[Diabetic nephropathy; clinical stage and prediction]

Diabetic nephropathy(DN) is the leading cause of end-stage renal disease in Japan. Clinical course of DN is divided into five stages. Stage 1 is a pre-nephropathy stage. Stage 2 is the period with microalbuminuria. Stage 3A is the stage with persistent macroproteinuria and well preserved renal function. Strict glycemic control and antihypertensive treatment with ACE inhibitors are capable of inducing remission in stage 2 of DN and probably in stage 3A. GFR less than 60 ml/min and urinary protein excretion more than 1 g/day are regarded as stage 3B. Serum creatinine concentration increases in stage 4. Antihypertensive therapy and low protein diet are major options of therapy both in stage 3B and 4. Stage 5 is the period with renal replacement therapy. Survival rate of patients on HD due to DN still remains unsatisfactory. Only 30-50% of type 2 diabetic patients develop DN, suggesting that there are several factors other than hyperglycemia which induce DN. Prediabetic hypertension and parenteral hypertension are regarded as predictors of DN. Smoking, male gender, and advanced age might be risk factors of DN. Recently it was demonstrated that insertion/deletion(I/D) polymorphism of angiotensin converting enzyme gene is associated with DN. In addition polymorphisms of several genes seem to be associated with DN. Development of DNA tips will make it possible to determine a number of gene polymorphisms. Accumulations of the information on gene polymorphisms from many patients with or without DN are expected to contribute detection of patients at high risk of developing DN.