Renal function tests
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Renal Function Tests
Renal function tests (RFTs) assess the ability of the kidneys to filter waste, maintain fluid/electrolyte balance, concentrate urine, and handle various solutes. They are categorized into glomerular function tests, tubular function tests, and additional blood/urine markers.
1. Glomerular Function Tests
Serum Creatinine
- End product of skeletal muscle creatine metabolism; excreted entirely by the kidneys.
- Normal: 0.8-1.2 mg/dL in adults; 0.4-0.8 mg/dL in young children; 0.5-1.0 mg/dL in pregnancy.
- Remains within normal range until approximately 50% of renal function is lost - this is the "creatinine blind spot."
- Unlike BUN, it is not significantly influenced by dietary intake.
- Measured classically by the Jaffe reaction (alkaline picrate + creatinine). False elevations occur with cephalosporins, ketones, glucose, ascorbic acid.
Glomerular Filtration Rate (GFR) and Its Estimation
Normal GFR is approximately 125 mL/min (or 90-110 mL/min on a 24h creatinine clearance).
The graph below illustrates the exponential rise of serum creatinine and BUN as GFR falls:
Note how both markers remain near-normal until GFR drops to ~50%, then rise steeply.
Three key GFR estimation formulas:
| Formula | Key Features | Limitations |
|---|---|---|
| Cockcroft-Gault | Uses age, weight, sex, serum Cr. Multiply by 0.85 for females. | Overestimates in obese patients |
| MDRD | Widely used; validated in CKD with GFR <60. Not reliable for GFR >60 mL/min/1.73 m² | Not validated in pregnancy, children, acutely ill |
| CKD-EPI | Uses creatinine, age, sex, race. More accurate at higher GFR values. Best predictor of ESRD risk and cardiovascular/all-cause mortality | Currently preferred formula |
Cockcroft-Gault formula:
Creatinine clearance (mL/min) = [(140 - age) × lean body weight (kg)] / [plasma Cr (mg/dL) × 72] Multiply by 0.85 for women.
Endogenous Creatinine Clearance (24-hour):
ClCr = (UCr × V) / (PCr × time in minutes)
- Normal: 90-110 mL/min (standardized: 70-140 mL/min)
- Requires a timed (usually 24-hour) urine collection plus a serum creatinine.
- Most accurate clinical measure without using exogenous markers.
Blood Urea Nitrogen (BUN)
- Urea = primary metabolite of protein catabolism; freely filtered and partially reabsorbed.
- Normal: 5-25 mg/dL.
- BUN is NOT elevated until ~75% of renal function is lost (less sensitive than creatinine).
- Non-renal factors affecting BUN:
| Elevated BUN | Decreased BUN |
|---|---|
| Reduced circulating volume (prerenal azotemia) | Liver disease |
| Catabolic states (GI bleeding, corticosteroids) | Malnutrition |
| High-protein diet | Sickle cell anemia |
| Tetracycline | SIADH |
BUN : Creatinine Ratio
- Normal: ~10:1
- Elevated (20:1 to 40:1): Dehydration, bilateral urinary obstruction, urinary extravasation (prerenal azotemia)
- Normal or low: Intrinsic renal disease, liver disease, overhydration
Cystatin C
- Produced by nearly all nucleated cells; freely filtered, completely reabsorbed by the proximal tubule.
- Less influenced by muscle mass, sex, or nutrition compared to creatinine.
- Superior to creatinine as a predictor of cardiovascular mortality.
- An early indicator of evolving chronic kidney disease.
- Increasingly used to calculate eGFR (CKD-EPI cystatin C equation available).
2. Tubular Function Tests
Urine Specific Gravity
- A direct index of the kidney's tubular concentrating ability.
- Normal range: 1.002-1.030.
- In diminished renal function, concentrating power progressively decreases until specific gravity becomes fixed at 1.006-1.010 (isosthenuria).
- Diluting ability (down to SG 1.002-1.004) is preserved much longer.
- Osmolality is a more precise measure: concentrated urine = ~1050 mOsm/kg (SG 1.030); fixed at plasma level = ~290 mOsm/kg (SG 1.010) = significant renal disease.
Urine Protein / Microalbuminuria
- Normal proteinuria: <150 mg/day (mainly Tamm-Horsfall protein).
- Dipstick: most sensitive to albumin; lower detection limit ~15 mg/dL.
- Microalbumin assay: detects as little as 0.3 mg/dL - sensitive marker of glomerular dysfunction.
- Urine beta-2-microglobulin and lysozyme: markers of tubular dysfunction.
Urine Glucose (Glycosuria)
- Glucose is freely filtered and reabsorbed entirely in the proximal tubule.
- Glycosuria occurs when tubular reabsorptive capacity is exceeded (diabetes mellitus) or tubular dysfunction lowers the reabsorption threshold (renal glycosuria).
3. Commonly Ordered Renal Panel (Reference Ranges)
| Test | Reference Range | Units |
|---|---|---|
| Blood urea nitrogen | 5-25 | mg/dL |
| Creatinine | 0.5-1.5 | mg/dL |
| Sodium | 133-147 | mmol/L |
| Potassium | 3.2-5.2 | mmol/L |
| Chloride | 94-110 | mmol/L |
| Bicarbonate (CO2) | 22-32 | mmol/L |
| Uric acid | 2.5-7.5 | mg/dL |
| Calcium | 8.5-10.5 | mg/dL |
| Phosphorus | 2.2-4.2 | mg/dL |
| Urine pH | 4.5-8.0 | - |
| Urine specific gravity | 1.002-1.030 | - |
| Urine RBC | 0-3 | /HPF |
| Urine WBC | 0-5 | /HPF |
| Urine casts | 0-2 | /LPF |
4. Novel Biomarkers
Beyond creatinine and cystatin C, several newer markers show promise for early/acute kidney injury (AKI) detection:
- KIM-1 (kidney injury molecule-1)
- NGAL (neutrophil gelatinase-associated lipocalin)
- IL-18 (interleukin-18)
- N-acetyl-beta-D-glucosaminidase (NAG)
- Uromodulin
- MicroRNA
These are especially relevant in perioperative settings where creatinine may take hours to days to reflect GFR changes.
5. GFR Staging and Clinical Significance
| % Normal GFR | Stage | Clinical Features |
|---|---|---|
| >50% | Mild insufficiency | Usually asymptomatic; BUN/Cr may be normal |
| ~30% | Moderate insufficiency | Biochemical changes; nocturia, anemia, Ca/P abnormalities |
| <30% | Severe insufficiency | Uremia: acidemia, volume overload, neurologic/cardiac/respiratory manifestations |
| 5-10% | End-stage renal disease (ESRD) | Renal replacement therapy required |
6. Screening for Chronic Kidney Disease (CKD)
The National Kidney Foundation recommends annual screening for high-risk groups (diabetes, hypertension, family history):
- eGFR - the primary test
- Microalbuminuria - sensitive early marker
CKD is defined as:
- GFR <60 mL/min/1.73 m², OR
- Albuminuria for ≥3 consecutive months
Sources: Smith and Tanagho's General Urology, 19th Ed. | Miller's Anesthesia, 10th Ed. | Quick Compendium of Clinical Pathology, 5th Ed.
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