Download PDF
Thromb Haemost 1994; 71(01): 019-025
DOI: 10.1055/s-0038-1642379
Review Article
Schattauer GmbH Stuttgart

Blood Fibrinolysis and the Response to Desmopressin in Glomerulonephritis

E J P Brommer
1   The Gaubius Laboratory IVVO-TNO, University of Leiden, Leiden, The Netherlands
,
A W L Van den Wall Bake
2   The Department of Nephrology, University Hospital Leiden, The Netherlands
,
G Dooijewaard
1   The Gaubius Laboratory IVVO-TNO, University of Leiden, Leiden, The Netherlands
,
B J Potter van Loon
2   The Department of Nephrology, University Hospital Leiden, The Netherlands
,
J J Emeis
1   The Gaubius Laboratory IVVO-TNO, University of Leiden, Leiden, The Netherlands
,
J J Weening
3   The Department of Pathology, University of Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received: 18 March 1993

Accepted after revision 28 September 1993

Publication Date:
12 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Fibrinolytic parameters and von Willebrand factor (VWF) antigen were measured in 22 patients with glomerulonephritis (GN) who underwent renal biopsy after desmopressin (DDAVP) infusion. Blood was collected immediately before and after DDAVP infusion, after one week, and 3–6 months later. The main abnormalities on admission were the following: the mean baseline levels of t-PA antigen and VWF were significantly higher in GN patients than in 22 healthy controls; the median t-PA activity and the mean scu-PA level were significantly lower than normal . The t-PA response to DDAVP was impaired in 7 patients (32%), the response of VWF in 9 patients (41%), and the u-PA: Ag response in 11 patients (50%). When the patients were stratified according to creatinine clearance rate, significant differences between the subgroups with severely and moderately impaired renal function were noted: the baseline levels of PAI activity and VWF were higher in patients with severe renal failure and the VWF response to DDAVP was significantly lower. The response of u-PA (not of t-PA or VWF) to DDAVP appeared to correlate with urine flow during the first 24 h, suggesting the dependence of u-PA release on intact nephrons. A series of 18 patients with adult-type polycystic kidney disease (APKD) with creatinine clearance rates in the same abnormal range as the GN patients, had lower mean PAI and a significantly higher mean scu-PA level. Normalization of scu-PA and t-PA:Ag levels during follow-up despite impaired renal function in GN, and the absence of depressed scu-PA levels in APKD suggest that the fibrinolytic abnormalities are independent of the impaired renal function per se, but associated with the acute stage of nephritis.

 

  • References

  • 1 Vassalli P, Simon G, Rouiller Ch. Electron microscopic study of glomerular lesions resulting from intravascular fibrin formation. Am J Pathol 1963; 43: 579-616
    PubMedSearch in Google Scholar
  • 2 Hoyer J, Michael AF, Hoyer LW. Immunofluorescent localization of antihemophilic factor and fibrinogen m human renal diseases. J Clin Invest 1974; 53: 1375-84
    CrossrefPubMedSearch in Google Scholar
  • 3 Takemura T, Yoshioka K, Akano N, Miyamoto H, Matsumoto K, Maki S. Glomerular deposition of cross-linked fibrin in human kidney diseases. Kidney Tnt 1987; 37: 107-11
    PubMedSearch in Google Scholar
  • 4 Müller-Berghaus G, Róka L, Lasch HG. Induction of glomerular microclot formation by fibrin monomer infusion. Thromb Diath Haemorrh 1973; 29: 275-82
    PubMedSearch in Google Scholar
  • 5 Margaretten W, Csavossy I, Mc Kay DG. An electron microscopic study of thrombin-induced disseminated intravascular coagulation. Blood 1967; 29: 169-81
    PubMedSearch in Google Scholar
  • 6 Vassalli P, Mc Cluskey RT. The pathogenic role of the coagulation process in rabbit Masugi nephritis. Am J Pathol 1964; 45: 653-66
    PubMedSearch in Google Scholar
  • 7 Briggs JD, Kwaan HC, Potter EV. The role of fibrinogen in renal disease. III. Fibrinolytic and anticoagulant treatment of nephrotoxic serum nephritis in mice. J Lab Clin Med 1969; 74: 715-24
    PubMedSearch in Google Scholar
  • 8 Min KW, Gyorkey F, Gyorkey P, Yium JJ, Eknoyan G. The morphogenesis of glomerular crescents in rapidly progressive glomerulonephritis. Kidney Int 1974; 5: 47-56
    CrossrefPubMedSearch in Google Scholar
  • 9 Tipping PG, Dowling JP, Holdsworth SR. Glomerular procoagulant activity in human proliferative glomerulonephritis. J Clin Invest 1988; 81: 119-25
    CrossrefPubMedSearch in Google Scholar
  • 10 Angles-Cano E, Balaton A, Le Bonniec B, Genot E, Elion J, Sultan Y. Production of monoclonal antibodies to the high fibrin-affinity, tissue-type plasminogen activator of human plasma. Demonstration of its endothelial origin by immunolocalization. Blood 1985; 66: 913-20
    PubMedSearch in Google Scholar
  • 11 Angles-Cano E, Rondeau E, Delarue F, Hagege J, Sultan Y, Sraer JD. Identification and cellular localization of plasminogen activators from human glomeruli. Thromb Haemostas 1985; 54: 688-92
    PubMedSearch in Google Scholar
  • 12 Aya N, Yoshioka K, Murakami K, Hino S, Okada K, Matsou O, Maki S. Tissue-type plasminogen activator and its inhibitor in human glomerulonephritis. J Path 1992; 166: 289-95
    CrossrefPubMedSearch in Google Scholar
  • 13 Tranquille N, Emeis JJ. Protein synthesis inhibition by cycloheximide does not affect the acute release of tissue-type plasminogen activator. Thromb Haemostas 1989; 61: 442-7
    PubMedSearch in Google Scholar
  • 14 Van Hinsbergh VW M, Van den Berg EA, Fiers W, Dooijewaard G. Tumor necrosis factor induces the production of urokinase-type plasminogen activator by human endothelial cells. Blood 1990; 75: 1991-8
    PubMedSearch in Google Scholar
  • 15 Wojta J, Hoover RL, Daniel TO. Vascular origin determines plasminogen activator expression in human endothelial cells. Renal endothelial cells produce large amounts of single chain urokinase type plasminogen activator. J Biol Chem 1989; 264: 2846-52
    PubMedSearch in Google Scholar
  • 16 Sakakibara K, Urano T, Takada Y, Takada A, Urinary UK. t-PA and urinary trypsin inhibitor in health and glomerular diseases. Thromb Res 1989; 56: 239-49
    CrossrefPubMedSearch in Google Scholar
  • 17 Iwamoto T, Nakashima Y, Sueishi K. Secretion of plasminogen activator and its inhibitor by glomerular epithelial cells. Kidney Int 1990; 37: 1466-76
    CrossrefPubMedSearch in Google Scholar
  • 18 Rondeau E, Angles-Cano E, Delarue F, Sultan Y, Sraer J-D. Polyunsaturated fatty acids increase fibrinolytic activity of human isolated glomeruli. Kidney Int 1986; 30: 701-5
    CrossrefPubMedSearch in Google Scholar
  • 19 Hasui Y, Suzumiya J, Symiyoshi A, Hashida S, Ishikawa E. Distribution of plasminogen activators in human kidney and male genital organs using a highly sensitive enzyme immunoassay. Thromb Res 1988; 51: 453-9
    CrossrefPubMedSearch in Google Scholar
  • 20 Lacave R, Rondeau E, Ochi S, Delarue F, Schleuning WD, Sraer J-D. Characterization of a plasminogen activator and its inhibitor in human mesangial cells. Kidney Int 1989; 35: 806-11
    CrossrefPubMedSearch in Google Scholar
  • 21 Sappino A-P, Huarte J, Vassalli J-D, Belin D. Sites of synthesis of urokinase and tissue-type plasminogen activators in the murine kidney. J Clin Invest 1991; 87: 962-70
    CrossrefPubMedSearch in Google Scholar
  • 22 Hong SY, Yang DH, Kim PN. Urokinase concentration in the renal artery and vein. Nephron 1992; 61: 176-80
    CrossrefPubMedSearch in Google Scholar
  • 23 Mannucci PM. Enhancement of plasminogen activator by vasopressin and adrenaline: a role of cyclic AMP?. Thromb Res 1974; 4: 539-49
    CrossrefPubMedSearch in Google Scholar
  • 24 Grant PJ, Medcalf RL. Hormonal regulation of haemostasis and the molecular biology of the fibrinolytic system. Clinical Science 1990; 78: 3-11
    CrossrefPubMedSearch in Google Scholar
  • 25 Levi M, ten Cate JW, Dooijewaard G, Sturk A, Brommer EJ P, Agnelli G. DDAVP induces systemic release of urokinasc-typc plasminogen activator. Thromb Haemostas 1989; 62: 686-9
    PubMedSearch in Google Scholar
  • 26 van dcr Poll T, Levi M, Biiller IIR, van Deventer SJ H, de Boer JP, Hack E, ten Cate JW. Fibrinolytic response to tumor necrosis factor in healthy subjects. J Exp Med 1991; 174: 729-32
    CrossrefPubMedSearch in Google Scholar
  • 27 Philippé J, Offner F, Declcrck PJ, Lcroux-Rocls G, Vogelaers D, Baele G, Collen D. Fibrinolysis and coagulation in patients with infectious disease and sepsis. Thromb Haemostas 1991; 65: 291-5
    PubMedSearch in Google Scholar
  • 28 Philippé J, Dooijewaard G, Offner F, Turion P, Baele G, Leroux-Roels G. Granulocyte elastase, tumor necrosis factor-a and urokinase levels as prognostic markers in severe infection. Thromb Haemostas 1992; 68: 19-23
    PubMedSearch in Google Scholar
  • 29 Sprengers E, Kluft C. Plasminogen activator inhibitors. Blood 1987; 69: 381-7
    PubMedSearch in Google Scholar
  • 30 Pannell R, Gurewich V. Pro-urokinase: a study of its stability in plasma and of a mechanism for its selective fibrinolytic effect. Blood 1986; 67: 1215-23
    PubMedSearch in Google Scholar
  • 31 Lijnen HR, Stump DC, Collen DC. Single-chain urokinase-type plasminogen activator: mechanism of action and thrombolytic properties. Semin Thromb Haemostas 1987; 13: 152-9
    Thieme ConnectPubMedSearch in Google Scholar
  • 32 Blasi F. Surface receptors for urokinase plasminogen activator. Fibrinolysis 1988; 2: 73-84
    PubMedSearch in Google Scholar
  • 33 Dosne A-M, Dubor F, Samama M. Importance of plasminogen activator inhibitor type 1 (PAI-1) for preventing single chain urokinase plasminogen activator (scu-PA) conversion into two-chain urokinase plasminogen activator (tcu-PA) in plasma in vitro. Thromb Res 1991; 63: 531-9
    CrossrefPubMedSearch in Google Scholar
  • 34 Baricos WH, Shah V. Proteolytic enzymes as mediators of glomerular injury. Kidney Int 1991; 40: 161-73
    CrossrefPubMedSearch in Google Scholar
  • 35 Bergstein JM, Michael AF. Cortical fibrinolytic activity in normal and diseased human kidneys. J Lab Clin Med 1972; 79: 702-9
    PubMedSearch in Google Scholar
  • 36 Rondeau E, Mougenot B, Lacave R, Peraldi MN, Kruithof EK O, Sraer JD. Plasminogen activator inhibitor 1 in renal fibrin deposits of human nephropathies. Clin Nephrol 1990; 33: 55-60
    PubMedSearch in Google Scholar
  • 37 Brommer EJ P, Barrett-Bergshoeff MM, Allen RA, Schicht I, Bertina RM, Schalekamp MADH. The use of desmopressin acetate (DDAVP) as a test of the fibrinolytic capacity of patients – Analysis of responders and non-responders. Thromb Haemostas 1982; 48: 156-61
    PubMedSearch in Google Scholar
  • 38 Mannucci PM, Canciani MT, Rota L, Donovan BS. Response of factor VIII/von Willebrand factor to DDAVP in healthy subjects and patients with haemophilia A and von Willebrand's disease. Br J Haematol 1981; 47: 283-93
    CrossrefPubMedSearch in Google Scholar
  • 39 Koppert PW, Huijsmans CM G, Nieuwenhuizen W. A monoclonal antibody, specific for human fibrinogen, fibrinopeptide A-containing fragments and not reacting with free fibrinopeptide A. Blood 1985; 66: 503-7
    PubMedSearch in Google Scholar
  • 40 Koppert PW, Koopman J, Haverkate F, Nieuwenhuizen W. Production and characterization of a monoclonal antibody reactive with a specific neoantigenic determinant (comprising B(3 54-118) in degradation products of fibrin and of fibrinogen. Blood 1986; 68: 437-41
    PubMedSearch in Google Scholar
  • 41 Verheijen JH, Mullaart E, Chang GT G, Kluft C, Wijngaards G. A simple, sensitive spectrophotometric assay for extrinsic (tissue-type) plasminogen activator applicable to measurements in plasma. Thromb Haemostas 1982; 48: 266-9
    PubMedSearch in Google Scholar
  • 42 Gaffney PH, Curtis AD. A collaborative study of a proposed international standard for tissue plasminogen activator (t-PA). Thromb Haemostas 1985; 53: 134-40
    PubMedSearch in Google Scholar
  • 43 Rijken DC, van Hinsbergh VW M, Sens EH C. Quantitation of tissue-type plasminogen activator in human endothelial cell cultures by use of an enzyme immunoassay. Thromb Res 1984; 33: 145-53
    CrossrefPubMedSearch in Google Scholar
  • 44 Binnema DJ, van Iersel JJ L, Dooijewaard G. Quantitation of urokinase antigen in plasma and culture media by use of an ELISA. Thromb Res 1986; 43: 569-77
    CrossrefPubMedSearch in Google Scholar
  • 45 Verheijen JH, Chang GT G, Kluft C. Evidence for the occurrence of a fast-acting inhibitor for tissue-type plasminogen activator in human plasma. Thromb Haemostas 1984; 51: 392-5
    PubMedSearch in Google Scholar
  • 46 Levi M, Lensing AW A, Biiller HR, Prandoni P, Dooijewaard G, Cuppini S, ten Cate JW. Deep vein thrombosis and fibrinolysis. Defective urokinase type plasminogen activator release. Thromb Haemostas 1991; 66: 426-9
    PubMedSearch in Google Scholar
  • 47 Ludlam CA, Peake IR, Allen N, Davies BL, Furlong RA, Bloom AL. Factor VIII and fibrinolytic response to deamino-8-D-arginine vasopressin in normal subjects and dissociate response in some patients with haemophilia and von Willebrand's disease. Br J Haematol 1980; 45: 499-511
    CrossrefPubMedSearch in Google Scholar
  • 48 Kobrinsky NL, Doyle JJ, Israels ED, Winter JS D, Cheang MS, Walker RD, Bishop AJ. Absent factor VIII response to synthetic vasopressin analogue (DDAVP) in nephrogenic diabetes insipidus. Lancet 1985; i: 1293-4
    PubMedSearch in Google Scholar
  • 49 Bichet DG, Razi M, Lonergan M, Arthus M-F, Papukna V, Kortas C, Barjon J-N. Hemodynamic and coagulation responses to l-desamino[8-D-arginine] vasopressin in patients with congenital nephrogenic diabetes insipidus. N Engl J Med 1988; 318: 881-7
    CrossrefPubMedSearch in Google Scholar
  • 50 Brommer EJ P, Brink H, Derkx FH M, Schalekamp MA H, Stibbe J. Normal homeostasis of fibrinolysis in nephrogenic diabetes insipidus in spite of defective V2-receptor-mediated responses of tissue plasminogen activator release. Eur J Clin Invest 1990; 20: 72-8
    PubMedSearch in Google Scholar
  • 51 Menzel D, Levi M, Peters M, Dooijewaard G, Monnens L, Ten Cate JW. Impaired fibrinolysis in haemolytic uremic syndrome of childhood. Blood 1991; 78: 216a
    PubMedSearch in Google Scholar
  • 52 Heilman RL, Offord KP, Holley KE, Velosa JA. Analysis of risk factors for patient and renal survival in crescentic glomerulonephritis. Am J Kidney Dis 1987; IX: 98-107
    PubMedSearch in Google Scholar
  • 53 Hinsbergh VW M, Bauer KA, Kooistra T, Kluft C, Dooijewaard G, Sherman ML, Nieuwenhuizen W. Progress of fibrinolysis during tumor necrosis factor infusions in humans. Concomitant increase in tissue-type plasminogen activator, plasminogen activator inhibitor type-1, and fibrin(ogen) degradation products. Blood 1990; 76: 2284-9
    PubMedSearch in Google Scholar
  • 54 Brommer EJ P, Dooijewaard G, Rijken DC, Kluft C, Emeis JJ, Brakman P. Progress in clinical fibrinolysis. In: Poller L. (ed) Recent advances in blood coagulation Number 6 Churchill Livingstone Edinburgh; 1993: 1-15
    Search in Google Scholar
  • 55 Mannucci PM, Åberg M, Nilsson IM, Robertson B. Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs. Br J Haemat 1975; 30: 81-93
    CrossrefPubMedSearch in Google Scholar
  • 56 Brommer EJ P, Schicht I, Wijngaards G, Verheijen JH, Rijken DC. Fibrinolytic activators and inhibitors in terminal renal insufficiency and in anephric patients. Thromb Haemostas 1984; 52: 311
    PubMedSearch in Google Scholar
  • 57 Zoja C, Corna D, Macconi D, Zilio P, Bertani T, Remuzzi G. Tissue plasminogen activator therapy of rabbit nephrotoxic nephritis. Lab Invest 1990; 62: 34-40
    PubMedSearch in Google Scholar
  • 58 Pollak VE, Glueck HI, Lebron-Berges A, Miller MA. Defibrination with Ancrod in glomerulonephritis: effects on clinical and histologic findings and on blood coagulation. Am J Nephrol 1982; 2: 195-207
    CrossrefPubMedSearch in Google Scholar
  • 59 Dosekun AK, Pollak VE, Glas-Greenwalt P. et al Ancrod in systemic lupus erythematosus with thrombosis. Clinical and fibrinolysis effects. Arch Int Med 1984; 144: 37-42
    CrossrefPubMedSearch in Google Scholar
  • 60 Glas-Greenwalt P, Kant SK, Dosekun A, Frazier J, Allen C, Pollak VE. Ancrod: normalization of fibrinolytic enzyme abnormalities in patients with lupus erythematosus and lupus nephritis. J Lab Clin Med 1985; 105: 99-107
    PubMedSearch in Google Scholar
  • 61 Kant KS, Pollak VE, Dosekun A, Glas-Greenwalt P, Weiss MA, Glueck HI. Lupus nephritis with thrombosis and abnormal fibrinolysis: effect of ancrod. J Lab Clin Med 1985; 105: 77-88
    PubMedSearch in Google Scholar