Uromodulina osoczowa jako marker funkcji nerki przeszczepionej

ORYGINALNY ARTYKUŁ

Uromodulina osoczowa jako marker funkcji nerki przeszczepionej

Monika Nowosiad-Magda 1 , Paulina Roszkowska 1 , Marek Myślak 2 , Iwona Wojciechowska-Koszko 1 , Leszek Domański 2 , Jacek Rożański 2 , Małgorzata Marchelek-Myśliwiec 2 , Kazimierz Ciechanowski 2 , Barbara Dołęgowska 1

1. Department of Microbiology, Immunology and Laboratory Medicine, Pomeranian Medical University, Szczecin, Poland
2. Department of Nephrology, Transplantology and Internal Diseases, Pomeranian Medical University, Szczecin, Poland

Opublikowany: 2019-01-07
DOI: 10.5604/01.3001.0013.6394
GICID: 01.3001.0013.6394
Dostępne wersje językowe: pl en
Wydanie: Postepy Hig Med Dosw 2019; 73 : 729-734

 

Abstrakt

Serum uromodulin (sURO) was recently found as a sensitive tubular marker in early chronic kidney disease stages. Thus far, mainly early uromodulin urinary excretion was tested in kidney recipients. The aim of our study was to conduct a long-lastinlong-term assessment of sURO in kidney graft function monitoring. Forty-one stable kidney recipients (aged 47 (13.7)) were studied around the 3rd month (3m) and the 2nd year (2y) after kidney transplantation. Sera were tested for sURO, creatinine and tacrolimus levels. Kidney biopsy was scored according to revised Banff 97 classification. sURO level (mean 66.06ng/ml at 3m; 77.81 at 2y) increased borderline significantly (P = 0.051) in time and significantly correlated with eGFR (3m RS = 0.46; 2y RS = 0.58), creatinine levels (RS respectively –0.55 and –0.56) and donor age (3m Rs = –0.33; 2y RS = –0.41). We observed borderline correlations between sURO and Banff biopsy scoring: 3m-sURO with arteriolar hyalinosis-ah (RS = –0.3, P = 0.06) and 2y-sURO with peritubular capillaritis-ptc (RS = 0.45, P = 0.07). Correlations of sURO with 3m tacrolimus levels (Rs = 0.3, P = 0.08) were borderline, however patients with CNI toxicity lesions in biopsy had sURO significantly lower (mean 3m-sURO 52.7 vs 83.1 ng/ml; 2y-sURO 61.9 vs 98.1 ng/ml). sURO can reflect kidney graft quality and function. sURO correlated with ptc, which is considered to be an early marker of a chronic antibody-mediated graft injury. Tacrolimus doesn’t influence sURO levels directly, but sURO is lower in patients with toxic kidney injury in biopsy.

Przypisy

  • 1. Bostom A., Steubl D., Garimella P.S., Franceschini N., Roberts M.B.,Pasch A., Ix J.H., Tuttle K.R., Ivanova A., Shireman T., Kim S.J., Gohh R.,Weiner D.E., Levey A.S., Hsu C.Y., et al.: Serum uromodulin: a biomarkerof long-term kidney allograft failure. Am. J. Nephrol., 2018; 47: 275–282 2 Bostom A.G., Steubl D., Friedman A.N.: Hypothesis: potential utilityof serum and urine uromodulin measurement in kidney transplantrecipients? Transplant. Direct, 2017; 3: e219
    Google Scholar
  • 2. and familial juvenile hyperuricaemic nephropathy. J. Med. Genet.,2002; 39: 882–892
    Google Scholar
  • 3. Bröcker V., Schubert V., Scheffner I., Schwarz A., Hiss M., BeckerJ.U., Scherer R., Haller H., Kreipe H.H., Mengel M., Gwinner W.:Arteriolar lesions in renal transplant biopsies: prevalence, progression,and clinical significance. Am. J. Pathol., 2012; 180: 1852–1862
    Google Scholar
  • 4. Dahan K., Devuyst O., Smaers M., Vertommen D., Loute G., PouxJ.M., Viron B., Jacquot C., Gagnadoux M.F., Chauveau D., BüchlerM., Cochat P., Cosyns J.P., Mougenot B., Rider M.H., et al.: A clusterof mutations in the UMOD gene causes familial juvenile hyperuricemic nephropathy with abnormal expression of uromodulin. J.Am. Soc. Nephrol., 2003; 14: 2883–2893
    Google Scholar
  • 5. Dawnay A.B., Cattell W.R.: Serum Tamm-Horsfall glycoproteinlevels in health and in renal disease. Clin. Nephrol., 1981; 15: 5–8
    Google Scholar
  • 6. de Matos A.C., Câmara N.O., REQUIãO-Moura L.R., Tonato E.J., FiliponiT.C., Souza-DURãO M. Jr, Malheiros D.M., Fregonesi M., BorrelliM., Pacheco-Silva A.: Presence of arteriolar hyalinosis in post-reperfusionbiopsies represents an additional risk to ischaemic injury inrenal transplant. Nephrology 2016; 21: 923–929
    Google Scholar
  • 7. Devuyst O., Dahan K., Pirson Y.: Tamm-Horsfall protein or uromodulin:new ideas about an old molecule. Nephrol. Dial. Transplant.,2005; 20: 1290–1294
    Google Scholar
  • 8. Fedak D., Kuźniewski M., Fugiel A., Wieczorek-Surdacka E., Przepiórkowska-Hoyer B., Jasik P., Miarka P., Dumnicka P., Kapusta M.,Solnica B., Sułowicz W.: Serum uromodulin concentrations correlatewith glomerular filtration rate in patients with chronic kidneydisease. Pol. Arch. Med. Wewn., 2016; 126: 995–1004
    Google Scholar
  • 9. Gibson I.W., Gwinner W., Bröcker V., Sis B., Riopel J., Roberts I.S.,Scheffner I., Jhangri G.S., Mengel M.: Peritubular capillaritis in renalallografts: prevalence, scoring system, reproducibility and clinicopathologicalcorrelates. Am. J. Transplant., 2008; 8: 819–825
    Google Scholar
  • 10. Hart T.C., Gorry M.C., Hart P.S., Woodard A.S., Shihabi Z., SandhuJ., Shirts B., Xu L., Zhu H., Barmada M.M., Bleyer A.J.: Mutations ofthe UMOD gene are responsible for medullary cystic kidney disease
    Google Scholar
  • 11. Kaden J., Groth J., May G., Liedvogel B.: Urinary Tamm-Horsfallprotein as a marker of renal transplant function. Urol. Res., 1994;22: 131–136
    Google Scholar
  • 12. Kobayashi K., Fukuoka S.: Conditions for solubilization of Tamm-Horsfall protein/uromodulin in human urine and establishment of asensitive and accurate enzyme-linked immunosorbent assay (ELISA)method. Arch. Biochem. Biophys., 2001; 388: 113–120
    Google Scholar
  • 13. Köttgen A., Glazer N.L., Dehghan A., Hwang S.J., Katz R., Li M.,Yang Q., Gudnason V., Launer L.J., Harris T.B., Smith A.V., Arking D.E.,Astor B.C., Boerwinkle E., Ehret G.B., et al.: Multiple loci associatedwith indices of renal function and chronic kidney disease. Nat Genet.,2009; 41: 712–717
    Google Scholar
  • 14. Kozakowski N., Herkner H., Böhmig G.A., Regele H., KornauthC., Bond G., Kikić Ž.: The diffuse extent of peritubular capillaritis inrenal allograft rejection is an independent risk factor for graft loss.Kidney Int., 2015; 88: 332–340
    Google Scholar
  • 15. Lerut E., Naesens M., Kuypers D.R., Vanrenterghem Y., Van DammeB.: Subclinical peritubular capillaritis at 3 months is associatedwith chronic rejection at 1 year. Transplantation, 2007; 83: 1416–1422
    Google Scholar
  • 16. Ling X.B., Sigdel T.K., Lau K., Ying L., Lau I., Schilling J., SarwalM.M.: Integrative urinary peptidomics in renal transplantationidentifies biomarkers for acute rejection. J. Am. Soc. Nephrol.,2010; 21: 646–653
    Google Scholar
  • 17. McLaughlin P.J., Aikawa A., Davies H.M., Ward R.G., Bakran A.,Sells R.A., Johnson P.M.: Uromodulin levels are decreased in urineduring acute tubular necrosis but not during immune rejection afterrenal transplantation. Clin. Sci., 1993; 84: 243–246
    Google Scholar
  • 18. Mo L., Huang H., Zhu X., Shapiro E., Hasty D.L., Wu X.R.: Tamm-Horsfall protein is a critical renal defense factor protecting againstcalcium oxalate crystal formation. Kidney Int., 2004; 66: 1159–1166
    Google Scholar
  • 19. Padmanabhan S., Melander O., Johnson T., Di Blasio A.M., LeeW.K., Gentilini D., Hastie C.E., Menni C., Monti M.C., Delles C., Laing S., Corso B., Navis G., Kwakernaak A.J., van der Harst P., et al.: Genome-wide association study of blood pressure extremes identifiesvariant near UMOD associated with hypertension. PLoS Genet.,2010; 6: e1001177
    Google Scholar
  • 20. Prajczer S., Heidenreich U., Pfaller W., Kotanko P., Lhotta K.,Jennings P.: Evidence for a role of uromodulin in chronic kidneydisease progression. Nephrol. Dial. Transplant., 2010; 25: 1896–1903
    Google Scholar
  • 21. Racusen L.C., Bagnasco S.M.: Peritubular capillaritis in the renalallograft takes center stage. Kidney Int., 2015; 88: 218–220
    Google Scholar
  • 22. Reznichenko A., Böger C.A., Snieder H., van den Born J., de BorstM.H., Damman J., van Dijk M.C., van Goor H., Hepkema B.G., HillebrandsJ.L., Leuvenink H.G., Niesing J., Bakker S.J., Seelen M., NavisG.; REGaTTA (REnal GeneTics TrAnsplantation) Groningen group.:UMOD as a susceptibilitygene for end-stage renal disease. BMCMed. Genet, 2012; 13: 78
    Google Scholar
  • 23. Reznichenko A., van Dijk M.C., van der Heide J.H., Bakker S.J.,Seelen M., Navis G.: Uromodulin in renal transplant recipients: elevatedurinary levels and bimodal association with graft failure. Am.J. Nephrol., 2011; 34: 445–451
    Google Scholar
  • 24. Risch L., Lhotta K., Meier D., Medina-Escobar P., Nydegger U.E.,Risch M.: The serum uromodulin level is associated with kidneyfunction. Clin. Chem. Lab. Med., 2014; 52: 1755–1761
    Google Scholar
  • 25. Schwartz R.H., Van Ess J.D., May A.G., Schenk E.A., FreemanR.B.: Tamm-Horsfall glycoproteinuria and renal allograft rejection.Transplantation, 1973; 16: 83–87
    Google Scholar
  • 26. Serafini-Cessi F., Malagolini N., Cavallone D.: Tamm-Horsfallglycoprotein:biology and clinical relevance. Am. J. Kidney Dis., 2003;42: 658–676
    Google Scholar
  • 27. Solez K., Colvin R.B., Racusen L.C., Haas M., Sis B., Mengel M.,Halloran P.F., Baldwin W., Banfi G., Collins A.B., Cosio F., David D.S.,Drachenberg C., Einecke G., Fogo A.B., et al.: Banff 07 classificationof renal allograft pathology: updates and future directions. Am. J.Transplant., 2008; 8: 753–760
    Google Scholar
  • 28. Steubl D., Block M., Herbst V., Nockher W.A., Schlumberger W.,Satanovskij R., Angermann S., Hasenau A.L., Stecher L., HeemannU., Renders L., Scherberich J.: Plasma uromodulin correlates withkidney function and identifies early stages in chronic kidney diseasepatients. Medicine 2016; 95: e3011
    Google Scholar
  • 29. Steubl D., Block M., Herbst V., Schlumberger W., Nockher A.,Angermann S., Schmaderer C., Heemann U., Renders L., ScherberichJ.: Serum uromodulin predicts graft failure in renal transplantrecipients. Biomarkers, 2017; 22: 171–177
    Google Scholar
  • 30. Trudu M., Janas S., Lanzani C., Debaix H., Schaeffer C., IkehataM., Citterio L., Demaretz S., Trevisani F., Ristagno G., GlaudemansB., Laghmani K., Dell’Antonio G.; SKIPOGH team, Loffing J., RastaldiM.P., et al.: Common noncoding UMOD gene variants induce salt-sensitivehypertension and kidney damage by increasing uromodulinexpression. Nat. Med., 2013; 19: 1655–1660
    Google Scholar
  • 31. Uslu A., Hür E., Şen Ç., Şen S., Akgün A., Taşlı F.A., Nart A., YilmazM., Töz H.: To what extent estimated or measured GFR couldpredict subclinical graft fibrosis: a comparative prospective studywith protocol biopsies. Transplant. Int., 2015; 28: 575–581
    Google Scholar
  • 32. Vyletal P., Bleyer A.J., Kmoch S.: Uromodulin biology and pathophysiology-an update. Kidney Blood Press. Res., 2010; 33: 456–475
    Google Scholar

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