A significant difference between eGFRcr and eGFRcys should not be dismissed
• Don't rely solely on creatinine: eGFRcr alone can overestimate kidney function in patients with reduced muscle mass
• Don't assume chronicity based on a single measurement: Confirm with repeat testing
• Don't overlook medication implications: Review and adjust dosages of renally-cleared medications based on the lower eGFR value

Follow-up Plan

• Repeat both measurements in 1-3 months to confirm stability or progression
• Evaluate for albuminuria if not already done
• Adjust medication dosages as needed based on the eGFRcr-cys value of 43
• Consider nephrology referral given the significant discrepancy and CKD Stage 3b classification