RENAL PROXIMAL AND DISTAL TUBULAR FUNCTION IS ATTENUATED IN DIABETES-MELLITUS TYPE-1 AS DETERMINED BY THE RENAL EXCRETION OF ALPHA(1)-MICROGLOBULIN AND TAMM-HORSFALL PROTEIN

Diabetic nephropathy is usually characterized by glomerular dysfunctio n; the view that tubular damage occurs as a consequence, however, has been disputed. To verify this hypothesis we compared glomerular with p roximal and distal tubular parameters in 62 patients with diabetes mel litus type I. The duration of disease ranged between 0 and 39 years an d the glomerular, proximal tubular, and distal tubular parameters were investigated in 24-h urine samples. Excretion of albumin as a marker of the glomerulum, alpha1-microglobulin and N-acetyl-beta-D-glucosamin idase as parameters of proximal tubule, and Tamm-Horsfall protein as p arameter of distal tubule were determined by sensitive enzyme-linked i mmunosorbent assays. Patients were divided into five groups (D1-D5) ac cording to the duration of diabetes as follows: D1, less than 1 year; D2, 1-4 years; D3, 5-9 years; D4, 10-14 years; D5, longer than 14 year s. Healthy individuals (n = 61) aged 3-42 years served as controls. Si gnificantly increased excretion of proximal tubular parameters were fo und in early course while albumin excretion was still in the normal ra nge. In addition, proximal tubular alpha1-microglobulin showed an incr ease during the course of diabetes duration, probably indicating an ea rly proximal tubular impairment. Distal tubular Tamm-Horsfall protein showed increasing excretion in D1-D4, which may reflect disturbance of the thick ascending loop of Henle. Our results therefore stress the i mportance of tubular parameters such as alpha1-microglobulin during ea rly diabetes mellitus type I since they may serve as early markers of renal dysfunction and may precede albumin excretion. The thick ascendi ng loop of Henle may play a decisive role in the course of diabetes me llitus and can be monitored by urinary THP-excretion of Tamm-Horsfall protein.