Kidney function test
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Kidney Function Tests (Renal Function Tests)
Kidney function tests assess the ability of the kidneys to filter waste, concentrate urine, and maintain fluid/electrolyte balance. They test both glomerular and tubular function.
1. Blood/Serum Tests
A. Serum Creatinine
| Source | Creatine/phosphocreatine breakdown in muscle |
| Normal (adult) | ~0.6–1.2 mg/dL (males); ~0.5–1.0 mg/dL (females) |
| Mechanism | Freely filtered at glomerulus; small amount secreted by tubules |
| Use | Most commonly used index of GFR |
Key limitations:
- Not renal-specific; heavily influenced by muscle mass, diet, drugs, fluid status
- A late marker — serum creatinine doesn't rise meaningfully until ~50% of GFR is lost (the "creatinine blind spot")
- A normal creatinine does not guarantee normal kidney function
- Changes within an individual are more sensitive than absolute values — the basis for AKI staging
"Although an increased serum creatinine generally equates with impaired kidney function, a normal serum creatinine does not necessarily equate with normal kidney function." — Tietz Textbook of Laboratory Medicine, 7th Ed.
B. Blood Urea Nitrogen (BUN) / Serum Urea
| Source | Urea cycle in the liver (catabolism of dietary/endogenous protein) |
| Normal BUN | 7–20 mg/dL |
| Normal serum urea | 2.5–6.7 mmol/L |
| Mechanism | Freely filtered; 40–70% passively reabsorbed by tubules |
Key points:
- BUN/Creatinine ratio >20:1 → suggests pre-renal cause (e.g., dehydration, low flow)
- Urea is flow-dependent: more back-diffusion with low urine flow states (e.g., pre-renal); less with high flow (e.g., pregnancy)
- Influenced by protein intake, GI bleeding, liver disease, hydration status — less specific than creatinine
C. BUN:Creatinine Ratio
| Ratio | Interpretation |
|---|---|
| 10–20 | Normal |
| >20 | Pre-renal azotemia (reduced renal perfusion) |
| <10 | Hepatic disease, malnutrition, rhabdomyolysis |
D. Serum Uric Acid
| Source | End product of purine catabolism (xanthine oxidase) |
| Normal | Males: 3.5–7.2 mg/dL; Females: 2.6–6.0 mg/dL |
| Mechanism | Filtered and partially reabsorbed; excreted in urine |
- Elevated in gout, renal failure, and conditions causing increased cell turnover
- During pregnancy, GFR increases → uric acid falls early; rises at term as tubular reabsorption increases
2. Glomerular Filtration Rate (GFR) — The Gold Standard
GFR is the primary measure of overall kidney function.
A. Inulin Clearance (True Gold Standard)
- Inulin: freely filtered, not secreted or reabsorbed
- Requires IV infusion + timed urine collection — impractical for routine use
- Normal GFR: ~100–120 mL/min/1.73 m²
B. Creatinine Clearance (CrCl)
Requires 24-hour urine collection:
$$\text{CrCl} = \frac{U_{Cr} \times V}{P_{Cr}} \times \frac{1.73}{\text{BSA}}$$
Where U = urine creatinine (mg/dL), V = urine volume rate (mL/min), P = plasma creatinine (mg/dL)
- Overestimates GFR by 10–40% because of tubular secretion of creatinine
- Inaccuracies due to incomplete urine collection
C. Estimated GFR (eGFR) — Most Widely Used Clinically
CKD-EPI equation (current standard):
- Uses serum creatinine, age, sex, race
- More accurate than older MDRD at GFR >60 mL/min/1.73 m²
Cockcroft-Gault formula:
$$\text{CrCl} = \frac{(140 - \text{age}) \times \text{weight (kg)}}{72 \times \text{serum creatinine (mg/dL)}} \times 0.85 \text{ (if female)}$$
GFR Staging (KDIGO):
| Stage | GFR (mL/min/1.73 m²) | Description |
|---|---|---|
| G1 | ≥90 | Normal |
| G2 | 60–89 | Mildly decreased |
| G3a | 45–59 | Mild–moderate |
| G3b | 30–44 | Moderate–severe |
| G4 | 15–29 | Severely decreased |
| G5 | <15 | Kidney failure |
D. Cystatin C
- Small protein produced by all nucleated cells, freely filtered, not secreted
- Better GFR estimate than creatinine in patients with abnormal muscle mass
- Less affected by gender, age, ethnicity, and diet
3. Urine Tests
A. Urinalysis (Dipstick + Microscopy)
| Component | Normal | Significance if Abnormal |
|---|---|---|
| Specific gravity | 1.003–1.030 | Low → impaired concentrating ability; isosthenuria (1.010) → tubular disease |
| pH | 4.5–8.0 | Fixed alkaline → RTA; alkaline + nitrites → urease-splitting UTI |
| Protein | Negative | Proteinuria → glomerular damage |
| Glucose | Negative | Glycosuria without hyperglycemia → proximal tubular disease |
| Blood/Hemoglobin | Negative | Hematuria → glomerulonephritis, stones, infection |
| Nitrites/Leukocyte esterase | Negative | UTI markers |
B. Proteinuria Quantification
| Method | Normal |
|---|---|
| Dipstick | Negative |
| Random urine protein/creatinine ratio | <0.2 |
| 24-hr urine protein | <150 mg/day |
| Albumin/creatinine ratio (ACR) | <30 mg/g (microalbuminuria: 30–300 mg/g) |
- Microalbuminuria is the earliest marker of diabetic nephropathy
- Proteinuria >3.5 g/day → nephrotic range
C. Urine Sodium & Fractional Excretion of Sodium (FeNa)
$$\text{FeNa} = \frac{U_{Na} \times P_{Cr}}{P_{Na} \times U_{Cr}} \times 100$$
| FeNa | Interpretation |
|---|---|
| <1% | Pre-renal AKI (kidneys avidly reabsorbing sodium) |
| >2% | Intrinsic renal (tubular) damage |
D. Urine Osmolality
- Normal: 50–1200 mOsm/kg
- Inability to concentrate urine (osmolality <300 in presence of dehydration) → tubular dysfunction or diabetes insipidus
E. Urine Creatinine & Electrolytes
- Used in clearance calculations
- Spot urine electrolytes help distinguish AKI subtypes
4. AKI Staging (KDIGO Classification)
| Stage | Serum Creatinine Criteria | Urine Output |
|---|---|---|
| 1 | Rise ≥0.3 mg/dL in 48h, or 1.5–1.9× baseline | <0.5 mL/kg/h for >6h |
| 2 | 2.0–2.9× baseline | <0.5 mL/kg/h for >12h |
| 3 | ≥3× baseline or ≥353 μmol/L or RRT initiated | <0.3 mL/kg/h for 24h or anuria for 12h |
5. Novel Biomarkers of AKI
| Marker | Significance |
|---|---|
| NGAL (neutrophil gelatinase-associated lipocalin) | Early tubular injury, rises 2–6h after AKI |
| KIM-1 (kidney injury molecule-1) | Proximal tubular injury |
| IL-18 | Ischemic AKI |
| Cystatin C | Earlier GFR change detection vs. creatinine |
Summary Table
| Test | What it Measures | Normal Value | Main Use |
|---|---|---|---|
| Serum creatinine | Glomerular filtration (indirect) | 0.6–1.2 mg/dL | Screening, AKI staging |
| BUN | Urea production + clearance | 7–20 mg/dL | Pre-renal vs. renal distinction |
| eGFR | Filtration rate | ≥90 mL/min/1.73 m² | CKD staging |
| CrCl (24h) | GFR estimate | 100–120 mL/min | Drug dosing |
| Urine protein/Cr ratio | Proteinuria | <0.2 | Glomerular disease |
| ACR | Microalbuminuria | <30 mg/g | Diabetic nephropathy screening |
| FeNa | Tubular Na handling | <1% pre-renal | AKI classification |
| Uric acid | Purine excretion | 3.5–7.2 mg/dL (M) | Gout, CKD |
| Cystatin C | GFR (muscle-independent) | Varies | Accurate eGFR |
Sources: Tietz Textbook of Laboratory Medicine, 7th Edition; Morgan and Mikhail's Clinical Anesthesiology, 7e; The Harriet Lane Handbook, 23rd Ed.
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