When serum creatinine concentration (SCr) reaches a value of more than 1.1 mg/dL for women and 1.2 mg/dL for men, it is considered elevated. A raised SCr usually indicates a decrease in renal function, mainly the glomerular filtration rate (GFR), with an associated rise in blood urea nitrogen (BUN) due to prerenal, renal, or postrenal causes.

Medications can increase SCr independent of a true reduction in GFR and concomitant rise in BUN, meaning that there is no real change in overall kidney function. These false estimates can occur through several broad mechanisms, including decreased creatinine secretion, serum assay interference, and enhanced creatinine production.

Some drugs inhibit tubular secretion, thereby decreasing SCr clearance without influencing GFR; these include the H2 blockers cimetidine and famotidine, dronedarone, pyrimethamine, salicylates, and trimethoprim. HIV treatments, such as cobicistat and dolutegravir, increase SCr and decrease estimated GFR due to lowered creatinine secretion by blocking organic cation transporters and by inhibiting the SLC47A1 gene, respectively. The poly (ADP-ribose) polymerase inhibitors olaparib and rucaparib potentially inhibit proximal tubule transporters, while tyrosine kinase inhibitors (ie, bosutinib, crizotinib, gefitinib, imatinib, pazopanib, sorafenib, and sunitinib) hinder SLC47A1-mediated creatinine secretion, thereby elevating SCr.

Drugs that interfere with alkaline picrate colorimetric assays, causing falsely elevated SCr readings, include cephalosporins (ie, cefoxitin and cephalothin), acetohexamide, high furosemide doses, methyldopa, and phenacemide. Flucytosine and lidocaine are also known to erroneously elevate SCr values in enzymatic assays.

SCr elevation due to enhanced creatinine output may stem from an increased intake of red meat or due to decreased estimated GFR (eGFR) in those taking creatine supplements.

Other drugs reported to alter SCr where the mechanism is only partly understood include fenofibrate, phenacemide, corticosteroids, and vitamin D derivatives.