Screening Labs for Diabetic Nephropathy
Screen for diabetic nephropathy annually using two tests: spot urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) calculated from serum creatinine. 1
When to Begin Screening
- Type 1 diabetes: Start screening 5 years after diagnosis 1, 2
- Type 2 diabetes: Start screening immediately at diagnosis 1, 2
The rationale differs between diabetes types: microalbuminuria rarely occurs early in type 1 diabetes, whereas type 2 diabetes is often present for years before clinical diagnosis, meaning kidney damage may already exist at the time of diagnosis. 1
Required Laboratory Tests
Primary Screening Tests (Both Required)
1. Spot Urine Albumin-to-Creatinine Ratio (UACR)
- Preferred method: Random spot urine collection measuring albumin-to-creatinine ratio 1, 2
- Optimal timing: First morning void is best to minimize diurnal variation and orthostatic proteinuria effects 1, 2, 3
- Alternative timing: If morning collection is not feasible, use consistent timing for serial measurements 1
2. Serum Creatinine for eGFR Calculation
- Measure serum creatinine to calculate estimated glomerular filtration rate (eGFR) 1, 2
- The 2021 CKD-EPI equation (without race) is the recommended calculation method 1
- eGFR identifies patients with reduced kidney function even when albuminuria is normal 4, 5
Interpretation of Results
UACR Categories
- Normal: <30 mg/g creatinine 1, 2, 3
- Moderately increased albuminuria (formerly "microalbuminuria"): 30-299 mg/g creatinine 1, 2, 3
- Severely increased albuminuria (formerly "macroalbuminuria"): ≥300 mg/g creatinine 1, 2, 3
eGFR Categories
- Normal or high: ≥90 mL/min/1.73 m² 1
- Mildly decreased: 60-89 mL/min/1.73 m² 1
- Moderately decreased: 30-59 mL/min/1.73 m² 1
- Severely decreased: 15-29 mL/min/1.73 m² 1
- Kidney failure: <15 mL/min/1.73 m² 1
Confirmation Requirements
Critical pitfall to avoid: A single abnormal test is insufficient for diagnosis due to significant day-to-day variability in albumin excretion. 1, 3
- Confirmation protocol: Two out of three specimens must be abnormal over a 3-6 month period to diagnose diabetic nephropathy 1, 3
- This requirement applies specifically to albuminuria testing 1, 3
Factors That Cause False Elevations
Temporary elevations in urinary albumin can occur with: 1, 3
- Exercise within 24 hours of collection 1, 3
- Acute infection or fever 1, 3
- Congestive heart failure 1, 3
- Marked hyperglycemia 1, 3
- Marked hypertension 1, 3
- Urinary tract infection with pyuria 1, 3
- Hematuria 1, 3
Evaluate and exclude these conditions before confirming diabetic nephropathy diagnosis. 3
Optional Confirmatory Test
Cystatin C-based eGFR can be considered in specific situations: 1
- When eGFR from creatinine is 45-59 mL/min/1.73 m² AND albuminuria is normal (UACR <30 mg/g) 1
- Provides confirmation of CKD diagnosis when creatinine-based eGFR alone is borderline 1
- Combining creatinine and cystatin C increases precision and reduces racial/ethnic bias 1
Monitoring Frequency After Diagnosis
Once diabetic nephropathy is diagnosed, increase monitoring frequency based on disease severity: 1
- Low risk (eGFR ≥60, UACR <30): Annual monitoring 1
- Moderate risk (eGFR 45-59 or UACR 30-299): Monitor 2-4 times per year 1
- High risk (eGFR <45 or UACR ≥300): Monitor 3-4 times per year 1
Common Pitfalls to Avoid
- Do not rely on standard urine dipstick: It only detects protein when excretion exceeds 300-500 mg/day, missing the critical early microalbuminuria stage 6
- Do not use isolated urine albumin concentration: Always use the albumin-to-creatinine ratio to adjust for urine concentration variability 1, 3
- Do not confuse urine creatinine with serum creatinine: Urine creatinine on UACR is merely a normalizing factor and does not assess kidney function 3
- Do not screen too early in type 1 diabetes: Screening before 5 years' duration has low yield 1
- Do not delay screening in type 2 diabetes: Screen immediately at diagnosis since disease duration before diagnosis is unknown 1