Journal Mobile Options
Table of Contents
Vol. 32, No. 3, 2010
Issue release date: September 2010
Section title: Original Report: Patient-Oriented, Translational Research
Am J Nephrol 2010;32:219–225
(DOI:10.1159/000317531)

Urinary Collagen IV and πGST: Potential Biomarkers for Detecting Localized Kidney Injury in Diabetes – A Pilot Study

Cawood T.J. · Bashir M. · Brady J. · Murray B. · Murray P.T. · O’Shea D.
aDepartments of Diabetes and Endocrinology, Christchurch Hospital, Christchurch, New Zealand; bDepartment of Endocrinology, cMetabolism Laboratory, St Vincent’s University Hospital, and dUniversity College Dublin School of Medicine and Medical Science, and Department of Nephrology and Clinical Pharmacology, Mater Misericordiae University Hospital, Dublin, Ireland

Do you have an account?

Register and profit from personalized services (MyKarger) Login Information

Please create your User ID & Password





Contact Information









I have read the Karger Terms and Conditions and agree.

Register and profit from personalized services (MyKarger) Login Information

Please create your User ID & Password





Contact Information









I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger (new!)
  • Unrestricted printing, no saving restrictions for personal use
  • Reduced rates with a PPV account
read more

Direct: USD 38.00
Account: USD 26.50

Select

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restriction apply

Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe

  • Automatic perpetual access to all articles of the subscribed year(s)
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select


Article / Publication Details

First-Page Preview
Abstract of Original Report: Patient-Oriented, Translational Research

Received: 4/27/2010
Accepted: 6/19/2010
Published online: 7/20/2010

Number of Print Pages: 7
Number of Figures: 1
Number of Tables: 3

ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)

For additional information: http://www.karger.com/AJN

Abstract

Background/Aims: Urinary biomarkers can identify damage to specific parts of the nephron. We performed a cross-sectional study to characterise the pattern of diabetic nephropathy using urinary biomarkers of glomerular fibrosis (collagen IV), proximal tubular damage (α-glutathione-S-transferase, GST) and distal tubular damage (πGST). Methods: Clinical data from 457 unselected patients attending a hospital diabetes clinic were collected. Spot urine samples were analysed for albumin and creatinine. Biomarkers were measured by enzyme-linked immunosorbent assay, and corrected to urinary creatinine. Results: All 3 biomarkers correlated weakly with albumin/creatinine ratios (Pearson correlation <0.2, p values <0.001). The most common abnormality was elevated urinary collagen IV (glomerular, 35%) compared to αGST (proximal tubule, 18%) or πGST (distal tubule, 15%). The proportion of patients with abnormal biomarker results increased across the normo-, micro- and macroalbuminuria groups, with collagen IV (26, 58, 65%) and πGST (11, 25, 35%) but not αGST. Conclusion: In patients with diabetes, these urinary biomarkers appear to identify renal damage that is related to, but distinct from, urine albumin/creatinine ratios. The markers of glomerular fibrosis and distal tubular damage related most closely to the degree of albuminuria. Longitudinal studies are now required to assess whether these biomarkers can detect early renal disease with greater specificity and sensitivity than the albumin/creatinine ratio.


Article / Publication Details

First-Page Preview
Abstract of Original Report: Patient-Oriented, Translational Research

Received: 4/27/2010
Accepted: 6/19/2010
Published online: 7/20/2010

Number of Print Pages: 7
Number of Figures: 1
Number of Tables: 3

ISSN: 0250-8095 (Print)
eISSN: 1421-9670 (Online)

For additional information: http://www.karger.com/AJN


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Excerpts from the US Renal Data Systems 2002 Annual Report: Atlas of end-stage renal disease in the United States. Am J Kidney Dis 2003;41:v–ix, S7–S254.
  2. Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T: Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care 2005;28:164–176.
  3. Bennett PH, Haffner S, Kasiske BL, Keane WF, Mogensen CE, Parving HH, Steffes MW, Striker GE: Screening and management of microalbuminuria in patients with diabetes mellitus: recommendations to the Scientific Advisory Board of the National Kidney Foundation from an ad hoc committee of the Council on Diabetes Mellitus of the National Kidney Foundation. Am J Kidney Dis 1995;25:107–112.
  4. Mogensen CE, Vestbo E, Poulsen PL, Christiansen C, Damsgaard EM, Eiskjær H, Froland A, Hansen KW, Nielsen S, Pedersen MM: Microalbuminuria and potential confounders. A review and some observations on variability of urinary albumin excretion. Diabetes Care 1995;18:572–581.
  5. Mattix HJ, Hsu CY, Shaykevich S, Curhan G: Use of the albumin/creatinine ratio to detect microalbuminuria: implications of sex and race. J Am Soc Nephrol 2002;13:1034–1039.
  6. Giorgino F, Laviola L, Cavallo Perin P, Solnica B, Fuller J, Chaturvedi N: Factors associated with progression to macroalbuminuria in microalbuminuric type 1 diabetic patients: the EURODIAB Prospective Complications Study. Diabetologia 2004;47:1020–1028.
  7. Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS: Regression of microalbuminuria in type 1 diabetes. N Engl J Med 2003;348:2285–2293.
  8. Rosolowsky ET, Niewczas MA, Ficociello LH, Perkins BA, Warram JH, Krolewski AS: Between hyperfiltration and impairment: demystifying early renal functional changes in diabetic nephropathy. Diabetes Res Clin Pract 2008;82(suppl 1):S46–S53.
  9. Ismail N, Becker B, Strzelczyk P, Ritz E: Renal disease and hypertension in non-insulin-dependent diabetes mellitus. Kidney Int 1999;55:1–28.
  10. Mogensen CE: Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984;310:356–360.
  11. Klein R, Klein BE, Moss SE, Cruickshanks KJ: Ten-year incidence of gross proteinuria in people with diabetes. Diabetes 1995;44:916–923.
  12. MacIsaac RJ, Tsalamandris C, Panagiotopoulos S, Smith TJ, McNeil KJ, Jerums G: Nonalbuminuric renal insufficiency in type 2 diabetes. Diabetes Care 2004;27:195–200.
  13. Macisaac RJ, Jerums G: Albuminuric and non-albuminuric pathways to renal impairment in diabetes. Minerva Endocrinol 2005;30:161–177.
  14. Jerums G, Premaratne E, Panagiotopoulos S, Clarke S, Power DA, MacIsaac RJ: New and old markers of progression of diabetic nephropathy. Diabetes Res Clin Pract 2008;82(suppl 1):S30–S37.
  15. Araki S, Haneda M, Koya D, Kashiwagi A, Uzu T, Kikkawa R: Clinical impact of reducing microalbuminuria in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2008;82(suppl 1):S54–S58.
  16. Tomino Y, Suzuki S, Azushima C, Shou I, Iijima T, Yagame M, Wang LN, Chen HC, Lai KN, Tan SY, Kim MJ: Asian multicenter trials on urinary type IV collagen in patients with diabetic nephropathy. J Clin Lab Anal 2001;15:188–192.
  17. Okonogi H, Nishimura M, Utsunomiya Y, Hamaguchi K, Tsuchida H, Miura Y, Suzuki S, Kawamura T, Hosoya T, Yamada K: Urinary type IV collagen excretion reflects renal morphological alterations and type IV collagen expression in patients with type 2 diabetes mellitus. Clin Nephrol 2001;55:357–364.
  18. Sundberg AG, Appelkvist EL, Backman L, Dallner G: Urinary pi-class glutathione transferase as an indicator of tubular damage in the human kidney. Nephron 1994;67:308–316.
  19. Shaw M: The use of histologically defined specific biomarkers in drug development with special reference to the glutathione S-transferases. Cancer Biomark 2005;1:69–74.
  20. Daemen JW, Oomen AP, Janssen MA, van de Schoot L, van Kreel BK, Heineman E, Kootstra G: Glutathione S-transferase as predictor of functional outcome in transplantation of machine-preserved non-heart-beating donor kidneys. Transplantation 1997;63:89–93.
  21. Maxwell PR, Gordon D, Coyle A: Differentiation between Renal Injury and Compensatory Responses by the Use of Specific Biomarkers; PhD Thesis. Stobhill Hospital Glasgow UK & Biotrin International Ltd, Dublin, 1999.
  22. Sundberg AG, Nilsson R, Appelkvist EL, Dallner G: ELISA procedures for the quantitation of glutathione transferases in the urine. Kidney Int 1995;48:570–575.
  23. Branten AJ, Mulder TP, Peters WH, Assmann KJ, Wetzels JF: Urinary excretion of glutathione S-transferases alpha and pi in patients with proteinuria: reflection of the site of tubular injury. Nephron 2000;85:120–126.
  24. Mauer SM, Steffes MW, Goetz FC, Sutherland DE, Brown DM: Diabetic nephropathy. A perspective. Diabetes 1983;32(suppl 2):52–55.

    External Resources

  25. Mauer SM, Steffes MW, Ellis EN, Sutherland DE, Brown DM, Goetz FC: Structural-functional relationships in diabetic nephropathy. J Clin Invest 1984;74:1143–1155.