MICROALBUMINURIA IN NIDDM IS CAUSED BY INCREASED EXCRETION OF UNMODIFIED ALBUMIN

After an intravenous infusion of L-arginine to inhibit tubular reabsor ption of albumin, glomerular clearance, renal clearance, and tubular r eabsorption of unmodified albumin (UMA) and glycated albumin (GA) were determined in 72 patients with NIDDM without (NIDDM-I; n = 47) or wit h microalbuminuria (NIDDM-II; n = 25) and in 24 healthy control subjec ts, Samples of serum albumin and dialyzed urine obtained 60 min before and during L-arginine infusion were applied to an affinity column to separate GA from UMA, and their albumin contents were assayed, The ser um level of GA in NIDDM patients was higher than that in control subje cts (P < 0.0001), Both UMA and GA were excreted in excess in NIDDIM-II as compared with the other two groups (P < 0.0001), and UMA comprised 80% of total albumin excretion, In NIDDM-II, tile glomerular clearanc e of UMA (2.5 +/- 0.16 > NIDDM-I [1.8 +/- 0.1] > control subjects [1.3 +/- 0.1 mu l/min], P < 0.001) and of GA (1.7 +/- 0.13 > NIDDM-I = con trol subjects [1.1 +/- 0.1 mu l/min], P < 0.001) were enhanced, as com pared with the other two groups, Renal clearance of UMA (1.3 +/- 0.13 mu l/min) and GA (0.89 +/- 0.09 mu l/min) in NIDDM-II was greater than that in control subjects (0.27 +/- 0.03, 0.19 +/- 0.02 mu l/min) or i n NIDDM-I (0.30 +/- 0.03, 0.11 +/- 0.01 mu l/min). Tubular reabsorptio n of UMA, as assessed by the difference between glomerular and renal c learances of albumin, in NIDDM-II (1.1 +/- 0.1 mu l/min) was less than in NIDDM-I (1.50 +/- 0.09 mu l/min), and that of GA in NIDDM-II was l ower than that in the other two groups, despite exaggerated glomerular clearance of GA and UMA in NIDDM-II, In summary, microalbuminuria in NIDDM is caused by increased excretion of UMA resulting from the decom pensated ability of tubular reabsorption, which is exceeded by increas ed glomerular clearance of UMA.