Populations	Interventions	Comparators	Outcomes
Individuals: With end-stage renal disease without contraindications to kidney transplant	Interventions of interest are: Kidney transplant from a living donor or deceased (cadaveric) donor	Comparators of interest are: Medical management Dialysis	Relevant outcomes include: Overall survival Morbid events Treatment-related mortality Treatment-related morbidity
Individuals: With a failed kidney transplant without contraindications to kidney transplant	Interventions of interest are: Kidney retransplant from a living donor or deceased (cadaveric) donor	Comparators of interest are: Medical management Dialysis	Relevant outcomes include: Overall survival Morbid events Treatment-related mortality Treatment-related morbidity

Background

End-Stage Renal Disease

ESRD refers to the inability of the kidneys to perform their functions (i.e., filtering wastes and excess fluids from the blood). ESRD, which is life-threatening, is also known as stage 5 chronic renal failure and is defined as a glomerular filtration rate less than 15 mL/min/1.73 m².^1,

Treatment

Dialysis is an artificial replacement for some kidney functions. Dialysis is used as a supportive measure in patients who do not want kidney transplants or who are not transplant candidates; it can also be used as a temporary measure in patients awaiting a kidney transplant.

Kidney transplant, using kidneys from deceased or living donors, is an accepted treatment of ESRD. Based on data from the Organ Procurement and Transplantation Network, in 2017, over 10300 kidney transplants were performed in the U. S. Since 1988, the cumulative number of kidney transplants is over 435500.^2, Of the cumulative total, 66% of the kidneys came from deceased donors and 34% from living donors.

Combined kidney and pancreas transplants and management of acute rejection of kidney transplant using either intravenous immunoglobulin or plasmapheresis are discussed in separate policies.

Regulatory Status

A kidney transplant is a surgical procedure and, as such, is not subject to regulation by the U.S. Food and Drug Administration.

The U.S. Food and Drug Administration regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation Title 21, parts 1270 and 1271. Kidney transplants are included in these regulations.

Related Policies

• Allogeneic Pancreas Transplant (Policy #088 in the Surgery Section)
• Intravenous Immunoglobulin (IVIG) Therapy (Policy #016 in the Drugs Section)
• Plasma Exchange (Policy #056 in the Treatment Section)

[NOTE: Combined kidney-pancreas transplant is addressed in a separate policy on 'Allogeneic Pancreas Transplant' (Policy #088 in the Surgery Section) and transplant donors and recipients are addressed in the 'Transplant Donor and Recipient Policy' (Policy #003 in the Surgery Section). The management of acute rejection of kidney transplant using either intravenous immunoglobulin (IVIG) or plasmapheresis are addressed in separate policies on 'Intravenous Immunoglobulin (IVIG) Therapy' (Policy #016 in the Drugs Section) and 'Plasma Exchange' (Policy #056 in the Treatment Section) respectively.

(NOTE: For Medicare Advantage, Medicaid and FIDE-SNP, please refer to the Coverage Sections below for coverage guidance.)]

1. Kidney transplants with either a living or cadaver donor is considered medically necessary for selected candidates with end-stage renal disease.
2. Kidney retransplant after a failed primary kidney transplant is considered medically necessary in members who meet criteria for kidney transplantation.
3. Kidney transplant is considered investigational in all other situations.

1. Known current malignancy, including metastatic cancer
2. Recent malignancy with high risk of recurrence
3. History of cancer with a moderate risk of recurrence
4. Systemic disease that could be exacerbated by immunosuppression
5. Untreated systemic infection making immunosuppression unsafe, including chronic infection
6. Other irreversible end-stage disease not attributed to kidney disease
7. Psychosocial conditions or chemical dependency affecting ability to adhere to therapy

FIDE-SNP Coverage:
For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.

[RATIONALE: This policy was created in 2009 and has been updated regularly with searches of the PubMed database. The most recent literature update was performed through June 10, 2019.

Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life, and ability to function-including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, two domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent one or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. Randomized controlled trials are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Kidney Transplant

Clinical Context and Test Purpose

The purpose of a kidney transplant in patients who have end-stage renal disease (ESRD) without contraindications to a kidney transplant is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does kidney transplantation improve the net health outcome in individuals with ESRD without contraindications to kidney transplant?

The following PICOs were used to select literature to inform this policy.

Patients

The relevant population of interest are individuals with end ESRD without contraindications to a kidney transplant.

Interventions

The therapy being considered is kidney transplant from a living or cadaveric donor which is provided in a hospital setting by specialized staff who are equipped to perform the surgical procedure and manage postsurgical care.

Comparators

The following therapies and practices are currently being used to make decisions about managing ESRD: medical management, including dialysis and medications to control symptoms.

Outcomes

The general outcomes of interest are overall survival (OS), elimination of the need for dialysis, and treatment-related adverse events (e.g., immunosuppression, graft failure, surgical complications, infections),with follow-up ranging from 30 days posttransplantation up to 10 years or more. See the Potential Contraindications section for detailed discussion.

Registry Studies

According to data analysis from the Organ Procurement and Transplantation Network (OPTN), between 2008 and 2015, the 1-year survival of patients undergoing an initial kidney transplant was 97.0% (95% confidence interval [CI], 96.8% to 97.1%).^2, Five-year survival was 85.8% (95% CI, 85.5% to 86.1%).

Krishnan et al (2015) published a study of 17681 patients in a U.K. transplant database who received a kidney transplant or were on a list to receive a kidney transplant.^3, Authors found significantly higher 1- and 5-year survival rates in patients who underwent a kidney transplant than in those who remained on dialysis (exact survival rates not reported).

Transplants Stratified by Donor Source

The United Network for Organ Sharing proposed an Expanded Criteria Donor (ECD) approach in 2002 to include brain-dead donors over 60 years or between 50 and 59 years old with 2 or more of the following criteria: serum creatinine level greater than 1.5 mg/dL, death caused by cerebrovascular accident, or history of high blood pressure.^4,

Querard et al (2016) conducted a systematic review and meta-analysis of studies comparing survival outcomes with ECD vs Standard Criteria Donor (SCD) kidney transplant recipients.^4, Reviewers identified 32 publications, 5 of which adjusted for potential confounding factors. A pooled analysis of 2 studies reporting higher rates of patient-graft failure for ECD kidney recipients found a significantly higher adjusted hazard ratio (HR) for patient-graft survival (HR=1.68; 95% CI; 1.32 to 2.12). Meta-analyses were not conducted for patient survival outcomes; however, 1 study (n=189) found a higher but nonsignificant difference in patient survival with ECD than with SCD (HR=1.97; 95% CI, 0.99 to 3.91) and another (n=13833) found a significantly increased risk of death with ECD than with SCD (HR=1.25; 95% CI, 1.12 to 1.40).

Pestana (2017) published a retrospective, single-center analysis of kidney transplants performed between 1998 and 2015 at a hospital in Brazil.^5, Of the 11436 transplants analyzed, 31% (n=3614) were performed under SCD, while 14% (n=1618) were performed under ECD. The number of ECD recipients increased over time, from 29 transplants in 1998-2000 to 450 transplants from 2013-2014. Patient survival with ECD increased from 1998-2002 to 2011-2014 (from 79.7% to 89.2%, p<0.001); a similar increase was noted in patient survival with SCD over the same time periods (from 73.1% to 85.2%, p<0.001). The study was limited by reliance on limited registry data.

Several studies have reported long-term outcomes in live kidney donors. The most appropriate control group to evaluate whether donors have increased risks of morbidity and mortality are individuals who meet the criteria for kidney donation but who did not undergo the procedure. These types of studies have provided mixed findings. For example, Segev et al (2010) found that donors had an increased mortality risk.^6, The authors analyzed data from a national registry of 80347 live donors in the U. S. who donated organs between April 1994 and March 2009 and compared their data with data from 9364 participants of the National Health and Nutrition Examination Survey (excluding those with contraindications to kidney donation). There were 25 deaths within 90 days of live kidney donation during the study period. Surgical mortality from live kidney donors was 3.1 per 10000 donors (95% CI, 2.0 to 4.6) and did not change over times, despite differences in practice and selection. Long-term risk of death was no higher for live donors than for age- and comorbidity-matched National Health and Nutrition Examination Survey III participants for all patients and also stratified by age, sex, and race.

Potential Contraindications to Kidney Transplant

Human Immunodeficiency Virus Infection

Patients infected with HIV may receive organs from HIV-positive donors under approved research protocols through the HIV Organ Policy Equity Act. As of November 2017, 6 hospitals performed 34 such transplants (23 kidney and 11 liver transplants), involving organs from 14 deceased donors. In a prospective, nonrandomized study, Muller et al (2015) noted that HIV-positive patients transplanted with kidneys from donors testing positive for HIV showed a 5-year survival rate of 74%.^7, Researchers noted that the HIV infection remained well-controlled and the virus was undetectable in the blood after transplantation.

Locke et al (2015) examined outcomes in 499 HIV-positive kidney transplant recipients identified in the Scientific Registry of Transplant Recipients.^8, Compared with early era transplants (2004-2007), patients transplanted more recently (2008-2011) had a significantly lower risk of death (HR=0.59; 95% CI, 0.39 to 0.90). The 5-year patient survival rate was 78.2% for patients transplanted in the early era and 85.8% for more recent transplants. In another study, Locke et al (2015) compared outcomes in 467 adult kidney transplant recipients with 4670 HIV-negative controls, matched on demographic characteristics.^9, Compared with HIV-negative controls, survival among HIV-positive transplant recipients was similar at 5 years posttransplant (83.5% vs 86.2%, p=0.06). At 10 years, HIV-positive transplant recipients had a significantly lower survival rate (51.6%) than HIV-negative patients (72.1%; p<0.001). The lower 10-year survival rate was likely due to HIV and hepatitis C virus (HCV) coinfection; survival rates at 10 years in HIV-monoinfected patients and HIV-negative patients were similar (88.7% vs 89.1%, p=0.50). Locke et al (2017) found significantly lower 5-year mortality rates in HIV-infected patients with ESRD who had kidney transplants compared with continued dialysis (adjusted relative risk [RR], 0.21; 95% CI, 0.10 to 0.42; p<0.001).^10,

In addition, Sawinski et al (2015) analyzed survival outcomes in patients infected with HIV, HCV, or HIV plus HCV.^11,The analysis included 492 HIV-infected patients, 5605 HCV-infected patients, 147 coinfected patients, and 117,791 noninfected patients. In a multivariate analysis, compared with noninfected patients, HIV-infected patients did not have an increased risk of death (HR=0.90; 95% CI, 0.66 to 1.24). However, HCV infection (HR=1.44; 95% CI, 1.33 to 1.56) and HIV and HCV coinfection (HR=2.26; 95% CI, 1.45 to 3.52) were both significantly associated with an increased risk of death.

Current OPTN policy permits HIV-positive transplant candidates.^12,

The British HIV Association and the British Transplantation Society (2017) updated their guidelines on kidney transplantation in patients with HIV disease.^13, These criteria may be extrapolated to other organs:

• Adherent with treatment, particularly antiretroviral therapy
• Cluster of differentiation 4 count greater than 100 cells/mL (ideally >200 cells/mL) for at least 3 months
• Undetectable HIV viremia (<50 HIV-1 RNA copies/mL) for at least 6 months
• No opportunistic infections for at least six months
• No history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma.

A meta-analysis by Fabrizi et al (2014) identified 18 observational studies comparing kidney transplant outcomes in patients with and without HCV infection.^14, The studies included 133350 transplant recipients. In an adjusted analysis, the risk of all-cause mortality was significantly higher in HCV-positive vs HCV-negative patients (RR=1.85; 95% CI, 1.49 to 2.31). Risks were elevated in various study subgroups examined by investigators. When the analysis was limited to the 4 studies from the U. S., the adjusted RR was 1.29 (95% CI, 1.15 to 1.44). In an analysis of 10 studies published since 2000, the RR was 1.84 (95% CI, 1.45 to 2.34). An analysis of disease-specific mortality suggested that at least part of the increased risk in mortality among HCV-positive individuals must have been due to chronic liver disease. In a meta-analysis of 9 studies, the risk of liver disease-related mortality was considerably elevated in patients infected with HCV than in those uninfected (odds ratio, 11.6; 95% CI, 5.54 to 24.4).

In the analysis by Sawinski et al (2015), described above, HCV infection was associated with an increased risk of mortality in kidney transplant patients compared with noninfected patients.^11,

Obesity

Several studies have found that obese kidney transplant patients have improved outcomes compared with patients on a waiting list matched by body mass index (BMI). Study results on whether morbid obesity is associated with an increased risk of adverse events after kidney transplant are conflicting.

In an analysis of kidney transplant data from the U.K., Krishnan et al (2015) reported on BMI data were available for 13536 patients.^3, They devised several BMI categories (i.e., <18.5 kg/m², 18.5 to <25 kg/m², 25 to <30 kg/m², 30 to <35 kg/m², and 35 to <40 kg/m²). For each BMI category, patient survival was significantly higher in those who underwent kidney transplants compared with those who remained on a waiting list. In a similar analysis of U.S. data, Gil et al (2013) noted that the risk of mortality at 1 year was significantly lower in patients who underwent transplantation than in those who remained on the waiting list for all BMI categories.^15, For example, the risk was lower for patients with a BMI of at least 40 kg/m² who received organs from donors who met standard criteria (HR=0.52; 95 CI, 0.37 to 0.72) and for patients with BMI 35 to 39 kg/m² who received organs from SCD donors (HR=0.34; 95% CI, 0.26 to 0.46).

Pieloch et al (2014) retrospectively reviewed data from the OPTN database.^16, The sample included 6055 morbidly obese patients (i.e., BMI, 35-40 kg/m²) and 24077 normal-weight individuals who underwent kidney transplant between 2001 and 2006. After controlling for potentially confounding factors, the overall 3-year patient mortality did not differ significantly between obese and normal-weight patients (HR=1.03; 05% CI, 0.96 to 1.12). Similar results were found for 3-year graft failure (HR=1.04; 95% CI, 0.98 to 1.11). In subgroup analyses, obese patients who were non-dialysis-dependent, nondiabetic, younger, receiving living donor transplants, and needing no assistance with daily living activities had significantly lower 3-year mortality rates than normal-weight individuals. For example, the odds for mortality between nondiabetic obese and normal-weight patients was 0.53 (95% CI, 0.44 to 0.63).

A multivariate analysis of the effect of obesity on transplant outcomes by Kwan et al (2016) included 191091 patients from the Scientific Registry of Transplant Recipients database.^17, Covariates in the analysis included age, sex, graft type, ethnicity, diabetes, peripheral vascular disease, dialysis time, and time period of transplantation. Multivariate regression analysis indicated that obese patients had a significantly increased risk of adverse transplant outcomes including delayed graft function, urine protein, acute rejection, and graft failure (p<0.001 for all outcomes). The risk of adverse outcomes of obesity increased with increasing BMI (e.g., see Table 1), and was independent of the effect of diabetes.

Table 1. Hazard Ratio of Graft Failure Relative to a Body Mass Index of 18.5 to 24.9 kg/m²

Body Mass Index, kg/m2	Hazard Ratio	95% Confidence Interval	p
25 to 29.9	1.015	0.983 to 1.047	0.416
30 to 34.9	1.104	1.065 to 1.145	<0.001
35 to 39.9	1.216	1.158 to 1.276	<0.001
40+	1.248	1.156 to 1.348	<0.001

Type 2 Diabetes

Kervinen et al (2018) looked at the probability of receiving renal transplantation and survival after transplantation for patients with type 2 diabetes (T2DM).^18, Using the Finnish Registry for Kidney Diseases, which included 5419 patients between the years 2000 and 2010, 1065 individuals with T2DM were identified, of which 105 received a kidney transplant during follow-up. The relative probability of renal transplantation was 0.25 (95% CI 0.20–0.30, p<0.001) for T2DM patients compared with non-diabetic patients. Survival probabilities at five years after transplantation were 88% for T2DM and 93% for non-diabetic patients (adjusted HR for death 1.39, 95% CI 0.82–2.35, p=0.227). The limitations of this study were the relatively small number of T2DM patients receiving kidney transplantation and almost all of these were from deceased donors. Also, the transplantation criteria for T2DM patients in Finland may give better survival rates in the study.

Lim et al (2017) evaluated all-cause mortality following kidney transplantation in patients with type 2 diabetes from Australia and New Zealand Dialysis and Transplant Registry.^19, Of 10714 transplant recipients during the study period, 985 (9%) had type 2 diabetes. The 10-year unadjusted OS in patients with an intact graft was 53% for individuals who had diabetes compared with 83% for transplant recipients who did not. The adjusted HR for all-cause mortality in patients with diabetes was 1.60 (95% CI, 1.37 to 1.86; p<0.001), with the excess risk of death attributable to both cardiovascular disease and infection. Graft survival rates at 1, 5, and 10 years were 94%, 85%, and 70% in patients with diabetes compared with 95%, 89%, and 78% in transplant recipients without diabetes (p<0.001), respectively.

Section Summary: Kidney Transplant

A large number of kidney transplants have been performed worldwide. Available data have demonstrated reasonably high survival rates after kidney transplant for appropriately selected patients and significantly higher survival rates for patients undergoing kidney transplant compared with those who remained on a waiting list. HIV infection has not been found to increase the risk of adverse events after kidney transplantation. Obesity and type 2 diabetes may increase the risk of adverse outcomes, and some data have suggested that kidney transplant recipients with HCV have worse outcomes than those without hepatitis C infection; however, data have not shown that patients with these conditions do not benefit from kidney transplants.

Kidney Retransplant

Clinical Context and Test Purpose

The purpose of kidney retransplants in patients who have a failed kidney transplant without contraindications to another kidney transplant is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this policy is: Does kidney retransplant improve net health outcomes in individuals with failed kidney transplants who do not have contraindications to another kidney transplant?

The following PICOs were used to select literature to inform this policy.

Patients

The relevant population of interest are individuals with a failed kidney transplant without contraindications to another kidney transplant.

Interventions

The therapy being considered is kidney retransplant from a living or cadaveric donor which is provided in a hospital setting by specialized staff who are equipped to perform the surgical procedure and manage postsurgical intensive care.

Comparators

The following therapies and practices are currently being used to make decisions about managing patients whose kidney transplant has failed: medical management including dialysis, self-care, and medications, including dietary supplements and diuretics.

Outcomes

The general outcomes of interest are OS, elimination of the need for dialysis, and treatment-related adverse events (e.g., immunosuppression, graft failure, surgical complications, infections), with follow-up ranging from immediate postsurgery to 30 days posttransplantation and long-term follow-up out to 10 years or more. See the Potential Contraindications section for detailed discussion.

Case Series

Barocci et al (2009) in Italy reported on long-term survival after kidney retransplantation.^20, There were 100 (0.8%) second transplants of 1302 kidney transplants performed at a single-center between 1983 and 2007. Among the second kidney recipients, 1-, 5-, and 10-year patient survival rates were 100%, 96%, and 92%, respectively. Graft survival rates at 1, 5, and 10 years were 85%, 72%, and 53%, respectively.

Registry Studies

According to data analysis from the OPTN between 2008 and 2015, the 1-year survival rate of patients undergoing a repeat kidney transplant was 97.1% (95% CI, 96.7% to 97.5%).^2, The 5-year patient survival rate after a repeat kidney transplant was 87.6% (95% CI, 86.8% to 88.4%).

Children

Gupta et al (2015) retrospectively analyzed OPTN data, focusing on patients who had an initial kidney transplant as children.^21, A total of 2281 patients were identified who had their first transplant when they were younger than 18 years and a second kidney transplant at any age. In multivariate analysis, the length of first graft survival and age at second graft were significantly associated with second graft survival. Specifically, the first graft survival time of more than five years was associated with better second graft survival. However, patients who were between 15 and 20 years old at second transplant were at increased risk of second kidney graft failure compared with patients in other age groups.

Potential Contraindications to Kidney Retransplant

HIV Infection

Shelton et al (2017) evaluated outcomes in HIV-infected patients undergoing kidney retransplantation.^22, In adjusted survival analysis, HIV-infected retransplant patients had a significantly increased risk of death compared with HIV-negative patients (HR=3.11; 95% CI, 1.82 to 5.34). Other factors significantly associated with increased risk of death after kidney retransplantation included recipient infection with HCV (HR=1.77; 95% CI, 1.32 to 2.38) and grafts from older donors (HR=1.01; 95 CI, 1.00 to 1.02). The analysis included only 22 HIV-infected patients, which is too small to draw conclusions about the appropriateness of kidney retransplantation in HIV-infected individuals.

Other contraindications are discussed in the section on initial kidney transplants.

Section Summary: Kidney Retransplant

Data have demonstrated reasonably high survival rates after kidney retransplants for appropriately selected patients (e.g., 5-year survival rates ranging from 87% to 96%).

Summary of Evidence

For individuals who have end-stage renal disease without contraindications to kidney transplant who receive a kidney transplant from a living donor or deceased (cadaveric) donor, the evidence includes registry data and case series. The relevant outcomes are OS, morbid events, and treatment-related mortality and morbidity. Data from large registries have demonstrated reasonably high survival rates after kidney transplant for appropriately selected patients and significantly higher survival rates for patients undergoing kidney transplant compared with those who remained on a waiting list. Kidney transplantation is contraindicated for patients in whom the procedure is expected to be futile due to comorbid disease or in whom posttransplantation care is expected to significantly worsen comorbid conditions. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have a failed kidney transplant without contraindications to kidney transplant who receive a kidney retransplant from a living donor or deceased (cadaveric) donor, the evidence includes registry data and case series. The relevant outcomes are OS, morbid events, and treatment-related mortality and morbidity. Data have demonstrated reasonably high survival rates after kidney retransplant (e.g., 5-year survival rates ranging from 87% to 96%) for appropriately selected patients. Kidney retransplantation is contraindicated for patients for whom the procedure is expected to be futile due to comorbid disease or for whom posttransplantation care is expected to significantly worsen comorbid conditions. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

SUPPLEMENTAL INFORMATION

Practice Guidelines and Position Statements

American Society of Transplant Surgeons et al

The American Society of Transplant Surgeons, the American Society of Transplantation, the Association of Organ Procurement Organizations, and the United Network for Organ Sharing (2011) issued a joint position statement recommending modifications to the National Organ Transplant Act of 1984.^23, The joint recommendation stated that the potential pool of organs from HIV-infected donors should be explored. With modern antiretroviral therapy, the use of these previously banned organs would open an additional pool of donors to HIV-infected recipients. The increased pool of donors has the potential to shorten waiting times for organs and decrease the number of waiting list deaths. The organs from HIV-infected deceased donors would be used for transplant only with patients already infected with HIV. In 2013, the HIV Organ Policy Equity Act permitting the use of this group of organ donors.

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials

Some currently unpublished trials that might influence this policy are listed in Table 2.

Table 2. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT03500315	HOPE in Action Prospective Multicenter, Clinical Trial of Deceased HIVD+ Kidney Transplants for HIV+ Recipients	360	Aug 2022

NCT: national clinical trial.]
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Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Kidney Transplant
Kidney Transplantation
Transplant, Kidney
Transplantation, Kidney
Renal Transplant

References:
1. National Kidney Foundation. Glomerular Filtration Rate (GFR). n.d.; https://www.kidney.org/atoz/content/gfr. Accessed July 27, 2018.

2. Organ Procurement and Transplantation Network. View Data Reports. n.d.; https://optn.transplant.hrsa.gov/data/view-data-reports/. Accessed July 27, 2018.

3. Krishnan N, Higgins R, Short A, et al. Kidney transplantation significantly improves patient and graft survival irrespective of BMI: a cohort study. Am J Transplant. Sep 2015;15(9):2378-2386. PMID 26147285.

4. Querard AH, Foucher Y, Combescure C, et al. Comparison of survival outcomes between Expanded Criteria Donor and Standard Criteria Donor kidney transplant recipients: a systematic review and meta-analysis. Transpl Int. Apr 2016;29(4):403-415. PMID 26756928.

5. Pestana JM. Clinical outcomes of 11,436 kidney transplants performed in a single center - Hospital do Rim. J Bras Nefrol. Aug 28 2017;39(3):287-295. PMID 28902233.

6. Segev DL, Muzaale AD, Caffo BS, et al. Perioperative mortality and long-term survival following live kidney donation. Jama. Mar 10 2010;303(10):959-966. PMID 20215610.

7. Muller E, Barday Z, Mendelson M, et al. HIV-positive-to-HIV-positive kidney transplantation--results at 3 to 5 years. N Engl J Med. 2015 372(7):613-620. PMID 25671253.

8. Locke JE, Reed RD, Mehta SG, et al. Center-level experience and kidney transplant outcomes in HIV-infected recipients. Am J Transplant. Aug 2015;15(8):2096-2104. PMID 25773499.

9. Locke JE, Mehta S, Reed RD, et al. A national study of outcomes among HIV-infected kidney transplant recipients. J Am Soc Nephrol. Sep 2015;26(9):2222-2229. PMID 25791727.

10. Locke JE, Gustafson S, Mehta S, et al. Survival benefit of kidney transplantation in HIV-infected patients. Ann Surg. Mar 2017;265(3):604-608. PMID 27768622.

11. Sawinski D, Forde KA, Eddinger K, et al. Superior outcomes in HIV-positive kidney transplant patients compared with HCV-infected or HIV/HCV-coinfected recipients. Kidney Int. Aug 2015;88(2):341-349. PMID 25807035.

12. Organ Procurement and Transplantation Network (OPTN). Organ Procurement and Transplantation Network Policies. 2018; https://optn.transplant.hrsa.gov/media/1200/optn_policies.pdf. Accessed July 20, 2018.

13. Working Party of the British Transplantation Society. Kidney and Pancreas Transplantation in Patients with HIV. Second Edition (Revised). British Transplantation Society Guidelines. Macclesfield, UK: British Transplantation Society; 2017.

14. Fabrizi F, Martin P, Dixit V, et al. Meta-analysis of observational studies: hepatitis C and survival after renal transplant. J Viral Hepat. May 2014;21(5):314-324. PMID 24716634.

15. Gill JS, Lan J, Dong J, et al. The survival benefit of kidney transplantation in obese patients. Am J Transplant. Aug 2013;13(8):2083-2090. PMID 23890325.

16. Pieloch D, Dombrovskiy V, Osband AJ, et al. Morbid obesity is not an independent predictor of graft failure or patient mortality after kidney transplantation. J Ren Nutr. Jan 2014;24(1):50-57. PMID 24070588.

17. Kwan JM, Hajjiri Z, Metwally A, et al. Effect of the obesity epidemic on kidney transplantation: obesity is independent of diabetes as a risk factor for adverse renal transplant outcomes. PLoS One. Nov 2016;11(11):e0165712. PMID 27851743.

18. Kervinen, MG, Lehto S, Helve J, et al. Type 2 diabetic patients on renal replacement therapy: Probability to receive renal transplantation and survival after transplantation. PLoS One. 2018 Aug 15;13(8):e0201478. PMID 30110346.

19. Lim WH, Wong G, Pilmore HL, et al. Long-term outcomes of kidney transplantation in people with type 2 diabetes: a population cohort study. Lancet Diabetes Endocrinol. Jan 2017;5(1):26-33. PMID 28010785.

20. Barocci S, Valente U, Fontana I, et al. Long-term outcome on kidney retransplantation: a review of 100 cases from a single center. Transplant Proc. May 2009;41(4):1156-1158. PMID 19460504.

21. Gupta M, Wood A, Mitra N, et al. Repeat kidney transplantation after failed first transplant in childhood: past performance informs future performance. Transplantation. Aug 2015;99(8):1700-1708. PMID 25803500.

22. Shelton BA, Mehta S, Sawinski D, et al. Increased mortality and graft loss with kidney retransplantation among human immunodeficiency virus (HIV)-infected recipients. Am J Transplant. Jan 2017;17(1):173-179. PMID 27305590.

23. American Society of Transplant Surgeons (ASTS), The American Society of Transplantation (AST), The Association of Organ Procurement Organizations (AOPO), et al. Statement on transplantation of organs from HIV-infected deceased donors. 2011; http://asts.org/docs/default-source/position-statements/transplantation-of- organs-from-hiv-infected-deceased-donors-july-22-2011.pdf?sfvrsn=4. Accessed July 27, 2018.

24. Centers for Medicare & Medicaid Services. Medicare Benefit Policy Manual: Chapter 11 - End Stage Renal Disease (ESRD). 2018; https://www.cms.gov/Regulations-and- Guidance/Guidance/Manuals/downloads/bp102c11.pdf. Accessed July 25, 2018.

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

50300
50320
50323
50325
50327
50328
50329
50340
50360
50365
50547