Low molecular weight (LMW) proteins pass easily through the glomerular filter and are almost completely reabsorbed by the proximal renal tubule in health. An increase in their urinary excretion implies failure of reabsorption and may signal tubular dysfunction. β2-microglobulin (B2M) is a sensitive marker of tubular dysfunction, but is unstable in acid urine, whilst only limited data are available for other LMW proteins. The aim of these studies was to determine the prevalence of elevated LMW protein excretion in children with renal disease and to identify factors influencing LMW protein excretion. Secondly, these studies sought to determine conditions where individual proteins might best indicate tubular dysfunction. Enzyme-linked immunosorbent assays were used to measure B2M, α1-microglobulin (A1M) and urine protein 1 (UP1) in plasma and urine, and retinol-binding protein (RBP) in urine. Albumin, the lysosomal enzyme N-acetyl-β-D-glucosaminidase (NAG), creatinine and pH were also measured in urine. Each protein excretion was expressed as a ratio to creatinine concentration. B2M showed instability in urine with pH below 6.0, RBP was unstable in urine below pH 5.0 following frozen storage whilst A1M and UP1 were stable at physiological pH. Two groups of apparently healthy children were studied, and normal ranges were established for protein excretion in random and overnight samples. A comparison of B2M, A1M, UP1, RBP and NAG excretion was undertaken in tubular disease and in glomerular disease. A1M, UP1 and NAG were correlated with increasing albumin excretion in steroid-sensitive nephrotic syndrome, in contrast to B2M and RBP. Compared with A1M, UP1 and NAG, RBP was more closely associated with tubulo-interstitial involvement histologically. There was abnormal RBP excretion in reflux nephropathy, with levels increasing according to the degree of scarring. Increased RBP excretion was also seen in cystic disease, neurogenic bladder, allograft rejection and chronic glomerular disease. RBP excretion was inversely correlated with glomerular filtration rate in reflux nephropathy and in glomerular disease. RBP excretion was increased in diabetic children and was correlated with albumin excretion and with metabolic control. LMW protein excretion is common in children with renal problems, and may be a marker of disease severity. RBP is the most suitable marker of tubular dysfunction.
| Identifer | oai:union.ndltd.org:ADTP/269286 |
| Date | January 1995 |
| Creators | Tomlinson, Paul Andrew |
| Publisher | ResearchSpace@Auckland |
| Source Sets | Australiasian Digital Theses Program |
| Detected Language | English |
| Rights | Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated., http://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm, Copyright: the author |
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