Comparative efficacy of alteplase and urokinase in pharmacomechanical thrombolysis of permanent double lumen hemodialysis catheters in children

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However, because UK is no longer available, alteplase has been reported as an alternative. In this study, we compared the efficacy and safety of alteplase with those of UK. Methods This retrospective analysis included patients undergoing hemodialysis with thrombotic occlusion from May 2014 to February 2025. The drug was administered as a bolus dose into the catheter and allowed to dwell for 60 minutes. The primary endpoint was the blockage resolution rate after the first thrombolytic agent. Results During the study period, 24 patients underwent pharmacological thrombolysis, with a total of 165 procedures performed, including 37 with alteplase and 128 with UK. The median age and weight at the time of thrombotic occlusion were significantly lower in the alteplase group than in the UK group (1.7 vs. 3.9 years and 6.4 vs. 14.4 kg; p < 0.01). The alteplase group had a higher success rate (34/37, 94%) than the UK group (96/128, 75%) (p = 0.038). When the first dose of alteplase was unsuccessful, a second dose successfully cleared the blockage in all instances. No serious adverse effects, such as bleeding events, were observed in either group. Conclusions This study suggests the superiority of alteplase over UK in managing thrombotic occlusions of PDLCs. Moreover, alteplase appears to be safe for use in children weighing < 10 kg, with no serious adverse events observed. Alteplase Hemodialysis Pediatric Permanent double-lumen catheters Thrombolytic agent Thrombolysis Urokinase Figures Figure 1 Introduction Pediatric patients with chronic kidney disease have three options for kidney replacement therapy: hemodialysis, peritoneal dialysis, and kidney transplantation [ 1 ]. For infants whose body size is too small to undergo kidney transplantation, peritoneal dialysis is the preferred option. However, when peritoneal dialysis is not feasible because of refractory peritonitis or a history of abdominal surgery, hemodialysis becomes necessary [ 1 ]. The small body size of pediatric patients often precludes the creation of an arteriovenous fistula. As a result, permanent double-lumen catheters (PDLCs) are placed in the body and used as vascular access for hemodialysis [ 1 ]. In pediatric hemodialysis, short catheters with a large diameter are commonly used, leading to a high incidence of infections and catheter-related thrombotic occlusions [ 1 ]. Among these complications, thrombotic occlusion is the most common cause of catheter failure and removal [ 2 ]. However, in pediatric patients, hemodialysis catheter insertion requires general anesthesia, and available vascular access sites are limited. Therefore, thrombolytic agents are widely used as the first-line treatment for occluded hemodialysis catheters, as recommended by the Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines [ 1 , 3 ]. Among thrombolytic agents, the guidelines recommend urokinase (UK); however, its supply has been suspended, making it currently unavailable for use [ 3 ]. The primary alternative reported is alteplase [ 1 , 3 ], the only thrombolytic agent approved by the U.S. Food and Drug Administration for restoring catheter function [ 4 ]. Numerous studies have demonstrated the efficacy of alteplase for catheter clearance, with a low incidence of complications [ 5 ]. Additionally, multiple reports have documented its effectiveness in treating PDLC occlusion in adult patients undergoing hemodialysis [ 6 – 8 ]. However, data on the efficacy and safety of alteplase for PDLC in pediatric hemodialysis patients remain scarce. This study aimed to evaluate whether alteplase can serve as an efficacious and safe alternative to UK for treating occluded PDLCs in pediatric patients undergoing hemodialysis. Materials and methods Study design and patient population This retrospective cohort study was conducted at a single institution, the Division of Nephrology and Rheumatology at the National Center for Child Health and Development. It included patients undergoing hemodialysis at our institution between May 2014 and February 2025 who received pharmacomechanical thrombolysis with UK or alteplase for thrombotic occlusion of a PDLC. The study aimed to compare the efficacy of UK and alteplase in improving thrombotic occlusions in PDLCs among pediatric patients undergoing hemodialysis. Data collection and analysis Demographic characteristics—including age and weight at the time of thrombotic occlusion, sex, primary kidney disease, dialysis initiation, catheter placement date, anatomical site and characteristics of vascular access, administered dose of UK or alteplase, catheter clearance outcomes (successful or unsuccessful), and the occurrence of adverse events—were retrospectively retrieved from the patients’ medical records and compared between the UK group and the alteplase (recombinant tissue plasminogen activator [rt-PA]) group. All statistical tests were conducted at a 0.05 level of significance. Results are presented as medians, based on the normality characteristics of each variable. Categorical variables are expressed as proportions. Treatment success rates following a 60 minutes dwell of alteplase or UK were analyzed using Fisher’s exact test. Study endpoints The primary endpoint was the blockage resolution rate after the first thrombolytic agent. The secondary endpoints were the blockage resolution rate after a subsequent thrombolytic agent, catheter survival, and the incidence of adverse events. Adverse events were defined as intracranial hemorrhage, gastrointestinal bleeding, hypotension, infection, or anaphylaxis. These events were monitored throughout the hospitalization period following thrombolytic therapy. Procedure protocol for thrombolytic agents Procedure protocol for thrombolytic agents When a thrombotic complete occlusion occurred in the PDLC, 1–2 mL of UK or alteplase was injected into the catheter lumen based on catheter size. Complete occlusion was defined as the inability to inject fluid or aspirate blood from a PDLC that had previously allowed both, resulting in the inability to perform hemodialysis. UK was prepared at a concentration of 10,000 units/mL, while alteplase was adjusted to 6,000,000 units/mL, based on previous reports [ 7 , 8 ]. The drug was administered as a bolus dose into the catheter, similar to an intracatheter heparin lock, and allowed to dwell for 60 minutes. After 60 minutes, an attempt was made to aspirate the remaining drug and any residual clot. Clinical success was defined as the complete retrieval of UK or alteplase after 60 minutes, allowing hemodialysis to proceed without issues. In cases of resolution failure, a second dose of UK or alteplase was administered into the PDLC lumen. Catheter function was reassessed 60 minutes after the second dose. Daily management of PDLCs To prevent thrombotic occlusions in PDLCs, proper catheter flushing and anticoagulation measures were consistently implemented. After dialysis, the catheter was forcefully flushed with normal saline using a 10-mL syringe to remove residual blood, followed by immediate clamping to prevent reflux and clot formation. Additionally, heparin was instilled into the catheter, slightly exceeding the inscribed fill volume. An overfill of 0.1–0.2 mL is recommended to enhance thrombosis prevention [ 9 ]. At our institution, on non-dialysis days, the heparin solution inside the catheter is first aspirated and discarded. A pull–push technique is then performed approximately five times using a syringe to maintain patency and prevent thrombosis. Finally, after flushing the catheter with normal saline to remove any residual blood, heparin (1,000 units/mL) is reinjected into the catheter lumen to ensure anticoagulation until the next dialysis session. Results Patient characteristics In total, 24 patients were eligible during the study period, all of whom received at least one dose of either alteplase or UK (Fig. 1 ). Three patients initially received UK because of prolonged hospital stays; however, after UK became unavailable, they were subsequently treated with alteplase (Fig. 1 ). The baseline characteristics of the study population are summarized in Table 1 . The sex distribution across the three groups was as follows: 56% male in the UK group, 40% male in the rt-PA group, and 67% male in the UK/rt-PA group. The median age at catheter insertion was 4.4 years in the UK group, 1.6 years in the rt-PA group, and 3.1 years in the UK/rt-PA group. All patients were using PDLCs (HEMO-CATH®; Medcomp, Inc.). Across all three groups, the primary catheter size was 8 French (Fr), and the most common insertion site was the internal jugular vein. The dose of UK or alteplase was determined based on catheter size, with 1 mL for an 8-Fr catheter and 1.5 mL for a 12.5-Fr catheter. Table 1 Baseline patient characteristics and catheter characteristics Variable UK group N = 16 rt-PA group N = 5 UK, rt-PA group N = 3 Male gender, n (%) 9 (56) 2 (40) 2 (67) Age at catheter insertion, years (IQR) 4.4 (1.8–8.5) 1.6 (0.6–3.0) 3.1 (2.4–3.8) Type of catheter, n (%) Hemocath 8Fr 14 (88) 5 (100) 2 (67) Hemocath 12.5Fr 2 (12) 0 (0) 1 (33) Catheter Site, n Internal jugular vein Right 7 3 2 Left 6 2 1 External jugular vein Right 2 0 0 Left 1 0 0 Primary disease, n (%) Nephrotic syndrome 6 (38) 1 (20) 0 (0) Congenital Anomalies of the Kidney and Urinary Tract 4 (25) 0 (0) 1 (33) Acute kidney injury 2 (13) 1 (20) 2 (67) Autosomal recessive polycystic kidney disease 1 (6) 2 (40) 0 (0) Others 3 (19) 1 (20) 0 (0) UK, urokinase; rt-PA, recombinant tissue plasminogen activator (alteplase); IQR, interquartile range; Fr, French; Table 2 presents the patient characteristics at the time of UK or alteplase use. The median age at the time of UK use was 3.9 years, while that for alteplase was 1.7 years; the patients in the rt-PA group were significantly younger (p < 0.01). Similarly, the median weight at the time of use was 14.4 kg for UK and 6.4 kg for alteplase, with the rt-PA group having a significantly lower weight (p < 0.01). Table 2 Patient characteristics at time of procedures Variable UK group N = 128 rt-PA group N = 37 p-value Age at procedure, years (IQR) 3.9 (3.0–6.3) 1.7 (1.5–3.0) < 0.01 < 1 year, n (%) 3 (2) 6 (16) 1–3 years, n (%) 66 (52) 26 (70) 4–6 years, n (%) 24 (19) 3 (8) 6 years <, n (%) 35 (27) 2 (5) Weight at procedure, kg (IQR) 14.4 (3.9–14.7) 6.4 (6.2–9.6) < 0.01 < 10 kg, n (%) 19 (15) 28 (76) 10–20 kg, n (%) 101 (79) 7 (19) 20 kg <, n (%) 8 (6) 2 (5) UK, urokinase; rt-PA, recombinant tissue plasminogen activator (alteplase); IQR, interquartile range Success rates by procedure type Clinical success was achieved in 96 of 128 procedures (75%) after a single dose of UK and in 34 of 37 procedures (92%) after a single dose of alteplase (p = 0.038), indicating that alteplase was significantly more effective (Table 3 ). Among the 32 procedures in which UK failed to resolve the clot after a single dose, a second dose was administered in 19 procedures, resulting in clinical success in 12 cases. Of the seven procedures where UK remained ineffective after a second dose, a third dose was given in five cases, leading to clinical success in three procedures. Additionally, in the UK group, two cases required catheter replacement due to failure of thrombus removal with UK. By contrast, among the three procedures in which alteplase failed after a single dose, all achieved clinical success with a second dose. Neither group experienced complications such as significant bleeding, hypotension, infection, or anaphylaxis. Table 3 Success rates by procedure type and catheter outcome UK group N = 128 rt-PA group N = 37 p-value Clinical success rate after the first dose, n (%) 96/128 (75) 34/37 (92) 0.038 Clinical success rate after the second dose, n (%) 12/19 (63) 3/3 (100) 0.52 Clinical success rate after the third dose, n (%) 3/5 (60) - - Catheter replacement due to failure of thrombolysis, n (%) 2/128 (2) 0/37 (0) 1.00 Adverse events, n (%) 0/152 (0) 0/40 (0) 1.00 UK, urokinase; rt-PA, recombinant tissue plasminogen activator (alteplase) Discussion This study demonstrated the efficacy of alteplase in managing thrombotic occlusions in PDLCs among pediatric patients undergoing hemodialysis. Alteplase achieved a significantly higher thrombolysis rate than UK, with a first-dose success rate of 92% and complete resolution in all patients requiring a second dose. Moreover, no significant complications were observed, confirming its favorable safety profile. Alteplase is a thrombolytic agent licensed for the treatment of cerebral and myocardial infarctions. It is a recombinant tissue plasminogen activator that binds to fibrin in thrombi and converts plasminogen to plasmin, leading to localized fibrinolysis. Unlike UK, which activates plasminogen in the bloodstream and increases systemic fibrinolytic activity, alteplase specifically targets thrombi, promoting localized clot dissolution. As a result, it achieves higher clinical success rates with fewer systemic effects [ 10 ]. Moreover, evidence suggests that UK has a delayed onset of action and a lower thrombolysis rate, particularly when not continuously infused, despite its relatively short half-life [ 11 ]. Therefore, alteplase is considered more effective than UK. The high efficacy of alteplase has been reported in previous studies; however, various techniques have been described for using alteplase to salvage thrombosed PDLCs, including systemic infusion, direct injection into the thrombus, and slow, prolonged infusion. Comparisons of its effectiveness with UK have shown that alteplase is equally or more effective than UK [ 7 , 8 ]. Although this study was conducted in adults, Pollo et al. [ 7 ] performed a randomized trial comparing the efficacy of alteplase and UK for completely occluded hemodialysis catheters. In their study, alteplase (1 mg/mL) was administered as a bolus injection into the catheter lumen and left to dwell for 40 minutes before attempting aspiration. The success rate was 95% in the alteplase group and 82% in the UK group. Although the difference was not statistically significant (p = 0.06), alteplase demonstrated slight superiority, and no serious adverse events were reported in either group. Although research on adults is more common, several reports have summarized the efficacy and safety of alteplase in pediatric patients [ 12 ]. However, available data suggest that only one report specifically focuses on its use in hemodialysis catheters for pediatric patients undergoing hemodialysis [ 13 ]. Bamgbola et al. [ 13 ] reported the use of alteplase to treat 11 thrombotic occlusions in hemodialysis catheters among 6 pediatric patients with a mean age of 12.8 ± 4.9 years. They described a method in which alteplase, diluted 10-fold in normal saline, was infused at a volume of 10 mL over more than 2 hours. The success rate for restoring catheter patency was 91%, with a 60% probability of primary patency at 32 weeks. Vital signs during and after alteplase infusion remained stable in all patients, and no adverse events were reported following its administration. In our study, we demonstrated a similarly high thrombus occlusion relief rate as reported in previous studies. Furthermore, unlike the study by Pollo et al. [ 7 ], our results showed that alteplase was significantly more effective than UK. The primary difference between our study and that of Bamgbola et al. [ 13 ], which focused on pediatric hemodialysis catheters, lies in the method of alteplase administration. In their study, alteplase was delivered as a low-dose, short-term infusion, whereas we administered a bolus dose, similar to an intracatheter heparin lock, allowing it to remain in the obstructed catheter for 60 minutes. While the administration method used by Bamgbola et al. [ 13 ] may also be effective, it may not be suitable for the rapid removal of obstruction when a catheter suddenly becomes blocked by blood clots in the dialysis room. By contrast, our protocol enables the resolution of catheter occlusion in as little as 60 minutes. This approach is more practical in clinical settings, as it allows for the prompt resolution of catheter occlusion. Another notable aspect of this study is that even when using the same administration method as in adults (bolus administration), alteplase was safely administered without any obvious adverse events, such as bleeding, even in infants under 1 year of age or those weighing < 10 kg. Furthermore, in this study, even when catheter occlusion was not resolved with a single dose of alteplase, all cases achieved resolution following additional doses. This is considered an advantage of alteplase over UK. Alteplase is a safe and effective thrombolytic agent for restoring the patency of PDLCs. However, cost is also an important consideration when selecting a thrombolytic agent. Alteplase is significantly more expensive, costing 36,569 yen per vial, compared with UK, which is priced at 4,704 yen per vial. Previous studies have shown that in terms of cost-effectiveness, the effectiveness and safety of alteplase can be maintained under two conditions: when vials are divided in the pharmacy and administered to multiple patients per use [ 14 ], and when alteplase is frozen and stored for later use [ 15 ]. However, implementing either of these approaches in Japan would be challenging. Despite its higher cost, alteplase remains a cost-effective alternative for patients undergoing hemodialysis with catheter occlusion when considering the cost of surgical catheter replacement. In this study, two patients in the UK group required catheter replacement because of unresolved thrombus occlusion, whereas no such cases were observed in the rt-PA group. To minimize the use of alteplase due to its high cost, careful daily catheter management is essential. This includes closing the catheter clamp before removing the syringe to prevent clot occlusion. This study has several limitations, including its small sample size and retrospective, single-center design. While increasing the sample size and conducting further studies are necessary, the limited number of pediatric patients undergoing hemodialysis makes randomized controlled trials challenging. Therefore, collaboration among multiple institutions is essential to further validate these findings. In conclusion, this is the first report worldwide to evaluate the efficacy and safety of bolus alteplase administration in pediatric patients undergoing hemodialysis. Despite cost concerns, our findings demonstrate that alteplase is more effective than UK and, with comparable safety, can serve as a viable alternative to UK. Declarations Competing interests Koichi Kamei received research funding from the Public Foundation of Vaccination Research Center and the Taiju Life Social Welfare Foundation. He also received donations from Chugai Pharmaceutical, Teijin Pharma, Kyowa Kirin, Taiho Pharmaceutical, Shionogi, Daiichi Sankyo, and Mitsubishi Tanabe Pharma, as well as lecture fees from Terumo. Consent to publish Written informed consent was obtained from the patients’ guardians for the publication of any potentially identifiable images or data included in this article. Funding No funds, grants, or other support was received for the submitted work. Author contributions All authors contributed to the study conception and design. Yuhi Takagi performed the data collection and analysis and prepared the manuscript. Manami Konishi, Satoshi Okada, and Masao Ogura collected data from the medical charts and reviewed the manuscript. Kentaro Nishi advised on the study protocol and revised the manuscript. Kochi Kamei advised on the study protocol, oversaw the work, and revised the manuscript. All authors read and approved the final manuscript. Acknowledgments We thank Angela Morben, DVM, ELS, from Edanz ( https://jp.edanz.com/ac ), for editing a draft of this manuscript. Data availability statement Not applicable. References Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2024) KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int 105(Suppl 4S):S117–S314. https://doi.org/10.1016/j.kint.2023.10.018 Sharma A, Zilleruelo G, Abitbol C, Montane B, Strauss J (1999) Survival and complications of cuffed catheters in children on chronic hemodialysis. Pediatr Nephrol 13:245–248. https://doi.org/10.1007/s004670050602 Lok CE, Huber TS, Lee T, KDOQI Vascular Access Guideline Work Group et al (2020) KDOQI clinical practice guideline for vascular access: 2019 update. Am J Kidney Dis 75(4 Suppl 2):S1–S164. https://doi.org/10.1053/j.ajkd.2019.12.001 Genentech I (2019) Cathflo Activase (Alteplase) [prescribing information]. 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Artif Organs 38(5):399–403. https://doi.org/10.1111/aor.12186 Supplementary Files GraphicalAbstract.pptx Cite Share Download PDF Status: Published Journal Publication published 06 Oct, 2025 Read the published version in Pediatric Nephrology → Version 1 posted Editorial decision: Major Revisions Needed 27 May, 2025 Reviewers agreed at journal 01 May, 2025 Reviewers invited by journal 28 Apr, 2025 Editor assigned by journal 25 Apr, 2025 First submitted to journal 24 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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17:26:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6522893/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6522893/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00467-025-06997-7","type":"published","date":"2025-10-06T15:56:54+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82147139,"identity":"f9aeb0dc-3e1d-4f3a-8ffe-96f1bb145323","added_by":"auto","created_at":"2025-05-07 06:59:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":13071,"visible":true,"origin":"","legend":"\u003cp\u003eDetails of patients treated with urokinase or alteplase\u003c/p\u003e\n\u003cp\u003eThree patients initially received urokinase (three procedures), but they were later treated with alteplase (three procedures) because of the unavailability of urokinase.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6522893/v1/0084624a8648b1404bd3646a.png"},{"id":93419459,"identity":"c14926b4-e6e8-4d89-8fab-fbaa11d9e605","added_by":"auto","created_at":"2025-10-13 16:01:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":670089,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6522893/v1/4fe35fb5-1d32-4312-a364-392021ccd32a.pdf"},{"id":82148311,"identity":"43d6dc4d-5049-48c5-bdf9-abd43c219335","added_by":"auto","created_at":"2025-05-07 07:07:14","extension":"pptx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":132063,"visible":true,"origin":"","legend":"","description":"","filename":"GraphicalAbstract.pptx","url":"https://assets-eu.researchsquare.com/files/rs-6522893/v1/44fc30ca3158bd4558406612.pptx"}],"financialInterests":"","formattedTitle":"Comparative efficacy of alteplase and urokinase in pharmacomechanical thrombolysis of permanent double lumen hemodialysis catheters in children","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePediatric patients with chronic kidney disease have three options for kidney replacement therapy: hemodialysis, peritoneal dialysis, and kidney transplantation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. For infants whose body size is too small to undergo kidney transplantation, peritoneal dialysis is the preferred option. However, when peritoneal dialysis is not feasible because of refractory peritonitis or a history of abdominal surgery, hemodialysis becomes necessary [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The small body size of pediatric patients often precludes the creation of an arteriovenous fistula. As a result, permanent double-lumen catheters (PDLCs) are placed in the body and used as vascular access for hemodialysis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn pediatric hemodialysis, short catheters with a large diameter are commonly used, leading to a high incidence of infections and catheter-related thrombotic occlusions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Among these complications, thrombotic occlusion is the most common cause of catheter failure and removal [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, in pediatric patients, hemodialysis catheter insertion requires general anesthesia, and available vascular access sites are limited. Therefore, thrombolytic agents are widely used as the first-line treatment for occluded hemodialysis catheters, as recommended by the Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Among thrombolytic agents, the guidelines recommend urokinase (UK); however, its supply has been suspended, making it currently unavailable for use [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The primary alternative reported is alteplase [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], the only thrombolytic agent approved by the U.S. Food and Drug Administration for restoring catheter function [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Numerous studies have demonstrated the efficacy of alteplase for catheter clearance, with a low incidence of complications [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Additionally, multiple reports have documented its effectiveness in treating PDLC occlusion in adult patients undergoing hemodialysis [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, data on the efficacy and safety of alteplase for PDLC in pediatric hemodialysis patients remain scarce. This study aimed to evaluate whether alteplase can serve as an efficacious and safe alternative to UK for treating occluded PDLCs in pediatric patients undergoing hemodialysis.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and patient population\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study was conducted at a single institution, the Division of Nephrology and Rheumatology at the National Center for Child Health and Development. It included patients undergoing hemodialysis at our institution between May 2014 and February 2025 who received pharmacomechanical thrombolysis with UK or alteplase for thrombotic occlusion of a PDLC. The study aimed to compare the efficacy of UK and alteplase in improving thrombotic occlusions in PDLCs among pediatric patients undergoing hemodialysis.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData collection and analysis\u003c/h3\u003e\n\u003cp\u003eDemographic characteristics\u0026mdash;including age and weight at the time of thrombotic occlusion, sex, primary kidney disease, dialysis initiation, catheter placement date, anatomical site and characteristics of vascular access, administered dose of UK or alteplase, catheter clearance outcomes (successful or unsuccessful), and the occurrence of adverse events\u0026mdash;were retrospectively retrieved from the patients\u0026rsquo; medical records and compared between the UK group and the alteplase (recombinant tissue plasminogen activator [rt-PA]) group. All statistical tests were conducted at a 0.05 level of significance. Results are presented as medians, based on the normality characteristics of each variable. Categorical variables are expressed as proportions. Treatment success rates following a 60 minutes dwell of alteplase or UK were analyzed using Fisher\u0026rsquo;s exact test.\u003c/p\u003e\n\u003ch3\u003eStudy endpoints\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint was the blockage resolution rate after the first thrombolytic agent. The secondary endpoints were the blockage resolution rate after a subsequent thrombolytic agent, catheter survival, and the incidence of adverse events. Adverse events were defined as intracranial hemorrhage, gastrointestinal bleeding, hypotension, infection, or anaphylaxis. These events were monitored throughout the hospitalization period following thrombolytic therapy.\u003c/p\u003e\n\u003ch3\u003eProcedure protocol for thrombolytic agents\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eProcedure protocol for thrombolytic agents\u003c/div\u003e \u003cp\u003eWhen a thrombotic complete occlusion occurred in the PDLC, 1\u0026ndash;2 mL of UK or alteplase was injected into the catheter lumen based on catheter size. Complete occlusion was defined as the inability to inject fluid or aspirate blood from a PDLC that had previously allowed both, resulting in the inability to perform hemodialysis. UK was prepared at a concentration of 10,000 units/mL, while alteplase was adjusted to 6,000,000 units/mL, based on previous reports [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The drug was administered as a bolus dose into the catheter, similar to an intracatheter heparin lock, and allowed to dwell for 60 minutes. After 60 minutes, an attempt was made to aspirate the remaining drug and any residual clot. Clinical success was defined as the complete retrieval of UK or alteplase after 60 minutes, allowing hemodialysis to proceed without issues. In cases of resolution failure, a second dose of UK or alteplase was administered into the PDLC lumen. Catheter function was reassessed 60 minutes after the second dose.\u003c/p\u003e\n\u003ch3\u003eDaily management of PDLCs\u003c/h3\u003e\n\u003cp\u003eTo prevent thrombotic occlusions in PDLCs, proper catheter flushing and anticoagulation measures were consistently implemented. After dialysis, the catheter was forcefully flushed with normal saline using a 10-mL syringe to remove residual blood, followed by immediate clamping to prevent reflux and clot formation. Additionally, heparin was instilled into the catheter, slightly exceeding the inscribed fill volume. An overfill of 0.1\u0026ndash;0.2 mL is recommended to enhance thrombosis prevention [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. At our institution, on non-dialysis days, the heparin solution inside the catheter is first aspirated and discarded. A pull\u0026ndash;push technique is then performed approximately five times using a syringe to maintain patency and prevent thrombosis. Finally, after flushing the catheter with normal saline to remove any residual blood, heparin (1,000 units/mL) is reinjected into the catheter lumen to ensure anticoagulation until the next dialysis session.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eIn total, 24 patients were eligible during the study period, all of whom received at least one dose of either alteplase or UK (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Three patients initially received UK because of prolonged hospital stays; however, after UK became unavailable, they were subsequently treated with alteplase (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The baseline characteristics of the study population are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The sex distribution across the three groups was as follows: 56% male in the UK group, 40% male in the rt-PA group, and 67% male in the UK/rt-PA group. The median age at catheter insertion was 4.4 years in the UK group, 1.6 years in the rt-PA group, and 3.1 years in the UK/rt-PA group. All patients were using PDLCs (HEMO-CATH\u0026reg;; Medcomp, Inc.). Across all three groups, the primary catheter size was 8 French (Fr), and the most common insertion site was the internal jugular vein. The dose of UK or alteplase was determined based on catheter size, with 1 mL for an 8-Fr catheter and 1.5 mL for a 12.5-Fr catheter.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline patient characteristics and catheter characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUK group\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;16\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ert-PA group\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUK, rt-PA group\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;3\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMale gender, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge at catheter insertion, years (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.4 (1.8\u0026ndash;8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.6 (0.6\u0026ndash;3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.1 (2.4\u0026ndash;3.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eType of catheter, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHemocath 8Fr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHemocath 12.5Fr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCatheter Site, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eInternal jugular vein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eExternal jugular vein\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLeft\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePrimary disease, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNephrotic syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCongenital Anomalies of the Kidney and Urinary Tract\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAcute kidney injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAutosomal recessive polycystic kidney disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eUK, urokinase; rt-PA, recombinant tissue plasminogen activator (alteplase); IQR, interquartile range; Fr, French;\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents the patient characteristics at the time of UK or alteplase use. The median age at the time of UK use was 3.9 years, while that for alteplase was 1.7 years; the patients in the rt-PA group were significantly younger (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Similarly, the median weight at the time of use was 14.4 kg for UK and 6.4 kg for alteplase, with the rt-PA group having a significantly lower weight (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics at time of procedures\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUK group\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;128\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ert-PA group\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;37\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at procedure, years (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.9 (3.0\u0026ndash;6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.7 (1.5\u0026ndash;3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1 year, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;3 years, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66 (52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u0026ndash;6 years, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6 years \u0026lt;, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight at procedure, kg (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.4 (3.9\u0026ndash;14.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.4 (6.2\u0026ndash;9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;10 kg, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u0026ndash;20 kg, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101 (79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e20 kg \u0026lt;, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eUK, urokinase; rt-PA, recombinant tissue plasminogen activator (alteplase); IQR, interquartile range\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSuccess rates by procedure type\u003c/h3\u003e\n\u003cp\u003eClinical success was achieved in 96 of 128 procedures (75%) after a single dose of UK and in 34 of 37 procedures (92%) after a single dose of alteplase (p\u0026thinsp;=\u0026thinsp;0.038), indicating that alteplase was significantly more effective (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Among the 32 procedures in which UK failed to resolve the clot after a single dose, a second dose was administered in 19 procedures, resulting in clinical success in 12 cases. Of the seven procedures where UK remained ineffective after a second dose, a third dose was given in five cases, leading to clinical success in three procedures. Additionally, in the UK group, two cases required catheter replacement due to failure of thrombus removal with UK. By contrast, among the three procedures in which alteplase failed after a single dose, all achieved clinical success with a second dose. Neither group experienced complications such as significant bleeding, hypotension, infection, or anaphylaxis.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSuccess rates by procedure type and catheter outcome\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUK group\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;128\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ert-PA group\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;37\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical success rate after the first dose, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e96/128 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34/37 (92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical success rate after the second dose, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/19 (63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/3 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical success rate after the third dose, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/5 (60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCatheter replacement due to failure of thrombolysis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/128 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/37 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdverse events, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/152 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/40 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eUK, urokinase; rt-PA, recombinant tissue plasminogen activator (alteplase)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated the efficacy of alteplase in managing thrombotic occlusions in PDLCs among pediatric patients undergoing hemodialysis. Alteplase achieved a significantly higher thrombolysis rate than UK, with a first-dose success rate of 92% and complete resolution in all patients requiring a second dose. Moreover, no significant complications were observed, confirming its favorable safety profile.\u003c/p\u003e \u003cp\u003eAlteplase is a thrombolytic agent licensed for the treatment of cerebral and myocardial infarctions. It is a recombinant tissue plasminogen activator that binds to fibrin in thrombi and converts plasminogen to plasmin, leading to localized fibrinolysis. Unlike UK, which activates plasminogen in the bloodstream and increases systemic fibrinolytic activity, alteplase specifically targets thrombi, promoting localized clot dissolution. As a result, it achieves higher clinical success rates with fewer systemic effects [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Moreover, evidence suggests that UK has a delayed onset of action and a lower thrombolysis rate, particularly when not continuously infused, despite its relatively short half-life [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Therefore, alteplase is considered more effective than UK.\u003c/p\u003e \u003cp\u003eThe high efficacy of alteplase has been reported in previous studies; however, various techniques have been described for using alteplase to salvage thrombosed PDLCs, including systemic infusion, direct injection into the thrombus, and slow, prolonged infusion. Comparisons of its effectiveness with UK have shown that alteplase is equally or more effective than UK [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Although this study was conducted in adults, Pollo et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] performed a randomized trial comparing the efficacy of alteplase and UK for completely occluded hemodialysis catheters. In their study, alteplase (1 mg/mL) was administered as a bolus injection into the catheter lumen and left to dwell for 40 minutes before attempting aspiration. The success rate was 95% in the alteplase group and 82% in the UK group. Although the difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.06), alteplase demonstrated slight superiority, and no serious adverse events were reported in either group. Although research on adults is more common, several reports have summarized the efficacy and safety of alteplase in pediatric patients [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, available data suggest that only one report specifically focuses on its use in hemodialysis catheters for pediatric patients undergoing hemodialysis [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Bamgbola et al. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] reported the use of alteplase to treat 11 thrombotic occlusions in hemodialysis catheters among 6 pediatric patients with a mean age of 12.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9 years. They described a method in which alteplase, diluted 10-fold in normal saline, was infused at a volume of 10 mL over more than 2 hours. The success rate for restoring catheter patency was 91%, with a 60% probability of primary patency at 32 weeks. Vital signs during and after alteplase infusion remained stable in all patients, and no adverse events were reported following its administration.\u003c/p\u003e \u003cp\u003eIn our study, we demonstrated a similarly high thrombus occlusion relief rate as reported in previous studies. Furthermore, unlike the study by Pollo et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], our results showed that alteplase was significantly more effective than UK. The primary difference between our study and that of Bamgbola et al. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], which focused on pediatric hemodialysis catheters, lies in the method of alteplase administration. In their study, alteplase was delivered as a low-dose, short-term infusion, whereas we administered a bolus dose, similar to an intracatheter heparin lock, allowing it to remain in the obstructed catheter for 60 minutes. While the administration method used by Bamgbola et al. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] may also be effective, it may not be suitable for the rapid removal of obstruction when a catheter suddenly becomes blocked by blood clots in the dialysis room. By contrast, our protocol enables the resolution of catheter occlusion in as little as 60 minutes. This approach is more practical in clinical settings, as it allows for the prompt resolution of catheter occlusion. Another notable aspect of this study is that even when using the same administration method as in adults (bolus administration), alteplase was safely administered without any obvious adverse events, such as bleeding, even in infants under 1 year of age or those weighing\u0026thinsp;\u0026lt;\u0026thinsp;10 kg. Furthermore, in this study, even when catheter occlusion was not resolved with a single dose of alteplase, all cases achieved resolution following additional doses. This is considered an advantage of alteplase over UK.\u003c/p\u003e \u003cp\u003eAlteplase is a safe and effective thrombolytic agent for restoring the patency of PDLCs. However, cost is also an important consideration when selecting a thrombolytic agent. Alteplase is significantly more expensive, costing 36,569 yen per vial, compared with UK, which is priced at 4,704 yen per vial. Previous studies have shown that in terms of cost-effectiveness, the effectiveness and safety of alteplase can be maintained under two conditions: when vials are divided in the pharmacy and administered to multiple patients per use [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], and when alteplase is frozen and stored for later use [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, implementing either of these approaches in Japan would be challenging. Despite its higher cost, alteplase remains a cost-effective alternative for patients undergoing hemodialysis with catheter occlusion when considering the cost of surgical catheter replacement. In this study, two patients in the UK group required catheter replacement because of unresolved thrombus occlusion, whereas no such cases were observed in the rt-PA group. To minimize the use of alteplase due to its high cost, careful daily catheter management is essential. This includes closing the catheter clamp before removing the syringe to prevent clot occlusion.\u003c/p\u003e \u003cp\u003eThis study has several limitations, including its small sample size and retrospective, single-center design. While increasing the sample size and conducting further studies are necessary, the limited number of pediatric patients undergoing hemodialysis makes randomized controlled trials challenging. Therefore, collaboration among multiple institutions is essential to further validate these findings.\u003c/p\u003e \u003cp\u003eIn conclusion, this is the first report worldwide to evaluate the efficacy and safety of bolus alteplase administration in pediatric patients undergoing hemodialysis. Despite cost concerns, our findings demonstrate that alteplase is more effective than UK and, with comparable safety, can serve as a viable alternative to UK.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eKoichi Kamei received research funding from the Public Foundation of Vaccination Research Center and the Taiju Life Social Welfare Foundation. He also received donations from Chugai Pharmaceutical, Teijin Pharma, Kyowa Kirin, Taiho Pharmaceutical, Shionogi, Daiichi Sankyo, and Mitsubishi Tanabe Pharma, as well as lecture fees from Terumo.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConsent to publish\u003c/h2\u003e \u003cp\u003e Written informed consent was obtained from the patients\u0026rsquo; guardians for the publication of any potentially identifiable images or data included in this article.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo funds, grants, or other support was received for the submitted work.\u003c/p\u003e\u003ch2\u003eAuthor contributions\u003c/h2\u003e \u003cp\u003eAll authors contributed to the study conception and design. Yuhi Takagi performed the data collection and analysis and prepared the manuscript. Manami Konishi, Satoshi Okada, and Masao Ogura collected data from the medical charts and reviewed the manuscript. Kentaro Nishi advised on the study protocol and revised the manuscript. Kochi Kamei advised on the study protocol, oversaw the work, and revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eWe thank Angela Morben, DVM, ELS, from Edanz (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://jp.edanz.com/ac\u003c/span\u003e\u003cspan address=\"https://jp.edanz.com/ac\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), for editing a draft of this manuscript.\u003c/p\u003e\u003ch2\u003eData availability statement\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2024) KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int 105(Suppl 4S):S117\u0026ndash;S314. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.kint.2023.10.018\u003c/span\u003e\u003cspan address=\"10.1016/j.kint.2023.10.018\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma A, Zilleruelo G, Abitbol C, Montane B, Strauss J (1999) Survival and complications of cuffed catheters in children on chronic hemodialysis. 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Artif Organs 38(5):399\u0026ndash;403. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/aor.12186\u003c/span\u003e\u003cspan address=\"10.1111/aor.12186\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Alteplase, Hemodialysis, Pediatric, Permanent double-lumen catheters, Thrombolytic agent, Thrombolysis, Urokinase","lastPublishedDoi":"10.21203/rs.3.rs-6522893/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6522893/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThrombotic occlusion of permanent double lumen catheters (PDLC) in hemodialysis has traditionally been treated with urokinase (UK), a thrombolytic agent. However, because UK is no longer available, alteplase has been reported as an alternative. In this study, we compared the efficacy and safety of alteplase with those of UK.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective analysis included patients undergoing hemodialysis with thrombotic occlusion from May 2014 to February 2025. The drug was administered as a bolus dose into the catheter and allowed to dwell for 60 minutes. The primary endpoint was the blockage resolution rate after the first thrombolytic agent.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eDuring the study period, 24 patients underwent pharmacological thrombolysis, with a total of 165 procedures performed, including 37 with alteplase and 128 with UK. The median age and weight at the time of thrombotic occlusion were significantly lower in the alteplase group than in the UK group (1.7 vs. 3.9 years and 6.4 vs. 14.4 kg; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). The alteplase group had a higher success rate (34/37, 94%) than the UK group (96/128, 75%) (p\u0026thinsp;=\u0026thinsp;0.038). When the first dose of alteplase was unsuccessful, a second dose successfully cleared the blockage in all instances. No serious adverse effects, such as bleeding events, were observed in either group.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis study suggests the superiority of alteplase over UK in managing thrombotic occlusions of PDLCs. Moreover, alteplase appears to be safe for use in children weighing\u0026thinsp;\u0026lt;\u0026thinsp;10 kg, with no serious adverse events observed.\u003c/p\u003e","manuscriptTitle":"Comparative efficacy of alteplase and urokinase in pharmacomechanical thrombolysis of permanent double lumen hemodialysis catheters in children","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 06:59:10","doi":"10.21203/rs.3.rs-6522893/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revisions Needed","date":"2025-05-27T16:00:23+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-05-01T07:44:41+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-28T07:16:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-25T07:02:13+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Nephrology","date":"2025-04-24T13:25:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"b9976d15-2afb-4f42-a9dd-ae75e9de48dc","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-13T15:58:49+00:00","versionOfRecord":{"articleIdentity":"rs-6522893","link":"https://doi.org/10.1007/s00467-025-06997-7","journal":{"identity":"pediatric-nephrology","isVorOnly":false,"title":"Pediatric Nephrology"},"publishedOn":"2025-10-06 15:56:54","publishedOnDateReadable":"October 6th, 2025"},"versionCreatedAt":"2025-05-07 06:59:10","video":"","vorDoi":"10.1007/s00467-025-06997-7","vorDoiUrl":"https://doi.org/10.1007/s00467-025-06997-7","workflowStages":[]},"version":"v1","identity":"rs-6522893","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6522893","identity":"rs-6522893","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}