INTRODUCTION AND DEFINITIONS
Increased urinary protein excretion may be an early clinical manifestation of diabetic nephropathy [1-6]. However, when assessing protein excretion, the urine dipstick is a relatively insensitive marker for initial increases in protein excretion, not becoming positive until protein excretion exceeds 300 to 500 mg/day (upper limit of normal less than 150 mg/day, with most individuals excreting less than 100 mg/day).
Using a specific assay for albumin is a more sensitive technique. The normal rate of albumin excretion is less than 30 mg/day (20 mcg/min); persistent albumin excretion between 30 and 300 mg/day (20 to 200 mcg/min) is called moderately increased albuminuria (the new terminology for what was formerly called "microalbuminuria" ) and, in patients with diabetes (particularly type 1 diabetes), may be indicative of early diabetic nephropathy, unless there is some coexistent renal disease. Albumin excretion above 300 mg/day (200 mcg/min) is considered to represent severely increased albuminuria (the new terminology for what was formerly called "macroalbuminuria" , and which is also called overt proteinuria, clinical renal disease, or dipstick positive proteinuria) .
Although these cut-offs defining moderately increased albuminuria and severely increased albuminuria facilitate determining the risk for progression of nephropathy, the risk of developing overt diabetic nephropathy is probably directly related to albumin excretion rates at all levels.
The clinical significance, screening, and management of moderately increased albuminuria in patients with type 2 diabetes will be reviewed here. In addition to being a possible marker of early diabetic nephropathy, moderately increased albuminuria is also associated with cardiovascular disease in both diabetic and nondiabetic patients. As will be described below, moderately increased albuminuria is often present at diagnosis in patients with type 2 diabetes and may reflect underlying cardiovascular disease rather than diabetic nephropathy.
The significance of moderately increased albuminuria in patients with type 1 diabetes, the mechanisms of moderately increased albuminuria, the association of moderately increased albuminuria with cardiovascular risk, and the treatment of overt diabetic nephropathy are discussed separately. (See "Moderately increased albuminuria (microalbuminuria) in type 1 diabetes mellitus" and "Moderately increased albuminuria (microalbuminuria) and cardiovascular disease" and "Treatment of diabetic nephropathy".)