Does creatinine (a waste product) affect kidney function?

Creatinine is a Marker of Kidney Function, Not a Cause of Kidney Dysfunction

Creatinine does not affect kidney function; it is merely a waste product that serves as a marker of kidney function. Serum creatinine is widely used to estimate glomerular filtration rate (GFR), but it is not itself a cause of kidney damage or dysfunction 1.

Understanding Creatinine and Kidney Function

What is Creatinine?

• Creatinine is a product of normal muscle turnover and metabolism
• It is freely filtered by the glomerulus, making it a useful marker of filtration function
• It does not directly impact kidney physiology or cause kidney damage

Limitations of Creatinine as a Kidney Function Marker

Despite its widespread use, creatinine has several important limitations:

1. Non-linear relationship with GFR:

   • GFR can fall significantly below normal with little or no increase in serum creatinine 1
   • This creates a "blind spot" where significant kidney dysfunction may be present despite normal-appearing creatinine levels

2. Influenced by non-renal factors:

   • Age, sex, race, muscle mass, diet, medications
   • Body size and total body volume
   • Muscle metabolism and protein intake 1

3. Delayed response to kidney injury:

   • Takes time to accumulate after kidney function declines
   • May not reflect acute changes in kidney function promptly 2

Clinical Implications

Proper Use of Creatinine Measurements

The guidelines recommend:

1. Use estimated GFR rather than creatinine alone:

   • Laboratories should use serum creatinine to compute GFR estimates using prediction equations 1
   • For adults, the MDRD equation or CKD-EPI equations are recommended
   • For children, the Schwartz or Counahan-Barratt equations are appropriate 1

2. Focus on trends rather than absolute values:

   • The trend in creatinine is often more important than the absolute value
   • A rising creatinine (e.g., from 100 to 200 μmol/L over 6 months) is more concerning than a stable elevated level 1

3. Consider context and other markers:

   • In dehydration, creatinine may rise due to reduced renal perfusion without actual kidney damage 3
   • The BUN/creatinine ratio typically increases (>20:1) in dehydration 3

Common Pitfalls to Avoid

1. Misinterpreting creatinine levels in CKD:

   • The same absolute reduction in kidney function produces different percentage changes in creatinine based on baseline function
   • After a 90% reduction in creatinine clearance, the rise in creatinine is 246% with normal baseline function but only 47% in stage 4 CKD 2

2. Relying solely on creatinine for diagnosis:

   • Serum creatinine alone should not be used to estimate kidney function level 1
   • There is no compelling evidence that initiation of dialysis based solely on measurement of kidney function leads to improvement in clinical outcomes 1

3. Confusing creatinine supplements with endogenous creatinine:

   • Creatine supplements may transiently increase serum creatinine without affecting actual kidney function 4, 5
   • This can lead to overdiagnosis of kidney disease

Conclusion

Creatinine is a valuable but imperfect marker of kidney function that does not itself affect kidney function. For accurate assessment of kidney health, clinicians should use estimated GFR based on prediction equations rather than creatinine alone, monitor trends over time, and consider the full clinical context when interpreting results.