Cigna Kidney Transplantation, Pancreas-Kidney Transplantation, and Pancreas Transplantation Alone - (0146) Form

Medical Coverage Policy: 0146

The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients.

Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document.

Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation.

Each coverage request should be reviewed on its own merits. Medical directors are expected to exercise clinical judgment where appropriate and have discretion in making individual coverage determinations. Where coverage for care or services does not depend on specific circumstances, reimbursement will only be provided if a requested service(s) is submitted in accordance with the relevant criteria outlined in the applicable Coverage Policy, including covered diagnosis and/or procedure code(s). Reimbursement is not allowed for services when billed for conditions or diagnoses that are not

Medical Coverage Policy: 0146 covered under this Coverage Policy (see “Coding Information” below). When billing, providers must use the most appropriate codes as of the effective date of the submission. Claims submitted for services that are not accompanied by covered code(s) under the applicable Coverage Policy will be denied as not covered.

Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations. This Coverage Policy addresses kidney transplantation, pancreas-kidney transplantation, and pancreas transplantation alone. See CP 0355 for liver-kidney transplantation.

Kidney Transplantation

Kidney transplantation is considered medically necessary when ANY of the following criteria are met:

• adults (i.e., >18 years of age) measured or calculated creatinine clearance or glomerular filtration rate (GFR) less than or equal to 20 mL/min/1.73m2.

• pediatric (i.e., ≤18 years of age) stage 4 chronic kidney disease (estimated GFR <30 mL/min per 1.73m2)
• end-stage renal disease (ESRD) on regularly administered dialysis

Simultaneous Pancreas-Kidney (SPK) Transplantation

Simultaneous pancreas-kidney (SPK) transplantation is considered medically necessary when BOTH of the following criteria are met:

• medical necessity for kidney transplantation is met, and
• EITHER of the following indications:
  • diabetes mellitus (if individual is at least 18 years old must be on insulin)
  • pancreatic exocrine insufficiency

Pancreas Transplantation Alone (PTA)

Pancreas transplantation is considered medically necessary for an individual who meets ONE of the following criteria:

• diabetes mellitus (if individual is at least 18 years old must be on insulin)
• pancreatic exocrine insufficiency
• requires the procurement or transplantation of a pancreas as part of a multiple organ transplant for technical reasons

Pancreas-After-Kidney (PAK) Transplantation

Pancreas-after-kidney transplantation (PAK) is considered medically necessary when pancreas transplantation criteria are met.

Medical Coverage Policy: 0146

Not Covered

Kidney, pancreas, or pancreas-kidney transplantation for an individual with ANY of the following contraindications to transplant surgery is considered not medically necessary:

• malignancy that is expected to significantly limit future survival
• persistent, recurrent or unsuccessfully treated major or systemic extra-renal infections
• systemic illness or comorbidities that would be expected to substantially negatively impact the successful completion and/or outcome of transplant surgery
• a pattern of demonstrated patient noncompliance which would place a transplanted organ at serious risk of failure
• human immunodeficiency virus (HIV) disease unless ALL of the following are noted:
  • CD4 count greater than 200 cells/mm3
  • HIV-1 ribonucleic acid (RNA) undetectable
  • Stable anti-retroviral therapy for more than three months
  • Absence of serious complications associated with HIV disease (e.g., opportunistic infection, including aspergillus, tuberculosis, coccidioidomycosis, or resistant fungal infections, or Kaposi’s sarcoma or other neoplasm)

Living donor pancreas transplantation (i.e., partial pancreas transplantation, segmental pancreas transplantation) is considered experimental, investigational or unproven. Mechanical preservation machines for use with kidneys and/or pancreas transplantation is considered experimental, investigational or unproven for ANY indication.

General Background

Kidney Transplantation

End-stage renal disease (ESRD) occurs when the kidneys are no longer able to function at a level that is necessary for day-to-day life. ESRD almost always follows chronic kidney failure, which may exist for 10–20 years or more before progression to ESRD. Glomerular filtration rate (GFR) is considered the best measure of kidney function. While the lower limit of normal GFR varies with age, a GFR level below 60 mL per minute per 1.73m2 represents loss of one half or more of the adult level of normal kidney function. A GFR of <30 mL/min/1.73 m2 is considered to be abnormal in all ages other than neonates. Kidney failure, (i.e., chronic kidney disease [CKD] stage 5) is defined as either a GFR below 15 mL per minute per 1.73 m2 which, in most cases is accompanied by signs and symptoms of uremia, or a need to start kidney replacement therapy (i.e., dialysis or transplantation) for the treatment of complications of decreased GFR.

Patients with advanced CKD (Kidney Disease Outcomes Quality Initiative [K/DOQITM] CKD Stages 4 and 5) have a high propensity for progression to ESRD in a relatively short period of time with well-known multiple comorbid conditions and poor outcomes. Kidney transplantation is the grafting of a kidney from either a living or deceased (i.e., cadaver) donor. Both pediatric and adult kidney transplant recipients have increased survival compared to patients who remain on dialysis. Kidney transplantation should be timed to occur as close as possible to when the recipient would be expected to require dialysis; however, transplantation should be delayed in patients who may regain kidney function (e.g., malignant hypertension, severe, acute tubular necrosis). Transplantation performed prior to the need for dialysis is called preemptive transplantation. It confers a survival advantage to the recipient and is more common for recipients of living-donor kidneys. Preemptive kidney transplant has been shown to provide better outcomes compared to transplant after any period of time on dialysis; however, because of

Medical Coverage Policy: 0146 the shortage of donors, preemptive transplantation may not be possible. Kidney transplantation is an accepted and successful treatment for many individuals with ESRD. The transplant evaluation should begin when it is clear that the patient is destined to develop ESRD. In the event of subsequent renal graft failure, retransplantation is often performed.

Calculation of glomerular filtration rate (GFR):

A new eGFR equation, the 2021 Chronic Kidney Disease Epidemiology Collaboration (2021 CKD-EPI) equation in which the race variable was removed and the coefficients for the other variables (age, sex, and serum creatinine) were recalibrated, was published (Inker, et al., 2021). Subsequently, the National Kidney Foundation and American Society of Nephrology Task Force recommended that the 2021 CKD-EPI equation be implemented for eGFR reporting (Delgado, et al., 2022). The Board of Directors of the Organ Procurement and Transplantation Network (OPTN) unanimously approved a measure to require transplant hospitals to use a race-neutral calculation when estimating a patient’s level of kidney function.

Effective July 27, 2022, OPTN now requires all transplant hospitals to use race-neutral calculations when estimating a candidate’s glomerular filtration rate (GFR) for any purpose covered by OPTN policy. Effective January 5, 2023, kidney programs are required to assess their waiting lists and correct waiting times for any Black kidney candidates disadvantaged by having their kidney function overestimated due to use of a race-inclusive calculation (OPTN, 2023).

A prospective cohort study used National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) public repository data for the Chronic Renal Insufficiency Cohort (CRIC) multicenter study (Zelnick, et al., 2021). For the present analysis, Zelnick et al. included the 1658 participants with chronic kidney disease (CKD) who self-identified as Black. Results demonstrated that inclusion of the race coefficient in the estimation of GFR was associated with greater bias in GFR estimation. Specifically, over a median follow-up time of 4 years, use of the race coefficient in the creatinine-based CKD-EPI equation was associated with an eGFR that was a mean of 4.8 mL/min/1.73m2 higher than when no race coefficient was used.

Not using the race coefficient to estimate GFR (vs the standard race-based calculation) was also associated with a 35% higher risk of achieving the transplant referral threshold of an eGFR less than 20 mL/min/1.73m2, with a decrease in median time to achievement of an eGFR less than 20 ml/min/1.73m2 of 1.9 years.

The authors concluded that the biases in race based GFR estimates, while numerically modest, may be associated with delays in potential preemptive transplant referral and eligibility among Black patients with CKD.

Living Donor Kidney Transplantation:

An integral part of the nation’s organ donation system is the living donor. Living donors can be related or unrelated to the recipient. Living kidney donation eliminates the recipient’s need for waiting time on a national waiting list, are often more successful, and can add psychological benefits to both donor and recipient. Nonetheless, the benefit to the recipient of a live-donor organ must outweigh the risks to the donor. In the absence of a living donor, many transplanted kidneys come from deceased (i.e., cadaver) organ donors.

Retransplantation:

In general, retransplantation is considered by some to be a controversial procedure, in part due to ethical concerns over the limited supply of organs. A wide range of donor, recipient and other transplant-related factors can influence graft survival. In the event of renal graft failure, renal replacement therapy consists of either dialysis or retransplantation. Although allograft survival is considered good, it is considerably less compared to the primary transplant. Candidates awaiting kidney retransplant are often allosensitized and may be less likely to receive a transplant than primary candidates. As a result, some transplant centers have developed ongoing efforts involving desensitization protocols to prevent antibody-mediated acute rejection.

Although desensitization protocols may be considered for deceased donor kidney, protocols are generally attempted with living donation so that antibody response against donor tissue can be monitored; patients proceed to transplant surgery only if antibody levels are low. Authors contend that desensitizing highly sensitive patients improves clinical outcomes (short- term patient and graft survival) however acute antibody-mediated rejection is a barrier in 20-30% of patients and there is no consensus regarding which protocol is ideal.

Pancreas Transplantation

The standard treatment for control of blood sugar levels in type I diabetes mellitus (DM) is the use of exogenous insulin; however, this does not entirely restore normal glucose metabolism. Most people who are newly diagnosed with type 2 diabetes are usually treated with a combination of diet, exercise, and an oral medication. Some oral medications (e.g., metformin) improve the body's response to insulin. Other medications cause the body to produce more insulin. Some people will need to add insulin or another injectable medication because their blood sugar levels are not controlled. Using a combination of treatments (oral medication plus insulin) generally means that the person can take a lower dose of insulin, compared with if insulin treatment is used alone.

Pancreas transplantation has been demonstrated to improve the quality of life of people with diabetes, primarily by eliminating acute complications. Pancreas transplantation eliminates the need for exogenous insulin, daily glucose monitoring and many dietary restrictions imposed by diabetes. Additional benefits of pancreas transplantation include the elimination of life-threatening risks of hypoglycemic unawareness and prevention and reversal of diabetic nephropathy.

Pancreas transplantation may be performed:

• alone (i.e., Pancreas Transplantation Alone [PTA]), or
• after a kidney transplant (i.e., Pancreas After Kidney [PAK])

simultaneously with kidney transplants (i.e., Simultaneous Pancreas-Kidney [SPK]) or Evidence in the scientific published literature supports pancreas transplantation as an appropriate therapeutic intervention for individuals with diabetes on insulin or who have pancreatic exocrine insufficiency who require or have previously had a kidney transplant. Pancreas transplantation is a well-established and accepted method of treatment for these individuals, particularly the type 1 diabetic.

More recently, pancreas transplant has become an accepted method of treatment for type 2 diabetics, with both short-term and long-term outcomes commensurate with type 1 diabetes patients. Gruessner et al. (2017) reported patient, pancreas, and kidney graft survival rates increased significantly over time and reached 95.8, 83.3, and 91.1%, respectively, at 3 years post-transplant for transplants performed between 2009 and 2015.

Living Donor Pancreas Transplantation:

The OPTN Policy document (8/01/2023, Policy 11: Allocation of Pancreas, Kidney-Pancreas, and Islets) does not address living donor pancreas transplant. Living (partial, segmental) donor pancreas transplantation has been performed in a few centers, including those outside the United States; however, it is not considered widespread in clinical practice. In many cases, the living pancreas donor is a relative of the recipient. In the United States living donor pancreas transplantation has been largely studied at one center, the University of Minnesota.

Between January 1, 1994 to May 1, 2013, a total of 46 living-donor segmental pancreas transplants (LDSPTx) including 40 SPK, 2 PAK, and 4 PA were performed at the University of Minnesota (Kirchner, et al., 2016). Kirchner et al. stated that the rate of LDSPTx has significantly decreased over the last few years (on intent) in order to assess donor outcomes and safety prior to actively continuing the living donor (LD) pancreas program.

The new onset of diabetes mellitus (DM) requiring oral hypoglycemic management was diagnosed in 7 (15%) donors and insulin-dependent DM in 5 (11%). LD pancreas transplantation (especially SPK) should be offered in carefully selected donor-recipient pairs if metabolic risks for the donor are minimized by careful pre-donation screening and meticulous post-donation follow-up with interventions to prevent significant weight gain. Kirchner et al. concluded that LDSPTx can be performed with good recipient outcomes. The donation is associated with donor morbidity including impaired glucose control. Donor morbidity can be minimized by using risk stratification model and pre-donation counseling on lifestyle modifications post-donation (Kirchner, et al., 2016).

The evidence for living donor pancreas transplantation is limited and primarily in the form of few retrospective reports and patient-registry data (Henderson, et al., 2018; Lam, et al., 2017; Kirchner, et al., 2016; Choi, et al., 2016; Sutherland, et al., 2012). Donor and recipient selection criteria for living donor pancreas transplantation have not been clearly defined in the medical literature. Long-term clinical outcomes for the donor and recipient have not been reported.

In the short-term, there is limited evidence supporting normalizing insulin production for selected recipients, but concerns remain regarding negative metabolic impact to donors.

Note: For islet cell transplantation, see Coverage Policy 0107 Pancreatic Islet Cell Transplantation.

Retransplantation:

For all three types of pancreas transplants, survival rates for a second transplant are lower than for the primary transplant, although an elective retransplant may be considered suitable for a select group of patients. The medical literature suggests in some patients, a retransplant could improve health outcomes after graft loss, although there is insufficient data regarding health outcomes associated with third and subsequent pancreas transplants to allow strong conclusions.

Contraindications – Kidney and/or Pancreas Transplantation

Although it may vary by transplant center, generally absolute contraindications to kidney transplantation include the following:

• Active infections
• Active malignancy (excluding non-melanoma skin cancers)
• Active substance use disorder (with center-specific policies on marijuana use)
• Reversible kidney failure
• Uncontrolled psychiatric disease
• Documented active and ongoing treatment nonadherence

A significantly shortened life expectancy is generally a contraindication to transplantation. Recipient age alone is not a contraindication to transplantation (Rossi/UpToDate, 2023).

Absolute contraindications for simultaneous pancreas-kidney (SPK) or pancreas after kidney (PAK) transplant that are adopted by most centers include:

• Age >65 years
• Non-insulin-requiring diabetes
• Body mass index (BMI) >35 kg/m2
• Advanced cardiopulmonary disease (ejection fraction below 30 percent, pulmonary artery systolic pressure >50 mmHg, or positive cardiac stress test with uncorrectable coronary artery disease)
• Heavy smoking (>1 pack per day or patients with moderate-to-severe smoking-related morbidities [coronary heart disease, symptomatic or documented cerebrovascular or peripheral vascular disease, chronic obstructive lung disease, history of noncutaneous malignancy])
• Severe peripheral vascular (aorto-iliac) disease
• Moderate to severe dysfunction in other (non-kidney) organ systems (lung, liver, central nervous system [CNS]) including cirrhosis, portal hypertension, advanced chronic obstructive pulmonary disease, dementia, or severe neurologic deficits

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Absolute contraindications specific to SPK and PAK transplant include:

• Active malignancy with the exception of nonmelanoma skin cancer or low-grade prostate cancer
• Severe local or systemic infection
• Active substance addiction or abuse
• Major psychiatric illness that cannot be managed sufficiently to enable posttransplant care and safety
• Inadequate psychosocial support and financial resources
• Poor overall functional and performance status (severe deconditioning or malnutrition, frailty, dementia, wheelchair user, need for chronic oxygen therapy)
• Chronic nonhealing wounds
• Projected life expectancy <5 years

Relative contraindications to simultaneous pancreas-kidney (SPK) or pancreas after kidney (PAK) transplantation may also vary depending upon the transplant center (Alhamad/UpToDate, 2023).

Professional Societies/Organizations – Kidney and/or Pancreas Transplantation

In 1984 the National Organ Transplantation Act directed the Secretary of HHS to ‘establish by contract the Organ Procurement and Transplantation Network (OPTN) which shall be a private, non-profit entity that has an expertise in organ procurement and transplantation’. The United Network for Organ Sharing (UNOS) is the current OPTN Contractor. OPTN policies are updated annually and are rules that govern operation of all member transplant hospitals, organ procurement organizations (OPOs) and histocompatibility labs in the U.S. Policies are made through a collaborative process involving committees, the board of directors and the public.

UNOS/OPTN Kidney Transplantation Waiting Time Criteria

8.3.A Waiting Time for Candidates Registered at Age 18 Years or Older

If a kidney candidate is 18 years or older on the date the candidate is registered for a kidney, then the candidate’s waiting time is based on the earliest of the following:

1. The candidate’s registration date with a glomerular filtration rate (GFR) or measured or estimated creatinine clearance (CrCl) less than or equal to 20 mL/min.
2. The date after registration that a candidate’s GFR or measured or estimated CrCl becomes less than or equal to 20 mL/min.
3. The date that the candidate began regularly administered dialysis as an End Stage Renal Disease (ESRD) patient in a hospital based, independent non-hospital based, or home setting.

8.3.B Waiting Time for Candidates Registered prior to Age 18

If a kidney candidate is less than 18 years old at the time of registration on the waiting list, then the candidate’s waiting time is based on the earlier of the following:

1. The date that the candidate registered on the waiting list regardless of clinical criteria.
2. The date that the candidate began regularly administered dialysis as an ESRD patient in a hospital based, independent non-hospital based, or home setting.

UNOS/OPTN Policies for Pancreas Transplant

11.2.A Pancreas Registration

Each candidate registered on the pancreas waiting list must meet ONE of the following requirements:

• Be diagnosed with diabetes
• Have pancreatic exocrine insufficiency
• Require the procurement or transplantation of a pancreas as part of a multiple organ transplant for technical reasons

11.2.B Combined Kidney-Pancreas Registration (i.e., Simultaneous Pancreas-Kidney [SPK])

Each candidate registered on the kidney-pancreas waiting list must be diagnosed with diabetes, or have pancreatic exocrine insufficiency with renal insufficiency.

11.3.A Kidney-Pancreas Waiting Time Criteria for Candidates Less than 18 Years Old

To accrue waiting time for a kidney-pancreas transplant, a kidney-pancreas candidate who is less than 18 years old at the time of kidney-pancreas registration does not have to meet the qualifying criteria according to Policy 11.4 B below.

11.3.B Kidney-Pancreas Waiting Time Criteria for Candidates At Least 18 Years Old

If a kidney-pancreas candidate is 18 years or older on the date the candidate is registered for a kidney-pancreas, then the candidate begins to accrue waiting time once the candidate has met ALL of the following conditions:

• Candidate is registered for a kidney-pancreas.
• Candidate qualifies for kidney waiting time according to Policy 8.3: Waiting Time.
• Candidate is on insulin.

Once a kidney-pancreas candidate begins to accrue waiting time, the candidate will remain qualified for waiting time.

Mechanical Preservation Machines

While a donated kidney is outside of the body it is starved of oxygen, the halting of circulation allows small clots to form, which damages the organ. This damage remains a major barrier to transplantation as it renders many organs unusable and is associated with decreased survival of the kidneys which are transplanted. Traditionally kidneys were kept in ice (termed static cold storage). Machines which drive cold (hypothermic machine perfusion) or warm (normothermic machine perfusion) solutions through donated kidneys aim to decrease the damage done during transport and therefore improve the outcomes for these kidneys (Tingle, et al., 2019).

U.S. Food and Drug Administration (FDA)

LifePort™ Kidney perfusion transporter (Organ Recovery Systems, Inc.) was FDA-approved July 31, 2003 (K021362).

Mechanical Preservation Machines

It is intended to be used for the continuous hypothermic machine perfusion of kidneys for the preservation, transportation, and eventual transplantation into a recipient. Organ Assist Products B.V. (an affiliation of XVIVO Perfusion AB) KIDNEY ASSIST-transport received 510k FDA-approval on January 20, 2022. The KIDNEY ASSIST-transport is intended to be used for the pulsatile hypothermic oxygenated machine perfusion of kidneys for the preservation, transport, and eventual transplantation into a recipient.

At present the normothermic Kidney Assist™ Device made by Organ Assist has not been FDA-approved. At present, there are no FDA-approved pancreas continuous perfusion devices.

Mechanical Preservation Machines - Professional Societies/Organizations

The OPTN Policies document, Policy 16 on Organ and Vessel Packaging, Labeling, Shipping, and Storage states the following regarding Mechanical Preservation Machine (16.3.E.ii): "Members may use a mechanical preservation machine to transport organs. A mechanical preservation machine may be reused only if it is properly cleaned and sanitized and all labels from previous donor organs are removed" (8/01/2023).

The OPTN Executive Committee Proposed Strategic Plan 2021-2024 lists the following Initiative, "Review policies to determine whether future changes will be necessary to encourage or facilitate machine perfusion of organs." A listed Key Metric includes "An increase in the number of transplants of machine perfused organs".

The 'First World Consensus Conference on Pancreas Transplantation' (Boggi, et al., 2021) stated that "No recommendation was drawn on the use of machine perfusion because of lack of clinical studies".

Mechanical Preservation Machines - Literature Review - Kidney

Published studies in the peer-reviewed literature demonstrate mixed findings when comparing mechanical preservation machines and cold storage transport. Hypothermic and normothermic machine perfusion is being studied in the hope of utilization with marginal or expanded criteria donor organs in donation after cardiac death and after brain death. The data remains insufficient to conclude these devices are medically necessary.

A randomized controlled trial was conducted in six US sites. Malinoski et al. (2023) randomly assigned brain-dead kidney donors (1349 kidneys) to undergo:

• ex situ kidney hypothermic machine perfusion (machine-perfusion group, N=511),
• therapeutic hypothermia (hypothermia group, N=359) or both (combination-therapy group, N=479).

Results demonstrated at 1 year, the frequency of graft survival was similar in the three groups. The trial was terminated early for expected futility in determining the superiority of a combination of hypothermia and machine perfusion as compared with machine perfusion alone. Interim analysis established the inferiority of hypothermia alone. An interim analysis also showed a lack of a benefit for the combination strategy over machine perfusion alone. The observed incidence of delayed graft function was reduced by 11 percentage points in the machine-perfusion group as compared with the hypothermia group (19% versus 30%).

Delayed graft function in the kidney transplant recipients (defined as the initiation of dialysis during the first 7 days after transplant) occurred in:

• 109 patients (30%) in the hypothermia group,
• 99 patients (19%) in the machine-perfusion group, and
• 103 patients (22%) in the combination-therapy group.

A total of 10 adverse events were reported, including cardiovascular instability in 9 donors and organ loss in 1 donor owing to perfusion malfunction. The authors noted that a limitation of the trial was the open design in which all health care providers were aware of the group assignments.

The authors noted that “However, the investigators were not involved in the outcome-assessment process” (Malinoski, et al. 2023; NCT02525510). A randomized controlled trial compared the outcome of donation after circulatory death (DCD) kidney transplants after conventional static cold storage (SCS) alone or SCS plus 1 hour of normothermic machine perfusion (NMP). A total of SCS (n = 147) or NMP (n = 143), and 277 (not 290) kidneys were included in the final intention-to-treat analysis. The brand device used was not stated. Donor and recipient characteristics for the Intention-To-Treat analysis population:

• White: SCS: 120 (82%); NMP: 116 (81%)
• Black: SCS: 17 (12%); NMP: 16 (11%)
• Asian: SCS: 9 (6%); NMP: 8 (6%).

The authors reported:

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Delayed graft function (DGF, defined as the requirement for dialysis in the first 7 d after transplant) occurred in 83 of 142 (58.5%) patients in the SCS arm and 82 of 135 (60.7%) patients in the NMP arm. No difference was observed between the arms (P = 0.62). Patient and graft survival were similar between the arms. • NMP was not associated with any increase in transplant thrombosis, infectious complications, or any other adverse events (Hosgood, et al., 2023).

In a randomized controlled trial that spanned ten kidney transplant centers in five European countries, Husen et al. (2021) compared short-term oxygenated hypothermic machine perfusion preservation (end-HMPO2) after SCS versus SCS alone. A total of 127 kidneys (48.5%) in the end-HMPO2 group versus 135 (51.5%) in the SCS group were successfully transplanted (262 kidneys). Kidney Assist transport devices (Organ Assist BV) were used. Results demonstrated no significant difference in one-year graft survival: 92.1% (n = 117) in the end-HMPO2 group vs 93.3% (n = 126) in the SCS group (P = .71). The secondary end point analysis showed no significant between-group differences for delayed graft function, primary nonfunction, estimated glomerular filtration rate, and acute rejection.

In a multi-country randomized controlled trial, Moers et al. (2009) randomly assigned one kidney from 336 consecutive deceased donors to machine perfusion and the other to cold storage (672 recipients). The primary end point was delayed graft function (requiring dialysis in the first week after transplantation). LifePort Kidney Transporter machines (Organ Recovery Systems) were used. Results demonstrated delayed graft function developed in 70 patients in the machine-perfusion group versus 89 in the cold-storage group (P = 0.01). One-year allograft survival was superior in the machine-perfusion group (94% vs. 90%, P = 0.04). Overall, 3-year graft survival was better for machine-perfused kidneys (91% vs. 87%; P = 0.04). Three-year graft survival after machine perfusion was also superior to that after cold storage for kidneys donated after brain death (91% vs. 86%; P = 0.02) but not for kidneys donated after circulatory death. The 3- year graft-survival advantage after machine perfusion was most pronounced for kidneys recovered from donors who had expanded criteria for donation (86% vs. 76%; P = 0.01) (Moers, et al., 2012).

Kox et al. (2018) performed a post-study (Moers 2009/2012) subgroup analysis after dividing the data set into four cold ischemia time (CIT) groups (less than 10 hours, 10-15 hours, 15-20 hours, and more than 20 hours). An analysis was performed to investigate whether the observed differences in delayed graft function (DGF) incidence would lead to a long-term effect of hypothermic machine perfusion (HMP) versus SCS on graft survival in each of the 4 CIT groups.

Mechanical Preservation Machines - Literature Review - Kidney

For HMP and SCS, respectively, the graft survival rates were 88.0% versus 81.3% for 0 to 10 hours of CIT, 91.9% versus 90.1% for 10 to 15 hours, 93.8% versus 88.5% for 15 to 20 hours, and 84.9% versus 83.7% for more than 20 hours of cold ischemia. There was no statistically significant 3-year graft survival benefit for HMP preserved kidneys in any of the four subgroups.

A randomized controlled trial conducted in China (Zhong, et al., 2017) compared the effect of machine perfusion (MP) and cold storage (CS) in protecting kidneys harvested from DCDs. A total of 141 kidney pairs from DCDs were randomized. One kidney from each donor was randomly assigned to MP and the contralateral kidney was assigned to CS. LifePort Kidney Transporter machines (Organ Recovery Systems) were used. Results demonstrated a 3-year graft survival rate in the MP group was significantly higher than that in the CS group (93% vs. 82%, P=0.036).

Mechanical Preservation Machines - Literature Review – Pancreas

Static cold storage (SCS) is still the standard method of preservation for pancreases. Hypothermic machine perfusion and normothermic machine perfusion (NMP) are under investigation, including animal and human reports. In contrast to other organs, the use of NMP in the pancreas is still limited by the injurious enzymes produced during perfusion. Future successful human trials will be crucial (Hamaoui, et al., 2019; Branchereau, et al., 2020).

Use Outside of the US

The NHS Organ Donor Register is the equivalent to the US' UNOS. In Japan, an Organ Transplant Law took effect in October 1997 and the Japan Organ Transplant Network (JOTNW) was established to deal with heart and liver transplants in addition to kidneys. The Canadian Organ Replacement Register (CORR) is a pan-Canadian information system and is responsible for maintaining a list of contact information for dialysis, transplant and organ procurement centers across Canada as well as producing in-depth reports and analyses on long-term trends on organ transplants. The Australia and New Zealand Organ Donation (ANZOD) Registry records and reports on organ donation within Australia and New Zealand.