Heme-Oxygenase and Kidney Transplantation: A Potential for Target Therapy?

Daniela Corona,Chiara Schipa,Rossella Gioco,Antonio Granata,Burcin Ekser,Pierfrancesco Veroux,Massimiliano Veroux,Massimo Caruso,Alessia Giaquinta

doi:10.3390/biom10060840

Daniela Corona, Chiara Schipa + Show 7 more

Open Access

https://doi.org/10.3390/biom10060840

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Journal: Biomolecules	Publication Date: May 30, 2020
Citations: 15	License type: CC BY 4.0

Affiliation: University of Catania, Ospedale Cannizzaro

Abstract

Kidney transplantation is a well-established therapy for patients with end-stage renal disease. While a significant improvement of short-term results has been achieved in the short-term, similar results were not reported in the long-term. Heme-oxygenase (HO) is the rate-limiting enzyme in heme catabolism, converting heme to iron, carbon monoxide, and biliverdin. Heme-oxygenase overexpression may be observed in all phases of transplant processes, including brain death, recipient management, and acute and chronic rejection. HO induction has been proved to provide a significant reduction of inflammatory response and a reduction of ischemia and reperfusion injury in organ transplantation, as well as providing a reduction of incidence of acute rejection. In this review, we will summarize data on HO and kidney transplantation, suggesting possible clinical applications in the near future to improve the long-term outcomes.

Highlights

Kidney transplantation is the preferred replacement therapy for patients with end-stage renal disease, and it significantly improves quality of life and patient survival when compared with maintenance dialysis [1]
Acute rejection and the delayed graft function (DGF), which is defined as the need for dialysis within the first week after transplantation [4,5,6,7], are probably the two main limiting factors of short- and long-term outcomes after kidney transplantation, when both are present simultaneously [4,5,6,7,8,9,10] (Figure 2)
In this review, we have focused on the role of HO iin kkiiddnneey ttrraannsspplantation (Figure 4), describing the potential protective effffect of HO induction and the potential target for ccuussttomized tthheerrapy, which could improve short- and long-term outcommeess ffoolllloowwiinngg kkiiddnneeyy ttrraannssppllaannttaattiioonn

Summary

Introduction

Kidney transplantation is the preferred replacement therapy for patients with end-stage renal disease, and it significantly improves quality of life and patient survival when compared with maintenance dialysis [1]. Acute rejection and the delayed graft function (DGF), which is defined as the need for dialysis within the first week after transplantation [4,5,6,7], are probably the two main limiting factors of short- and long-term outcomes after kidney transplantation, when both are present simultaneously [4,5,6,7,8,9,10] (Figure 2). A recent study investigating the impact of duration of DGF on the risk of acute rejection and graft loss found that compared with kidney transplant recipients experiencing a DGF duration of 1 to 4 days, the adjusted hazard ratio for a duration of 5 to 7, 8 to 13, and 14 days or longer raised significantly to 1.13, 1.44, and 1.99 (P < 0.001), respectively, for acute rejection and 1.10, 1.45, and 1.60, respectively, for death-censored graft loss, suggesting that there was a direct time-dependent effect between DGF and the risk of acute rejection and death-censored graft loss [3]

Ischemic Injury and Hypoxic Adaption

Type of Donor

Acute and Chronic Rejection and Immunosuppression

Findings

Potential Therapeutic Targets and Final Considerations