How is chronic kidney disease (CKD) determined using Glomerular Filtration Rate (GFR)?

Determining Chronic Kidney Disease Using GFR

Chronic kidney disease is diagnosed when either kidney damage is present for ≥3 months OR when GFR is <60 mL/min/1.73 m² for ≥3 months, regardless of whether kidney damage markers are present. 1

Diagnostic Criteria for CKD

CKD diagnosis requires meeting at least one of two criteria, both sustained for a minimum of 3 months 1:

• Kidney damage (structural or functional abnormalities) with or without decreased GFR, evidenced by:

  • Pathological abnormalities 1
  • Elevated urinary albumin-to-creatinine ratio (ACR) 1
  • Abnormalities in urine microscopy or blood tests 1
  • Imaging abnormalities (reduced kidney size, cortical thinning) 1

• GFR <60 mL/min/1.73 m² for ≥3 months, with or without other markers of kidney damage 1

GFR-Based Staging System

CKD severity is classified into five stages based solely on GFR level 1:

• Stage 1: GFR ≥90 mL/min/1.73 m² (kidney damage must be present) 1
• Stage 2: GFR 60-89 mL/min/1.73 m² (kidney damage must be present) 1
• Stage 3: GFR 30-59 mL/min/1.73 m² (moderate decrease) 1
• Stage 4: GFR 15-29 mL/min/1.73 m² (severe decrease) 1
• Stage 5: GFR <15 mL/min/1.73 m² or on dialysis (kidney failure) 1

Critical distinction: Stages 1 and 2 require evidence of kidney damage (albuminuria, imaging abnormalities, etc.) in addition to the GFR threshold, while stages 3-5 are defined by GFR alone regardless of other markers. 1

How to Estimate GFR in Clinical Practice

Initial Assessment

Use creatinine-based estimated GFR (eGFRcr) as the initial assessment tool for all adults at risk for CKD. 1 The most current KDIGO 2024 guidelines recommend using eGFRcr equations that incorporate serum creatinine, age, sex, and race. 1

Never rely on serum creatinine alone to assess kidney function, as it grossly overestimates GFR—patients can maintain seemingly normal creatinine levels (e.g., 1.3 mg/dL) despite significantly reduced GFR. 1

Enhanced Accuracy with Cystatin C

When cystatin C is available, use the combined creatinine-cystatin C equation (eGFRcr-cys) for more accurate GFR staging (Grade 1B recommendation). 1 This combination equation is particularly recommended when eGFRcr is less accurate and GFR affects clinical decision-making. 1

Situations where eGFRcr-cys provides superior accuracy include 1:

• Extremes of muscle mass (severe malnutrition, obesity, amputation, muscle wasting) 1
• Vegetarian diet or creatine supplement use 1, 2
• Extremes of age or body size 1
• When eGFRcr and clinical presentation are discordant 1

When to Measure GFR Directly

Measured GFR (mGFR) using plasma or urinary clearance of exogenous filtration markers should be obtained when accurate GFR determination will impact treatment decisions and estimated GFR is thought to be inaccurate. 1 Iohexol plasma clearance is the preferred exogenous marker. 1

Specific indications for mGFR include 1:

• Calculation of doses for potentially toxic drugs excreted by kidneys 1
• Rapidly changing kidney function 1
• Paraplegia or quadriplegia 1
• Diseases of skeletal muscle 1

Establishing Chronicity (The 3-Month Rule)

Do not diagnose CKD based on a single abnormal eGFR or ACR measurement, as this could represent acute kidney injury (AKI) or acute kidney disease (AKD) rather than chronic disease. 1

Chronicity can be established through 1:

• Review of past GFR measurements/estimations showing persistence ≥3 months 1
• Review of past albuminuria or proteinuria measurements 1
• Imaging findings (reduced kidney size, cortical thinning) 1
• Kidney biopsy showing fibrosis and atrophy 1
• Medical history of conditions known to cause CKD (diabetes, hypertension) 1
• Repeat measurements within and beyond the 3-month timepoint 1

However, consider initiating CKD treatments at first presentation of decreased GFR or elevated ACR if CKD is deemed likely based on other clinical indicators (e.g., longstanding diabetes with retinopathy, hypertension with left ventricular hypertrophy). 1

Common Pitfalls to Avoid

The 24-hour creatinine clearance does not improve GFR estimation over prediction equations and is fraught with collection errors. 1 It should only be used when mGFR is unavailable and eGFRcr-cys is thought to be inaccurate. 1

Serum creatinine is affected by non-GFR factors including muscle mass, dietary intake, tubular secretion, and extrarenal excretion, making it an unreliable standalone marker. 1 This is why prediction equations incorporating multiple variables are essential. 1

GFR naturally declines with age at approximately 1% per year after age 30-40, so by age 70, renal function may have declined by 40% even in healthy individuals. 1 This physiological decline must be distinguished from pathological CKD.

Testing Strategy for At-Risk Populations

Test individuals at risk using both urine albumin measurement (ACR) and eGFR assessment. 1 High-risk groups include 1:

• Adults with diabetes or hypertension 1
• Family history of CKD 1
• Age >60 years 1
• Racial/ethnic minorities in the US 1

Following incidental detection of elevated ACR, hematuria, or low eGFR, repeat testing is mandatory to confirm CKD presence. 1