Markers of renal tubular dysfunction measured annually do not predict risk of microalbuminuria in the first few years after diagnosis of Type I diabetes.
OBJECTIVE
Early detection of risk of microalbuminuria could prevent early renal damage. We investigated whether urine retinol binding protein and N-acetyl-glucosaminidase could predict the risk of microalbuminuria in a large cohort of children followed from diagnosis of Type I (insulin-dependent) diabetes mellitus.


METHODS
Subjects under 16 years of age within a georaphically defined region were recruited at diagnosis of Type I (insulin-dependent) diabetes mellitus. Annually, albumin-, retinol binding protein- and N-acetyl-glucosaminidase- to creatinine ratios were each measured in 3 urine samples.


RESULTS
A total of 511 subjects were followed for a median of 6 years (range: 1-14). Microalbuminuria (males: > or = 3.5 mg/mmol; females: > or = 4.0 mg/mmol, in 2 out of 3 urines) developed in 78 subjects (36 male). The cumulative probability of microalbuminuria was 40% after 12 years duration of diabetes. Retinol-binding-proteinuria (men: > or = 21 microg/mmol; women > or = 33 microg/mmol) developed in 217 subjects (152 men). The cumulative probability of retinol-binding-proteinuria was 67 % after 12 years duration of diabetes. The cumulative probability of retinol-binding-proteinuria was 40 % before the onset of microalbuminuria and 59% in subjects who did not subsequently develop microalbuminuria. Retinol-binding-proteinuria developed at a higher rate with increasing HbA1c than microalbuminuria. N-acetyl-glucosaminidase-uria (males: > or = 56 micromol-pnp x h(-1) x mmol(-1); females: > or = 46 micromol-pnp h(-1) x mmol(-1)) developed in 477 subjects. The cumulative probability of N-acetylglucosaminidase-uria was 98 % after 10 years of diabetes duration. The cumulative probability of N-acetyl-glucosaminidase-uria was 73 % in the years before the onset of microalbuminuria and 97 % in subjects without microalbuminuria. The probability of Nacetyl-glucosaminidase-uria was 99 % with an HbA1c greater than or equal to 14.5 %.


CONCLUSIONS
Raised amounts of urine retinol binding protein and N-acetyl-glycosaminidase are related to HbA1c and the duration of diabetes. They occur in the majority of subjects and are not early markers for the risk of microalbuminuria.
Division of Public Health and Primary Health Care, University of Oxford, UK.
C J
CJ
Schultz
R N
RN
Dalton
H A
HA
Neil
T
T
Konopelska-Bahu
D B
DB
Dunger
D000118:Acetylglucosaminidase / Q000652:urine; D000293:Adolescent; D000419:Albuminuria / Q000175:diagnosis / Q000652:urine*; D015415:Biomarkers / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000652:urine*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007223:Infant; D007684:Kidney Tubules / Q000503:physiopathology*; D008297:Male; D011627:Puberty; D012177:Retinol-Binding Proteins / Q000652:urine; D013997:Time Factors
D000118:Acetylglucosaminidase; D015415:Biomarkers; D006442:Glycated Hemoglobin; D012177:Retinol-Binding Proteins