Challenges of Serum Creatinine Level in GFR Assessment and Drug Dosing Decisions in Kidney Injury.

Abstract

Serum creatinine (SCr) is widely regarded as a standard biomarker for assessing glomerular filtration rate (GFR) and is commonly used to guide dose adjustments for renally eliminated drugs. However, the application of SCr as a marker for evaluating GFR and drug dosing in kidney injury has significant limitations that are often overlooked in clinical practice. This oversight can result in subtherapeutic drug concentrations or adverse drug reactions due to inappropriate dosing adjustments based on SCr levels alone. This review aimed to highlight the factors affecting serum creatinine (SCr) and the challenges associated with using SCr as a biomarker for assessing GFR and adjusting drug doses with regard to its limitations and variability. The findings of this review underscore the complexity of SCr regulation, which is affected by its synthesis, metabolism, and excretion processes (glomerular filtration, tubular secretion, tubular reabsorption and extra-renal elimination), and disease states (such as trauma-induced hyperfiltration and HIV) and the use of medications (drug-creatinine interactions) lead to altered renal excretion of creatinine, either increasing or decreasing its levels. Additionally, the renal excretion pathways for drugs and creatinine are not entirely the same, making it difficult to use creatinine to evaluate drug renal excretion. In conclusion, SCr is an imperfect index of GFR and adjusting drug dosing, and the development of multi-biomarker panels, incorporating biomarkers from different excretory pathways-particularly those involving tubular transport-holds promise for improving the evaluation of renal excretory function and ensuring safer and more effective drug dosing.