Currently Used Methods to Evaluate the Efficacy of Therapeutic Drugs and Kidney Safety

Abstract

Kidney diseases with kidney failure or damage, such as chronic kidney disease (CKD) and acute kidney injury (AKI), are common clinical problems worldwide and have rapidly increased in prevalence, affecting millions of people in recent decades. A series of novel diagnostic or predictive biomarkers have been discovered over the past decade, enhancing the investigation of renal dysfunction in preclinical studies and clinical risk assessment for humans. Since multiple causes lead to renal failure, animal studies have been extensively used to identify specific disease biomarkers for understanding the potential targets and nephropathy events in therapeutic insights into disease progression. Mice are the most commonly used model to investigate the mechanism of human nephropathy, and the current alternative methods, including in vitro and in silico models, can offer quicker, cheaper, and more effective methods to avoid or reduce the unethical procedures of animal usage. This review provides modern approaches, including animal and nonanimal assays, that can be applied to study chronic nonclinical safety. These specific situations could be utilized in nonclinical or clinical drug development to provide information on kidney disease.

Keywords: acute kidney injury; alternative methods; biomarkers; chronic kidney disease; kidney disease models.

Figure 1

Biomarkers of kidney injury: the traditionally used markers in blood and urine are predictive, diagnostic, and prognostic characteristics of the different processes of kidney injury. Serum and urinary biomarkers of kidney disease facilitate earlier detection and prevention to establish effective therapies.

Figure 2

Schematic representation of identification techniques, protein assays, bioinformatics techniques, and molecular dynamics simulations for drug safety and efficacy assays.

Figure 3

Flowchart of various CADD methods used in drug discovery (abbreviations: CADD: computer-aided drug design; QM: quantum mechanical; MM: molecular mechanical; QSAR: quantitative structure-activity relationship).