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The clinical content and references are curated and reviewed by myself; however, AI was used to assist in organizing, paraphrasing, and formatting the information presented.
Quick Reference
  • Normal Range: Males 0.7-1.3 mg/dL; Females 0.6-1.1 mg/dL
  • Critical Values: >10 mg/dL or rapid rise >0.5 mg/dL/day
  • Primary Use: Assessment of kidney function and GFR estimation
  • Sample Type: Serum (venous blood)
  • AKI Criteria: Rise of ≥0.3 mg/dL in 48h or ≥1.5x baseline in 7 days
  • Key Point: More specific than BUN; doesn't rise until ~50% GFR lost
  • Important: Affected by muscle mass, diet, and certain medications (trimethoprim, cimetidine)

Test Description

What is Creatinine?

Serum creatinine is a waste product produced from the normal breakdown of muscle tissue and creatine phosphate during muscle metabolism.

Creatinine and Kidney Function

Creatinine is an excellent endogenous marker of glomerular filtration rate (GFR) because:

  • Freely filtered: Passes through glomeruli without restriction
  • Minimally reabsorbed: Little to no reabsorption by renal tubules
  • Minimally secreted: Only small amounts secreted by tubules
  • Steady production: Produced at a relatively constant rate (dependent on muscle mass)

Under steady-state conditions, serum creatinine levels inversely reflect kidney function:

  • Normal kidney function: Efficient creatinine clearance keeps serum levels low
  • Declining kidney function: Decreased creatinine clearance causes serum levels to rise

Physiological Production

Creatinine is formed in muscle from the non-enzymatic conversion of creatine and phosphocreatine. Daily production is relatively constant and proportional to muscle mass:

  • Adult males: Produce approximately 20-25 mg/kg/day
  • Adult females: Produce approximately 15-20 mg/kg/day
  • Elderly: Lower production due to decreased muscle mass
  • Athletes: Higher baseline due to increased muscle mass
Normal Ranges
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Population Normal Range (mg/dL) SI Units (μmol/L)
Adult Males 0.7-1.3 62-115
Adult Females 0.6-1.1 53-97
Children (2-12 years) 0.3-0.7 27-62
Adolescents (13-17 years) 0.5-1.0 44-88
Elderly (>65 years) 0.6-1.2 53-106
Pregnancy 0.4-0.9 35-80
Important Considerations:
  • Normal creatinine does NOT rule out kidney disease (can be normal until GFR drops below 50%)
  • Creatinine rises exponentially as GFR declines (doubling of creatinine = ~50% loss of kidney function)
  • Individual baselines vary significantly based on muscle mass, age, sex, and ethnicity
  • Small changes in creatinine may represent significant changes in kidney function
Clinical Significance

Elevated Creatinine (Azotemia)

Elevated serum creatinine indicates impaired kidney function or increased creatinine production:

Renal Causes (Most Common)

  • Acute Kidney Injury (AKI): Rapid rise in creatinine (≥0.3 mg/dL increase within 48 hours or ≥1.5x baseline within 7 days)
  • Chronic Kidney Disease (CKD): Sustained elevation over ≥3 months
  • Glomerular diseases: Glomerulonephritis, nephrotic syndrome
  • Tubular diseases: Acute tubular necrosis (ATN), interstitial nephritis
  • Vascular diseases: Renal artery stenosis, hypertensive nephropathy
  • Obstructive uropathy: Bilateral obstruction (stones, BPH, tumors)

Prerenal Causes (Decreased Renal Perfusion)

  • Volume depletion: Dehydration, hemorrhage, excessive diuresis
  • Decreased cardiac output: Heart failure, cardiogenic shock
  • Hypotension: Septic shock, distributive shock
  • Renal artery stenosis: Bilateral or solitary kidney
  • Hepatorenal syndrome: Advanced liver disease

Postrenal Causes (Obstruction)

  • Bilateral ureteral obstruction: Stones, blood clots, tumors
  • Bladder outlet obstruction: BPH, neurogenic bladder, stricture
  • Single functioning kidney: Any unilateral obstruction

Decreased Creatinine

Low creatinine is less clinically significant but may indicate:

  • Decreased muscle mass: Malnutrition, cachexia, muscular dystrophy
  • Liver disease: Severe cirrhosis (decreased creatine synthesis)
  • Pregnancy: Increased GFR and expanded volume
  • Advanced age: Sarcopenia and muscle wasting
  • Prolonged immobilization: Muscle atrophy
Acute Kidney Injury (AKI) Criteria

The KDIGO (Kidney Disease: Improving Global Outcomes) definition of AKI is based on creatinine changes:

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Stage Serum Creatinine Criteria Urine Output Criteria
Stage 1 1.5-1.9x baseline OR ≥0.3 mg/dL increase <0.5 mL/kg/h for 6-12 hours
Stage 2 2.0-2.9x baseline <0.5 mL/kg/h for ≥12 hours
Stage 3 3.0x baseline OR ≥4.0 mg/dL OR initiation of RRT <0.3 mL/kg/h for ≥24 hours OR anuria ≥12 hours
AKI Clinical Pearls:
  • Creatinine lags behind actual kidney injury by 24-48 hours (not real-time)
  • In rapidly progressive AKI, creatinine may underestimate severity initially
  • Baseline creatinine may be unknown in many ED patients (assume 0.8-1.0 mg/dL if unknown)
  • Small absolute changes (0.3 mg/dL) are clinically significant in AKI diagnosis
Chronic Kidney Disease (CKD) Staging

CKD is staged primarily by eGFR (estimated glomerular filtration rate), which is calculated using serum creatinine. While creatinine alone doesn't define CKD stages, it inversely correlates with eGFR:

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CKD Stage eGFR (mL/min/1.73m²) Approximate Creatinine* Description
Stage 1 ≥90 <1.2 mg/dL Normal GFR with kidney damage
Stage 2 60-89 ~1.2-1.6 mg/dL Mild reduction in GFR
Stage 3a 45-59 ~1.6-2.0 mg/dL Mild-moderate reduction
Stage 3b 30-44 ~2.0-3.0 mg/dL Moderate-severe reduction
Stage 4 15-29 ~3.0-6.0 mg/dL Severe reduction
Stage 5 <15 >6.0 mg/dL Kidney failure (ESRD)

*Approximate creatinine values vary significantly based on age, sex, race, and muscle mass

Estimated GFR (eGFR) Calculation

Serum creatinine is used to calculate eGFR, which provides a more accurate assessment of kidney function than creatinine alone. The most commonly used equations are:

CKD-EPI Equation (2021)

Current Gold Standard (Race-Free)

eGFR = 142 × min(SCr/κ, 1)α × max(SCr/κ, 1)-1.200 × 0.9938Age × [1.012 if female]

Where: SCr = serum creatinine (mg/dL), κ = 0.7 (females) or 0.9 (males), α = -0.241 (females) or -0.302 (males)

MDRD Equation (Legacy)

Older Equation (Less Accurate)

eGFR = 175 × SCr-1.154 × Age-0.203 × [0.742 if female]

eGFR Calculation Pearls

  • CKD-EPI is more accurate than MDRD, especially at higher GFR values
  • 2021 CKD-EPI removed race coefficient due to lack of biological basis
  • eGFR is automatically reported by most labs when creatinine is ordered
  • eGFR may be inaccurate in extremes of body composition (very muscular, amputees, malnutrition)
Creatinine Clearance (CrCl)

Creatinine clearance can be measured using 24-hour urine collection or estimated using formulas:

Cockcroft-Gault Equation

Estimated Creatinine Clearance

CrCl = [(140 - Age) × Weight (kg)] / (72 × SCr) × [0.85 if female]

The Cockcroft-Gault equation estimates creatinine clearance and is commonly used for medication dosing adjustments (especially in pharmacology), while eGFR (CKD-EPI) is preferred for CKD diagnosis and staging.

CrCl vs eGFR:
  • CrCl (Cockcroft-Gault): Used for drug dosing, not normalized to body surface area
  • eGFR (CKD-EPI): Used for CKD staging, normalized to 1.73m² body surface area
  • The two values are NOT interchangeable
  • Use CrCl for medication dosing per package inserts; use eGFR for CKD diagnosis
Interfering Factors

Factors Increasing Creatinine

  • Increased muscle mass: Athletes, bodybuilders (higher baseline)
  • Dietary intake: High protein intake, cooked meat (especially red meat)
  • Medications: Trimethoprim, cimetidine, fenofibrate (block tubular secretion)
  • Rhabdomyolysis: Massive muscle breakdown releases creatinine
  • Ketoacidosis: Acetoacetate interferes with Jaffe method
  • Dehydration: Hemoconcentration and prerenal azotemia

Factors Decreasing Creatinine

  • Decreased muscle mass: Elderly, amputees, malnutrition, muscular dystrophy
  • Pregnancy: Increased GFR and dilution
  • Severe liver disease: Decreased creatine synthesis
  • Vegetarian diet: Lower creatine intake
  • Prolonged immobilization: Muscle wasting

Medications Affecting Creatinine

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Medication Effect Mechanism
Trimethoprim ↑ Creatinine Blocks tubular secretion (no true GFR change)
Cimetidine ↑ Creatinine Blocks tubular secretion
Fenofibrate ↑ Creatinine Reduces creatinine production and secretion
NSAIDs ↑ Creatinine Prerenal (decreased renal perfusion)
ACE inhibitors/ARBs ↑ Creatinine Decreased efferent arteriole tone (functional, acceptable <30% rise)
Aminoglycosides ↑ Creatinine Direct nephrotoxicity
Clinical Pearls
"Creatinine doesn't rise until you've lost 50% of kidney function": This is a common teaching point. Due to the non-linear relationship between GFR and creatinine, significant kidney damage can occur before creatinine becomes abnormal.
Doubling of creatinine ≈ 50% loss of GFR: Each doubling represents approximately halving of kidney function.
Small changes matter in AKI: A rise of just 0.3 mg/dL meets KDIGO AKI criteria and is clinically significant. Don't dismiss small increases!
Creatinine lags behind acute injury: It takes 24-48 hours for creatinine to reflect changes in GFR. In acute settings, BUN may rise first.
Check baseline trends: A rise from 0.7 to 1.0 mg/dL may be more concerning than a stable 1.3 mg/dL in a muscular patient. Context matters!
Use with BUN:Cr ratio: Helps differentiate prerenal (>20:1) from intrinsic renal causes (10-20:1). This guides fluid management.
ACE-I/ARB "bump": Up to 30% increase in creatinine is acceptable after starting ACE inhibitors or ARBs (hemodynamic effect). Greater increases suggest bilateral renal artery stenosis - hold the medication!
Normal creatinine in elderly: May reflect decreased muscle mass rather than normal kidney function. Always calculate eGFR - don't be fooled by "normal" numbers.
Meat consumption effect: Eating cooked meat can transiently increase creatinine by 10-30% for 4-8 hours. Consider timing of last meal if values seem off.
Muscle injury releases creatinine: Rhabdomyolysis, seizures, or extreme exercise can elevate creatinine independent of kidney function. Check CK if suspected.
References
  1. Kratz, A., Ferraro, M., Sluss, P. M., & Lewandrowski, K. B. (2004). Laboratory reference values. New England Journal of Medicine, 351, 1548-1564.
  2. Lee, M. (Ed.). (2009). Basic skills in interpreting laboratory data. Ashp.
  3. Farinde, A. (2021). Lab values, normal adult: Laboratory reference ranges in healthy adults. Medscape.
  4. Nickson, C. (n.d.). Critical Care Compendium. Life in the Fast Lane • LITFL.
  5. Farkas, Josh MD. (2015). Table of Contents - EMCrit Project. EMCrit Project.
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