Abstract
Type IV collagen is a major component released from the glomerular and tubular basement membranes. To investigate the alteration of renal type IV collagen turnover in early stage diabetic nephropathy, urinary type IV collagen was measured by a highly sensitive one‐step sandwich enzyme immunoassay (EIA). Urinary samples were obtained from 94 diabetic patients without overt proteinuria. Among those patients, 61 were normoalbuminuric and 33 patients were in the microalbuminuric group. Levels of urinary type IV collagen were serially examined at the start of this study and again one year later. The levels of urinary type IV collagen in patients in the microalbuminuric group were significantly higher than those in the normoalbuminuric group (P < 0.01). There was a significant correlation between the concentration of urinary albumin and urinary type IV collagen in both groups (P < 0.05). Twenty‐eight patients (45.3%) in the normoalbuminuric group who showed an abnormal elevation of urinary type IV collagen in comparison to the reference range of normal healthy adults (normal range; less than 3.5 μg/g · Cr). Seven (25%) out of these 28 normoalbuminuric patients with increased urinary type IV collagen progressed to the microalbuminuric group one year later. The levels of urinary type IV collagen in such patients were significantly increased. In the 21 patients who stayed within the normoalbuminuric group, the urinary type IV collagen levels were significantly decreased one year later. It appears that the levels of urinary type IV collagen might reflect ongoing alteration of the extracellular matrix (ECM) turnover and might define more specifically the early stage diabetic nephropathy than the detection of microalbuminuria. It is concluded that the serial measurement of urinary type IV collagen can be a useful marker for detecting renal injury in diabetes. J. Clin. Lab. Anal. 12:378–382, 1998. © 1998 Wiley‐Liss, Inc.
Keywords: urinary type IV collagen, diabetic nephropathy
References
- 1. Incidence by primary disease in 1997. In An Overview of Regular Dialysis Treatment in Japan. Jpn Soc Dial Ther 1997, pp 48.
- 2. Hayashi H, Karasawa R, Inn H, et al.: An electron microscopic study of glomeruli in Japanese patients with non‐insulin dependent diabetes mellitus. Kidney Int 41: 749–757, 1992. [DOI] [PubMed] [Google Scholar]
- 3. Mauer SM, Steffes MW, Ellis EN, Sutherland DER, Brown DM, Goetz FC: Structural‐functional relationships in diabetic nephropathy. J Clin Invest 74: 1143–1155, 1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Hogemann B, Balleisen L, Rauterberg J, Voss B, Gerlach U: Basement membrane components (7S collagen, laminin P1) are increased in sera of diabetic and activate platelets in vitro. Haemostasis 16: 428–432, 1986. [DOI] [PubMed] [Google Scholar]
- 5. Hayashi Y, Makino H, Ota Z: Serum and urinary concentrations of type IV collagen and laminin as a marker of microangiopathy in diabetes. Diabetic Med 9: 366–370, 1992. [DOI] [PubMed] [Google Scholar]
- 6. Yagame M, Suzuki D, Jinde K, et al.: Significance of urinary type IV collagen in patients with diabetic nephropathy using a highly sensitive one‐step sandwich enzyme immunoassay. J Clin Lab Anal 11: 110–116, 1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Kuzuya N: Report of the committee of diagnostic criteria of diabetes mellitus by the glucose tolerance test. J Jpn Diab Soc 13: 17–20, 1970. [Google Scholar]
- 8. Hashida S, Imagawa M, Inoue S, Ruan K‐H, Ishikawa E: More useful maleimide compounds for the conjugation of Fab′ to horseradish peroxide through thiol groups in the hinge. J Appl Biochem 6: 56–63, 1984. [PubMed] [Google Scholar]
- 9. Ishikawa E, Imagawa M, Hashida S, Hamaguchi Y, Ueno T: Enzymelabeling of antibodies and their fragments for enzyme immunoassay and immunohistochemical staining. J Immunoassay 4: 209–327, 1983. [DOI] [PubMed] [Google Scholar]
- 10. Bos ES, Van der Doelen AA, Rooy NV, Schuurs AHWM: 3, 3′5, 5′‐Tetramethylbenzidine as an Ames test negative chromogen for horseradish peroxidase in enzyme‐immunoassay. J Immunoassay 2: 187–204, 1981. [DOI] [PubMed] [Google Scholar]
- 11. Obata K, Iwata K, Ichida T, et al.: One step sandwich enzyme immunoassay for human type IV collagen using monoclonal antibodies. Clin Chim Acta 181: 293–304, 1989. [DOI] [PubMed] [Google Scholar]
- 12. Yagame M, Kim Y, Zhu D, et al.: Differential distribution of type IV collangen chains in patients with diabetic nephropathy in non‐insulin‐dependent diabetes mellitus. Nephron 70: 42–48, 1995. [DOI] [PubMed] [Google Scholar]
- 13. Nelich A, Schleicher E: Immunohistochemical localization of extracellular matrix components in human diabetic glomerular lesions. Am J Pathol 139: 889–899, 1991. [PMC free article] [PubMed] [Google Scholar]
- 14. Falk RJ, Scheinman JI, Mauer SM, Michael AF: Polyantigenic expansion of basement membrane constituents in diabetic nephropathy. Diabetes 32 (suppl 2 ):34–39, 1983. [DOI] [PubMed] [Google Scholar]
- 15. Jinde K, Yagame M, Suzuki D, Naka R, Sakai H, Miyazaki M: In situ hybridization of MMP‐3 and TIMP‐1 mRNA in glomeruli from non‐insulin‐dependent diabetes patients with diabetic nephropathy. Abstract of the XIIIth International Congress of Nephrology, 1995, p 195.
- 16. Takizawa H, Satoh T, Kurusu A, et al.: Increase of urinary type IV collagen in normoalbuminuric patients with impaired glucose tolerance (IGT). Nephron 79: 474–475, 1998. [DOI] [PubMed] [Google Scholar]