Confirming Proteinuria in Diabetic Kidney Disease and Evaluating Hematuria
How to Confirm Proteinuria in DKD
Use a spot urine albumin-to-creatinine ratio (ACR) on a first-morning void specimen, and confirm with 2 of 3 specimens collected over 3-6 months showing abnormal values (ACR ≥30 mg/g) to establish persistent albuminuria. 1
Preferred Testing Method
- Measure urinary albumin (not total protein) in diabetic patients using spot urine ACR rather than timed collections 1
- First-morning void specimens are optimal to avoid orthostatic proteinuria confounding, though random specimens are acceptable for initial screening 1
- Laboratories should report ACR in mg albumin/g creatinine with a reference range of ≤30 mg/g 1
Confirmation Protocol
- Obtain 2 of 3 specimens within 3-6 months showing ACR >30 mg/g to confirm persistent albuminuria 1
- This confirmation step is critical because albumin excretion has high day-to-day variability (>20% between measurements) 1, 2
- Patients should refrain from vigorous exercise for 24 hours before sample collection 1
Classification Thresholds
- Normal: ACR ≤30 mg/g 1
- Microalbuminuria (moderately increased): ACR 30-300 mg/g 1
- Macroalbuminuria (severely increased): ACR >300 mg/g 1
When to Use Total Protein Instead
- At very high proteinuria levels (spot urine protein-to-creatinine ratio 500-1,000 mg/g), measurement of total protein is acceptable 1
- Report as mg protein/g creatinine with normal range <200 mg/g 1
Red Flag: Hematuria in DKD
The presence of hematuria (active urinary sediment) in a diabetic patient with proteinuria is a red flag requiring investigation for alternative causes of kidney disease beyond DKD. 1
When to Suspect Non-Diabetic Kidney Disease
Consider other causes of CKD when any of the following are present: 1
- Absence of diabetic retinopathy (especially important in type 1 diabetes >10 years duration)
- Active urinary sediment including hematuria, red blood cell casts, or dysmorphic RBCs
- Low or rapidly decreasing GFR (>25% decline with change in GFR category)
- Rapidly increasing proteinuria or nephrotic syndrome
- Refractory hypertension
- Signs or symptoms of other systemic disease
30% reduction in GFR within 2-3 months after initiating ACE inhibitor or ARB
Diagnostic Approach When Hematuria is Present
Hematuria can cause false-positive protein results on dipstick testing, so confirm with quantitative ACR measurement. 3, 2
- Exclude urinary tract infection, which can cause both transient proteinuria and hematuria 1, 3, 2
- Evaluate for glomerulonephritis, which typically presents with hematuria, proteinuria, and active sediment 1
- Consider kidney biopsy for definitive diagnosis when clinical features suggest non-diabetic kidney disease 1
Specific Criteria Supporting DKD Diagnosis
In most diabetic patients, CKD should be attributed to DKD if: 1
- Macroalbuminuria is present (ACR >300 mg/g), OR
- Microalbuminuria is present WITH diabetic retinopathy, OR
- In type 1 diabetes of ≥10 years duration with microalbuminuria
The absence of these features—particularly the presence of hematuria without retinopathy—mandates evaluation for alternative diagnoses. 1
Common Pitfalls to Avoid
- Do not rely on a single ACR measurement for diagnosis; biological variability is substantial 1, 2
- Do not test during conditions causing transient proteinuria: fever, marked hyperglycemia, congestive heart failure, vigorous exercise within 24 hours, or urinary tract infection 1, 3
- Do not use timed 24-hour urine collections for routine screening; spot ACR is preferred 1
- Do not ignore hematuria in diabetic patients—it suggests non-diabetic kidney disease requiring further investigation 1
- Do not assume all proteinuria in diabetics is DKD, especially without retinopathy or with atypical features 1