Introduction
Renal health
Creatinine clearance (CrCl) rate
Creatinine test
Glomerular filtration rate (GFR)
Blood urea nitrogen)-to-creatinine ratio
Albumin-to-creatinine ratio
References
Further reading
Introduction
Creatinine is essentially a metabolite of creatine phosphate, a compound that acts as a source of energy in muscle. In other words, creatinine is a waste product generated from the normal wear and tear of muscles of the human body. Creatinine is present in the bloodstream (serum creatinine) and is filtered out of the body at a constant rate by the kidneys (glomerulus and the proximal tubule).
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Renal health
A creatinine test would therefore be indicative of kidney function. Creatinine is a useful indicator of renal health because it is excreted in the urine as an unchanged and easily measured by-product of muscle metabolism. In a healthy kidney, little or no creatinine is reabsorbed, whereas, in kidney disease, the creatinine concentration in the blood may increase.
The creatinine concentration in the urine and blood can therefore be used to calculate the rate at which the kidney is clearing creatinine – the creatinine clearance (CrCl) rate that is indicative of the kidneys' performance in removing the waste products from the blood. The CrCl rate is correlated with the glomerular filtration rate (GFR) for the clinical assessment of renal function.
Creatinine clearance (CrCl) rate
The typical range for CrCl rate for men, 19 to 75 years old is 77 to 160 mL/min/body surface area (BSA). The typical ranges, by age, for creatinine clearance in women aged 18 to 29 years, 30 to 39 years, 40 to 49 years, 50 to 59 years, and 60 to 72 years are 78 to 161 mL/min/BSA, 72 to 154 mL/min/BSA, 67 to 146 mL/min/BSA, 62 to 139 mL/min/BSA, and 56 to 131 mL/min/BSA. Results lower than the typical range for a particular age group may indicate poor kidney function or conditions that affect blood flow to the kidneys.
In the muscles, creatine is converted to phosphocreatine in a reversible reaction with adenosine triphosphate (ATP), mediated by creatine kinase. When ATP is depleted during exercise, the ADP so formed is rephosphorylated in a reaction with the phosphocreatine. Phosphocreatine and creatine cyclize nonenzymatically to form creatinine, which is then excreted by renal glomeruli and not reabsorbed by tubules. Therefore, the amount of creatinine excreted in the urine (creatinine clearance) is related to the amount of phosphocreatine present in the body and is indicative of lean muscle mass.
The serum creatinine content varies with age, sex, race, gender, and body size. Men tend to have higher creatinine levels than women due to their greater skeletal mass. The typical range for serum creatinine for adult men is 0.74 to 1.35 mg/dL and for women is 0.59 to 1.04 mg/dL. During kidney dysfunction, serum creatinine concentrations may increase to 1000 mM, and values above 140 mM indicate that renal function needs further assessment. Values above 530 mM are indicative of severe renal problems. In urine, 0.5 to 3.3 g per day of creatinine is normally excreted.
Creatinine test
A creatinine test may be advised by a doctor or healthcare provider to (i) make a diagnosis if you have signs or symptoms of kidney disease, (ii) to screen for kidney disease if you have diabetes, high blood pressure, or other conditions that increase the risk of kidney disease, (iii) to monitor kidney disease treatment or progression, (iv) to monitor for side effects of drugs that may include kidney damage or altered kidney function or (v) to monitor the function of a transplanted kidney.
Decreased excretion of creatinine also indicates muscle degeneration, and creatinuria can indicate a muscle-wasting disease such as muscular dystrophy or a result of creatine supplementation. In general, many athletes, bodybuilders, and young males take creatine as a supplement to increase their muscle bulk and endurance during resistance training. They typically start with a five-day loading phase of 20 g creatine daily.
What is creatine and how does it work?
Much of the creatine is excreted in the urine in the first five hours after ingestion. Creatine is found at low concentrations in the plasma and higher concentrations in erythrocytes. Erythrocyte creatine concentrations decrease with the age of the cell and thus can be used to determine cell age. The role of creatine in erythrocytes has not been defined, but the concentration can be increased by creatine supplementation.
A standard blood test is used to measure creatinine levels in your blood (serum creatinine), although overnight fasting may be required before the test. For a creatinine urine test, a 24-hour urine sample is usually collected in containers. For either of the tests, an individual may need to avoid eating meat (since creatine can also be obtained from eating meat) for a certain period before the test and stop creatine supplementation for a certain period.
Creatinine can be analyzed in automatic colorimetric analyzers using the Jaffe method, by gas chromatography-mass spectrometry (GC–MS) after derivatization, or simultaneously with creatine by high-performance liquid chromatography (HPLC), HPLC-MS or capillary electrophoresis (CE). Enzyme-based methods for both creatine and creatinine are used for colorimetric analyses and in biosensors with a variety of transducers. Creatine can be converted to creatinine to be analyzed by the Jaffe reaction. Fluorescence analyses and methods involving partial least squares (PLS) with ultraviolet (UV), infrared (IR), or near-infrared (NIR) spectra can also be used.
Glomerular filtration rate (GFR)
Creatinine levels vary among individuals, and therefore, the glomerular filtration rate (GFR) is preferred for evaluating renal function. The formula for calculating GFR takes into account the serum creatinine count and other factors, such as age and sex. GFR below 60 for ≥3 months or GFR above 60 with signs of kidney damage such as proteinuria are indicative of renal dysfunction.
GFR is a useful indicator of kidney function, although calculations using the CrCl rate will give an overestimation of the GFR in cases of severe renal dysfunction, because the proximal tubule secretes excess amounts of creatinine, thereby increasing the overall amount of total creatinine cleared. Drugs that can be used to minimize this excess secretion include cimetidine and trimethoprim and these can therefore be used to improve the accuracy of eGFR.
Blood urea nitrogen)-to-creatinine ratio
An alternative to using CrCl calculations and eGFR to indicate renal function is to interpret the plasma concentration of creatinine along with the blood urea level. A test called the BUN (blood urea nitrogen)-to-creatinine ratio is therefore also used as a measure of kidney health, with BUN rising, the more kidney function decreases.
Albumin-to-creatinine ratio
In addition to creatinine and GFR assessments, a urine examination is usually performed to evaluate the renal profile of individuals. As part of the urine analysis, the ACR (albumin-to-creatinine ratio) is calculated to determine the presence of albumin in the urine. Albumin is a protein in the blood, and healthy kidneys generally don't filter it out of the blood, so there should be little to no albumin found in the urine.
ACR above 30 mg/g (healthy kidney ACR for adult men is below 17 mg/g and for adult women is below 25 mg/g) may indicate kidney disease, even if the GFR is >60. A higher than typical result may be a sign of kidney disease. In particular, the result may indicate a complication of diabetes called diabetic nephropathy or diabetic kidney disease. Elevated levels of albumin also point to a higher risk of progression of kidney disease.
Further Reading
Coffee and genetics: A complex blend impacting kidney health