What laboratory tests are recommended for the diagnosis and management of Chronic Kidney Disease (CKD)?

Laboratory Testing for Chronic Kidney Disease

For CKD diagnosis and management, measure both serum creatinine with calculated eGFR and urine albumin-to-creatinine ratio (ACR) as your core laboratory tests, performed at least annually in all CKD patients, with more frequent monitoring based on disease severity. 1

Essential Initial Laboratory Tests

Primary Assessment

• Serum creatinine with eGFR calculation: Use the CKD-EPI equation for estimating GFR from creatinine (eGFRcr) as your initial assessment tool 1
• Urine albumin-to-creatinine ratio (ACR): Measure on a spot urine sample rather than 24-hour collections, as ACR is the preferred method for detecting and quantifying albuminuria 1, 2
• Repeat abnormal tests: Following incidental detection of elevated ACR, hematuria, or low eGFR, repeat within 3 months to confirm chronicity and establish CKD diagnosis 1

Enhanced Accuracy Testing

• Cystatin C measurement: Add cystatin C to calculate combined eGFRcr-cys in adults with eGFRcr 45-59 mL/min/1.73 m² who lack other markers of kidney damage, as this confirms CKD diagnosis in two-thirds of borderline cases 1
• Combined creatinine-cystatin C equation (eGFRcr-cys): Use this when greater accuracy is needed for clinical decision-making, particularly when creatinine-based estimates may be unreliable due to extremes of muscle mass, diet, or medications 1, 3

Monitoring Frequency by CKD Stage

The frequency of laboratory monitoring should escalate with disease severity 1, 2:

• CKD Stage 1-2 (eGFR ≥60): Annually 2
• CKD Stage 3a (eGFR 45-59): Every 6-12 months 1, 2
• CKD Stage 3b (eGFR 30-44): Every 6 months 1, 2
• CKD Stage 4 (eGFR 15-29): Every 3-5 months 1, 2
• CKD Stage 5 (eGFR <15): Every 1-3 months 1, 2

Increase monitoring frequency beyond these standards when initiating hemodynamically active medications, observing rapid eGFR decline, or detecting doubling of ACR 1, 2

Additional Laboratory Tests for CKD Complications

Mineral and Bone Metabolism

• Serum calcium and phosphate: Monitor when eGFR falls below 60 mL/min/1.73 m² to screen for metabolic bone disease 2
• Parathyroid hormone (PTH) and 25-hydroxyvitamin D: Measure when eGFR <60 mL/min/1.73 m² to assess for secondary hyperparathyroidism 2, 4

Electrolytes and Acid-Base

• Serum potassium: Monitor in all patients on ACE inhibitors, ARBs, or diuretics due to hyperkalemia or hypokalemia risk 2, 4
• Serum bicarbonate: Assess for metabolic acidosis, which requires correction to prevent CKD progression 2, 4, 5

Hematologic Parameters

• Complete blood count: Monitor for anemia, a common complication requiring evaluation and treatment 4, 5

Clinically Significant Changes Requiring Evaluation

Recognize these thresholds that exceed normal laboratory variability 1, 2:

• eGFR decline >20% on subsequent testing warrants investigation for causes of progression 1, 2
• eGFR decline >30% after initiating hemodynamically active therapies (ACE inhibitors, ARBs, SGLT2 inhibitors) requires evaluation, though initial declines ≤30% with SGLT2 inhibitors are expected and should not prompt discontinuation 1, 2
• Doubling of ACR on repeat testing exceeds laboratory variability and demands evaluation for progression 1, 2

Laboratory Quality and Reporting Standards

Creatinine Measurement

• Use enzymatic assays instead of Jaffe method, as the latter has interference from many drugs and substances 1
• Ensure creatinine assays are traceable to isotope-dilution mass spectrometry (IDMS) reference method 1, 6
• Process blood samples with appropriate timing to minimize variability 1

Albuminuria Reporting

• Laboratories should report ACR in addition to albumin concentration, not concentration alone 1
• Discontinue use of the term "microalbuminuria" in laboratory reports, as albuminuria exists on a continuum of risk 1
• Participate in external quality assessment schemes for both urine albumin and creatinine measurements 1

Point-of-Care Testing Considerations

Point-of-care devices may be used where laboratory access is limited, but must meet the same quality standards 1:

• Ensure POCT devices for creatinine generate eGFR using regionally consistent equations 1
• POCT devices for albuminuria should measure both albumin and creatinine to produce ACR 1
• Verify that POCT ACR devices detect ≥85% of patients with significant albuminuria (ACR ≥30 mg/g) 1

Common Pitfalls to Avoid

• Never rely on serum creatinine alone without calculating eGFR, as this leads to significant errors in assessing kidney function, particularly in elderly patients or those with altered muscle mass 3, 6
• Do not assume chronicity from a single abnormal eGFR or ACR, as this could represent acute kidney injury or acute kidney disease rather than CKD 1
• Recognize non-GFR determinants of creatinine including muscle mass, diet (particularly meat intake), and medications that affect tubular secretion 3
• Avoid using age-adjusted definitions of CKD, as there are no age-adjusted definitions for other chronic diseases like diabetes or hypertension 1

Risk Stratification Using Laboratory Results

Use validated risk equations incorporating both eGFR and ACR to estimate absolute risk of kidney failure in patients with CKD stages 3-5 1:

• 5-year kidney failure risk of 3-5%: Threshold for nephrology referral 1
• 2-year kidney failure risk >10%: Timing for multidisciplinary care 1
• 2-year kidney failure risk >40%: Initiate modality education and preparation for kidney replacement therapy 1