Concert Genetics Genetic Testing: Kidney Disorders Form

# Concert Genetics Genetic Testing: Kidney Disorders

Concert Genetics Genetic Testing: Kidney Disorders  
V2.2024  
Date of Last Revision: 04/24  

[Revision log](Revision log)  
[Coding Implications](Coding Implications)  

## CONCERT GENETICS GENETIC TESTING: KIDNEY DISORDERS

See [Important Reminder](Important Reminder) at the end of this policy for important regulatory and legal information.

### OVERVIEW

Inherited kidney disorders and inherited disorders that indirectly affect the kidneys can be more common, such as autosomal dominant polycystic kidney disease, or more rarely Lowe syndrome and Fabry disease. Identifying the genetic cause of an inherited kidney disorder can help direct treatment, inform family members, and contribute to the overall understanding of the genetic etiology of chronic kidney disease. More advanced next-generation sequencing, such as exome sequencing and comprehensive genetic testing panels, are emerging as a first-line diagnostic method for patients with chronic kidney disease.

### POLICY REFERENCE TABLE

#### Coding Implications

This clinical policy references Current Procedural Terminology (CPT®). CPT is a registered trademark of the American Medical Association. All CPT codes and descriptions are copyrighted 2023, American Medical Association. All rights reserved. CPT codes and CPT descriptions are from the current manuals and those included herein are not intended to be all-inclusive and are included for informational purposes only. Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should refer to the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursements of covered services.

The tests and associated laboratories and CPT codes contained within this document serve only as examples to help users navigate claims and corresponding criteria; as such, they are not comprehensive and are not a guarantee of coverage or non-coverage. Please see the [Concert Genetics Platform](Concert Genetics Platform) for a comprehensive list of registered tests.

| Criteria Sections | Example Tests (Labs) | Common CPT Codes | Common ICD Codes | Ref |
|-------------------|---------------------|-----------------|-----------------|-----|
| Polycystic Kidney Disease | | | | |
| Targeted Variant Analysis | Targeted Mutation Analysis for a Known Familial Variant | 81403 | Q61, N18 | 2, 8 |
| Single gene or Multigene Panel | Autosomal Dominant Polycystic Kidney Disease via the PKD1 Gene (PreventionGenetics, part of Exact Sciences) | 81407, 81479 |  | 1, 2 |
|  | PKD2 Full Gene Sequencing and Deletion/Duplication (Invitae) | 81406, 81479 |  |  |
|  | Autosomal Recessive Polycystic Kidney Disease (ARPKD) via the PKHD1 Gene (PreventionGenetics, part of Exact Sciences) | 81408, 81479 |  |  |
|  | Autosomal Dominant Polycystic Kidney Disease (ADPKD) via the GANAB Gene (PreventionGenetics, part of Exact Sciences) | 81479 |  |  |
|  | Autosomal Dominant Polycystic Kidney Disease (ADPKD) via the DNAJB11 Gene (PreventionGenetics, part of Exact Sciences) |  |  |  |
|  | Hereditary Cystic Kidney Diseases Panel (PreventionGenetics, part of Exact Sciences) | 81404, 81405, 81406, 81407, 81408, 81479 |  |  |
|  | Polycystic Kidney Disease Panel (GeneDx) |  |  |  |
| Comprehensive Kidney Disease Panels | | | | |
| Comprehensive Kidney Disease Panels | RenaSight (Natera) | 81401, 81402, 81403, 81404, 81405, 81406, | N00-N08, N10-N19, Q61, R31 | 3 |

|  |  | 81407, 81408, 81479 |  |  |
|---------------------|-------------------------------------------------------------|-----------------|-----------------|-----|
|  | KidneySeq Version 5 Comprehensive Testing (Iowa Institute of Human Genetics) |  |  |  |
|  | RenalZoom (DNA Diagnostic Laboratory - Johns Hopkins Hospital) |  |  |  |
| APOL1-Mediated Kidney Disease | | | | |
| APOL1-Targeted Variant Analysis | Apolipoprotein L1 (APOL1) Renal Risk Variant Genotyping (Quest Diagnostics) | 0355U | N00-N08, N10-N19 | 9 |
|  | APOL1 Genotype, Varies (Mayo Clinic Laboratories) | 81479 |  |  |
| Donor-Derived Cell Free DNA for Kidney Transplant Rejection | | | | |
| Donor-Derived Cell Free DNA for Kidney Transplant Rejection | Allousure Kidney (CareDx, Inc.) | 81479 | T86.11, T86.12, Z94.0 | 7 |
|  | Prospera Kidney (Natera) |  |  |  |
|  | Viracor TRAC Kidney dd-cfDNA (Viracor Eurofins) | 0118U |  |  |
| Other Covered Kidney Disorders | | | | |
| Other Covered Kidney Disorders | See list below | 81400, 81401, 81402, 81403, 81404, 81405, 81406, 81407, 81408, 0268U |  | 4, 5, 6 |

### OTHER RELATED POLICIES

This policy document provides criteria for hereditary kidney disorders. Please refer to:

- **Genetic Testing: Multisystem Inherited Disorders, Intellectual Disability, and Developmental Delay** for criteria related to genetic disorders that affect multiple organ systems
- **Genetic Testing: Hereditary Cancer Susceptibility** for criteria related to von Hippel Lindau (VHL) syndrome and other hereditary cancer syndromes.



\*Clinical features for a specific disorder may be outlined in resources such as GeneReviews, OMIM, National Library of Medicine, Genetics Home Reference, or other scholarly source.

### DEFINITIONS

1. Close relatives include first, second, and third degree blood relatives on the same side of the family:

   a. First-degree relatives are parents, siblings, and children

   b. Second-degree relatives are grandparents, aunts, uncles, nieces, nephews, grandchildren, and half siblings  
   c. Third-degree relatives are great grandparents, great aunts, great uncles, great grandchildren, and first cousins

2. Full siblings are individuals who share the same biological parents.

### BACKGROUND AND RATIONALE

#### Polycystic Kidney Disease - Targeted Variant Analysis

##### Genetic Support Foundation

The Genetic Support Foundation’s Genetics 101 information on genetic testing says the following about testing for familial pathogenic variants:

Genetic testing for someone who may be at risk for an inherited disease is always easier if we know the specific genetic cause. Oftentimes, the best way to find the genetic cause is to start by testing someone in the family who is known or strongly suspected to have the disease. If their testing is positive, then we can say that we have found the familial pathogenic (harmful) variant. We can use this as a marker to test other members of the family to see who is also at risk.

##### GeneReviews: Polycystic Kidney Disease, Autosomal Dominant and Polycystic Kidney Disease, Autosomal Recessive

GeneReviews is an expert-authored review of current literature on a genetic disease, and goes through a rigorous editing and peer review process before being published online.

Per GeneReviews, autosomal recessive polycystic kidney disease (ARPKD) is due to biallelic mutations in the PKHD1 gene. Testing is possible for siblings of an affected individual in whom both of the causative mutations are identified

#### Polycystic Kidney Disease - Single Gene or Multigene Panel

##### GeneReviews: Polycystic Kidney Disease, Autosomal Dominant and Polycystic Kidney Disease, Autosomal Recessive

GeneReviews is an expert-authored review of current literature on a genetic disease, and goes through a rigorous editing and peer review process before being published online.

The recommended polycystic kidney disease testing for autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) is as follows:

“ADPKD should be suspected in individuals with the following:

- Multiple bilateral renal cysts and the absence of manifestations suggestive of a different renal cystic disease  
- Cysts in other organs, especially the liver, but also seminal vesicles, pancreas, and arachnoid membrane…  
- Hypertension in an individual younger than age 35 years  
- An intracranial aneurysm…”

“Autosomal recessive polycystic kidney disease (ARPKD) should be suspected in individuals with bilaterally enlarged, diffusely echogenic kidneys…[and] one or more of the following:…Clinical/laboratory signs of congenital hepatic fibrosis (CHF) that leads to portal hypertension…”

“The renal diagnostic criteria for ARPKD detected by ultrasonography are:

- Increased renal size (in relation to normative size based on age and size of the affected individual);  
- Increased echogenicity;  
- Poor corticomedullary differentiation”

“[In] Childhood and young adulthood…The hepatobiliary abnormalities with progressive portal hypertension are often the prominent presenting features.”

#### Comprehensive Kidney Disease Panels

##### Hays et al (2020)

“We propose the following approach, based on a review of current literature and our practical experience. This approach assumes individuals have already undergone an initial nephrologic workup, including biochemical and serologic testing, imaging of the kidneys, and renal biopsy if indicated.

…[A]fter a negative or inconclusive initial workup, a patient is considered to have KDUE [kidney disease of unknown etiology] and may then be stratified according to the probability of a genetic disease. We consider higher probability patients as those with the following risk factors:

early-onset disease (age <40 years), a positive family history of CKD [chronic kidney disease], consanguinity, extrarenal anomalies, cystic renal disease, or congenital nephropathy”. (p. 594)

### APOL1-Mediated Kidney Disease

##### Freedman et al (2021)

A multidisciplinary group of experts and patient advocates performed a systematic review and created consensus-based guidelines in 2021 to guide health care providers in APOL1-associated neuropathy. The guidelines recommend the following:

“…APOL1 testing should be considered in all patients of African ancestry with kidney disease and in any patient with kidney disease and a family member with a confirmed APOL1 high-risk genotype.” (p. 1768)

Regarding the definition of “high-risk phenotype”: “Two copies of the APOL1 variants (G1/G1, G1/G2, G2/G2) are commonly referred to as a ‘high-risk’ genotype…” (p. 1765)

### Donor-Derived Cell-Free DNA for Kidney Transplant Rejection

##### Knight et al (2019)

A publication in the journal Transplantation entitled “Donor-specific Cell-free DNA as a Biomarker in Solid Organ Transplantation. A Systematic Review” stated the following:

In summary, donor-derived cfDNA shows promise as a biomarker for the detection of acute transplant graft injury. It has potential to reduce the need for protocol biopsy surveillance, allowing for a more targeted diagnostic approach. Detection of injury occurs before clinical manifestation, meaning that there is a window for earlier detection and treatment of AR [acute rejection] and other causes of graft injury with the potential to improve outcomes. It may also facilitate the detection of under immunosuppression and find use as a tool for monitoring during immunosuppression minimization. Further studies are required to validate the thresholds for further investigation and intervention, determine the optimum frequency for monitoring, and to identify whether prospective monitoring using dd-cfDNA can indeed improve transplant outcomes compared to current practice. (p. 280)

| Reviews, Revisions, and Approvals | Revision Date | Approval Date |
|----------------------------------|--------------|--------------|
| Policy developed.                | 03/23        | 03/23        |

CENTENE
Corporation

Concert Genetics Genetic Testing: Kidney Disorders
V2.2024
Date of Last Revision: 04/24

Important Reminder
This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. “Health Plan” means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.

The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions, and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures.

This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed at any time.

This clinical policy does not constitute medical advice, medical treatment, or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care and are solely responsible for the medical advice or treatment of member/enrollees. This clinical policy is not intended to recommend treatment for member/enrollees. Member/enrollees should consult with their treating physician in connection with diagnosis and treatment decisions.

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CENTENE
Corporation

Concert Genetics Genetic Testing: Kidney Disorders
V2.2024
Date of Last Revision: 04/24

Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan.

This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, member/enrollees, and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, member/enrollees and their representatives agree to be bound by such terms and conditions by providing services to member/enrollees and/or submitting claims for payment for such services.

Note: For Medicaid member/enrollees, when state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy.

Note: For Medicare member/enrollees, to ensure consistency with the Medicare National Coverage Determinations (NCD) and Local Coverage Determinations (LCD), all applicable NCDs and LCDs and Medicare Coverage Articles should be reviewed prior to applying the criteria set forth in this clinical policy. Refer to the CMS website at http://www.cms.gov for additional information.

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