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What are the major limitations of serum creatinine as a clinical index of kidney disease?
Creatinine is generated from the breakdown of creatine in muscle, distributed throughout total body water, and excreted by the kidneys primarily by glomerular filtration. Although the serum level is affected primarily by the level of GFR, it is also affected by other physiologic processes, such as tubular secretion, generation, and extrarenal excretion of creatinine.
The below table lists the factors that limit use of creatinine as estimated GFR. Due to variation in these processes among individuals and over time within individuals, especially creatinine generation, the cutoff for normal versus abnormal serum creatinine concentration differs among groups.
In addition, assays for serum creatinine vary across clinical laboratories, leading to differences in GFR estimates for the same patient when creatinine is measured in different labs.
Factors That Limit Use of Estimated Glomerular Filtration Rate from Creatinine and Cystatin C
Creatinine | Cystatin C | |
|---|---|---|
| Factors affecting generation | Decreased eGFR from:• large muscle mass• high-protein diet• ingestion of cooked meat• creatine supplementsIncreased eGFR by:• small muscle mass• amputation• muscle wasting diseases | Decreased eGFR in hyperthyroidismIncreased eGFR in:• hypothyroidism• obesity• glucocorticoid use• inflammation (higher CRP, lower serum albumin, higher WBC)• smokingOlder ageMale genderElevated urine proteinMalignancies |
| Factors affecting tubular reabsorption and secretion | Decreased eGFR by drug-induced inhibition of secretion (See list in the text) | Not known |
| Factors affecting extrarenal elimination | Decreased eGFR by inhibition of gut creatininase by antibiotics.Increased eGFR by:• dialysis• large losses of extracellular fluid (e.g., drainage of pleural fluid or ascites) | Increased eGFR by large losses of extracellular fluid (e.g., drainage of pleural fluid or ascites) |
| Interference with assays | Spectral interferences• bilirubin• some drugsChemical interference• glucose• ketones• bilirubin• some drugs | Not known |
CRP, C-reactive protein; eGFR , estimated glomerular filtration rate; WBC, white blood cell.Sources of Error in Interpretation of Estimated GFR from creatinine and cystatin C.
