Centene kidney genetic testing Coverage Update

Coverage Criteria

APOL1 Targeted Variant Analysis (Medically Necessary)

APOL1 Targeted Variant Analysis: Covered when ALL of the following are met

APOL1 criteria: Targeted variant analysis for APOL1 high-risk genotype (0355U, 81479) is medically necessary when: A) the member/enrollee has kidney disease, AND B) the member/enrollee meets at least one of the following: is of African ancestry OR has a family member with a confirmed APOL1 high-risk genotype (G1/G1, G1/G2, or G2/G2).

Genetic and molecular testing coverage criteria

Coverage for genetic testing (comprehensive panels, APOL1 targeted testing, dd-cfDNA) is supported when clinical features or intended use align with guideline-based indications.

KDIGO-informed indications: Genetic testing may be informative for: high prevalence of monogenic subtypes in the clinical category; early age of onset of CKD; syndromic/multisystem features; consanguinity; possibility of identifying a condition amenable to targeted treatment; CKD/kidney failure of unknown etiology when biopsy would not be informative.

Derived from KDIGO 2024 guidance

Comprehensive kidney disease panels: Covered when ALL of: patient has KDUE after initial nephrologic workup; presence of risk factors such as age <40, positive family history (first- or second-degree relative), consanguinity, extrarenal anomalies, or congenital nephropathy; or syndromic/multisystem features suggesting a genetic cause.

Policy added these criteria based on literature and guidelines

APOL1 targeted testing: 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.

Per Freedman et al. 2021 consensus

Donor-derived cfDNA for transplant rejection: Covered when the test is used for intended purposes: to assist evaluation of immunosuppression adequacy in lieu of biopsy when biopsy would inform management; to further evaluate allograft status after physician-assessed pretest; as a rule-out test in validated populations with clinical suspicion of rejection; or to assess rejection when biopsy results are inconclusive or insufficient.

Aligned with CMS MolDX LCD and society guidance

This policy explicitly defines the medical necessity and investigational scope for four test types used in evaluation of inherited kidney disorders and post-transplant monitoring. Polycystic kidney disease panels, comprehensive kidney disease panels, APOL1 targeted variant analysis, and donor‑derived cell‑free DNA (dd‑cfDNA) are each addressed with specific criteria. Tests that meet the listed, test‑specific criteria are considered medically necessary; use of these tests for indications outside those specified is considered investigational (not covered) unless otherwise noted in the policy updates. The policy updates also align dd‑cfDNA coverage with LCD and society guidance and add covered PLA codes where appropriate.

The prior policy item for Polycystic Kidney Disease Targeted Variant Analysis has been retired. Tests for targeted PKD variant analysis will now be reviewed under the organization’s General Approach to Genetic and Molecular Testing policy rather than using the former PKD‑specific criteria.

Polycystic kidney disease panels (examples: CPT 81404–81408, 81479) are covered only when the member meets the specified clinical features (e.g., multiple bilateral renal cysts; extrarenal cysts such as hepatic or pancreatic; hypertension <35 years; bilaterally enlarged, diffusely echogenic kidneys). Use of PKD panels for any other indications is considered investigational (not covered).

Comprehensive kidney disease panels (examples: CPT 81401–81408, 81479) are covered when the member has chronic kidney disease of unknown etiology after a standard nephrologic workup and meets at least one risk factor for a genetic etiology (for example: onset <40 years, first‑ or second‑degree relative with CKD, consanguinity, cystic renal disease, congenital nephropathy, or syndromic/multisystem features). Comprehensive panels are investigational for indications beyond those listed.

Donor‑derived cell‑free DNA assays for kidney transplant monitoring (examples: PLA/0493U/0118U/0508U/0509U, 81479) are covered when used for post‑transplant evaluation as specified: the member has had a kidney transplant, the test has not been performed in the prior 12 months, and the intended use meets criteria such as clinical signs of acute rejection, inconclusive biopsy, or monitoring adequacy of immunosuppression. Use of dd‑cfDNA for indications outside the specified post‑transplant monitoring purposes is considered investigational. The policy was updated to change dd‑cfDNA from prior non‑coverage to covered when LCD and society criteria are met and to add covered PLA codes consistent with the LCD.

Targeted APOL1 variant analysis (example code 0355U, and 81479) is covered when the member has kidney disease and either is of African ancestry or has a family member with a confirmed APOL1 high‑risk genotype (G1/G1, G1/G2, or G2/G2). APOL1 targeted testing is considered investigational for other indications.

Donor‑derived cell‑free DNA testing was previously listed as non‑covered in earlier versions of this policy. That status has been revised: dd‑cfDNA is now covered for the specified post‑transplant intended uses when documentation and clinical context align with the CMS MolDX LCD and supporting society guidance. Providers should document intended use (for example, to assist evaluation of immunosuppression adequacy or to evaluate an allograft when biopsy is inconclusive) and follow prior‑authorization requirements and coding guidance including newly added PLA codes.

Covered Indications

inv-35: Indications to establish or confirm diagnosis of inherited kidney disorders and dd-cfDNA monitoring for transplant rejection

Covered indications where genetic or molecular testing may establish or confirm diagnosis, or assist post-transplant management; tests must meet the specific criteria below.

Inherited kidney disorders diagnosis: Genetic testing to establish or confirm diagnoses such as polycystic kidney disease, Alport syndrome, congenital nephrotic syndrome, C3 glomerulopathy, cystinosis, Fabry disease, cystinuria, aHUS, primary hyperoxaluria, or other rare genetic kidney disorders is considered medically necessary when clinical features consistent with the disorder are present.

CKD of unknown etiology (KDUE): Evaluation of CKD of unknown etiology after a negative or inconclusive initial nephrologic workup (history and physical, biochemical/serologic testing, imaging, and renal biopsy if indicated) — consider comprehensive panel testing when risk factors for genetic disease are present (eg age <40, positive family history, consanguinity, extrarenal anomalies, congenital nephropathy).

APOL1 testing indication: APOL1 targeted variant analysis is indicated for patients of African ancestry with kidney disease and for patients with a family member who has a confirmed APOL1 high-risk genotype.

Eligibility Requirements

Eligibility requirements for each covered test type are defined within their respective criteria sets. This block is a placeholder for top‑level eligibility nodes (e.g., transplantation status, prior nephrologic workup completed, ancestry/family history) that feed the detailed criteria for each test.

This placeholder represents additional top‑level eligibility nodes (such as age thresholds, documented clinical features, or prior testing intervals) that are evaluated against the specific test criteria to establish medical necessity.

This placeholder represents district‑level eligibility items (for example, documentation of family history, confirmation of APOL1 high‑risk genotype in a relative, or presence of syndromic features) that inform APOL1 and comprehensive panel decisions.

This placeholder captures eligibility nodes related to timing and prior procedures (for example, dd‑cfDNA not performed within the last 12 months, and completion of standard nephrologic workup prior to comprehensive panel ordering).

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required to establish medical necessity for donor-derived cell-free DNA (dd-cfDNA) testing per the listed clinical criteria. Ensure PA is obtained before ordering when coverage is dependent on policy criteria.

Affected codes: covered PLA and CPT/HCPCS codes per LCD and policy reference table
PA frequency limit: testing considered only if not performed in the prior 12 months unless clinical circumstances justify otherwise

Billing Rule

Donor-derived cfDNA Prior Authorization / Coding Note

Donor-derived cfDNA testing is covered when aligned with the CMS MolDX LCD and relevant specialty society guidance. PLA (proprietary lab analyte) codes have been added to the covered code set to maintain consistency with the LCD.

Coding Examples

Polycystic Kidney Disease Panels (examples)CPTCovered

81404	Targeted genomic sequence analysis panels (listed for polycystic kidney disease panels)
81405	Targeted genomic sequence analysis panels
81406	Targeted genomic sequence analysis panels
81407	Targeted genomic sequence analysis panels
81408	Targeted genomic sequence analysis panels
81479	Unlisted molecular pathology procedure

Comprehensive Kidney Disease Panels (examples)CPTCovered

81401	Exome or comprehensive molecular test (listed for comprehensive kidney disease panels)
81402	Exome or comprehensive molecular test
81403	Exome or comprehensive molecular test
81404	See above
81405	See above
81406	See above
81407	See above
81408	See above
81479	Unlisted molecular pathology procedure

APOL1 Targeted Variant AnalysisCPTCovered

0355U	APOL1 targeted variant analysis (proprietary code)
81479	Unlisted molecular pathology procedure

Donor-Derived Cell-free DNA for Kidney Transplant RejectionCPTCovered

0493U	Donor-derived cell-free DNA assay (example)
0118U	Donor-derived cell-free DNA assay (example)
0508U	Donor-derived cell-free DNA assay (example)
0509U	Donor-derived cell-free DNA assay (example)
81479	Unlisted molecular pathology procedure

Associated ICD-10 Codes (examples)ICD-10

T86.11	Kidney transplant complication diagnosis code referenced
T86.12	Kidney transplant complication diagnosis code referenced

Example covered CPT/PLA codes referenced in policymixedCovered

81408	Unlisted multigene or targeted genetic testing (as referenced in policy's Other Covered Kidney)
0268U	PLA code referenced as covered for APOL1 or other kidney testing (policy added covered PLA codes)

Age for higher probability of genetic disease

Age threshold< 40 years

ContextUsed to define early-onset kidney disease as a risk factor for higher probability of a genetic cause

Policy useQualifies patient as higher probability for genetic disease when KDUE after standard workup

Not Covered / Investigational

Use of the listed genetic and molecular tests for indications other than those explicitly specified in the medically necessary criteria is considered investigational and not covered. This applies to polycystic kidney disease panels, comprehensive kidney disease panels, APOL1 targeted analysis, and dd‑cfDNA when used outside their defined intended uses.

Prior non‑coverage of dd‑cfDNA for transplant rejection has been rescinded where coverage is supported by the CMS MolDX LCD and society guidance; dd‑cfDNA is now covered for the specified post‑transplant uses when documentation and clinical intent meet the policy criteria. All other investigational statements for genetic testing that fall outside the stated criteria remain in effect.

Background

Background: Inherited kidney disorders (for example, autosomal dominant and autosomal recessive polycystic kidney disease, Alport syndrome, Fabry disease, primary hyperoxaluria) can affect management, prognostication, and family counseling. Next‑generation sequencing approaches including targeted multigene panels and exome sequencing are increasingly used after standard nephrologic workup to identify a molecular diagnosis. In post‑transplant care, peripheral blood dd‑cfDNA assays provide a noninvasive biomarker to assist evaluation for allograft rejection or to inform management when biopsy is inconclusive. KDIGO and other guideline sources report that genetic testing can identify actionable variants in a meaningful subset of patients with CKD, particularly those with early‑onset disease, syndromic features, or family history.

Definitions

Close relatives — definition

DefinitionClose relatives include first-, second-, and third-degree blood relatives on the same side of the family

First-degree examplesParents, siblings, and children

Second-degree examplesGrandparents, aunts, uncles, nieces, nephews, grandchildren, half-siblings

Third-degree examplesGreat-grandparents, great-aunts, great-uncles, great-grandchildren, first cousins

KDUE — definition and context

TermKidney disease of unknown etiology (KDUE)

Definition

OpenPayer

Genetic Testing: Kidney Disorders (Genetic & Molecular Testing Coverage Criteria)