The role of suPAR in kidney diseases
 
More details
Hide details
1
Katedra Chorób Wewnętrznych, Diabetologii i Nefrologii, Wydział Lekarski z Oddziałem Lekarsko-Dentystycznym w Zabrzu, Śląski Uniwersytet Medyczny w Katowicach
 
2
Oddział Nefrologii, Wojewódzki Szpital Specjalistyczny nr 4 w Bytomiu
 
 
Corresponding author
Beata Łącka-Gaździk   

Katedra Chorób Wewnętrznych, Diabetologii i Nefrologii, Wydział Lekarski z Oddziałem Lekarsko-Dentystycznym w Zabrzu, Śląski Uniwersytet Medyczny w Katowicach, 3-go Maja 13/15, 41-800 Zabrze, Polska
 
 
Ann. Acad. Med. Siles. 2017;71:265-274
 
KEYWORDS
TOPICS
ABSTRACT
Chronic kidney disease (CKD) is unquestionably a problem of social significance because it affects about 10% of the population. There is a search for biomarkers which could help select persons out of such a large group of patients with a high risk of disease progression and of its complications. The major cause of death in patients with end-stage renal disease are cardiovascular diseases. Accelerated atherosclerosis in this group of patients is associated with a chronic inflammatory state. The new biological marker of inflammation suPAR (soluble urokinase-type plasminogen activator receptor), is the focus of attention of the authors of this report. The relationship of suPAR with urinary tract infections and focal segmental glomerulosclerosis is also very interesting from the clinical perspective. The perception of suPAR as a blood circulating factor, inducing FSGS, throws new light on the pathomechanism of this medical condition, while unveiling promising therapeutic perspectives. A better understanding of the pathogenesis of the diseases discussed will help to reduce the unacceptably high mortality rate in patients with CKD. At present, common assaying of suPAR is not yet possible in the context of the above-mentioned issues. Nevertheless, studies are ongoing which may explain the still unclear issues concerning the relationship of the biomarker with the mentioned kidney diseases. Perhaps, follo-wing their results suPAR assays may in the near future become routine diagnostics means in selected kidney diseases.
REFERENCES (71)
1.
Rutkowski B. Przewlekła choroba nerek – diagnostyka i leczenie. Via Medica, Gdańsk 2012: VII-VIII; s. 86–87.
 
2.
Rutkowski B., Lichodziejewska-Niemierko M., Grenda R., Czekalski S., Durlik M., Bautembach S. Raport o stanie leczenia nerkozastępczego w Polsce – 2009. Gdańsk 2012.
 
3.
Thuno M., Macho B., Eugen-Olsen J. suPAR: the molecular crystal ball. Dis. Markers 2009; 27(3): 157–172.
 
4.
Szczeklik A. Choroby wewnętrzne. Medycyna Praktyczna. Kraków 2006, s. 1394–1399; 1337–1340.
 
5.
Thielemann A., Kopczyński Z. Zaburzenia układu fibrynolitycznego u chorych na raka. Nowiny Lek. 2012; 81(2): 164–169.
 
6.
Xu L.B., Chi N., Shi W. Amiloride, a urokinase-type plasminogen activator receptor (uTPA) inhibitor, reduces proteinuria in podocytes. Genet. Mol. Res. 2015; 14(3): 9518–9529.
 
7.
Resnati M., Guttinger M., Valcamonica S., Sidenius N., Blasi F., Fazioli F. Proteolytic cleavage of the urokinase receptor substitutes for the agonist-induced chemotactic effect. EMBO J. 1996; 15(7): 1572–1582.
 
8.
Wilhelm O.G., Wilhelm S., Escott G.M., Lutz V., Magdolen V., Schmitt M., Rifkin D.B., Wilson E.L., Graeff H., Brunner G. Cellular glycosylphosphatidylinositol-specific phospholipase D regulates urokinase receptor shedding and cell surface expression. J. Cell Physiol. 1999; 180(2): 225–235.
 
9.
Hoyer-Hansen G., Pessara U., Holm A. Pass J, Weidle U, Danø K, Behrendt N. Urokinase-catalysed cleavage of the urokinase receptor requires an intact glycolipid anchor. Biochem. J. 2001; 358(Pt3): 673–679.
 
10.
Wei C., El Hindi S., Li J. Fornoni A., Goes N., Sageshima J., Maiguel D., Karumanchi S.A., Yap H.K., Saleem M., Zhang Q., Nikolic B., Chaudhuri A., Daftarian P., Salido E., Torres A., Salifu M., Sarwal M.M., Schaefer F., Morath C., Schwenger V., Zeier M., Gupta V., Roth D., Rastaldi M.P., Burke G., Ruiz P., Reiser J. Circulating urokinase receptor as a causa of focal segmental glomerulosclerosis. Nat. Med. 2011; 17(8): 952–960.
 
11.
Florquin S., van den Berg J.G., Olszyna D.P. Claessen N., Opal S.M., Weening J.J., van der Poll T. Relase of urokinase plasminogen activator receptor during urosepsis and ednotoxemia. Kidney Int. 2001; 59(6): 2054–2061.
 
12.
Gustafsson A., Ajeti V., Ljunggren L. Detection of suPAR in the saliva of healthy young adults: comparison with plasma levels. Biomark Insights 2011; 6: 119–125.
 
13.
Tzanakaki G., Paparoupa M., Kyprianou M., Barbouni A., Eugen-Olsen J., Kourea-Kremastinou J. Elevated soluble urokinase receptor values in CSF, age and bacterial meningitis infection are independent and additive risk factors of fatal outcome. Eur. J. Clin. Microbiol. Infect. Dis. 2012; 31(6): 1157–1162.
 
14.
Leandersson P., Kalapotharakos G., Henic E., Borgfeldt H., Petzold M., Høyer-Hansen G., Borgfeldt C. A Biomarker Panel Increases the Diagnostic Performance for Epithelial Ovarian Cancer Type I and II in Young Women. Anticancer Res. 2016; 36(3): 957–965.
 
15.
Shen J., Wang Q., Wang J. Su G.H., Wang J., Guo S.H., Liu Y.A., Wu Z., Liu R.F., Li X., Guo X.J., Cao J., Zhang Y.H., Wang Z.Y. Analysis of soluble urokinase plasminogen activator receptor in multiple myeloma for predicting prognosis. Oncol. Lett. 2015; 10(4): 2403–2409.
 
16.
Kasanq C., Kalluvya S., Majinge C., Kongola G., Mlewa M., Massawe I., Kabyemera R, Magambo K., Ulmer A., Klinker H., Gschmack E., Horn A., Koutsilieri E., Preiser W., Hofmann D., Hain J., Müller A., Dölken L., Weissbrich B., Rethwilm A, Stich A., Scheller C. Effects of Prednisolone on Disease Progression in Antiretroviral-Untreated HIV Infection: A 2-Year Randomized, Double-Blind Placebo-Controlled Clinical Trial. PLoS One 2016; 11(1): e0146678.
 
17.
Outinen T.K., Tervo L., Makela S., Huttunen R., Mäenpää N., Huhtala H., Vaheri A., Mustonen J., Aittoniemi J. Plasma levels of soluble urokinase-type plasminogen activator receptor associate with the clinical severity of acute Puumala hantavirus infection. PLoS One 2013; 8(8): e71335.
 
18.
Siahanidou T., Margeli A., Tsirogianni C., Charoni S., Giannaki M., Vavourakis E., Charisiadou A., Papassotiriou I. Clinical value of plasma soluble urokinase-type plasminogen activator receptor levels in term neonates with infection or sepsis: a prospective study. Mediators Inflamm. 2014; 2014: 375702.
 
19.
Backes Y., van der Sluijs K.F., Mackie D.P., Tacke F., Koch A., Tenhunen J.J., Schultz M.J. Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systemic review. Intensive Care Med. 2012; 38(9): 1418–1428.
 
20.
Koch A., Voigt S., Kruschinski C., Sanson E., Dückers H., Horn A., Yagmur E., Zimmermann H., Trautwein C., Tacke F. Circulating soluble urokinase plasminogen activator receptor is stably elevated during the first week of treatment in the intensive care unit and predicts mortality in critically ill patients. Crit. Care 2011; 15(1): R63.
 
21.
Eugen-Olsen J., Andersen O., Linneberg A., Ladelund S., Hansen T.W., Langkilde A., Petersen J., Pielak T., Møller L.N., Jeppesen J., Lyngbaek S., Fenger M., Olsen M.H., Hildebrandt P.R., Borch-Johnsen K., Jørgensen T., Haugaard S.B. Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population. J. Intern. Med. 2010; 268(3): 296–308.
 
22.
Wittenhagen P., Andersen J.B., Hansen A., Lindholm L., Rønne F., Theil J., Tvede M., Eugen-Olsen J. Plasma soluble urokinase plasminogen activator receptor in children with urinary tract infection. Biomark Insights. 2011; 6: 79–82.
 
23.
O’Shaughnessy M.M., Montez-Rath M.E., Lafayette R.A., Winkelmayer W.C. Patient characteristics and outcomes by GN subtype in ESRD. Clin. J. Am. Soc. Nephrol. 2015; 10(7): 1170–1178.
 
24.
Radha S., Afroz T., Prasad Ch.R. Sridhar G., Rajaram K.G., Reddy S. Focal segmental glomerulosclerosis in renal allografts: Is it possible to diagnose the etiology? Indian J. Nephrol. 2015; 25(2): 82–85.
 
25.
Couser W. Reccurent glomerulonephritis in the renal allograft: an update of selected areas. Exp. Clin. Transplant. 2005; 3(1): 283–288.
 
26.
Savin V.J., Sharma R., Sharma M., McCarthy E.T., Swan S.K., Ellis E., Lovell H., Warady B., Gunwar S., Chonko A.M., Artero M., Vincenti F. Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N. Engl. J. Med. 1996; 334(14): 878–883.
 
27.
Kashgary A., Sontrop J.M., Li L., Al-Jaishi A.A., Habibullah Z.N., Alsolaimani R., Clark W.F. The role of plasma exchange in treating post-transplant focal segmental glomerulosclerosis: A systematic review and meta-analysis of 77 case-reports and case-series. BMC Nephrol. 2016; 17(1): 104.
 
28.
Kemper M.J., Wolf G., Muller-Wiefel D.E. Transmission of glomerular permeability factor from a mother to her child. N. Engl. J. Med. 2001; 344(5): 386–387.
 
29.
Shankland S.J., Pollak M.R. A suPAR circulating factor causes kidney disease. Nat. Med. 2011; 17(8): 926–927.
 
30.
Reiser J., Wei C., Tumlin J. Soluble urokinase receptor and focal segmental glomerulosclerosis. Curr. Opin. Nephrol. Hypertens. 2012; 21(4): 428–432.
 
31.
Wei C., Sigdel T.K., Sarwal M.M., Reiser J. Circulating CD40 autoantibody and suPAR synergy drives glomerular injury. Ann. Transl. Med. 2015; 3(19): 300.
 
32.
Go A.S., Chertow G.M., Fan D., McCulloch C.E., Hsu C.Y. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N. Eng. J. Med. 2004; 351(13): 1296–1305.
 
33.
Henry R.M., Kostense P.J., Bos G., Dekker J.M., Nijpels G., Heine R.J., Bouter L.M., Stehouwer C.D. Mild renal insufficiency is associated with increased cardiovascular mortality: The Hoorn Study. Kidney Int. 2002; 62(4): 1402–1407.
 
34.
Piotrowski W., Waśkiewicz A., Cicha-Mikołajczyk A. Global cardiovascular mortality risk in the adult Polish population: prospective assessment of the cohorts studied in multicentre national WOBASZ and WOBASZ Senior studies. Kardiol. Pol. 2016; 74(3): 262–273.
 
35.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. Suppl. 2013; 3: 1–150.
 
36.
Inoue A., Wada H., Takagi M., Yamamuro M., Mukai K., Nakasaki T., Shimura M., Hiyoyama K., Deguchi H., Gabazza E.C., Mori Y., Nishikawa M., Deguchi K., Shiku H. Hemostatic abnormalities in patients with thrombotic complications on maintenance hemodialysis. Clin. App. Thromb. Hemost. 2000; 6(2): 100–103.
 
37.
Morange P.E., Bickel C., Nicaud V., Schnabel R., Rupprecht H.J., Peetz D., Lackner K.J., Cambien F., Blankenberg S., Tiret L. Haemostatic factors and the risk of cardiovascular death in patients with coronary artery disease: the AtheroGene study. Arterioscler. Thromb. Vasc. Biol. 2006; 26(12): 2793––2797.
 
38.
Sakkinen P.A., Cushman M., Psaty B.M., Rodriguez B., Boineau R., Kuller L.H., Tracy R.P. Relationship of plasmin generation to cardiovascular disease risk factors in elderly men and women. Arterioscler. Thromb. Vasc. Biol. 1999; 19(3): 499–504.
 
39.
Mezzano D., Tagle R., Panes O., Pérez M., Downey P., Muñoz B., Aranda E., Barja P., Thambo S., González F., Mezzano S., Pereira J. Hemostatic disorder of uremia: the platelet defect, main determinant of the prolonged bleeding time, is correlated with indices of activation of coagulation and fibrinolysis. Thromb. Haemost. 1996; 76(3): 312–321.
 
40.
Ito T., Niwa T., Matsui E. Fibrinolytic activity in renal disease. Clin. Chim. Acta 1972; 36(1): 145–151.
 
41.
Pawlak K., Pawlak D., Myśliwiec M. Excess soluble urokinase-type plasminogen activator receptor in the plasma of dialysis patients correlates with increased fibrinolytic activity. Thromb. Res. 2007; 119(4): 475–480.
 
42.
Pawlak K., Pawlak D., Myśliwiec M. Tissue factor and urokinase-type plazminogen activator system are related to the presence of cardiovascular disease in hemodialysis patients. Thromb. Res. 2007; 120(6): 871–876.
 
43.
Pawlak K., Ulazka B., Myśliwiec M., Pawlak D. Vascular endothelial growth factor and uPA/suPAR system in early and advanced chronic kidney disease patients: a new link between angiogenesis and hyperfibrinolysis? Transl. Res. 2012; 160(5): 346–354.
 
44.
Makin A. J., Chung N.A., Silverman S.H., Lip G.Y. Vascular endothelial growth factor and tissue factor in patients with established peripheral artery disease: a link between angiogenesis and thrombogenesis? Clin. Sci. 2003; 104(4): 397–404.
 
45.
Migdalski A., Kotschy M., Jawien A. Tissue factor, tissue factor pathway inhibitor and vascular endothelial growth factor-A in carotid atherosclerotic plaques. Eur. J. Vasc. Endovasc. Surg. 2005; 30(1): 41–47.
 
46.
Shen B.Q., Lee D.Y., Cortopassi K.M., Damico L.A., Zioncheck T.F. Vascular endothelial growth factor KDR receptor signaling potentiates tumor necrosis factor-induced tissue factor expression in endothelial cells. J. Biol. Chem. 2001; 276(7): 5281–5286.
 
47.
Kroon M.E., Koolwijk P., Vermeer M.A., van der Vecht B., van Hinsbergh V.W. Vascular endothelial growth factor enhances the expression of urokinase receptor in human endothelial cells via protein kinase C activation. Thromb. Haemost. 2001; 85(2): 296–302.
 
48.
Blann A.D., Belgore F.M., McCollum C.N., Silverman S., Lip P.L., Lip G.Y. Vascular endothelial growth factor and its receptor, Flt-1, in the plasma of patients with coronary or peripheral atherosclerosis, or type II diabetes. Clin. Sci. 2002; 102(2): 187–194.
 
49.
Toschi V., Gallo R., Lettino M., Fallon J.T., Gertz S.D., Fernández-Ortiz A., Chesebro J.H., Badimon L., Nemerson Y., Fuster V., Badimon J.J. Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. Circulation 1997; 95(3): 594–599.
 
50.
Khurana R., Simons M., Martin J.F., Zachary I.C. Role of angiogenesis in cardiovascular disease: a critical appraisal. Circulation 2005; 112(12): 1813–1824.
 
51.
Pawlak K., Buraczewska-Buczko A., Myśliwiec M., Pawlak D. Hyperfibrinolysis, uPA/suPAR system, kynurenines, and the prevalence of cardiovascular disease in patients with chronic renal failure on conservative treatment. Am. J. Med. Sci. 2010; 339(1): 5–9.
 
52.
Prager G.W., Breuss J.M., Streurer S., Mihaly J., Binder B.R. Vascular endothelial growth factor (VEGF) induces rapid prourokinase (pro-uPA) activation on the surface of endothelial cells. Blood 2004; 103(3): 955-62.
 
53.
Houck K.A., Leung D.W., Rowland A.M., Winer J., Ferrara N. Dual regulation of vascular endothelial growth factor bioavailability by genetic and proteolytic mechanisms. J. Biol. Chem. 1992; 267(36): 26031–26037.
 
54.
Tang W.H., Friess H., di Mola F.F., Schilling M., Maurer C., Graber H.V., Dervenis C., Zimmermann A., Büchler M.W. Activation of the serine proteinase system in chronic kidney rejection. Transplantation 1998; 65(12): 1628–1634.
 
55.
Gueler F., Rong S., Mengel M., Park J.K., Kiyan J., Kirsch T., Dumler I., Haller H., Shushakova N. Renal urokinase-type plasminogen activator (uPA) receptor but not uPA deficiency strongly attenuates ischemia reperfusion injury and acute kidney allograft rejection. J. Immunol. 2008; 181(2): 1179–1189.
 
56.
Fuhrman B. The urokinase system in the pathogenesis of atherosclerosis. Atherosclerosis 2012; 222(1): 8–14.
 
57.
Stenvinkel P. Malnutrition and chronic inflammation as risk factors for cardiovascular disease in chronic renal failure. Blood Purif. 2001; 19: 143–151.
 
58.
Almroth G., Lonn J., Uhlin F., Nayeri F., Brudin L., Andersson B., Hahn-Zoric M. Fibroblast growth factor 23, hepatocyte growth factor, interleukin-6, high-sensitivity C-reactive protein and soluble urokinase plasminogen activator receptor. Inflammation markers in chronic haemodialysis patients? Scand. J. Immunol. 2013; 78(3): 285–290.
 
59.
Anand N., Chandrasekaran S.C., Alam M.N. The malnutrition inflamma-tion complex syndrome- the missing factor in the perio-chronic kidney disease interlink. J. Clin. Diagn. Res. 2013; 7(4): 763–767.
 
60.
Pecoits-Filho R., Lindholm B., Stenvinkel P. The malnutrition, inflammation, and atherosclerosis (MIA) syndrome – the heart of the matter. Nephrol. Dial. Transplant. 2002; 17: 28–31.
 
61.
Stenvinkel P., Heimburger O., Lindholm B., Kaysen G.A., Bergstrom J. Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome). Nephrol. Dial. Transplant. 2000; 15: 953–960.
 
62.
Almroth G., Lonn J., Uhlin F., Brudin L., Andersson B., Hahn-Zoric M. Sclerostin, TNF-alpha and interleukin-18 correlate and are together with Klotho related to other growth factors and cytokines in haemodialysis patients. Scand. J. Immunol. 2016; 83(1): 58–63.
 
63.
Pelletier S., Dubourg L., Carlier M.C., Hadj-Aissa A., Fouque D. The relation between renal function and serum sclerostin in adult patients with CKD. Clin. J. Am. Soc. Nephrol. 2013; 8: 819–823.
 
64.
Desjardins L., Liabeuf S., Olivieira R.B., Louvet L., Kamel S., Lemke H.D., Vanholder R., Choukroun G., Massy Z.A. Uremic toxicity and sclerostin in chronic kidney disease patients. Nephrol. Ther. 2014; 10: 463–470.
 
65.
Kirkpantur A., Balci M., Turkvatan A., Afsar B. Independent association between serum sclerostin levels and carotid artery atherosclerosis in prevalent haemodialysis patients. 2015 Clin. Kidney J. 2015; 8(6): 737–743.
 
66.
Liu Y.W., Su C.T., Chang Y.T., Tsai W.C., Su Y.R., Wang S.P., Yang C.S., Tsai L.M., Chen J.H., Sung J.M. Elevated serum interleukin-18 level is associated with all-cause mortality in stable hemodialysis patients independently of cardiac dysfunction. PLoS One 2014; 9(3): e89457.
 
67.
Andersen O., Eugen-Olsen J., Kofoed K., Iversen J., Haugaard SB. Soluble urokinase plasminogen activator receptor is a marker of dysmetabolism in HIV-infected patients receiving highly active antiretroviral therapy. J. Med. Virol. 2008; 80(2): 209–216.
 
68.
Riisbro R., Christensen I.J., Hogdall C., Brunner N., Hogdall E. Soluble urokinase plasminogen activator receptor measurements: influence of sample handling. Int. J. Biol. Markers 2001; 16(4): 233–239.
 
69.
Sier C.F., Sidenius N., Mariani A., Aletti G., Agape V., Ferrari A., Casetta G., Stephens R.W., Brünner N., Blasi F. Presence of urokinase-type plasminogen activator receptor in urine of cancer patients and its possible clinical relevance. Lab. Invest. 1999; 79(6): 717–722.
 
70.
Mustjoki S., Sidenius N., Sier C.F., Blasi F., Elonen E., Alitalo R., Vaheri A. Soluble urokinase receptor levels correlate with number of circulating tumor cells in acute myeloid leukemia and decrease rapidly during chemotherapy. Cancer Res. 2000; 60(24): 7126–7132.
 
71.
Hayek S.S., Sever S., Ko Y.A., Trachtman H., Awad M., Wadhwani S., Altintas M.M., Wei C., Hotton A.L., French A.L., Sperling L.S., Lerakis S., Quyyumi A.A., Reiser J. Soluble urokinase receptor and chronic kidney disease. N. Engl. J. Med. 2015; 373, 20: 1916–1925.
 
eISSN:1734-025X
Journals System - logo
Scroll to top