Understanding Creatinine and Kidney Function
Serum creatinine is an important but imperfect marker of kidney function that must be interpreted carefully, as it does not provide an accurate standalone assessment of glomerular filtration rate (GFR) and can significantly underestimate the severity of kidney dysfunction. 1
Relationship Between Creatinine and Kidney Function
What is Creatinine?
- Creatinine is an endogenous compound produced mainly from muscle catabolism and released into the blood
- Production is relatively stable in a given person, making its clearance useful for kidney function assessment
- Normal serum creatinine ranges:
- Men: 0.8-1.3 mg/dL (70-115 μmol/L)
- Women: 0.6-1.0 mg/dL (55-90 μmol/L) 1
Limitations of Serum Creatinine
- When serum creatinine significantly increases, GFR has already decreased by at least 40% 1
- Serum creatinine is affected by factors unrelated to kidney function:
- Muscle mass (lower in elderly, women, malnourished patients)
- Diet (protein intake)
- Age
- Sex
- Medications (e.g., trimethoprim can cause spuriously high levels) 1
- Creatinine does not increase linearly with declining GFR 1
- GFR can fall significantly below normal with little or no increase in serum creatinine 1
Better Assessment Methods
Estimated GFR (eGFR)
- eGFR should be used instead of serum creatinine alone 1
- Calculated using prediction equations that incorporate:
- Serum creatinine
- Age
- Sex
- Race
- Body size (in some equations) 1
- Common formulas:
- MDRD (Modification of Diet in Renal Disease) Study equation
- CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)
- Cockcroft-Gault equation 1
When to Use Alternative Methods
- For acute changes in renal function, serum creatinine should be used rather than eGFR 1
- Direct measurement of GFR may be necessary in:
- Extremes of age and body size
- Severe malnutrition or obesity
- Diseases of skeletal muscle
- Paraplegia or quadriplegia
- Vegetarian diet
- Rapidly changing kidney function 1
Classification of Kidney Function
Stages of Chronic Kidney Disease (CKD)
| Stage | Description | GFR (mL/min/1.73 m²) |
|---|---|---|
| 1 | Kidney damage with normal or increased GFR | ≥90 |
| 2 | Mild decrease in GFR | 60-89 |
| 3 | Moderate decrease in GFR | 30-59 |
| 4 | Severe decrease in GFR | 15-29 |
| 5 | Kidney failure | <15 or dialysis |
| [1] |
Clinical Implications
Monitoring Kidney Function
- Trend in creatinine is often more important than absolute value 1
- A rising creatinine from 100 to 200 μmol/L over 6 months is more concerning than stable creatinine at 220 μmol/L 1
- In patients with advanced liver disease or low muscle mass, standard creatinine-based methods may overestimate kidney function 2
Prognostic Value
- Baseline serum creatinine has significant prognostic value for mortality
- Patients with serum creatinine ≥1.7 mg/dL have more than three times higher 8-year mortality than those with lower levels 3
Best Practices for Clinical Use
Recommendations for Clinicians
- Never use serum creatinine alone to assess kidney function 1
- Use eGFR for routine assessment of kidney function
- Consider trends in creatinine rather than isolated values
- Be aware that "normal" creatinine levels may mask significant reductions in GFR
- Use alternative methods in patients with abnormally low muscle mass
Special Populations
- In elderly patients: creatinine may not reflect age-related decline in GFR due to concomitant decline in muscle mass 1
- In patients with cirrhosis: impaired hepatic production of creatine (precursor of creatinine) may lead to falsely low values 1
- In patients with heart failure: monitor renal function closely when initiating medications that affect kidney function 1
By understanding the relationship between creatinine and kidney function, clinicians can better interpret laboratory values, accurately assess renal function, and make appropriate clinical decisions to improve patient outcomes.