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DOI: 10.1055/s-0033-1343113
Thromboembolische Komplikationen bei nephrotischem Syndrom
Thromboembolic complications in nephrotic syndromePublikationsverlauf
29. August 2012
10. Dezember 2012
Publikationsdatum:
15. Mai 2013 (online)
![](https://www.thieme-connect.de/media/dmw/201321/lookinside/thumbnails/10.1055-s-0033-1343113-1.jpg)
Zusammenfassung
Zu den wichtigsten extrarenalen Folgen eines nephrotischen Syndroms (NS) zählen thromboembolische Komplikationen. Neben tiefer Beinvenenthrombose und Lungenembolie zeigt sich bei NS sehr häufig eine Nierenvenenthrombose. Aufgrund einer Vermehrung des prokoagulatorischen und antifibrinolytischen sowie einer Verminderung des antikoagulatorischen Potenzials führt eine multifaktorielle Störung des hämostatischen Gleichgewichts zu einer Hyperkoagulabilität bei NS, die durch eine Erhöhung der Blutviskosität und eine endotheliale Dysfunktion aggraviert wird. Zirkulierende Antikörper gegen α-Enolase, einem Plasmin(ogen)-bindenden Protein, sowie die Möglichkeit, dass in spezifischer Weise bestimmte Moleküle renal eliminiert werden, werden als Ursache für die besondere Häufigkeit von thromboembolischen Komplikationen bei idiopathischer membranöser Nephropathie diskutiert. Die Serum-Albuminkonzentration stellt ein indirektes Maß für die Thrombosegefährdung bei NS dar. In Anwendung der aktuellen Glomerulonephritis-Leitlinie von KDIGO (Kidney Disease: Improving Global Outcomes) empfiehlt sich bei NS mit einer Serum-Albumkonzentration < 25 g/l und dem Vorhandensein von mindestens einem zusätzlichen thrombogenen Risikofaktor eine primärprophylaktische Antikoagulation („konditionierte Prophylaxe“) mit einem oralen Vitamin K-Antagonisten (Zielbereich: INR 2–3), solange die Serum-Albuminkonzentration < 30 g/l ist.
Abstract
Thromboembolic complications are among the most important extrarenal consequences of nephrotic syndrome (NS). In addition to deep vein thrombosis in the legs and pulmonary embolism, NS is very frequently accompanied by renal vein thrombosis. Due to enhanced procoagulatory and antifibrinolytic potential and reduced anticoagulatory potential, multifactor disruption of hemostatic equilibrium leads to hypercoagulability in NS patients, which is aggravated by an increase in blood viscosity and endothelial dysfunction. Circulating antibodies against α-enolase, a plasmin(ogen)-binding protein, and the possibility of certain molecules being renally eliminated in specific manner are discussed as reasons for the particular frequency of thromboembolic complications in patients with idiopathic membranous nephropathy. Serum albumin concentration is an indicator for the risk of thrombosis in NS patients. When applying the current KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for glomerulonephritis to NS patients with a serum albumin concentration of less than 25 g/l and at least one additional thrombogenic risk factor, primary prophylactic anticoagulation (“conditioned prophylaxis”) with an orally administered vitamin K antagonist (target INR 2–3) is recommended as long as the serum albumin concentration is less than 30 g/l.
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Literatur
- 1 Addis T. Glomerular nephritis, diagnosis and treatment. 1. New York: MacMillan; 1948: 216
- 2 Akoglu H, Agbaht K, Piskinpasa S et al. High frequency of aspirin resistance in patients with nephrotic syndrome. Nephrol Dial Transplant 2012; 27: 1460-1466
- 3 Andrassy K, Ritz E, Bommer J. Hypercoagulability in the nephrotic syndrome. Klin Wochenschr 1980; 58: 1029-1036
- 4 André E, Voisin P, André JL et al. Hemorheological and hemostatic parameters in children with nephrotic syndrome undergoing steroid therapy. Nephron 1994; 68: 184-191
- 5 Appel GB, Blum CB, Chien S et al. The hyperlipidemia of the nephrotic syndrome. Relation to plasma albumin concentration, oncotic pressure, and viscosity. N Engl J Med 1985; 312: 1544-1548
- 6 Barbour SJ, Greenwald A, Djurdjev O et al. Disease-specific risk of venous thromboembolic events is increased in idiopathic glomerulonephritis. Kidney Int 2012; 81: 190-195
- 7 Bazzi C, Petrini C, Rizza V et al. Characterization of proteinuria in primary glomerulonephritides. SDS-PAGE patterns: clinical significance and prognostic value of low molecular weight („tubular“) proteins. Am J Kidney Dis 1997; 29: 27-35
- 8 Bazzi C, Petrini C, Rizza V et al. Characterization of proteinuria in primary glomerulonephritides: urinary polymers of albumin. Am J Kidney Dis 1997; 30: 404-412
- 9 Beck LH, Bonegio RG, Lambeau G et al. M-type phospholipase A₂ receptor as antigen in idiopathic membranous nephropathy. N Engl J Med 2009; 361: 11-21
- 10 Bellomo R, Atkins RC. Membranous nephropathy and thromboembolism: is prophylactic anticoagulation warranted?. Nephron 1993; 63: 249-254
- 11 Böhler T, Linderkamp O, Leo A et al. Increased aggregation with normal surface charge and deformability of red blood cells in children with nephrotic syndrome. Clin Nephrol 1992; 38: 119-124
- 12 Bramham K, Hunt BJ, Goldsmith D. Thrombophilia of nephrotic syndrome in adults. Clin Adv Hematol Oncol 2009; 7: 368-372
- 13 Bruns S, Maurin N. Haemostasis and fibrinolysis disorders in glomerulonephritis with nephrotic syndrome, taking renal biopsy into account. Thromb Haemost 1993; 69: 628
- 14 Cameron JS. Coagulation and thromboembolic complications in the nephrotic syndrome. Adv Nephrol Necker Hosp 1984; 13: 75-114
- 15 Carvalho AC, Colman RW, Lees RS. Platelet function in hyperlipoproteinemia. N Engl J Med 1974; 290: 434-438
- 16 Cecchin E, De Marchi S, Panarello G et al. Rheological abnormalities of erythrocyte deformability and increased glycosylation of hemoglobin in the nephrotic syndrome. Am J Nephrol 1987; 7: 18-21
- 17 Charlesworth JA, Gracey DM, Pussell BA. Adult nephrotic syndrome: non-specific strategies for treatment. Nephrology (Carlton) 2008; 13: 45-50
- 18 Chen M, Zhou PD, Zhao MH et al. Normalbuminaemia is associated with IgA nephropathy in primary glomerulopathy with nephrotic-range proteinuria in Chinese patients. Nephrol Dial Transplant 2011; 26: 1247-1252
- 19 de Sain-van der Velden MG, Rabelink TJ, Reijngoud DJ et al. Plasma α₂ macroglobulin is increased in nephrotic patients as a result of increased synthesis alone. Kidney Int 1998; 54: 530-535
- 20 Dogra GK, Watts GF, Herrmann S et al. Statin therapy improves brachial arterial endothelial function in nephrotic syndrome. Kidney Int 2002; 62: 550-557
- 21 Donadio JV, Anderson CF, Mitchell JC et al. Membranoproliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy. N Engl J Med 1984; 310: 1421-1426
- 22 European Confederation of Laboratory Medicine. European urinalysis guidelines. Scand J Clin Lab Invest Suppl 2000; 231: 1-86
- 23 Gandrille S, Aiach M. Albumin concentration influences fibrinolytic activity in plasma and purified systems. Fibrinolysis 1990; 4: 225-232
- 24 George CR, Clark WF, Cameron JS. The role of platelets in glomerulonephritis. Adv Nephrol Necker Hosp 1975; 5: 19-65
- 25 Glassock RJ. Prophylactic anticoagulation in nephrotic syndrome: a clinical conundrum. J Am Soc Nephrol 2007; 18: 2221-2225
- 26 Glassock RJ. The pathogenesis of idiopathic membranous nephropathy: a 50-year odyssey. Am J Kidney Dis 2010; 56: 157-167
- 27 Gupta K, Iskandar SS, Daeihagh P et al. Distribution of pathologic findings in individuals with nephrotic proteinuria according to serum albumin. Nephrol Dial Transplant 2008; 23: 1595-1599
- 28 Hofstra JM, Beck LH, Beck DM et al. Anti-phospholipase A₂ receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 2011; 6: 1286-1291
- 29 Hoxha E, Kneißler U, Stege G et al. Enhanced expression of M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy. Kidney Int 2012; 82: 797-804
- 30 Joergensen KA, Stoffersen E. On the inhibitory effect of albumin on platelet aggregation. Thromb Res 1980; 17: 13-18
- 31 Joles JA, Stroes ES, Rabelink TJ. Endothelial function in proteinuric renal disease. Kidney Int 1999; 56 Suppl (Suppl. 71) S57-S61
- 32 Kambham N, Markowitz GS, Valeri AM et al. Obesity-related glomerulopathy: an emerging epidemic. Kidney Int 2001; 59: 1498-1509
- 33 Kanfer A. Coagulation factors in nephrotic syndrome. Am J Nephrol 1990; 10 Suppl (Suppl. 01) 63-68
- 34 Kauffmann RH, Veltkamp JJ, Van Tilburg NH et al. Acquired antithrombin III deficiency and thrombosis in the nephrotic syndrome. Am J Med 1978; 65: 607-613
- 35 Kerjaschki D. Pathomechanisms and molecular basis of membranous glomerulopathy. Lancet 2004; 364: 1194-1196
- 36 Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO clinical practice guideline for glomerulonephritis. Kidney Int Suppl 2012; 2: 139-274
- 37 Kim HS, Fine DM, Atta MG. Catheter-directed thrombectomy and thrombolysis for acute renal vein thrombosis. J Vasc Interv Radiol 2006; 17: 815-822
- 38 Kincaid-Smith P, Saker BM, Failey KF. Anticoagulants in „irreversible“ acute renal failure. Lancet 1968; II: 1360-1363
- 39 Kirschkamp T, Schmid-Schönbein H, Weinberger A et al. Effects of fibrinogen and α₂-macroglobulin and their apheretic elimination on general blood rheology and rheological characteristics of red blood cell aggregates. Ther Apher Dial 2008; 12: 360-367
- 40 Klassen J, Sugisaki T, Milgrom F et al. Studies on multiple renal lesions in Heymann nephritis. Lab Invest 1971; 25: 577-585
- 41 Kuhlmann U, Steurer J, Bollinger A et al. Inzidenz und klinische Bedeutung von Thrombosen und thromboembolischen Komplikationen bei Patienten mit nephrotischem Syndrom. Schweiz Med Wochenschr 1981; 111: 1034-1040
- 42 Lam KK, Lui CC. Successful treatment of acute inferior vena cava and unilateral renal vein thrombosis by local infusion of recombinant tissue plasminogen activator. Am J Kidney Dis 1998; 32: 1075-1079
- 43 Laville M, Aguilera D, Maillet PJ et al. The prognosis of renal vein thrombosis: a re-evaluation of 27 cases. Nephrol Dial Transplant 1988; 3: 247-256
- 44 Lefaucheur C, Stengel B, Nochy D et al. Membranous nephropathy and cancer: epidemiologic evidence and determinants of high-risk cancer association. Kidney Int 2008; 70: 1510-1517
- 45 Lionaki S, Derebail VK, Hogan SL et al. Venous thromboembolism in patients with membranous nephropathy. Clin J Am Soc Nephrol 2012; 7: 43-51
- 46 Livio M. “Hypercoagulability” in the nephrotic syndrome. In: Remuzzi G, Rossi EC, eds. Haemostasis and the kidney. London: Butterworths; 1989: 145-152
- 47 Llach F. Hypercoagulability, renal vein thrombosis, and other thrombotic complications of nephrotic syndrome. Kidney Int 1985; 28: 429-439
- 48 Llach F, Papper S, Massry SG. The clinical spectrum of renal vein thrombosis: acute and chronic. Am J Med 1980; 69: 819-827
- 49 Mahmoodi BK, ten Kate MK, Waanders F et al. High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: results from a large retrospective cohort study. Circulation 2008; 117: 224-230
- 50 Mannucci PM, Valsecchi C, Bollasso B et al. High plasma levels of protein C activity and antigen in the nephrotic syndrome. Thromb Haemost 1986; 55: 31-33
- 51 Maurin N. Heparinresistenz und Antithrombinmangel. Med Klin (Munich) 2009; 104: 441-449
- 52 McGinley E, Lowe GD, Boulton-Jones M et al. Blood viscosity and haemostasis in the nephrotic syndrome. Thromb Haemost 1983; 49: 155-157
- 53 Mercadal L, Montcel ST, Nochy D et al. Factors affecting outcome and prognosis in membranous lupus nephropathy. Nephrol Dial Transplant 2002; 17: 1771-1778
- 54 Orth SR, Ritz E. The nephrotic syndrome. N Engl J Med 1998; 338: 1202-1211
- 55 Pabinger-Fasching I, Lechner K, Niessner H et al. High levels of plasma protein C in nephrotic syndrome. Thromb Haemost 1985; 18: 5-7
- 56 Pancholi V, Fischetti VA. alpha-enolase, a novel strong plasmin(ogen) binding protein on the surface of pathogenic streptococci. J Biol Chem 1998; 273: 14503-14515
- 57 Praga M, Morales E, Herrero JC et al. Absence of hypoalbuminemia despite massive proteinuria in focal segmental glomerulosclerosis secondary to hyperfiltration. Am J Kidney Dis 1999; 33: 52-58
- 58 Rabelink TJ, Zwaginga JJ, Koomans HA et al. Thrombosis and hemostasis in renal disease. Kidney Int 1994; 46: 287-296
- 59 Remuzzi G, Mecca G, Marchesi D et al. Platelet hyperaggregability and the nephrotic syndrome. Thromb Res 1979; 16: 345-354
- 60 Robert A, Olmer M, Sampol J et al. Clinical correlation between hypercoagulability and thrombo-embolic phenomena. Kidney Int 1987; 31: 830-835
- 61 Rostoker G, Durand-Zaleski I, Petit-Phar M et al. Prevention of thrombotic complications of the nephrotic syndrome by the low-molecular-weight heparin enoxaparin. Nephron 1995; 69: 20-28
- 62 Rydzewski A, Mysiliwiec M, Soszka J. Concentration of three thrombin inhibitors in the nephrotic syndrome in adults. Nephron 1986; 42: 200-203
- 63 Sagripanti A, Barsotti G. Hypercoagulability, intraglomerular coagulation, and thromboembolism in nephrotic syndrome. Nephron 1995; 70: 271-281
- 64 Sarasin FP, Schifferli JA. Prophylactic oral anticoagulation in nephrotic patients with idiopathic membranous nephropathy. Kidney Int 1994; 45: 578-585
- 65 Schlegel N. Thromboembolic risks and complications in nephrotic children. Semin Thromb Hemost 1997; 23: 271-280
- 66 Schreiner GE. The nephrotic syndrome. In: Strauss MB, Welt LG, eds. Diseases of the kidney. Boston, Massachusetts: Little, Brown & Co; 1963: 335-444
- 67 Sethi S, Fervenza FC. Membranoproliferative glomerulonephritis – a new look at an old entity. N Engl J Med 2012; 366: 1119-1131
- 68 Singhal R, Brimble KS. Thromboembolic complications in the nephrotic syndrome: pathophysiology and clinical management. Thromb Res 2006; 118: 397-407
- 69 Stahl RAK, Hoxha E, Helmchen U. Membranöse Glomerulonephritis: Diffenziertere Therapien durch Autoantikörperbestimmung?. Dtsch Med Wochenschr 2011; 136: 1733-1737
- 70 Terrier B, Degand N, Guilpain P et al. Alpha-enolase: a target of antibodies in infectious and autoimmune diseases. Autoimmun Rev 2007; 6: 176-182
- 71 Thaler E, Balzar E, Kopsa H et al. Acquired antithrombin III deficiency in patients with glomerular proteinuria. Haemostasis 1978; 7: 257-272
- 72 Ueda N, Kawaguchi S, Niinomi Y et al. Effect of corticosteroids on coagulation factors in children with nephrotic syndrome. Pediatr Nephrol 1987; 1: 286-289
- 73 Vaziri ND. Nephrotic syndrome and coagulation and fibrinolytic abnormalities. Am J Nephrol 1983; 3: 1-6
- 74 Vaziri ND, Alikhani S, Patel B et al. Increased levels of protein C activity, protein C concentration, total and free protein S in nephrotic syndrome. Nephron 1988; 49: 20-23
- 75 Vassalli P, Simon G, Rouiller G. Electron microscopic study of glomerular lesions resulting from intravascular fibrin formation. Am J Pathol 1963; 43: 579-617
- 76 Vigano-D’Angelo S, D’Angelo A, Kaufman CE et al. Protein S deficiency occurs in the nephrotic syndrome. Ann Intern Med 1987; 107: 42-47
- 77 Wagoner RD, Stanson AW, Holley KE et al. Renal vein thrombosis in idiopathic membranous glomerulopathy and nephrotic syndrome: incidence and significance. Kidney Int 1983; 23: 368-374
- 78 Wakui H, Imai H, Komatsuda A et al. Circulating antibodies against alpha-enolase in patients with primary membranous nephropathy (MN). Clin Exp Immunol 1999; 118: 445-450
- 79 Weger N, Stawicki SP, Roll G et al. Bilateral renal vein thrombosis secondary to membraneous glomerulonephritis: successful treatment with thrombolytic therapy. Ann Vasc Surg 2006; 20: 411-414
- 80 Wysokinski WE, Gosk-Bierska I, Greene EL et al. Clinical characteristics and long-term follow-up of patients with renal vein thrombosis. Am J Kidney Dis 2008; 51: 224-232
- 81 Yoshida Y, Shiiki H, Iwano M et al. Enhanced expression of plasminogen activator inhibitor 1 in patients with nephrotic syndrome. Nephron 2001; 88: 24-29
- 82 Zwaginga JJ, Koomans HA, Sixma JJ et al. Thrombus formation and platelet-vessel wall interaction in the nephrotic syndrome under flow conditions. J Clin Invest 1994; 93: 204-211