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Kidney Function Tests - Biochemistry
Sources: Harper's Illustrated Biochemistry 32nd Ed | Tietz Textbook of Laboratory Medicine 7th Ed | Goldman-Cecil Medicine | Harriet Lane Handbook 23rd Ed | Barash's Clinical Anesthesia 9th Ed | Morgan & Mikhail's Clinical Anesthesiology 7th Ed
Overview
Kidney function tests assess the ability of the kidneys to filter waste, concentrate urine, and maintain fluid/electrolyte balance. They are grouped into:
- Tests of Glomerular Function
- Tests of Tubular Function
- Urinalysis
1. URINALYSIS (First-Line Assessment)
A complete urinalysis is the first step in evaluating kidney function. It includes:
| Test | Normal Value | Clinical Significance |
|---|
| Appearance | Colorless to pale amber, clear | Dark/turbid = concentrated urine, infection, proteinuria |
| Specific gravity | 1.003 - 1.030 | Reflects concentrating ability; isosthenuria (1.010) = tubular disease |
| pH | 4.5 - 8 (avg 5-6) | Alkaline urine = UTI with urea-splitting organisms |
| Protein | < 150 mg/24 hr (< 30 mg albumin) | Proteinuria = glomerular disease |
| Glucose | Absent | Glycosuria without hyperglycemia = tubular dysfunction (Fanconi) |
| Ketones | Absent | Seen in DKA, starvation |
| Blood/Hb | Absent | Hematuria, hemoglobinuria |
| Nitrite | Absent | Gram-negative bacterial infection |
| Bilirubin/Urobilinogen | Absent / Trace | Liver disease indicators |
Dipstick ("Reagent Strip") Testing - a rapid point-of-care method. Automated readers reduce inter-operator variability. Timing of color change must be carefully monitored (30 seconds to 2 minutes depending on analyte).
2. TESTS OF GLOMERULAR FUNCTION
A. Serum Creatinine
- Source: Creatinine is the end product of creatine phosphate metabolism in skeletal muscle
- Normal values: ~0.6-1.2 mg/dL (men); ~0.5-1.0 mg/dL (women)
- A significant rise in serum creatinine only occurs after ~50% decline in GFR - making it a test of poor sensitivity for early renal disease
- Despite this limitation, it is the most widely used and practical filtration marker
- Why better than urea: Blood creatinine is not significantly affected by non-renal factors, making it a more specific indicator of renal function
(Harper's Biochemistry 32nd Ed, Tests of Kidney Function)
B. Blood Urea Nitrogen (BUN)
- Source: Urea is produced in the liver as the end product of protein catabolism (urea cycle)
- Normal BUN: ~10-20 mg/dL
- BUN:Creatinine ratio: Normally 10:1 to 20:1 (in mg/dL)
- Ratio > 20:1 → Prerenal azotemia (dehydration, cardiac failure, GI bleed)
- Ratio < 10:1 → Intrinsic renal disease, low protein intake, liver disease
- Limitations of BUN: Affected by many non-renal factors:
- Elevated by: high protein diet, GI bleeding, fever, corticosteroids, dehydration
- Decreased by: malnutrition, liver disease, SIADH
(Goldman-Cecil Medicine; Comprehensive Clinical Nephrology 7th Ed)
C. Serum Uric Acid
- End product of purine catabolism
- Elevated in renal failure and contributes to CKD progression
- Higher serum uric acid is a risk factor for CKD progression
- Can form uric acid crystals in acidic urine (visible on urinalysis)
D. Creatinine Clearance (CrCl) - Estimates GFR
Formula:
CrCl (mL/min) = [U × V] / P
Where:
-
U = urine creatinine concentration (mg/dL)
-
V = urine volume per minute (total volume ÷ 1440 min for 24-hr collection)
-
P = plasma creatinine concentration (mg/dL)
-
Normal GFR: ~120 ± 25 mL/min (men); ~95 ± 20 mL/min (women)
-
GFR declines ~10% per decade after age 30
-
CrCl slightly overestimates GFR because creatinine is also secreted by tubules
-
In children, corrected to body surface area: CrCl (mL/min/1.73 m²)
(Barash's Clinical Anesthesia 9e; Morgan & Mikhail's Clinical Anesthesiology 7e)
E. Estimated GFR (eGFR) - Predictive Formulas
Three commonly used equations:
| Formula | Variables Used | Best For |
|---|
| Cockcroft-Gault | Age, weight, sex, serum creatinine | Drug dosing |
| MDRD | Age, sex, race, serum creatinine | Stable CKD |
| CKD-EPI | Age, sex, race, serum creatinine | Higher GFR values; most accurate |
Cockcroft-Gault formula:
eGFR (mL/min) = (140 - age) × weight(kg) / (Cr × 72) × 0.85 (for females)
- MDRD underestimates GFR in patients with GFR > 60 mL/min/m²
- CKD-EPI is more accurate across a wider range and is currently preferred
(Barash's Clinical Anesthesia 9e)
F. Gold Standard - Inulin Clearance
- Inulin is an exogenous polysaccharide that is:
- Freely filtered at the glomerulus
- Neither reabsorbed nor secreted by tubules
- Excreted only in urine
- Requires intravenous infusion at constant rate - not practical for routine use
- Other gold standards: ⁵¹Cr-EDTA or ⁹⁹Tc-DTPA clearance (expensive, cumbersome)
G. Cystatin C
- A low-molecular-weight protein produced at a constant rate by all nucleated cells
- Accumulates in circulation with renal impairment
- Theoretical advantages over creatinine:
- Less affected by muscle mass, age, sex
- More sensitive early marker of GFR decline
- Not yet replaced creatinine in routine practice
(Miller's Anesthesia 10e; Brenner & Rector's The Kidney)
3. PROTEINURIA - Key Glomerular Marker
| Type | Amount | Significance |
|---|
| Normal | < 150 mg/24 hr total; < 30 mg albumin/24 hr | Below detection on routine tests |
| Microalbuminuria | 30-300 mg albumin/24 hr | Early marker of renal damage in diabetes mellitus |
| Macroalbuminuria/Proteinuria | > 300 mg/24 hr | Established nephropathy |
| Nephrotic-range proteinuria | > 3.5 g/24 hr | Nephrotic syndrome |
- Most common cause: loss of integrity of the glomerular basement membrane (glomerular proteinuria)
- Dominant protein in glomerular proteinuria = albumin
(Harper's Biochemistry 32nd Ed)
4. TESTS OF TUBULAR FUNCTION
A. Urine Concentrating Ability
- Tests vasopressin (ADH)-controlled water reabsorption in the distal tubule
- Water deprivation test: Urine osmolality should rise to > 800 mOsm/kg in normal kidneys
- Isosthenuria (specific gravity fixed at 1.010) = loss of concentrating/diluting ability = severe tubular damage
B. Urine Osmolality
- Reflects concentrating ability more accurately than specific gravity
- Normal urine osmolality: 50-1200 mOsm/kg (varies with hydration)
C. Tubular Maximum (Tm) Tests
- Measure maximum tubular reabsorptive/secretory capacity
- e.g., Tm for glucose = ~375 mg/min; renal threshold for glucose = ~180 mg/dL serum glucose
D. Fractional Excretion of Sodium (FeNa)
FeNa (%) = (urine Na × plasma Cr) / (plasma Na × urine Cr) × 100
| FeNa | Interpretation |
|---|
| < 1% | Prerenal azotemia (Na avidly reabsorbed) |
| > 2% | Intrinsic renal (ATN) or post-renal cause |
5. CKD CLASSIFICATION (Based on eGFR)
| Stage | GFR (mL/min/1.73 m²) | Description |
|---|
| G1 | ≥ 90 | Normal or high |
| G2 | 60-89 | Mildly decreased |
| G3a | 45-59 | Mild-moderate decrease |
| G3b | 30-44 | Moderate-severe decrease |
| G4 | 15-29 | Severely decreased |
| G5 | < 15 | Kidney failure (dialysis needed) |
- GFR < 60 mL/min = criteria for CKD
- GFR < 15 mL/min = uremic symptoms; may require dialysis
Quick Summary Table - Key Kidney Biochemistry Values
| Test | Normal Value | Significance if Elevated |
|---|
| Serum creatinine | 0.6-1.2 mg/dL (men) | Impaired GFR (rises after 50% loss of GFR) |
| BUN | 10-20 mg/dL | Azotemia; also elevated in dehydration, GI bleed |
| BUN:Creatinine ratio | 10:1 to 20:1 | >20 = prerenal; <10 = hepatic/malnutrition |
| GFR (normal) | 90-140 mL/min | <60 = CKD; <15 = kidney failure |
| Urine protein | <150 mg/24 hr | Proteinuria = glomerular disease |
| Microalbuminuria | 30-300 mg/24 hr | Early diabetic nephropathy |
| Urine specific gravity | 1.003-1.030 | Fixed at 1.010 = isosthenuria = tubular damage |