Can We Better Understand, Diagnose, and Treat Ketamine-Induced Uropathy, and Can It Be Reversed? ICI-RS 2024.

Introduction: Ketamine, a versatile anesthetic, has seen increased recreational use, leading to significant health issues, including ketamine-induced uropathy (KIU). KIU manifests with lower urinary tract symptoms (LUTS) and can involve the upper urinary tract. This study aims to provide a comprehensive overview of KIU, addressing its pathophysiology, diagnostic strategies, and treatment options; and to define/identify future research priorities.

Methods: During the 2024 meeting of the International Consultation on Incontinence Research Society (ICI-RS) in Bristol, a dedicated Proposal (P) convened to explore KIU. This initiative involved a thorough review of existing literature, expert presentations, and consensus-driven discussions. The methodology ensured a comprehensive exploration of KIU from both clinical and pre-clinical perspectives, leading to actionable research recommendations.

Results: Understanding the mechanisms of KIU is crucial for developing effective treatment options targeting specific pathophysiological pathways. Key findings include bladder fibrosis driven by transforming growth factor-β1 (TGF-β1), elevated purinergic responses and upregulated P2X1 purinoceptor expression, decreased barrier function due to increased expression of antiproliferative factor (APF), and functional loss of the bladder through Cav1.2 channel blockade. Research indicates that fibrosis, typically considered irreversible, may be mitigated. However, the exact timing and extent of fibrosis initiation and its impact on long-term outcomes require further research. LUTS typically improve after ketamine cessation but relapse upon resumption, indicating a hypersensitivity mechanism involving elevated serum IgE levels. Advanced stages of KIU do not always correlate with LUTS severity, shedding light on potential systemic effects and the need for evaluating liver enzymes. Furthermore, psychological dependency on ketamine, due to its positive perceptive and mood-altering effects, complicates cessation efforts. Long-term management requires a holistic approach, integrating medical treatments and supportive measures to help patients navigate life with potentially irreversible complications.

Conclusion: This comprehensive review spans from fundamental pathology to practical clinical management, addressing both urological and systemic complications, and bridging insights from animal models to human applications. Developing effective treatment strategies necessitates addressing both the physical and psychological aspects of ketamine dependency.