Is a lab Glomerular Filtration Rate (GFR) calculation based on Blood Urea Nitrogen (BUN)/Creatinine (Cr) reliable for assessing kidney function in patients with suspected kidney disease?

Is Lab GFR Calculation Based on BUN/Cr Reliable?

No, GFR calculation should not be based on BUN/Cr ratio alone—instead, use creatinine-based estimating equations (eGFRcr) like MDRD or CKD-EPI for initial assessment, recognizing these have important limitations, and add cystatin C measurement (eGFRcr-cys) when accuracy is critical or confounding factors exist. 1, 2

The Fundamental Problem with Serum Creatinine Alone

Clinicians should never use serum creatinine concentration as the sole means to assess kidney function. 1 The evidence is clear on why:

• Serum creatinine is affected by multiple non-GFR factors including creatinine secretion, generation, and extrarenal excretion, making it an unreliable standalone marker. 1
• GFR must decline to approximately half the normal level before serum creatinine rises above the upper limit of normal. 1
• Up to 25% of people (particularly thin, elderly women) have significantly reduced eGFR (<60 mL/min/1.73 m²) despite serum creatinine values within the reference interval. 3
• In cancer patients, approximately 60% had abnormal renal function by eGFR but only 5% by serum creatinine alone. 2

The BUN/Cr ratio is not a validated method for GFR estimation and does not appear in any major kidney disease guidelines. 1

The Recommended Approach: Creatinine-Based Estimating Equations

Use prediction equations that incorporate serum creatinine along with age, sex, race, and sometimes body size as the initial assessment. 1

The validated equations include:

• MDRD equation: More accurate for GFR <90 mL/min/1.73 m² and does not require height or weight. 1
• Cockcroft-Gault equation: Widely used but less accurate than MDRD, particularly in elderly patients where it consistently underestimates GFR. 1, 2
• 2021 CKD-EPI equation: The most recent race-free equation that provides reasonable initial assessment in most adults. 2

Clinical laboratories should automatically report eGFR alongside serum creatinine measurements. 1

Critical Limitations: When eGFRcr Is Unreliable

eGFRcr is fundamentally "not sufficiently accurate and precise" compared to measured GFR. 1, 2 Specific situations where eGFRcr fails:

Extremes of Muscle Mass

• Very low muscle mass (elderly, malnourished, muscle wasting diseases) causes overestimation of GFR. 1, 2
• Very high muscle mass (bodybuilders, athletes) causes underestimation of GFR. 2
• Paraplegia or quadriplegia significantly alters creatinine generation. 1

Dietary Factors

• Vegetarian diets reduce creatinine generation. 1
• High-protein diets and creatine supplements increase creatinine independent of kidney function. 2
• Low-protein and ketogenic diets alter non-GFR determinants of creatinine. 2

Chronic Illness States

• Advanced cirrhosis with high cell turnover compromises accuracy. 2
• Cancer with high catabolism/inflammation renders eGFRcr unreliable. 2
• Heart failure, severe malnutrition, and catabolic consuming diseases all affect creatinine generation. 2

Body Composition Extremes

• Obesity class III (BMI >40 kg/m²) significantly reduces eGFRcr accuracy. 2
• Extremes of body size in either direction compromise reliability. 1

Medication Effects

• Trimethoprim, cimetidine, and other drugs that decrease tubular secretion alter creatinine without changing GFR. 2
• Anabolic steroids and hormone treatments affect creatinine generation. 2

When and How to Use Better Methods

Add Cystatin C for Improved Accuracy

Measure cystatin C and calculate eGFRcr-cys when eGFRcr is expected to be inaccurate and GFR affects clinical decision-making. 1, 2 This is a Grade 1C recommendation from KDIGO 2024. 1

Cystatin C advantages:

• Less influenced by muscle mass, diet, age, sex, and race compared to creatinine. 2
• Produced by all nucleated cells, providing more consistent generation. 2
• The combined creatinine-cystatin C equation (eGFRcr-cys) demonstrates superior accuracy. 1, 2

Important caveats: High catabolic states and exogenous steroid use can affect cystatin C accuracy. 2

Measure GFR Directly When Precision Is Critical

Use measured GFR with exogenous filtration markers (iothalamate, iohexol, inulin) when treatment decisions critically depend on precise GFR. 1, 2, 4

Specific indications for measured GFR:

• Kidney-cleared chemotherapy dosing. 2
• Rapidly changing kidney function. 1
• Calculation of doses for potentially toxic drugs excreted by kidneys. 1
• Clinical trials requiring precise GFR. 2

If measured GFR is unavailable and eGFRcr-cys is thought inaccurate, consider timed urine collections for measured creatinine clearance. 1, 2

Common Pitfalls to Avoid

• Never assume "normal" creatinine means normal kidney function, especially in elderly patients with low body weight where significant renal impairment can exist despite near-normal creatinine. 5
• Do not ignore clinical context suggesting altered creatinine generation—extremes of muscle mass, dietary intake, or catabolic states require alternative assessment. 2
• Ensure laboratory standardization: Creatinine assay methods significantly affect accuracy, with Jaffe method overestimating by 5-15% compared to enzymatic methods. 2 Laboratories must calibrate to international reference standards. 1
• Recognize equation-specific limitations: Both Cockcroft-Gault and MDRD formulas failed to reach K/DOQI accuracy standards in validation studies, with 29-32% of subjects misclassified. 2
• For medication dosing, use Cockcroft-Gault formula as most drug dosing guidelines were established using this equation, despite its limitations. 5

Practical Algorithm

1. Initial assessment: Use eGFRcr from automated laboratory reporting with MDRD or CKD-EPI equation. 1
2. Assess for confounders: Review muscle mass, diet, medications, chronic illness, and body composition. 2
3. If confounders present or critical decision: Measure cystatin C and calculate eGFRcr-cys. 1, 2
4. If eGFRcr-cys still unreliable or precision critical: Obtain measured GFR with exogenous markers. 1, 2
5. If measured GFR unavailable: Consider 24-hour urine creatinine clearance as last resort. 1