Renal proximal and distal tubular function is attenuated in diabetes mellitus type 1 as determined by the renal excretion of ?1-microglobulin and Tamm-Horsfall protein

Abstract

Diabetic nephropathy is usually characterized by glomerular dysfunction; the view that tubular damage occurs as a consequence, however, has been disputed. To verify this hypothesis we compared glomerular with proximal and distal tubular parameters in 62 patients with diabetes mellitus type I. The duration of disease ranged between 0 and 39 years and the glomerular, proximal tubular, and distal tubular parameters were investigated in 24-h urine samples. Excretion of albumin as a marker of the glomerulum, alpha 1-microglobulin and N-acetyl-beta-D-glucosaminidase as parameters of proximal tubule, and Tamm-Horsfall protein as parameter of distal tubule were determined by sensitive enzyme-linked immunosorbent assays. Patients were divided into five groups (D1-D5) according 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 years. Healthy individuals (n = 61) aged 3-42 years served as controls. Significantly increased excretion of proximal tubular parameters were found in early course while albumin excretion was still in the normal range. In addition, proximal tubular alpha 1-microglobulin showed an increase during the course of diabetes duration, probably indicating an early 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 importance of tubular parameters such as alpha 1-microglobulin during early diabetes mellitus type I since they may serve as early markers of renal dysfunction and may precede albumin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Side Effects of Antiepileptic Drugs on Renal Tubular Function in Childhood-onset Epilepsy

“…α1-microglobulin is a low-molecular weight protein and is almost completely reabsorbed by renal proximal tubules after glomerular filtration; therefore, under normal conditions only minimal amounts of this protein are detected in the urine. Increased urinary excretion of this protein is primarily the result of either increased plasma concentration or decreased tubular absorption 14) . Because β 2-microglobulin and α1-microglobulin have a similar isoelectric point and molecular size and are absorbed by the same receptor, we can predict that β 2-microglobulin and α1-microglobulin shift parallel to each other in vivo.…”

Evaluation of nephrotoxicity with renal antigens in children: Role of Tamm-Horsfall protein

“…Urine or amniotic fluid, preserved with sodium azide 0.1%, are stored in a refrigerator (4 °C) for assay within 4 days. Storage containers made from palstic material are used since THP sticks to glass, thus reducing its concentration [7,11]. If THP could not be determined immediately specimens were frozen at -24°C until determination.…”

Urinary α1-Microglobulin as a Marker of Nephropathy in Type 2 Diabetic Asian Subjects in Singapore

“…Urinary ␣ 1 -microglobulin has been found to be higher, when compared with normal control subjects, in both type 1 (12) and type 2 diabetic subjects (13) and present even without clinical nephropathy (14,15). In type 2 diabetic subjects, ␣ 1 -microglobulin excretion was directly correlated with albuminuria (16) and HbA 1c levels (17) and decreased with improved glycemic control (17,18).…”