Medical Policy: 07.03.09 
Original Effective Date: November 2009 
Reviewed: October 2016 
Revised: October 2016 


Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.


Description:

Transplantation of the pancreas is a treatment method for patients with insulin dependent diabetes mellitus. Pancreas transplantation can restore glucose control and is intended to prevent, halt or reverse the secondary complications from diabetes mellitus. Replacement of the pancreas may be performed alone, following a kidney transplant, or simultaneously with a kidney transplant.

 

Pancreas Transplant Alone (PTA)

Pancreas transplant alone (PTA) may be indicated for patients with uncontrolled type 1 diabetes mellitus (i.e. abnormal hemoglobin A1c, inability to maintain blood glucose levels in a normal range) but adequate renal function. The purpose of PTA is to control the blood glucose levels and prevent diabetes-related complications such as retinopathy, neuropathy, or end-stage renal disease.

Evidence in the scientific published medical literature is mixed regarding survival rates and improved outcomes with PTA, however, pancreas transplant is an appropriate option for individuals with diabetes mellitus who have complications, since it can improve quality of life and is the single most effective method of achieving tight glucose control.

 

Simultaneous Pancreas-Kidney (SPK)/Pancreas-after-Kidney (PAK)

Kidney failure is a major complication of diabetes mellitus and, as a result, most potential pancreas transplant recipients are also uremic. Due to poor five year survival rate of individuals with diabetes mellitus who are on dialysis,kidney transplantation is the treatment of choice for patients with diabetes mellitus who have end stage renal disease (ESRD) and are on dialysis.

Individuals with type 1 diabetes mellitus and impending or established ESRD who have minimal or limited secondary complications of diabetes mellitus are considered optimal candidates for kidney transplantation. Simultaneous pancreas-kidney (SPK) transplant is performed to correct complications of type 1 diabetes mellitus and renal failure with reliance on dialysis. In individuals with type 1 diabetes mellitus who have had a successful kidney transplantation to correct previous uremia, PAK is performed to improve quality of life by: 1) eliminating the need for exogenous insulin and its associated difficulty controlling glucose levels; and 2) to limit secondary diabetic complications, including retinopathy, neuropathy, nephropathy and vasculopathy.

There are some data on outcomes in patients with type 2 compared with type 1 diabetes. In 2011, Sampaio et. al. published an analysis of date from the United Network for Organ Sharing (UNOS) database. The investigators compared outcomes in 6141 patients with type 1 diabetes and 582 patients with type 2 diabetes who underwent SPK between 2000 and 2007. In adjusted analyses, outcomes were similar between the two groups. After adjusting for other factors such as body weight, dialysis time, and cardiovascular comorbidities, type 2 diabetes was not associated with an increased risk of pancreas or kidney graft failure or mortality compared with type 1 diabetes.   

Evidence in the scientific published medical literature supports SPK and PAK transplantation as an appropriate therapeutic intervention of individuals with diabetes mellitus who require or have previously had a kidney transplant. The evidence suggests longstanding normoglycemia can halt or even reverse diabetic lesions in various organs such as the heart and kidney, surgical complication rates are low, and with immunosuppressive medication long term allograft and patient survival are excellent. SPK and PAK is a well established and accepted method of treatment for these individuals.

 

Type II Diabetes Mellitus

Pancreas transplant is not typically used for the treatment of individuals with type 2 diabetes mellitus. Individuals with type 2 produce some insulin, however for unknown reasons the body is unable to use it effectively. While in general there is no simple laboratory test to distinguish between type 1 and type 2 diabetes mellitus, C-Peptide levels are often used to verify insulinopenia, in combination with a documented clinical exam and/or insulin sensitivity and resistance testing. Identifying individuals with type 2 diabetes mellitus who are candidates for pancreas transplant can be challenging. C-peptide levels increase in the presence of renal disease and there is limited information regarding C-peptide levels for defining the type of diabetes in study subjects with ESRD.

Typically a person with type 2 diabetes mellitus has a normal C-peptide level. A fasting C-peptide level that is < 110% of the lower limit of normal of the laboratory’s measurement method and a concurrently obtained fasting glucose of <  225 mg/dL is indicative of insulinopenic type 2 diabetes mellitus.

Pancreas transplantation have been proposed to achieve insulin independence in persons with type 2 diabetes mellitus. Although the evidence in the peer reviewed medical literature is limited pancreas transplantation is an alternative treatment for insulin dependent individuals with type II diabetes mellitus.

 

Retransplantation

The last four decades have seen a significant and progressive improvement in outcomes for pancreas transplantation. Improvements in immunosuppression, surgical technique and post-transplant management have all contributed to better graft survival. However, despite refinements in surgical technique, technical failure is defined by the International Pancreas Transplant Registry as graft loss secondary to vascular thrombosis, bleeding, anastomotic leaks or infection/pancreatitis and is responsible for more than 50% of all pancreas grafts lost in the first 6 months following transplantation. Thrombosis accounts for more than one-half of these technical failures, and may be influenced by donor and recipient factors, preservation and ischemic injury, immunological issues and surgical technique.

The decision to retransplant the pancreas after an early graft failure is complex. Prior to proceeding with retransplantation, a careful analysis of the factors contributing to the technical failure must be undertaken and reversible risk factors must be addressed. Surgical issues leading to thrombosis such as improper suturing of the vascular anastomosis, poor positioning of the allograft or inadequate hemostasis may be the primary cause of graft thrombosis. However, there may be no obvious surgical cause for graft loss identified. Reconfirming the tissue typing with the original donor and evaluating the patient for hypercoagulable state should be considered prior to attempting retransplantation in order to guide anticoagulation and immunosuppression management for the second graft.

Following appropriate evaluation for the causes of graft thrombosis, repeat pancreas transplantation may be considered, although the optimal timing for retransplantation remains somewhat controversial. From a surgical perspective, retransplanting in the early post-pancreatectomy period may be preferable because extensive adhesions have not yet formed. This facilitates placing the new graft in the same anatomic site as the prior transplant. Some previous studies suggest that immediate retransplantation is associated with similar graft and patient survival as primary transplants, others indicate that this approach is associated with higher incidence of post-operative complications and rejection leading to premature loss of the second graft.

Although there are no standard guidelines regarding multiple pancreas transplants, each transplant center has its own guidelines based on experience. Some transplant centers may wait to allow reconstitution of the immune system before initiating retransplant with an augmented immunosuppression protocol.

 

Summary

Based on the medical literature pancreas transplant may be considered medically necessary in patients who are undergoing, or have undergone, kidney transplantation for renal failure. It may also be considered medically necessary as a stand-alone treatment in patients with hypoglycemia unawareness and labile diabetes, despite optimal medical therapy and in whom severe complications have developed. The evidence suggest that transplantation can restore glucose control and prevent, halt or reverse the secondary complications from diabetes mellitus. Pancreas transplant alone (PTA), simultaneous pancreas-kidney (SPK) and pancreas-after-kidney (PAK) is well established and  accepted methods of treatment for these individuals.

 

Practice Guidelines and Position Statements

American Diabetes Association

In 2004, the American Diabetes Association issued a position statement regarding recommendations for pancreas transplantation in patients with type 1 diabetes. The recommendations are based on the American Diabetes Association’s technical review on “Pancreas and Islet Transplantation for Patients with Diabetes Mellitus.”

Successful pancreas transplantation has been demonstrated to be efficacious in significantly improving the quality of life of people with diabetes, primarily by eliminating the need for exogenous insulin, frequent daily blood glucose measurements, and many of the dietary restrictions improved by the disorder. Transplantation can also eliminate the acute complications of diabetes.

Recommendations

  1. Pancreas transplantation should be considered an acceptable therapeutic alternative to continued insulin therapy in diabetic patients with imminent or established end stage renal disease who have had or plan to have a kidney transplant, because the successful addition of a pancreas does not jeopardize patient survival, may improve kidney survival, and will restore normal glycemia. Such patients also must meet the medical indications and criteria for kidney transplantation and not have excessive surgical risk for the dual transplant procedure. Medicare and other third party payers of medical care should include coverage for pancreas transplant procedures meeting these criteria. The pancreas transplant may be done simultaneous to a kidney transplant.
  2. In the absence of indications for kidney transplantation, pancreas transplantation should only be considered a therapy in patients who exhibit these three criteria: 1) a history of frequent, acute, and severe metabolic complications (hypoglycemia, hyperglycemia, keotacidosis) requiring medical attention; 2) clinical and emotional problems with exogenous insulin therapy that are so severe as to be incapacitating; and 3) consistent failure of insulin based management to prevent acute complications. Program guidelines for ensuring an objective multidisciplinary evaluation of the patient’s condition and eligibility for transplantation should be established and followed. Third party payer coverage is appropriate only where such guidelines and procedures exist.

 

American Society of Transplantation

In 2013 the American Society of Transplantation issued a 3rd edition guideline on transplantation infectious diseases that includes criteria for transplantation for HIV infected individuals. The criteria for transplantation for HIV infected individuals for kidney/pancreas transplants includes the following:

  • Meet center specific inclusion criteria
  • CDC count > 200 cells/uL during 3 months before transplantation
  • Undetectable HIV viral load while receiving antiretroviral therapy
  • Documented compliance with a stable antiretroviral regimen
  • Absence of active opportunistic infection and malignancy
  • Absence of chronic wasting or severe malnutrition
  • History of hepatitis B or C with lack of evidence of advanced fibrosis or cirrhosis
  • Acceptable of life-long pneumocystis prophylaxis
  • Donor free of hepatitis C
  • Appropriate follow up with providers experienced in the management of HIV
  • Ready access to immunosuppressive medication therapeutic drug monitoring

 

Organ Procurement and Transplantation Network

In 2016 the following is the allocation policies of the Organ Procurement and Transplantation Network for the Allocation of Pancreas and Kidney-Pancreas:

 

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 of transplantation of a pancreas as part of a multiple organ transplant for technical reasons

 

Combined Kidney-Pancreas Registration

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

 

Waiting Time
  • 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 below.
  • 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 kidney-pancreas, then the candidate begins to accrue waiting time once the candidate has met all of the following conditions:

    • The candidate is registered for a kidney-pancrea
    • The candidate qualifies for a kidney-pancrea
    • The candidate meets at least one of the following criteria:
      • Is on insulin and C-peptide less than or equal to 2 ng/mL
      • Is on insulin and C-peptide greater than 2 ng/mL and has a body mass index (BMI) less than or equal to the maximum allowable BMI

Note: The OPTN Contractor may not modify the maximum allowable BMI to exceed 30mg/m2


Prior Approval:

 

Prior approval is required. Submit a prior approval now.


Policy:

See also Medical Policy 07.03.01 Pancreatic Islet Cell Transplant

See also Medical Policy 01.01.26 Artificial Pancreas Device System

 

Pancreas Transplant Alone (PTA)

Pancreas transplant alone (PTA) may be considered medically necessary in patients who have insulin-dependent diabetes mellitus with severe disabling and life threatening hypoblycemic unawareness due to labile diabetes despite optimal medical management.

 

Pancreas after Kidney (PAK)

Pancreas transplant after a prior kidney transplant (PAK) may be considered medically necessary in patients with insulin-dependent diabetes.

 

Simultaneous Pancreas-Kidney Transplant (SPK) (H3)

Simultaneous pancreas-kidney transplant (SPK) may be considered medically necessary in insulin-dependent diabetics with impending or established renal failure.

 

Pancreas transplant alone (PTA), pancreas transplant after prior kidney transplant (PAK), or simultaneous pancreas-kidney transplant (SPK) performed for any other conditions not listed above will be considered not medically necessary.

 

Retransplantation

Pancreas transplant alone (PTA), pancreas after kidney (PAK) or simultaneous pancreas-kidney (SPK) retransplantation after a failure of the primary graft may be considered medically necessary provided the individual meets the transplant criteria above.

 

Policy Guidelines

Pancreas Specific

Candidates for pancreas transplant alone should additionally meet 1 of the following severity of illness criteria:

  • Documentation of severe hypoglycemia awareness as evidenced by chart notes or emergency department visits; or
  • Documentation of potentially life-threatening labile diabetes, as evidenced by chart notes or hospitalization for diabetic ketoacidosis. 

In addition, most pancreas transplant patients will have type 1 diabetes mellitus. Those transplant candidates with type 2 diabetes mellitus, in addition to being insulin dependent, should also not be obese (body mass index (BMI) should be 30 or less).

 

Multiple Transplants

Although there are no standard guidelines regarding multiple pancreas transplants, the following information may aid in case review:

  • If there is early graft loss resulting from technical factors (e.g. venous thrombosis), a retransplant may generally be performed without substantial additional risk.
  • Long-term graft losses may result from chronic rejection, which is associated with increased risk of infection following long-term immunosuppression, and sensitization, which increases the difficulty of finding a negative cross-match. Some transplant centers may wait to allow reconstitution of the immune system before initiating retransplant with an augmented immunosuppression protocol. 

 

Potential contraindications to pancreas transplant include:

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



Procedure Codes and Billing Guidelines:

  • To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.
  • 48554; Transplantation of pancreatic allograft
  • 50360 Renal allotransplantation, implantation of graft; without recipient nephrectomy
  • 50365 Renal allotransplantation, implantation of graft; with recipient nephrectomy
  • S2065 Simultaneous pancreas kidney transplantation

Selected References:

  • Aguera ML, Navarro MD, Perez-Calderon R et al. Simultaneous pancreas-kidney transplant: a single-center long-term outcome. J Nephrol. 2007 Mar-Apr; 20(2):173-6.
  • Bunnapradist S, Cho YW, Cecka JM et al Kidney allograft and patient survival in type 1 diabetic recipients of cadaveric kidney alone versus simultaneous pancreas/kidney transplants: a multivariate analysis of the UNOS database. J Am Soc Nephrol. 2003 Jan;14(1):208-13.
  • Humar A, Ramcharan T, Kandaswamy R et al. Pancreas after kidney transplants. Am J Surg. 2001 Aug;182(2):155-61.
  • Humar A, Kandaswamy R, Drangstveit MB et al. Surgical risks and outcome of pancreas retransplants. Surgery. 2000 Jun;127(6):634-40.
  • Johnson SR, Cherikh WS, Kauffman HM et al. Retransplantation after post-transplant lymphoproliferative disorders: an OPTN/UNOS database analysis. Am J Transplant. 2006 Nov;6(11):2743-9.
  • Kizilel S, Garfinkel M, Opara E. The bioartificial pancreas: progress and challenges. Diabetes Technol Ther. 2005 Dec;7(6):968-85.
  • Lipshutz GS, Wilkinson AH. Pancreas-kidney and pancreas transplantation for the treatment of diabetes mellitus. Endocrinol Metab Clin North Am. 2007 Dec;36(4):1015-38.
  • Sutherland DE, Gruessner AC. Long-term results after pancreas transplantation. Transplant Proc 2007;39(7):2323-5.
  • Scalea JR, Burler CC, Munivenkatappa RB et al. Pancreas transplant alone as an independent risk factor for the development of renal failure: a retrospective study. Transplantation 2008;86(12):1789-94.
  • Hirshberg B. The cardinal features of recurrent autoimmunity in simultaneous pancreas-kidney transplant recipients. Curr Diab Rep 2010; 10(5):321-2.
  • Fridell JA, Mangus RS, Hollinger EF et al. The case for pancreas after kidney transplantation. Clin Transplant 2009; 23(4):447-53.
  • Kleinclauss F, Fauda M, Sutherland DE et al. Pancreas after living donor kidney transplants in diabetic patients: impact on long-term kidney graft function. Clin Transplant 2009; 23(4):437-46.
  • Schenker P, Vonend O, Kruger B et al. Long-term results of pancreas transplantation in patients older than 50 years. Transpl Int. 2011 Feb; 24(2):136-42. doi: 10.1111/j.1432-2277.2010.01172.x. Epub 2010 Oct 13.
  • Afaneh C, Rich BS, Aull MJ et al. Pancreas transplantation: does age increase morbidity? J transplant. 2011; 2011:596801. Epub 2011 Jun 4.
  • Gruessner AC. 2011 update on pancreas transplantation: comprehensive trend analysis of 25,000 cases followed up over the course of twenty-four years at the International Pancreas Transplant Registry (IPTR). Rev Diabet Stud. 2011 Spring; 8(1):6-16. Epub 2011 May 10.
  • Sampaio MS, Kuo HT, Bunnapradist S. Outcomes of simultaneous pancreas-kidney transplantation in type 2 diabetic recipients. Clin J AM Soc Nephrol. 2011 May;6(5):1198-206. Epub 2011 Mar 24.
  • UpToDateExternal Site Pancreas and Islet Transplantation in Diabetes Mellitus. R. Paul Robertson, M.D.. Topic last updated April 30, 2013.
  • United Network for Organ Sharing (UNOS): Pancreas Allocation Policy. September 1, 2013.
  • CMSExternal Site National Coverage Determination for Pancreas Transplants (260.3).
  • UpToDateExternal SitePatient Selection for an Immunologic Issues Relating to Kidney-Pancreas Transplantation in Diabetes Mellitus. Topic last updated February 3, 2016. 
  • Medscape. Pancreas TransplantationExternal SiteUpdated June 12, 2013.
  • Medscape. Kidney-Pancreas TransplantationExternal SiteUpdated September 18, 2013. 
  • American Diabetes AssociationExternal Site Pancreas Transplantation.  Diabetes Care 2004 Jan;27 (suppl 1): s105-s105 
  • National Kidney FoundationExternal SitePancreas Transplant.
  • Organ Procurement and Transplant NetworkExternal Site(OPTN). Allocation of Pancreas, Kidney-Pancreas and Islets. October 2016. 
  • Gruessner Angelika C, 2011 Update on Pancreas Transplantation: Comprehensive Trend Analysis of 25,000 Cases Followed up over the Course of Twenty-Four years at the International Pancreas Transplant Registry (IPTR). Journal of the Society of Biomedical Diabetes Research, April 2011. Published online May 10, 2011. Doi:10.1900/RDS.2011.8.6
  • E.F. Hollinger, J.A. Powelson, et. al. Immediate Retransplantation for Pancreas Allograft Thrombosis, American Journal of Transplantation 2009; 9:740-745.
  • National Guideline ClearinghouseExternal SiteClinical Practice Guideline for Diabetes Mellitus Type 1. May 2012.
  • National Institute of Health (NIH). Microencapsulation of Pancreatic Islets for use in Bioartificial Pancreas.
  • Sampaio MS, Kuo HT, Bunnapradist S. Outcomes of simultaneous pancreas-kidney transplantation in type 2 diabetic patients. Clin J Am Soc Nephrol 2011;6(5):1198-1206
  • Gruessner AC, Sutherland DE, Gruessner RW. Long-term outcome after pancreas transplantation. Curr Opin Organ Transplant 2012 Feb;17(1):100-5. PMID 22186094
  • Blumberg E.A., Rogers C.C., The American Society of Transplantation Infectious Diseases Guidelines 3rd Edition, Human Immunodeficiency Virus in Solid Organ Transplantation. American Journal of Transplantation Volume 13,Issue s4 March 2013 pages 169-178
  • Buron F, Thaunat O, Demuylder-Mischler S, et.al. Pancreas retransplantation: a second chance for diabetic patients? Transplantation 2013 Jan 27;95(2):347-52. PMID 23222920
  • Van Dellen D, Worthington J, Mitu-Pretorian OM, et. al. Mortality in diabetes: pancreas transplantation is associated with significant survival benefit. Nephrol Dial Transplant 2013 May;28(5):1315-22. PMID 23512107
  • Bazerbachi F, Selzner M, Marquez MA, et. al. Pancreas-after-kidney versus synchronous pancreas-kidney- transplantation: comparison of intermediate term results. Transplantation 2013 Feb 15;95(3):489-94. PMID 23183776
  • Seal J, Selzner M, Laurence J, et. al. Outcomes of pancreas retransplantation after simultaneous kidney-pancreas transplantation are comparable to pancreas after kidney transplantation alone. Transplantation 2015 Mar;99(3):623-8. PMID 25148379
  • Siskind E, Maloney C, Akerman M, et.al. An analysis of pancreas transplantation outcomes based on age groupings – an update of the UNOS database. Clin Transplant 2014 Sep;28(9):990-4. PMID 24954160
  • UpToDateExternal Site Pancreas and Islet Transplantation in Diabetes Mellitus. R Paul Robertson M.D., Topic last updated March 7, 2016. li>

Policy History:

  • October 2016 - Annual Review, Policy Revised
  • November 2015 - Annual Review, Policy Revised
  • December 2014 - Annual Review, Policy Revised
  • January 2014 - Annual Review, Policy Renewed
  • March 2013 - Annual Review, Policy Renewed
  • March 2012 - Annual Review, Policy Renewed
  • April 2011 - Annual Review, Policy Renewed

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

*Current Procedural Terminology © 2012 American Medical Association. All Rights Reserved.