EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Key words : Delayed graft function, Hypothermic perfusion, India, Normothermic perfusion, Organ preservation, Perfusate, Transplant economics

Kidney transplantation is the most effective solution for end-stage kidney disease, particularly in resource-challenged countries like India where the availability and affordability of dialysis vary.¹ Deceased organ donation in India has shown measurable growth over the past decade (Figure 1). According to data from National Organ and Tissue Transplant Organization (NOTTO), the number of deceased donors increased from 408 deceased donors in 2014 to 1128 deceased donors in 2024, while total deceased donor transplants rose from 1030 to 3403 during the same period. Deceased donor kidney transplants increased from 628 transplants in 2014 to 1918 transplants in 2024, and deceased donor liver transplants increased from 325 to 952 during this period.²

Donation after circulatory death (DCD) is an untapped opportunity that has gained progress in India, although a structured national DCD program is still needed. Tertiary care institutes have reported early experience with kidney transplant from DCD donors, demonstrating feasibility in the Indian scenario.^3,4 Importantly, reported Indian DCD cases have largely involved uncontrolled DCD (Maastricht category II/IV) scenarios, and controlled DCD pathways are not routinely established within the national deceased donation framework. The growing rate of deceased donation and the acceptance of marginal donors, such as extended criteria donors (ECD) and DCD, require preservation methods that enhance graft viability and allow for assessment before implantation.⁵

Static cold storage (SCS) has been the main preservation method for deceased donor organs, in which a preservation solution is used to flush the organ once at the time of procurement. However, machine perfusion has become a vital complement to SCS, improving graft survival and transplant outcomes.^5-8 Machine perfusion includes both hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP), each having its own advantages.⁹ Here, we present evidence-based recommendations tailored for India on the integration of machine perfusion in kidney transplantation. Although kidney transplantation remains the primary focus of this document, high-level evidence from liver perfusion trials has informed several preservation strategies, particularly oxygenated hypothermic perfusion and viability assessment paradigms, due to shared pathop-hysiological mechanisms of ischemia-reperfusion injury.

Development of Recommendations

Evidence-based recommendations were developed in collaboration with the NOTTO, Ministry of Health and Family Welfare, Government of India. A multi-disciplinary panel of experts was constituted, comprising transplant nephrologists, transplant surgeons, representatives from NOTTO, and clinicians from transplant centers where machine perfusion has been undertaken. A structured review of PubMed-indexed literature on machine perfusion in kidney transplantation was also conducted, which focused on randomized controlled trials, systematic reviews, meta-analyses, registry studies, and major inter-national guidelines. For areas where kidney-specific randomized data were limited, mechanistic insights from liver perfusion trials were referenced to inform preservation strategies. Draft recommen-dations were prepared based on available evidence and contextualized to the Indian health care framework. The draft document was circulated among panel members for review and iterative refinement. Recommendations were finalized through expert consensus following structured discussions, ensuring alignment with current scientific evidence and national transplant policy considerations.

Patient selection and indications
In Indian medical practice, where late referrals and comorbid conditions are frequently observed among both donors and recipients, the cautious use of machine perfusion is essential¹⁰ (Table 1). Hypothermic machine perfusion is advised for every DCD kidney and is highly recommended for ECD grafts as it greatly decreases the incidence of delayed graft function (DGF) and enhances early graft survi-val rates.¹¹ Normothermic machine perfusion should be considered for kidneys deemed high-risk (KDPI >85%, prolonged cold ischemia time of >12 hours, or unclear biopsy results); NMP allows for real-time assessment of metabolic and functional status.¹²

Timing and technique
Ongoing HMP from the moment of retrieval until implantation is the best approach,¹³ although end-ischemic HMP is an acceptable alternative in Indian facilities with limited resources. Normothermic machine perfusion should be started 1 to 2 hours before implantation, requiring 60 to 90 minutes to provide reliable viability information.¹⁴ The optimal application of this method is in tertiary hospitals equipped with advanced support.

Perfusate composition and additives
The formulation of the perfusate affects both functionality and cost. Medical centers in India should customize their usage according to what is available. Table 1 depicts various Indian adaptations.

For HMP, the use of University of Wisconsin (UW)-MPS or Institute Georges Lopez-1 (IGL-1) solution is advisable, with essential additives being allopurinol, mannitol, glutathione, and dexamethasone. Tempera-ture should be maintained between 0 °C and 12 °C.15

For NMP, the use of red blood cell-based perfusates enriched with insulin, amino acids, vasodilators, antibiotics, and electrolytes is preferred. Arterial pressure should be kept at 25 to 30 mm Hg. Because NMP maintains organs at near-physiological temperatures, temperature should be kept between 35 °C and 38 °C.16

Functional assessment and viability testing
In resource-limited settings like India, lower threshold criteria should guide organ acceptance. Various functional parameters and thresholds for NMP viability assessment have been depicted in Table 1^14,17,18 with Indian adaptations.

Clinical Outcomes

Machine perfusion was first deployed by army hospitals in India. Per data from Army Hospital Research and Referral, New Delhi, 1-year graft outcomes in HMP were better compared with SCS in all patients. However, in cases with cold ischemia time of >8 hours, significantly better urine output and estimated glomerular filtration rate were shown in HMP (Table 2). In addition, HMP decreased the rates of DGF and duration of stay in the hospital.

A growing body of evidence has supported the superiority of HMP, particularly hypothermic oxygenated perfusion (HOPE), over SCS in both liver and kidney transplant (Table 3). In liver transplants, especially from DCD donors, HOPE significantly reduces non-anastomotic biliary strictures, early allograft dysfunction, and graft loss, with improved survival (DHOPE-DCD trial,¹⁹ Schlegel and colleagues,²⁰ and multiple meta-analyses^21,22). In kidney transplantation, multiple studies, including the landmark trial by Moers and colleagues,²³ systematic reviews by O’Callaghan and colleagues²⁴ and Tingle and colleagues,²⁵ and the real-world implementation in the Netherlands reported by Brat and colleagues,²⁶ consistently showed that HMP significantly reduces DGF, particularly in DCD and ECD grafts, and improves graft survival.^23-26

The use of oxygenated HMP (HOPE) has shown further promise in preclinical and clinical studies, especially for DCD grafts. In a recent trial, Malinoski and colleagues confirmed that machine perfusion was superior to donor hypothermia, and the combination of both strategies provided no added benefit.27 On the other hand, NMP has shown mixed results; although NMP may reduce early allograft dysfunction, this technique has yet to demonstrate consistent advantages in long-term outcomes or survival over HMP or HOPE.^21,22

Cost-Effectiveness and Policy Considerations

In India’s hybrid public-private health care system, targeted utilization of HMP for DCD/ECD grafts could be economically efficient,^28,29 and national initiatives like the National Organ Transplant Prog-ramme and the Ayushman Bharat system can consider provision of services of HMP devices and devices based on such technologies from the “Make in India” initiative. Transplant and retrieval centers might partner to create collaborative regional perfusion centers.

Implementation Strategy and National Recom-mendations

National recommendations are as follows: (1) edu-cate perfusion officers, nephrologists, and transplant coordinators; (2) advise each tertiary center to have at least 1 HMP unit; NMP units should be present in top-tier teaching hospitals; and (3) adopt NMP for organ reconditioning in high-KDPI or rejected grafts.

Evidence from landmark trials6,11 have demon-strated that HMP reduces DGF and improves graft survival, particularly in ECD and DCD donors. Integrating structured training for perfusion officers, nephrologists, and transplant coordinators can ensure technical competency, while standardizing practices can provide uniformity and quality control. Equipping every tertiary transplant center with at least 1 HMP unit can guarantee baseline access, while situating NMP units in top-tier teaching hospitals can allow for regional expertise and advanced graft reconditioning. Selective NMP use for high-KDPI or initially declined kidneys, guided by viability testing and registry-driven monitoring, can maximize donor organ utilization. A phased, centrally coordinated approach (Table 4) combines capacity building, infrastructure development, and national oversight to deliver sustainable, evidence-based improvements in transplant practice.

Machine perfusion can be considered for integration into the national transplant framework in India to improve organ usage, decrease DGF, and facilitate rational evaluation of grafts. However, before implementation, further multicenter studies from different regions of the country are recommended. The use of HMP is backed by scientific evidence, as per robust global and emerging Indian data, and NMP shows promise for functional diagnostics and graft reconditioning. Strategic investments are needed in indigenous technologies, educating transplant professionals, and developing regional infrastructure to increase the accessibility and affordability of machine perfusion and to improve the graft outcomes.

Volume: 24 Issue: 5 May 2026

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