Kidney-targeted therapies: A quantitative perspective

Chronic and acute kidney disease constitute a worldwide health burden, but are still lacking efficient therapeutics. Current medication such as anti-inflammatory steroids causes systemic side effects, and is unable to stop the progression of the disease. Efforts have been devoted towards the development of renal-targeted therapies, however, no such approach has reached the clinic, yet. Here, we critically review the current status of renal-targeted drugs and delivery strategies. Specifically, we focus on the quantitative aspect of delivery by compiling information on kidney-to-liver ratios and also investigating to which degree the implementation of a targeting functionality increases the distribution of the drug to the kidney. As we show, two types of functional outcomes can be distinguished: (i) Targeting to the kidney goes along with an increase in kidney-to-liver ratio. This, we denote as direct targeting; (ii) the accumulation of the drug in the kidney increases, but the kidney-to-liver ratio remains unchanged, thereby the carrier leads to a general uptake enhancement. Overall, the most effective targeting was reached with receptor and transporter directed strategies. Reaching glomerular cells and the avoidance of liver accumulation for nanoparticulate formulations pose the greatest challenges.