Display options
Cite
Jacobs-Cachá C, Torres IB, López-Hellín J, et al. Fascin-1 is released from proximal tubular cells in response to calcineurin inhibitors (CNIs) and correlates with isometric vacuolization in kidney transplanted patients. Am J Transl Res. 2017;9(9):4173-4183
Jacobs-Cachá, C., Torres, I. B., López-Hellín, J., Cantarell, C., Azancot, M. A., Román, A., Moreso, F., Serón, D., Meseguer, A., & Sarró, E. (2017). Fascin-1 is released from proximal tubular cells in response to calcineurin inhibitors (CNIs) and correlates with isometric vacuolization in kidney transplanted patients. American journal of translational research, 9(9), 4173-4183.
Jacobs-Cachá, Conxita, et al. "Fascin-1 is released from proximal tubular cells in response to calcineurin inhibitors (CNIs) and correlates with isometric vacuolization in kidney transplanted patients." American journal of translational research vol. 9,9 (2017): 4173-4183.
Jacobs-Cachá C, Torres IB, López-Hellín J, Cantarell C, Azancot MA, Román A, Moreso F, Serón D, Meseguer A, Sarró E. Fascin-1 is released from proximal tubular cells in response to calcineurin inhibitors (CNIs) and correlates with isometric vacuolization in kidney transplanted patients. Am J Transl Res. 2017 Sep 15;9(9):4173-4183. eCollection 2017. PMID: 28979691; PMCID: PMC5622260.
Copy Download .nbib Format: NLM
Share it on

Am J Transl Res. 2017 Sep 15;9(9):4173-4183. eCollection 2017.

Fascin-1 is released from proximal tubular cells in response to calcineurin inhibitors (CNIs) and correlates with isometric vacuolization in kidney transplanted patients.

American journal of translational research

Conxita Jacobs-Cachá, Irina B Torres, Joan López-Hellín, Carme Cantarell, María A Azancot, Antonio Román, Francesc Moreso, Daniel Serón, Anna Meseguer, Eduard Sarró

Affiliations

  1. Renal Physiopathology Group, Vall d'Hebron Research Institute (VHIR)-CIBBIM NanomedicinePasseig Vall d'Hebron 119-129, 08035, Barcelona, Spain.
  2. Department of Nephrology, Vall d'Hebron University Hospital, Autonomous University of BarcelonaPasseig Vall d'Hebron 119-129, 08035, Barcelona, Spain.
  3. Department of Pneumology, Vall d'Hebron University Hospital, Autonomous University of BarcelonaPasseig Vall d'Hebron 119-129, 08035, Barcelona, Spain.
  4. Department of Biochemistry and Molecular Biology, Faculty of Medicine, Autonomous University of BarcelonaBellaterra (Barcelona), Spain.

PMID: 28979691 PMCID: PMC5622260

Abstract

Immunosuppression based on calcineurin inhibitors (CNIs) has greatly improved organ transplantation, although subsequent nephrotoxicity significantly hinders treatment success. There are no currently available specific soluble biomarkers for CNI-induced nephrotoxicity and diagnosis relies on renal biopsy, which is costly, invasive and may cause complications. Accordingly, identification of non-invasive biomarkers distinguishing CNI-induced kidney tubular damage from that of other etiologies would greatly improve diagnosis and enable more precise dosage adjustment. For this purpose, HK-2 cells, widely used to model human proximal tubule, were treated with CNIs cyclosporine-A and FK506, or staurosporine as a calcineurin-independent toxic compound, and secretomes of each treatment were analyzed by proteomic means. Among the differentially secreted proteins identified, only fascin-1 was specifically released by both CNIs but not by staurosporine. To validate fascin-1 as a biomarker of CNI-induced tubular toxicity, fascin-1 levels were analyzed in serum and urine from kidney-transplanted patients under CNIs treatment presenting or not isometric vacuolization (IV), which nowadays represents the main histological hallmark of CNI-induced tubular damage. Patients with chronic kidney disease (CKD) and healthy volunteers were used as controls. Our results show that urinary fascin-1 was only significantly elevated in the subset of CNI-treated patients presenting IV. Moreover, fascin-1 anticipated the rise of sCr levels in serially collected urine samples from CNI-treated pulmonary-transplanted patients, where a decline in kidney function and serum creatinine (sCr) elevation was mainly attributed to CNIs treatment. In conclusion, our results point towards fascin-1 as a putative soluble biomarker of CNI-induced damage in the kidney tubular compartment.

Keywords: Fascin-1; biomarkers; calcineurin inhibitors (CNIs); nephrotoxicity; transplant

Conflict of interest statement

None.

References

  1. Proteomics. 2011 Feb;11(4):794-804 - PubMed
  2. Clin J Am Soc Nephrol. 2009 Feb;4(2):481-508 - PubMed
  3. Am J Transplant. 2014 Feb;14(2):272-83 - PubMed
  4. N Engl J Med. 2003 Dec 11;349(24):2326-33 - PubMed
  5. Kidney Int. 1994 Jan;45(1):48-57 - PubMed
  6. Am J Transplant. 2011 Dec;11(12):2635-46 - PubMed
  7. In Vitro Cell Dev Biol Anim. 1994 Sep;30A(9):562-7 - PubMed
  8. BMC Nephrol. 2013 Jan 17;14 :17 - PubMed
  9. Transplant Proc. 2013 Jan-Feb;45(1):122-8 - PubMed
  10. Am J Kidney Dis. 2004 Mar;43(3):405-14 - PubMed
  11. Z Klin Chem Klin Biochem. 1974 Jul;12(7):336-43 - PubMed
  12. Anticancer Res. 2012 Mar;32(3):847-60 - PubMed
  13. Curr Biol. 2014 Jul 7;24(13):1492-9 - PubMed
  14. Transplant Proc. 2011 Oct;43(8):3064-7 - PubMed
  15. Cancer Sci. 2011 Jun;102(6):1228-35 - PubMed
  16. Transplant Proc. 2009 Jun;41(5):1660-5 - PubMed
  17. Electrophoresis. 2004 May;25(9):1327-33 - PubMed
  18. Biomark Med. 2014;8(10):1247-62 - PubMed
  19. Pediatr Nephrol. 2010 May;25(5):889-97 - PubMed
  20. Clin Transplant. 2015 Apr;29(4):294-300 - PubMed
  21. Transpl Int. 1992;5 Suppl 1:S87-92 - PubMed
  22. Scand J Clin Lab Invest Suppl. 2008;241:73-7 - PubMed
  23. Clin Chem. 2012 Apr;58(4):680-9 - PubMed
  24. Transplantation. 2004 Aug 27;78(4):549-56 - PubMed
  25. Toxicol Appl Pharmacol. 2012 Jan 15;258(2):275-87 - PubMed
  26. Transplantation. 1999 Nov 15;68(9):1356-61 - PubMed
  27. Transplantation. 1998 Dec 27;66(12):1736-40 - PubMed
  28. J Pathol. 2011 Jul;224(3):289-300 - PubMed
  29. J Transplant. 2012;2012:563404 - PubMed
  30. Kidney Int. 2011 Dec;80(11):1138-45 - PubMed
  31. Am J Pathol. 2005 Aug;167(2):395-407 - PubMed
  32. Nephrol Dial Transplant. 2009 Nov;24(11):3265-8 - PubMed
  33. Nat Protoc. 2006;1(1):16-22 - PubMed
  34. Toxicol In Vitro. 2009 Sep;23(6):1170-8 - PubMed
  35. Nat Clin Pract Nephrol. 2006 Jul;2(7):398-404; quiz following 404 - PubMed
  36. J Extracell Vesicles. 2012 Sep 11;1:null - PubMed
  37. Am J Pathol. 2004 May;164(5):1807-15 - PubMed

Publication Types