Creatinine
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body (depending on muscle mass).
Physiology
Creatinine is mainly filtered by the kidney, though a small amount is actively secreted. There is little-to-no tubular reabsorption of creatinine. If the filtering of the kidney is deficient, blood levels rise. As a result, creatinine levels in blood and urine may be used to calculate creatinine clearance (ClCr), which reflects the glomerular filtration rate (GFR). The GFR is clinically important because it is a measurement of renal function. However, in cases of severe renal dysfunction, the creatinine clearance rate will be overestimated because the active secretion of creatinine will account for a larger fraction of the total creatinine cleared.
A more complete estimation of renal function can be made when interpreting the blood (plasma) concentration of creatinine along with that of urea. In the USA, urea concentration is given as blood urea nitrogen (BUN), in mg/dL. In other countries, including those of Europe, urea concentration is measured and quoted in mmol/L.
The ratio of urea to creatinine can indicate other problems besides those intrinsic to the kidney. For example, a urea level raised out of proportion to the creatinine may indicate a pre-renal problem such as dehydration.
Men tend to have higher levels of creatinine because they have more skeletal muscle than women. Vegetarians tend to have lower creatinine levels, because vegetables contain no creatinine.
Diagnostic use
Measuring serum creatinine is a simple test and it is the most commonly used indicator of renal function. A rise in blood creatinine levels is observed only with marked damage to functioning nephrons. Therefore, this test is not suitable for detecting early stage kidney disease. A better estimation of kidney function is given by the creatinine clearance test. Creatinine clearance can be accurately calculated using serum creatinine concentration and some or all of the following variables: sex, age, weight, and race as suggested by the American Diabetes Association without a 24 hour urine collection.[1] Some laboratories will calculate the ClCr if written on the pathology request form; and, the necessary age, sex, and weight are included in the patient information.
Interpretation
In the United States, creatinine is typically reported in mg/dL, while in Canada and Europe μmol/litre may be used. 1 mg/dL of creatinine is 88.4 μmol/l.
The typical reference ranges are 0.5 to 1.0 mg/dL (about 45-90 μmol/l) for women and 0.7 to 1.2 mg/dL (60-110 μmol/l) for men. While a baseline serum creatinine of 2.0 mg/dL (150 μmol/l) may indicate normal kidney function in a male body builder, a serum creatinine of 0.7 mg/dL (60 μmol/l) can indicate significant renal disease in a frail old woman.
More important than absolute creatinine level is the trend of serum creatinine levels over time.
Creatinine levels may increase when ACE inhibitors (ACEI) or angiotensin-II receptor blockers (ARBs) are used in the treatment of chronic heart failure (CHF). Using both ACEI & ARB concomitantly will increase creatinine levels to a greater degree than either of the two drugs would individually. An increase of <30% is to be expected with ACEI or ARB use.
Serum Creatinine Variability
The use of serum creatinine as a marker of glomerular filtration and kidney injury relies on certain convenience assumptions. Those assumptions include that creatinine is only filtered by the kidney, its excretion rate shows little variability among individuals and over time, and measurement is accurate and reproducible. In fact, none of the previous assumptions are true.[2] Creatinine is actually filtered and secreted and has been shown to have significant variability with age, sex, ethnicity, and diet.[3] For that, the trend of following renal function based on previously set reference intervals for the general population has largely been replaced by following changes in serum creatinine or creatinine clearance in an individual compared to their baseline. However, to detect pathological changes in serum creatinine one must first consider the existing variance in measurements related to biological and analytical influences.
Rosano and Brown were among the first to examine intra-individual day-to-day creatinine variability by following two individuals for the period of two months. They showed a combined analytical and biological variability of 0.18 – 0.2 mg/dL with analytical variances accounting for the most significant difference.[4] The intra-individual variance for creatinine has been discussed in many studies with values ranging from 4.7 to 6.1% in healthy individuals.[5][6][7] Reinhard et al showed that in patients with pre-existing renal function the variance in serum creatinine can almost reach 8.9%.
The inter-individual variance in creatinine is not as well established, although Reinhard also showed a variance of 14.4% in healthy individuals.[5] Many laboratory factors can have a noted effect on serum creatinine measurements including calibration which can account for changes of up to 0.23 mg/dL,[8] unexplained variance among labs (0.07 mg/dl) and unexplained variance with time (0.053 mg/dL).[9]
CT Scans
The creatinine level is usually measured before performing a contrast-enhanced Computed tomography (CT) scan. In a small proportion of patients the administration of iodine based contrast can cause kidney damage. This may be more likely or severe in patients with an elevated baseline serum creatinine level and, again, in rare cases may require temporary or permanent dialysis. The risk can be reduced somewhat in higher-risk patients by choosing a low-osmolality contrast medium.
See also
- Cystatin C - novel marker of kidney function.
- Creatinine clearance
References
- ↑ Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T (2005). "Diabetic nephropathy: diagnosis, prevention, and treatment". Diabetes Care. 28 (1): 164–76. PMID 15616252.
- ↑ National Kidney Foundation (2002). "K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification". Am J Kidney Dis. 39 (2 Suppl 1): S1–266. PMID 11904577.
- ↑ Perrone RD, Madias NE, Levey AS (1992). "Serum creatinine as an index of renal function: new insights into old concepts". Clin Chem. 38 (10): 1933–53. PMID 1394976.
- ↑ Rosano TG, Brown HH (1982). "Analytical and biological variability of serum creatinine and creatinine clearance: implications for clinical interpretation". Clin Chem. 28 (11): 2330–1. PMID 7127791.
- ↑ 5.0 5.1 Reinhard M, Erlandsen EJ, Randers E (2009). "Biological variation of cystatin C and creatinine". Scand J Clin Lab Invest. 69 (8): 831–6. doi:10.3109/00365510903307947. PMID 19929276.
- ↑ Toffaletti JG, McDonnell EH (2008). "Variation of serum creatinine, cystatin C, and creatinine clearance tests in persons with normal renal function". Clin Chim Acta. 395 (1–2): 115–9. doi:10.1016/j.cca.2008.05.020. PMID 18573244.
- ↑ Bandaranayake N, Ankrah-Tetteh T, Wijeratne S, Swaminathan R (2007). "Intra-individual variation in creatinine and cystatin C." Clin Chem Lab Med. 45 (9): 1237–9. doi:10.1515/CCLM.2007.256. PMID 17848122.
- ↑ Coresh J, Astor BC, McQuillan G, Kusek J, Greene T, Van Lente F; et al. (2002). "Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate". Am J Kidney Dis. 39 (5): 920–9. doi:10.1053/ajkd.2002.32765. PMID 11979335.
- ↑ Joffe M, Hsu CY, Feldman HI, Weir M, Landis JR, Hamm LL; et al. (2010). "Variability of creatinine measurements in clinical laboratories: results from the CRIC study". Am J Nephrol. 31 (5): 426–34. doi:10.1159/000296250. PMC 2883847. PMID 20389058.
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