Variability in drug response: towards more personalized diabetes care

Efficacy of renoprotective therapies in patients with chronic kidney disease (CKD) is highly variable. Strikingly, despite optimally dosed renin-angiotensin-aldosterone system (RAAS) inhibitors, every third patient does not respond to the treatment, with consequent ongoing renal function loss and eventually renal failure. Obviously, it is of great clinical importance to elucidate the mechanisms underlying therapy resistance, and to design strategies for its circumvention.Although the term “personalized medicine” was already used in literature decades ago the subject has attracted relatively little attention in the nephrology literature in the last decade [1]. The emphasis in randomized controlled clinical trials, which form the basis for clinical practice guidelines, has been on the comparison of fixed drug regimens at a population level but not on the individual level [2]. Considering the large between personal differences in therapy response to any particular renoprotective regimen, it is highly likely that much would be gained if the response in poor responders could be improved to the level of good responders. This requires specific focus on personalized approach. In contrast to oncology, where personalized therapy approaches has driven pharmacological innovation for a long time, the nephrology community has not (yet) completely embraced this personalized routine. This thesis describes various studies to assess the variability in response to current and new interventions and investigates ways to improve the individual therapy response to treatment resistant patients.

Dissertation: http://hdl.handle.net/11370/d62bc4c9-54af-4863-a744-87053a1b643b