Hypothesis / aims of study
Recreational ketamine use has become increasingly popular in the last decade. Ketamine abuse can lead to severe inflammation of the bladder, resulting in debilitating lower urinary tract symptoms (LUTS), pain and haematuria. It can also lead to upper urinary tract (UUT) involvement, by mechanical ureteral obstruction at the bladder wall, by high bladder pressure with or without vesicoureteral reflux or by direct involvement of the urothelium of the UUT. UUT involvement may ultimately result in renal insufficiency in this young patient population. This study aimed to identify risk factors from baseline evaluations associated with UUT involvement in patients with ketamine induced uropathy (KIU).
Study design, materials and methods
Patients visiting a dedicated KIU outpatient clinic between December 2019 and December 2024 were included in a cross-sectional study. A history of renal or ureteral surgery were exclusion criteria. Structured patient history, blood tests, urine samples and imaging of the UUT either with ultrasonography or computed tomography (CT) were performed during the first visit. UUT involvement was defined as the presence of hydronephrosis on imaging, and was correlated with demographics, and items from the first visit (Table 1). Descriptive analysis, independent t-test (continuous variables), Chi-square test (categorical variables) and binary logistic regression were performed with SPSS (version 27, IBM). Statistical significance was set at p<0.05.
Results
A total of 171 patients (122 (71%) male) were included for analysis (Table 1). A total of 26 (15%) patients had UUT involvement. The univariate analysis is presented in Table 1. UUT involvement was associated with loin pain, micturition frequency, maximum voided volume < 100 mL, gross and microscopic haematuria, estimated Glomerular Filtration Rate <70mL/min/m2, proteinuria and leukocyturia, Binary logistic regression analysis (Table 2) yielded an Odds Ratio (OR) for UUT involvement of 25.64 (95% confidence interval (CI) 2.45-250, p=0.006) for maximum voided volume <100mL and of 1.06 (95%CI 1.01-1.12, p=0.026) for an eGFR <70mL/min/m2.
Interpretation of results
Our study showed a prevalence of 15% of UUT involvement in a cohort of KIU patients. This is consistent with previous research (1). We did not observe an association between age, or intensive ketamine use (dose and duration) and UUT involvement.
As expected, we found a strong association between the presence of loin pain and UUT involvement, defined as hydronephrosis on imaging. Together with gross haematuria, these clinical symptoms can be useful to identify patients at risk of having UUT involvement.
A maximum voided volume smaller than 100 mL has a very high OR of 25.64 of having UUT involvement. It is hypothesized that UUT involvement occurs secondarily to bladder deterioration, where a small functional bladder capacity is present (partly) due to a thickened bladder wall. This can lead to reduction in bladder compliance and either obstruction at the ureterovesical junction or vesicoureteral reflux at higher bladder pressures.
The finding of proteinuria and a reduced eGFR in a considerable number of patients indicate potential irreversible renal damage. This is alarming in this young patient population. In addition to other measures to ameliorate pain and LUTS, prompt drainage of the UUT is therefore recommended.
Concluding message
For clinicians, it is important to consider the presence of UUT involvement as a secondary consequence of KIU as early as possible. In this study, we showed that risk factors associated with UUT involvement can be identified from a baseline analysis of KIU patients, which could facilitate stratification of patients who require closer monitoring or urgent intervention. Notably, we found that low functional bladder capacity is strongly associated with UUT involvement, emphasizing its potential role as a key risk factor in clinical assessment.