Creatinine - Kresser Institute Membership Site

Marker Name: Creatinine

REFERENCE RANGES FOR CREATININE:

Laboratory reference range:
Male and female: 0.76–1.27 mg/dL

Functional reference range:
Male: 0.85–1.1 mg/dL
Female: 0.7 – 1.0 mg/dL

DESCRIPTION:

Creatinine is a soluble waste product of muscle catabolism. While creatinine has no known physiological action, measurement of creatinine in the blood and urine is a useful means of assessing kidney function. Since creatinine is formed at a relatively constant rate and is almost completely filtered by the kidneys, levels of the molecule in blood provide a reasonable estimate of glomerular filtration rate (GFR).¹

Adenosine triphosphate (ATP) is an important carrier of cellular energy in all human cells, but it is especially important in skeletal muscle cells. ATP utilization can change dramatically between muscle fibers at rest and during active contraction.² The creatine kinase enzyme in muscle fibers can use creatine phosphate to phosphorylate adenosine diphosphate (ADP), forming ATP.³ The eventual waste product is creatinine, which can be formed from either creatine or creatine phosphate.

Approximately 98 percent of endogenous creatinine comes from skeletal muscle.⁴ Creatinine is both created and excreted at a relatively constant rate under normal conditions. The urinary creatinine excretion rate is proportional to muscle mass; roughly one gram of creatinine is excreted every 24 hours for every 17 to 22 kilograms of muscle.^4,5 Creatinine is freely filtered in the kidneys by the glomerulus and is not reabsorbed, secreted, or metabolized by the nephron.⁶ As such, the serum creatinine concentration can be used to approximate the glomerular filtration rate—serum levels of creatinine rise as glomerular filtration rate decreases.⁷ GFR is even more precisely estimated by combining information about serum creatinine level, age, gender, and ethnicity of the patient.⁸

An elevated level of creatinine in the blood is called hypercreatininemia, though this term is rarely used clinically. Transient elevations in creatinine may be due to hypovolemia or dehydration, which occurs in the context of an elevated blood urea nitrogen (BUN) (e.g., prerenal azotemia).¹ Short-term elevations in serum creatinine may be due to an acute kidney issue such as acute interstitial nephritis, obstructive nephropathy, or acute tubular necrosis.⁹ Long-term elevations usually reflect chronic kidney disease, such as nephrosclerosis.⁹ Not all elevations in blood creatinine levels indicate problems with the kidneys. Rhabdomyolysis, for example, may increase creatinine levels in the blood by increasing release of creatinine from ruptured muscle cells. However, rhabdomyolysis can cause acute renal failure from increased urinary myoglobin.¹⁰ Certain medications may interfere with laboratory methods used to measure serum creatinine. Cefoxitin and flucytosine can spuriously increase serum creatinine levels if the laboratory uses the alkaline picrate method.¹¹ Moreover, acetoacetate produced during diabetic ketoacidosis can also erroneously increase creatinine levels measured by this method.¹¹

Abnormally low levels of serum creatinine could theoretically be due to abnormally increased glomerular filtration rate; however, this is not a clinically important issue in practical terms.¹² Low creatinine levels generally reflect reduced muscle mass and, by extension, decreased body-wide creatinine production by skeletal muscle.¹² Severe protein malnutrition and advanced liver disease may decrease blood creatinine levels.

Creatinine is routinely measured as part of the basic metabolic panel or complete metabolic panel.¹ Creatinine may also be measured as part of the creatinine clearance test, which will also include a measurement of creatinine in the urine.¹³ The gold standard creatinine clearance test is usually determined from a 24-hour urine collection.¹⁴

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:^9,11,12,15

Increased muscle mass
Dehydration/hypovolemia
Kidney diseases
- Nephrosclerosis
- Interstitial nephritis (acute and chronic)
- Prerenal azotemia
- Obstructive nephropathy
- Renal vascular disease
- Glomerulonephritis (acute or chronic)
- Pyelonephritis
- Acute tubular necrosis
- Interstitial nephritis
- End-stage renal disease
Ureteral obstruction
Rhabdomyolysis
Congestive heart failure
Hepatorenal syndrome
Thrombotic thrombocytopenic purpura
Shock
Drugs
- Trimethoprim
- Cimetidine
- Cobicistat

Low in:^12,16-18

Low muscle mass
Severe protein malnutrition
Advanced liver disease
Guillain-Barré syndrome

FUNCTIONAL RANGE INDICATIONS:

High in:

Strenuous exercise (especially weight lifting; creatinine is released during muscle breakdown)
Mild dehydration (BUN, hemoglobin, hematocrit, and red blood cells may also be elevated)
Enlarged prostate
Pregnancy
Many other pathological conditions involving muscle catabolism

Low in:

Decreased muscle mass (observed in the elderly and/or those with chronic illness)
Inadequate dietary protein intake (observed in vegetarians and vegans)
Impaired protein digestion
Impaired liver function (albumin and aminotransferases will also often be abnormal)

References: