What laboratory tests are recommended for a patient suspected of having kidney failure, particularly those with a history of kidney disease, diabetes, or hypertension?

Laboratory Tests for Kidney Failure

Core Blood Tests

For any patient with suspected kidney failure, immediately order serum creatinine with eGFR calculation using the 2009 CKD-EPI equation, complete electrolyte panel, and blood urea nitrogen. 1, 2

• Serum creatinine is the primary marker and must be measured using an assay with calibration traceable to international standard reference materials 2, 3
• Estimated GFR (eGFR) should be calculated using the 2009 CKD-EPI equation rather than relying on serum creatinine alone 1, 4
• Blood urea nitrogen (BUN) helps calculate the BUN-to-creatinine ratio to differentiate prerenal, intrinsic renal, and postrenal causes 4, 3
• Complete electrolyte panel including sodium, potassium, chloride, calcium, phosphorus, magnesium, and bicarbonate to identify complications and guide management 4, 2, 3
• Complete blood count to evaluate for anemia and other hematologic abnormalities 1, 5

When Creatinine-Based eGFR May Be Inaccurate

• Cystatin C should be used as a confirmatory test in specific circumstances when eGFR based on serum creatinine is less accurate, such as extremes of muscle mass, malnutrition, or amputation 1, 2
• The combined creatinine-cystatin C equation provides improved accuracy in certain populations 2

Core Urine Tests

Obtain a first-morning spot urine sample for albumin-to-creatinine ratio (ACR) and perform urinalysis with microscopy. 1, 2

• Urine albumin-to-creatinine ratio (ACR) from an untimed spot urine specimen is the preferred method for detecting and quantifying proteinuria 1, 4

  • First-morning collections are optimal to avoid confounding from orthostatic proteinuria 1
  • Report as mg albumin/g creatinine with reference range ≤30 mg/g 1
  • Confirm persistent albuminuria by repeating in 2 of 3 tested samples if values exceed 30 mg/g 1

• Urinalysis with microscopy to detect cells, casts, and crystals that help differentiate causes of renal failure 2, 3, 5

  • Red blood cell casts suggest glomerulonephritis
  • White blood cell casts indicate interstitial nephritis or pyelonephritis
  • Muddy brown casts suggest acute tubular necrosis

• Fractional excretion of sodium (FENa) to differentiate prerenal from intrarenal causes 2, 6, 5

  • FENa <1% suggests prerenal azotemia
  • FENa >1% indicates intrinsic renal damage
  • Urine sodium concentration alone has high specificity (>85%) for prerenal AKI when <20 mEq/L 6

Imaging Studies

Renal ultrasound should be performed in most patients, particularly older men and those with unexplained kidney failure, to evaluate kidney size, echogenicity, and rule out obstruction. 1, 2, 3

• Unenhanced CT of the abdomen and pelvis may be useful for characterizing hydronephrosis and determining the level and cause of obstruction 1, 2
• Avoid iodinated contrast in acute kidney injury unless there is an overriding clinical question that cannot be answered with alternative imaging 1, 2

Interpretation Framework

GFR Categories for Risk Stratification

• G1: ≥90 mL/min/1.73m² (normal or high) 2, 3
• G2: 60-89 mL/min/1.73m² (mildly decreased) 2, 3
• G3a: 45-59 mL/min/1.73m² (mildly to moderately decreased) 2, 3
• G3b: 30-44 mL/min/1.73m² (moderately to severely decreased) 2, 3
• G4: 15-29 mL/min/1.73m² (severely decreased) 2, 3
• G5: <15 mL/min/1.73m² (kidney failure) 2, 3

Albuminuria Categories

• A1: <30 mg/g (normal to mildly increased) 1, 2, 3
• A2: 30-300 mg/g (moderately increased, formerly "microalbuminuria") 1, 2, 3
• A3: >300 mg/g (severely increased, formerly "macroalbuminuria") 1, 2, 3

Risk for progression and cardiovascular disease increases with lower GFR and higher albuminuria categories, and the increase is at least additive. 1

Confirming Chronicity vs. Acute Injury

Review past history and previous measurements to determine duration of kidney disease. 1

• If duration is ≥3 months, chronic kidney disease (CKD) is confirmed 1, 2
• If duration is <3 months or unclear, patients may have CKD, acute kidney injury (AKI), or both—repeat tests accordingly 1
• A single abnormal test result is insufficient for diagnosis of chronic kidney disease 2, 3

Additional Context-Specific Tests

For Patients on Specific Medications

• Serum potassium monitoring for patients on ACE inhibitors, ARBs, or diuretics due to risk of hyperkalemia or hypokalemia 4
• Recheck serum creatinine within 1-2 weeks after initiating or adjusting doses of ACE inhibitors, ARBs, or diuretics 4

For Suspected Glomerular Disease or Systemic Illness

• Complement levels (C3, C4), antinuclear antibodies, anti-GBM antibodies, ANCA panel may be indicated 1
• Serum and urine protein electrophoresis for suspected monoclonal gammopathy or multiple myeloma 3

For CKD Complications

• Parathyroid hormone (PTH) and phosphorus for patients with eGFR <60 mL/min/1.73m² to screen for mineral metabolism disorders 4

Critical Action Thresholds

Refer to nephrology immediately when: 4, 2

• eGFR <30 mL/min/1.73m² (Stage 4 or 5 CKD)
• Creatinine increase >50% from baseline or rapid eGFR decline suggesting acute-on-chronic kidney injury
• ACR >300 mg/g (severely increased albuminuria)
• Serum creatinine >2.5 mg/dL (>250 µmol/L)
• Unexplained hematuria with proteinuria

Monitoring Frequency After Initial Diagnosis

Tailor monitoring frequency to GFR and albuminuria categories: 4, 2, 3

• Stage 3 CKD (eGFR 30-59): recheck every 6-12 months 4
• Stage 4 CKD (eGFR 15-29): recheck every 3-5 months 4
• Stage 5 CKD (eGFR <15): recheck every 1-3 months 4
• More frequent monitoring for rapidly declining kidney function or higher albuminuria categories 2, 3

Important Caveats

• Certain medications (trimethoprim, cimetidine) and substances can interfere with creatinine measurements, affecting eGFR accuracy 2, 3
• Patients should refrain from vigorous exercise for 24 hours before urine sample collection to avoid false-positive proteinuria 1
• Normal-sized kidneys on imaging do not exclude chronic kidney disease, as renal size is initially preserved in diabetic nephropathy and infiltrative disorders 2
• In acute kidney injury superimposed on chronic kidney disease, interpreting results requires comparison to baseline values 2