PURPOSE OF REVIEW: In the last decade many attempts have been made to reduce the high residual risk of end-stage kidney disease and cardiovascular disease in patients with diabetic kidney disease by targeting a variety of risk markers. Subsequent analyses revealed that the variation in individual drug response to the tested interventions partly explains why these trials did not result in additional kidney or cardiovascular protection. This review summarizes recent insights regarding individual variation in drug response. Additionally, we explore novel approaches to incorporate this drug response variability in the design of new clinical trials. RECENT FINDINGS: Recent studies suggest that a plausible explanation for individual therapy resistance emanates from intrinsic individual characteristics such as genetic make-up or volume status and is likely only partially explained by drug characteristics such as the dose or type of intervention. Biomarker-based enrichment strategies to identify high-risk individuals and/or those who are more likely to respond to interventions offer opportunities to tailor therapies to individual patients. SUMMARY: Individual drug response variability is a recognized phenomenon in clinical practice. It is time to implement novel approaches that take into account this response variability in the design of new trials in diabetic kidney disease in order to define optimal therapies for individual patients.
PURPOSE OF REVIEW: In the last decade many attempts have been made to reduce the high residual risk of end-stage kidney disease and cardiovascular disease in patients with diabetic kidney disease by targeting a variety of risk markers. Subsequent analyses revealed that the variation in individual drug response to the tested interventions partly explains why these trials did not result in additional kidney or cardiovascular protection. This review summarizes recent insights regarding individual variation in drug response. Additionally, we explore novel approaches to incorporate this drug response variability in the design of new clinical trials. RECENT FINDINGS: Recent studies suggest that a plausible explanation for individual therapy resistance emanates from intrinsic individual characteristics such as genetic make-up or volume status and is likely only partially explained by drug characteristics such as the dose or type of intervention. Biomarker-based enrichment strategies to identify high-risk individuals and/or those who are more likely to respond to interventions offer opportunities to tailor therapies to individual patients. SUMMARY: Individual drug response variability is a recognized phenomenon in clinical practice. It is time to implement novel approaches that take into account this response variability in the design of new trials in diabetic kidney disease in order to define optimal therapies for individual patients.
Authors: Michele Provenzano; Maria Chiara Pelle; Isabella Zaffina; Bruno Tassone; Roberta Pujia; Marco Ricchio; Raffaele Serra; Angela Sciacqua; Ashour Michael; Michele Andreucci; Franco Arturi Journal: Front Med (Lausanne) Date: 2021-06-04