What Is Creatinine and Why Does It Increase?

Creatinine is an organic compound produced by metabolism which, under normal conditions, is excreted in the urine by the kidneys.

Written and verified by el biólogo Samuel Antonio Sánchez Amador.

Last update: 22 April, 2023

What is creatinine? It’s an organic waste compound formed from the breakdown of creatine, an essential amino acid for energy in muscle tissue. High levels of creatinine in the blood and low in the urine usually indicate kidney disease or will mean that the functioning of the kidneys is being affected.

According to epidemiological studies, chronic kidney disease (CKD) is a serious public health problem, as it affects 10% of the population at any given place and time. Therefore, individual monitoring of blood creatinine levels is essential.

The importance of the kidneys

Before diving fully into the world of creatinine, it’s important to contextualize renal function at a physiological level. According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the kidneys filter about 190 liters of blood per day, which translates into 2 liters of urine every 24 hours.

Such is the importance of renal function that it’s estimated that, on average, 22% of individual cardiac output is used to pump blood to these organs. Among the most important functions of the kidneys we find the following:

• Excreting waste substances through urine: The function of urine is to accumulate disposable metabolic substances produced by the body. Among them, we find urea, ammonia, uric acid, and creatinine.
• Regulating body homeostasis: The kidneys regulate plasma volume, blood ion concentration, acid-base balance, osmolarity, and blood pressure. All these mechanisms allow the body to be in a constant physiological balance.
• Secreting hormones: Such as erythropoietin, renin, calcitriol, or kallikrein.
• Carrying out gluconeogenesis: Allows the synthesis of glucose from amino acids and other precursors during periods of fasting. Although the liver is in charge of this function almost by itself, 10% of the process is carried out in the kidneys.

Unfortunately, like any organic material, these organs are also susceptible to disease. According to the National Library of Medicine of the United States, cysts, cancers, stones, and kidney infections are relatively common pathologies.

What is creatinine?

Now that we have explained renal function briefly from a medical and physiological point of view, it’s time to focus on the compound that concerns us here: creatinine and its excretion method.

As we have said, creatinine is a metabolic waste generated from the degradation of creatine. We can cite some general particularities:

• Creatinine is produced from creatine by the loss of a water molecule.
• Creatinine is 99.5% filtered in the glomerulus of the nephron —the most basic structure of the kidney— and its exchange at the tubular level is almost nil. This means that the entire amount of filtered creatinine is entirely excreted in the urine and nothing is reabsorbed.
• It’s a compound of endogenous origin, that is, produced by the organism.
• The levels of creatinine in blood and urine depend on each patient, based on their age, weight, and muscle mass.

According to scientific fact sheets, creatinine is a non-enzymatic metabolic product of creatine and phosphocreatine that, under normal conditions, is produced at a constant rate from skeletal muscle tissue. It accounts for about 2% daily of the creatine reserve in people.

About creatine

Creatine is a nitrogenous organic acid that is used to obtain energy. According to the Mayo Clinic, the body converts creatine into phosphocreatine and stores it in the muscles.

Phosphocreatine is the immediate source for obtaining ATP (energy) in muscle cells. For this reason, certain athletes take creatine orally to improve their athletic performance and increase muscle mass.

Furthermore, this compound is also used for medical purposes as it’s used to treat some brain disorders, congestive heart failure, and other conditions. Even so, it should be noted that there’s insufficient data to justify total effectiveness in these pathologies.

The creatinine test

According to the United States National Library of Medicine, there are techniques that measure creatinine levels in the blood and urine. As this waste product is produced on a daily basis by muscular activity, an accumulation may indicate a kidney problem that modifies its filtering capacity.

1. Blood creatinine test

As you can imagine, to obtain the sample for this test, blood must be drawn from the patient. Blood creatinine values are often used simultaneously with urea values to quantify renal function.

A normal blood creatinine result is 0.7 to 1.3 milligrams of the compound per deciliter of blood for men. In the case of women —who tend to have lower values— the appropriate concentration is 0.6 to 1.1 milligrams per deciliter.

Although these values are the standard, a woman or a man may have slightly higher figures than those indicated here depending on their muscle mass and physical condition. Obviously, the more energy expended by the muscles and the more phosphocreatine used, the more creatinine will circulate in the blood and be excreted in the urine.

For example, an elite athlete can show up to 2 milligrams of creatinine per deciliter of blood without this being considered a medical problem.

2. Urine creatinine test

The rationale is the same here as in the previous case, but this time a urine sample is analyzed. The values in this case are much higher, as the amount of creatinine that’s excreted is calculated and not the amount circulating in the blood:

• Normal urine creatinine values can be 500 to 2,000 milligrams a day.
• It’s estimated that a man under normal conditions will excrete 14 to 26 milligrams of creatine per kilogram of weight.
• In the case of women, a value of 11 to 20 milligrams of creatine per kilogram of weight is calculated.

According to the Kidshealth.org medical portal, the results of the urine creatinine test are usually ready in about 24 to 48 hours. Therefore, it’s an effective method to detect any physiological or metabolic irregularity related to the kidneys quickly.

What do abnormal results mean?

When the amount of creatine in the blood is estimated to be too high or too low in the urine, it’s time to start suspecting some irregularity in the kidneys. Sources already cited inform us that abnormal values can mean the following:

• Obstruction of the urinary tract, such as kidney stones
• Kidney failure or organ damage
• Bacterial infections in the kidney
• Death of the cells of the renal tubules, caused by certain drugs or the ingestion of toxic compounds
• Heart failure or complications in diabetes

If suspicious results are observed, the doctor may ask for a creatinine clearance test. In this case, the concentrations of this compound in both blood and urine are compared, which gives a better idea about kidney function.

No need to be alarmed too soon

Although it’s true that high blood creatinine levels can mean a kidney disease, this isn’t always the case. The factors we’ll list below can upset the values outside the normal limits:

• Percentage of muscle mass: A large muscle mass raises serum creatinine levels, while sarcopenia—a lack of muscle—decreases them.
• Protein intake: Diets based on red meat or a recent intake of them can temporarily increase blood creatinine levels. On the other hand, vegans and vegetarians tend to have lower values.
• Drugs: Certain drugs and drugs temporarily inhibit tubular secretion of creatinine.
• Pregnancy.

Creatinine is a compound with great diagnostic value

As you have been able to see, it’s clear that creatinine is an essential metabolic waste compound when diagnosing certain renal pathologies in the patient. It’s usually measured along with others such as urea, also indicative of the filtering capacity of the kidneys.

Blood and urine creatinine levels may vary depending on the gender, physical constitution, and age of the patient. Other anecdotal factors such as diet also modify the results, so multiple variables must be taken into account when interpreting them.