Reference range (interval) for serum creatinine

Routine laboratory assessment of renal function depends on estimating glomerular filtration rate from serum creatinine concentration. Serum creatinine concentration is age- and gender-dependent. A recently published study aimed to establish age-stratified and gender-specific reference intervals for serum creatinine concentration among the Chinese population. 

The methodology for the study was based closely on the rigorous expert recommendations for determining reference intervals contained in the Clinical and Laboratory Standards Institute (CLSI) document CLSI C28-A3. The process began with careful selection of healthy volunteers from an initial study population of 3640 aged 60-89 years and 2487 aged 18-59 years. 

Physical examination and clinical testing of each was used to confirm a ”healthy” status for reference individuals. Exclusion criteria included: a diagnosis of any chronic or acute disease; surgery in the past 6 months; drug prescription in the past 2 weeks; excessive smoking or alcohol use; body mass index outside healthy limits; abnormal laboratory test results; abnormal chest X-ray or abnormal ultrasound scan of heart, liver, lungs or kidney.

Blood for serum creatinine was collected according to a standard protocol designed to minimize preanalytical/physiological variation. This included direction to avoid strenuous exercise and alcohol for 3 days prior to blood collection and to fast overnight before the day of blood collection. 

Blood was collected after resting for at least 30 minutes, and the recovered serum analyzed within 2 hours of blood collection using a well-validated, commonly used enzyme-based automated method.

After exclusion of ”non-healthy” volunteers and those with “outlier” serum creatinine concentrations, the serum creatinine results of 1691 (856 male, 835 female) healthy volunteers were used to construct 95 % reference intervals by excluding the lowest and highest 2.5 percentile values. 

Gaussian distribution was confirmed, as was the well-documented statistically significant gender difference (serum creatinine significantly higher among men). No statistically significant difference was noted with respect to age for those in the age range of 18-59 years so these were combined to construct two reference intervals: one for males (59-91 µmol/L) and one for females (41-66 µmol/L). 

Serum concentration was, however, found to increase with age for those aged >60 years so individual male and female reference intervals were constructed for each of the following three age ranges: 60-69 years (males: 53-94 µmol/L, females: 44-75 µmol/L); 70-79 years (males: 57-106 µmol/L, females: 46-82 µmol/L); and 80-89 years (males: 59-111 µmol/L, females: 45-91 µmol/L). 

In discussion of their study the authors compare their results with other similar studies, including the Nordic reference interval project (NORDIC) study, and note that most other investigators did not partition creatinine values according to age over the age of 60 and so produced just one adult reference interval for all males over the age of 18 years and one for all females over the age of 18 years.