During the development to overt nephropathy, diabetic patients go through several characteristic stages of renal disease, moving from normo- to micro- to macroalbuminuria. Microalbuminuria is defined as a urinary albumin excretion between 20 and 200 μg/min; values <20 μg/min are designated as normoalbuminuria, and values >200 μg/min are designated as macroalbuminuria. Only with macroalbuminuria does the glomerular filtration rate (GFR) fall consistently. The decisive intermediary endpoints are postponement or prevention of micro/macroalbuminuria and reduction or prevention of the fall in GFR (stronger endpoint), with postponement of end-stage renal disease as a final end-point. Good metabolic control can prevent or postpone the development of microalbuminuria, the earliest sign of diabetic renal disease. The ideal realistic therapeutic window may be an HbA1c value between 7 and 8.5% (mean reference value 5.5%). Thus, efforts should aimed at implementing the best possible control before the onset of microalbuminuria, with the other important aim of minimizing hypoglycemic side effects. In patients with microalbuminuria, blood pressure gradually increases, and early antihypertensive treatment becomes crucial. Good glycemic control (with the same glycemic goal as above) may be difficult to achieve in some of these patients, but it is still important. With overt nephropathy, defined as clinical proteinuria, a relentless decline in GFR is inflicted, unless patients are carefully treated with antihypertensive agents, often in combination therapy. Good metabolic control is still strongly warranted because patients with high HbA1c progress much more rapidly. The natural history of the rate of fall in GFR may be reduced from 12 to 3 ml · min−1 · year−1, but genetic factors may be involved; the ACE-genotype DD seems to progress more rapidly during treatment. Protein restriction is also of some interest. Early screening is recommended in all guidelines, with emphasis on testing for albuminuria, including microalbuminuria, along with careful control of glycemia and blood pressure.

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