Creatine Case Study

Case Study


Learning Goals /
Concept Map

Creatine and Related Compounds


Amino Acids

Creatine in the Body


Creatine-Creatinine Equilibrium

Creatine Test for Kidney Function


Regulation and Ethics

Amine & Nitrile Chemistry

Laboratory Synthesis

Chemical Analysis

Creatine-Phosphocreatine Equilibrium

Uses & Side Effects

Creatinine Test for Kidney Function

Creatinine, the purported final breakdown product of creatine catabolism[1], is primarily (90-95%) filtered by the kidney’s glomeruli, with the remaining 5-10% secreted by the kidney’s distal tubule[2].  As a result, creatinine levels in the blood and urine are often used to evaluate kidney function.  As kidney function declines, the amount of creatinine found in the blood increases because the rate at which the kidneys remove the creatinine from the blood decreases[1].  Let’s learn more about the importance of the kidneys and the evaluation of kidney function.

Kidney Function

The kidneys are two bean-shaped organs that are located near the middle of the back, just below the rib cage.

Healthy kidneys remove waste and excess fluid from the blood while returning nutrients to the blood.  This occurs at the nephrons where the glomerular membrane, which separates the blood vessels from the tubule, allows the waste products and excess fluid to pass into the tubule while keeping blood cells and protein in the bloodstream.  The waste products and excess fluid eventually exit the kidneys by way of the ureters to the bladder where they are excreted through the urethra as urine.  By removing excess fluid from the blood, the kidneys maintain a constant water volume and consequently regulate blood pressure.  The kidneys also maintain the concentrations of various ions in the body, thereby helping to maintain both the acid/base concentration in the blood and calcium levels in the body.  Finally, the kidneys are vital in stimulating red blood cell production[3,4,5].
Tests for Kidney Function
Clearly, optimal kidney function is vital for good health, and it is important to have methods for evaluating whether the kidneys are functioning properly.  As we have seen, creatinine excretion is primarily due to filtration by the kidneys[2], so levels of creatinine in the blood and urine are good indicators of renal function[6].  Consequently, physicians use the serum creatinine, urine creatinine, and creatinine clearance tests described below.
Serum (Blood) Creatinine Test
The serum creatinine test is a blood test.  This test helps to determine whether kidney function has diminished because healthy kidneys normally remove waste products, such as creatinine, from the blood and eliminate them in the urine.  Therefore, when blood creatinine levels increase, it is an indication that kidney function is decreasing.  In general, when the serum creatinine level doubles, the kidney filtration rate has decreased by half [7].  However, it is important to establish a normal blood creatinine level prior to administering a serum creatinine test because normal levels of blood creatinine vary due to age, sex, and muscle mass[6,7].  In addition, creatinine levels also change during pregnancy because the kidney filtration rate increases, resulting in a decrease in the serum creatinine level[7].  An abnormal increase in serum creatinine levels may indicate a variety of renal disorders[1,7]
Urine Creatinine Test
In contrast, the urine creatinine test measures the amount of creatinine excreted in the urine by the kidneys.  Urine samples are often collected over a 24-hour period and compared to serum creatinine levels, as described below. This test is used to detect muscle damage or degeneration, as well as high protein food intake, among other conditions[8].
Creatinine Clearance Test
The serum creatinine test and the urine creatinine test are combined when performing a creatinine clearance test.  Creatinine clearance is defined by the equation below[1]:

When the kidneys start to fail, they are less effective at removing creatinine—the end product of creatine metabolism—from the body.  Therefore, the concentration of creatinine in the blood increases, and the creatinine clearance decreases[1].  An abnormal creatinine clearance test may indicate a variety of conditions, including dehydration, shock, cancer, congestive heart failure, and renal failure (both acute and chronic)[9].
Effect of Creatine Supplementation on Creatinine Excretion
As we have seen, creatine is converted irreversibly into creatinine in the body and is then excreted in the urine by the kidneys.  We might expect that increased creatine levels from supplementation would lead to stress on the kidneys and higher levels of urinary creatinine.  However, different studies have produced conflicting results.  Some researchers have reported that short-term creatine supplementation (over a five-day period) leads to increased urinary creatinine levels that correspond to the elevated levels of creatine in muscle; these elevated urinary creatinine levels return to normal once creatine intake ends[10].  However, others have reported that short-term creatine supplementation leads to increased levels of creatine in the urine but no change in creatinine levels[11].  A review of the literature has suggested that creatine supplementation—both short- and long-term—has a minimal effect on creatinine clearance and kidney function in healthy young adults but that further research is needed on older adults and those with impaired kidney function[12].  Of course, as we have seen with the second case study, individual differences can cause people to react differently to creatine supplementation.


[1] Wyss, Markus; Kaddurah-Daouk, Rima. “Creatine and Creatinine Metabolism.” Physiol. Rev., 2000, 80(3), 1107-1213.
[2] Graves, John W. “Diagnosis and Management of Chronic Kidney Disease.” Mayo Clinic Proc., 2008, 83(9), 1064-1069.
[3] Moore, Keith L.; Dalley, Arthur F. Clinically Oriented Anatomy, 4th ed. Lippincott Williams & Wilkins: New York, 1999; pp 279-280.
[4] Guyton, Arthur C.; Hall, John E. Textbook of Medical Physiology, 9th ed. Saunders: Philadelphia, 1996; pp 298-316.
[5] “How Your Kidneys Work.” HowStuffWorks. (accessed Dec 2009).
[6] Peters, John P.; Van Slyke, Donald D. “Creatine and Creatinine,” in Quantitative Clinical Chemistry: Interpretations. The Williams & Wilkins Company: Baltimore, 1946; Vol. 1, Ch. 12, pp 897-936.
[7] “Creatinine test.” Gale Encyclopedia of Medicine, Gale Research. Updated Apr 2001. (accessed Dec 2009).
[8] “Creatinine – urine.” Medline Plus, National Institutes of Health, Bethesda, MD. Updated Aug 2009. (accessed Dec 2009).
[9] “Creatinine clearance.” Medline Plus, National Institutes of Health, Bethesda, MD. Updated Aug 2009. (accessed Dec 2009).
[10] Hultman, E.; Soderland, K.; Timmons, J. A.; Cederblad, G.; Greenhaff, P. L. “Muscle Creatine Loading in Man.” J. Appl. Physiol., 1996, 81, 232-237.
[11] Burke, Darren G.; Smith-Palmer, Truis; Holt, Laurence E.; Head, Brian; Chilibeck, Philip D. “The Effect of 7 Days of Creatine Supplementation on 24-Hour Urinary Creatine Excretion.” J. Strength Cond. Res., 2001, 15(1), 59-62.
[12] Pline, Kurt A.; Smith, Curtis L. “The Effect of Creatine Intake on Renal Function.” Ann. Pharmacotherapy, 2005, 39(6), 1093-1096.