Recreational ketamine use was first reported in the 1970’s and it has become increasingly popular over the last two decades (3). Norketamine is the active metabolite in ketamine and is excreted via the urinary system. The direct toxic effects of ketamine on the epithelial lining of the bladder allows urine to seep through, it then has the potential to reach the inner layers and cause deeper damage (2) often leading to a reduction in the anatomical capacity of the bladder. For that reason lower urinary tract symptoms (LUTS) are highly prevalent in this group. The bladder is not the only affected organ, the upper urinary  tract can be affected secondarily due to a bladder high pressure leading to hydronephrosis , usually bilateral; this has been reported in up to 30% of users (1) or the ureters can be affected directly by the toxic effect of ketamine causing wall thickening and stenosis. 

There is some evidence that the duration of use correlates with the severity of LUTS (1). It is not clear whether the amount used or the duration of consumption is related to bladder capacity reduction as well as upper tract involvement. It is worth noting that there is currently no universal definition of what is considered a large amount of ketamine or what constitutes a prolonged duration of use. 

The aim of our study is to identify the theoretical correlation between the amount of ketamine consumed (grams per week) LUTS, anatomical bladder capacity reduction and upper tract involvement.

A prospective study was conducted in a tertiary centre in the South West of the UK. Inclusion criteria were male and female patients aged 16 and over with previous and current consumption of Ketamine and secondary LUTS. All patients completed symptom questionnaires (ICIQ FLUTS and MLUTS), answered questions regarding dosage (grams /week) and time of usage. Blood tests including eGFR were performed in every case. Patients without complete investigations or information were excluded from the analysis.  A sub-analysis of patients in the cohort who had undergone an anatomical bladder capacity measurement was performed. 

R software, version 4.3.0, was used for statistical analysis. The characteristics of the study were summarised using descriptive statistics. To determine the distribution of numerical variables, measures of central tendency and dispersion were calculated, and frequency distributions for categorical variables. Normality of the numerical variables was evaluated through the Shapiro-Wilk test and the Fisher’s exact and Mann Whitney u tests were used to evaluate statistically significant differences, with a significance level of 5%.

There were 54 patients included in the study. 31 (57.4%) female and 23 (42.6%) male. The median age was 32. We defined “low use” as less than 30g of ketamine per week and “high use” as more than 30g per week. Time of consumption was divided in 1- 5 years vs over 5 years of use.

Kidney function was considered normal when the eGFR was 90 or above. 12 (22.2%) had an abnormal result(p=0.99). Interestingly out of the 12 patients found to have hydronephrosis on imaging 8 were in the low use group and 4 in the high use group(p=0.70). Fifteen patients had ureteric involvement on imaging (stenosis or ureteric fibrosis) 11 were from the low use group and 4 from the high use group (p=0.50)  Based on these findings we were unable to find a correlation between the amount of ketamine used and either upper tract involvement or renal dysfunction. 

We were able to demonstrate an association between urinary frequency and higher consumption(p=0.03). However, all the other symptoms evaluated with consumption dose did not reach statistical significance (Table 1).  The group with over 5 years of consumption presented more nocturia (p=0.02) and pelvic pain (p=0.02) (Table2)

Anatomical bladder capacity was lower in patients with higher consumption (smallest was 40mls) compared to patients with lower consumption (400mls). Consumption of over 5 years was also associated with lower anatomical bladder volumes 170 ml vs 271.  However no statistical significance was reached in either (p=0.20 and p=0.30) . We can hypothesize that dose and time are related to the damage but no statistical significance was found, this is likely due to the small number of patients in the sub analysis. 

Incidentally we also demonstrated a clear association between dose and time. Patients with a consumption over 5 years significantly consumed  higher doses p=0.003 (table 2). Suggesting that the effect of ketamine decreases over time and people increase the dose over time to experience the same effects.

Ketamine induced LUTS especially urinary frequency, nocturia and pelvic pain are  correlated with the amount and time of ketamine use. In this study we could not demonstrate a correlation between either dose or time with upper tract involvement or impaired kidney function. Patients with higher or longer consumption have a tendency for smaller bladder capacities without reaching statistical significance in our study.

Chan, EOT et al (2022) Systematic review and meta-analysis of ketamine associated uropathy. Hong Kong Medical Journal. 28)6_ 466-474
Li, CC (2019) A survey for ketamine abuse and it’s relation to the lower urinary tract symptoms in Taiwan. Scientific Reports.
Yee, CH et al (2017) The Risk of Upper Urinary Tract Involvement in Patients With Ketamine-Associated Uropathy. International Neurourology Journal. Volume 21(2) 128-132