How is Glomerular Filtration Rate (GFR) used to assess kidney function?

Glomerular Filtration Rate (GFR): Assessment of Kidney Function

GFR is the single best overall measure of kidney function and should be estimated using prediction equations (MDRD or Cockcroft-Gault in adults) rather than relying on serum creatinine alone. 1

Why GFR is the Gold Standard

GFR represents the volume of blood filtered by the glomerulus per minute and serves as the most accurate indicator of overall kidney function in both health and disease. 1 The measurement is standardized to body surface area and reported as mL/min/1.73 m². 1

• Normal GFR in young adults is approximately 120-130 mL/min/1.73 m² 1, 2
• GFR physiologically declines by approximately 1% per year after age 30-40 1
• A GFR below 60 mL/min/1.73 m² represents loss of half or more of normal adult kidney function 1, 2

Clinical Application: CKD Staging

The K/DOQI guidelines use GFR to classify chronic kidney disease (CKD) into five stages, with GFR <60 mL/min/1.73 m² for ≥3 months defining CKD regardless of the presence of kidney damage. 1

The staging system is: 1, 2

• Stage 1: GFR ≥90 with kidney damage present
• Stage 2: GFR 60-89 with kidney damage present
• Stage 3: GFR 30-59 (moderate decrease)
• Stage 4: GFR 15-29 (severe decrease)
• Stage 5: GFR <15 or dialysis (kidney failure)

This classification allows standardized communication between providers and facilitates treatment decisions based on level of kidney function rather than diagnosis alone. 1

How to Estimate GFR in Clinical Practice

Initial Assessment

Use serum creatinine with an estimating equation (eGFRcr) as the initial test for all patients. 1 Clinical laboratories should automatically report estimated GFR alongside creatinine measurements. 3

For adults, use the MDRD Study equation or Cockcroft-Gault equation: 1, 3

The Cockcroft-Gault equation is: 1

• GFR = [(140 - age) × body weight (kg) × 0.85 if female] / [72 × serum creatinine (mg/dL)]

These equations account for age, sex, race, and body size—factors that affect creatinine generation. 1

When Initial eGFR May Be Inaccurate

If eGFRcr is expected to be inaccurate or more precision is needed for clinical decision-making, measure cystatin C and calculate eGFRcr-cys (combined creatinine-cystatin C equation). 1

Situations requiring cystatin C measurement include: 1

• Extremes of muscle mass (very low or very high)
• Vegetarian diet or creatine supplement use 3
• Malnutrition or muscle wasting 3
• Amputation 3

For the highest accuracy when even eGFRcr-cys is insufficient, directly measure GFR using plasma clearance of exogenous filtration markers (iohexol, iothalamate, or ⁵¹Cr-EDTA). 1 This is appropriate for high-consequence decisions like kidney donation approval or certain chemotherapy regimens. 4

Pediatric Patients

In children, use the revised Schwartz formula: 1

• eGFR = 0.413 × [height (cm) / serum creatinine (mg/dL)]

This provides bedside estimation without requiring timed urine collections. 1

Critical Pitfalls to Avoid

Never use serum creatinine concentration alone to assess kidney function. 1, 2, 3 This is the most common error in clinical practice.

Why Serum Creatinine Alone Fails

• Creatinine is affected by muscle mass, age, sex, diet, and medications—not just GFR 1, 2
• Patients can maintain seemingly normal creatinine levels (e.g., 1.3 mg/dL) despite significantly reduced GFR 1
• In elderly patients, age-related muscle loss masks declining kidney function, keeping creatinine falsely "normal" 1, 2
• Minor creatinine elevations can represent substantial GFR reductions 2

24-Hour Urine Collections Are Not Recommended

Do not routinely use 24-hour creatinine clearance—prediction equations are more accurate and practical. 1, 3 The MDRD equation shows tighter correlation with measured GFR than 24-hour creatinine clearance. 1

Reserve timed urine collections only for: 3

• Exceptional dietary intake (vegetarian, creatine supplements)
• Extremes of muscle mass
• Assessment of nutritional status

At very low GFR levels (<20 mL/min), creatinine clearance progressively overestimates true GFR by up to twofold. 1

Clinical Significance of Reduced GFR

GFR <60 mL/min/1.73 m² is associated with increased prevalence of complications including hypertension, anemia, malnutrition, bone disease, neuropathy, and reduced quality of life. 2

• Decreased GFR is an independent predictor of cardiovascular disease and death, even in elderly patients 1
• Drug dosing must be adjusted based on GFR to prevent toxicity 1
• Patients with CKD should be considered highest risk for subsequent cardiovascular events 1

Early detection through GFR assessment allows interventions that can prevent or delay progression to kidney failure. 2