The Need for Novel Therapeutic Directions in Autosomal Dominant Polycystic Kidney Disease Patient Care

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disorder and is characterized by the progressive growth of multiple kidney cysts, leading to kidney failure in most patients. The management of ADPKD, which up to a decade ago was limited to supportive measures to preserve kidney function and prevent complications, has evolved with the regulatory approval of disease-modifying agents. This review provided an overview of the current status and future perspectives of treatment for ADPKD. At present, the only drugs approved to slow disease progression are the vasopressin V2-receptor antagonist tolvaptan and, in Italy, the somatostatin analog octreotide long-acting release for the subset of patients with stage 4 CKD. However, various therapeutic strategies are under clinical investigation. These include not only repurposed pharmacological agents, namely sodium-glucose cotransporter-2 inhibitors, metformin, and glucagon-like peptide-1 receptor agonists, but also innovative therapies which is the case for a monoclonal antibody against pregnancy-associated plasma protein-A, microRNA-17 inhibitors, and the polycystin-1 correcting agent VX-407. Dietary interventions, such as caloric restriction and ketogenic diets, are being tested in clinical trials as well and could complement pharmacotherapy to slow disease progression. Moreover, the rapid advancements in the field of gene therapy for ADPKD suggest that this approach, though as yet only explored at experimental level, could be translated into clinical practice in future to correct the underlying genetic defect, and potentially reverse disease pathogenesis, thereby improving patient outcomes.