Describe the relationship between creatinine clearance and serum creatinine. (60% of marks) What are the limitations in using serum creatinine to assess renal function in the critically ill? (40% of marks)

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College Answer

This was a straightforward question of core CICM material. Most candidates were able to describe the Fick equation as it related to clearance, and then relate it to Glomerular Filtration Rate (GFR). Formula relating GFR to serum creatinine were often quoted incorrectly, graphs poorly constructed and/or labelled and many answers were very superficially answered. 
Better candidates were able to relate the graph to functional nephron loss and hence serum creatinine. The non-linear relationship between nephron mass (and function) and the serum creatinine was poorly appreciated by many. The nature of the variability of creatinine production with age, sex, ethnicity etc. was often omitted, as were the factors involved in the variability in an ICU patient.

Discussion

  • Serum creatinine (Scr is a small molecule, a product of muscle metabolism, which is eliminated only by glomerular filtration and tubular secretion
  • Creatinine clearance is the volume of plasma cleared of creatinine per unit time
    • It can be measured by 24 -hour creatinine collection and calculated from the equation CLcr = Ucr / Scr  where Ucr  is the amount of creatinine excreted via the urine
    • It can be estimated using a predictive equation such as Cockcroft-Gault formula, which estimates the Ucr on the basis of age and body weight
  • Relationship between serum creatinine and creatinine clearance:
    • Both creatinine clearance and the serum creatinine can be used as a surrogate measure of the glomerular filtration rate
    • Serum creatinine increases as renal function decreases
    • This relationship is non-linear:
      relationship of glomerular filration and serum creatinine
      i.e. significant changes in glomerular filtration can occur before this is reflected in the serum creatinine
  • Limitations of serum creatinine as a biomarker of renal function:
    • In general:
      • It increases with dietary protein consumption
      • It decreases with fasting and vegetarian diet
      • Tubular secretion is affected by drugs (eg. cimetidine)
      • Scr takes time to accumulate (may not reflect severity of ARF)
    • In the critically ill:
      • Large fluid resuscitation volumes can dilute the Scr, giving the appearance of improving renal function
      • Extracorporeal circuits (eg. CRRT and ECMO) can mask a raised creatinine by diluting, dialysing or adsorbing this substance
  • Limitation of estimated creatinine clearance:
    • It an estimate of creatinine clearance, not the GFR
    • It relies on the incorporation of age, sex, ethnicity and other factors for its accuracy
    • It is unreliable in demographic extremes, eg. extremes of age, weight, muscle mass and muscle metabolism
    • The level of inaccuracy increases with extremes of renal function. 

References

Shemesh, Ovadia, et al. "Limitations of creatinine as a filtration marker in glomerulopathic patients." Kidney Int 28.5 (1985): 830-838

Delanaye, Pierre, Etienne Cavalier, and Hans Pottel. "Serum creatinine: not so simple!." Nephron 136.4 (2017): 302-308.

Perrone, Ronald D., Nicolaos E. Madias, and Andrew S. Levey. "Serum creatinine as an index of renal function: new insights into old concepts." Clinical chemistry 38.10 (1992): 1933-1953.

Bleiler, Roberta E., and Harold P. Schedl. "Creatinine excretion: variability and relationships to diet and body size." The Journal of laboratory and clinical medicine 59.6 (1962): 945-955.

Mayersohn, Michael, KENNETH A. Conrad, and R. A. M. A. N. U. J. Achari. "The influence of a cooked meat meal on creatinine plasma concentration and creatinine clearance." British journal of clinical pharmacology 15.2 (1983): 227-230.

Pottel, Hans, et al. "Establishing age/sex related serum creatinine reference intervals from hospital laboratory data based on different statistical methods." Clinica chimica acta 396.1-2 (2008): 49-55.

Bauer, John H., Charles S. Brooks, and Rebecca N. Burch. "Clinical appraisal of creatinine clearance as a measurement of glomerular filtration rate." American Journal of Kidney Diseases 2.3 (1982): 337-346.

Cockcroft, Donald W., and Henry Gault. "Prediction of creatinine clearance from serum creatinine." Nephron 16.1 (1976): 31-41.