What is the implication of a Cystatin C (Cystatin C) test result of 1.04 and a Cystatin C-based estimated Glomerular Filtration Rate (eGFR) of 70.0 on the diagnosis and treatment plan of a patient with previously suspected Chronic Kidney Disease (CKD) stage 3 based on creatinine-based eGFR measurements in the high 50's?

Cystatin C Testing Confirms CKD Stage 3a: Use Combined Equation for All Clinical Decisions

Your cystatin C-based eGFR of 70 mL/min/1.73 m² does NOT rule out CKD—instead, you should use the combined creatinine-cystatin C equation (eGFRcr-cys), which will provide the most accurate assessment and likely confirms Stage 3a CKD requiring appropriate management. 1

Understanding the Discordance Between Your Two eGFR Values

Your situation demonstrates a classic discordance pattern where:

• Creatinine-based eGFR: ~57 mL/min/1.73 m² (high 50's)
• Cystatin C-based eGFR: 70 mL/min/1.73 m²

The KDIGO guidelines explicitly state that when there is discordance between creatinine and cystatin C estimates, the combined equation (eGFRcr-cys) demonstrates superior performance and should be used for all clinical decision-making. 1 This is not a situation where you simply choose the "better" number—the combined equation mathematically integrates both biomarkers to provide the most accurate estimate. 1

Why the Combined Equation is Superior

The combined creatinine-cystatin C equation significantly outperforms either marker alone:

• eGFRcr-cys accuracy: 94.9% within 30% of measured GFR 2
• eGFRcr alone accuracy: 50% in discordant cases 2
• eGFRcys alone accuracy: 73% in discordant cases 2

When eGFR values differ by more than 20% between methods (as in your case), the combined equation is substantially more accurate than either alone. 2 The correct GFR classification rate is 62% for eGFRcr-cys compared to only 38% for eGFRcr alone and 45% for eGFRcys alone. 1

What Your Combined eGFR Likely Shows

Based on your values (creatinine-based ~57, cystatin C-based 70), your combined eGFRcr-cys is approximately 64 mL/min/1.73 m², which places you in Stage 3a CKD. 1 This is the value that should guide all clinical decisions, not the cystatin C-based estimate alone.

The KDIGO Confirmatory Testing Strategy

The KDIGO guidelines recommend measuring cystatin C in adults with eGFRcreat 45-59 mL/min/1.73 m² without markers of kidney damage to confirm CKD diagnosis. 3 However, the interpretation is NOT simply "if eGFRcys >60, CKD is ruled out." 3

The proper interpretation according to KDIGO:

• If eGFRcys OR eGFRcr-cys is <60 mL/min/1.73 m², CKD is confirmed 3
• If eGFRcys AND eGFRcr-cys are >60 mL/min/1.73 m², CKD is not confirmed 3

In your case, while eGFRcys is 70 (>60), the combined eGFRcr-cys is approximately 64 (<60), which confirms Stage 3a CKD. 1

Why Your Creatinine-Based eGFR Was Lower

When eGFRcys is higher than eGFRcr, 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 Low muscle mass is a common cause of this discordance pattern, resulting in lower creatinine generation independent of kidney function. 1

However, this does NOT mean your kidney function is normal—it means the combined equation provides the most accurate assessment by accounting for both biomarkers' strengths and limitations. 1

Critical Clinical Implications

Medication Dosing

The combined eGFRcr-cys value (~64 mL/min/1.73 m²) should be used for ALL medication dosing decisions. 1 Using the creatinine-based eGFR may underestimate true kidney function, potentially leading to inappropriate dose reductions, while using the cystatin C-based eGFR alone would overestimate kidney function and risk medication toxicity. 1

CKD Management

Your diagnosis is Stage 3a CKD (eGFRcr-cys ~64 mL/min/1.73 m²), which requires appropriate CKD management including:

• Blood pressure control targeting <130/80 mmHg if tolerated 1
• Assessment for albuminuria if not already done 1
• Cardiovascular risk reduction strategies 1
• Monitoring for CKD progression 1
• Nephrology referral consideration based on progression rate and other risk factors 1

Ongoing Monitoring

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. 1

Important Caveats About Cystatin C

While cystatin C is superior to creatinine in many situations, it has its own non-GFR determinants:

• Thyroid dysfunction (hypothyroidism increases cystatin C, hyperthyroidism decreases it) 1
• High levels of inflammation 1
• Exogenous steroid use 1
• Very high catabolic states 1

These factors should be considered when interpreting your results, though they do not negate the superiority of the combined equation. 1

What to Request from Your Laboratory

Ask your laboratory to calculate and report the combined creatinine-cystatin C eGFR (eGFRcr-cys) using the 2012 CKD-EPI equation. 2 The KDOQI commentary recommends reporting both eGFRcys and eGFRcr-cys whenever cystatin C is measured. 3, 2 This ensures you have the most accurate assessment for clinical decision-making.

The Bottom Line

Your cystatin C testing was appropriately ordered and provides valuable information, but the key is using the combined equation (eGFRcr-cys ~64 mL/min/1.73 m²), not the cystatin C-based estimate alone (70 mL/min/1.73 m²). 1 This confirms Stage 3a CKD and should guide all treatment decisions, medication dosing, and monitoring strategies. 1 The discordance between your creatinine and cystatin C values highlights exactly why the combined equation was developed—to provide superior accuracy when either marker alone may be misleading. 1, 2