Question 1(p.2)

College Answer

It was expected candidates would describe that both these are surrogate measures for
Glomerular filtration rate. Credit was given for clear definitions, formula and normal values
(such as plasma clearance is the volume of plasma cleared per unit time). It was expected
candidates could explain that serum creatinine results from a balance of creatinine produced
and excreted and hence the slow response time and limitations for its use because of changes
in both production and excretion.
Extra credit was given for appreciating the non linear relationship between changes in serum
creatinine and creatinine clearance and that significant changes in glomerular filtration can
occur before this is reflected in the serum creatinine. Comment on the problems of dilution
with acute changes in fluid balance and that tubular secretion of creatinine can occur when
the serum creatinine concentration is high both gained extra marks.
Syllabus D1 2
Reference Ganong 22nd edition 699-728

Discussion

• Serum creatinine (S_cr)  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 CL_cr = U_cr / S_cr  where U_cr  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 U_cr 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:
    
    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)
    • S_cr takes time to accumulate (may not immediately 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. 

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.