Skip to main content
PMC home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1993 May;46(5):465–469. doi: 10.1136/jcp.46.5.465

Beta 2-glycoprotein-1 (apolipoprotein H) excretion and renal tubular malfunction in diabetic patients without clinical proteinuria.

M Lapsley 1, F V Flynn 1, P A Sansom 1
PMCID: PMC501261  PMID: 8320329

Abstract

AIM--To compare the urinary excretion of beta 2-glycoprotein-1 with that of two other markers of early tubular disorder in diabetic patients without clinical proteinuria. METHODS--The urinary excretion of retinol binding protein, beta 2-glycoprotein-1, and N-acetyl-beta-D-glucosaminidase was measured in 90 known diabetic patients who had a negative reagent strip test for proteinuria. RESULTS--Among 43 patients with urinary albumin excretion within the reference range, 23 (53%) had raised urinary N-acetyl-beta-D-glucosaminidase activity, five (12%) increased excretion of beta 2-glycoprotein-1, and five (12%) increased loss of retinol binding protein. Among 47 patients with an albumin excretion of 0.9-7.9 mg/mmol creatinine, 42 (89%) had increased urinary N-acetyl-beta-D-glucosaminidase, 23 (49%) an increased output of beta 2-glycoprotein-1, and 16 (34%) a raised excretion of retinol binding protein. The excretion of these markers of tubular defects seldom exceeded two and a half times the upper reference limit and the differences between the findings in the insulin dependent and non-insulin dependent patients with similar albumin excretion were small and insignificant. CONCLUSIONS--In diabetic patients with a negative dipstick test for proteinuria: (a) assay of urinary beta 2-glycoprotein-1 may be a more sensitive test for the detection of impaired tubular reabsorption of protein than measurement of retinol-binding protein; (b) assay of N-acetyl-beta-D-glucosaminidase can detect tubular injury at a time when protein reabsorption remains normal; and (c) impaired renal tubular function may be present in the absence of evidence of glomerular malfunction.

Full text

PDF
469

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abrass C. K. Diabetic proteinuria. Glomerular or tubular in origin? Am J Nephrol. 1984;4(6):337–346. doi: 10.1159/000166849. [DOI] [PubMed] [Google Scholar]
  2. Bernard A. M., Vyskocil A. A., Mahieu P., Lauwerys R. R. Assessment of urinary retinol-binding protein as an index of proximal tubular injury. Clin Chem. 1987 Jun;33(6):775–779. [PubMed] [Google Scholar]
  3. Bernard A., Amor A. O., Goemare-Vanneste J., Antoine J. L., Lauwerys R., Colin I., Vandeleene B., Lambert A. Urinary proteins and red blood cell membrane negative charges in diabetes mellitus. Clin Chim Acta. 1990 Oct 15;190(3):249–262. doi: 10.1016/0009-8981(90)90178-u. [DOI] [PubMed] [Google Scholar]
  4. Christensen E. I., Rennke H. G., Carone F. A. Renal tubular uptake of protein: effect of molecular charge. Am J Physiol. 1983 Apr;244(4):F436–F441. doi: 10.1152/ajprenal.1983.244.4.F436. [DOI] [PubMed] [Google Scholar]
  5. Cohnen G. Immunochemical quantitation of beta2-glycoprotein I in various diseases. J Lab Clin Med. 1970 Feb;75(2):212–216. [PubMed] [Google Scholar]
  6. Evrin P. E., Wibell L. The serum levels and urinary excretion of 2 -microglobulin in apparently healthy subjects. Scand J Clin Lab Invest. 1972 Feb;29(1):69–74. doi: 10.3109/00365517209081057. [DOI] [PubMed] [Google Scholar]
  7. Feldt-Rasmussen B., Mathiesen E. R., Deckert T. Effect of two years of strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetes. Lancet. 1986 Dec 6;2(8519):1300–1304. doi: 10.1016/s0140-6736(86)91433-9. [DOI] [PubMed] [Google Scholar]
  8. Flynn F. V., Lapsley M., Sansom P. A., Cohen S. L. Urinary excretion of beta 2-glycoprotein-1 (apolipoprotein H) and other markers of tubular malfunction in "non-tubular" renal disease. J Clin Pathol. 1992 Jul;45(7):561–567. doi: 10.1136/jcp.45.7.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gibb D. M., Tomlinson P. A., Dalton N. R., Turner C., Shah V., Barratt T. M. Renal tubular proteinuria and microalbuminuria in diabetic patients. Arch Dis Child. 1989 Jan;64(1):129–134. doi: 10.1136/adc.64.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Groop L., Mäkipernaa A., Stenman S., DeFronzo R. A., Teppo A. M. Urinary excretion of kappa light chains in patients with diabetes mellitus. Kidney Int. 1990 Apr;37(4):1120–1125. doi: 10.1038/ki.1990.94. [DOI] [PubMed] [Google Scholar]
  11. Hemmingsen L., Skaarup P. The 24-hour excretion of plasma proteins in the urine of apparently healthy subjects. Scand J Clin Lab Invest. 1975 Jul;35(4):347–353. doi: 10.1080/00365517509095751. [DOI] [PubMed] [Google Scholar]
  12. Holm J., Hemmingsen L., Nielsen N. V. Relationship between the urinary excretion of albumin and retinol-binding protein in insulin-dependent diabetics. Clin Chim Acta. 1988 Sep 30;177(1):101–105. doi: 10.1016/0009-8981(88)90312-9. [DOI] [PubMed] [Google Scholar]
  13. Jung K., Pergande M., Schimke E., Ratzmann K. P., Ilius A. Urinary enzymes and low-molecular-mass proteins as indicators of diabetic nephropathy. Clin Chem. 1988 Mar;34(3):544–547. [PubMed] [Google Scholar]
  14. Lapsley M., Sansom P. A., Marlow C. T., Flynn F. V., Norden A. G. Beta 2-glycoprotein-1 (apolipoprotein H) excretion in chronic renal tubular disorders: comparison with other protein markers of tubular malfunction. J Clin Pathol. 1991 Oct;44(10):812–816. doi: 10.1136/jcp.44.10.812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Martin P., Hampton K. K., Walton C., Tindall H., Davies J. A. Microproteinuria in type 2 diabetes mellitus from diagnosis. Diabet Med. 1990 May;7(4):315–318. doi: 10.1111/j.1464-5491.1990.tb01396.x. [DOI] [PubMed] [Google Scholar]
  16. Martin P., Walton C., Chapman C., Bodansky H. J., Stickland M. H. Increased urinary excretion of transferrin in children with type 1 diabetes mellitus. Diabet Med. 1990 Jan;7(1):35–40. doi: 10.1111/j.1464-5491.1990.tb01304.x. [DOI] [PubMed] [Google Scholar]
  17. Mogensen C. E. Angiotensin converting enzyme inhibitors and diabetic nephropathy. BMJ. 1992 Feb 8;304(6823):327–328. doi: 10.1136/bmj.304.6823.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mogensen C. E., Christensen C. K. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med. 1984 Jul 12;311(2):89–93. doi: 10.1056/NEJM198407123110204. [DOI] [PubMed] [Google Scholar]
  19. Mogensen C. E. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med. 1984 Feb 9;310(6):356–360. doi: 10.1056/NEJM198402093100605. [DOI] [PubMed] [Google Scholar]
  20. Mutti A., Alinovi R., Ghiggeri G. M., Bergamaschi E., Candiano G., Rasi A., Gusmano R., Franchini I., Borghetti A. Urinary excretion of brush-border antigen and plasma proteins in early stages of diabetic nephropathy. Clin Chim Acta. 1990 Apr 30;188(2):93–100. doi: 10.1016/0009-8981(90)90153-j. [DOI] [PubMed] [Google Scholar]
  21. Norden A. G., Flynn F. V. Degradation of beta 2-microglobulin in infected urine by leukocyte elastase-like activity. Clin Chim Acta. 1983 Oct 31;134(1-2):167–176. doi: 10.1016/0009-8981(83)90194-8. [DOI] [PubMed] [Google Scholar]
  22. Norden A. G., Fulcher L. M., Lapsley M., Flynn F. V. Excretion of beta 2-glycoprotein I (apolipoprotein H) in renal tubular disease. Clin Chem. 1991 Jan;37(1):74–77. [PubMed] [Google Scholar]
  23. Rowe D. J., Anthony F., Polak A., Shaw K., Ward C. D., Watts G. F. Retinol binding protein as a small molecular weight marker of renal tubular function in diabetes mellitus. Ann Clin Biochem. 1987 Sep;24(Pt 5):477–482. doi: 10.1177/000456328702400509. [DOI] [PubMed] [Google Scholar]
  24. Sansom P. A., Marlow C. T., Lapsley M., Flynn F. V. A sandwich enzyme-linked immunosorbent assay for beta 2-glycoprotein I. Ann Clin Biochem. 1991 May;28(Pt 3):283–289. doi: 10.1177/000456329102800315. [DOI] [PubMed] [Google Scholar]
  25. Sherman R. L., Drayer D. E., Leyland-Jones B. R., Reidenberg M. M. N-acetyl-beta-glucosaminidase and beta 2-microglobulin. Their urinary excretion in patients with renal parenchymal disease. Arch Intern Med. 1983 Jun;143(6):1183–1185. doi: 10.1001/archinte.143.6.1183. [DOI] [PubMed] [Google Scholar]
  26. Shima K., Hirota M., Fukuda M., Tanaka A. Determination of urinary lysozyme for potential detection of tubular dysfunction in diabetic nephropathy. Clin Chem. 1986 Oct;32(10):1818–1822. [PubMed] [Google Scholar]
  27. Teppo A. M., Groop L. Urinary excretion of plasma proteins in diabetic subjects. Increased excretion of kappa light chains in diabetic patients with and without proliferative retinopathy. Diabetes. 1985 Jun;34(6):589–594. doi: 10.2337/diab.34.6.589. [DOI] [PubMed] [Google Scholar]
  28. Topping M. D., Forster H. W., Dolman C., Luczynska C. M., Bernard A. M. Measurement of urinary retinol-binding protein by enzyme-linked immunosorbent assay, and its application to detection of tubular proteinuria. Clin Chem. 1986 Oct;32(10):1863–1866. [PubMed] [Google Scholar]
  29. Viberti G. C., Hill R. D., Jarrett R. J., Argyropoulos A., Mahmud U., Keen H. Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet. 1982 Jun 26;1(8287):1430–1432. doi: 10.1016/s0140-6736(82)92450-3. [DOI] [PubMed] [Google Scholar]
  30. Viberti G. C., Pickup J. C., Jarrett R. J., Keen H. Effect of control of blood glucose on urinary excretion of albumin and beta2 microglobulin in insulin-dependent diabetes. N Engl J Med. 1979 Mar 22;300(12):638–641. doi: 10.1056/NEJM197903223001202. [DOI] [PubMed] [Google Scholar]
  31. Viberti G., Keen H. The patterns of proteinuria in diabetes mellitus. Relevance to pathogenesis and prevention of diabetic nephropathy. Diabetes. 1984 Jul;33(7):686–692. doi: 10.2337/diab.33.7.686. [DOI] [PubMed] [Google Scholar]
  32. Watts G. F., Powell M., Rowe D. J., Shaw K. M. Low-molecular-weight proteinuria in insulin-dependent diabetes mellitus: a study of the urinary excretion of beta 2-microglobulin and retinol-binding protein in alkalinized patients with and without microalbuminuria. Diabetes Res. 1989 Sep;12(1):31–36. [PubMed] [Google Scholar]
  33. Whiting P. H., Ross I. S., Borthwick L. Serum and urine N-acetyl-beta-D-glucosaminidase in diabetics on diagnosis and subsequent treatment, and stable insulin dependent diabetics. Clin Chim Acta. 1979 Mar 15;92(3):459–463. doi: 10.1016/0009-8981(79)90227-4. [DOI] [PubMed] [Google Scholar]
  34. Yuen C. T., Kind P. R., Price R. G., Praill P. F., Richardson A. C. Colorimetric assay for N-acetyl-beta-D-glucosaminidase (NAG) in pathological urine using the omega-nitrostyryl substrate: the development of a kit and the comparison of manual procedure with the automated fluorimetric method. Ann Clin Biochem. 1984 Jul;21(Pt 4):295–300. doi: 10.1177/000456328402100411. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES