What are the diagnostic criteria for diabetic nephropathy?

Diagnosis of Diabetic Nephropathy

Diabetic nephropathy is diagnosed by persistent albuminuria (urinary albumin excretion >30 mg/24h or urinary albumin-to-creatinine ratio [UACR] >30 mg/g), persistent reduction in estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m², or both, for at least 3 months in patients with diabetes. 1

Diagnostic Criteria

Primary Diagnostic Tests

1. Albuminuria Assessment:

   • Preferred Method: Spot urine albumin-to-creatinine ratio (UACR) 1, 2
   • Classification:

     Category	UACR (mg/g)	24-hour collection (mg/24h)	Timed collection (μg/min)
     Normal (A1)	<30	<30	<20
     Moderately increased (A2)	30-299	30-299	20-199
     Severely increased (A3)	≥300	≥300	≥200

2. eGFR Measurement:

   • Persistent reduction in eGFR below 60 mL/min/1.73 m² 1
   • Used in conjunction with albuminuria to diagnose and stage CKD

Confirmation Requirements

• Persistence: Two of three specimens collected within a 3-6 month period should be abnormal to confirm diagnosis 1, 2
• First-morning urine samples are preferred to avoid confounding factors 2

Clinical Presentation Patterns

1. Classical Phenotype:

   • Progressive increase in albuminuria followed by decline in GFR 3
   • Typical progression: microalbuminuria → macroalbuminuria → declining GFR → ESRD

2. Alternative Phenotypes:

   • Non-albuminuric DKD: Declining GFR without significant albuminuria 3, 4
   • Albuminuria regression: Initial albuminuria that improves over time 3
   • Rapid GFR decline: Accelerated loss of kidney function 3

Screening Recommendations

• Type 1 Diabetes: Begin screening 5 years after diagnosis 1
• Type 2 Diabetes: Begin screening at diagnosis 1
• Frequency: Annual screening of UACR, eGFR, and blood pressure 1, 4

Factors That May Confound Diagnosis

Several factors can temporarily increase urinary albumin excretion:

• Exercise within 24 hours 1, 2
• Acute illness or infection 1, 2
• Fever 1
• Congestive heart failure 1
• Marked hyperglycemia 1, 2
• Marked hypertension 1, 2
• Urinary tract infection 2
• Menstruation 2

Differential Diagnosis Considerations

Up to 30% of patients with diabetic kidney disease may have other causes of CKD on kidney biopsy 1. Consider alternative or additional diagnoses when:

• Active urinary sediment (red or white blood cells, cellular casts) 1
• Rapidly increasing albuminuria 1
• Nephrotic syndrome 1
• Rapidly decreasing eGFR 1
• Absence of retinopathy (particularly in type 1 diabetes) 1

When to Consider Nephrology Referral

Refer to nephrology when:

• Uncertain etiology of kidney disease 1, 2
• Continuously increasing urinary albumin levels despite treatment 1
• Continuously decreasing eGFR 1
• eGFR <30 mL/min/1.73 m² 1
• Difficult-to-control hypertension 2
• Presence of hematuria or other urinary abnormalities 2

Emerging Diagnostic Approaches

While not yet implemented in routine clinical care, research is exploring new biomarkers to improve early detection:

• Urinary biomarkers: NGAL, transferrin, NAG 5
• Serum biomarkers: netrin-1, osteopontin, adiponectin 5

The diagnosis of diabetic nephropathy is critical for initiating appropriate management strategies that can slow disease progression and reduce cardiovascular risk, as patients with diabetic nephropathy have significantly higher mortality rates compared to diabetic patients without nephropathy 6, 7.