NATURAL-HISTORY OF EARLY DIABETIC NEPHROPATHY - WHAT ARE THE EFFECTS OF THERAPEUTIC INTERVENTION

Several studies have shown that lowering of blood pressure slows the r ate of progression of diabetic renal disease. Some placebo-controlled studies have also shown that angiotensin-converting enzyme (ACE) inhib itors decrease or stabilize albuminuria in incipient nephropathy and s low the rate of progression of advanced nephropathy. However, it is no t yet clear if prolonged treatment with ACE inhibitors or with other a gents exerts a specific renoprotective effect in incipient diabetic ne phropathy. It is proposed that such an effect should be independent fr om changes in systemic blood pressure and should be characterized by a melioration of the rate of rise of albumin excretion rate (AER) and th e rate of fall of glomerular filtration rate (GFR) and independence fr om changes in other parameters known to influence AER (glycemic contro l, protein intake, sodium intake). In addition, there should be eviden ce that the potentially reversible effects of therapeutic intervention on AER and GFR are translated to long-term changes in renal function and structure. This paper reviews the evidence on which the concept of renoprotection is based, with particular reference to choice of end p oints, heterogeneity of study groups, and complexities of the disease process, and relates this evidence to the natural history of nephropat hy in type I and type II diabetes. Based on the above, an assessment i s made of the comparative effects of ACE inhibitors and other antihype rtensive agents on AER and GFR. It is suggested that longitudinal intr a-individual analysis of both variables may be necessary in order to d etermine whether ACE inhibitors exert greater renoprotection than calc ium channel blockers or other antihypertensive agents.