Microalbuminuria in NIDDM is caused by increased excretion of unmodified albumin.
After an intravenous infusion Of L-arginine to inhibit tubular reabsorption of albumin, glomerular clearance, renal clearance, and tubular reabsorption of unmodified albumin (UMA) and glycated albumin (GA) were determined in 72 patients with NIDDM without (NIDDM-I; n = 47) or with microalbuminuria (NIDDM-II; n = 25) and in 24 healthy control subjects. 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 serum level of GA in NIDDM patients was higher than that in control subjects (P < 0.0001). Both UMA and GA were excreted in excess in NIDDM-II as compared with the other two groups (P < 0.0001), and UMA comprised 80% of total albumin excretion. In NIDDM-II, the glomerular clearance of UMA (2.5 +/- 0.16 > NIDDM-I [1.8 +/- 0.1] > control subjects [1.3 +/- 0.1 microliter/min], P < 0.001) and of GA (1.7 +/- 0.13 > NIDDM-I = control subjects [1.1 +/- 0.1 microliter/min], P < 0.001) were enhanced, as compared with the other two groups. Renal clearance of UMA (1.3 +/- 0.13 microliter/min) and GA (0.89 +/- 0.09 microliter/min) in NIDDM-II was greater than that in control subjects (0.27 +/- 0.03, 0.19 +/- 0.02 microliter/min) or in NIDDM-I (0.30 +/- 0.03, 0.11 +/- 0.01 microliter/min). Tubular reabsorption of UMA, as assessed by the difference between glomerular and renal clearances of albumin, in NIDDM-II (1.1 +/- 0.1 microliter/min) was less than in NIDDM-I (1.50 +/- 0.09 microliter/min), and that of GA in NIDDM-II was lower 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 decompensated ability of tubular reabsorption, which is exceeded by increased glomerular clearance of UMA.
Ishibashi
F
F
Ishibashi Clinic, Hiroshima, Japan.
D000328:Adult; D000419:Albuminuria; D001120:Arginine; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology / Q000652:urine*; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced; D006801:Humans; D007668:Kidney / Q000502:physiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012709:Serum Albumin / Q000032:analysis*; D000093423:Glycated Serum Albumin
D001120:Arginine; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D000093423:Glycated Serum Albumin