What are the stages of diabetic nephropathy classification based on glomerular filtration rate (GFR) and albuminuria?

Diabetic Nephropathy Classification Based on GFR and Albuminuria

Diabetic nephropathy is classified using both glomerular filtration rate (GFR) and albuminuria levels, with five GFR stages and three albuminuria categories forming a comprehensive classification system that predicts risk of progression to end-stage renal disease. 1

GFR Categories

• G1: Normal or high GFR (≥90 mL/min/1.73 m²) 1
• G2: Mildly decreased GFR (60-89 mL/min/1.73 m²) 1
• G3a: Mildly to moderately decreased GFR (45-59 mL/min/1.73 m²) 1
• G3b: Moderately to severely decreased GFR (30-44 mL/min/1.73 m²) 1
• G4: Severely decreased GFR (15-29 mL/min/1.73 m²) 1
• G5: Kidney failure (<15 mL/min/1.73 m²) 1

Albuminuria Categories

• A1: Normal to mildly increased albuminuria (<30 mg/g creatinine) 1
• A2: Moderately increased albuminuria (30-299 mg/g creatinine), previously termed microalbuminuria 1
• A3: Severely increased albuminuria (≥300 mg/g creatinine), previously termed macroalbuminuria 1

Integrated Classification and Risk Assessment

The combination of GFR and albuminuria categories creates a matrix that better predicts risk of progression to end-stage renal disease than either parameter alone 1. This classification system has replaced the traditional five-stage model of diabetic nephropathy that was based solely on albuminuria progression 1.

• Stages A1/G1 and A1/G2 are considered stable disease with low risk 1
• All other combinations indicate increasing risk of progression to end-stage renal failure 1
• The risk increases from green (lowest), yellow, orange, red, to dark red (highest) as both GFR decreases and albuminuria increases 1

Clinical Implications and Monitoring

• Patients with stages A1/G1 and A1/G2 should undergo annual measurements 1
• Yellow risk category requires monitoring at least once per year 1
• Orange risk category requires monitoring twice per year 1
• Red risk category requires monitoring three times per year 1
• Dark red risk category requires monitoring four times per year 1

Important Diagnostic Considerations

• Albumin-to-creatinine ratio (ACR) from a spot urine sample is preferred over 24-hour collections for screening and diagnosis 1
• At least 2-3 measurements over a 6-month period should be performed to confirm the diagnosis 1
• Exercise within 24 hours, infection, fever, heart failure, marked hyperglycemia, hypertension, pyuria, and hematuria can falsely elevate urinary albumin excretion 1

Pathophysiological Progression

• Early nephropathy begins with glomerular hyperfiltration and microalbuminuria 2
• Traditionally, GFR decline was thought to occur only after development of macroalbuminuria 3
• However, newer evidence shows GFR can decline before the onset of overt nephropathy, particularly in type 2 diabetes 3
• There is no strict correlation between GFR and microalbuminuria, as they can progress independently 1

Referral to Nephrology

• Patients with GFR <30 mL/min/1.73 m² should be referred to a nephrologist 1
• Patients with severely increased albuminuria (A3) should be referred regardless of GFR 1
• Patients with atypical presentations (e.g., kidney disease without retinopathy in type 1 diabetes) should be considered for nephrology referral and possible kidney biopsy 1

This classification system helps clinicians assess risk, guide monitoring frequency, determine appropriate interventions, and make timely referrals to nephrology care, all of which can significantly impact morbidity and mortality in diabetic nephropathy 1.