More accurate diagnosis and staging of CKD while assessing the risk of progression with eGFR blood tests

Estimated glomerular filtration rate (eGFR) blood tests are a key marker to help clinicians detect, stage, and risk-stratify chronic kidney disease (CKD). eGFR is usually assessed using serum creatinine (eGFRcr), but serum creatine may be influenced by muscle mass, dietary intake, hydration, age, and gender. Adding cystatin C (eGFRcr-cys) improves accuracy, as cystatin C is less influenced by these factors. Using both markers in the CKD-EPI 2021 combined equation (eGFRcr-cys) offers the most accurate GFR estimation for clinical decision yielding a more accurate estimate of GFR and guiding accurate clinical decisions. 

In this article:

Clinical challenge | Why it matters | Ordering recommendations | Interpreting test results | Next steps | Supporting resources

Clinical challenge: When to use the combined eGFRcr-cys blood test

2024 KDIGO CKD guidelines recommend using eGFRcr-cys in clinical situations when eGFRcr is less accurate and GFR affects clinical decision-making. This includes individuals with¹

• A CKD stage of 3A or greater (eGFR < 60)
• An elevated uACR (uACR ≥ 30 mg/dL)
• A high- or low-meat diet
• Extremes of body mass

In these situations, cystatin C is a clinically useful complement to creatinine when serum creatinine may not be reliable and a higher precision in eGFR is needed.²

Why it matters: Improve accuracy of CKD staging and assessment of progression risk

More accurate CKD staging

The combined eGFRcr-cys equation is a more precise estimate of GFR than using either creatinine or cystatin C alone. Using both markers in the CKD-EPI 2021 combined equation (eGFRcr-cys) offers the most accurate GFR estimation for clinical decision-making. 

eGFR discordance prediction of kidney failure, cardiovascular events, and mortality

Discordance between creatinine-based and cystatin C–based eGFR is associated with adverse outcomes. In the Chronic Kidney Disease Prognosis Consortium, 11% of outpatient participants had a cystatin C–based eGFR that was ≥30% lower than their creatinine-based eGFR, and this discordance was associated with higher rates of all-cause mortality, cardiovascular events, and kidney failure.³

This insight can be considered a risk signal that can help clinicians determine CKD stage and treatment plans, while also guiding risk-factor management and follow-up care for patients.

Ordering recommendations: Combined eGFRcr-cys blood tests

In addition to the traditional Kidney Profile, Quest Diagnostics offers the KDIGO-recommended Estimated Glomerular Filtration Rate (eGFR) with Creatinine and Cystatin C test eGFRcr-cys to accurately stage CKD in patients when eGFR using serum creatinine alone may be unreliable.

Recommended test: Estimated Glomerular Filtration Rate (eGFR) with Creatinine and Cystatin C

Estimated Glomerular Filtration Rate (eGFR) with Creatinine and Cystatin C

• Test code: 13581
• CPT® code: 82565, 82610*

KDIGO guidelines recommend eGFRcr-cys in clinical situations when eGFRcr is potentially less accurate. This includes individuals with

• CKD stage of 3A or greater (eGFR < 60)
• Elevated uACR (uACR ≥ 30 mg/dL)
• High- or low-meat diet
• Extremes of body mass

Related tests

Kidney Profile

The Quest Kidney Profile includes eGFR and uACR tests, enabling earlier CKD detection with a single test code.

• Test code: 39165
• CPT codes: 82043, 82565, 82570

Components include Creatinine [375] and Albumin, Random Urine with Creatinine [6517].

Note: Each of the component tests may also be ordered individually.  

Cystatin C with Glomerular Filtration Rate, Estimated (eGFR)

• Test code: 34588
• CPT code: 82610*

Creatinine

• Test code: 375
• CPT code: 82565

Laboratory Testing for Chronic Kidney Disease Diagnosis and Management (multiple tests)

Testing for Comorbidities and Complications of Chronic Kidney Disease (multiple tests)

* CPT code is subject to a Medicare Limited Coverage Policy and may require a signed ABN when ordering.

Note: The CPT codes provided are based on American Medical Association guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Interpreting test results: Prognosis of CKD stages based on eGFRcr-cys blood test values

The primary use case of the eGFRcr-cys blood test is to appropriately stage a patient’s CKD diagnosis. Higher levels of eGFR indicate earlier stages of CKD, while lower levels point to higher stages. Refer to the following chart to match the test results to the likely CKD stage, from stage 1 to end-stage renal disease.^a

Recognizing eGFR discordance

When reviewing test results, providers should take note when eGFRcys levels are ≥30% lower than eGFRcr. This discordance can be due to inflammation, hypothyroidism, hyperthyroidism, steroid therapy, obesity, smoking, and diabetes, and should prompt further monitoring as it is associated with significantly higher rates of kidney failure, cardiovascular events, and mortality. 

Next steps based on CKD stage

Once you have an eGFRcr-cys blood test result, use it to tighten both staging and risk-based management. The stage of the patient’s CKD will inform care and treatment, but next steps generally include the following 6:

• Stage 1: Refer patient to a nephrologist and focus on monitoring kidney function over time and managing underlying conditions, such as diabetes.
• Stage 2: Target risk reduction through lifestyle modifications to protect kidney function and help slow the damage from CKD.
• Stage 3: Slow progression and manage emerging complications (such as anemia, hyperkalemia, bone mineral disorders, and/or metabolic acidosis and protein-energy wasting) through medications and healthy lifestyle changes to help prevent or delay advancing to later stages.
• Stage 4: Prepare the patient for possible kidney replacement and aggressive complication management through medication.
• Stage 5: Engage therapy options such as dialysis or kidney transplant to help the patient survive once the kidneys have failed or are close to failure.

Additionally, for patients with clinically meaningful eGFR discordance, treat the result as an indicator of high risk, as this pattern is associated with higher rates of kidney failure, cardiovascular events, and mortality.³

Supporting resources