Background:
Autosomal dominant polycystic kidney disease (ADPKD) is the
most common life-threatening genetic disease in humans, affecting approximately 1 in 500
people. ADPKD is characterized by cyst growth in the kidney leading to progressive parenchymal
damage and is the underlying pathology in approximately 10% of patients requiring
hemodialysis or transplantation for end-stage kidney disease. The two proteins that are mutated
in ADPKD, polycystin-1 and polycystin-2, form a complex located on the primary cilium
and the plasma membrane to facilitate calcium ion release in the cell. There is currently
no Food and Drug Administration (FDA)-approved therapy to cure or slow the progression of
the disease. Rodent ADPKD models do not completely mimic the human disease, and therefore
preclinical results have not always successfully translated to the clinic. Moreover, the
toxicity of many of these potential therapies has led to patient withdrawals from clinical trials.
Results:
Here, we review compounds in clinical trial for treating ADPKD, and we examine
the feasibility of using a kidney-targeted approach, with potential for broadening the therapeutic
window, decreasing treatment-associated toxicity and increasing the efficacy of agents that
have demonstrated activity in animal models. We make recommendations for integrating kidney-
targeted therapies with current treatment regimes, to achieve a combined approach to
treating ADPKD.
Conclusion:
Many compounds are currently in clinical trial for ADPKD yet, to date, none are
FDA-approved for treating this disease. Patients could benefit from efficacious pharmacotherapy,
especially if it can be kidney-targeted, and intensive efforts continue to be focused on
this goal.
Management of targeted therapies in cancer patients with chronic kidney disease, or on haemodialysis: An Associazione Italiana di Oncologia Medica (AIOM)/Societa’ Italiana di Nefrologia (SIN) multidisciplinary consensus position paper
