CurrentBlue Cross Blue Shield - NebraskaPolicy M.82

MA Specialty Testing: Nephrology (Preauthorization Required)

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Defines preauthorization-required coverage criteria for genetic and specialty laboratory testing for known or suspected kidney disorders, including testing for potential living donors and APOL1 analysis; applies to Blue Cross Blue Shield - Nebraska members.

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CurrentBlue Cross Blue Shield - NebraskaPolicy M.82

MA Specialty Testing: Nephrology (Preauthorization Required)

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Sign up for Blue Cross Blue Shield - Nebraska Policy M.82 alerts

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Policy Summary

PayerBlue Cross Blue Shield - Nebraska

PolicyMA Specialty Testing: Nephrology (Preauthorization Required)

Policy CodePolicy M.82

Change TypeNo material changes

Effective DateMay 1, 2026

Next Review DateJan 1, 2027

Key ActionObtain preauthorization before ordering specialty nephrology genetic testing listed in the policy.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

05-01-2026Effective

APOL1APOL1

449NGS panel genes

3Guideline refs

Coverage Criteria for Nephrology Genetic Testing

Polycystic Kidney Disease — Indications

Genetic testing using a polycystic kidney disease panel to confirm or establish a diagnosis of polycystic kidney disease (PKD) may be considered reasonable and necessary when:

PKD clinical features: Member has any of: 1) kidney cysts; OR 2) cysts in organs other than the kidneys (especially the liver, seminal vesicles, pancreas, or arachnoid membrane); OR 3) bilaterally enlarged and diffusely echogenic kidneys.

From policy PKD section

Comprehensive Kidney Disease Panels — Indications

Genetic testing for kidney disease via a comprehensive kidney disease panel may be considered reasonable and necessary when:

CKD of unknown etiology pathway: Member has chronic kidney disease with an undetermined cause after undergoing standard of care workup (e.g., history and physical, biochemical testing, renal imaging, renal biopsy if indicated) AND meets at least one of the specified risk features.

Requirement I.A then 1.a-h

Risk features (one or more): Onset of chronic kidney disease under 50 years of age; OR one or more first-degree relatives with chronic kidney disease; OR consanguineous family history; OR cystic renal disease; OR congenital nephropathy; OR syndromic/multisystem features; OR possibility of identifying a condition amenable to targeted treatment; OR member is being waitlisted for kidney transplant AND a close relative is considering kidney donation to the member.

List I.A.1.a-h

Asymptomatic donor pathway: Member is asymptomatic AND being considered as a kidney donor AND has at least one first-degree relative with kidney disease suggestive of autosomal dominant or X-linked inheritance AND no causative mutation has been established yet for the family's kidney disease.

I.B and subcriteria

APOL1-Targeted Variant Analysis — Indications

Targeted variant analysis for the APOL1 high-risk genotype may be considered reasonable and necessary when:

APOL1 testing criteria: Member has kidney disease AND the member meets at least one of the following: member is of African ancestry; OR member has a close relative with a confirmed APOL1 high-risk genotype (G1/G1, G1/G2, or G2/G2).

Policy APOL1 section; high-risk genotype defined as G1/G1, G1/G2, or G2/G2

Other Genetic Kidney Disorders — Indications

Genetic testing to establish or confirm one of the listed rare genetic kidney disorders may be considered reasonable and necessary when the member demonstrates clinical features consistent with the disorder.

Listed disorders: Alport syndrome; C3 glomerulopathy; congenital nephrotic syndrome; cystinosis; cystinuria; Fabry disease; genetic familial atypical hemolytic uremic syndrome (aHUS); primary hyperoxaluria.

Policy Other Covered Kidney Disorders I.A

Referenced clinical indications (partial)

Clinical scenarios and coding indicated in these sections

Indications referenced: Testing recommended for living unrelated donors with significant family history (CKD of unknown etiology or early-onset CKD, cystic kidney disease, congenital disease with extrarenal signs, or aHUS) and NKF guidance supports large multi-disease kidney panels.

From NKF guidance and policy text (living donor and NKF algorithm)

APOL1 guidance: Consider APOL1 testing in patients of African ancestry with kidney disease OR any patient with kidney disease and a family member with a confirmed APOL1 high-risk genotype.Two APOL1 risk variants (G1/G1, G1/G2, G2/G2)

Consensus guideline cited (Freedman et al.)

Coverage criteria (not present in these chunks)

No explicit criteria in provided chunks: These chunks contain code listings, example gene-test mappings and references but do not include conditional coverage criteria or medical necessity rules.

See other sections of the policy for medical necessity criteria.

Genetic testing for polycystic kidney disease panels, comprehensive kidney disease panels, and APOL1-targeted variant analysis is considered not reasonable and necessary when the specific clinical criteria and pathways described in the policy are not met. For PKD panels the policy states testing is not reasonable and necessary for all other indications beyond the listed clinical features (e.g., kidney cysts, extrarenal cysts, or bilaterally enlarged echogenic kidneys). For comprehensive panels and APOL1 targeted analysis the policy likewise indicates testing is not reasonable and necessary for indications other than those listed in the respective sections.

The provided policy chunks do not specify additional explicit exclusion conditions beyond the general statements that testing is not reasonable and necessary when the listed indications are not met. Guidance cited (for example, NKF algorithm recommendations) describes when testing is recommended but does not add discrete exclusion lists in these sections.

The document pages included in these chunks primarily list procedure and gene examples and do not state explicit exclusions. No specific exclusion criteria are presented in the referenced code- and gene-listing material.

Where the policy identifies covered indications, it also makes clear that testing outside those indications is not supported: genetic testing using a polycystic kidney disease panel, a comprehensive kidney disease panel, or APOL1 targeted variant analysis is not reasonable and necessary for indications other than those specifically listed in each section (for example, absence of the PKD clinical features, failure to meet CKD-of-unknown-etiology pathways, or lack of kidney disease plus ancestry/family risk for APOL1).

Within the provided chunks there are no additional explicit statements labeling other specific tests or codes as not medically necessary; the policy instead uses section-level determinations that testing is not reasonable and necessary when the listed clinical criteria are not satisfied.

The code and gene listings in the referenced pages do not include standalone not medically necessary determinations. The policy’s not-reasonable-or-necessary conclusions are tied to whether request-specific clinical criteria are met rather than to the listed codes themselves in these chunks.

Procedure and Coding Information

Example covered CPT/HCPCS codes referencedmixedCovered

81404	Listed in reference table (comprehensive and PKD panels)
81405	Listed in reference table (comprehensive and PKD panels)
81406	Listed in reference table (comprehensive and PKD panels)
81407	Listed in reference table (comprehensive and PKD panels)
81408	Listed in reference table (comprehensive and PKD panels)
81479	Unlisted molecular pathology procedure (used for varied APOL1/genotype testing examples)
81401	Listed in comprehensive kidney disease panels
81402	Listed in comprehensive kidney disease panels
81403	Listed in comprehensive kidney disease panels
81400	Listed in other covered kidney disorders

1–10 of 12

1/2

Notable listed CPT/PLA codesmixed

0268U	HEM ATYP HEMOLYTIC UREMC SYND GEN SEQ ALY 15 GEN
0355U	APOL1 RISK VARIANTS
0628U	NFRO KDN DS GENETIC COND RNL DS PNL SLV NGS 449
81400	MOLECULAR PATHOLOGY PROCEDURE LEVEL 1

Molecular pathology CPT codes and level descriptionsCPT

81401	MOLECULAR PATHOLOGY PROCEDURE LEVEL 2
81402	MOLECULAR PATHOLOGY PROCEDURE LEVEL 3
81403	MOLECULAR PATHOLOGY PROCEDURE LEVEL 4
81404	MOLECULAR PATHOLOGY PROCEDURE LEVEL 5
81405	MOLECULAR PATHOLOGY PROCEDURE LEVEL 6
81406	MOLECULAR PATHOLOGY PROCEDURE LEVEL 7
81407	MOLECULAR PATHOLOGY PROCEDURE LEVEL 8

Molecular pathology CPT levels (examples shown)CPT

81406	MOLECULAR PATHOLOGY PROCEDURE LEVEL 6
81407	MOLECULAR PATHOLOGY PROCEDURE LEVEL 8

Molecular pathology CPT levels and unlistedCPT

81408	MOLECULAR PATHOLOGY PROCEDURE LEVEL 9
81479	UNLISTED MOLELCULAR PATHOLOGY PROCEDURE

Age thresholds for testing eligibility

Primary age thresholdOnset of chronic kidney disease under 50 years of age (qualifies for comprehensive kidney disease panel assessment).

NKF guidance noteNKF algorithm recommends consideration of large multi-disease kidney panel testing for certain living donors and high-risk scenarios; supports early-onset thresholds referenced in policy.

Higher-probability referencesOther sources cited in policy context note higher probability of genetic causes at younger ages (examples note age <40 in literature), but policy-specific actionable threshold is <50 years.

Prior Authorization, Documentation, and Billing Guidance

Prior Authorization

Preauthorization required for listed nephrology genetic tests

Preauthorization is required for specialty nephrology genetic testing panels; example CPT/HCPCS codes listed include 81400–81408, 81479, 0268U, and 0355U. Submit requests through the payer’s preauthorization process before performing testing.

Example listed codes: 81400–81408, 81479, 0268U, 0355U

Prior Authorization

Preauthorization required for listed codes

Preauthorization is required for the listed nephrology specialty genomic tests and CPT-PLA/CPT4 codes shown in the policy (for example 0268U, 0355U, 0628U, and multiple 8140x codes). Requests must reference the specific procedure code being requested.

Notable listed codes: 0268U, 0355U, 0628U, 81400–81407

Background and Rationale

Genetic testing has a defined role in diagnosing and managing inherited kidney disorders. The policy notes that testing can confirm or establish diagnoses such as polycystic kidney disease, APOL1-associated risk, Alport syndrome, and other rare genetic kidney disorders when clinical features are consistent with the condition. It also highlights clinical scenarios where testing is particularly relevant—examples include early-onset or unexplained chronic kidney disease, evaluation of potential living donors with significant family history, and situations where identification of a genetic cause may affect management or transplant decision-making. External guidance (for example, NKF working-group recommendations) is cited to support use of large multi-disease kidney panels in appropriate clinical contexts.

Definitions and Key Terms

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, and half-siblings.

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

APOL1 high-risk genotype definition

APOL1 high-risk genotype (concise)Two copies of APOL1 risk variants: G1/G1, G1/G2, or G2/G2.

Policy testing requirement

Policy Summary

PayerBlue Cross Blue Shield - Nebraska

PolicyMA Specialty Testing: Nephrology (Preauthorization Required)

Policy CodePolicy M.82

Change TypeNo material changes

Effective DateMay 1, 2026

Next Review DateJan 1, 2027

Key ActionObtain preauthorization before ordering specialty nephrology genetic testing listed in the policy.

SourceLink

On This Page

Preauthorization required for molecular pathology codes

Preauthorization is required for specialty molecular pathology procedure codes included in the policy such as molecular pathology procedure levels and the unlisted molecular pathology procedure (examples: 81406, 81407, 81408, 81479).

Example molecular pathology codes requiring authorization: 81406, 81407, 81408, 81479

Step Therapy

Step therapy — none specified

No step therapy requirements are specified in this policy for nephrology genetic testing; providers should follow the preauthorization instructions but are not required to document prior therapeutic steps for genetic testing.

Step Therapy

Step therapy — none specified in these chunks

No step therapy requirements are specified in these sections of the policy.

Documentation Required

Required clinical documentation

Clinical documentation must demonstrate the diagnostic indication and relevant clinical features supporting medical necessity for genetic testing requests.

Describe the diagnostic indication and relevant nephrology findings (e.g., imaging, biopsy, biochemical testing)
Include results of standard nephrology workup performed prior to genetic testing

Documentation Required

Clinical documentation to include (family history, indication, donor status)

When requesting comprehensive kidney disease panels or APOL1 testing, include family history and specific indication details (e.g., living unrelated donor evaluation, CKD of unknown etiology, early-onset CKD, cystic kidney disease, congenital disease with extrarenal signs, aHUS, or family member with confirmed APOL1 high‑risk genotype).

Family history: first‑degree relatives with CKD or consanguinity
Donor status: indicate if member is being considered as a kidney donor or a close relative is considering donation
Clinical indication: CKD of unknown etiology after standard workup, early-onset CKD, cystic disease, congenital syndromic features, aHUS

Denial Risk

PKD panel denial triggers

Genetic testing using a polycystic kidney disease (PKD) panel is not reasonable and necessary when the member does not meet the policy’s specified clinical features (i.e., absence of kidney cysts, extra‑renal cysts, or bilaterally enlarged and diffusely echogenic kidneys).

Denial likely if none of the PKD clinical features (kidney cysts; cysts in other organs; bilaterally enlarged diffusely echogenic kidneys) are documented

Denial Risk

Comprehensive panel denial triggers

Comprehensive kidney disease panel requests will be considered not reasonable and necessary if the policy criteria are not met — for example, if CKD of unknown etiology after standard workup is not documented or none of the listed risk features (such as onset <50 years, first‑degree relative with CKD, cystic renal disease, etc.) are present.

Denial likely if standard workup is not documented or required risk features (I.A.1.a–h) are absent

Denial Risk

APOL1 testing denial triggers

APOL1 targeted variant analysis is not reasonable and necessary for indications outside the policy — specifically if the member has kidney disease but is neither of African ancestry nor has a close relative with a confirmed APOL1 high‑risk genotype.

Denial likely if the member with kidney disease does not have African ancestry and no close relative has a confirmed APOL1 high‑risk genotype

Billing Rule

Procedure and diagnosis code pairs required for Quick Code Search

Use the payer’s Quick Code Search feature and enter both a procedure and diagnosis code pair. Missing or incorrect code pairs may cause the request to not be processed or to be held for review.

Enter at least the first 3 characters of the procedure and diagnosis codes when adding a code pair
Both a procedure and diagnosis code are required for the Quick Code Search

Note

Other provider actions — see full policy

The provided chunk set does not add additional explicit provider actions beyond those above; consult the full policy for any other authorization or documentation requirements not shown here.

Targeted APOL1 variant analysis is considered reasonable and necessary when the member has kidney disease and is of African ancestry or has a close relative with a confirmed high-risk genotype (G1/G1, G1/G2, G2/G2).

Literature definitionConsensus guidance describes presence of two APOL1 variants as commonly referred to as a 'high-risk' genotype.

APOL1 high-risk genotype (alternate entry)

Alternate phrasingPresence of two pathogenic APOL1 risk variants (G1/G1, G1/G2, or G2/G2) commonly referred to as a 'high-risk' genotype.

Clinical contextPolicy notes APOL1 testing should be considered in patients of African ancestry with kidney disease and in any patient with kidney disease and a family member with a confirmed high-risk genotype.

Use in decisionsHigh-risk genotype status is used to determine eligibility for targeted APOL1 variant analysis per policy criteria.

Comprehensive kidney disease panel definition (example: 449 genes)

DefinitionLarge multi-disease kidney panel testing that can include hundreds of genes relevant to renal disease (example in policy: NGS panel of 449 genes).

Typical use casesUsed for CKD of unknown etiology after standard workup, living donor evaluation with significant family history, and syndromic or early-onset presentations.

Example PLA code0628U referenced for a 449-gene renal disease NGS panel in the policy's code listings.

Molecular pathology procedure, Level 8

Level descriptionMolecular pathology procedure, Level 8: examples include analysis of 26–50 exons by DNA sequence analysis, mutation scanning, duplication/deletion variants of >50 exons, or sequence analysis of multiple genes on one platform.

Example genes includedPolicy example listings for Level 8 include COL4A4, COL4A5 and other full gene sequences relevant to renal disorders.

Coding contextCorresponds to CPT level codes listed in the policy code tables for molecular pathology services.

Molecular pathology procedure, Level 9

Level descriptionMolecular pathology procedure, Level 9: examples include analysis of >50 exons in a single gene by DNA sequence analysis.

Example genes includedPolicy examples for Level 9 include full gene sequence listings such as COL4A3, COL4A5, and PKHD1 relevant to kidney disease and Alport/PKD testing.

Relevant CPT codeLevel 9 corresponds to CPT 81408 in the policy's molecular pathology code listings.

Unlisted molecular pathology procedure (CPT 81479)

Code and descriptionCPT 81479 — Unlisted molecular pathology procedure (used for molecular pathology tests not described by existing level codes).

Policy usage note81479 is listed in the policy's code tables for tests that cannot be captured by the specified molecular pathology level codes.

Full descriptionUnlisted molecular pathology procedure — full description as provided in the policy code section.