Aktivierung der Gerinnung und diabetische Nephropathie

J. H. M. Beimler; K. Andrassy

doi:10.1055/s-0037-1619520

Hämostaseologie, Table of Contents

Hamostaseologie 2001; 21(04): 167-170
DOI: 10.1055/s-0037-1619520

Original article

Schattauer GmbH

Aktivierung der Gerinnung und diabetische Nephropathie

Coagulation activation and diabetic nephropathy

J. H. M. Beimler

¹Medizinische Universitätsklinik, Sektion Nephrologie, Heidelberg

,

K. Andrassy

¹Medizinische Universitätsklinik, Sektion Nephrologie, Heidelberg

› Author Affiliations

Abstract

Zusammenfassung

Patienten mit Diabetes mellitus besitzen eine erhöhte kardiovaskuläre Mortalität und Morbidität. In der Gruppe der Patienten mit diabetischer Nephropathie ist das Risiko, an einem kardiovaskulären Ereignis zu versterben, besonders hoch. Die Mikroalbuminurie stellt einen bedeutenden Vorhersagewert der Gesamtmortalität bei bestehendem Diabetes mellitus dar. In der Pathogenese vaskulärer Erkrankungen spielen neben kardiovaskulären Risikofaktoren auch Störungen der Hämostase eine wichtige Rolle. Verschiedene Untersuchungen des hämostatischen Systems lassen eine Aktivierung der Gerinnung bei diabetischen Patienten erkennen; man findet Störungen des Gleichgewichts hämostatischer Faktoren und der endothelialen Zelloberfläche. Bereits in der Frühphase einer diabetischen Nephropathie besteht eine enge Assoziation zwischen der Mikroalbuminurie und dem erhöhten Risiko atherothrombotischer Ereignisse. Eine Reihe von hämostatischen Parametern kann mit dem Ausmaß der bestehenden Albuminausscheidung im Urin korreliert werden.

Summary

Patients with diabetes mellitus show an increased cardiovascular mortality and morbidity. Microalbuminuria has been shown to be an independent predictor of mortality in diabetes mellitus. Beside the cardiovascular risk factors abnormalities of haemostasis play an important role in the pathogenesis of vascular disease. There are several studies indicating an activation of the coagulation system in diabetic patients including abnormalities of haemostatic factors and the endothelial cell surface. Microalbuminuria, the early stage of diabetic nephropathy, is associated with an increased risk of atherothrombosis. Several haemostatic parameters have been positivly correlated with the urinary albumin excretion rate.

Schlüsselwörter

Diabetes - Gerinnung - Gerinnungsaktivierung - diabetische Nephropathie - Mikroalbuminurie

Keywords

Diabetes mellitus - coagulation - diabetic nephropathy - microalbuminuria

Full Text

References

Literatur
1 Altieri DC. Coagulation assembly on leucocytes in transmembrane signaling and cell adhesion. Blood 1993; 81: 569-79.
2 Bazzan M, Gruden G, Stella S, Vaccarino A, Tamponi G, Olivetti C, Giunti S, Cavallo-Perin P. Microalbuminuria in IDDM is associated with increased expression of monocyte procoagulant activity. Diabetologia 1998; 41: 767-71.
3 Berg TJ, Bangstad H-J, Torjesen PH, Osterby R, Bucula R, Hanssen KF. Advanced glycation end products in serum predict changes in the kidney morphology of patients with insulin dependent diabetes mellitus. Metabolism 1997; 46: 661-5.
4 Bierhaus A, Illmer T, Kasper M. Advanced glycation and product mediated induction of tissue factor in cultured endothelial cells is dependent on RAGE. Circulation 1997; 96: 2262-71.
5 Blann AD, Taberner DA. Annotation: A reliable marker of endothelial dysfunction: does it exist?. Br J Haematol 1995; 90: 244-8.
6 Bucala R, Tracey KJ, Cerami A. Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes. J Clin Invest 1991; 87: 432-8.
7 Collier A, Rumley A, Rumley AG. Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria. Diabetes 1992; 41: 909-13.
8 Deckert T, Feldt-Rasmussen B, Borch-Johnson K, Jensen T, Kofoed-Enevoldsen A. Albuminuria reflects widespread vascular damage. The steno hypothesis. Diabetologia 1989; 32: 219-26.
9 Deckert T, Kofoed-Enevoldsen A, Borch-Johnsen K, Feldt-Rasmussen B, Jensen T. Microalbuminuria. Implication for micro- and macro-vascular disease. Diabetes Care 1992; 9: 1181-91.
10 Feldt-Rasmussen B. Increased transcapillary escape rate of albumin in type 1 (insulin-dependent) diabetic patients with microalbuminuria. Diabetologia 1986; 29: 282-6.
11 Fuller JH, Keen H, Jarrett RJ. et al. Haemostatic variables associated with diabetes and its complications. Br Med J 1979; 2: 964-6.
12 Gruden G, Bazzan M, Stella S, Pagano G, Pileri A, Cavallo Perin P. Microalbuminuria in insulin-dependent diabetes is associated with high levels of prothrombin fragment 1+2. Thromb Res 1993; 72: 541-6.
13 Gruden G, Cavallo Perrin P, Bazzan M, Stella S, Vuolo A, Pagano G. PAI-1 and factor VII-activity are higher in insulin-dependent diabetic patients with microalbuminuria. Diabetes 1994; 43: 426-9.
14 Gruden G, Olivetti C, Cavallo Perrin P, Bazzan M, Stella S, Tamponi G, Pagano G. Activated protein C resistance in type 1 diabetes. Diabetes Care 1997; 20: 424-5.
15 Hirano T, Ookubo K, Kashiwazaki K, Tajima H, Yoshino G, Adachi M. Vascular endothelial markers, von Willebrand factor and thrombomodulin index, are specifically elevated in type 2 diabetic patients with nephropathy: comparison of primary renal disease. Clinica Chimica Acta 2000; 299: 65-75.
16 Ibbotson SH, Rayner H, Stickland MH, Davies JA, Grant PJ. Thrombin generation and factor VIII:C levels in patients with type 1 diabetes complicated by nephropathy. Diabet Med 1993; 10: 336-40.
17 Jensen T, Bjerre-Knudsen J, Feldt-Rasmussen B, Deckert T. Features of endothelial dysfunction in early diabetic nephropathy. Lancet 1989; 1: 461-3.
18 Jensen T, Borch-Johnsen K, Kofoed-Enevoldsen A, Deckert T. Coronary heart disease in young type 1 (insulin-dependent) diabetic patients with and without diabetic nephropathy: incidence and risk factors. Diabetologia 1987; 30: 144-8.
19 Jensen T. Increased plasma level of von Wille-brand factor in type 1 (insulin dependent) diabetic patients with incipient diabetic nephropathy. Br Med J 1989; 298: 27-8.
20 Jude B, Fontaine P. Modification of monocyte procoagulant activity in diabetes mellitus. Seminars in Thrombosis and Haemostasis 1991; 445-6.
21 Kannel WB, D’Agostino RB, Wilson PW, Belanger AJ, Gagnon DR. Diabetes, fibrinogen and risk of cardiovascular disease: the Framingham experience. Am Heart J 1990; 120: 672-6.
22 Kario K, Matsuo T, Kobayashi H, Matsuo M, Sakata T, Miyata T. Activation of tissue factor induced coagulation and endothelial cell dysfunction in non-insulin dependent diabetic patients with microalbuminuria. Arterioscler Thromb Vasc Biol 1995; 15: 1114-20.
23 Knobl P, Schernthaner G, Schnack C, Pietschmann P, Griesmacher A, Prager R, Muller M. Thrombogenic factors are related to urinary albumin excretion rate in type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993; 36: 1045-50.
24 Leurs PB, Van Oerle R, Wolffenbuttel BHR, Hamulyak K. Increased tissue factor pathway inhibitor (TFPI) and coagulation in patients with insulin-dependent diabetes mellitus. Thromb Haemost 1997; 77: 472-6.
25 Mattock MB, Morrish NJ, Viberti G, Keen H, Fitzgerald AP. Prospective study of microalbuminuria as predictor for mortality in NIDDM. Diabetes 1992; 41: 736-41.
26 Meade TW, Mellows S, Brozovic M. et al. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; 2: 533-7.
27 Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity onset diabetes. N Engl J Med 1984; 310: 356-60.
28 Morrish NJ, Stevens LK, Head J, Fuller JH, Jarrett RJ. A prospective study of mortality among middle-aged diabetic patients (The London cohort of the WHO Multinational Study of vascular disease in diabetics) I: causes and death rates. Diabetologia 1990; 33: 538-41.
29 Morrish NJ, Stevens LK, Head J, Fuller JH, Jarrett RJ, Keen H. A prospective study of mortality among middle-aged diabetic patients (The London cohort of the WHO Multinational Study of Vascular Disease in Diabetics) II: associated risk factors. Diabetologia 1990; 33: 542-8.
30 Myrup B, Rossing P, Jensen T, Gram J, Kluft C, Jespersen J. Procoagulant activity and intimal dysfunction in IDDM. Diabetologia 1995; 38: 73-8.
31 Osterman H, Van de Loo J. Factors of the hemostatic system in diabetic patients. Haemostasis 1986; 16: 386-416.
32 Ross R. The pathogenesis of atherosclerosis: an update. N Engl J Med 1987; 314: 488-90.
33 Rossing P, Hougaard P, Borch-Johnson K, Parving HH. Predictors of mortality in insulin dependent diabetes: 10 year observational follow up study. BMJ 1996; 313: 779-84.
34 Saito M, Kumabashiri I, Jokaji H. The levels of protein C and protein S in plasma in patients with type II diabetes mellitus. Thromb Res 1988; 52: 479-86.
35 Sakariassen KS, Bolhuis PA, Sixma JJ. Human blood platelet adhesion to artery subendothelium is mediated by factor VIII-von Wille-brand factor bound to subendothelium. Nature 1979; 279: 636-8.
36 Schmidt AM, Yan SD, Stern DM. The dark side of glucose. Nat Med 1995; 1: 1002-4.
37 Solerte SB, Fioravanti M. Hemodynamic alterations in long-term insulin dependent diabetic patients with overt nephropathy: role of blood hyperviscosity and plasma protein changes. Clin Nephrol 1987; 28: 138-43.
38 Tarnow L, Stehouver CDA, Emeis JJ, Poirier O, Cambien F, Hansen BV, Parving HH. Plasminogen activator inhibitor-1 and apolipoprotein E gene polymorphism and diabetic angiopathy. Nephrol Dial Transplant 2000; 15: 625-30.
39 Uchman B, Bang NU, Rathbun MJ, Fineberg NS, Davidson KK, Fineberg SE. Effects of insulin-immuncomplexes on human blood monocyte and endothelial cells procoagulant activity. J Lab Clin Med 1988; 112: 652-9.
40 Vlassara H, Fuh H, Donelly T, Cybulsky M. Advanced glycation end products promote adhesion molecule (VCAM-1, ICAM-1) expression and atheroma formation in normal rabbits. Molecular Medicine 1995; 1: 447-56.
41 Vukovich T, Schernthaner G. Decreased protein C levels in patients with insulin dependent diabetes mellitus. Diabetes 1986; 35: 617-9.
42 Vukovich TC, Schernthaner G, Knöbl PN, Hay U. The effect of near normoglycaemic control on plasma factor VIII/von Willebrand factor and fibrin degradation products in insulin dependent diabetic patients. J Clin Endocrinol Metab 1989; 69: 84-9.
43 Yan SD, Schmidt AM, Anderson GM, Zhang J, Brett J, Zou YS, Pinsky D, Stern D. Enhanced cellular oxidant stress by interaction of advanced glycation end products with their receptors/binding proteins. J Biol Chem 1994; 269: 9889-97.