Selected Kidney Function Tests
Customize your policy alerts
Sign up for Aetna Policy 0775 alerts
Get alerted when Policy 0775 changes without checking for updates manually.
Monitor payer policy activity
Defines coverage stance for a set of selected kidney function tests and assays (including which tests are considered experimental/investigational) for Aetna members and the clinical contexts in which they are addressed.
No material clinical or coverage changes in this revision.
Coverage Criteria and Evidence Summary
Experimental / Investigational
The following tests are considered experimental and investigational because their effectiveness has not been established:
Listed tests are considered experimental and investigational in the policy text.
Recommended approach for APOL1 genotyping (research/clinical practice suggestions)
Testing and use considered appropriate when ALL of the following are met (inferred from text):
Policy text advises prudence and limiting APOL1 testing to high-risk individuals who provide informed consent.
Based on randomized pilot study procedures and policy recommendation to pair testing with disclosure and CDS.
Evidence and performance summaries
Evidence-based findings and performance characteristics from cited studies
Summarizes cohort/survey data and the policy's call for additional research.
Based on Khan et al (2022) findings.
Derived from Chan et al and validation cohort performance metrics.
Reflects reported associations between risk stratification and downstream care.
Evidence-based coverage considerations
Coverage considerations based on evidence and stated limitations
Summarizes PromarkerD limitations and NICE conclusions.
Reflects Coresh et al and Ehrich et al study findings.
Based on verification/validation studies, device pilot trial and MB-102 physicochemical data.
Investigational / early clinical evidence
Summary of available evidence and status
Describes device verification, MB-102 analytic properties, and early human pilot trial status.
RenalVysion (Nephrocor) is a marketed urine-based “liquid biopsy” that combines urine cytopathology with urine chemistries (creatinine, protein, beta-2 microglobulin, microalbumin). However, there are no published studies demonstrating its performance for diagnosing or monitoring kidney disease and no professional society recommends its use for these indications. Randomized controlled studies comparing RenalVysion to standard approaches (proteinuria, hematuria, and eGFR measurement) are needed before it can be considered established for clinical use.
Routine screening of unselected populations with APOL1 genotyping or other investigational kidney-risk tests is not supported by the available evidence. The policy advises that testing be considered primarily for high-risk individuals (for example, persons with CKD or HIV) and only after an informed discussion of potential advantages and trade‑offs. This prudent, targeted approach reflects insufficient evidence to recommend population-level screening at this time.
Mayo Clinic Laboratories has stated that the currently available APOL1 genotype assay (“APOL1 Genotype, Varies”) is not useful for clinical management of individuals with APOL1 risk genotypes. This position underscores the limited current clinical utility of APOL1 genotyping outside selected research or high‑risk, counseled settings.
NaviDKD is a biomarker-based blood test intended to predict long-term diabetic kidney disease risk, but it has not been cleared by the U.S. Food and Drug Administration and there are no published peer‑reviewed studies demonstrating its effectiveness. Given the absence of external validation and regulatory clearance, NaviDKD is unsupported for routine coverage based on the current evidence presented in this document.
Multiple emerging tests (metabolite panels such as GFRNMR, biomarker panels like PromarkerD, and other proprietary algorithms) have not been validated across diverse racial/ethnic populations and clinical settings. The authors and reviews cited note limitations including homogeneous cohorts, limited sample sizes, storage/assay variability, and lack of demonstrated impact on clinical management or patient outcomes. Because generalizability and clinical utility have not been established, these tests remain investigational.
The transdermal GFR measurement system using the MB‑102 fluorescent tracer and the Brilliance (MediBeacon) device has been evaluated in early human pilot work and a completed clinical trial, but the findings have not been published. The provided text does not include any explicit policy coverage exclusions for this transdermal system in the sections reviewed.
Select novel biomarker assays and proprietary algorithm-based tests are listed as experimental and investigational in this policy and therefore considered not established for the indications addressed. Examples specifically named include KidneyIntelX, PromarkerD, NaviDKD, GFRNMR, APOL1 genotyping, RenalVysion, and the use of transdermal systems with pyrazine‑based fluorescent agents for GFR measurement.
There is insufficient evidence to support widespread APOL1 genotyping outside of targeted, informed testing in patients at higher risk (for example, those with CKD or HIV) who opt for testing after counseling. Guidance in the source emphasizes prudence given uncertain impact on outcomes, limited management interventions, and variable generalizability of existing data.
Certain candidate biomarker panels have demonstrated low incremental predictive power in validation studies. For example, analysis of a 17‑marker panel found that although several markers were associated with eGFR decline, their individual contribution beyond clinical predictors was small and overall predictive power was low — suggesting such panels are unlikely to be useful for routine clinical decision‑making without further development and validation.
The National Institute for Health and Care Excellence (NICE) review concluded there are key uncertainties about PromarkerD, noting limited evidence and a need for studies that demonstrate how test results lead to changes in management and improved patient outcomes. These unresolved questions imply PromarkerD currently has limited evidence and may be considered not medically necessary for routine use until stronger validation and outcome data are available.
The sections reviewed list multiple technologies as investigational or describe early-stage evidence, but they do not uniformly include explicit “not medically necessary” declarations for every technology discussed. For example, while several tests are labeled experimental/investigational, the text does not provide an explicit not‑medically‑necessary statement for the transdermal fluorescent GFR measurement within the provided chunks.
Codes, Risk Strata, and Score Cut-offs
| 0105U | Nephrology (chronic kidney disease), multiplex electrochemiluminescent immunoassay (ECLIA) of tumor necrosis factor receptor 1A, receptor superfamily 2 (TNFR1, TNFR2), and kidney injury molecule-1 (KIM-1) combined with longitudinal clinical data, including APOL1 genotype if available, and plasma (isolated fresh or frozen), algorithm reported as probability score for rapid kidney function decline (RKFD). |
| 0602T | Glomerular filtration rate (GFR) measurement(s), transdermal, including sensor placement and administration of a single dose of fluorescent pyrazine agent. |
| 0603T | Glomerular filtration rate (GFR) monitoring, transdermal, including sensor placement and administration of more than one dose of fluorescent pyrazine agent, each 24 hours. |
| 0259U | Nephrology (chronic kidney disease), nuclear magnetic resonance spectroscopy measurement of myo-inositol, valine, and creatinine, algorithmically combined with cystatin C (by immunoassay) and demographic data to determine estimated glomerular filtration rate (GFR), serum, quantitative (GFRNMR). |
| 0355U | APOL1 (apolipoprotein L1) (eg, chronic kidney disease), risk variants (G1, G2). |
| 0384U | Nephrology (chronic kidney disease), carboxymethyllysine, methylglyoxal hydroimidazolone, and carboxyethyl lysine by liquid chromatography with tandem mass spectrometry (LC-MS/MS) and HbA1c and estimated glomerular filtration rate (GFR), with risk score reported for predictive progression to high-stage kidney disease (NaviDKD/PromarkerD category). |
| 0385U | Nephrology (chronic kidney disease), apolipoprotein A4 (ApoA4), CD5 antigen-like (CD5L), and insulin-like growth factor binding protein 3 (IGFBP3) by enzyme-linked immunoassay (ELISA), plasma, algorithm combining results with HDL, estimated glomerular filtration rate (GFR) and clinical data reported as a risk score for developing diabetic kidney disease (PromarkerD). |
| I10 - I16.2 | Hypertensive diseases |
| N18.1 - N18.9 | Chronic kidney disease (CKD) |
| N19 | Unspecified kidney failure |
| N26.2 | Page kidney |
| R10.0 - R10.13 R10.30 - R10.33 R10.84 | Abdominal pain |
| R31.0 | Gross hematuria |
| R60.0 - R60.9 | Edema, not elsewhere classified |
| R94.4 | Abnormal results of kidney function studies |
| E11.00 - E11.9 | Type II diabetes |
| E11.21 - E11.29 | Type 2 diabetes mellitus with kidney complications |
Provider Actions, Prior Authorization, and Billing Guidance
Billing and Coding — Unsupported/Not Covered Test Codes
Certain novel renal tests listed in this policy are identified as experimental/investigational and CPT codes for these tests are not covered when billed for the indications in this CPB. When ordering or billing, providers should support medical necessity in the chart and ensure documentation aligns with the clinical indication.
- CPT codes listed in the policy (e.g., 0105U, 0259U, 0355U, 0384U, 0602T, 0603T, 0385U) are identified as NOT COVERED for the indications listed in this CPB.
- ICD-10 diagnosis codes noted in the policy (examples: I10–I16.2, N18.1–N18.9, N19, E11.00–E11.9, E11.21–E11.29) are referenced as not covered for the CPB-listed indications — confirm the applicable diagnosis supports testing before billing.
- If testing is pursued, document the clinical indication and supporting data (e.g., CKD stage, uACR, eGFR, diabetes status) in the medical record to justify medical necessity.
APOL1 Genotyping — Informed Consent and High‑Risk Testing Only
For APOL1 genotyping, testing is recommended only for high‑risk individuals after informed patient choice. Providers should obtain documented informed consent that includes discussion of benefits, limitations, potential psychosocial impact, and implications for treatment or future therapies.
- Limit APOL1 genotype testing to high‑risk patients (e.g., patients with CKD, HIV, or other indications described in the policy) who explicitly opt in after counseling.
- Document that the patient received counseling on test meaning, uncertainty about therapy changes, potential insurance/employment implications, and that testing was voluntary.
- If future APOL1‑targeted therapies become available, documentation should include rationale linking genotype to therapy selection.
Prior Authorization — Not Specified in Policy
The policy does not specify payer prior authorization requirements for APOL1 genotyping, KidneyIntelX, MediBeacon transdermal GFR measurement, or several other novel tests. Providers should verify current Aetna prior authorization policies and local medical management rules before ordering these tests.
- No explicit prior authorization instructions are provided in this policy section — check payer portals or medical policy guidance for any authorization requirements prior to testing.
- When prior authorization is not specified, submit supporting clinical documentation with claims to reduce denial risk (see billing/coding callout).
NaviDKD — Prior Authorization Likely / High Denial Risk
Some novel tests lacking FDA clearance or peer‑reviewed evidence (e.g., NaviDKD) are likely to require prior authorization and may be denied without robust clinical justification. Anticipate denials for tests with limited evidence of clinical utility.
- NaviDKD: not FDA‑cleared and no peer‑reviewed effectiveness data — expect prior authorization requirements and probable noncoverage without documented investigational/ research context.
- Provide detailed clinical rationale, prior therapy history, and any investigational protocol documentation if seeking coverage for NaviDKD.
PromarkerD and Similar Tests — Prior Authorization Likely; Evidence Uncertainty May Trigger Noncoverage
For PromarkerD and other prognostic protein‑biomarker panels, evidence uncertainty may prompt payers to require prior authorization or deny coverage. Use of these tests should be supported by documentation showing intended impact on management.
- PromarkerD: limited evidence and NICE-identified uncertainties — anticipate prior authorization requests to demonstrate how results will change management and improve outcomes.
- Document intended downstream actions (e.g., intensified monitoring, referral, medication changes) tied to test results when requesting authorization.
GFRNMR and Transdermal GFR Measurement — Stepwise Testing Expectation
Emerging metabolite‑panel GFR tests (GFRNMR) and transdermal MB‑102 approaches are at proof‑of‑concept or early clinical study stages and are not replacements for standard eGFR measures. Providers should expect stepwise testing expectations and limited coverage.
- GFRNMR: considered investigational; if used, expect it to be an adjunct or research tool rather than a substitute for standard serum creatinine/cystatin C eGFR assessment.
- Transdermal MB‑102 (MediBeacon): clinical trials completed but published outcomes limited; no explicit coverage or authorization guidance in this policy — verify payer rules before use.
- Document standard eGFR and uACR results alongside any experimental test when submitting for review.
Documentation and Clinical Data to Support Billing (uACR, eGFR, Intended Management)
Support the clinical indication in the medical record when billing for any of the investigational tests listed. The KidneyIntelX studies noted that availability of urine albumin‑to‑creatinine ratio (uACR) improves predictive performance; include uACR and eGFR data in documentation when applicable.
- Include contemporaneous uACR and eGFR values in the chart when ordering predictive tests (e.g., KidneyIntelX) because model performance depends on these inputs.
- If KidneyIntelX or similar tests are ordered, document how results would change clinical management (e.g., SGLT2 initiation, specialist referral) to support medical necessity.
- When billing investigational CPT codes, attach clinical notes, lab values, prior therapies, and informed consent (if genetic testing) to reduce denial risk.
No Explicit Authorization/Coverage Instruction — Confirm with Payer
Where the policy provides no explicit provider action or authorization rule for a given technology, contact Aetna medical policy or provider services for clarification and follow usual processes for investigational test review.
- If no coverage/authorization guidance is available in the policy, obtain pre‑service confirmation from the payer.
- Maintain clear documentation of attempts to obtain authorization and rationale for testing if performed under research or compassionate‑use contexts.
KidneyIntelX — Document Downstream Management Changes
KidneyIntelX results have been associated with downstream changes in care (increased SGLT2 inhibitor prescribing, referrals, and visit frequency). When using such tests, document intended and actual management changes to demonstrate clinical utility.
- Document baseline therapy and any medication changes (e.g., SGLT2 initiation), referrals, or monitoring frequency that occur after testing to support clinical utility.
- Include KidneyIntelX score and risk category in notes and link to specific management decisions when submitting prior authorization or appeal documentation.
Background and Scope
Chronic kidney disease (CKD) is common, often asymptomatic, and routinely detected by measurements of proteinuria, hematuria, and estimated GFR. Novel assays and devices are being developed to improve risk prediction and GFR assessment, but many lack peer‑reviewed evidence, regulatory clearance, or demonstrated impact on management. The policy highlights the need for randomized or well‑validated comparative studies before these novel approaches can be recommended for routine clinical use.
Definitions and Test Descriptions
Policy Revision History
Policy effective date established for Clinical Policy Bulletin No. 0775 (Selected Kidney Function Tests).
Policy underwent last review (documented as Last Review: 10/11/2023).
Next scheduled policy review date set (Next Review: 08/22/2024).
OpenPayer is powered by Trek Health's payer performance platform. Trek continuously ingests, validates, and normalizes Transparency in Coverage data alongside payer policies and other commercial payer data to create a structured payer intelligence foundation. OpenPayer uses this foundation to deliver personalized search results, dynamically generated policy pages, and tailored policy monitoring based on each user's payers, specialties, billing codes, and areas of interest. The same intelligence powers broader payer performance workflows, including reimbursement benchmarking, contract evaluation, payer negotiations, and financial decision-making.