What Is Creatinine?
Creatinine is an endogenous substance formed by the metabolism of creatine phosphate in the skeletal muscles. It is produced at a relatively constant rate and is freely filtered by the glomerulus. Creatinine is thus considered as an ideal substance for use in evaluating kidney health since it is neither appreciably reabsorbed nor secreted.
Normal serum creatinine levels vary slightly according to reporting laboratory. However, the typical normal creatinine range for men is between 0.7 and 1.4 mg/dl, where the conventional unit is milligram per deciliter. In the SI unit of measurement (micromole per liter), the creatinine normal range is between 62 to 124 μmol/L.
Women are more likely to have lower creatinine levels owing to their lesser muscle mass compared to men. Muscular males tend to have high creatinine levels especially if they consume a high-protein diet typical of body builders. Children naturally tend to have lower creatinine levels than either men or women. The commonly accepted reference values are:
Conventional Unit ( mg/dl)
0.7 to 1.4
62 to 124
0.6 to 1.3
53 to 115
0.4 to 1.2
35 to 106
In evaluating kidney health using serum creatinine level, the kidney reserve is such that 50% of the kidney function must be lost before creatinine level is blood is raised. Moreover serum creatinine level usually parallels the severity of the kidney disease. Creatinine levels rise or fall depending on a number of factors. High creatinine levels may be caused by one or more of the following factors:
- Gender – females generally have low creatinine levels;
- Low muscle mass or decreased muscle mass due to muscle wasting disease or atrophy;
- Medicines such as Thiazide and Vancomycin.
Meanwhile high creatinine levels may be a result of one or more of the following factors:
- Congestive cardiac failure;
- Gender – Males tend to have more muscle mass;
- Medicines such as Amothericin B, Captopril, Cephalosphorins, Kanamycin;
- Old age
- Renal diseases such as glomerulonephritis, pyelonephritis, renal failure, urinary obstruction, etc.
Elevated creatinine levels may also have their etiology on pre-renal, renal, and post-renal conditions. Diseases which cause elevated creatinine tend to reduce blood flow towards the kidney. These underlying etiologies either increase creatinine synthesis or increase kidney perfusion. The following diseases, conditions, or practices may cause elevated creatinine by increased synthesis of the substance:
- Drugs such as phenacemide;
- High protein diet;
- Muscle necrosis;
- Muscular hypertrophy;
- Severe exercise;
- Use of anabolic steroids.
Meanwhile decreased renal perfusion which elevates creatinine may be caused by ascites and cirrhosis. Higher than normal creatinine levels may be also intrinsic in nature or directly associated with kidney disease such as:
- Decreased tubular secretion;
- Drugs which include Cimetidine, Probeneoid, and Trimethroprim;
Finally, underlying causes of elevated creatinime considered as post renal are those which cause obstruction in the urinary tract. This includes:
- Benign prostatic hyperplasia;
- Carcinoma of the bladder, prostate, or ureters;
- Retroperitoneal tumor.
There are two test modes in measuring creatinine levels: the blood and the urine test modes.
The creatinine clearance test is a specific measurement for kidney function based on glomerular filtration. This test is a metric of the rate at which the kidney clears creatinine from the blood. In more general terms, clearance of a substance refers to the imaginary volume of plasma from which the substance has to be completely extracted in order to provide a cue for the kidney to excrete that particular quantity within one minute. The volume of the substance is expressed in milliliters (ml.). Creatinine clearance is used to estimate GFR.
Use of the creatinine clearance test as GFR marker has both advantages and disadvantages. Among the advantages are:
- Simplicity of the technique;
- Spontaneous conversion of creatinine phosphate to creatinine; the conversion is non-enzymatic;
- Creatinine is not affected by diet and exercise;
- Continuous production of creatinine ensures that the serum creatinine level will not fluctuate, such that blood may be collected from a patient any time.
However, there are also disadvantages of utilizing creatinine clearance as GFR marker:
- Creatinine clearance overestimates the GFR by about 10 to 20 ml per ml. Since creatinine is filtered by the glomeruli, and is actually secreted by the tubules, the excretion comprises 10% by tubular component. When the GFR is reduced, the secretion component is increased and thus the result is violated;
- When GFR is severely reduced, extra-renal secretion increases. This results in the degradation of the major route by intestinal bacterial flora;
- Urine creatinine excretion is decided by the muscle mass and there is a need for a correction factor by including the body surface area;
- Creatinine clearance has a blind area where very early stages of GFR decrease may not be detected by creatinine clearance;
- Creatinine clearance naturally decreased for older people.
To perform the clearance test by using blood, a venipuncture is done. For infants and small children, the venipuncture is replaced by a heelstick puncture in order to fill a capillary pipette. The blood is collected at the midpoint of the urine collection period.
A decreased creatinine clearance is a very sensitive indicator of decline in GFR. Clearance value of up to 75% of the average normal value suggests normal function of the kidneys. Change in plasma creatinine which may not readily show abnormal function may, however display substantial changes in the value of the clearance.
To illustrate, suppose that the plasma creatinine level is 1 mg/dl and the clearance is 100 ml/minute, a rise in plasma creatinine by another mg (i.e., 2 mg/dl) will decrease the value of the clearance by 50%. Other substances will not show such a drastic drop in the clearance value.
The creatinine clearance test is very helpful in long-term monitoring of patients with renal insufficiency. Particularly the rise and fall of the clearance value has significant implications under a protein-restricted diet. When the protein content of the diet is relatively constant, any change induced by varying dietary creatinine is short -lived. This is because of the slow rate of conversion of creatine to creatinine in muscle and the resulting turnover averages only about 1% per day.
Meanwhile, for the urine test, urine is collected in 4-hour, 12-hour or 24-hour period. The excretion of creatinine for a given person is fairly constant. Hence, the 24-hour urine creatinine level is used as a check on the completeness of a 24-hour urine collection. It is of no help in the assessment of renal function unless it is done in conjunction with the creatinine clearance test. Here are the reference values:
14 to 26
124 to 230
11 to 20
97 to 177
Protein Creatinine Ratio
The protein creatinine ratio had been proven to be predictive of declining kidney function among non-diabetic patients with chronic renal disease. This test is also useful both as a screening test or a longitudinal test for following the level of proteinuria. There is thus reason to believe that that the protein creatinines test, otherwise called the albumin creatinine test, is more quantitative than the very simple dipstick screening process.
However, there are limitations in using this test:
- Collection of first-void sample in the morning may underestimate the 24-hour protein excretion because patients with proteinuria tend to have decreased readings.
- Storage time and temperature affects the sample which requires that the sample is processed shortly after collection.
- Creatinine concentration is extremely variable and this causes different ratios between people who have similar excretion rates.
Creatinine urine assessment integrates measurement of protein level, particularly microalbumin, helps detect diabetic kidney damage. It should be noted that most urine dipstick test can not detect microalbumin. Moreover, microalbumin can be correlated with creatinine levels to evaluate significance. The onset of renal complications from diabetes is first predicted by the detection of microalbuminuria. Detection of microalbumin in urine is also associated with heart disease; thus, patients afflicted with diabetes and hypertension should submit to regular screening for two tests: GFR and microalbumin.
Serum protein levels normally have the following reference values in the normal range:
- Total protein, 6.7 to 8 gm%;
- Albumin, 3 to 5 gm%;
- Globulin, 2 to 3 gm%;
- Albumin to globulin ratio (A/G ratio), 1.7:1. Note that in nephrotic syndrome, the albumin levels increase leading to reversal of A/G ratio.
Creatinine is a metabolic product of the muscles and is a very significant substance in the body. Elevated levels alert people of the possibility of kidney disease, whereas levels lower than normal may be hints of liver disease. People should strive for balanced or normal levels as a marker of good kidney and liver function. Such balance can be achieved by good dietary habits, regular exercise, good sleep, and regular medical check-up.