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 kidney reduced function.
What is Creatinine?
Creatinine is a waste product created from the normal wear and tear of muscles . It is produced from creatine, a protein needed to generate the energy for muscle contractions . 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]. The creatinine level 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, the alkalinity or acidity (pH) and temperature influences 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. The bacteria may lower creatinine and therefore antibiotics might increase creatinine levels .
Factors That Determine Creatinine Production
The amount of creatinine produced depends on the muscle mass of an individual .
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) .
Creatinine Measurement is 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 .
Measurement of Creatinine Clearance
The most direct method for measuring the 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:
- it requires the continuous collection of samples for 24 hours
- it can be miscalculated if the urinal samples are not collected properly
- it varies depending on the site of collection 
- it varies depending on the day of collection 
Measurement of 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, it is not toxic meaning that high levels do not 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 .
Conventional doctors will look at high or low creatinine levels and often not mention anything. Sometimes, a lab result may be in the reference range, but not actually be in the optimal range. Reference ranges are not the same as an optimal range. This is why creatinine even in the ‘normal’ range can be unhealthy and indicate that certain processes in the body aren’t optimal.
Normal Creatinine Range
Adult males greater than 15 years old: 0.76 – 1.27 mg/dL.
Adult females greater than 15 years old: 0.57 – 1.0 mg/dL.
- Men: 0.6 to 1.2 mg/dL; 53 to 106 μmol/L
- 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
Symptoms of High Creatinine Levels
- 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
Causes of High Creatinine
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. Seek treatment for the underlying disease.
High creatinine can be caused by:
- Dehydration 
- A diet high in protein 
- Cooked meat. This happens because cooking converts the creatine present in meat (which is muscle) into creatinine [19, 20]
- Vigorous exercise [19, 21]
- Creatine supplements 
- Kidney disorders/diseases [22, 23]
- Hypothyroidism 
Some drugs 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 [25, 26, 27]
- Anticonvulsants such as phenacemide (Phenurone) 
- Acetaminophen (Tylenol, Panadol, paracetamol) 
Diet/Lifestyle that Increases Blood Creatinine Levels
It could be that your creatinine levels are higher but you don’t have any underlying condition.
1) High Protein Diet
Increased physical activity has been associated with high creatinine levels in healthy individuals .
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 .
Consumption of commercially available creatine supplements to increase exercise performance can be a cause of kidney injury.
Healthy young people that consumed creatine had moderately high creatinine levels in the blood .
However, there is a reported case of higher creatinine levels after creatine consumption, as a result of kidney injury (interstitial nephritis) which was reversible after hospitalization and treatment .
5) Cooked Meat
Consumption of cooked meat increases the levels of blood creatinine in healthy individuals independently of their age .
While being cooked, the creatinine content of meat increases – especially in high temperatures .
Risks with High Creatinine
Kidney disease is the greatest risk factor with higher creatinine, but here are some other diseases that may be increased.
1) Heart Disease Risk
Middle-aged males with high levels of blood creatinine have a high risk of heart disease .
Elevated levels of blood creatinine coincide with increased risk of death within a year after heart attack episodes .
Elevated levels, in combination with protein levels in the urine (proteinuria), are good predictors for the development of cardiovascular diseases as well as death .
2) Stroke Risk
Studies in middle-aged men showed a significant stroke risk for individuals with high levels of blood creatinine. This observation applied to both healthy as well as men suffering from high blood pressure .
3) Prostate Cancer
Increased levels of creatinine, but within the normal range, showed an increased risk for development of prostate cancer in a study carried out in Finnish males between 50 and 69 years old .
In prostate cancer cases which are resistant to hormonal treatments, elevated creatinine levels are correlated with fewer chances of survival .
Risks With Increased Blood Creatinine Levels
1) Kidney Disease
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 .
3) Heart Failure
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.
4) Muscle Wasting
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 appear between 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 .
Drugs that Increase Blood Creatinine Levels
Antibiotics such as aminoglycoside, cephalosporin, and amphotericin B can injure kidneys, which elevates the levels of blood creatinine .
Antibiotics such as trimethoprim/sulfamethoxazole (Bactrim, Cotrim, Septra) and cefoxitin (Mefoxin) can 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 .
Amongst the disadvantages of the use of cyclosporine as a drug is toxicity against the kidneys. Apart from affecting various types of cells that build up the kidneys, cyclosporin also interferes with the blood circulation in the kidneys (hemodynamics) .
Patients with rheumatoid arthritis that were prescribed with Cyclosporine-A, showed increased levels of blood creatinine in comparison to non-prescribed patients .
3) Non-steroidal Anti-Inflammatory Drugs (NSAID)
These drugs which include aspirin, ibuprofen, indomethacin (Indocid, Indocin), and naproxen are commonly available and used without prescription 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 [50, 25, 26, 27].
4) Angiotensin-Converting Enzyme (ACE) Inhibitors
ACE inhibitors are used for patients that suffer from hypertension. 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 side-effects including small increases in the levels of creatinine in the blood. Despite this increase, the usage of diuretics is a method used to control kidney failure even for long periods .
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) can increase creatinine .
How to Lower Elevated Creatinine Levels
- Avoid 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 the levels may increase above optimum .
- Avoid creatine and creatine-based supplements.
- Avoid strenuous exercise [19, 21].
- 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.
Supplements that can help and are beneficial for kidney function:
- Alpha lipoic acid [58, 59]
- Salvia miltiorrhiza (red sage) 
- Nettle (Urtica dioica) 
- Astragalus [62, 63]
- Ginseng [64, 65, 66, 67, 68]
- Chamomile 
- Spirulina – protects the kidneys [70, 71, 72]
- Chitosan 
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.
2) Chamomile Tea
In rats, chamomile tea can reduce the levels of blood creatinine in the kidneys .
3) Siberian Ginseng
Siberian ginseng is a natural medicine for kidney-related diseases.
Rats that consumed Siberian ginseng extracts, had reduced blood toxins, including creatinine, after bacterial infection .
Turmeric is a spice that can also be a natural medicine in India and other parts of Asia.
However, Turmeric should be used with caution as its high content in phosphorous and potassium can lead to a further increase of creatinine in the blood, especially in patients with kidney dysfunction .
Chitosan can reduce the levels of creatinine when used for patients that suffer from chronic kidney failure .
6) Stinging Nettle
7) Less Sodium, and Phosphorous
Increased sodium consumption, and salt in general limits urination and leads 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 .
Drug Approaches to Lower Creatinine
Ketosteril is a drug that doctors often prescribe to treat kidney dysfunction. Although it does not reduce the levels of creatinine directly, it lowers the levels of urea which in turn helps decrease creatinine .
2) Calcium Channel Blockers
Calcium channel antagonists normally help reduce blood pressure. By enlarging the blood vessels they increase the blood flow to the kidneys which helps in creatinine clearance .
Causes of Low Creatinine
Low creatinine can also be caused by:
- Malnutrition 
- Muscle wasting (in illness or aging) [23, 84, 85]
- Extreme weight loss [56, 86]
- Liver disorders 
- Limb amputation (lower is normal) 
- Pregnancy (lower is normal) 
If low creatinine is caused by an underlying disease, seek medical treatment.
Risks with Low Creatinine
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) .
How to Increase Creatinine
Adjust your diet. Make sure you are well nourished and your diet contains enough protein.
Supplements that can help:
- Protein supplements
Other Tests to Get
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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