Vascular fibrinoid necrosis in the urinary bladder of ketamine abusers: A new finding that may provide a clue to the pathogenesis of ketamine‐induced vesicopathy

Chen, Yen-Chang; Jhang, Jia‐Fong; Hsu, Yung‐Hsiang; Kuo, Hann‐Chorng

doi:10.1111/luts.12221

Cited by 8 publications

(3 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent finding of fibrinoid necrosis along the wall of blood vessels supports the role of the immune system in KC pathogenesis 37 . Fibrinoid necrosis is a lesion caused by an immune reaction and subsequent release of inflammatory mediators with thrombosis, which occurs when antigen‐antibody complexes are deposited in the arterial walls 37 .…”

Section: Evidencementioning

confidence: 96%

What urologists need to know about ketamine‐induced uropathy: A systematic review

Castellani

Pirola

Gubbiotti

et al. 2020

Neurourology and Urodynamics

View full text Add to dashboard Cite

Aims: Ketamine is a general anesthetic. Dissociative effects and low cost led ketamine becoming an illegal recreational drug in young adults. Ketamineinduced uropathy (KIU) is one of the complications observed in abusers. This study aimed to provide a systematic literature review on KIU clinical presentation, pathophysiology, and treatments. Methods: We performed the literature search in PubMed, Web of Science, Scopus, and Embase using the terms ketamine and bladder. English papers on human and animal studies were accepted. Results: A total of 75 papers were selected. Regular ketamine users complain about severe storage symptoms and pelvic pain. Hydronephrosis may develop in long-term abusers and is correlated to the contracted bladder, ureteral stenosis, or vesicoureteral reflux due to ureteral involvement and/or bladder fibrosis. Cystoscopy shows ulcerative cystitis. Ketamine in urine might exert direct toxicity to the urothelium, disrupting its barrier function and enhancing cell apoptosis. The presence of ketamine/ions in the bladder wall result in neurogenic/IgE-mediated inflammation, stimulation of the inducible nitric oxide synthase-cytokines-cyclooxygenase pathway with persistent inflammation and fibrosis. Abstinence is the first therapeutic step. Anti-inflammatory drugs, analgesics and anticholinergics, intravesical instillation of hyaluronic acid, hydrodistension and intravesical injection of botulin toxin-A were helpful in patients with early-stage KIU. In patients with end-stage disease, the control of intractable symptoms and the increase of bladder capacity were the main recommendations to perform augmentation enterocystoplasty.Conclusions: KIU is becoming a worldwide health concern, which should be taken into account in the differential diagnosis of ulcerative cystitis. K E Y W O R D S cystitis, inflammation, ketamine, lower urinary tract symptoms, substance-related disorders, urinary tract 1050 | CASTELLANI ET AL.

show abstract

Section: Evidencementioning

confidence: 96%

What urologists need to know about ketamine‐induced uropathy: A systematic review

Castellani

Pirola

Gubbiotti

et al. 2020

Neurourology and Urodynamics

View full text Add to dashboard Cite

show abstract

“…The subsequent pathophysiology includes the thickening of the endothelial basement membrane, chronic inflammation, interstitial fibrosis, and a decrease in the density of microvessels [ 25 ]. Histopathological findings in the ketamine cystitis bladder show ulcerative cystitis with fibrinoid necrosis within small- and medium-sized arterioles [ 26 ] [ Figure 6 ]. These microvascular injuries may involve antigen–antibody immune complexes in the arterial walls, inflammation, and autoimmune-mediated vascular congestion [ 4 ].…”

Section: P Athophysiologymentioning

confidence: 99%

“… Histopathological finding of ketamine cystitis shows thickening of the endothelial basement membrane (arrow), chronic inflammation, interstitial fibrosis, and fibrinoid necrosis within small- and medium-sized arterioles [ 26 ] …”

Section: P Athophysiologymentioning

confidence: 99%

Pathophysiology, clinical presentation, and management of ketamine-induced cystitis

Jhang

Birder

Kuo

2023

Tzu Chi Medical Journal

View full text Add to dashboard Cite

A BSTRACT Ketamine is illegally used as a recreational drug in many Asian countries. Long-term ketamine abusers often develop irritable bladder symptoms that gradually develop into more severe urinary frequency and urgency and eventually into a painful ulcerated bladder. These patients typically have reduced functional bladder capacity, increased bladder sensation, detrusor overactivity, severe urgency, urinary incontinence, and bladder contracture. Ketamine metabolites can cause severe inflammation of the urothelium, urothelial barrier deficits, vascular endothelial fibrinoid changes, increased oxidative stress, and bladder wall fibrosis. A decrease in bladder compliance, urinary tract infection, severe bladder pain with a full bladder, and painful micturition are also common symptoms. Finally, with continued abuse of ketamine, hydronephrosis, ureteral stricture, vesicoureteral reflux, and renal failure may develop. Cessation of ketamine is the mainstay of treatment. Lower urinary tract symptoms usually relapse if patients reuse ketamine after stopping. In cases of severe ketamine cystitis, only augmentation enterocystoplasty can relieve bladder pain and restore normal lower urinary tract function. This article reviews the underlying pathophysiology, clinical characteristics, and management of ketamine cystitis.

show abstract

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

Hervé,

Aronsson,

Ochoa

et al. 2024

Neurourology and Urodynamics

View full text Add to dashboard Cite

IntroductionKetamine, 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.MethodsDuring 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.ResultsUnderstanding 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.ConclusionThis 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.

show abstract

Vascular fibrinoid necrosis in the urinary bladder of ketamine abusers: A new finding that may provide a clue to the pathogenesis of ketamine‐induced vesicopathy

Cited by 8 publications

References 5 publications

What urologists need to know about ketamine‐induced uropathy: A systematic review

What urologists need to know about ketamine‐induced uropathy: A systematic review

Pathophysiology, clinical presentation, and management of ketamine-induced cystitis

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

Contact Info

Product

Resources

About