Positive and negative false estimates of serum creatinine

Abstract

Accurate and precise measurement of serum creatinine is very important for assessment of kidney function. However, false estimates of serum creatinine have been found due to interference by both exogenous and endogenous substances which have been attributed to factors such as decreased or inhibited tubular secretion of creatinine, interference with serum creatinine assays and increased production of creatinine. Several drugs cause positive and negative interference through these mechanisms resulting in false positive and negative estimates of serum creatinine which may affect glomerular filtration rate (GFR) calculation also. Endogenous substances also affect the creatinine assay systems resulting in false estimate of serum creatinine concentration. Therefore, the awareness about the drug-induced or endogenous substance-induced false estimates of serum creatinine and preanalytical errors in blood sampling is important. Some remedial measures to avoid these interferences are: (i) avoiding blood draws from indwelling catheter, (ii) giving preference to fasting blood specimen and (iii) selecting the suitable analytical method for creatinine estimation (based on the information about the drugs being given to the concerned patient).

Drug dosing using estimated glomerular filtration rate: Misclassification due to metamizole interference in a creatinine assay

“…In addition to metamizole, other substances can also affect creatinine values. 28 Since peroxide is necessary for enzymatic reactions, antioxidant agents can lead to a negative bias. 29 Catecholamine interference is also known, leading to significant decrease in some platforms, mainly with the use of dobutamine and norepinephrine.…”

A Review of Specific Biomarkers of Chronic Renal Injury and Their Potential Application in Nonclinical Safety Assessment Studies

“…11,12,112,[128][129][130][131][132][133][134] While the majority of creatinine is filtered unchanged through the glomerulus into the urinary filtrate, over 40% may be secreted via renal transporters depending on the species, and this transport may be affected by drugs. 12,[135][136][137] Tubular secretion can be increased to up to 50% of total renal elimination as GFR declines and can be supplemented with increased extrarenal elimination via the gastrointestinal tract. 11,130,138,139 Creatinine production differs between patients with stable CKD and those with progressive disease due to comorbidities, further limiting its utility.…”

“…In addition, several drugs can compete or interfere with the renal creatinine transporter system resulting in spurious changes. 5,[10][11][12][13] For animals such as dogs that are generally on meat diets, creatinine is vulnerable to diet-related variability (eg, higher creatinine with meat vs casein-based diets) and other factors including muscle mass and body weight (ie, higher serum creatinine levels with larger muscle mass), housing, circadian and seasonal variation, hydration status, physical activity, drug treatment, and age. 14 In humans, AKI is defined as damage or loss of kidney function for a duration of 7 to 90 days after an AKI initiating event which would parallel renal injury occurring during the acute/subacute nonclinical toxicity study time frame.…”

Lithium heparin interference in the Abbott enzymatic creatinine assay: the significance of under-filled tubes

“…2 These are now the method of choice recommended by clinical guidelines. However, enzymatic methods are not without problems 3 ; interference from haemoglobin, bilirubin and glucose still occurs, for example, albeit to a lesser extent than with the Jaffe methodology. We report for the first time the potential for significant overestimation of creatinine by the Abbott Architect enzymatic creatinine assay in under-filled lithium heparin tubes.…”