Clinical UM Guideline

This document addresses kidney transplantation, involving the removal of the kidney from a deceased or living donor with the implantation into a single recipient.

Note: Please see the following related transplant documents for additional information:

• TRANS.00008 Liver Transplantation
• TRANS.00011 Pancreas Transplantation and Pancreas Kidney Transplantation

Note: Members must meet the clinical indications as well as the general individual selection criteria for the transplantation to be considered medically necessary.

Medically Necessary:

Kidney transplantation from a deceased or a living donor is considered medically necessary for selected individuals with end stage renal disease*. The clinical indications leading to end stage renal disease include, but are not limited to, one of the conditions listed below.

*Note: See Definition section for further information on end stage renal disease.

Clinical Indications:

• Congenital Disorders
  • Aplasia
  • Hypoplasia
  • Horseshoe Kidney
• Toxic Nephropathies
  • Lead nephropathy
  • Analgesic nephropathy
  • Metabolic Disorders
  • Hyperoxaluria
  • Nephrocalcinosis
  • Gout
  • Amyloidosis
  • Cystinosis
• Hereditary Nephropathies
  • Alport's syndrome
  • Polycystic kidney disease
  • Medullary cystic disease
• Irreversible Acute Renal Failure
  • Cortical necrosis
  • Hemolytic uremic syndrome
  • Acute and subacute glomerulonephritis
  • Anaphylactoid purpura (Henoch-Schonlein)
• Irreversible Chronic Renal Failure
  • Chronic pyelonephritis
  • Diabetic nephropathy
  • Chronic glomerulonephritis
  • Hypertensive nephrosclerosis
  • Goodpasture's disease
  • Hypocomplementemic nephritis
  • Steroid-resistant nephrotic syndrome
  • Toxic nephropathy (including nephropathy related to cyclosporine/tacrolimus toxicity)
  • Chronic allograft nephropathy (that is, chronic rejection)
• Tumors Requiring Nephrectomy
  • Renal carcinoma
  • Wilms’ tumor
  • Tuberous sclerosis
• Renal Vascular Diseases
  • Renal artery occlusion
  • Renal vein thrombosis
• Obstructive Uropathy
  • Acquired
  • Congenital
• Trauma requiring nephrectomy
• Other Indications
  • Scleroderma
  • Polyarteritis (periarteritis nodosa)
  • Multiple Myeloma
  • Lupus Erythematosus
  • Macroglobulinemia
  • Wegner's Disease
  • Etiology unknown (documented chronic renal failure of at least 6-8 weeks duration)

Retransplantation
Repeat transplant due to acute or chronic graft failure is considered medically necessary.

Simultaneous Liver Kidney Transplantation
Kidney transplant as part of a simultaneous liver kidney (SLK) transplantation is considered medically necessary when criteria for liver transplantation are met and when one of the following are met:

• The individual has acute renal failure secondary to either hepatorenal syndrome or acute kidney injury; either of which have required at least 6 weeks of dialysis therapy; or
• The individual has chronic kidney disease with a measured creatinine clearance of less than or equal to 30cc/min; or
• The individual has prolonged acute kidney failure or kidney failure of unknown cause and a renal biopsy showing fixed renal damage.

Not Medically Necessary:

Kidney transplantation for conditions other than end stage renal disease is considered not medically necessary.

Kidney transplantation as part of a simultaneous liver kidney (SLK) transplant is considered not medically necessary, if one of the above SLK criteria is not met.

Note: For multi-organ transplant requests, criteria must be met for each organ requested. In those situations, an individual may present with a concurrent medical condition which may be considered an exclusion or a comorbidity that would preclude a successful outcome, but would be treated with the additional organ transplant. Such cases will be reviewed on an individual basis for coverage determination to assess the member’s candidacy for transplantation.

General Individual Selection Criteria

In addition to having one of the clinical indications above, the member must not have a contraindication as defined by the American Society of Transplantation in Guidelines for the Referral and Management of Patients Eligible for Solid Organ Transplantation (2001) listed below.*

Absolute Contraindications- for Transplant Recipients include, but are not limited to, the following:

1. Metastatic cancer
2. Ongoing or recurring infections that are not effectively treated
3. Serious cardiac or other ongoing insufficiencies that create an inability to tolerate transplant surgery
4. Serious conditions that are unlikely to be improved by transplantation as life expectancy can be finitely measured
5. Demonstrated patient noncompliance, which places the organ at risk by not adhering to medical recommendations
6. Potential complications from immunosuppressive medications are unacceptable to the patient
7. Acquired immune deficiency syndrome (AIDS) (diagnosis based on Centers for Disease Control and Prevention [CDC] definition of CD4 count, 200cells/mm³) unless the following are noted:
   1. CD4 count greater than 200cells/mm³ for greater than 6 months
   2. HIV-1 RNA undetectable
   3. On stable anti-retroviral therapy greater than 3 months
   4. No other complications from AIDS (for example, opportunistic infection, including aspergillus, tuberculosis, coccidioidomycosis, resistant fungal infections, Kaposi’s sarcoma or other neoplasm)
   5. Meeting all other criteria for kidney transplantation

*Steinman, Theodore, et al. Guidelines for the Referral and Management of Patients Eligible for Solid Organ Transplantation. Transplantation. 2001; 71 (9):1189-1204.

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

When services are Not Medically Necessary:
For the procedure codes listed above when criteria are not met or for situations designated in the Clinical Indications section as not medically necessary.

Approximately 37 million Americans were reported to have chronic kidney disease (CKD), with nearly 131,000 requiring initiation of treatment for kidney failure known as end stage renal disease (ESRD) each year (CDC, 2022). There was a steady rise in the rate of ESRD from 1980 to 2011; the incident rate of ESRD has started to decline. As of January 2024, the Organ Procurement and Transplantation Network (OPTN) reported that there were 95,949 Americans on the wait list for kidney transplantation and, in 2023, a total of 27,332 kidney transplants were performed (OPTN, 2024). According to data from the OPTN, for individuals receiving primary kidney transplants between 2008 and 2015, the 1-, 3- and 5-year survival rates were 97.1%, 92.9% and 86.3%, respectively.

A kidney transplant involves the surgical removal of a kidney from a deceased or living donor and implantation into a recipient. A donor left kidney is usually transplanted to the right iliac fossa with the renal artery anastomosed end-to-end to the hypogastric artery and the renal vein end-to-side to the common iliac vein. The ureter is implanted into the bladder and (under special conditions) a uretero-ureteral anastomosis or ureteropyelostomy may be performed.

Hepatorenal syndrome is a severe complication of liver cirrhosis or other severe liver disease. Features of hepatorenal syndrome are renal dysfunction caused by abnormalities in the arterial circulation and the vasoactive systems, resulting in renal vasoconstriction and renal insufficiency. There are two types of hepatorenal syndrome. Type I hepatorenal syndrome occurs when renal function is rapidly reduced and has an ominous prognosis which is usually reversed by liver transplantation. Type II hepatorenal syndrome occurs when renal failure does not progress rapidly. It can be quite difficult to distinguish these two conditions in individuals with severe liver disease. Liver transplantation is the recognized treatment for hepatorenal syndrome (Davis, 2005; Marik, 2006).

Concern has been raised since the introduction of the MELD (model for end-stage liver disease) prioritization for liver transplant that some recipients that undergo combined liver and kidney transplantation may have reversible renal failure. To address this issue, the American Society of Transplantation and American Society of Transplant Surgeons met in March 2006 to review post-MELD data on the impact of renal function on liver waitlist and transplant outcomes and the result of simultaneous liver kidney transplantation. This committee issued a consensus statement with regard to simultaneous liver-kidney (SLK) transplantation summarized below (Davis, 2007):

• In the setting of chronic kidney disease, a measured creatinine clearance of less than or equal to 30cc/min was considered the appropriate threshold for SLK transplantation.
• In the setting of acute renal failure secondary to hepatorenal syndrome or acute kidney injury, renal dysfunction requiring dialysis reflects a decreased capacity for renal recovery and SLK transplantation is considered appropriate. The committee through consensus established a six (6) weeks dialysis duration threshold prior to SLK transplantation.
• In individuals with prolonged acute kidney failure or kidney failure of unknown cause and a renal biopsy showing fixed renal damage (e.g. greater than 30-50% glomerulosclerosis, arteriolar hyalinosis, tubular atrophy, interstitial fibrosis) SLK may be medically necessary.
• In the setting of acute renal failure including hepatorenal syndrome not requiring dialysis, SLK transplantation was not felt to be medically necessary or appropriate. In reaching this consensus, the committee determined that liver transplant recipients with a glomerular filtration rate (GFR) of less than 30cc/min had a 1-year post-transplant survival of 81.5% and only 25/1648 (1.5%) of these recipients were listed for kidney transplant within a year of liver transplantation.

The 2020 Kidney Disease Improving Clinical Outcomes (KDIGO) clinical practice guideline on evaluation and management of candidates for kidney transplantation, developed by an international group of experts, recommended that individuals with chronic kidney disease who are expected to reach end-state kidney disease be considered for kidney transplantation, except for individuals with the following conditions:

• Multiple myeloma, light chain deposition disease or heavy chain deposition disease unless they have successfully received a curative treatment;
• AL amyloidosis with significant extrarenal involvement;
• Decompensated cirrhosis (these individuals can be considered for SLK);
• Severe irreversible obstructive or restrictive lung disease; and
• Severe uncorrectable symptomatic cardiac disease determined by a cardiologist to preclude transplantation.

In addition, the KDIGO guideline recommends that kidney transplant evaluation be delayed for individuals with the following conditions until they have been satisfactorily managed:

• Unstable psychiatric disorder or current substance abuse disorder that affects decision-making and puts the individual at an unacceptable level of post-transplant risk;
• Ongoing health-compromising behavior;
• Active infection that is not properly treated (excluding hepatitis C);
• Active malignancy other than indolent and low-grade cancers;
• Active symptomatic cardiac disease that has not been evaluated by a cardiologist;
• Active symptomatic peripheral arterial disease;
• Recent stroke or transient ischemic attack;
• Active peptic ulcer disease, diverticulitis, acute pancreatitis, gallstone or gallbladder disease or inflammatory bowel disease;
• Acute hepatitis; or
• Severe hyperparathyroidism.

In 2017, United Network of Organ Sharing (UNOS) implemented policy changes for SLK transplantation based on changes the UNOS/Organ Procurement and Transplant Network (OPTN) board recommended. The decision was made based on subjective criteria to implement the new SLK allocation policy to standardize utilization for SLK. Individuals meeting the SLK allocation policy are defined based on the following criteria: sustained kidney injury with estimated glomerular filtration rate (eGFR) < 60 mL/min for 90 days or more with a final eGFR <30 mL/min. (UNOS, 2022)

Controlled HIV infection is not considered a contraindication to kidney transplant (Chadban, 2020). In 2019, Zheng and colleagues published a meta-analysis of studies on outcomes after kidney transplantation in HIV-positive individuals. The meta-analysis included 27 cohort studies and 1670 case series published between July 2003 and May 2018. The authors found a pooled 1-year survival rate of 97% and a 5-year survival rate of 94%.

Allotransplantation: The transfer of cells, tissues, or whole organs from one individual to another within the same species.

Chronic renal disease: The permanent loss of kidney function.

End stage renal disease: Persistent decline in renal function as documented by falling creatinine clearance in an individual diagnosed with a renal disease whose natural history is progression to renal impairment requiring current or impending renal replacement (dialysis or transplant).

Nephropathy: Refers to damage or disease of the kidney.

Peer Reviewed Publications:

1. Bleyer AJ, Donaldson LA, McIntosh M, et al. Relationship between underlying renal disease and renal transplantation outcome. Am J Kidney Dis. 2001; 37(6):1152-1161.
2. Cecka JM. The UNOS Scientific Renal Transplant Registry - 2000. Clin Transpl. 2000:1-18.
3. Davis CL. Impact of pretransplant renal failure: when is listing for kidney-liver indicated? Liver Transpl. 2005; 11(11 Suppl 2):S35-S44.
4. Chadban SJ, Ahn C, Axelrod DA et al. KDIGO Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation. Transplantation. 2020; 104(4S1 Suppl 1):S11-S103.
5. Davis C, Feng S, Sung R, et al. Simultaneous liver-kidney transplantation: Evaluation to decision making. Am J Transplant. 2007; 7(7):1702-1709.
6. Gjertson DW, Cecka JM. Determinants of long-term survival of pediatric kidney grafts reported to the United Network for Organ Sharing kidney transplant registry. Pedatr Transplant. 2001; 5(1):5-15.,
7. Gjertson DW, Cecka JM. Living unrelated donor kidney transplantation. Kidney Int. 2000; 58(2):491-498.
8. Ishitani M, Isaacs R, Norwood V, et al. Predictors of graft survival in pediatric living-related kidney transplant recipients. Transplantation. 2000; 70(2):288-292.
9. 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.
10. Marik PE, Wood K, Starzl TE. The course of type 1 hepato-renal syndrome post liver transplantation. Nephrol Dial Transplant. 2006; 21(2):478-482.
11. Martínez-Vaquera S, Navarro Cabello MD, López-Andreu M, et al. Outcomes in renal transplantation with expanded-criteria donors. Transplant Proc. 2013; 45(10):3595-3598.
12. 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. 2014; 24(1):50-57.
13. Steinman T, Becker BN, Frost AE, et al. Guidelines for the referral and management of patients eligible for solid organ transplantation. Transplantation. 2001; 71(9):1189-1204.
14. Tejani A, Sullivan EK. Do six-antigen-matched cadaver donor kidneys provide better graft survival to children compared with one-haploidentical living-related donor transplants? Pediatr Transplant. 2000; 4(2):140-145.
15. Zheng X, Gong L, Xue W, Zeng S, Xu Y, Zhang Y, Hu X. Kidney transplant outcomes in HIV-positive patients: a systematic review and meta-analysis. AIDS Res Ther. 2019;16(1):37.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American Society of Nephrology. Available at: https://www.asn-online.org/. Accessed on January 22, 2024.
2. Centers for Disease Control and Prevention. National chronic kidney disease basics. Last reviewed February 28, 2022. Available at: https://www.cdc.gov/kidneydisease/basics.html. Accessed on January 22, 2024.
3. Organ Procurement and Transplantation Network. National Data. Available at: https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/. Accessed on January 22, 2024.
4. United Network for Organ Sharing. Available at: http://www.unos.org/. Accessed on January 22, 2024.
   • Policy 8 Kidney Allocation. Last updated December 13, 2023.
   • Policy 9.9 Liver-Kidney Allocation. Last updated January 10, 2024.

Hepatorenal Syndrome
Kidney Transplantation
Renal Allotransplantation
Renal Transplantation
Transplantation, Kidney

Federal and State law, as well as contract language including definitions and specific coverage provisions/exclusions, and Medical Policy take precedence over Clinical UM Guidelines and must be considered first in determining eligibility for coverage. The member's contract benefits in effect on the date that services are rendered must be used. Clinical UM Guidelines, which address medical efficacy, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and we reserve the right to review and update Clinical UM Guidelines periodically. Clinical UM guidelines are used when the plan performs utilization review for the subject. Due to variances in utilization patterns, each plan may choose whether or not to adopt a particular Clinical UM Guideline. To determine if review is required for this Clinical UM Guideline, please contact the customer service number on the back of the member's card.

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