Journal of Nephrology

, Volume 32, Issue 1, pp 139–150 | Cite as

Novel markers of graft outcome in a cohort of kidney transplanted patients: a cohort observational study

  • C. Alfieri
  • A. Regalia
  • G. Moroni
  • D. Cresseri
  • F. Zanoni
  • M. Ikehata
  • P. Simonini
  • M. P. Rastaldi
  • G. Tripepi
  • C. Zoccali
  • C. Chatziantoniou
  • Piergiorgio MessaEmail author
Original Article


Renal biopsy (RBx) informs about kidney transplantation (KTx) prognosis. In our observational study the prevalence of histological anomalies and the prognostic role of CD45, vimentin (VIM) and periostin (POSTN) in KTx-RBx have been evaluated. One hundred forty-six KTx-RBx (2009-2012) were analysed for general histology and in immunohistochemistry for CD45, VIM and POSTN. Clinical data of the 146-KTx patients were collected at the RBx time (T0), 6 and 12 months before and after RBx. Follow-up time was 21 ± 14 months. Glomerulosclerosis was 20% glomeruli/biopsy. Tubular atrophy (TA), Interstitial infiltrate (I-Inf) and interstitial fibrosis (IF) were slight in 21–18% and 25%, moderate in 22–30% and 26% and severe in 30–18% and 28% of patients. Fifty-eight percent of patients had lesions compatible with IF-TA. CD45, VIM and POSTN correlated to each-other and to TA, I-Inf and IF. VIM and POSTN correlated to GS. CD45 and VIM correlated directly to renal function (RF) and 25(OH)VitD, while POSTN inversely to 25(OH)VitD. Thirty patients restarted dialysis (HD+). HD+ had lower T0-eGFR, and higher CD45, VIM and POSTN than HD−. POSTN resulted the strongest in discriminate for HD+ . CD45, VIM and POSTN correlate to each-other and predict graft outcome. POSTN was the strongest in discriminate for HD+. 25(OH)VitD might influence inflammation and fibrosis in KTx.


Renal transplantation Fibrosis Inflammation Markers Graft outcome 


Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical statement

The protocol was conducted according to the ethical principles of the Helsinki Convention, and each patient signed an informed consent. All data have been analysed anonymously.


  1. 1.
    Mengel M et al (2007) Infiltrates in protocol biopsies from renal allografts. Am J Transplant 7:356–365CrossRefGoogle Scholar
  2. 2.
    Zeisberg M, Kalluri R (2004) The role of epithelial-to-mesenchymal transition in renal fibrosis. J Mol Med 82:175–181CrossRefGoogle Scholar
  3. 3.
    Moreso F et al (2007) Immunephenotype of glomerular and interstitial infiltrating cells in protocol renal allograft biopsies and histological diagnosis. Am J Transplant 7:2739–2747CrossRefGoogle Scholar
  4. 4.
    Hansson J et al (2014) Evidence for a morphologically distinct and functionally robust cell type in the proximal tubules of human kidney. Hum Pathol 45(2):382–393CrossRefGoogle Scholar
  5. 5.
    Rastaldi MP et al (2002) Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies. Kidney Int 62:137–146CrossRefGoogle Scholar
  6. 6.
    Doliana R, Bot S, Bonaldo P, Colombatti A (2000) EMI, a novel cysteine-rich domain of EMILINs and other extracellular proteins, interacts with the gC1q domains and participates in multimerization. FEBS Lett 484:164–168CrossRefGoogle Scholar
  7. 7.
    Sorocos K et al (2011) Expression patterns and roles of periostin during kidney and ureter development. J Urol 186:1537–1544CrossRefGoogle Scholar
  8. 8.
    Wallace DP et al (2013) Periostin promotes renal cyst growth and interstitial fibrosis in polycystic kidney disease. Kidney Int 85:845–854CrossRefGoogle Scholar
  9. 9.
    Levey AS et al (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130:461–470CrossRefGoogle Scholar
  10. 10.
    Walker PD, Cavallo T, Bonsib SM (2004) Ad hoc committee on renal biopsy guidelines of the renal pathology society: Practice guidelines for the renal biopsy. Mod Pathol 17:1555–1563CrossRefGoogle Scholar
  11. 11.
    Sis B et al (2010) Banff ‘09 meeting report: antibody mediated graft deterioration and implementation of Banff working groups. Am J Transplant 10:464–471CrossRefGoogle Scholar
  12. 12.
    Solez K et al (2007) Banff 05 meeting report: differential diagnosis of chronic allograft injury and elimination of chronic allograft nephropathy (CAN). Am J Transplant 7:518–526CrossRefGoogle Scholar
  13. 13.
    U S Renal Data System (2011) Annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, BethesdaGoogle Scholar
  14. 14.
    Alarrayed S et al (2011) Why does kidney allograft fail? A long-term single-center experience. Saudi J Kidney Dis Transpl. 22:818–824Google Scholar
  15. 15.
    Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh MJ (2000) Improved graft survival and renal transplantation in the United States, 1988 to 1996. N Engl J Med 342:605–612CrossRefGoogle Scholar
  16. 16.
    El-Zoghby ZM et al (2009) Identifying specific causes of kidney allograft loss. Am J Transplant 9:527–535CrossRefGoogle Scholar
  17. 17.
    Cosio FG, Gloor JM, Sethi S, Stegall MD (2008) Transplant glomerulopathy. Am J Transplant 8:492–496CrossRefGoogle Scholar
  18. 18.
    Naesens M, Kuypers DR, De Vusser K, Evenepoel P, Claes K, Bammens B, Meijers B, Sprangers B, Pirenne J, Monbaliu D, Jochmans I, Lerut E (2014) The histology of kidney transplant failure: a long-term follow-up study. Transplantation 98(4):427–435CrossRefGoogle Scholar
  19. 19.
    Gago M, Cornell LD, Kremers WK, Stegall MD, Cosio FG (2012) Kidney allograft inflammation and fibrosis, causes and consequences. Am J Transplant 12:1199–1207CrossRefGoogle Scholar
  20. 20.
    Nankivell BJ et al (2001) Effect of histological damage on long-term kidney transplant outcome. Transplantation 71:515–523CrossRefGoogle Scholar
  21. 21.
    Serón D (2009) Interstitial fibrosis and tubular atrophy in renal allograft protocol biopsies as a surrogate of graft survival. Transpl Proc 41:769–770CrossRefGoogle Scholar
  22. 22.
    Roufosse C, Simmonds N, Clahsen-van Groningen M, Haas M, Henriksen KJ, Horsfield C, Loupy A, Mengel M, Perkowska-Ptasińska A, Rabant M, Racusen LC, Solez K, Becker JU (2018) A 2018 reference guide to the banff classification of renal allograft pathology. Transplantation 102:1795–1814CrossRefGoogle Scholar
  23. 23.
    Doorenbos CRC, van den Born J, Navis G, de Borst MH (2009) Possible renoprotection by vitamin D in chronic renal disease: beyond mineral metabolism. Nat Rev Nephrol 5:691–700CrossRefGoogle Scholar
  24. 24.
    Li YC (2010) Renoprotective effects of vitamin D analogs. Kidney Int 78:134–139CrossRefGoogle Scholar
  25. 25.
    Li YC (2012) Vitamin D: roles in renal and cardiovascular protection. Curr Opin Nephrol Hypertens 21:72–79CrossRefGoogle Scholar
  26. 26.
    Barros X, Rodríguez NY, Fuster D, Rodas L, Esforzado N, Mazza A, Rubello D, Campos F, Tapias A, Torregrosa JV (2016) Comparison of two different vitamin D supplementation regimens with oral calcifediol in kidney transplant patients. J Nephrol 29:703–709CrossRefGoogle Scholar
  27. 27.
    Messa P, Regalia A, Alfieri CM (2017) Nutritional vitamin D in renal transplant patients: speculations and reality. Nutrients 9(6):550CrossRefGoogle Scholar
  28. 28.
    Gago M, Cornell LD, Kremers WK, Stegall MD, Cosio FG (2012) Kidney allograft inflammation and fibrosis, causes and consequences. Am J Transplant 12:1199–1207CrossRefGoogle Scholar
  29. 29.
    Wei Y, Shao R (2006) Transduction of a mesenchyme-specific gene periostin into 293T cells induces cell invasive activity through epithelial-mesenchymal transformation. J Biol Chem 281(28):19700–19708CrossRefGoogle Scholar
  30. 30.
    Alfieri C et al (2015) Discoidin domain receptor-1 and periostin: new players in chronic kidney disease. Nephrol Dial Transplant 30:1965–1971CrossRefGoogle Scholar
  31. 31.
    Oka T et al (2007) Genetic manipulation of periostin expression reveals a role in cardiac hypertrophy and ventricular remodeling. Circ Res 101:313–321CrossRefGoogle Scholar
  32. 32.
    Sen K et al (2011) Periostin is induced in glomerular injury and expressed de novo in interstitial renal fibrosis. Am J Pathol 179:1756–1767CrossRefGoogle Scholar
  33. 33.
    Satirapoj B et al (2014) Urine periostin as a biomarker of renal injury in chronic allograft nephropathy. Transplant Proc 46:135–140CrossRefGoogle Scholar
  34. 34.
    Corren J et al (2011) Lebrikizumab treatment in adults with asthma. N Engl J Med 365:1088–1098CrossRefGoogle Scholar
  35. 35.
    Masuoka M et al (2012) Periostin promotes chronic allergic inflammation in response to Th2 cytokines. J Clin Investig 122:2590–2600CrossRefGoogle Scholar
  36. 36.
    Guerrot D et al (2012) Identification of periostin as a critical marker of progression/reversal of hypertensive nephropathy. PLoS One 7:e31974CrossRefGoogle Scholar

Copyright information

© Italian Society of Nephrology 2019

Authors and Affiliations

  • C. Alfieri
    • 1
  • A. Regalia
    • 1
  • G. Moroni
    • 1
  • D. Cresseri
    • 1
  • F. Zanoni
    • 1
  • M. Ikehata
    • 2
  • P. Simonini
    • 2
  • M. P. Rastaldi
    • 2
  • G. Tripepi
    • 3
  • C. Zoccali
    • 3
  • C. Chatziantoniou
    • 4
    • 5
  • Piergiorgio Messa
    • 1
    • 6
    Email author
  1. 1.Unit of Nephrology, Dialysis and Kidney TransplantationFondazione Istituto di Ricerca e Cura a Carattere Scientifico Cà Granda Ospedale Maggiore PoliclinicoMilanItaly
  2. 2.Research Laboratory of NephrologyFondazione Istituto di Ricerca e Cura a Carattere Scientifico Cà Granda Ospedale Maggiore PoliclinicoMilanItaly
  3. 3.Unit of Renal Diseases and HypertensionCNR-IFC (National Research Centre, Institute of Clinical Physiology), Clinical Epidemiology of Renal Diseases and Hypertension UnitReggio CalabriaItaly
  4. 4.Institut National de la Santé Et de la Recherche Médicale, UMR S 1155ParisFrance
  5. 5.Sorbonne Université, Bâtiment Recherche, Tenon HospitalParisFrance
  6. 6.Università degli studi di MilanoMilanItaly

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