1. American Diabetes Association
• ACE, angiotensin-converting enzyme
ARB, angiotensin receptor blocker
• DCCB, dihydropyridine calcium channel blocker
• ESRD, end-stage renal disease: GFR, glomerular filtration rate
• UKPDS, United Kingdom Prospective Diabetes Study
Diabetes has become the most common single cause of end-stage renal disease (ESRD) in the U.S.and Europe; this is due to the facts that 1) diabetes, particularly type 2, is increasing in prevalence; 2) diabetes patients now live longer; and 3) patients with diabetic ESRD are now being accepted for treatment in ESRD programs where formerly they had been excluded. In the U.S., diabetic nephropathy accounts for about 40% of new cases of ESRD, and in 1997, the cost for treatment of diabeticpatients with ESRD was in excess of $15.6 billion. About 20–30% of patients with type 1 or type 2 diabetes develop evidence of nephropathy, but in type 2 diabetes, a considerably smaller fraction of these progress to ESRD. However, because of the much greater prevalence of type 2 diabetes, such patients constitute over half of those diabetic patients currently starting on dialysis. There isconsiderable racial/ethnic variability in this regard, with Native Americans, Hispanics (especially Mexican-Americans), and African-Americans having much higher risks of developing ESRD than non-Hispanic whites with type 2 diabetes. Recent studies have now demonstrated that the onset and course of diabetic nephropathy can be ameliorated to a very significant degree by several interventions, but theseinterventions have their greatest impact if instituted at a point very early in the course of the development of this complication. This position statement is based on recent review articles that discuss published research and issues that remain unresolved and provides recommendations regarding the detection, prevention, and treatment of early nephropathy.
NATURAL HISTORY OFDIABETIC NEPHROPATHY
The earliest clinical evidence of nephropathy is the appearance of low but abnormal levels (≥ 30 mg/day or 20 μg/min) of albumin in the urine, referred to as microalbuminuria, and patients with microalbuminuria are referred to as having incipient nephropathy. Without specific interventions, ∼80% of subjects with type 1 diabetes who develop sustained microalbuminuria have theirurinary albumin excretion increase at a rate of ∼10–20% per year to the stage of overt nephropathy or clinical albuminuria (≥300 mg/24 h or ≥200 μg/min) over a period of 10–15 years, with hypertension also developing along the way. Once overt nephropathy occurs, without specific interventions, the glomerular filtration rate (GFR) gradually falls over a period of several years at a rate that is highlyvariable from individual to individual (2–20 ml · min−1 · year−1). ESRD develops in 50% of type 1 diabetic individuals with overt nephropathy within 10 years and in >75% by 20 years.
A higher proportion of individuals with type 2 diabetes are found to have microalbuminuria and overt nephropathy shortly after the diagnosis of their diabetes, because diabetes is actually present for many yearsbefore the diagnosis is made and also because the presence of albuminuria may be less specific for the presence of diabetic nephropathy, as shown by biopsy studies. Without specific interventions, 20–40% of type 2 diabetic patients with microalbuminuria progress to overt nephropathy, but by 20 years after onset of overt nephropathy, only ∼20% will have progressed to ESRD. Once the GFR begins tofall, the rates of fall in GFR are again highly variable from one individual to another, but overall, they may not be substantially different between patients with type 1 and patients with type 2 diabetes. However, the greater risk of dying from associated coronary artery disease in the older population with type 2 diabetes may prevent many with earlier stages of nephropathy from progressing to...