Thromboelastography and Traditional Coagulation Testing in Non-ICU-Admitted Patients with Acute Kidney Injury: An Observational Cohort Study.

INTRODUCTION: This study aimed to elucidate the coagulation disorders in non-ICU patients with acute kidney injury (AKI) and their contribution to clotting-related outcomes of intermittent kidney replacement therapy (KRT). METHODS: We included non-ICU-admitted patients with AKI requiring intermittent KRT, clinically having a risk of bleeding and against systemic anticoagulant use during KRT between April and December 2018. The premature termination of treatment due to circuit clotting was considered a poor outcome. We analyzed the characteristics of thromboelastography (TEG)-derived and traditional coagulation parameters and explored the potential-affecting factors. RESULTS: In total, 64 patients were enrolled. Hypocoagulability was detected in 4.7%-15.6% of patients by a combination of the traditional parameters, i.e., prothrombin time (PT)/international normalized ratio, activated partial PT, and fibrinogen. No patient had hypocoagulability observed on TEG-derived reaction time; only 2.1%, 3.1%, and 10.9% of patients had hypocoagulability on TEG-derived kinetic time (K-time), α-angle, and maximum amplitude (MA), respectively, which were also platelet-related coagulation parameters, despite 37.5% of the cohort having thrombocytopenia. In contrast, hypercoagulability was more prevalent, involving 12.5%, 43.8%, 21.9%, and 48.4% of patients on TEG K-time, α-angle, MA, and coagulation index (CI), respectively, although thrombocytosis was only in 1.5% of the cohort. Patients with thrombocytopenia showed lower fibrinogen level (2.6 vs. 4.0 g/L, p = 0.00), α-angle (63.5° vs. 73.3°, p = 0.00), MA (53.5 vs. 66.1 mm, p = 0.00), and CI (1.8 vs. 3.6, p = 0.00) but higher thrombin time (17.8 vs. 16.2 s, p = 0.00) and K-time (2.0 vs. 1.2 min, p = 0.00) than those with a platelet count over 100 × 109/L. 41 patients were treated with heparin-free protocol, and 23 were treated with regional citrate anticoagulation (RCA). The premature termination rate was 41.5% on heparin-free patients, while 8.7% of patients underwent an RCA protocol (p = 0.006). Heparin-free protocol was the strongest adverse factor to poor outcomes. A heparin-free subgroup analysis found that the circuit clotting risk was increased by 61.7% with a 10 × 109/L elevation in platelet count (odds ratio [OR] = 1.617, p = 0.049) and decreased by 67.5% following a second increase of PT (OR = 0.325, p = 0.041). No significant correlation was found between TEG parameters and premature circuit clotting. CONCLUSIONS: Most non-ICU-admitted patients with AKI had normal-to-enhanced hemostasis and activated platelet function based on TEG results, as well as a high rate of premature circuit clotting when receiving heparin-free protocol despite thrombocytopenia. Further studies are needed to better determine the use of TEG in respect to management of anticoagulation and bleeding complications in AKI patients with KRT.

Efficacy and Safety of Paclitaxel-Coated Balloon Angioplasty for Dysfunctional Arteriovenous Fistulas: A Multicenter Randomized Controlled Trial.

RATIONALE & OBJECTIVE: Previous studies have illustrated the potential superiority of drug-coated balloons (DCBs) in maintaining patency after initial angioplasty for arteriovenous fistula (AVF) dysfunction due to stenosis. Our trial evaluated the efficacy and safety of DCBs for preventing fistula restenosis in Chinese hemodialysis patients. STUDY DESIGN: Multicenter, prospective, randomized, open-label, blinded end point, controlled trial. SETTINGS & PARTICIPANTS: A total of 161 hemodialysis patients with fistula dysfunction from 10 centers in China. INTERVENTION: Participants were randomized 1:1 to treatment with initial dilation followed by DCB angioplasty or conventional high-pressure balloon (HPB) angioplasty. OUTCOMES: The primary end point was target lesion primary patency defined as the target lesion intervention-free survival in conjunction with an ultrasonography-measured peak systolic velocity ratio (PSVR) ≤2.0 at 6 months. The secondary end points included 1) device, technical, clinical, and procedural success; 2) major adverse events; 3) degree of target lesion stenosis at 6 months; and 4) clinically driven target lesion and target shunt revascularization within 12 months. RESULTS: The percentage with target lesion primary patency as defined by a PSVR ≤2.0 was higher in the DCB group than in the control group (65% vs 37%, respectively; rate difference, 28% [95% CI, 13%-43%]; P <0.001) at 6 months. The target lesion and target shunt intervention-free survival of the DCB group were not superior to those of the control group at 6 months (P = 0.3 and P = 0.2, respectively) but were superior at 12 months (target lesion intervention-free survival: 73% for DCB vs 58% for control [P = 0.04]; target shunt intervention-free survival: 73% for DCB vs 57% for control [P = 0.04]). The average degree of target lesion stenoses at 6 months was not significantly different between the 2 groups (44% ± 16% for DCB vs 49% ± 18% for control; P = 0.09). There were no significant differences in major adverse events or in device, technical, clinical, or procedural success rates between the groups. LIMITATIONS: Small sample size; short follow-up period; procedural differences between the 2 groups such as unequal inflation times and balloon lengths. CONCLUSIONS: Compared to conventional HPB angioplasty, DCB treatment achieved superior primary patency defined using PSVR measured at 6 months and superior intervention-free survival of both the target lesion and the target shunt at 12 months without evidence of greater adverse events. FUNDING: Funded by ZhuHai Cardionovum Medical Device Co., Ltd. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT02962141.

T cell responses to peptides of Goodpasture autoantigen in patients with anti-glomerular basement membrane disease.

AIM: Cell-mediated autoimmunity, especially autoreactive T cells, is crucial in the initiation of anti-glomerular membrane (GBM) disease. Epitopes for T cells on Goodpasture autoantigen are not fully defined. This study investigated T cell epitopes in anti-GBM patients, aiming to identify the epitopes and their clinical significance. METHODS: Peripheral blood mononuclear cells (PBMC) were collected from 13 patients with anti-GBM disease. Twenty-four overlapping linear peptides were synthesized covering the whole sequence of human α3(IV)NC1. PBMC response to each peptide was detected by proliferation assay. Their associations with clinical features were further analyzed. RESULTS: Peripheral blood mononuclear cells proliferative responses to linear peptides on α3(IV)NC1 could be detected in all patients. Five major epitopes were identified as stimulatory in over half of the patients: α3(IV)NC1127-148 (P14) (69.2%), α3(IV)NC1159-178 (77.8%), α3(IV)NC1179-198 (55.6%), α3(IV)NC1189-208 (P19) (75.0%) and α3(IV)NC1141-154 (57.1%). P14 and P19 were highly recognized in patients comparing with healthy controls (69.2% vs. 0.0%, P = 0.011; 75.0% vs. 0.0%, P = 0.021, respectively). CONCLUSION: T cell proliferation to linear epitopes was detected in human anti-GBM disease. α3127-148 was a mutual T and B cell epitope, implying its initial role in epitope spreading process.

Polyethyleneimine-treated polyacrylonitrile membrane hemofilter for critically ill patients receiving anticoagulant-free prolonged intermittent renal replacement therapy: a single-center, prospective, self-controlled pilot study.

BACKGROUND: Critically ill patients requiring renal replacement therapy (RRT) are at risk of disease-related bleeding. Systemic heparinization should be avoided. AN69ST, a polyethyleneimine-treated polyacrylonitrile (AN69) membrane hemofilter, can be primed with heparin, improving its local anticoagulative activity. Prolonged intermittent RRT (PI-RRT) is of shorter duration and cheaper, considered as an alternative to continuous RRT. This study was performed to compare the success rate of anticoagulant-free PI-RRT using AN69ST versus AN69 membrane hemofilter. We also evaluated risk factors for filter clotting. METHODS: This crossover, double-blind, randomized study included patients requiring PI-RRT but at high bleeding risk treated with AN69ST and AN69 hemo filters. The success rate of RRT, filter lifespan and severity of filter clotting were compared between the hemo filters. Factors associated with the filter clotting risk were analyzed with a Cox proportional hazards model. RESULTS: This study included 60 patients (mean age, 68.1 ± 15.8 years). Thirty-three (55.0%) patients were in the intensive care unit, 34 (56.8%) had disease-related thrombocytopenia, and 14 (23.3%) had local hemorrhagic diseases. The success rate of PI-RRT with the AN69ST and AN69 hemofilter was 51.7% and 50.9%, respectively (P > 0.05). The mean PI-RRT duration was 543.1 ± 119.0 min in the completed sessions and 387.3 ± 140.8 min in the prematurely terminated sessions, without significant difference between AN69ST and AN69 hemofilters. Cox regression analysis showed that age (odds ratio [OR], 1.023 per year), platelet count (OR, 1.07 per 10 × 109/L), hemoglobin concentration (OR, 1.035 per 1 g/L), and activated partial thromboplastin time (aPTT; OR, 0.973 per second) were associated with a hemofilter clotting risk. The AN69ST hemofilter lifespan was significantly prolonged averaging an extra 251.7 min in patients with an aPTT of <35.3 s, hemoglobin concentration of >83 g/L and platelet count of <70 × 109/L. CONCLUSIONS: Anticoagulant-free PI-RRT by a heparin-primed AN69ST hemofilter reached a 51.7% success rate. The risk of premature clotting of the extracorporeal circuit remains unsatisfactory. For select patients at high risk of bleeding, the heparin-primed AN69ST hemofilter may be more appropriate for anticoagulation-free PI-RRT. TRIAL REGISTRATION: https://www.clinicaltrials.gov ; study number: NCT02355873 . Release Date 01/21/2015.

Plasma exchange and rituximab treatments in primary membranous nephropathy combined with crescentic glomerulonephritis: A case report.

RATIONALE: Crescent formation is rare in primary membranous nephropathy (MN). Anti-phospholipase A2 receptor (PLA2R) antibodies are detectable in these patients. The mechanism and treatments are unknown. PATIENT CONCERNS: A 72-year-old female patient who presented with nephrotic syndrome, hematuria, and rapidly progressive kidney dysfunction. DIAGNOSES: Kidney biopsy was performed and the diagnosis was MN in combination with crescentic glomerulonephritis. Circulating anti-PLA2R IgG3 and IgG4 were detected of high level. INTERVENTIONS: The patient received plasma exchange and rituximab besides corticosteroids. OUTCOMES: The patient achieved complete remission of proteinuria and recovery of kidney function after the clearance of anti-PLA2R antibodies. LESSON: This case suggests a pathogenic role of anti-PLA2R antibodies in the mechanism of crescent formation in MN, which may need intensive therapy to eliminate the antibodies quickly.

Anti-glomerular basement membrane disease: outcomes of different therapeutic regimens in a large single-center Chinese cohort study.

Anti-glomerular basement membrane (GBM) disease usually presents with rapidly progressive glomerulonephritis accompanied by pulmonary hemorrhage. The low incidence and fulminant course of disease preclude a large randomized controlled study to define the benefits of any given therapy. We conducted a retrospective survey of 221 consecutive patients seen from 1998 to 2008 in our hospital, and report here the patient and renal survival and the risk factors affecting the outcomes. Considering the similar clinical features of the patients, we could compare the effects of 3 different treatment regimens: 1) combination therapy of plasmapheresis and immunosuppression, 2) steroids and cytotoxic agents, and 3) steroids alone.The patient and renal survival rates were 72.7% and 25.0%, respectively, at 1 year after disease presentation. The serum level of anti-GBM antibodies (increased by 20 U/mL; hazard ratio [HR], 1.16; p = 0.009) and the presentation of positive antineutrophil cytoplasmic antibodies (ANCA) (HR, 2.18; p = 0.028) were independent predictors for patient death. The serum creatinine at presentation (doubling from 1.5 mg/dL; HR, 2.07; p < 0.001) was an independent predictor for renal failure.The combination therapy of plasmapheresis plus corticosteroids and cyclophosphamide had an overall beneficial effect on both patient survival (HR for patient mortality, 0.31; p = 0.001) and renal survival (HR for renal failure, 0.60; p = 0.032), particularly patient survival for those with Goodpasture syndrome (HR for patient mortality, 0.29; p = 0.004) and renal survival for those with anti-GBM nephritis with initial serum creatinine over 6.8 mg/dL (HR for renal failure, 0.52; p = 0.014). The treatment with corticosteroids plus cyclophosphamide was found not to improve the renal outcome of disease (p = 0.73). In conclusion, the combination therapy was preferred for patients with anti-GBM disease, especially those with pulmonary hemorrhage or severe renal damage. Early diagnosis was crucial to improving outcomes.