Background/Aims: Carpal tunnel syndrome (CTS) is a major complication that occurs in the musculoskeletal system in patients on long-term hemodialysis (HD). Pentosidine is an advanced glycation endproduct (AGE) and there is evidence that shows AGEs contribute to the pathogenesis of the complications in patients undergoing HD. The aim of this study is to investigate whether pentosidine accumulates in the carpal ligament in patients undergoing HD with CTS in comparison with idiopathic CTS. Methods: Carpal ligaments and skin were obtained during surgery from 28 patients with CTS undergoing HD and 13 patients with idiopathic CTS (ID CTS). Pentosidine was measured by HPLC after hydrolysis of the samples, and amyloid deposits in the samples of HD CTS were examined histologically. Results: Pentosidine levels in ligament and skin were significantly higher in HD CTS than ID CTS. On the other hand, there was no difference in pyridinoline which is a physical cross-link between HD and ID CTS. Amyloid deposits were observed in 14 ligament samples, whereas there was none in 14 other samples. There was no significant difference in pentosidine and pyridinoline in ligament, pentosidine in skin, duration of HD and serum β2-microglobulin between the amyloid+ group and the amyloid– group. Conclusion: A greater concentration of pentosidine in the carpal ligament in HD patients compared with idiopathic patients suggests that an accumulation of AGEs contributes to one of the pathologies of occurrence of CTS in patients undergoing HD.

Keywords:
Amyloid, β2-Microglobulin, Pyridinoline, Cross-links
1.
Makita Z, Bucala R, Rayfield EJ, Friedman EA, Kaufman M, Korbet SM, Barth RH, Winston SA, Fur H, Montague KR: Reactive glycosylation end products in diabetic uremia and treatment of renal failure. Lancet 1994;343:1519–1522.
2.
Sell DR, Monnier VM: Structure elucidation of a senescence cross-link from human extracellular matrix. J Biol Chem 1989;264:21597–21602.
3.
Lyons TJ, Silvestri G, Dunn JA, Dyer DG, Baynes JW: Role of glycation in modification of lens crystallines in diabetic senile cataracts. Diabetes 1991;40:1010–1015.
4.
Uchiyama A, Ohishi T, Takahashi M, Kushida K, Inoue T, Fujie M, Horiuchi K: Fluorophores from aging human articular cartilage. J Biochem 1991;110:714–718.
5.
Monnier VM, Sell DR, Nagaraj R, Miyata S, Grandhee S, Odetti P, Ibrahim SA: Maillard reaction-mediated molecular damage to extracellular matrix and other tissue proteins in diabetes, aging, and uremia. Diabetes 1992;41 (suppl 2):36–41.
6.
Sell DR, Carlson EC, Monnier VM: Differential effects of type 2 (non-insulin-dependent) diabetes mellitus on pentosidine formation in skin and glomerular basement membrane. Diabetologia 1993;36:936–941.
7.
Takahashi M, Ohishi T, Aoshima H, Kawana K, Kushida K, Inoue T, Horiuchi K: The Maillard protein cross-link pentosidine in urine from diabetic patients. Diabetologia 1993;36:664–667.
8.
Hoshino H, Takahashi M, Kushida K, Ohishi T, Kawana K, Inoue T: Quantitation of the crosslinks, pyridinoline, deoxypyridinoline, and pentosidine, in human aorta with dystrophic calcification. Atherosclerosis 1995;112:39–46.
9.
Takahashi M, Hoshino H, Kushida K, Inoue T: Direct measurement of crosslinks, pyridinoline, deoxypyridinoline, and pentosidine, in the hydrolysate of tissues using high-performance liquid chromatography. Anal Biochem 1995;232:158–162.
10.
Gejyo F, Yamada T, Odani S, Nakagawa Y, Arakawa M, Kunitomo T, Kataoka H, Suzuki M, Hirasawa T, Shirahama A, Choen AS, Shmid K: A new form of amyloid protein associated with chronic HD was identified as β2-microglobulins. Biochem Biophys Res Commun 1985;129:701–706.
11.
Schwarz A, Keller F, Seyfert S, Poll W, Molzahn M, Distler A: Carpal tunnel syndrome: A major complication in long term HD patients. Clin Nephrol 1984;22:133–137.
12.
Bartova V, Zima T: Diagnosis and treatment of carpal tunnel syndrome. Renal Failure 1993;15:533–537.
13.
Takasu S, Takatsu S, Kunimoto K, Kokumai Y: Serum hyaluronic acid and interleukin-6 as possible markers of carpal tunnel syndrome in chronic HD patients. Artif Organs 1994;18:420–424.
14.
Fujimoto D, Akiba K, Nakamura N: Isolation and characterization of a fluorescent material in bovine Achilles tendon collagen. Biochem Biophys Res Commun 1977;76:1124–1129.
15.
Kohno H: High sensitive latex photometric immunoassay in clinical chemistry; in Miyaki K, Kanno T, Ishikawa E (eds): Clinical Biochemistry. Amsterdam, Elsevier Science, 1992, pp 225–229.
16.
Cui J, Hayama M, Hochi M: A new amyloid stain by phenol Congo red. Pathol Clin Med 1986;4:1229–1232.
17.
Monnier VM, Marucus G, Abdelhamid E, David RS: The mechanism of collagen cross-linking in diabetes: A puzzle nearing resolution. Diabetes 1996;45(suppl 3):S67–S72.
18.
Sakata S, Takahashi M, Kushida K, Oikawa M, Hoshino H, Denda M, Inoue T: The relationship between pentosidine and HD-related connective tissue disorders. Nephron 1998;78:260–265.
19.
Halliwell B, Gutteridge JMC: The importance of free radicals and catalytic metal ions in human disease. Mol Aspect Med 1985;8:89–193.
20.
Miguel A, Miguel A, Linares M: Evidence of an increased susceptibility to lipid peroxidation in red blood cell of chronic renal failure patients. Nephron 1988;50:64–65.
21.
Paul JL, Sall ND, Poignet JL: Lipid peroxidation abnormalities in hemodialysed patients. Nephron 1993;64:106–109.
22.
Dyer DG, Blackledge JA, Thorpe JSR, Bynes JW: Formation of pentosidine during nonenzymatic browning of proteins by glucose. J Biol Chem 1991;266:11654–11660.
23.
Grandhee SK, Monnier VM: Mechanism of formation of the Maillard protein cross-link pentosidine. J Biol Chem 1991;266:11649–11653.
24.
Takahashi M, Kushida K, Ishihara C, Denda M, Inoue T: Plasma pentosidine levels in uremic patients before and after HD. Scand J Urol Nephrol 1995;29:131–134.
25.
Eyre DR: Collagen cross-linking amino acids. Methods Enzymol 1987;144:115–139.
26.
Miyata T, Taneda S, Kawai R, Ueda Y, Horiuchi S, Hara M, Maeda K, Monnier VM: Identification of pentosidine as a native structure for advanced glycation end products in β2-microglobulin containing amyloid fibrils in patients with dialysis related amyloidosis. Proc Natl Acad Sci USA 1996;93:2353–2358.
1998
Copyright / Drug Dosage / Disclaimer
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.
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 government 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.
You do not currently have access to this content.