Nonproteinuric diabetic nephropathy: when diabetics don't read the textbook.

Diabetic nephropathy (DN) refers to the structural and functional changes in the kidneys of patients with diabetes mellitus (type 1 or 2). A subset of patients with presumed DN may not have overt proteinuria as a prerequisite to renal failure, contrary to the classical paradigm. No animal model fully recapitulates the human subset. All studies on this subject are observational and most lack biopsy data. Many mechanisms have been postulated, including use of renin-angiotensin system agents, recurrent bouts of acute kidney injury, genetic predisposition, and renal lesions other than DN. A well-designed biopsy study and a series of intervention trials are needed to fully understand this entity.