High creatinine

Creatinine is derived mainly from muscle metabolism

• proportional to muscle mass
• virtually all excreted by the kidneys
• usually produced at a more steady rate for a given individual compared to urea
• plasma creatinine is used as a measure of renal function.

Creatinine levels may be raised secondary to various factors:

• renal impairment/failure
• destruction of muscle
• high dietary intake of meat
• hypothyroidism
• Afro-Caribbeans race - higher average muscle mass in Afro-Caribbean
• increase in musculature (e.g. bodybuilding) - related to increased muscle mass ± increased protein intake
• drugs
  • testosterone therapy
  • e.g. cimetidine, trimethoprim, sulphamethoxazole, fibric acid derivatives - reduced tubular secretion of creatinine (1,2)
  • e.g. somecephalosporins - interference with alkaline picrate assay for creatinine
  • e.g. corticosteroids and vitamin D metabolites - probably modify the production rate and the release of creatinine (2)
• artifactual e.g. diabetic ketoacidosis (3)

Levels may be reduced secondary to various factors:

• increasing age - age-related decline in muscle mass
• females - reduced muscle mass
• malnutrition/ muscle wasting/ amputation - reduced muscle mass ± reduced protein intake
• vegetarian diet - decrease in creatinine generation
• hyperthyroidism (4)

Notes:

• plasma creatinine is not a sensitive marker for changes in GFR when renal function is near normal, or high. Indeed, people may lose 50% of normal GFR and have a borderline high creatinine, eg 150 mcmol/L

Reference:

1. Stein A (Consultant Nephrologist, University Hospitals Coventry and Warwickshire). Lecture (6/12/06): eGFR as a basis for the CKD guidelines.
2. Andreev E et al. A rise in plasma creatinine that is not a sign of renal failure: which drugs can be responsible? J Intern Med. 1999 Sep;246(3):247-52
3. Molitch ME et al. Spurious serum creatinine elevations in ketoacidosis.Ann Intern Med. 1980 Aug;93(2):280-1
4. Manetti L et al. Thyroid function differently affects serum cystatin C and creatinine concentrations.J Endocrinol Invest. 2005 Apr;28(4):346-9.