Effects of Ischemia-Reperfusion Injury in Kidney Transplantation: Risk Factors and Early and Long-Term Outcomes in a Single Center

Chronic kidney disease (CKD) is increasing in most countries and kidney transplantation is the best option for those patients requiring renal replacement therapy. Therefore, there is a significant number of patients living with a functioning kidney allograft. However, progressive kidney allograft functional deterioration remains unchanged despite of major advances in the field. After the first post-transplant year, it has been estimated that this chronic allograft damage may cause a 5% graft loss per year. Most studies focused on mechanisms of kidney graft damage, especially on ischemia-reperfusion injury, alloimmunity, nephrotoxicity, infection and disease recurrence. Thus, therapeutic interventions focus on those modifiable factors associated with chronic kidney allograft disease (CKaD). There are strategies to reduce ischemia-reperfusion injury, to improve the immunologic risk stratification and monitoring, to reduce calcineurin-inhibitor exposure and to identify recurrence of primary renal disease early. On the other hand, control of risk factors for chronic disease progression are particularly relevant as kidney transplantation is inherently associated with renal mass reduction. However, despite progress in pathophysiology and interventions, clinical advances in terms of long-term kidney allograft survival have been subtle. New approaches are needed and probably a holistic view can help. Chronic kidney allograft deterioration is probably the consequence of damage from various etiologies but can be attenuated by kidney repair mechanisms. Thus, besides immunological and other mechanisms of damage, the intrinsic repair kidney graft capacity should be considered to generate new hypothesis and potential therapeutic targets. In this review, the critical risk factors that define CKaD will be discussed but also how the renal mechanisms of regeneration could contribute to a change chronic kidney allograft disease paradigm.

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Safety and Efficacy of Treprostinil (Remodulin®) In Reducing Ischemia-Reperfusion Injury During Kidney Transplantation

Case Medical Research ◽

10.31525/ct1-nct04005469 ◽

2019 ◽

Author(s):

Keyword(s):

Kidney Transplantation ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Safety And Efficacy

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Influence of long-term treatment with glyceryl trinitrate on remote ischemic conditioning

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00114.2018 ◽

2018 ◽

Vol 315 (1) ◽

pp. H150-H158 ◽

Cited By ~ 16

Author(s):

Marie Hauerslev ◽

Sivagowry Rasalingam Mørk ◽

Kasper Pryds ◽

Hussain Contractor ◽

Jan Hansen ◽

...

Keyword(s):

Endothelial Function ◽

Glyceryl Trinitrate ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Rat Myocardium ◽

Remote Ischemic Conditioning ◽

Ischemic Conditioning ◽

Human Endothelium

Remote ischemic conditioning (RIC) protects against sustained myocardial ischemia. Because of overlapping mechanisms, this protection may be altered by glyceryl trinitrate (GTN), which is commonly used in the treatment of patients with chronic ischemic heart disease. We investigated whether long-term GTN treatment modifies the protection by RIC in the rat myocardium and human endothelium. We studied infarct size (IS) in rat hearts subjected to global ischemia-reperfusion (I/R) in vitro and endothelial function in healthy volunteers subjected to I/R of the upper arm. In addition to allocated treatment, rats were coadministered with reactive oxygen species (ROS) or nitric oxide (NO) scavengers. Rats and humans were randomized to 1) control, 2) RIC, 3) GTN, and 4) GTN + RIC. In protocols 3 and 4, rats and humans underwent long-term GTN treatment for 7 consecutive days, applied subcutaneously or 2 h daily transdermally. In rats, RIC and long-term GTN treatment reduced mean IS (18 ± 12%, P = 0.007 and 15 ± 5%, P = 0.002) compared with control (35 ± 13%). RIC and long-term GTN treatment in combination did not reduce IS (29 ± 12%, P = 0.55 vs. control). ROS and NO scavengers both attenuated IS reduction by RIC and long-term GTN treatment. In humans, I/R reduced endothelial function ( P = 0.01 vs. baseline). Separately, RIC and long-term GTN prevented the reduction in endothelial function caused by I/R; given in combination, prevention was lost. RIC and long-term GTN treatment both protect against rat myocardial and human endothelial I/R injury through ROS and NO-dependent mechanisms. However, when given in combination, RIC and long-term GTN treatment fail to confer protection. NEW & NOTEWORTHY Remote ischemic conditioning (RIC) and long-term glyceryl trinitrate (GTN) treatment protect against ischemia-reperfusion injury in both human endothelium and rat myocardium. However, combined application of RIC and long-term GTN treatment abolishes the individual protective effects of RIC and GTN treatment on ischemia-reperfusion injury, suggesting an interaction of clinical importance.

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