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.
- Factors that Affect Blood Creatinine Levels
- Negative Effects of Creatinine
- Symptoms of High Creatinine Levels (R)
- Methods to Reduce High Creatinine Levels
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 (R).
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 creatine of creatine phosphate (PCr= high energy creatine) in muscles. This process does not require energy consumption. Biochemical studies have shown that the alkalinity or acidity (pH) and temperature influences this process as well (R, R).
More specifically, an alkaline and low-temperature environment favor the form of creatine whereas acidic and high-temperature environments favor creatinine (R).
Microorganisms can also convert creatine to creatinine but this mechanism requires specific enzymatic activities. Bacteria capable of this type of creatine breakdown have been found in body parts many animals, including the human gut (R).
Factors That Determine Creatinine Production
The amount of creatinine produced depends on the muscle mass of an individual (R).
Although healthy adults maintain stable levels, those of children, older and sick individuals show a great variation (R).
Especially in the case of illness, the levels of creatinine decrease. This decrease is related to the loss of muscle mass (muscle wasting) (R).
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) (R).
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 (R).
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 (R).
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 (R).
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 (R).
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
- can be miscalculated if the urinal samples are not collected properly
- varies depending on the site of collection (R)
- varies depending on the day of collection (R)
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 (R).
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 (R).
Factors that Affect Blood Creatinine Levels
Antibiotics such as aminoglycoside, cephalosporin, and amphotericin B can injure kidneys, which elevates the levels of blood creatinine (R).
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 (R).
Amongst the disadvantages of the use of cyclosporine as a drug, is the toxicity against the kidneys. Apart from affecting various types cells that build up the kidneys, cyclosporin also interferes with the blood circulation in the kidneys (hemodynamics) (R).
Patients with rheumatoid arthritis that were prescribed with Cyclosporine-A, showed increased levels of blood creatinine in comparison to non-prescribed patients (R).
3) Non-steroidal Anti-Inflammatory Drugs (NSAID)
These drugs which include aspirin, ibuprofen 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 (R).
4) Angiotensin-Converting Enzyme (ACE) Inhibitors
ACE inhibitors are used for patients that suffer from hypertension. Upon 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 with failure prior to the treatment (R).
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 rather safe method to control kidney failure even for long periods (R).
6) High Protein Diet
7) Excessive Exercise
Increased physical activity has been associated with high creatinine levels in healthy individuals. However, the study does not exclude the possibility that this increase was a secondary effect due to the higher protein consumption by the people tested (R).
8) Body Weight
Studies in healthy individuals show a direct correlation between body weight and the levels of blood creatinine. This correlation is significant for both adult men and women (R).
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 (R).
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 (R).
10) Cooked Meat
Consumption of cooked meat increases the levels of blood creatinine in healthy individuals independently of their age (R).
While being cooked, the creatinine content of meat increases especially in high temperatures (R).
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 (R).
12) Heart Failure
Studies from European hospitals suggest that increase of creatinine levels and impairment of kidney function was a common phenomenon among patients with heart failure (R).
On the contrary, a study in patients with heart failure that received kidney transplants shows 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 (R).
Therefore, the causality of the connection between heart failure and kidney dysfunction is still under debate.
13) Muscle Waste
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 (R).
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 waste can be a factor that interferes with the proper diagnosis of kidney failure amongst hospitalized patients (R).
Hematuria is the presence of blood in the urine. It is also indicative of infections or a symptom of cancer. (R)
Cases of hematuria in combination with high levels of serum creatinine are often associated with kidney disease. (R)
Negative Effects of Creatinine
1) Creatinine Increases Heart Disease Risk
Middle-aged males with high levels of blood creatinine have a high risk for heart disease (R).
Elevated levels of blood creatinine coincide with increased risk of death within a year after heart attack episodes (R).
Elevated levels, in combination with protein levels in the urine (proteinuria), are good predictors for the development of cardiovascular diseases as well as death (R).
2) Creatinine Increases Stroke Risk
Studies in middle-aged men showed a significant stroke risk for individuals with high levels of serum creatinine. This observation applied to both healthy as well as men suffering from high blood pressure (R).
3) Creatinine May Cause 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 (R).
In prostate cancer cases which are resistant to hormonal treatments, elevated creatinine levels are correlated with fewer chances of survival (R).
Symptoms of High Creatinine Levels (R)
- 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
Methods to Reduce High Creatinine Levels
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
3) Herb Mixture
A stinging nettle, Erowid Syrian Rue, and Sicilian sumac mixture decreased the creatinine levels of diabetic rats (R).
4) 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 (R).
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 further increase of creatinine in the blood, especially in patients with kidney dysfunction (R).
6) Less Sodium, Potassium, and Phosphorous
Oats help to decrease high blood pressure which is one of the factors that can increase creatinine (R).
Chitosan can reduce the levels of creatinine when used for patients that suffer from chronic kidney failure (R).
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 (R).
10) Calcium Channel Blockers
- Biochemical experiments propose that each day 1.0-1.3 % of a number of creatine converts to creatinine ( pH 7.0 – 7.2, 38 ౦ C) (R).
- Although the levels were high, they were still within the normal range (~20 units higher than the average normal value) (R).
- Doctors usually recommend ketosteroid in combination with a low-protein diet, as itself supplies the body with plenty of amino acids. (R)
- Metolazone diminishes swelling and helps in controlling the blood pressure. Although beneficial, treatment with metolazone has side-effects including small increases in the Cr levels in the blood. Despite this increase, the usage of diuretics is a rather safe method to control kidney failure (R).
- Clearance = (UCr x V)/ PCr (R).
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