Design of kidney-targeted drug-carrier conjugates for the inhibition of profibrotic signaling cascades

In the past decades, the worldwide number of patients with chronic kidney disease (CKD) has increased remarkably and it is expected that this increasing trend will continue during the coming years (1). At this moment, therapy is focused on the prevention of progressive CKD by treatment of the underlying causes, such as hypertension, diabetes and obesity. CKD is asymptomatic in the initial stage and is often diagnosed in a stage at which treatment of the underlying cause alone is not sufficient to stop loss of kidney function. As a consequence, CKD will gradually progress to end-stage renal disease (ESRD) and renal dialysis or kidney transplantation are then the only possibilities for patients to survive. Because of the lack of clinically available drugs that can halt the progression of CKD and the seriousness of the disease, there is a high need for novel drugs. This thesis focuses on the intracellular delivery of drugs into the proximal tubular cells of the kidneys. Tubulointerstitial fibrosis is one of the common hallmarks of progressive CKD and renal drug targeting to the proximal tubular cells can be of great value in the development of therapeutics that halt or reverse tubulointerstitial fibrosis.