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To identify predictors for the development of early hypertensive nephropathy, 88 previously untreated patients with mild-to-moderate essential hypertension (World Health Organization stage I or II) were re-examined after 6 years of follow-up. According to previous results, protein excretion, urinary excretion of N-acetyl-β-glucosaminidase (NAG), serum NAG concentration and glomerular filtration rate (creatinine clearance) may predict the change in renal function.Serum creatinine level increased significantly, but none of the patients developed serum creatinine of > 1.3 mg/dl. An elevated protein excretion between 200 and 500 mg/day at baseline (microproteinuria), urinary NAG excretion, serum NAG concentration and blood pressure control during treatment were not related to serum creatinine level at follow-up or change in serum creatinine level throughout the 6 years of follow-up. In contrast, a high creatinine clearance at baseline was related to a marked rise in serum creatinine level after 6 years. The patients with a clear-cut increase in serum creatinine level of > 0.2 mg/dl (n = 23) were characterized by a significantly higher pretreatment blood pressure at the worksite and a significantly greater initial creatinine clearance than the patients with no significant change in serum creatinine level. In the two groups age, blood pressure level during therapy, and the intensity and duration of blood pressure control were not different.In patients with uncomplicated essential hypertension, microproteinuria, NAG parameters and treatment blood pressure level did not predict the change in serum creatinine level in the first 6 years of follow-up. A high creatinine clearance (suggesting glomerular hyperfiltration) emerged as a clinical diagnostic marker of early hypertensive nephropathy.