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 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)
Pfleiderer
S
S
Kinderklinik, Albert-Ludwigs-Universität, Freiburg.
Zimmerhackl
L B
LB
Kinne
R
R
Manz
F
F
Schuler
G
G
Brandis
M
M
D000118:Acetylglucosaminidase / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000510:Alpha-Globulins / Q000652:urine*; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000503:physiopathology*; D006441:Hemoglobin A / Q000378:metabolism; D006801:Humans; D007678:Kidney Glomerulus / Q000503:physiopathology; D007686:Kidney Tubules, Distal / Q000503:physiopathology*; D007687:Kidney Tubules, Proximal / Q000503:physiopathology*; D008875:Middle Aged; D009088:Mucoproteins / Q000652:urine*; D058949:Uromodulin
D000510:Alpha-Globulins; D001786:Blood Glucose; D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin; C016001:alpha-1-microglobulin; D006441:Hemoglobin A; D000118:Acetylglucosaminidase