#2976 Comparison of standard versus high dose urokinase for dysfunctional tunneled dialysis catheters in haemodialysis patients: a randomized controlled trial

Abstract Background and Aims Tunneled dialysis catheters (TDCs) remain a frequent first-line vascular access for patients with end-stage kidney disease (ESKD) undergoing haemodialysis (HD), who do not have a functioning arteriovenous fistula or graft. TDC dysfunction is a common complication in these patients and thrombolytic therapy is frequently used to restore catheter patency prior to a TDC exchange, which is more invasive and costly, and invariably requiring hospitalization. Urokinase is preferred over recombinant tissue plasminogen activator due to cost and logistic concerns, however, what constitutes the most effective dose remains unsettled. We therefore aimed to study if a higher dose (30,000 unit per catheter lumen) is more effective in restoring catheter patency without a higher risk of adverse effects compared to standard dosing (20,000 unit per lumen) in a multi-ethnic Asian setting. Method Patients who meet eligibility criteria were randomized via block randomization method to standard or high dose groups. A successful final outcome was defined as restoration of catheter patency allowing for uneventful HD and discharge to outpatient dialysis centres (DCs) for chronic dialysis. For successful cases, follow up phone calls to DCs are performed at 1 and 6 months. Post-instillation, patients were also monitored for 12 hours for bleeding events. Clinical and outcome data were collected and statistical analysis was performed using the SPSS program (version 25). Results 44 catheters in 43 patients were studied. 54.5% were male with a mean age of 60.2 ± 13.5 years, 77.3% had diabetes mellitus as cause of ESKD with a median dialysis vintage of 1.2 years (range 0.03–14.5). 95.5% of patients had previously initiated HD via TDC, 40.9% had a previous failed AVF and 79.6% were awaiting AVF creation or maturation. There was no difference in baseline characteristics between standard and high dose groups. Mean dwell time was 9.7 ± 6.0 hours. Overall, a successful outcome was achieved in 65.9% of all catheters; and in 63.6% versus 68.2% for standard and high dose groups respectively (P = 0.750). In those with a successful outcome, 62.1% (18/29) developed recurrent dysfunction at a mean duration of 57.8±45.3 days. This occurred in 57.1% (8/14) versus 66.7% (10/15) in the standard and high dose groups respectively (P = 0.597). TDC was eventually removed in 37.9% of these patients, for reasons not due to TDC dysfunction (6 patients who cannulated AVF successfully, 1 patient who weaned off dialysis and 4 due to sepsis). Recurrence of TDC dysfunction was numerically higher in the standard group at 1 month (30.8% versus 7.7%, P = 0.135) and similar at 6 months in both groups (85.7% versus 90.9%, P = 0.732, in standard and high dose, respectively) after censoring for TDC removal not due to dysfunction. Time to TDC exchange did not differ between standard and high dose groups (mean 55 ± 59.6days versus 60.3 ± 32.6days, respectively, P = 0.857). There were no adverse events throughout the study period. At 6 months, only 6 catheters remained in the study (3 from each group); 25 were exchanged due to dysfunction, 12 were removed for other reasons, and 1 patient died. During TDC exchange, fibrin sheath was present in 66.7% of cases on pullback venogram (63.6% versus 69.2% in standard versus high dose groups, respectively, P = 0.772). Conclusion High dose urokinase may result in a higher catheter patency rate at 1 month, although there is no difference between high and standard doses in restoring or maintaining catheter patency at 6 months in this small study. Urokinase remains an important adjunct treatment to salvage catheters for a quarter of patients who are awaiting AVF creation or recovering from acute kidney injury. Recurrence of TDC dysfunction is high and tends to occur within a mean of 57.8 ± 45.3 days overall, likely due to presence of a fibrin sheath which is demonstrated in about two-thirds of TDCs in both groups. Higher doses are safe and can ease drug preparation and administration for 60,000 unit vials used locally.