Aim: It is important to find biomarkers that identify the graft quality in kidney transplantation. Results & methodology: The level of SLPI in the cold preservation solution was used as a marker to predict early kidney graft function after transplantation. Before transplantation, kidneys were washed and SLPI was measured in the discarded solution. A retrospective analysis showed that patients with delayed graft function or rejection episodes in post-trasplant, had higher SLPI concentrations in the perfusion solution than patients without delayed graft function or rejections. Furthermore, SLPI could discriminate between patients with better or worse estimated glomerular filtration rate among low-risk patients (kidney donor profile index <80). Discussion & conclusion: These results suggest that the SLPI concentration in the perfusion solutions could be a predictor of short-term organ function and a complement to the kidney donor profile index score.

Graphical abstract

Keywords:

References

1. Yarlagadda SG, Coca SG, Garg AX et al. Marked variation in the definition and diagnosis of delayed graft function: a systematic review. Nephrol. Dial. Transplant. 23(9), 2995–3003 (2008).
MedlineGoogle Scholar
2. Ojo AO, Wolfe RA, Held PJ, Port FK, Schmouder RL. Delayed graft function: risk factors and implications for renal allograft survival. Transplantation 63(7), 968–974 (1997).
Medline CASGoogle Scholar
3. Zeraati AA, Naghibi M, Kianoush S, Ashraf H. Impact of slow and delayed graft function on kidney graft survival between various subgroups among renal transplant patients. Transplant. Proc. 41(7), 2777–2780 (2009).
Medline CASGoogle Scholar
4. Carmellini M, Vistoli F, Boggi U, Bellini R, Mosca F. Delayed graft function incidence as predictive variable of survival of kidney grafts retrieved from elderly donors. Transplant. Proc. 32(1), 128–130 (2000).
Medline CASGoogle Scholar
5. Schiavelli R, Rosés J, Di Tullio D et al. Delayed graft function in kidney transplant recipients. Nefrología Diálisis y Trasplante 35(4), 182–187 (2015).
Google Scholar
6. Dare AJ, Pettigrew GJ, Saeb-Parsy K. Preoperative assessment of the deceased-donor kidney: from macroscopic appearance to molecular biomarkers. Transplantation 97(8), 797–807 (2014).
Medline CASGoogle Scholar
7. Thompson RC, Ohlsson K. Isolation, properties, and complete amino acid sequence of human secretory leukocyte protease inhibitor, a potent inhibitor of leukocyte elastase. Proc. Natl Acad. Sci. USA 83(18), 6692–6696 (1986).
Medline CASGoogle Scholar
8. Doumas S, Kolokotronis A, Stefanopoulos P. Anti-inflammatory and antimicrobial roles of secretory leukocyte protease inhibitor. Infect. Immun. 73(3), 1271–1274 (2005).
Medline CASGoogle Scholar
9. Lentsch AB, Yoshidome H, Warner RL, Ward PA, Edwards MJ. Secretory leukocyte protease inhibitor in mice regulates local and remote organ inflammatory injury induced by hepatic ischemia/reperfusion. Gastroenterology 117(4), 953–961 (1999).
Medline CASGoogle Scholar
10. Odaka C, Mizuochi T, Yang J, Ding A. Murine macrophages produce secretory leukocyte protease inhibitor during clearance of apoptotic cells: implications for resolution of the inflammatory response. J. Immun. 171(3), 1507–1514 (2003).
Medline CASGoogle Scholar
11. Wilflingseder J, Sunzenauer J, Toronyi E et al. Molecular pathogenesis of post-transplant acute kidney injury: assessment of whole-genome mRNA and miRNA profiles. PLoS ONE 9(8), e104164 (2014).
MedlineGoogle Scholar
12. Tateosian NL, Costa MJ, Guerrieri D, Barro A, Mazzei JA, Eduardo Chuluyan H. Inflammatory mediators in exhaled breath condensate of healthy donors and exacerbated COPD patients. Cytokine 58(3), 361–367 (2012).
Medline CASGoogle Scholar
13. Teo SH, Endre ZH. Biomarkers in acute kidney injury (AKI). Best. Pract. Res. Clin. Anaesthesiol. 31(3), 331–344 (2017).
MedlineGoogle Scholar
14. Sallenave JM. Secretory leukocyte protease inhibitor and elafin/trappin-2: versatile mucosal antimicrobials and regulators of immunity. Am. J. Respir. Cell Mol. Biol. 42(6), 635–643 (2010).
Medline CASGoogle Scholar
15. Moledina DG, Parikh CR. Phenotyping of acute kidney injury: beyond serum creatinine. Semin. Nephrol. 38(1), 3–11 (2018).
Medline CASGoogle Scholar
16. Van Balkom BWM, Gremmels H, Ooms LSS et al. Proteins in preservation fluid as predictors of delayed graft function in kidneys from donors after circulatory death. Clin. J. Am. Soc. Nephrol. 12(5), 817–824 (2017).
MedlineGoogle Scholar
17. Malyszko J, Lukaszyk E, Glowinska I, Durlik M. Biomarkers of delayed graft function as a form of acute kidney injury in kidney transplantation. Sci. Rep. 5, 11684 (2015).
Medline CASGoogle Scholar
18. Ambrosi N, Arrosagaray V, Guerrieri D et al. α-lipoic acid protects against ischemia-reperfusion injury in simultaneous kidney–pancreas transplantation. Transplantation 100(4), 908–915 (2016).
Medline CASGoogle Scholar
19. Casciato P, Ambrosi N, Caro F et al. α-lipoic acid reduces post-reperfusion syndrome in human liver transplantation – a pilot study. Transplant. Int. 31(12), 1357–1368 (2018).
Medline CASGoogle Scholar
20. Zens TJ, Danobeitia JS, Leverson G et al. The impact of kidney donor profile index on delayed graft function and transplant outcomes: a single-center analysis. Clin. Transplant. 32(3), e13190 (2018).
MedlineGoogle Scholar
21. OPTN Kidney Committee. A guide to calculating and interpreting the kidney donor profile index (KDPI). 7, (2012). https://optn.transplant.hrsa.gov/media/1512/guide_to_calculating_interpreting_kdpi.pdf
Google Scholar
22. Gandolfini I, Buzio C, Zanelli P et al. The kidney donor profile index (KDPI) of marginal donors allocated by standardized pretransplant donor biopsy assessment: distribution and association with graft outcomes. Am. J. Transplant. 14(11), 2515–2525 (2014).
Medline CASGoogle Scholar

Vol. 13, No. 11

Supplemental Materials

Metrics

Downloaded 156 times

History

Received 16 November 2018

Accepted 16 May 2019

Published online 5 August 2019

Published in print August 2019

Information

Keywords

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/bmm-2018-0428

Author contributions

NG Ambrosi participated in the performance of the experiments, data analysis and drafted the manuscript. F Caro participated in the performance of the experiments. F Osella, LD Álvarez, F Sánchez pF Toniolo and D Guerrieri participated in the performance of the experiments. C Incardona participated with edition and revision of the manuscript. The author is an employee of GADOR Argentina SA. D Casadei participated in the conception and design of research, the edition and revision of the manuscript. E Chuluyan participated in conception and design of research, analysis of data, interpretation of the results, edited and revised the manuscript and approved final version of manuscript. The authors declare no conflicts of interest.

Acknowledgments

The secretarial work of S Basualdo is gratefully acknowledged.

Disclosure

The founding sponsors had no role in the interpretation and writing of the manuscript.

Financial & competing interests disclosure

This work was supported by Fundación del 3er Milenio, ANPCYT PICT2014-2504 and PICT2016-0859, Fundación GADOR, UBACYT2018. The authors declare that C Incardona is the medical director of GADOR SA. The founding sponsors had no role in the interpretation and writing of the manuscript. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The manuscript in English was edited by American Journal of Experts.

Ethical conduct of research

This retrospective and descriptive study was approved by an institutional review board. The clinical and research activities reported are consistent with the Principles of the Declaration of Istanbul as outlined in the ‘Declaration of Istanbul on Organ Trafficking and Transplant Tourism’.

PDF download

SLPI in the perfusion solution helps to identify graft quality in kidney transplants

Abstract

Graphical abstract

References