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Chronic kidney disease (CKD) requires collaborative and comprehensive management. CKD progresses through stages and can lead to end-stage kidney disease (ESKD) if untreated. Interprofessional collaboration and patient education are crucial, enabling patients to manage their health and improve their quality of life.Diagnostic approach for chronic kidney diseaseThe diagnosis of CKD primarily focuses on the glomerular filtration rate (GFR), which assesses kidney function by measuring how well...
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Renal clearance is a crucial parameter in pharmacokinetics that quantifies the rate at which the kidneys excrete a drug. It represents a constant fraction of the central volume of distribution containing the drug that the kidney eliminates per unit of time.
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Kidney-targeted therapies: A quantitative perspective.

Alexander H van Asbeck1, Jürgen Dieker1, Milou Boswinkel1

  • 1Dept. of Biochemistry (286), Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands.

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Developing effective renal-targeted therapies for kidney disease remains a challenge. This review analyzes drug delivery strategies, highlighting receptor and transporter-directed methods as most promising for improving kidney drug distribution.

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Area of Science:

  • Pharmacology
  • Nephrology
  • Drug Delivery Systems

Background:

  • Chronic and acute kidney diseases represent a significant global health issue with limited therapeutic options.
  • Current treatments, like anti-inflammatory steroids, have systemic side effects and fail to halt disease progression.
  • Existing renal-targeted therapies have not yet reached clinical application.

Purpose of the Study:

  • To critically review the current landscape of renal-targeted drugs and delivery strategies.
  • To quantitatively assess drug delivery to the kidney by analyzing kidney-to-liver ratios.
  • To evaluate the impact of targeting functionalities on drug distribution within the kidney.

Main Methods:

  • Compilation and analysis of existing data on kidney-to-liver ratios for various drug delivery systems.
  • Investigation into the effectiveness of different targeting strategies in enhancing renal drug accumulation.
  • Categorization of targeting outcomes into direct targeting and general uptake enhancement.

Main Results:

  • Two primary functional outcomes of renal targeting were identified: direct targeting (increased kidney-to-liver ratio) and general uptake enhancement (increased kidney accumulation without altered ratio).
  • Receptor- and transporter-directed strategies demonstrated the most effective targeting to the kidney.
  • Nanoparticulate formulations face challenges in targeting glomerular cells and avoiding liver accumulation.

Conclusions:

  • Receptor and transporter-mediated targeting represent the most effective strategies for enhancing drug delivery to the kidney.
  • Overcoming challenges in targeting specific renal cells and minimizing off-target accumulation, particularly in the liver for nanoparticles, is crucial for clinical translation.