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Glomerular filtration rate (GFR, single bolus 51Cr-EDTA technique), serum creatinine and serum beta 2-microglobulin concentrations were measured simultaneously in 49 insulin-dependent diabetics with diabetic nephropathy. GFR ranged from 148 to 23 ml/min/1.73 m2. Inverse serum concentrations of creatinine and beta 2-microglobulin showed a significant correlation with GFR over the whole range of values, r = 0.87 and r = 0.90, respectively (p less than 0.001). In the 31 patients with a GFR less than 80 ml/min/1.73 m2, serum concentration of creatinine and beta 2-microglobulin were within the normal range in 12 and 9 patients, respectively. With GFR below 60 ml/min/1.73 m2, all patients had elevated serum beta 2-microglobulin concentrations, while 24% of the patients still had normal creatinine concentration. Linear regression analysis between log GFR and log serum beta 2-microglobulin showed a better relationship than between log GFR and log serum creatinine, slope -0.90 and -0.57, respectively, p less than 0.01. A prospective study for up to 70 months was performed in 18 of the patients. The study showed a closer relationship between the individual rate of decline in log GFR and log serum beta 2-microglobulin compared to log GFR versus log serum creatinine, p less than 0.01. Neither serum creatinine nor serum beta 2-microglobulin can be used as methods for screening of early impairment of renal function (GFR less than 80 ml/min/1.73 m2 in diabetic nephropathy. Our study suggests that serum beta 2-microglobulin is more ideal endogenous marker for GFR estimation than serum creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)