In type 1 diabetes, the pathologic changes to the glomerulus occur in a somewhat predictable sequence, with hypertrophy of the glomeruli and thickening of the basement membrane seen early in the disease course. Expansion of the mesangium then follows and leads to the clinical manifestation of proteinuria. As the disease progresses, there is progressive glomerular damage and increasing amounts of albuminuria, with eventual reduction of the GFR and, ultimately, ESRD.

In type 2 diabetes, these events may be temporally compressed, with impaired renal function appearing as an early manifestation. To some extent this difference may reflect the fact that diagnosis often does not occur until later in the disease course; however, it may also reflect increased patient age in this population and the frequent presence of comorbid hypertension.

PRESENTATION AND DIAGNOSIS

The earliest clinical manifestation of diabetic nephropathy is known as microalbuminuria, defined as 30 to 300 mg of albumin per gram of creatinine in a spot urine sample, a quantity of protein that cannot reliably be detected on a urine dipstick. As the disease progresses, macroalbuminuria ensues (> 300 mg/g of creatinine in a spot sample), which can be detected on a dipstick and is a marker of overt nephropathy. In some cases, proteinuria may be severe enough to cause the full nephrotic syndrome. The final stages of DN are characterized by a progressive decline in renal function, which can lead to ESRD.