Centene Genetic Kidney Testing Coverage Update

Coverage Criteria for Genetic and Molecular Testing

Targeted Variant Analysis

Covered when ALL of the following are met

PKD targeted variant for ADPKD: PKD1, PKD2, GANAB, or DNAJB11 targeted variant analysis (81403) to establish a diagnosis of autosomal dominant polycystic kidney disease is medically necessary when the member has a close relative with a known pathogenic or likely pathogenic variant in one of these genes.

PKHD1 targeted variant for ARPKD: PKHD1 targeted variant analysis (81403) to establish a diagnosis of autosomal recessive polycystic kidney disease is medically necessary when the member has a biological full sibling with known biallelic pathogenic or likely pathogenic variants in PKHD1.

Investigational uses: Targeted variant analysis for these genes is investigational for all other indications.

Single Gene or Multigene Panel for PKD

Covered when ALL of the following are met

Test types: Sequencing and/or deletion/duplication analysis of PKD1, PKD2, GANAB, DNAJB11, or PKHD1 or multigene panel analysis (CPTs such as 81404–81408, 81479) to confirm or establish a diagnosis of polycystic kidney disease is medically necessary when the member has any one of the listed clinical features of polycystic kidney disease.

Clinical features (one required): 1) Multiple bilateral renal cysts; OR 2) Cysts in organs other than the kidneys (especially liver, seminal vesicles, pancreas, arachnoid membrane); OR 3) Hypertension younger than age 35; OR 4) Intracranial aneurysm; OR 5) Bilaterally enlarged and diffusely echogenic kidneys; OR 6) Poor corticomedullary differentiation; OR 7) Hepatobiliary abnormalities with progressive portal hypertension; OR 8) Congenital hepatic fibrosis with portal hypertension.

Investigational uses: Sequencing or multigene panel analysis for these genes is investigational for all other indications.

Comprehensive Kidney Disease Panels

Covered when ALL of the following are met

Standard workup and CKD of undetermined cause: Genetic testing via a comprehensive kidney disease panel (e.g., CPTs 81401, 81402, 81403, 81404, 81405, 81406, 81407, 81408, 81479) is medically necessary when the member has chronic kidney disease with an undetermined cause after undergoing standard-of-care workup (history and physical, biochemical testing, renal imaging, or renal biopsy).

Additional requirement (one of list): AND the member meets at least one of the following: onset of chronic kidney disease under 40 years of age, a positive family history of CKD, consanguinity, extrarenal anomalies, cystic renal disease, or congenital nephropathy.

Investigational uses: Comprehensive kidney disease panels are investigational for all other indications.

APOL1 Targeted Variant Analysis

Covered when ALL of the following are met

APOL1 testing criteria: Targeted variant analysis for APOL1 high-risk genotype (G1/G1, G1/G2, G2/G2) (0355U, 81479) is medically necessary when the member has kidney disease AND the member is of African ancestry OR has a family member with a confirmed APOL1 high-risk genotype.

Investigational uses: APOL1 targeted variant analysis is investigational for all other indications.

Donor-Derived Cell-Free DNA

dd-cfDNA stance: Peripheral blood donor-derived cell-free DNA (dd-cfDNA) for management after renal transplantation (e.g., detection of acute rejection or graft dysfunction) is considered investigational for all indications.

Other Covered Kidney Disorders

Covered when ALL of the following are met

Rare genetic kidney disorders: Genetic testing to establish or confirm listed genetic kidney disorders (for example: Alport syndrome, C3 glomerulopathy, congenital nephrotic syndrome, cystinosis, cystinuria, Fabry disease, familial atypical HUS, primary hyperoxaluria) is medically necessary when the member demonstrates clinical features consistent with the specific disorder.

Other disorders: Genetic testing to establish or confirm diagnoses of other kidney disorders not specifically discussed will be evaluated according to the General Approach to Genetic and Molecular Testing policy criteria.

Covered indications and supporting clinical criteria

Coverage is informed by established clinical indications and literature; testing is considered when specific clinical features or family information indicate hereditary kidney disease.

Familial variant testing: Targeted familial pathogenic variant testing is appropriate when a familial pathogenic variant has been identified in an affected family member; use that variant to test at-risk relatives.

supported by Genetics 101 guidance

ADPKD/ARPKD testing: Single-gene or multigene panel testing for ADPKD or ARPKD should be considered in individuals meeting clinical diagnostic criteria (e.g., multiple bilateral renal cysts, extrarenal cysts, early-onset hypertension, bilaterally enlarged diffusely echogenic kidneys, poor corticomedullary differentiation, or hepatobiliary abnormalities consistent with CHF).

supported by GeneReviews

Comprehensive panels for KDUE: After a negative or inconclusive initial nephrologic workup (biochemical/serologic testing, imaging, renal biopsy if indicated), consider comprehensive kidney disease panels for KDUE, especially for early-onset disease (<40 years), positive family history, consanguinity, extrarenal anomalies, cystic renal disease, or congenital nephropathy.

Use of genetic tests listed in this policy that are explicitly designated as investigational is not supported. Examples include targeted variant analyses or sequencing/panel testing when performed for indications the policy labels investigational, and use of donor-derived cell-free DNA (dd-cfDNA) assays for transplant rejection or graft dysfunction. When an indication is investigational in this policy, requests for coverage may be denied consistent with the policy wording.

Peripheral blood donor-derived cell-free DNA assays for management after renal transplantation are considered investigational for all indications. This includes use for detection of acute renal transplant rejection and detection of graft dysfunction; such testing is not covered under the medical necessity criteria in this policy.

Coverage of services described in this policy is subject to the member's specific benefit plan terms, conditions, exclusions, and limitations. This policy provides medical necessity guidance but does not guarantee payment; final coverage determinations are made in accordance with the applicable coverage documents and plan provisions.

Statements in this policy that label a test or use as investigational are interpreted as not medically necessary for those indications. For example, donor-derived cell-free DNA for detection of acute rejection or graft dysfunction is considered investigational and therefore not medically necessary for those uses.

Specific Covered Indications

Diagnostic testing to establish or confirm inherited kidney disorders, APOL1 genotyping in specified populations, and comprehensive panels when CKD undetermined after standard workup

Diagnostic testing for inherited kidney disorders: Diagnostic testing to establish or confirm inherited kidney disorders (including PKD, ARPKD, and other listed genetic kidney diseases), APOL1 risk genotyping in persons of African ancestry or with a family member with a confirmed high-risk genotype, and comprehensive panels when CKD remains of undetermined cause after standard workup are covered as detailed in this policy.

Familial pathogenic variant testing; single-gene/multigene panels for ADPKD/ARPKD; comprehensive panels for KDUE; APOL1 testing; donor-derived cfDNA mention

Familial pathogenic variant testing is appropriate when a pathogenic variant has been identified in an affected family member; that specific variant should be used to test at-risk relatives.

supported by Genetics 101 guidance and policy rationale

ADPKD/ARPKD panels:

Procedure and Diagnosis Codes

Referenced CPT/registry codesmixed

81401	Comprehensive kidney disease panel (referenced)
81402	Comprehensive kidney disease panel (referenced)
81403	Targeted variant analysis / testing for known familial variant
81404	Multigene panel sequencing
81405	Multigene panel sequencing
81406	Single gene sequencing (e.g., PKD2)
81407	Single gene sequencing (e.g., PKD1)
81408	Single gene sequencing (e.g., PKHD1)
81479	Unlisted molecular pathology procedure (used for various tests)
0355U	APOL1 targeted variant analysis (registry/LDT code)

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Referenced ICD-10 codes/rangesICD-10

N00-N08	Acute nephritic syndromes (ICD-10 ranges referenced for panels)
N10-N19	Renal failure and other kidney disorders (ICD-10 ranges referenced for panels)
Q61	Congenital malformations of kidney (ICD-10 referenced)
R31	Hematuria (ICD-10 referenced)
T86.11	Kidney transplant complication (ICD-10 referenced for dd-cfDNA)
T86.12	Kidney transplant complication (ICD-10 referenced for dd-cfDNA)
Z94.0	Kidney transplant status (ICD-10 referenced for dd-cfDNA)

Disorders: added codesCPT | HCPCS

81400
81401
81402
81403
81404
81405
81406
81407
81408
0268U

Provider Actions and Documentation Requirements

Prior Authorization

Prior Authorization Required for Added Genetic Test Codes

Prior authorization is required for newly added or updated genetic test codes before service. Submit prior authorization requests per the member's plan guidelines and include the specific test codes and clinical indication.

Affected CPT/HCPCS examples: 81400, 81401, 81402, 81403, 81404, 81405, 81406, 81407, 81408, 0268U, 0355U, 0118U (as applicable to the policy)
Include date of onset of CKD and results of prior diagnostic workup when requesting auth

Denial Risk

Investigational Indications May Be Denied

Tests or indications designated investigational in this policy may be denied. Examples include donor-derived cell-free DNA (dd-cfDNA) testing for kidney transplant rejection and other indications listed as investigational.

Eligibility and Patient Selection

Eligibility for covered genetic testing generally requires clinical evidence or family information that supports a hereditary kidney disorder. For targeted familial variant analysis, eligibility requires a close relative with a known pathogenic or likely pathogenic variant (or for PKHD1, a biological full sibling with known biallelic pathogenic variants).

APOL1 targeted testing is eligible when the member has kidney disease and either is of African ancestry or has a family member with a confirmed APOL1 high-risk genotype (two risk variants: G1/G1, G1/G2, or G2/G2).

Comprehensive kidney disease panels are eligible when the member has chronic kidney disease of undetermined cause after a standard nephrologic workup (history/physical, biochemical testing, imaging, or renal biopsy) and meets at least one additional risk criterion such as onset of CKD under 40 years of age or other listed clinical risk factors.

Prior to ordering comprehensive panels, documentation should show completion of an initial nephrologic workup (biochemical/serologic testing, imaging, and renal biopsy if indicated). After a negative or inconclusive workup, consider comprehensive testing for KDUE, particularly in patients with early-onset disease (<40 years), positive family history, consanguinity, extrarenal anomalies, or congenital nephropathy.

For familial pathogenic variant testing, eligibility depends on identifying the familial pathogenic variant in an affected family member when possible; start testing with the affected relative and then test at-risk relatives for that specific variant.

Genetic testing for diagnostic confirmation of ADPKD/ARPKD via single-gene or multigene testing is eligible when the member meets the listed clinical diagnostic features such as multiple bilateral renal cysts, extrarenal cysts, early-onset hypertension, or characteristic imaging findings.

Not Covered / Investigational

The following uses and tests are explicitly listed as investigational and not covered: targeted variant analysis or sequencing/panel analysis when performed for indications the policy defines as investigational; comprehensive panels or single-gene testing outside the specified medical necessity criteria; and donor-derived cell-free DNA (dd-cfDNA) for transplant rejection or graft dysfunction monitoring. Coverage for investigational indications is excluded under this policy.

This policy does not enumerate all plan-level exclusions. Explicit coverage exclusions and limitations are determined by the member's benefit documents and plan policies; where plan documents differ, those documents govern coverage decisions.

Background and Rationale

Inherited kidney disorders vary in prevalence and presentation; identifying a genetic cause can inform management and family counseling. For ADPKD and related disorders, literature and clinical guidance recommend starting with targeted familial testing when a familial pathogenic variant is known, and considering single-gene or multigene testing when clinical features meet diagnostic criteria. Next-generation sequencing–based approaches, including comprehensive panels and exome-based methods, are increasingly used after standard nephrologic evaluation for patients with chronic kidney disease of undetermined etiology. APOL1 testing is supported by consensus guidance for patients of African ancestry or those with a family member with a confirmed high-risk APOL1 genotype. Donor-derived cfDNA has shown promise as a biomarker for transplant monitoring but remains investigational pending further validation.

Definitions

Close relatives / Full siblings

Definition of close relativesClose relatives include first-, second-, and third-degree blood relatives on the same side of the family (first-degree: parents, siblings, children; second-degree: grandparents, aunts, uncles, nieces, nephews, grandchildren, half-siblings; third-degree: great-grandparents, great aunts/uncles, great-grandchildren, first cousins)

Definition of full siblingsFull siblings are individuals who share the same biological parents.

Scope for family-history documentationReferences to a 'close relative' in coverage criteria refer to the degree definitions above when documenting a family member with a pathogenic variant.

Close relatives / Full siblings (clarification)

Close relatives (summary)Includes first-, second-, and third-degree blood relatives on the same side of the family (see first-, second-, third-degree lists)

OpenPayer

Genetic Testing: Kidney Disorders (Coverage Criteria)

Coverage Criteria for Genetic and Molecular Testing

Specific Covered Indications

Procedure and Diagnosis Codes

Provider Actions and Documentation Requirements

Eligibility and Patient Selection

Not Covered / Investigational

Background and Rationale

Definitions