What is the use of cystatin C (Cystatin C) lab tests in assessing kidney function?

Use of Cystatin C Laboratory Testing

Cystatin C should be used as a confirmatory test when creatinine-based eGFR is less accurate, particularly in patients with eGFRcreat 45-59 mL/min/1.73 m² without albuminuria, and when combined with creatinine provides the most accurate kidney function assessment for clinical decision-making. 1, 2

Primary Clinical Applications

Confirmatory Testing for CKD Diagnosis

• Measure cystatin C in adults with eGFRcreat 45-59 mL/min/1.73 m² who lack markers of kidney damage when CKD confirmation is needed. 1, 2
• If eGFRcys or eGFRcreat-cys is ≥60 mL/min/1.73 m², CKD diagnosis is not confirmed, and these patients have very low risk for CKD complications. 1, 2
• This approach prevents misclassification of CKD, as creatinine-based estimates alone can incorrectly categorize patients. 1

Situations Where Creatinine-Based eGFR Is Less Accurate

Use cystatin C when creatinine reliability is compromised: 1, 2

• Extremes of muscle mass (low muscle mass, sarcopenia, obesity class III, athletes)
• Elderly patients where age-related muscle loss affects creatinine
• Children with chronic liver disease
• Patients with altered dietary protein intake
• Chronic liver disease where creatinine metabolism is affected

Optimal Testing Strategy

Combined Marker Approach

• The combination of creatinine and cystatin C (eGFRcreat-cys) provides the most accurate GFR estimation and is superior to either marker alone. 1, 2
• When cystatin C is ordered, laboratories should report both eGFRcys and eGFRcreat-cys to allow clinicians both values for decision-making. 1
• The combined equation improves precision for medication dosing, particularly for drugs with narrow therapeutic windows like carboplatin in cancer patients. 2

Risk Stratification and Prognosis

• Cystatin C-based estimates improve prediction of adverse outcomes including cardiovascular events, kidney failure, and mortality beyond what creatinine provides. 2, 3
• In meta-analysis of 90,750 participants, 23% with eGFRcreat 60-74 mL/min/1.73 m² had eGFRcys <60 mL/min/1.73 m², indicating substantial underdiagnosis when using creatinine alone. 2
• Large discrepancies between eGFRcr and eGFRcys (where cystatin C shows lower function) identify vulnerable patients at higher risk for acute kidney injury, medication adverse events, and mortality. 4

Advantages Over Creatinine Alone

Biological Superiority

• Cystatin C is independent of age, sex, and muscle mass, making it particularly valuable in populations where creatinine is unreliable. 2
• Produced at constant rate by all nucleated cells, freely filtered, not secreted, and completely catabolized in tubules without returning to bloodstream. 2
• Detects kidney dysfunction at earlier stages than creatinine, especially in diabetes. 2

Clinical Performance

• Fewer non-GFR determinants compared to creatinine, avoiding limitations related to diet and muscle mass. 5
• More strongly associated with all-cause mortality and cardiovascular events than creatinine-based estimates. 5
• Improves sensitivity and specificity of CKD diagnosis and detection of harmful acute and chronic kidney function changes. 4

Reporting Standards

Laboratory Requirements

• Use only assays with calibration traceable to international standard reference material. 2
• Report cystatin C concentration rounded to nearest 100th when expressed as mg/L. 1, 2
• Report eGFRcys and eGFRcreat-cys rounded to nearest whole number relative to body surface area of 1.73 m² using units mL/min/1.73 m². 1
• Report values <60 mL/min/1.73 m² as "decreased." 1

Important Limitations and Caveats

Non-GFR Factors Affecting Cystatin C

• Thyroid dysfunction can affect cystatin C levels independently of renal function. 2
• Smoking and certain malignancies may influence levels. 2
• These factors are less problematic than the multiple confounders affecting creatinine but should be considered in interpretation. 2

Practical Barriers

• Not widely available in many countries including parts of the U.S. and Canada, though availability is improving. 2
• Cost is higher than creatinine, but the "triple marker" panel (creatinine, cystatin C, urine albumin-to-creatinine ratio) is affordable in high-income settings. 2
• Lack of evidence for cost-effectiveness remains the biggest implementation barrier. 2

When NOT to Use Routinely

• Cystatin C may not be required for routine longitudinal monitoring after CKD diagnosis is established in clinically stable patients, though creatinine remains standard for follow-up. 1, 2
• Initial assessment should still use serum creatinine and GFR estimating equation as the clinical standard. 1

Special Populations

High-Value Testing Scenarios

• Cardiovascular disease patients for risk assessment. 2
• Diabetes patients for earlier detection of kidney dysfunction. 2
• Cancer patients receiving nephrotoxic chemotherapy for dose individualization. 2
• Liver transplant recipients for accurate GFR estimation. 2
• Heart failure patients for risk stratification and prognosis. 2