Nephrotic syndrome in diabetic kidney disease: an evaluation and update of the definition.
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.


METHODS
Diagnostic test study.


METHODS
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.


METHODS
Baseline measures of proteinuria (total protein and albumin excretion and protein-creatinine and albumin-creatinine ratios). Linear regression to relate measures.


METHODS
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.


CONCLUSIONS
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.
Stoycheff
Nicholas
N
Division of Nephrology, Tufts Medical Center, Boston, MA 02111, USA. nstoycheff@tuftsmedicalcenter.org
Stevens
Lesley A
LA
Schmid
Christopher H
CH
Tighiouart
Hocine
H
Lewis
Julia
J
Atkins
Robert C
RC
Levey
Andrew S
AS
D000419:Albuminuria / Q000652:urine; D003404:Creatinine / Q000652:urine; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000652:urine; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000175:diagnosis* / Q000652:urine
D003404:Creatinine