Anti-proteinuric effects of glycosaminoglycan-based drugs

Current Opinion in Molecular Therapeutics

Volumn 9, Issue 4, 2007, Pages 364-377

  Wijnhoven, Tessa J M ^a,b   Lensen, Joost F M ^a   Rops, Angelique L ^a   McCarthy, Kevin J ^c   Van Der Vlag, Johan ^a   Berden, Jo H M ^a,b   Van Den Heuvel, Lambert P W J ^b   Van Kuppevelt, Toin H ^a  

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^b RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^c LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

Author keywords

Filtration; Glycosaminoglycan; Heparan sulfate; Kidney; Proteinuria

Indexed keywords

AGRIN; ALBUMIN; ARDEPARIN; CERTOPARIN; COLLAGEN TYPE 18; DALTEPARIN; DANAPAROID; ENOXAPARIN; FONDAPARINUX; GLYCOSAMINOGLYCAN; GLYPICAN; HEPARAN SULFATE; HEPARANASE; HEPARIN; NADROPARIN; PARNAPARIN; PERLECAN; PROTEOHEPARAN SULFATE; REVIPARIN; SULODEXIDE; SYNDECAN; TINZAPARIN; UNCLASSIFIED DRUG; VESSEL DUE F;

CELL STRUCTURE; DIABETIC NEPHROPATHY; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; EXTRACELLULAR MATRIX; GLOMERULUS BASEMENT MEMBRANE; GLOMERULUS FILTRATION; HUMAN; KIDNEY; KIDNEY FAILURE; KIDNEY FUNCTION; KIDNEY TUBULE ABSORPTION; MEMBRANOUS GLOMERULONEPHRITIS; NONHUMAN; PODOCYTE; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN STRUCTURE; PROTEINURIA; REVIEW;

ANIMALS; CARBOHYDRATE CONFORMATION; CARBOHYDRATE SEQUENCE; CYTOKINES; FIBRINOLYTIC AGENTS; GLUCURONIDASE; GLYCOSYLATION END PRODUCTS, ADVANCED; HEPARAN SULFATE PROTEOGLYCANS; HEPARIN; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; KIDNEY; KIDNEY GLOMERULUS; MOLECULAR SEQUENCE DATA; PROTEINURIA;

EID: 34547887952     PISSN: 14648431     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (153)

1. Preuss HG: Basics of renal anatomy and physiology. Clin Lab Med (1993) 13(1):1-11.
2. Deen WM, Lazzara MJ, Myers BD: Structural determinants of glomerular permeability. Am J Physiol Renal Physiol (2001) 281(4):F579- F596.
3. Tryggvason K, Pettersson E: Causes and consequences of proteinuria: The kidney filtration barrier and progressive renal failure. J Intern Med (2003) 254(3):216-224.
4. Tryggvason K, Wartiovaara J: How does the kidney filter plasma? Physiology (2005) 20:96-101.
5. Miner JH: Renal basement membrane components. Kidney Int (1999) 56(6):2016-2024.
6. D'Amico G, Bazzi C: Pathophysiology of proteinuria. Kidney Int (2003) 63(3):809-825.
7. Kashif W, Siddiqi N, Dincer AP, Dincer HE, Hirsch S: Proteinuria: How to evaluate an important finding. Cleve Clin J Med (2003) 70(6):535-547.
8. Venkat KK: Proteinuria and microalbuminuria in adults: Significance, evaluation, and treatment. South Med J (2004) 97(10):969-979.
9. Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A: Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia (1989) 32(4):219-226. •• This paper describes the loss of HS in type 1 diabetic patients with albuminuria, which is not only indicative of renal disease, but may also be associated with an increased risk of retinopathy and vascular dysfunction.
10. Deckert T, Kofoed-Enevoldsen A, Norgaard K, Borch-Johnsen K, Feldt-Rasmussen B, Jensen T: Microalbuminuria. Implications for micro- and macrovascular disease. Diabetes Care (1992) 15(9):1181-1191.
11. McGowan T, McCue P, Sharma K: Diabetic nephropathy. Clin Lab Med (2001) 21(1):111-146.
12. Zoccali C, Mallamaci F, Tripepi G: Traditional and emerging cardiovascular risk factors in end-stage renal disease. Kidney Int (2003) (Suppl 85):S105-S110.
13. Prydz K, Dalen KT: Synthesis and sorting of proteoglycans. J Cell Sci (2000) 113(2):193-205.
14. Sugahara K, Kitagawa H: Recent advances in the study of the biosynthesis and functions of sulfated glycosaminoglycans. Curr Opin Struct Biol (2000) 10(5):518-527.
15. Kanwar YS, Jakubowski ML, Rosenzweig LJ: Distribution of sulfated glycosaminoglycans in the glomerular basement membrane and mesangial matrix. Eur J Cell Biol (1983) 31(2):290-295. • This paper reports that the predominant GAG present in the GBM and mesangial matrix is HS, but that the compositions of GBM and mesangial matrix differ, as chondroitin sulfate is exclusively present in the mesangial matrix.
16. Smetsers TF, van de Westerlo EM, ten Dam GB, Overes IM, Schalkwijk J, van Muijen GN, van Kuppevelt TH: Human single-chain antibodies reactive with native chondroitin sulfate detect chondroitin sulfate alterations in melanoma and psoriasis. J Invest Dermatol (2004) 122(3):707-716.
17. Goode NP, Shires M, Crellin DM, Aparicio SR, Davison AM: Alterations of glomerular basement membrane charge and structure in diabetic nephropathy. Diabetologia (1995) 38(12):1455-1465.
18. Esko JD, Lindahl U: Molecular diversity of heparan sulfate. J Clin Invest (2001) 108(2):169-173.
19. Lindahl U, Kusche-Gullberg M, Kjellen L: Regulated diversity of heparan sulfate. J Biol Chem (1998) 273(39):24979-24982.
20. Esko JD, Selleck SB: Order out of chaos: Assembly of ligand binding sites in heparan sulfate. Annu Rev Biochem (2002) 71:435-471. •• This review describes the complexity of HS biosynthesis, resulting in the formation of heterogenous HS chains with a high degree of structural diversity in and between chains.
21. Sasisekharan R, Venkataraman G: Heparin and heparan sulfate: Biosynthesis, structure and function. Curr Opin Chem Biol (2000) 4(6):626-631.
22. Voglmeir J, Voglauer R, Wilson IB: XT-II, the second isoform of human peptide-O-xylosyltransferase, displays enzymatic activity. J Biol Chem (2007) 282(9):5984-5990.
23. Kusche-Gullberg M, Kjellen L: Sulfotransferases in glycosaminoglycan biosynthesis. Curr Opin Struct Biol (2003) 13(5):605-611.
24. van den Born J, Pikas DS, Pisa BJ, Eriksson I, Kjellen L, Berden JH: Antibody-based assay for N-deacetylase activity of heparan sulfate/heparin N-deacetylase/N-sulfotransferase (NDST): Novel characteristics of NDST-1 and -2. Glycobiology (2003) 13(1):1-10.
25. Xu D, Tiwari V, Xia G, Clement C, Shukla D, Liu J: Characterization of heparan sulphate 3-O-sulphotransferase isoform 6 and its role in assisting the entry of herpes simplex virus type 1. Biochem J (2005) 385(2):451-459.
26. Morimoto-Tomita M, Uchimura K, Werb Z, Hemmerich S, Rosen SD: Cloning and characterization of two extracellular heparin-degrading endosulfatases in mice and humans. J Biol Chem (2002) 277(51):49175-49185.
27. Turnbull J, Powell A, Guimond S: Heparan sulfate: Decoding a dynamic multifunctional cell regulator. Trends Cell Biol (2001) 11(2):75-82.
28. Baglin T, Barrowcliffe TW, Cohen A, Greaves M: Guidelines on the use and monitoring of heparin. Br J Haematol (2006) 133(1):19-34.
29. Antman EM: The search for replacements for unfractionated heparin. Circulation (2001) 103(18):2310-2314.
30. Hetzel GR, Sucker C: The heparins: All a nephrologist should know. Nephrol Dial Transplant (2005) 20(10):2036-2042.
31. Cheng JW: Fondaparinux: A new antithrombotic agent. Clin Ther (2002) 24(11):1757-1769.
32. Bame KJ: Heparanases: Endoglycosidases that degrade heparan sulfate proteoglycans. Glycobiology (2001) 11(6):91R-98R. • This paper provides a clear overview of heparanase, which is an endo-β-D-glucuronidase that cleaves HS chains from PG core protein and degrades them to small oligosaccharides.
33. Weitz JI: Low-molecular-weight heparins. N Engl J Med (1997) 337(10):688-698.
34. Denzer AJ, Schulthess T, Fauser C, Schumacher B, Kammerer RA, Engel J, Ruegg MA: Electron microscopic structure of agrin and mapping of its binding site in laminin-1. EMBO J (1998) 17(2):335-343.
35. Groffen AJ, Ruegg MA, Dijkman H, van de Velden TJ, Buskens CA, van den Born J, Assmann KJ, Monnens LA, Veerkamp JH, van den Heuvel LP: Agrin is a major heparan sulfate proteoglycan in the human glomerular basement membrane. J Histochem Cytochem (1998) 46(1):19-27.
36. Noonan DM, Fulle A, Valente P, Cai S, Horigan E, Sasaki M, Yamada Y, Hassell JR: The complete sequence of perlecan, a basement membrane heparan sulfate proteoglycan, reveals extensive similarity with laminin A chain, low density lipoprotein-receptor, and the neural cell adhesion molecule. J Biol Chem (1991) 266(34):22939-22947.
37. Iozzo RV, Cohen IR, Grassel S, Murdoch AD: The biology of perlecan: The multifaceted heparan sulphate proteoglycan of basement membranes and pericellular matrices. Biochem J (1994) 302(3):625-639.
38. Saarela J, Rehn M, Oikarinen A, Autio-Harmainen H, Pihlajaniemi T: The short and long forms of type XVIII collagen show clear tissue specificities in their expression and location in basement membrane zones in humans. Am J Pathol (1998) 153(2):611-626.
39. Tumova S, Woods A, Couchman JR: Heparan sulfate proteoglycans on the cell surface: Versatile coordinators of cellular functions. Int J Biochem Cell Biol (2000) 32(3):269-288.
40. Abrink M, Grujic M, Pejler G: Serglycin is essential for maturation of mast cell secretory granule. J Biol Chem (2004) 279(39): 40897-40905.
41. Capila I, Linhardt RJ: Heparin-protein interactions. Angew Chem Int Ed Engl (2002) 41(3):391-412. • This review describes the binding of HS to, and modulation of, a wide variety of proteins involved in numerous important biological processes.
42. Lever R, Page CP: Novel drug development opportunities for heparin. Nat Rev Drug Discov (2002) 1(2):140-148.
43. Rops AL, Van Der Vlag J, Lensen JF, Wijnhoven TJ, Van Den Heuvel LP, Van Kuppevelt TH, Berden JH: Heparan sulfate proteoglycans in glomerular inflammation. Kidney Int (2004) 65(3):768-785.
44. Jenniskens GJ, Veerkamp JH, van Kuppevelt TH: Heparan sulfates in skeletal muscle development and physiology. J Cell Physiol (2006) 206(2):283-294.
45. Raats CJ, Bakker MA, Hoch W, Tamboer WP, Groffen AJ, van den Heuvel LP, Berden JH, van den Born J: Differential expression of agrin in renal basement membranes as revealed by domain-specific antibodies. J Biol Chem (1998) 273(28):17832-17838.
46. Raats CJ, Van Den Born J, Berden JH: Glomerular heparan sulfate alterations: Mechanisms and relevance for proteinuria. Kidney Int (2000) 57(2):385-400.
47. Gekle M: Renal tubule albumin transport. Annu Rev Physiol (2005) 67:573-594.
48. Christensen EI, Gburek J: Protein reabsorption in renal proximal tubule-function and dysfunction in kidney pathophysiology. Pediatr Nephrol (2004) 19(7):714-721.
49. van den Born J, van den Heuvel LP, Bakker MA, Veerkamp JH, Assmann KJ, Berden JH: A monoclonal antibody against GBM heparan sulfate induces an acute selective proteinuria in rats. Kidney Int (1992) 41(1):115-123.
50. Kanwar YS, Linker A, Farquhar MG: Increased permeability of the glomerular basement membrane to ferritin after removal of glycosaminoglycans (heparan sulfate) by enzyme digestion. J Cell Biol (1980) 86(2):688-693. •• This is an early study of the perfusion of isolated rat kidneys with the HS-degrading enzyme heparinase III, which results in increased permeability of the GBM for native ferritin and albumin.
51. Kanwar YS, Rosenzweig LJ, Kerjaschki DI: Glycosaminoglycans of the glomerular basement membrane in normal and nephrotic states. Ren Physiol (1981) 4(2-3):121-130.
52. Daniels BS: Increased albumin permeability in vitro following alterations of glomerular charge is mediated by the cells of the filtration barrier. J Lab Clin Med (1994) 124(2):224-230.
53. van den Hoven MJ, Rops AL, Bakker MA, Aten J, Rutjes N, Roestenberg P, Goldschmeding R, Zcharia E, Vlodavsky I, van der Vlag J, Berden JH: Increased expression of heparanase in overt diabetic nephropathy. Kidney Int (2006) 70(12):2100-2108. •• This paper suggests that loss of HS in the GBM as a result of degradation by heparanase may participate in the pathogenesis of diabetes-induced proteinuria.
54. Tamsma JT, van den Born J, Bruijn JA, Assmann KJ, Weening JJ, Berden JH, Wieslander J, Schrama E, Hermans J, Veerkamp JH et al: Expression of glomerular extracellular matrix components in human diabetic nephropathy: Decrease of heparan sulphate in the glomerular basement membrane. Diabetologia (1994) 37(3):313-320. • This study demonstrated that HS expression in the GBM of proteinuric patients with diabetic nephropathy is decreased.
55. van den Born J, van den Heuvel LP, Bakker MA, Veerkamp JH, Assmann KJ, Weening JJ, Berden JH: Distribution of GBM heparan sulfate proteoglycan core protein and side chains in human glomerular diseases. Kidney Int (1993) 43(2):454-463.
56. Makino H, Ikeda S, Haramoto T, Ota Z: Heparan sulfate proteoglycans are lost in patients with diabetic nephropathy. Nephron (1992) 61(4):415-421.
57. Deckert T, Feldt-Rasmussen B, Djurup R, Deckert M: Glomerular size and charge selectivity in insulin-dependent diabetes mellitus. Kidney Int (1988) 33(1):100-106.
58. Maxhimer JB, Gattuso P, Prinz RA, Xu X: Heparanase-1 expression and gene regulation in diabetic nephropathy. J Surg Res (2003) 114(2):279.
59. Mitsuhashi H, Tsukada Y, Ono K, Yano S, Naruse T: Urine glycosaminoglycans and heparan sulfate excretions in adult patients with glomerular diseases. Clin Nephrol (1993) 39(5):231-238.
60. van den Born J, van Kraats AA, Bakker MA, Assmann KJ, van den Heuvel LP, Veerkamp JH, Berden JH: Selective proteinuria in diabetic nephropathy in the rat is associated with a relative decrease in glomerular basement membrane heparan sulphate. Diabetologia (1995) 38(2):161-172.
61. Kramer A, van den Hoven M, Rops A, Wijnhoven T, van den Heuvel L, Lensen J, van Kuppevelt T, van Goor H, van der Vlag J, Navis G, Berden JH: Induction of glomerular heparanase expression in rats with adriamycin nephropathy is regulated by reactive oxygen species and the renin-angiotensin system. J Am Soc Nephrol (2006) 17(9):2513-2520. • This paper reports for the first time that glomerular heparanase expression is upregulated by angiotensin II and hydroxyl radicals.
62. Nakayama K, Natori Y, Sato T, Kimura T, Sugiura A, Sato H, Saito T, Ito S: Altered expression of NDST-1 messenger RNA in puromycin aminonucleoside nephrosis. J Lab Clin Med (2004) 143(2):106-114.
63. Wijnhoven TJ, Lensen JF, Wismans RG, Lamrani M, Wevers RA, Rops AL, van der Vlag J, Berden JH, van den Heuvel LP, van Kuppevelt TH: In vivo degradation of heparan sulfate in the glomerular basement membrane does not result in proteinuria. J Am Soc Nephrol (2007) 18(3):823-832. •• This paper reports that in vivo removal of HS from the rat GBM by heparinase III does not result in acute proteinuria, indicating that GBM HS does not play a direct role in the charge-selective permeability of the GBM.
64. Zcharia E, Metzger S, Chajek-Shaul T, Aingorn H, Elkin M, Friedmann Y, Weinstein T, Li JP, Lindahl U, Vlodavsky I: Transgenic expression of mammalian heparanase uncovers physiological functions of heparan sulfate in tissue morphogenesis, vascularization, and feeding behavior. FASEB J (2004) 18(2):252-263.
65. Harvey SJ, Jarad G, Cunningham J, Rops AL, van der Vlag J, Berden JH, Moeller MJ, Holzman LB, Burgess RW, Miner JH: Disruption of glomerular basement membrane charge through podocyte-specific mutation of agrin does not alter glomerular permselectivity. Am J Pathol (2007) 171(1):139-152.
66. Rossi M, Morita H, Sormunen R, Airenne S, Kreivi M, Wang L, Fukai N, Olsen BR, Tryggvason K, Soininen R: Heparan sulfate chains of perlecan are indispensable in the lens capsule but not in the kidney. EMBO J (2003) 22(2):236-245.
67. Morita H, Yoshimura A, Inui K, Ideura T, Watanabe H, Wang L, Soininen R, Tryggvason K: Heparan sulfate of perlecan is involved in glomerular filtration. J Am Soc Nephrol (2005) 16(6):1703-1710.
68. Chen S, Holzman L, Yamaguchi Y, Woods A, McCarthy DJ, McCarthy KJ: Elimination of heparan sulfate glycosaminoglycans (HS-GAG) from the glomerular basement membrane (GBM) using Cre-Lox technology has profound effects on podocyte ultrastructure and function. J Am Soc Nephrol (2006) 17(4 Suppl 2):Nr TH-FC114.
69. van den Born J, Gunnarsson K, Bakker MA, Kjellen L, Kusche-Gullberg M, Maccarana M, Berden JH, Lindahl U: Presence of N-unsubstituted glucosamine units in native heparan sulfate revealed by a monoclonal antibody. J Biol Chem (1995) 270(52):31303-31309.
70. Ten Dam GB, Kurup S, van de Westerlo EM, Versteeg EM, Lindahl U, Spillmann D, van Kuppevelt TH: 3-O-sulfated oligosaccharide structures are recognized by anti-heparan sulfate antibody HS4C3. J Biol Chem (2006) 281(8):4654-4662.
71. Wijnhoven TJ, Lensen JF, Rops AL, van der Vlag J, Kolset SO, Bangstad HJ, Pfeffer P, van den Hoven MJ, Berden JH, van den Heuvel LP, van Kuppevelt TH: Aberrant heparan sulfate profile in the human diabetic kidney offers new clues for therapeutic glycomimetics. Am J Kidney Dis (2006) 48(2):250-261.
72. van den Born J, Pisa B, Bakker MA, Celie JW, Straatman C, Thomas S, Viberti GC, Kjellen L, Berden JH: No change in glomerular heparan sulfate structure in early human and experimental diabetic nephropathy. J Biol Chem (2006) 281(40):29606-29613.
73. Gelberg H, Healy L, Whiteley H, Miller LA, Vimr E: In vivo enzymatic removal of α2→6-linked sialic acid from the glomerular filtration barrier results in podocyte charge alteration and glomerular injury. Lab Invest (1996) 74(5):907-920.
74. Christensen EI, Birn H: Megalin and cubilin: Synergistic endocytic receptors in renal proximal tubule. Am J Physiol Renal Physiol (2001) 280(4):F562-F573.
75. Dunn CJ, Sorkin EM: Dalteparin sodium. A review of its pharmacology and clinical use in the prevention and treatment of thromboembolic disorders. Drugs (1996) 52(2):276-305.
76. Ofosu FA: Pharmacological actions of sulodexide. Semin Thromb Hemost (1998) 24(2):127-138.
77. Neely JL, Carlson SS, Lenhart SE: Tinzaparin sodium: A low-molecular-weight heparin. Am J Health Syst Pharm (2002) 59(15):1426-1436.
78. Polkinghorne KR, McMahon LP, Becker GJ: Pharmacokinetic studies of dalteparin (Fragmin), enoxaparin (Clexane), and danaparoid sodium (Orgaran) in stable chronic hemodialysis patients. Am J Kidney Dis (2002) 40(5):990-995.
79. Sagedal S, Hartmann A, Sundstrom K, Bjornsen S, Fauchald P, Brosstad F: A single dose of dalteparin effectively prevents clotting during haemodialysis. Nephrol Dial Transplant (1999) 14(8):1943-1947.
80. van der Pijl JW, van der Woude FJ, Geelhoed-Duijvestijn PH, Frolich M, van der Meer FJ, Lemkes HH, van Es LA: Danaparoid sodium lowers proteinuria in diabetic nephropathy. J Am Soc Nephrol (1997) 8(3):456-462. • This paper reports that danaparoid (a mixture of sulfated GAGs consisting mainly of HS) reduces albuminuria in type 1 diabetic patients.
81. Samama MM, Gerotziafas GT: Evaluation of the pharmacological properties and clinical results of the synthetic pentasaccharide (fondaparinux). Thromb Res (2003) 109(1):1-11.
82. Linhardt RJ, Gunay NS: Production and chemical processing of low molecular weight heparins. Semin Thromb Hemost (1999) 25(Suppl 3):5-16. • This detailed review describes the different methods for depolymerization of heparin to synthesize LMW heparins.
83. Fareed J, Leong WL, Hoppensteadt DA, Jeske WP, Walenga J, Wahi R, Bick RL: Generic low-molecular-weight heparins: Some practical considerations. Semin Thromb Hemost (2004) 30(6):703-713.
84. Gambaro G, Cavazzana AO, Luzi P, Piccoli A, Borsatti A, Crepaldi G, Marchi E, Venturini AP, Baggio B: Glycosaminoglycans prevent morphological renal alterations and albuminuria in diabetic rats. Kidney Int (1992) 42(2):285-291.
85. Gambaro G, Venturini AP, Noonan DM, Fries W, Re G, Garbisa S, Milanesi C, Pesarini A, Borsatti A, Marchi E et al: Treatment with a glycosaminoglycan formulation ameliorates experimental diabetic nephropathy. Kidney Int (1994) 46(3):797-806.
86. Myrup B, Hansen PM, Jensen T, Kofoed-Enevoldsen A, Feldt-Rasmussen B, Gram J, Kluft C, Jespersen J, Deckert T: Effect of lowdose heparin on urinary albumin excretion in insulin-dependent diabetes mellitus. Lancet (1995) 345(8947):421-422.
87. Tamsma JT, van der Woude FJ, Lemkes HH: Effect of sulphated glycosaminoglycans on albuminuria in patients with overt diabetic (type 1) nephropathy. Nephrol Dial Transplant (1996) 11(1):182-185. • This study demonstrated that the LMW heparin enoxaparin reduces albuminuria in type 1 diabetic patients.
88. Volpi N, Cusmano M, Venturelli T: Qualitative and quantitative studies of heparin and chondroitin sulfates in normal human plasma. Biochim Biophys Acta (1995) 1243(1):49-58.
89. Poplawska A, Szelachowska M, Topolska J, Wysocka-Solowie B, Kinalska I: Effect of glycosaminoglycans on urinary albumin excretion in insulin-dependent diabetic patients with micro- or macroalbuminuria. Diabetes Res Clin Pract (1997) 38(2):109-114.
90. Szelachowska M, Poplawska A, Topolska J, Kinalska I, Grimaldi M, Szelanowska M, Jopdska J: A pilot study of the effect of the glycosaminoglycan sulodexide on microalbuminuria in type I diabetic patients. Curr Med Res Opin (1997) 13(9):539-545.
91. Skrha J, Perusicova J, Pont'uch P, Oksa A: Glycosaminoglycan sulodexide decreases albuminuria in diabetic patients. Diabetes Res Clin Pract (1997) 38(1):25-31.
92. Dedov I, Shestakova M, Vorontzov A, Palazzini E: A randomized, controlled study of sulodexide therapy for the treatment of diabetic nephropathy. Nephrol Dial Transplant (1997) 12(11):2295-2300.
93. Gambaro G, Kinalska I, Oksa A, Pont'uch P, Hertlova M, Olsovsky J, Manitius J, Fedele D, Czekalski S, Perusicova J et al: Oral sulodexide reduces albuminuria in microalbuminuric and macroalbuminuric type 1 and type 2 diabetic patients: The Di.N.A.S. randomized trial. J Am Soc Nephrol (2002) 13(6):1615-1625. •• This paper describes the ameliorating effect of the GAG-based drug sulodexide, which contains 80% fast-moving heparin and 20% dermatan sulfate, on albuminuria in both micro- and macroalbuminuric type 1 and 2 diabetic patients.
94. Achour A, Kacem M, Dibej K, Skhiri H, Bouraoui S, El May M: One year course of oral sulodexide in the management of diabetic nephropathy. J Nephrol (2005) 18(5):568-574.
95. Solini A, Vergnani L, Ricci F, Crepaldi G: Glycosaminoglycans delay the progression of nephropathy in NIDDM. Diabetes Care (1997) 20(5):819-823.
96. Sorrenti G, Grimaldi M, Canova N, Palazzini E, Melchionda N: Glycosaminoglycans as a possible tool for micro- and macroalbuminuria in diabetic patients. A pilot study. J Int Med Res (1997) 25(2):81-86.
97. van der Pijl JW, Lemkes HH, Frolich M, van der Woude FJ, van der Meer FJ, Van Es LA: Effect of danaparoid sodium on proteinuria, von Willebrand factor, and hard exudates in patients with diabetes mellitus type 2. J Am Soc Nephrol (1999) 10(6):1331-1336.
98. Marshall SM, Hansen KW, Osterby R, Frystyk J, Orskov H, Flyvbjerg A: Effects of heparin on renal morphology and albuminuria in experimental diabetes. Am J Physiol (1996) 271(2 Pt 1):E326-E332.
99. Krzossok S, Birck R, Koeppel H, Schnulle P, Waldherr R, van der Woude FJ, Braun C: Treatment of proteinuria with low-molecular-weight heparin after renal transplantation. Transplant Int (2004) 17(8):468-472.
100. Morita Y, Makino H, Ota K, Akiyama K, Ota Z: Beneficial effect of low molecular weight heparin ("fragmin") on proteinuria of proliferative glomerulonephritis. Clin Nephrol (1994) 42(5):346-347.
101. Rostoker G, Durand-Zaleski I, Petit-Phar M, Ben Maadi A, Jazaerli N, Radier C, Rahmouni A, Mathieu D, Vasile N, Rosso J et al: Prevention of thrombotic complications of the nephrotic syndrome by the low-molecular-weight heparin enoxaparin. Nephron (1995) 69(1):20-28.
102. Pieroni F, Costa RS, Coimbra TM: Effects of glycosaminoglycans on the glomerular changes induced by adriamycin. Res Exp Med (Berl) (1995) 195(6):373-379.
103. Benchetrit S, Golan E, Podjarny E, Green J, Rashid G, Bernheim J, Hershkovitz R: Low molecular weight heparin reduces proteinuria and modulates glomerular TNF-α production in the early phase of adriamycin nephropathy. Nephron (2001) 87(2):155-160.
104. Deepa PR, Varalakshmi P: The cytoprotective role of a lowmolecular-weight heparin fragment studied in an experimental model of glomerulotoxicity. Eur J Pharmacol (2003) 478(2-3):199-205.
105. van Bruggen MC, Walgreen B, Rijke TP, Corsius MJ, Assmann KJ, Smeenk RJ, van Dedem GW, Kramers K, Berden JH: Heparin and heparinoids prevent the binding of immune complexes containing nucleosomal antigens to the GBM and delay nephritis in MRL/lpr mice. Kidney Int (1996) 50(5):1555-1564.
106. Ceol M, Nerlich A, Baggio B, Anglani F, Sauer U, Schleicher E, Gambaro G: Increased glomerular α1 (IV) collagen expression and deposition in long-term diabetic rats is prevented by chronic glycosaminoglycan treatment. Lab Invest (1996) 74(2):484-495.
107. Nader HB, Buonassisi V, Colburn P, Dietrich CP: Heparin stimulates the synthesis and modifies the sulfation pattern of heparan sulfate proteoglycan from endothelial cells. J Cell Physiol (1989) 140(2):305-310.
108. Bjornson Granqvist A, Ebefors K, Saleem MA, Mathieson PW, Haraldsson B, Nystrom JS: Podocyte proteoglycan synthesis is involved in the development of nephrotic syndrome. Am J Physiol Renal Physiol (2006) 291(4):F722-F730.
109. Somlo S, Mundel P: Getting a foothold in nephrotic syndrome. Nat Genet (2000) 24(4):333-335.
110. Kerjaschki D: Caught flat-footed: Podocyte damage and the molecular bases of focal glomerulosclerosis. J Clin Invest (2001) 108(11):1583-1587.
111. Pagtalunan ME, Miller PL, Jumping-Eagle S, Nelson RG, Myers BD, Rennke HG, Coplon NS, Sun L, Meyer TW: Podocyte loss and progressive glomerular injury in type II diabetes. J Clin Invest (1997) 99(2):342- 348.
112. Steffes MW, Schmidt D, McCrery R, Basgen JM: Glomerular cell number in normal subjects and in type 1 diabetic patients. Kidney Int (2001) 59(6):2104-2113.
113. Dalla Vestra M, Masiero A, Roiter AM, Saller A, Crepaldi G, Fioretto P: Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes. Diabetes (2003) 52(4):1031-1035.
114. Koop K, Eikmans M, Baelde HJ, Kawachi H, De Heer E, Paul LC, Bruijn JA: Expression of podocyte-associated molecules in acquired human kidney diseases. J Am Soc Nephrol (2003) 14(8):2063-2071. • This study demonstrated reorganisation of the podocyte foot process structure with foot process effacement, apical displacement of the slit diaphragm and a reduced expression of the slit diaphragm-associated protein in a number of human kidney diseases with a decreased GBM HS expression.
115. Nakamura T, Ushiyama C, Suzuki S, Hara M, Shimada N, Ebihara I, Koide H: Urinary excretion of podocytes in patients with diabetic nephropathy. Nephrol Dial Transplant (2000) 15(9):1379-1383.
116. Patari A, Forsblom C, Havana M, Taipale H, Groop PH, Holthofer H: Nephrinuria in diabetic nephropathy of type 1 diabetes. Diabetes (2003) 52(12):2969-2974.
117. Naggi A, Casu B, Perez M, Torri G, Cassinelli G, Penco S, Pisano C, Giannini G, Ishai-Michaeli R, Vlodavsky I: Modulation of the heparanase-inhibiting activity of heparin through selective desulfation, graded N-acetylation, and glycol splitting. J Biol Chem (2005) 280(13):12103-12113. •• This paper describes the inhibition of heparanase activity by heparin derivatives differing in degrees of 2-O- and 6-O-sulfation, N-acetylation and glycol splitting of nonsulfated uronic acid residues.
118. Kumar N, Bentolila A, Domb AJ: Structure and biological activity of heparinoid. Mini Rev Med Chem (2005) 5(5):441-447.
119. Holt RC, Webb NJ, Ralph S, Davies J, Short CD, Brenchley PE: Heparanase activity is dysregulated in children with steroid-sensitive nephrotic syndrome. Kidney Int (2005) 67(1):122-129.
120. Levidiotis V, Kanellis J, Ierino FL, Power DA: Increased expression of heparanase in puromycin aminonucleoside nephrosis. Kidney Int (2001) 60(4):1287-1296.
121. Levidiotis V, Freeman C, Tikellis C, Cooper ME, Power DA: Heparanase is involved in the pathogenesis of proteinuria as a result of glomerulonephritis. J Am Soc Nephrol (2004) 15(1):68-78.
122. Park IS, Kiyomoto H, Abboud SL, Abboud HE: Expression of transforming growth factor-β and type IV collagen in early streptozotocin-induced diabetes. Diabetes (1997) 46(3):473-480.
123. Wolf G, Chen S, Ziyadeh FN: From the periphery of the glomerular capillary wall toward the center of disease: Podocyte injury comes of age in diabetic nephropathy. Diabetes (2005) 54(6):1626-1634.
124. Nakamura T, Fukui M, Ebihara I, Osada S, Nagaoka I, Tomino Y, Koide H: mRNA expression of growth factors in glomeruli from diabetic rats. Diabetes (1993) 42(3):450-456. •• This paper reports increased glomerular mRNA expression of a number of heparin/HS-binding growth factors in diabetic rats.
125. Ceol M, Gambaro G, Sauer U, Baggio B, Anglani F, Forino M, Facchin S, Bordin L, Weigert C, Nerlich A, Schleicher ED: Glycosaminoglycan therapy prevents TGF-β1 overexpression and pathologic changes in renal tissue of long-term diabetic rats. J Am Soc Nephrol (2000) 11(12):2324- 2336.
126. Young BA, Johnson RJ, Alpers CE, Eng E, Gordon K, Floege J, Couser WG, Seidel K: Cellular events in the evolution of experimental diabetic nephropathy. Kidney Int (1995) 47(3):935-944.
127. de Vriese AS, Tilton RG, Elger M, Stephan CC, Kriz W, Lameire NH: Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes. J Am Soc Nephrol (2001) 12(5):993-1000.
128. Hoshi S, Nomoto K, Kuromitsu J, Tomari S, Nagata M: High glucose induced VEGF expression via PKC and ERK in glomerular podocytes. Biochem Biophys Res Commun (2002) 290(1):177-184.
129. Mezzano SA, Droguett MA, Burgos ME, Ardiles LG, Aros CA, Caorsi I, Egido J: Overexpression of chemokines, fibrogenic cytokines, and myofibroblasts in human membranous nephropathy. Kidney Int (2000) 57(1):147-158.
130. Roestenberg P, van Nieuwenhoven FA, Wieten L, Boer P, Diekman T, Tiller AM, Wiersinga WM, Oliver N, Usinger W, Weitz S, Schlingemann RO, Goldschmeding R: Connective tissue growth factor is increased in plasma of type 1 diabetic patients with nephropathy. Diabetes Care (2004) 27(5):1164- 1170.
131. Wahab NA, Yevdokimova N, Weston BS, Roberts T, Li XJ, Brinkman H, Mason RM: Role of connective tissue growth factor in the pathogenesis of diabetic nephropathy. Biochem J (2001) 359(1):77-87.
132. Cooper LT Jr, Hiatt WR, Creager MA, Regensteiner JG, Casscells W, Isner JM, Cooke JP, Hirsch AT: Proteinuria in a placebo-controlled study of basic fibroblast growth factor for intermittent claudication. Vasc Med (2001) 6(4):235-239.
133. Mazue G, Newman AJ, Scampini G, Della Torre P, Hard GC, Iatropoulos MJ, Williams GM, Bagnasco SM: The histopathology of kidney changes in rats and monkeys following intravenous administration of massive doses of FCE 26184, human basic fibroblast growth factor. Toxicol Pathol (1993) 21(5):490-501.
134. Floege J, Kriz W, Schulze M, Susani M, Kerjaschki D, Mooney A, Couser WG, Koch KM: Basic fibroblast growth factor augments podocyte injury and induces glomerulosclerosis in rats with experimental membranous nephropathy. J Clin Invest (1995) 96(6):2809-2819.
135. Bustos C, Gonzalez E, Muley R, Alonso JL, Egido J: Increase of tumour necrosis factor α synthesis and gene expression in peripheral blood mononuclear cells of children with idiopathic nephrotic syndrome. Eur J Clin Invest (1994) 24(12):799-805.
136. Cho BS, Yoon SR, Jang JY, Pyun KH, Lee CE: Up-regulation of interleukin-4 and CD23/FcεRII in minimal change nephrotic syndrome. Pediatr Nephrol (1999) 13(3):199-204.
137. Wendt T, Tanji N, Guo J, Hudson BI, Bierhaus A, Ramasamy R, Arnold B, Nawroth PP, Yan SF, D'Agati V, Schmidt AM et al: Glucose, glycation, and RAGE: Implications for amplification of cellular dysfunction in diabetic nephropathy. J Am Soc Nephrol (2003) 14(5):1383-1395.
138. Myint KM, Yamamoto Y, Doi T, Kato I, Harashima A, Yonekura H, Watanabe T, Shinohara H, Takeuchi M, Tsuneyama K, Hashimoto N et al: RAGE control of diabetic nephropathy in a mouse model: Effects of RAGE gene disruption and administration of lowmolecular weight heparin. Diabetes (2006) 55(9):2510-2522. • This study suggests that RAGE antagonists are useful therapeutics for the treatment of diabetic nephropathy.
139. Kunika K, Yamaoka T, Itakura M: Damage of charge-dependent renal tubular reabsorption causes diabetic microproteinuria. Diabetes Res Clin Pract (1997) 36(1):1-9.
140. Turner G, Coates P, Warren S, Woodhead JS, Peters JR: Proximal tubular reabsorption of growth hormone and sodium/fluid in normo- and microalbuminuric insulin-dependent diabetes mellitus. Acta Diabetol (1997) 34(1):27-32.
141. Seiler MW, Rennke HG, Venkatachalam MA, Cotran RS: Pathogenesis of polycation-induced alterations ("fusion") of glomerular epithelium. Lab Invest (1977) 36(1):48-61.
142. Vehaskari VM, Root ER, Germuth FG Jr, Robson AM: Glomerular charge and urinary protein excretion: Effects of systemic and intrarenal polycation infusion in the rat. Kidney Int (1982) 22(2):127-135.
143. Takeda T, McQuistan T, Orlando RA, Farquhar MG: Loss of glomerular foot processes is associated with uncoupling of podocalyxin from the actin cytoskeleton. J Clin Invest (2001) 108(2):289-301.
144. Vogtlander NP, Dijkman H, Bakker MA, Campbell KP, van der Vlag J, Berden JH: Localization of α-dystroglycan on the podocyte: From top to toe. J Histochem Cytochem (2005) 53(11):1345-1353.
145. Turnbull JE, Hopwood JJ, Gallagher JT: A strategy for rapid sequencing of heparan sulfate and heparin saccharides. Proc Natl Acad Sci USA (1999) 96(6):2698-2703. • This paper describes a strategy for the sequencing of heparin and HS oligosaccharides.
146. Prabhu A, Venot A, Boons GJ: New set of orthogonal protecting groups for the modular synthesis of heparan sulfate fragments. Org Lett (2003) 5(26):4975-4978.
147. Petitou M, van Boeckel CA: A synthetic antithrombin III binding pentasaccharide is now a drug! What comes next? Angew Chem Int Ed
148. Noti C, de Paz JL, Polito L, Seeberger PH: Preparation and use of microarrays containing synthetic heparin oligosaccharides for the rapid analysis of heparin-protein interactions. Chemistry (2006) 12(34):8664-8686.
149. Dennissen MA, Jenniskens GJ, Pieffers M, Versteeg EM, Petitou M, Veerkamp JH, van Kuppevelt TH: Large, tissue-regulated domain diversity of heparan sulfates demonstrated by phage display antibodies. J Biol Chem (2002) 277(13):10982-10986.
150. van de Westerlo EM, Smetsers TF, Dennissen MA, Linhardt RJ, Veerkamp JH, van Muijen GN, van Kuppevelt TH: Human single chain antibodies against heparin: Selection, characterization, and effect on coagulation. Blood (2002) 99(7):2427-2433.
151. Lensen JF, Rops AL, Wijnhoven TJ, Hafmans T, Feitz WF, Oosterwijk E, Banas B, Bindels RJ, van den Heuvel LP, van der Vlag J, Berden JH, van Kuppevelt TH: Localization and functional characterization of glycosaminoglycan domains in the normal human kidney as revealed by phage display-derived single chain antibodies. J Am Soc Nephrol (2005) 16(5):1279-1288. • This paper describes the distribution of specific HS epitopes, defined by phage display-derived antibodies, in the normal human kidney.
152. Tryggvason K, Patrakka J, Wartiovaara J: Hereditary proteinuria syndromes and mechanisms of proteinuria. N Engl J Med (2006) 354(13):1387-1401.
153. van Kuppevelt TH, Veerkamp JH: Application of cationic probes for the ultrastructural localization of proteoglycans in basement membranes. Microsc Res Tech (1994) 28(2):125-140.