BACKGROUND: Nephrotic syndrome is defined as urine total protein excretion 
greater than 3.5 g/d or total protein-creatinine ratio greater than 3.5 g/g, low 
serum albumin level, high serum cholesterol level, and peripheral edema. These 
threshold levels have not been rigorously evaluated in patients with diabetic 
kidney disease or by using urine albumin excretion, the preferred measure of 
proteinuria in patients with diabetes.
STUDY DESIGN: Diagnostic test study.
SETTING & PARTICIPANTS: Adults with type 2 diabetes, hypertension, and urine 
total protein level greater than 0.9 g/d enrolled in the Irbesartan in Diabetic 
Nephropathy Trial.
INDEX TEST: Baseline measures of proteinuria (total protein and albumin 
excretion and protein-creatinine and albumin-creatinine ratios). Linear 
regression to relate measures.
REFERENCE TEST: Other signs and symptoms of nephrotic syndrome at baseline 
(serum albumin < 3.5 g/dL, serum total cholesterol > 260 mg/dL or use of a 
statin, and edema or use of a loop diuretic); progression of chronic kidney 
disease during follow-up (doubling of baseline serum creatinine level or 
requirement for dialysis or kidney transplantation). Logistic regression to 
relate index and reference tests.
RESULTS: In 1,608 participants, total urine protein level of 3.5 g/d was 
equivalent to urine albumin level of 2.2 g/d (95% confidence interval, 1.4 to 
3.5). Of 1,467 participants, 641 (44%) had urine total protein level of 3.5 g/d 
or greater at baseline, 132 (9%) had other signs and symptoms of nephrotic 
syndrome at baseline, and 385 (26%) had progression of kidney disease during a 
mean follow-up of 2.6 years. Areas under the receiver operating curves for 
measures of proteinuria were 0.80 to 0.83 for other signs and symptoms of 
nephrotic syndrome and 0.72 to 0.74 for kidney disease progression. Threshold 
levels for nephrotic-range proteinuria and albuminuria were close to the points 
of maximal accuracy for both outcomes.
LIMITATIONS: Study population limits generalizability; inability to adjust for 
several variables known to affect serum albumin levels; lack of spot urine 
samples.
CONCLUSIONS: The historical definition of nephrotic-range proteinuria appears 
reasonable in patients with diabetic kidney disease. Equivalent thresholds for 
nephrotic-range albuminuria and albumin-creatinine ratio are 2.2 g/d and 2.2 
g/g, respectively.