Clinical and Interpretive

Measurement of creatinine is useful in diagnosing and monitoring treatment of acute and chronic renal diseases, adjusting the dosage of renally excreted medications, and monitoring renal transplant recipients.

Serum creatinine measurement is used in estimating GFR for people with chronic kidney disease (CKD) and those with risk factors for CKD (diabetes, hypertension, cardiovascular disease, and family history of kidney disease).

In muscle metabolism, creatinine is synthesized endogenously from creatine and creatine phosphate. Creatinine is removed from the plasma by glomerular filtration into the urine without being reabsorbed by the tubules to any significant extent. Renal tubular secretion also contributes a small quantity of creatinine to the urine. As a result, creatinine clearance often overestimates the true glomerular filtration rate (GFR) by 10% to >20%.

Determinations of creatinine and renal clearance of creatinine are of value in the assessment of kidney function. Serum or blood creatinine levels in renal disease generally do not increase until renal function is substantially impaired.

GFR is estimated using the 2021 CKD-EPI equation.  Methods that use cystatin C are recommended to confirm estimated GFR in adults who are at risk for or have chronic kidney disease.

Because serum creatinine is inversely correlated with glomerular filtration rate (GFR), when renal function is near normal, absolute changes in serum creatinine reflect larger changes than do similar absolute changes when renal function is poor. Because of the imprecision of serum creatinine as an assessment of GFR, there may be clinical situations where a more accurate GFR assessment must be performed: iothalamate or inulin clearance are superior to serum creatinine. Several factors may influence serum creatinine independent of changes in GFR. For instance, creatinine generation is dependent upon muscle mass. Thus, young, muscular males may have significantly higher serum creatinine levels than elderly females, despite having similar GFRs. Also, because some renal clearance of creatinine is due to tubular secretion, drugs that inhibit this secretory component (eg, cimetidine and trimethoprim) may cause small increases in serum creatinine without an actual decrease in GFR.

The following interferences have been reported:
-Calcium dobesilate (Dexium) at levels of ≥5 mg/dL may cause falsely low results
-N-ethylglycine at therapeutic concentrations and DL
-proline at concentrations ≥1 mmol/L may give falsely high results
-Dobutamine can lead to falsely low results
-Hemolyzed specimens from patients with hemoglobin F (Hbg F) values ≥600 mg/dL interfere with the test. For patients with normal Hgb, no interference is expected for Hgb levels <1,000 mg/dL
-Total bilirubin >25 mg/dL interferes with this assay
-Ascorbic acid >300 mg/L interferes with this assay
-In patients receiving catecholamines (dopamine, dobutamine, epinephrine, and norepinephrine) falsely low results might be observed
-Calcium dobesilate (eg, Dexium), Levodopa and ?-methyldopa cause artificially low creatinine results

The following do not interfere with this assay:
-Ketone bodies
-Cephalosporin antibiotics