Humoral immunity to SARS-CoV-2 in kidney transplant recipients and dialysis patients: IgA and IgG patterns unraveled after SARS-CoV-2 infection and vaccination.

BACKGROUND: Infection with SARS-CoV-2 in high-risk groups such as kidney transplant and dialysis patients is shown to be associated with a more serious course of the disease. Four years after the start of the COVID-19 pandemic, crucial knowledge on the immune responses in these patient groups is still lacking. Therefore, this study aimed at investigating the humoral immune response after a SARS-CoV-2 infection compared to vaccination as well as the evolution of immunoglobulins over time. METHODS: Kidney transplant recipients, patients on haemodialysis or on peritoneal dialysis and healthy controls were included in this longitudinal multicenter study. SARS-CoV-2 anti-RBD, anti-NP and anti-S1S2 immunoglobulin G (IgG) and A (IgA) as well as the neutralizing antibody capacity were measured. RESULTS: Kidney transplant recipients had a significantly better humoral response to SARS-CoV-2 after infection (86.4%) than after a two-dose mRNA vaccination (55.8%) while seroconversion was comparable in patients on haemodialysis after infection (95.8%) versus vaccination (89.4%). In individuals without prior COVID-19, the IgG levels after vaccination were significantly lower in kidney transplant recipients when compared to all other groups. However, the IgA titres remained the highest in this patient group at each time point, both after infection and vaccination. A history COVID-19 was associated with higher antibody levels after double-dose vaccination in all patient categories and, while decreasing, titres remained high six months after double-dose vaccination. CONCLUSION: Kidney transplant recipients had a more robust humoral response to SARS-CoV-2 following infection compared to a two-dose mRNA vaccination, while patients on haemodialysis exhibited comparable seroconversion rates. Notably, individuals with prior COVID-19 exhibited higher IgG levels in response to vaccination. Hybrid immunity is thus the best possible defence against severe COVID-19 disease and seems also to hold up for these populations. Next, it is not clear whether the higher IgA levels in the kidney transplant recipients is beneficial for neutralizing SARS-CoV-2 or if it is a sign of disease severity.

Prevalence of Liver Steatosis in Tuberous Sclerosis Complex Patients: A Retrospective Cross-Sectional Study.

Introduction: Tuberous sclerosis complex (TSC) is a genetic disease caused by pathogenetic variants in either the TSC1 or TSC2 genes. Consequently, the mechanistic target of the rapamycin complex 1 (mTORC1) pathway, a regulator of cell growth, metabolism, and survival, becomes inappropriately activated, leading to the development of benign tumors in multiple organs. The role of mTORC1 in lipid metabolism and liver steatosis in TSC patients has not been well-studied, and clinical data on liver involvement in this population are scarce. Methods: We conducted a retrospective, cross-sectional study to compare liver steatosis in TSC patients with age-, sex-, BMI-, and diabetes status-matched controls. Participants with a definite diagnosis of TSC were recruited from the TSC clinic at UZ Brussel. Liver steatosis was quantified using the fat signal fraction from in-phase and out-of-phase MRI, with a threshold of ≥5% defining the presence of steatosis. We also evaluated the prevalence of liver angiomyolipomata in the TSC group and analyzed risk factors for both liver steatosis and angiomyolipomata. Results: The study included 59 TSC patients and 59 matched controls. The mean fat signal fraction was 4.0% in the TSC group and 3.9% in the controls, showing no significant difference (two-tailed Wilcoxon signed ranks test, p = 0.950). Liver steatosis was observed in 15.3% of TSC patients compared to 23.7% of the controls, which was not statistically significant (two-tailed McNemar test, p = 0.267). Liver angiomyolipomata were identified in 13.6% of the TSC cohort. Conclusions: Our study, describing in detail the liver phenotype of TSC patients, did not reveal a significant difference in the prevalence of MRI-assessed liver steatosis in a large cohort of TSC patients compared to a closely matched control group.

Relapse rate in children with nephrotic syndrome during the SARS-CoV-2 pandemic.

BACKGROUND: Viral upper respiratory tract infections trigger nephrotic syndrome relapses. Few data exist on the impact of the SARS-CoV-2 pandemic on the risk of relapse in children with idiopathic nephrotic syndrome (INS). METHODS: In a Belgian and Italian cohort of children with INS, we performed a retrospective analysis on the number and duration of relapses observed in 3 different periods in 2020: first COVID period, February 15-May 31; second COVID period, June 1-September 14; third COVID period, September 15-December 31. Relapse rates were compared to those of the previous 5 years (PRECOVID period). For the years 2019 and 2020, all causes and INS relapse-related hospitalizations were recorded. Hospitalizations and deaths due to SARS-CoV-2 infection were also recorded. In the Belgian cohort, SARS-CoV-2 serologies were performed. RESULTS: A total of 218 patients were enrolled, and 29 (13.3%) were diagnosed with new-onset INS during the COVID period. Relapse rates per 1000 person-days were as follows: 3.2 in the PRECOVID period, 2.7 in the first COVID period, 3.3 in the second COVID period, and 3.0 in the third COVID period. The incidence rate ratio for the total COVID period was 0.9 (95%CI 0.76 to 1.06; P = 0.21) as compared to the PRECOVID period. During 2020, both the proportion of patients hospitalized for recurrence (14.2% vs. 7.6% in 2019; P = 0.03) and the rate of hospitalization for recurrence (IRR 1.97 (95%CI 1.35 to 2.88); P = 0.013) were higher compared to 2019. In December 2020, anti-SARS-CoV-2 antibodies were detected in 31% of the Belgian cohort. Patients with positive and negative SARS-CoV-2 serology did not differ significantly in relapse rate (2.4 versus 4.2 per 1000 person-days). The number of new INS cases remained similar between 2020, 2019, and 2018. CONCLUSION: The first year of the SARS-CoV-2 pandemic did not significantly affect the relapse rate in children with INS. No serious infections were reported in this population of immunosuppressed patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

SARS-CoV-2 mRNA vaccination is not associated with the induction of anti-HLA or non-HLA antibodies.

BACKGROUND: SARS-CoV-2 vaccination is strongly recommended in kidney transplant recipients (KTR) and dialysis patients. Whether these vaccinations may trigger alloantibodies, is still debated. METHODS: In the current study we evaluated the effect of SARS-CoV-2 mRNA vaccines on anti-Human Leukocyte Antigen (HLA) and 60 anti-non-HLA antibody profiles in clinically stable KTR and dialysis patients. In total, we included 28 KTR, 30 patients on haemodialysis, 25 patients on peritoneal dialysis and 31 controls with a positive seroresponse 16-21 days after the first dose of either the SARS-CoV-2 mRNA BNT162b2 or mRNA-1273 vaccine. Both anti-HLA and anti-non-HLA antibodies were determined prior to vaccination and 21 to 35 days after the second vaccine dose. RESULTS: Overall, the proportion of patients with detectable anti-HLA antibodies was similar before and after vaccination (class I 14% vs. 16%, p = 0.48; class II 25% before and after vaccination). After vaccination, there was no pattern in 1) additionally detected anti-HLA antibodies, or 2) the levels of pre-existing ones. Additional anti-non-HLA antibodies were detected in 30% of the patients, ranging from 1 to 5 new anti-non-HLA antibodies per patient. However, the clinical significance of anti-non-HLA antibodies is still a matter of debate. To date, only a significant association has been found for anti-non-HLA ARHGDIB antibodies and long-term kidney graft loss. No additionally developed anti-ARHGDIB antibodies or elevated level of existing anti-ARHGDIB antibodies was observed. CONCLUSION: The current data indicate that SARS-CoV-2 mRNA vaccination does not induce anti-HLA or anti-non-HLA antibodies, corroborating the importance of vaccinating KTR and dialysis patients.

Seroconversion rate after primary vaccination with two doses of BNT162b2 versus mRNA-1273 in solid organ transplant recipients: a systematic review and meta-analysis.

BACKGROUND: In the general population, the seroconversion rate after primary vaccination with two doses of an anti-severe acute respiratory syndrome coronavirus 2 messenger RNA (mRNA) vaccine reaches nearly 100%, with significantly higher antibody titers after mRNA-1273 vaccination compared to BNT162b2 vaccination. Here we performed a systematic review and meta-analysis to compare the antibody response after two-dose mRNA-1273 versus BNT162b2 vaccination in solid organ transplant (SOT) recipients. METHODS: A systematic literature review was performed using PubMed, Web of Science and the Cochrane Library and original research papers were included for a meta-analysis to calculate vaccine-specific seroconversion rates for each of the mRNA vaccines. Next, the pooled relative seroconversion rate was estimated. RESULTS: Eight studies that described the development of antibodies against receptor-binding domain (RBD) and/or spike protein were eligible for meta-analysis. Two of these studies also reported antibody titers. The meta-analysis revealed lower seroconversion rates in SOT recipients vaccinated with two doses of BNT162b2 {44.3% [95% confidence interval (CI) 34.1-54.7]} as compared with patients vaccinated with two doses of mRNA-1273 [58.4% (95% CI 47.2-69.2)]. The relative seroconversion rate was 0.795 (95% CI 0.732-0.864). CONCLUSIONS: This systematic review and meta-analysis indicates that in SOT recipients, higher seroconversion rates were observed after vaccination with mRNA-1273 compared with BNT162b2.

Risk for excessive anticoagulation during hemodialysis is associated with type of vascular access and bedside coagulation testing: Results of a cross-sectional study.

Background: Recommendations and practice patterns for heparin dosing during hemodialysis show substantial heterogeneity and are scantly supported by evidence. This study assessed the variability in unfractionated heparin (UFH) dosing during hemodialysis and its clinical and biological anticoagulatory effects, and identified explanatory factors of heparin dosing. Methods: Cross-sectional study assessing UFH dosing, coagulation tests - activated partial thromboplastin time (aPTT) and activated clotting time (ACT) before dialysis start, 1 h after start and at treatment end (4 h) - and measurement of residual blood compartment volume of used dialyzers. Results: 101 patients, 58% male, with a median dialysis vintage of 33 (6-71) months received hemodialysis using a total UFH dose of 9,306 ± 4,079 (range 3,000-23,050) IU/session. Use of a dialysis catheter (n = 56, 55%) was associated with a 1.4 times higher UFH dose (p < 0.001) irrespective of prior access function. aPTT increased significantly more than ACT both 1 h and 4 h after dialysis start, independent of the dialysis access used. 53% of patients with catheter access and ACT ratio < 1.5, 1 h after dialysis start had simultaneous aPTT ratios > 2.5. Similar findings were present at 1 h for patients with AVF/AVG and at dialysis end for catheter use. No clinically significant clotting of the extracorporeal circuit was noted during the studied sessions. Dialyzer's blood compartment volume was reduced with a median of 9% (6-20%) without significant effect of UFH dose, aPTT or ACT measurements and vascular access type. Conclusion: UFH dose adaptations based on ACT measurements frequently result in excessive anticoagulation according to aPTT results. Higher doses of UFH are used in patients with hemodialysis catheters without evidence that this reduces dialyzer clotting.

Dialyzer Performance During Hemodialysis Without Systemic Anticoagulation Using a Heparin-Grafted Dialyzer Combined With a Citrate-Enriched Dialysate: Results of the Randomized Crossover Noninferiority EvoCit Study.

RATIONALE & OBJECTIVE: The EvoCit study was designed to evaluate performance of a heparin-grafted dialyzer during hemodialysis with and without systemic anticoagulation. STUDY DESIGN: Randomized, crossover, noninferiority trial. Noninferiority was defined as a difference of≤10% for the primary outcome. SETTING & PARTICIPANTS: Single hemodialysis center; 26 prevalent patients treated with 617 hemodialysis sessions. INTERVENTIONS: Hemodialysis using a heparin-grafted dialyzer combined with a 1.0mmol/L citrate-enriched dialysate ("EvoCit") without systemic anticoagulation compared with hemodialysis performed with a heparin-grafted dialyzer with systemic heparin ("EvoHep"). Patients were randomly allocated to a first period of 4 weeks and crossed over to the alternative strategy for a second period of 4 weeks. OUTCOMES: The primary end point was the difference in Kt/Vurea between EvoCit and EvoHep. Secondary end points were urea reduction ratio, middle molecule removal, treatment time, thrombin generation, and reduction in dialyzer blood compartment volume. RESULTS: The estimated difference in Kt/Vurea between EvoCit and EvoHep was-0.03 (95% CI, -0.06 to-0.007), establishing noninferiority with mean Kt/Vurea of 1.47±0.05 (SE) for EvoCit and 1.50±0.05 for EvoHep. Noninferiority was also established for reduction ratios of urea and ß2-microglobulin. Premature discontinuation of dialysis was required for 4.2% of sessions among 6 patients during EvoCit and no sessions during EvoHep. Effective treatment time was 236±5 minutes for EvoCit and 238±1 minutes for EvoHep. Thrombin generation was increased and there was greater reduction in dialyzer blood compartment volume after treatments with EvoCit compared with EvoHep. LIMITATIONS: The effects of avoiding systemic anticoagulation on clinical outcomes were not evaluated. CONCLUSIONS: EvoCit is noninferior to EvoHep with respect to solute clearance but results in a greater number of shortened treatments, more membrane clotting, and greater thrombin generation TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT03887468.

Sodium-glucose cotransporter 2 inhibitors: renal outcomes according to baseline albuminuria.

Sodium-glucose co-transporter 2 inhibitors (SGLT2is) reduce albuminuria and hard renal outcomes (decline of renal function, renal replacement therapy and renal death) in patients with/without type 2 diabetes at high cardiovascular or renal risk. The question arises whether baseline albuminuria also influences renal outcomes with SGLT2is as reported with renin-angiotensin-aldosterone system inhibitors. Post hoc analyses focusing on albuminuria and renal outcomes of four cardiovascular outcome trials [EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), CANVAS (Canagliflozin Cardiovascular Assessment Study), DECLARE-TIMI 58 (Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) and VERTIS CV (Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial)] and some renal data from two heart failure trials [Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) and EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction)] showed renal protection with SGLT2is without significant interaction (P > 0.10) when comparing renal outcomes according to baseline levels (A1, A2 and A3) of urinary albumin:creatinine ratio (UACR), a finding confirmed in a dedicated meta-analysis. Two trials [CREDENCE (Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy) and DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease)] specifically recruited patients with CKD and UACRs of 200-5000 mg/g. A post hoc analysis of CREDENCE that distinguished three subgroups according to UACR (300-1000, 1000-3000 and >3000 mg/g) showed a greater relative reduction in UACR in patients with lower baseline albuminuria levels (P for interaction = 0.03). Patients with a UACR >1000 mg/g showed a significantly greater reduction in absolute (P for interaction < 0.001) and a trend in relative (P for interaction = 0.25) risk of renal events versus those with lower UACR levels. In conclusion, baseline UACR levels do not significantly influence the nephroprotection by SGLT2is, yet the greater protection in patients with very high UACRs in CREDENCE deserves confirmation. The underlying mechanisms of renal protection with SGLT2is might be different in patients with or without (high) UACR.

In Search of an Efficient Complexing Agent for Oxalates and Phosphates: A Quantum Chemical Study.

Limiting gastrointestinal oxalate absorption is a promising approach to reduce urinary oxalate excretion in patients with idiopathic and enteric hyperoxaluria. Phosphate binders, that inhibit gastrointestinal absorption of dietary phosphate by the formation of easily excretable insoluble complexes, are commonly used as a treatment for hyperphosphatemia in patients with end-stage renal disease. Several of these commercially available phosphate binders also have affinity for oxalate. In this work, a series of metallic cations (Li+, Na+, Mg2+, Ca2+, Fe2+, Cu2+, Zn2+, Al3+, Fe3+ and La3+) is investigated on their binding affinity to phosphate and oxalate on one side and anionic species that could be used to administer the cationic species to the body on the other, e.g., acetate, carbonate, chloride, citrate, formate, hydroxide and sulphate. Through quantum chemical calculations, the aim is to understand the competition between the different complexes and propose possible new and more efficient phosphate and oxalate binders.

Prevention of tunneled cuffed catheter dysfunction with prophylactic use of a taurolidine urokinase lock: A randomized double-blind trial.

BACKGROUND: The efficacy and cost-effectiveness of prophylactic thrombolytic locks in hemodialysis patients at high-risk of thrombotic dialysis catheter dysfunction is uncertain. We investigated this question in a double-blinded randomized controlled study. METHODS: Prevalent hemodialysis patients from 8 Belgian hemodialysis units, with ≥2 separate episodes of thrombotic dysfunction of their tunneled cuffed catheter during the 6 months before inclusion, were randomized to either: taurolidine heparin locks thrice weekly (control arm) or the same locks twice a week combined with taurolidine urokinase locks once a week before the longest interval without HD (TaurolockU arm). The primary efficacy outcome was the incidence rate of catheter thrombotic dysfunction requiring thrombolytic locks to restore function. RESULTS: 68 hemodialysis patients (32 controls, 36 urokinase) were followed during 9875 catheter days between May 2015 and June 2017. Incidence rate of thrombotic catheter dysfunction was 4.8 in TaurolockU vs 12.1/1000 catheter days in control group (rate ratio 0.39; 95%CI 0.23-0.64). 15/36 (42%) catheters in the treatment group required at least one therapeutic urokinase lock vs 23/32 (72%) in the control group (P = 0.012). The two groups did not differ significantly in catheter-related bloodstream infection and combined cost of prophylactic and therapeutic catheter locks. The TaurolockU group had a numerically higher number of episodes of refractory thrombosis. CONCLUSIONS: Prophylactic use of urokinase locks is highly effective in reducing the number of thrombotic catheter dysfunctions in catheters with a history of recurring dysfunction. Prophylactic use of urokinase locks did not reduce the overall costs associated with catheter locks and was associated with a numerically higher number of episodes of refractory thrombosis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036255.

Does kidney transplantation with a standard or expanded criteria donor improve patient survival? Results from a Belgian cohort.

BACKGROUND: Changes in recipient and donor factors have reopened the question of survival benefits of kidney transplantation versus dialysis. METHODS: We analysed survival among 3808 adult Belgian patients waitlisted for a first deceased donor kidney transplant from 2000 to 2012. The primary outcome was mortality during the median waiting time plus 3 years of follow-up after transplantation or with continued dialysis. Outcomes were analysed separately for standard criteria donor (SCD) and expanded criteria donor (ECD) kidney transplants. We adjusted survival analyses for recipient age (20-44, 45-64 and ≥65 years), sex and diabetes as the primary renal disease. RESULTS: Among patients ≥65 years of age, only SCD transplantation provided a significant survival benefit compared with dialysis, with a mortality of 16.3% [95% confidence interval (CI) 13.2-19.9] with SCD transplantation, 20.5% (95% CI 16.1-24.6) with ECD transplantation and 24.6% (95% CI 19.4-29.5) with continued dialysis. Relative mortality risk was increased in the first months after transplantation compared with dialysis, with equivalent risk levels reached earlier with SCD than ECD transplantation in all age groups. CONCLUSIONS: The results of this study suggest that older patients might gain a survival benefit with SCD transplantation versus dialysis, but any survival benefit with ECD transplantation versus dialysis may be small.

A preventable cause of transplant hydroureteronephrosis: inguinal herniation of the transplant ureter: case report and review of the literature.

BACKGROUND: Transplant ureter obstruction is an important cause of graft loss after kidney transplantation. Most cases occur early after transplantation and are related to surgical causes or ischaemic strictures. Underlying mechanisms of late ureteral obstruction are less well understood. CASE REPORT: We present the case of a 61-year-old man who showed gradual decline in renal allograft function and hydronephrosis nine years after transplantation, due to an inguinal herniation of the transplant ureter. After urinary diversion using a percutaneous nephrostomy, graft function restored and the patient underwent surgery. The ureter was reduced from the inguinal hernia and re-implanted in the bladder, with primary closure of the abdominal wall defect. Postoperative course was uneventful and serum creatinine returned to baseline levels. DISCUSSION: Search of relevant literature revealed a number of similar cases, which allowed identification of risk factors associated to the development of uretero-inguinal herniation leading to obstructive nephropathy. Diagnosis of this rare cause of transplant dysfunction and operative treatment strategies are discussed. CONCLUSIONS: Inguinal herniation of the transplant ureter leading to ureteral obstruction is a rare, probably underreported, cause graft of dysfunction. Therefore, we advocate elective repair of inguinal or incisional hernias in renal transplant recipients.

Variability in the incidence of renal replacement therapy over time in Western industrialized countries: A retrospective registry analysis.

INTRODUCTION: A growing number of patients started renal replacement therapy (RRT) in Western industrialized countries between 1980 an early 2000s. Thereafter reports from national and international registries suggest a trend towards stabilization and sometimes a decrease in the incidence rate. AIM: To investigate the differences in overall and age-specific incidence rates between industrialized countries from 1998 until 2013. Secondly, to investigate changes in incidence rates over time and their association with specific age categories. METHOD: We extracted the unadjusted overall incidence of RRT and age-specific incidence rates from renal registry reports in Europe, the United States, Canada, Australia and New Zealand. Time trends in the incidence rate by country and age categories were analyzed by Joinpoint regression analysis. RESULTS: The incidence rate in 2013 ranged from 89 per million population (pmp) in Finland to 363 pmp in the US. Incidence rates in the lower age categories (20-64 year) were similar between countries and remained stable over time. Higher incidence countries were characterized by higher numbers of patients in both the 65-74 and ≥75 year categories starting RRT. Joinpoint analysis confirmed that most countries had significant reductions in the incidence rate at the end of the study period. These reductions were explained by lower numbers of older patients starting RRT and were observed also in countries with lower overall incidence rates. CONCLUSION: This study confirmed different incidence rates of RRT between industrialized countries worldwide. Countries with the highest overall incidence rates also had the highest incidence rates in the oldest age categories. Since the early 2000's the number of older patients starting RRT is either stabilizing or even decreasing in most countries. This reduction is universal and is also observed in countries with previously low incidence rates.

Hemodialysis Does Not Induce Detectable Activation of the Contact System of Coagulation.

INTRODUCTION: Systemic anticoagulation is administered during hemodialysis to prevent clotting of the extracorporeal circuit. The role of contact system activation in thrombin generation during hemodialysis using current era dialyzer membranes is unknown. METHODS: We performed a single-center randomized crossover study. Ten patients treated with hemodialysis underwent 3 standardized hemodialysis sessions. For every patient, each session was performed with a different type of dialyzer membrane (polyphenylene [PP], polymethylmetacrylate [PMMA], polyethylenimine-coated polyacrylonitrile [AN69ST]). Blood samples were collected before and 5, 15, 30, 90, and 240 minutes after blood pump start to evaluate coagulation activation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [PF1+2], activated factor XII [FXIIa], kallikrein, activated factor XI [FXIa]). Plasma of healthy volunteers (n = 20) was used as a reference. RESULTS: Baseline TAT and PF1+2 levels were higher in hemodialysis patients compared to healthy controls (median [interquartile range] for TAT: 3.3 [2.9-4.2] vs. 2.4 [2.3-2.5] µg/l [P = 0.0002] and for PF1+2: 647 [478-737] vs. 138 [125-254] pmol/l [P < 0.0002]). Despite the use of systemic anticoagulation, TAT further increased during treatment, with the increase starting after 30 minutes (median TAT at t240: 9.0 µg/l (PP), 5.5 µg/l (PMMA), and 7.2 µg/l (AN69ST), all P < 0.05 vs. baseline). Contact system markers FXIIa and kallikrein did not differ significantly between dialysis patients and healthy controls, whereas baseline FXIa levels were significantly lower in dialysis patients compared to healthy controls (P = 0.001). Levels of all contact system markers remained unchanged during hemodialysis with all types of dialyzer membranes. CONCLUSION: Routine hemodialysis using systemic heparin anticoagulation induces coagulation activation without measurable contact system activation.

Efficacy of urokinase lock to treat thrombotic dysfunction of tunneled hemodialysis catheters: A retrospective cohort study.

BACKGROUND:: There are few data to inform decisions about the optimal management of occluded tunneled cuffed hemodialysis catheters with thrombolytic locking solutions. The effect of dose, dwell-time, and number of administrations remains controversial. METHODS:: In this retrospective single-center review of tunneled cuffed catheters used between 2010 and 2014, restoration of blood flow as well as pre- and post-pump pressures after either short (30 min) or prolonged (48-72 h) administration of 100,000 IU of urokinase locking solution was evaluated in all thrombotic dysfunctions. We also assessed if multiple urokinase locks for the same thrombotic dysfunction event were more efficient to restore catheter performance than single administration. RESULTS:: Data on 773 thrombotic events in 148 patients (236 catheters) were collected during observation period. After urokinase treatment, blood flow and pre-pump pressure improved (median of 50 mL/min and 20 mmHg) whereas post-pump pressure decreased (median of 15 mmHg) (all P < 0.0001). The short thrombolytic procedure, used in more severely dysfunctional catheters, resulted in significantly larger improvements in catheter function than the long procedure. Multiple administrations for the same thrombotic event further improved access function in case of persisting dysfunction after first lock but had no added beneficial effect if blood flow and/or pump pressures were normalized after first urokinase lock. CONCLUSION:: Both short and prolonged administration of urokinase locks were efficient in restoring blood flow and pre- and post-pump pressures in dialysis catheters with thrombotic dysfunction. Multiple urokinase locks provide added benefit on these outcomes only in case of persisting dysfunction after the first lock.