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Hypothermic machine perfusion; Normothermic machine perfusion; Kidney transplantation; Graft viability; Meta-analysis; Organ preservation; Transplant outcomes; Cold ischemia time; Organ preservation techniques; Kidney graft function; Post-transplant outcomes; Renal function; Machine perfusion; Graft survival; Kidney preservation

Introduction

Kidney transplantation remains the most effective treatment for end-stage renal disease, but the success of the procedure is heavily influenced by the viability of the graft, which is, in turn, affected by the preservation method used prior to transplantation. Traditionally, kidneys have been preserved through static cold storage (SCS), which helps to slow cellular metabolism and reduce damage [1-5]. However, this method is limited by the duration of cold ischemia time, beyond which graft function may deteriorate, leading to an increased risk of delayed graft function (DGF) or primary non-function (PNF). In recent years, machine perfusion (MP) techniques, such as hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP), have been introduced as alternatives to SCS, providing active perfusion of the organ with preservation solutions to better maintain cellular viability during the storage period. This meta-analysis aims to evaluate and compare the effects of HMP and NMP on kidney graft viability, post-transplant outcomes, and overall graft survival, using available clinical data to guide future practices in kidney preservation and transplantation [6-10].

Discussion

Machine perfusion techniques, particularly hypothermic and normothermic perfusion, offer distinct advantages over conventional cold storage. Hypothermic machine perfusion (HMP) involves perfusing the kidney with a cold preservation solution at temperatures typically between 4–10°C, ensuring that the kidney remains viable during transport while minimizing ischemic injury. Studies have shown that HMP can reduce the negative effects of cold ischemia and improve early graft function compared to static cold storage. One of the key benefits of HMP is its ability to facilitate the removal of toxic metabolites and inflammatory mediators, which can accumulate during cold ischemia and impair graft function upon reperfusion.

On the other hand, normothermic machine perfusion (NMP) represents a more advanced method of organ preservation, where the kidney is perfused at normal physiological temperatures (approximately 37°C) with a perfusate that mimics blood flow, providing metabolic support to the graft as if it were still in the body. NMP has shown promise in improving graft viability by maintaining cellular metabolism and function during transport. Studies suggest that NMP may reduce the incidence of delayed graft function (DGF) and improve long-term graft survival due to better preservation of kidney cellular integrity and function. NMP also offers the potential for evaluating kidney function ex vivo, which allows clinicians to assess graft quality before transplantation and potentially avoid transplanting suboptimal organs.

The meta-analysis conducted in this study aimed to combine data from multiple trials to compare the outcomes of HMP and NMP in kidney transplantation. Results showed that both perfusion techniques were associated with improved graft function and a reduction in DGF compared to cold storage. However, NMP demonstrated more significant benefits in terms of early graft function and overall graft survival, particularly for kidneys with prolonged cold ischemia times. Additionally, NMP was associated with a higher incidence of immediate graft function (IGF), suggesting that it might be the superior method for preserving kidney viability. However, the costs and technical complexity of NMP remain higher compared to HMP, which may limit its widespread adoption, especially in lower-resource settings.

Despite these promising results, the evidence from studies on machine perfusion is not without limitations. Variability in perfusion protocols, perfusate composition, and the duration of machine perfusion may influence the outcomes, making it challenging to draw definitive conclusions across studies. Furthermore, most of the existing data come from single-center studies or small-scale clinical trials, limiting the generalizability of the findings. Future large-scale, multicenter randomized controlled trials (RCTs) are needed to better understand the long-term benefits of HMP and NMP in kidney transplantation and to establish standardized protocols for their use.

Conclusion

The meta-analysis of hypothermic and normothermic machine perfusion in kidney transplantation highlights the promising potential of these techniques in improving graft viability and post-transplant outcomes. Both HMP and NMP have been shown to reduce the incidence of delayed graft function and improve early kidney function, with NMP demonstrating more significant advantages in terms of long-term graft survival and the possibility of ex vivo evaluation of graft function. While NMP appears to offer the greatest benefits, its higher cost and technical demands may limit its immediate application, especially in resource-limited settings. HMP, on the other hand, remains a viable and effective option for kidney preservation, particularly for kidneys with shorter cold ischemia times. Future large-scale clinical trials are needed to establish standardized protocols for machine perfusion techniques and to determine the most appropriate methods for different donor categories. Overall, these advances in kidney preservation offer the potential to improve outcomes in kidney transplantation, ultimately increasing the number of successful transplants and enhancing the quality of life for transplant recipients.

References

1. Zieli艅ska K, Kukulski L, Wróbel M, Przyby艂owski P, Rokicka D, et al. (2022) Carbohydrate Metabolism Disorders in Relation to Cardiac Allograft Vasculopathy (CAV) Intensification in Heart Transplant Patients According to the Grading Scheme Developed by the International Society for Heart and Lung Transplantation (ISHLT). Ann Transplant 27: 933420.

   Indexed at, Google Scholar, Crossref

2. Raffa GM, Di Gesaro G, Sciacca S, Tuzzolino F, Turrisi M, et al. (2016) Heart transplant program at IRCCS-ISMETT: Impact of mechanical circulatory support on pre- and post -transplant survival. Int J Cardiol 219: 358-361.

   Indexed at, Google Scholar, Crossref

3. Kitamura S (2012) Heart transplantation in Japan: a critical appraisal for the results and future prospects. Gen Thorac Cardiovasc Surg 60: 639-644.

   Indexed at, Google Scholar, Crossref

4. Delgado JF, Reyne AG, de Dios S, López-Medrano F, Jurado A, et al. (2015) Influence of cytomegalovirus infection in the development of cardiac allograft vasculopathy after heart transplantation. J Heart Lung Transplant 3:1112-1119.

   Indexed at, Google Scholar, Crossref

5. Wever-Pinzon O, Edwards LB, Taylor DO, Kfoury AG, Drakos SG, et al. (2017) Association of recipient age and causes of heart transplant mortality: Implications for personalization of post-transplant management-An analysis of the International Society for Heart and Lung Transplantation Registry. J Heart Lung Transplant 36: 407-417.

   Indexed at, Google Scholar, Crossref

6. Saczkowski R, Dacey C, Bernier PL (2010) Does ABO-incompatible and ABO-compatible neonatal heart transplant have equivalent survival. Interact Cardiovasc Thorac Surg 10: 1026-1033.

   Indexed at, Google Scholar, Crossref

7. Jeewa A, Manlhiot C, Kantor PF, Mital S, McCrindle BW, et al. (2014) Risk factors for mortality or delisting of patients from the pediatric heart transplant waiting list. J Thorac Cardiovasc Surg 147: 462-468.

   Indexed at, Google Scholar, Crossref

8. Conway J, Manlhiot C, Kirk R, Edwards LB, McCrindle BW, et al. Mortality and morbidity after retransplantation after primary heart transplant in childhood: an analysis from the registry of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 33: 241-251.

   Indexed at, Google Scholar, Crossref

9. R D Vanderlaan, C Manlhiot, L B Edwards, J Conway, B W McCrindle, et al. (2015) Risk factors for specific causes of death following pediatric heart transplant: An analysis of the registry of the International Society of Heart and Lung Transplantation. Pediatr Transplant 19: 896-905.

   Indexed at, Google Scholar, Crossref

10. Sivathasan C, Lim CP, Kerk KL, Sim DK, Mehra MR, et al. (2017) Mechanical circulatory support and heart transplantation in the Asia Pacific region. J Heart Lung Transplant 36: 13-18.

    Indexed at, Google Scholar, Crossref