Diagnostic Tests for Impaired Renal Function
Serum creatinine and estimated glomerular filtration rate (eGFR) combined with urine albumin measurement are the cornerstone tests for diagnosing impaired renal function, with cystatin C-based eGFR recommended as an additional confirmatory test when available. 1
Primary Diagnostic Tests
First-Line Testing
Serum creatinine with eGFR calculation
- Recommended as the initial test for all patients 1
- Should be combined with urine albumin measurement for comprehensive assessment
- Limitations: affected by muscle mass, age, and nutritional status
Urine albumin-to-creatinine ratio (ACR)
- Essential complement to eGFR for complete kidney function assessment 1
- Detects early kidney damage before GFR decline
- Should be measured in random spot urine samples
Confirmatory Testing
- Cystatin C-based eGFR (eGFRcr-cys)
- Recommended when available to improve GFR staging accuracy 1
- Less influenced by muscle mass, age, and diabetes than creatinine
- Combined creatinine-cystatin C equations provide the least bias in GFR estimation
Specialized Diagnostic Tests
Biomarkers of Tubular Injury
Neutrophil gelatinase-associated lipocalin (NGAL)
- Useful for differentiating acute tubular necrosis (ATN) from other causes of AKI 1
- Urinary NGAL performs better than serum NGAL
- Cutoff value of 220-244 μg/g creatinine helps differentiate ATN from prerenal azotemia
- May predict 90-day mortality in certain conditions
Kidney injury molecule-1 (KIM-1)
- Biomarker upregulated by tubular injury 1
- Helps identify tubular damage
Other tubular injury markers
- N-acetyl-β-D-glucosaminidase
- α-glutathione S-transferase
- Interleukin-18
Functional Assessment Tests
Fractional excretion of sodium (FENa)
- Reflects sodium handling more accurately than urinary sodium alone 1
- FENa <1% suggests prerenal causes (including hepatorenal syndrome)
- FENa >1% suggests structural causes like ATN
- Limited specificity (only 14%) in patients with cirrhosis
Fractional excretion of urea (FEUrea)
- Better discriminator between functional and structural causes of AKI 1
- Not modified by diuretic use
- FEUrea <28.16% has sensitivity of 75% and specificity of 83% in separating hepatorenal syndrome from other causes
Imaging Studies
Renal ultrasound
- Evaluates kidney size, echogenicity, and structural abnormalities 1
- Small echogenic kidneys suggest chronic kidney disease
- Helps exclude post-renal obstruction
Cross-sectional imaging (CT/MRI)
Establishing Chronicity
To determine if kidney disease is chronic (present for >3 months), consider:
- Review of past GFR measurements
- Review of past albuminuria/proteinuria measurements
- Imaging findings (reduced kidney size, cortical thinning)
- Kidney pathological findings (fibrosis, atrophy)
- Medical history of conditions known to cause CKD 1
Clinical Application Algorithm
Initial screening:
- Measure both serum creatinine (with eGFR calculation) AND urine albumin-to-creatinine ratio 1
- If abnormal, repeat to confirm findings
If abnormalities confirmed:
- Add cystatin C measurement for more accurate GFR assessment 1
- Perform renal ultrasound to assess structure and exclude obstruction
For acute changes:
- Measure tubular biomarkers (NGAL, KIM-1) to differentiate between functional and structural causes 1
- Calculate FENa and FEUrea to help determine etiology
For suspected specific etiologies:
- Consider additional testing based on clinical presentation (e.g., renovascular imaging for suspected renovascular hypertension) 1
Important Caveats
- Single abnormal eGFR or ACR values should not be used to diagnose CKD - confirmation with repeat testing is essential 1
- Establishing chronicity (>3 months duration) is crucial for distinguishing CKD from AKI 1
- Biomarkers like NGAL are not yet widely available for clinical use in many settings 1
- Renal vein renin assays have high rates of false-positive and false-negative results and are not recommended as screening tests for renovascular hypertension 1
By systematically applying these diagnostic tests, clinicians can accurately identify impaired renal function, determine its chronicity, and guide appropriate management to improve patient outcomes.