Chronic kidney disease (CKD) is defined as abnormal kidney structure or function that is present >3 months and has health implications.¹ An estimated 35.5 million people in the United States have CKD, but about 90% are unaware that they are affected.² High-risk populations include individuals with hypertension, diabetes, or both, about 80% of whom may not have received guideline-concordant assessment.³ In addition, individuals are at higher risk of having CKD if they are obese, are of older age (≥65 years), had previous kidney damage, or have a family history of CKD.¹ Overall, CKD awareness is suboptimal and has not improved over the last 2 decades.⁴

Diagnostic criteria for CKD include an impaired glomerular filtration rate (GFR) or the presence of 1 or more other markers of kidney damage.¹ Markers of kidney damage include a histologic abnormality, structural abnormality, history of kidney transplantation, abnormal urine sediment, tubular disorder–caused electrolyte abnormality, or a urinary albumin level that is elevated above normal (albuminuria).

Identifying and treating CKD earlier in the disease continuum may prevent or delay adverse outcomes. Patients categorized as having high risk for end-stage renal disease are >10 times as likely as low-risk patients to have kidney failure within 5 years, yet about half remain unaware of their CKD.⁴ Knowledge of the presence of CKD may guide lifestyle changes that mitigate risk factors that are common to kidney- and cardiac-related disease.⁴ The risk of cardiovascular events and death increases with increasing CKD severity.³ Thus, monitoring and managing patients with CKD are also important for decreasing morbidity and mortality.⁵

Test availability

This Test Guide discusses the use of laboratory tests that may help identify CKD and monitor and manage disease progression, comorbidities, and complications. The tests discussed include measurement and estimation of GFR as well as markers of kidney damage. A list of applicable tests is provided in the Table. Test offerings range from health screenings for abnormal eGFR, proteinuria, and/or albuminuria, to tests for management of CKD and its comorbidities and complications. The information in this Test Guide is provided for informational purposes only and is not intended as medical advice. A physician’s test selection and interpretation, diagnosis, and patient management decisions should be based on their education, clinical expertise, and assessment of the patient.

Table: Tests Used in Diagnosis and Management of Chronic Kidney Disease^a,b

Test selection and interpretation

Measured GFR (mGFR)

Methods used to directly measure GFR have limitations and are usually reserved for specific circumstances, such as determining correct drug dosing in therapy that requires the most accurate assessment of kidney function, or when clinical decision-making is affected by having disparate results for estimated GFR (see “Estimated GFR” section).

The gold standard for mGFR is the inulin clearance method, but this test is difficult to perform in clinical practice. Direct measurement of creatinine clearance (test code 7943) and urea clearance (test code 7329[X]) can be used to assess residual kidney function, and the average of the 2 values is similar to GFR measured by inulin clearance (<20 mL/min/1.73 m2) in patients not on dialysis.⁶ However, this method of calculating GFR is prone to error due to inaccurate timing of blood sampling, incomplete urine collection over 24 hours, or overcollection of urine beyond 24 hours.^6,7

Estimated GFR (eGFR)

Given that direct measurement of GFR may be problematic, eGFR, using either creatinine- or cystatin C–based measurements or both, is most often used to diagnose CKD in clinical practice.

Creatinine-based eGFR

GFR is typically estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.⁴ The CKD-EPI equation uses serum-creatinine measurements (test code 375), patient age (≥18 years old), and patient sex; patient race (African versus non-African ancestry) is no longer considered.^8,9

Because it is influenced by certain health conditions, muscle mass, and diet, creatinine-based eGFR may be imprecise for certain individuals, such as pregnant women, patients with acute illness or serious comorbid conditions, people with extremes of muscle mass (eg, bodybuilders, patients with amputation, paraplegia, muscle-wasting disease, or a neuromuscular disorder), patients suffering from malnutrition, those with a vegetarian or low-meat diet, and those taking creatine dietary supplements. In addition, confirmation of GFR using another method may be required to avoid misclassification of some patients.

Cystatin C–based eGFR

Being less influenced by diet and muscle mass, cystatin C–based eGFR testing (test code 94588) is appropriate for patients in whom creatinine-based results may be misleading.⁵ The eGFR is calculated using cystatin C measurements calibrated to International Federation of Clinical Chemistry (IFCC) certified reference material, along with the patient’s age and sex, according to the CKD-EPI 2012 equation.¹⁰

A large meta-analysis has shown cystatin C–based eGFR improves risk classification for adverse outcomes (death, cardiovascular disease-related death, and end-stage renal disease) across diverse populations.¹¹ However, cystatin C–based eGFR may be more affected by some non-GFR determinants such as thyroid disorders, corticosteroid use, and smoking.⁷ In addition, associations of elevated cystatin C levels with diabetes, obesity, and inflammation have been reported.^11,12 Interpretation of eGFR is particularly challenging for patients with severe obesity (BMI >40); for this group, creatinine-based eGFR may be overestimated and the utility of cystatin C–based eGFR needs to be further investigated.¹³

Creatinine- plus cystatin C–based eGFR

When cystatin C–based eGFR is available, the Kidney Disease Improving Global Outcomes (KDIGO) guideline recommends using creatinine- plus cystatin C–based eGFR (test code 13581) as the most accurate estimate of GFR.¹ Wang et al found 30% of patients had discordant eGFR based on creatinine vs cystatin C alone; when creatinine- plus cystatin C–based eGFR was used, those with the largest discordance in values had estimates closer to mGFR.¹⁴ This eGFR is calculated using the CKD-EPI 2021 creatinine-cystatin C equation.⁹

Albuminuria and proteinuria

Albuminuria indicates increased glomerular permeability, a characteristic of CKD. The quantity of urine albumin is strongly correlated to risk of both kidney disease progression¹⁵ and cardiovascular disease¹and is assessed with either the urine albumin-creatinine ratio (ACR, test code 6517) or albumin excretion rate over 24 hours (test code 15281).

The urine ACR obtained from a random specimen, but preferably a “first morning sample,”¹ is more convenient and appropriate than a 24-hour specimen collection in the context of CKD. A urine ACR result of ≥30 mg/g (albumin excretion rate ≥30 mg/24 hours) is evidence of moderately increased albuminuria and ACR ≥300 mg/g (albumin excretion rate ≥300 mg/24 hours) is evidence of severely increased albuminuria relative to healthy young adults.¹

A carefully performed 24-hour specimen collection is more accurate than random urine ACR and appropriate in some circumstances (eg, in glomerular disease when small discrepancies between the random and 24-hour results may influence high-risk therapeutic dosing).¹⁶

Proteinuria may also indicate increased glomerular permeability and CKD, but it may have other causes that are characterized by elevated nonalbumin proteins.¹ In addition, measurement of urine protein is less precise and less sensitive than measuring albumin, making assessment of albuminuria preferable over proteinuria in evaluating CKD risk. Pediatric patients are an exception as they are more likely to have tubular proteinuria and elevated nonalbumin proteins than adults. These proteins reflect dysfunctional protein resorption in CKD. Consequently, KDIGO recommends testing for both protein-creatine ratio (test code 1715) and ACR in children.¹

GFR, ACR, and disease management

A GFR <60 mL/min/1.73 m2 for >3 months and/or urine ACR ≥30 mg/g for >3 months define CKD.¹ Combined, these test results provide a “Kidney Profile” (test code 39165) for diagnosing and managing CKD in patients based on their risk of disease progression (Figure 1).^1,17-19

Figure 1. Monitoring Chronic Kidney Disease Using eGFR and Urine Albumin-Creatinine Ratio (Kidney Profile, test code 39165): Frequency and Follow-up

KDIGO provides guidance for CKD screening and disease management based on eGFR and ACR values presented in Figure 1. Screening may be provided in a primary care or non-nephrology medical speciality setting with recommended referral to specialist kidney care for specific individuals for

• Planning and preparation for kidney replacement therapy if eGFR <30 mL/min/1.73 m2 
• Further evaluation and management if ACR ≥300 mg/g in combination with hematuria or ACR consistently ≥700 mg/g

KDIGO also provides CKD treatment recommendations based, in part, on eGFR and ACR values presented in Figure 1 combined with patient characteristics including age; presence or absence of hypertension, diabetes, heart failure, or atrial fibrillation; and kidney transplantation or dialysis treatment status. Details are provided in the guideline.¹

In addition, using these results combined with patient demographics, the 5-year risk for end-stage renal disease can be calculated using the Kidney Failure Risk equation (KidneyFailureRisk.com).⁴ Worsening eGFR or ACR is also associated with a proportional increase in risk in the following 10 outcomes: all-cause mortality, cardiovascular mortality, kidney failure/replacement therapy, acute kidney injury, hospitalization, myocardial infarction, stroke, heart failure, atrial fibrillation, and peripheral artery disease.¹

eGFR-ACR testing has been incorporated into a panel for atherosclerotic cardiovascular disease (ASCVD) risk assessment (test code 92053). Approaches to monitoring cardiovascular disease risk, diabetes, and other comorbidities¹ and complications associated with the various stages of CKD are provided in Figure 2.⁵ Panels also supplement eGFR with tests for electrolytes and hepatic function, which are useful for monitoring CKD and comorbidities (see Table).

Figure 2. Testing for Comorbidities and Complications of Chronic Kidney Disease