Creatinine is an indicator of kidney function. In this article, we discuss how it is produced, disposed of, as well as why it is an important indicator of kidney disease or reduced kidney function.
What is Creatinine?
Its production essentially reflects lean body mass, and because this mass changes little from day to day, the production rate is also fairly constant. Women, children, and older people tend to have lower levels of creatinine compared to adult men because they have less muscle mass .
Creatinine is removed from the body by the kidneys, which filter almost all of it from the blood into the urine. That is why blood levels are usually a good indicator of how well your kidneys are working [3, 1].
Creatinine levels can be tested as a part of your basic metabolic panel (BMP) or your comprehensive metabolic panel (CMP).
During energy production, muscles generate creatinine. More specifically, it is a waste product of the breakdown of creatine, an important molecule for muscle metabolism. The consumption of cooked meat can also introduce it to the body.
Soon after its production, creatinine is transported via the blood to the kidneys, where it gets filtered. Finally, the body releases it in the urine .
An individual that has a stable muscle mass, produces daily a constant amount of creatinine. Therefore blood levels should also be stable.
Creatinine is produced from the breakdown of creatine phosphate in the muscles. Studies have shown that consumption of creatine, alkalinity or acidity (pH), and temperature can influence this process as well [5, 6].
Microorganisms found in the human gut and stool can also break down creatinine in the body. These microorganisms in the gut can increase in situations where creatinine is high, such as in kidney failure. Some scientists believe that these bacteria may lower creatinine and that antibiotics might increase creatinine levels .
The amount of creatinine produced depends on the muscle mass of an individual .
Other factors, such as age, sex, ethnicity, diet, etc., also contribute to its production .
Creatinine in the blood increases with increased muscle mass .
Although healthy adults maintain stable levels of creatinine, children, older and sick individuals show a great variation .
Especially in the case of serious illness, the levels of creatinine decrease. This decrease is related to the loss of muscle mass (muscle wasting) .
An Indicator of Kidney Function
Kidneys are the organs that filter the blood and remove toxic substances and excess water. This filtering cleans the blood and maintains a constant stable environment in the body (homeostasis) .
Creatinine, like other waste molecules, enters the kidney and get filtered in specialized compartments (glomeruli). After filtering, it is discarded through the tubules in the urine and filtered blood exits the kidneys .
As creatinine gets filtered out from the blood in the kidneys, elevated levels are often associated with kidney dysfunction and kidney-related diseases. The status of kidney function can be estimated by measuring the creatinine clearance or indirectly by its levels in the blood .
The most direct method for measuring creatinine clearance is the collection of urine samples for a time period of 24 hours and a blood sample. Alternatively, a formula that uses the blood levels of creatinine, age, weight, and gender can also be used to calculate clearance .
Despite the method of calculation used, the value of creatinine clearance shows how much gets removed from the blood by the kidneys and this provides an estimation of kidney function .
Although creatinine clearance provides one of the most direct and cost-free methods to estimate kidney function, its measurement has several disadvantages:
- requires the continuous collection of samples for 24 hours
- can be miscalculated if the urinal samples are not collected properly
- varies depending on the site of collection 
- varies depending on the day of collection 
Blood Creatinine Levels
A more indirect method of kidney function measurement is by estimating the levels of creatinine in the blood. High levels in the blood are often associated with reduced kidney function, although other factors can also increase or decrease its levels.
In principle, creatine is not toxic, meaning that high levels do not directly lead to the development of diseases. However, high levels are indicative of disease .
Although examining the levels of creatinine in the blood is a widely used and quite easy method to estimate the possibility of kidney failure, it entails certain disadvantages and its interpretation requires cautiousness .
Normal Blood Creatinine Range
Lab results are commonly shown as a set of values known as a “reference range”, which is sometimes referred to as a “normal range”. A reference range includes the upper and lower limits of a lab test based on a group of otherwise healthy people.
The normal blood creatinine range is considered to be:
- Men: 0.6 to 1.2 mg/dL (milligrams per deciliter); 53 to 106 μmol/L (micromoles per liter)
- Women: 0.5 to 1.1 mg/dL; 44 to 97 μmol/L
- Teenagers: 0.5 to 1.0 mg/dL
- Children: 0.3 to 0.7 mg/dL
Your healthcare provider will compare your lab test results with reference values to see if any of your results fall outside the range of expected values. By doing so, you and your healthcare provider can gain clues to help identify possible conditions or diseases.
Some lab-to-lab variability occurs due to differences in equipment, techniques, and chemicals used. Don’t panic if your result is slightly out of range – as long as it’s in the normal range based on the laboratory that did the testing, your value is normal.
However, it’s important to remember that a normal test doesn’t mean a particular medical condition is absent. Your doctor will interpret your results in conjunction with your medical history and other test results.
Remember that a single test isn’t enough to make a diagnosis. Your doctor will interpret this test, taking into account your medical history and other tests. A result that is slightly low/high may not be of medical significance, as this test often varies from day to day and from person to person.
High Blood Creatinine Levels
A high level of creatinine will not cause symptoms on its own. Even if you have above-normal levels you may notice no change.
However, high creatinine is often caused by an underlying disease that affects kidney function, such as kidney disease, diabetes, high blood pressure, or hypothyroidism. In these cases, you will experience the symptoms of the underlying disease/disorder.
Therefore, symptoms may include:
- Reduced urine output
- Darkened color of urine
- Swelling around the eyes, in the face, feet, etc
- Back pain or waist pain
- Fatigue, lethargy
- Low fever
- Loss of appetite
- Confused or disoriented
- Shortness of breath
Seek treatment for the underlying disease.
Creatinine levels may be higher in people who don’t have any underlying condition. The following factors have been associated with increased creatinine levels. However, have in mind that many of the described studies focused on associations. Therefore, the factors listed here may not be directly causing higher creatinine levels.
1) High Protein Diet
Increased physical activity has been associated with high creatinine levels in healthy individuals in studies .
3) Being Muscular
Studies in healthy individuals show a direct correlation between muscle mass and the levels of blood creatinine. This correlation is significant for both adult men and women .
Healthy young people that consumed creatine had moderately high creatinine levels in the blood .
There is a reported case of higher creatinine levels after creatine consumption as a result of kidney injury (interstitial nephritis) that was reversible after hospitalization and treatment .
5) Cooked Meat
According to one study, consumption of cooked meat increases the levels of blood creatinine in healthy individuals independently of their age .
Researchers found that while being cooked, the creatinine content of meat increases – especially in high temperatures .
The following diseases have been associated with high creatinine in the blood. In most cases, a cause-and-effect relationship has not been established. Large-scale, differently-designed studies are needed.
1) Heart Disease
Middle-aged males with high levels of blood creatinine had a higher risk of heart disease in one study .
Elevated levels of blood creatinine coincided with increased risk of death within a year after heart attack episodes in another study .
Some scientists consider that elevated levels, in combination with protein levels in the urine (proteinuria), may be predictors for the development of cardiovascular disease as well as death .
Studies in middle-aged men suggested an association between stroke risk and high levels of blood creatinine. This observation was applied to both healthy as well as men suffering from high blood pressure. However, their findings have yet to be properly verified .
3) Prostate Cancer
Increased levels of creatinine, but within the normal range, were linked with an increased risk of the development of prostate cancer in one study carried out in Finnish males between 50 and 69 years old .
According to another research group, in prostate cancer cases resistant to hormonal treatments, elevated creatinine levels have been correlated with reduced chances of survival .
The exact link between creatinine blood levels and prostate cancer remains unclear and larger follow-up studies are needed before any conclusions can be drawn.
Causes shown here are commonly associated with high blood creatinine. Work with your doctor or other health care professional for an accurate diagnosis.
High levels of blood creatinine and low urine creatinine usually points to kidney disease or another condition that affects kidney function.
- Dehydration 
- A diet high in protein 
- Cooked meat. This happens because cooking converts the creatine present in meat (which is muscle) into creatinine [20, 32]
- Vigorous exercise [20, 33]
- Creatine supplements 
- Kidney disorders/diseases [34, 35]
- Hypothyroidism 
Some drugs may also cause high creatinine levels:
- Antibiotics such as trimethoprim/sulfamethoxazole (Bactrim, Cotrim, Septra) and cefoxitin (Mefoxin) 
- Histamine H2 receptor blockers that inhibit stomach acid production: cimetidine (Tagamet), famotidine (Pepcid), and ranitidine (Zantac) 
- NSAIDs such as indomethacin (Indocid, Indocin) and ibuprofen [37, 38, 39]
- Anticonvulsants such as phenacemide (Phenurone) 
- Acetaminophen (Tylenol, Panadol, paracetamol) 
Creatinine is most commonly checked to measure kidney function. If creatinine is high, it may indicate kidney disease or impaired kidney function.
Diabetes often results in elevated levels of creatinine as a result of impaired clearance in the kidneys. Diabetes can cause injury in the blood vessels of the kidneys which in turn reduces the ability of the kidneys to filter the blood from waste products including creatinine .
Studies from European hospitals suggest that increased creatinine and impairment of kidney function was a common phenomenon among patients with heart failure .
A study in 103 patients with heart failure and end-stage kidney disease who received kidney transplants showed an improvement of heart function and increased survival after transplantation. The group of patients whose heart function improved the most after kidney transplantation had the lowest levels of blood creatinine .
Therefore, the effect may go both ways; kidney disease may contribute to heart disease, and heart disease may contribute to kidney disease since the kidneys are connected to the cardiovascular system.
The levels of blood creatinine are related to a high degree with muscle mass. Often patients lose a great part of their muscle mass within the first week of hospitalization which results in lower levels of blood creatinine .
If these patients also suffer from kidney disease (which would increase the levels of creatinine), the levels of creatinine might be within the normal range. Thus, muscle wasting can be a factor that interferes with the proper diagnosis of kidney failure amongst hospitalized patients .
Hematuria is the presence of blood in the urine. It is also indicative of infections or a symptom of cancer .
Cases of hematuria in combination with high levels of serum creatinine are often associated with kidney disease .
Please discuss your medications with your healthcare provider. They will assess your test results taking into account your medications and other relevant factors to determine whether a result outside of the reference range means something for you.
Contact your doctor or pharmacist if you notice medication side effects such as tiredness, dry or itchy skin, blood in your urine, or anything else out of the ordinary.
Call your doctor for medical advice about side effects. In the US, you may report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada, you may report side effects to Health Canada at 1-866-234-2345.
With this in mind, the following medications may increase creatinine levels in some people:
Antibiotics such as aminoglycoside, cephalosporin, and amphotericin B can injure the kidneys, which elevates the levels of blood creatinine .
Antibiotics such as trimethoprim/sulfamethoxazole (Bactrim, Cotrim, Septra) and cefoxitin (Mefoxin) may also increase creatinine 
Cyclosporine is a commonly used drug that acts as immunosuppressant and is often prescribed to patients with allergies, autoimmune diseases (AIDS, atopic dermatitis) or after transplantation .
Cyclosporine may cause kidney damage in some cases and interfere with the blood circulation in the kidneys (hemodynamics) .
In one study, patients with rheumatoid arthritis that were prescribed with Cyclosporine-A had increased levels of blood creatinine in comparison to non-prescribed patients .
3) Non-steroidal Anti-Inflammatory Drugs (NSAID)
These drugs–including aspirin, ibuprofen, indomethacin (Indocid, Indocin), and naproxen–are commonly available and often used over-the-counter to treat pain, inflammation, or fever. A recent study reports the development of acute kidney injury in adolescent, non-patient individuals after consumption of NSAID which was also followed by elevated levels of blood creatinine. However, kidney damage from NSAIDs is rare [50, 37, 38, 39].
4) Angiotensin-Converting Enzyme (ACE) Inhibitors
ACE inhibitors are used for patients that suffer from hypertension. In one study, in the first 2 weeks of treatment with ACE inhibitors, the levels of creatinine in the blood increased (~30% above normal). ACE inhibitor-induced elevated creatinine only affected the kidney function of patients who had kidney failure prior to the treatment .
Diuretics such as metolazone are often prescribed to patients suffering from kidney failure (renal insufficiency and nephrotic syndrome). Although beneficial, treatment with metolazone has been linked with small increases in the levels of creatinine in the blood. Nonetheless, diuretics are often prescribed to control kidney failure long-term .
6) Histamine H2 receptor blockers
Histamine H2 receptor blockers that inhibit stomach acid production can increase creatinine: cimetidine (Tagamet), famotidine (Pepcid), and ranitidine (Zantac) 
Anticonvulsants such as phenacemide (Phenurone) can increase creatinine .
Acetaminophen (Tylenol, Panadol, paracetamol) may also increase creatinine, according to one study .
Factors that May Lower Blood Creatinine
Dialysis is a common treatment for people with kidney disease. This medical procedure is used in people whose kidneys can’t remove waste products effectively.
Your doctor may also prescribe medication to manage your symptoms of kidney disease. Some drugs used in kidney disease patients include water pills (diuretics), medications for lowering high blood pressure, erythropoietin, and others.
It’s important to speak with your doctor if your blood creatine is high. Your doctor should diagnose and treat any underlying conditions causing your high blood creatine levels.
You may try the complementary approaches listed below if you and your doctor determine that they could be appropriate for improving your kidney health (and potentially lowering your blood creatine levels).
Discuss the strategies listed here with your doctor. Remember that none of them should ever be done in place of what your doctor recommends or prescribes.
Overview of Complementary Approaches
- Reduce protein – kidneys must work harder when there’s more protein in the diet. A high-protein diet can further aggravate kidney function .
- Decrease phosphorus-containing foods such as soft drinks, artificial sweeteners, snack foods, and processed foods. If creatinine is not filtered efficiently, neither is phosphorus, and its levels may increase .
- Avoid creatine and creatine-based supplements.
- Avoid strenuous exercise [20, 33].
- Lose some weight if overweight. Weight loss can increase your kidney health and decrease creatinine levels .
- Increase fluid intake, try to drink at least two liters of water a day! High blood creatinine may be a result of dehydration .
- Increase dietary fiber! It improves kidney health and can lower blood creatinine levels . Fruits, veggies, whole grains and legumes are good sources of fiber.
Vigorous exercise has been shown to temporarily cause muscle damage and breakdown, which increases creatine levels. Exercise in moderation, don’t overdo it .
Increasing the intake of fluids which do not contain caffeine, decreases the levels of creatinine in the blood. Increased hydration leads to increased urination and thus higher creatinine clearance.
Increased sodium consumption, and salt in general limit urination and lead to an accumulation of waste products in the blood.
A diet with restricted sodium, potassium, and phosphorus in conventional medicine can help in the decrease of blood creatinine levels especially in cases of kidney disease .
Creatine supplements increase creatinine levels in the blood in healthy people. If your goal is to take the strain off your kidneys and reduce your creatinine levels, avoid creatine supplements .
Do not take any supplements or herbal preparations (including teas) before consulting your doctor first. Many common supplements and herbs can interact with medications.
Here are some supplements and herbs that people commonly use for kidney health to discuss with your doctor:
- Alpha lipoic acid [59, 60]
- Salvia miltiorrhiza (red sage) 
- Nettle (Urtica dioica) 
- Astragalus [63, 64]
- Ginseng [65, 66, 67, 68, 69]
- Chamomile 
- Spirulina [71, 72, 73]
- Chitosan 
In rats, chamomile tea can reduce the levels of blood creatinine in the kidneys. There have been no reports of toxicity in humans, however, the safety of chamomile in people with kidney disease has not been established [76, 77].
Siberian ginseng is traditionally used for kidney-related diseases, though clinical trials are lacking. In rats, siberian ginseng extracts reduced blood toxins, including creatinine, after bacterial infection. Human studies are needed .
Turmeric is a spice that is used in traditional medicine in India and other parts of Asia. However, the effects of curcumin – the main active ingredient of turmeric – on kidney health in humans is unknown. In salt-sensitive rats on a high salt diet, it can lower the levels of blood creatinine .
However, caution is advised as turmeric’s high phosphorus and potassium content can lead to a further increase of creatinine in the blood, especially in patients with kidney dysfunction .
Low Blood Creatinine
Causes shown here are commonly associated with this low blood creatinine. Work with your doctor or other health care professional for an accurate diagnosis.
Low blood creatinine can also be caused by:
- Malnutrition 
- Muscle wasting (in illness or aging) [35, 83, 84]
- Extreme weight loss [56, 85]
- Liver disorders 
- Limb amputation (lower is normal) 
- Pregnancy (lower is normal) 
If low creatinine is caused by an underlying disease, seek medical treatment.
Potential Link to Diabetes
People with lower creatinine (0.4 – 0.6 mg/dl) were at a 91% increased risk of type 2 diabetes, compared to those with more normal levels (0.71 and 0.80 mg/dl) .
However, no large-scale studies have replicated these findings. What’s more, these studies do not suggest that low creatinine causes people to die. These studies dealt with associations, while creatinine is just a lab marker that can point to certain processes in the body.
Factors that May Increase Blood Creatinine
Most importantly, work with your doctor to treat any underlying conditions causing your low creatinine levels.
You may try the additional strategies listed below if you and your doctor determine that they could be appropriate. None of these strategies should ever be done in place of what your doctor recommends or prescribes.
Adjust your diet. Make sure you are well-nourished and your diet contains enough protein.
Protein supplements and creatine may increase creatinine levels in some people. Do not take them before consulting a doctor.
A high creatinine level does not necessarily mean the person has chronic kidney disease but indicates the need for other tests. These include glomerular filtration rate (eGFR), blood urea nitrogen (BUN), creatinine clearance rate (CrCl), phosphate, calcium, sodium (Na), potassium (K), and glucose.
Irregular Creatinine Levels?
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