Serum Albumin Does Not Decrease in Diabetic Nephropathy—Urinary Albumin Increases
The question confuses serum albumin with urinary albumin excretion. In diabetic nephropathy, urinary albumin increases (albuminuria), not serum albumin decreases. Serum albumin only decreases in advanced disease when nephrotic syndrome develops with massive proteinuria.
Understanding the Distinction
Urinary Albumin (What Actually Increases)
The hallmark of diabetic nephropathy is increasing urinary albumin excretion, not decreasing serum albumin 1, 2, 3.
The earliest clinical evidence is microalbuminuria, defined as 30-300 mg/24h or 30-300 mg/g creatinine, representing incipient nephropathy 1, 2, 3.
Without intervention, 80% of type 1 diabetic patients with sustained microalbuminuria progress to macroalbuminuria (>300 mg/24h) over 10-15 years 1, 2, 3.
Albuminuria reflects glomerular damage allowing albumin to leak from blood into urine 4.
Serum Albumin (What Happens Later)
Serum albumin remains normal in early and moderate diabetic nephropathy 5, 6.
Low serum albumin (hypoalbuminemia) only develops in advanced disease with nephrotic syndrome, defined as proteinuria >3.5 g/24h 2, 5.
When hypoalbuminemia occurs, it results from massive urinary albumin losses exceeding hepatic synthesis capacity 5, 6.
Hypoalbuminemia in diabetic nephropathy is associated with worse renal prognosis and higher risk of progression to end-stage renal disease 6.
Clinical Progression Pattern
Early Stage (Microalbuminuria)
Intermediate Stage (Macroalbuminuria/Overt Nephropathy)
- Urinary albumin: >300 mg/24h 1, 2
- Serum albumin: Usually still normal 6
- GFR: Beginning to decline 1, 3
Advanced Stage (Nephrotic Syndrome)
- Urinary albumin: Often >3.5 g/24h 2
- Serum albumin: Decreased (<35 g/L, often <25 g/L) 5, 6
- GFR: Significantly reduced 1, 3
- Clinical signs: Edema, especially periorbital 5
Critical Diagnostic Considerations
Two of three urine specimens collected within 3-6 months should be abnormal before confirming albuminuria, as excretion varies significantly 1, 2, 3.
Transient elevations occur with exercise within 24 hours, infection, fever, marked hyperglycemia, or marked hypertension 1, 2.
If proteinuria exceeds 3.5 g/24h (nephrotic range), investigate for non-diabetic causes of kidney disease 2.
Other red flags requiring alternative diagnosis consideration include absence of diabetic retinopathy, rapidly decreasing GFR, or active urinary sediment 2.
Monitoring Recommendations
Screen annually using urinary albumin-to-creatinine ratio in a random spot urine collection 1.
Monitor estimated GFR alongside albuminuria, as some patients develop decreased GFR without increased albuminuria 1, 7.
Continuously increasing urinary albumin levels warrant nephrology referral, especially if eGFR <30 mL/min/1.73 m² 1.