Chronic Kidney Disease: Laboratory Support of Diagnosis and Management
Chronic kidney disease (CKD) affects about 37 million people in the United States, with about 90% not knowing they have it.1 The disease affects kidney structure and function yet may have no signs or symptoms in its early stages. However, patients with CKD can progress to end-stage renal disease (ESRD) and the need for dialysis, and have a higher risk of cardiovascular events and death.2,3 As such, diagnosis of CKD and monitoring of kidney function in patients with CKD are important for decreasing morbidity and mortality.4
This article will discuss CKD, its risk factors and comorbidities, and how the laboratory can assist in diagnosis and management.
Scope of the Problem and Risk Factors for CKD
The National Kidney Foundation estimates that around 80 million persons in the United States are at risk for developing CKD,5 and the risk of cardiovascular events and death increases with increasing CKD severity.2 Patients at high risk for ESRD are more than 10 times as likely as low-risk patients to have kidney failure within 5 years, but about half of them are not aware they have CKD.3 Knowing an individual has CKD can help guide lifestyle changes that mitigate risk factors common to kidney- and cardiac-related disease (see Sidebar).3
Assessing Kidney Function and Damage
CKD is defined as an abnormality of kidney structure or function that is present for more than 3 months and can adversely affect health.6 The primary diagnostic criterion is a decreased glomerular filtration rate (GFR).6 CKD may also be diagnosed based on the presence of 1 or more other markers of kidney damage, such as histological abnormalities, structural abnormalities, history of kidney transplantation, abnormal urine sediment, tubular disorder-caused electrolyte abnormality, or an increased urinary albumin level (albuminuria).6
GFR and Kidney Function
GFR can be measured directly, but direct measurement methods are complicated and not suitable for use in general clinical practice.6 Hence, GFR is typically assessed using an estimated (eGFR) value calculated based on either serum creatinine or cystatin C levels:
- Creatinine-based eGFR is recommended for initial assessment of GFR, according to the Kidney Disease Improving Global Outcomes (KDIGO) 2012 international guideline.6 The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation7 is generally used to calculate the eGFR (See Sidebar).
- An eGFR based on serum creatinine level, however, is influenced by diet and muscle mass.7 Thus, results may not accurately reflect the true GFR in patients with serious comorbid conditions, individuals with extremes of muscle mass (eg, bodybuilders, patients who have had an amputation), patients who are malnourished or obese, persons who are vegetarians or are on a low-meat diet, people taking creatine dietary supplements, and pregnant women.
- Cystatin C-based eGFR uses serum cystatin C levels to calculate an eGFR and is therefore less influenced by diet and muscle mass.12
- An eGFR based on cystatin C has been shown to improve overall risk stratification for adverse outcomes, including cardiovascular disease-related death, ESRD, and all-cause mortality.13 On the other hand, a cystatin C-based eGFR may be more affected than creatinine-based eGFR by conditions such as thyroid disorders, corticosteroid use, smoking, diabetes, obesity, and inflammation.13-15
Given the above considerations, creatinine-based eGFR is recommended for patients who do not have contraindications.6 The KDIGO guideline recommends using cystatin C-based eGFR to confirm CKD when creatinine-based eGFR indicates a mild to moderately high risk of CKD progression (45 to 59 mL/min/1.73 m2) in a patient without albuminuria.6
Urine Albumin-Creatinine Ratio and Kidney Damage
The presence of albuminuria indicates increased glomerular permeability, which is a characteristic of CKD and an indication of kidney damage.6 Albuminuria is assessed with either the urine albumin-creatinine ratio (ACR) or albumin excretion rate over 24 hours.6
A urine ACR ≥30 mg/g (albumin excretion rate ≥30 mg/24 hours) is diagnostic of albuminuria (30 to 300 mg/g was formerly referred to as microalbuminuria, and >300 mg/g as macroalbuminuria).6
Proteinuria (urinary total protein-creatinine ratio ≥150 mg/g) may indicate increased glomerular permeability and CKD but can also be seen in other conditions (eg, myeloma).6
Management of CKD: eGFR and ACR
An eGFR <60 mL/min/1.73 m2 for >3 months and/or urine ACR ≥30 mg/g for >3 months indicates the presence of CKD.6 An eGFR and ACR provide a “kidney profile” recommended by the National Kidney Foundation for diagnosing and managing chronic kidney disease in at-risk patients.2,4,6,16 Importantly, the results are independent risk predictors of major adverse cardiovascular events (myocardial infarction or stroke).17
A summary of the frequency of monitoring CKD based on the risk of disease progression as assessed using eGFR and urine ACR (kidney profile) is available at
In addition, the Kidney Failure Risk equation (KidneyFailureRisk.com) uses ACR and eGFR to estimate the risk of persons developing CKD and progressing to ESRD.
CKD and COVID-19
Data are still accumulating on the relation between COVID-19 and CKD. However, research is showing that prior CKD can be associated with more severe COVID-19 disease and that COVID-19 can result in acute kidney injury.18,19