Use Of Plasma Exchange Research Articles

Late use of Plasma Exchange in Acute Liver Failure: The Battle is Lost?

Late use of Plasma Exchange in Acute Liver Failure: The Battle is Lost?

How to make a decision for the use of plasma exchange in patients with acute liver failure?

How to make a decision for the use of plasma exchange in patients with acute liver failure?

Toward a Restrictive Use of Plasma Exchanges in Thrombotic Microangiopathies.

Toward a Restrictive Use of Plasma Exchanges in Thrombotic Microangiopathies.

The use of plasma exchange with albumin replacement in the management of Alzheimer's disease: a scoping review.

AD is a progressive neurodegenerative disorder causing significant cognitive decline and impaired daily functioning. Current treatments offer only modest relief, and many amyloid-targeting therapies have failed, prompting exploration of alternative approaches such as PE with albumin replacement. This scoping review systematically maps the literature on PE with albumin replacement in AD management, focusing on outcomes, methodologies, and reported benefits and risks. A comprehensive search in PubMed, supplemented by reference scanning and hand-searching, identified studies involving PE with albumin replacement in AD patients. Data charting and critical appraisal were conducted using standardized tools. Seven primary studies from the AMBAR (Alzheimer Management by Albumin Replacement) trial met the inclusion criteria, consistently reporting improvements in cognitive function, positive neuroimaging results, and favorable neuropsychiatric outcomes. For instance, one study found a significant slowing of cognitive decline (p < 0.05) among patients receiving PE with albumin replacement. Another study showed better preservation of hippocampal volume and improved brain perfusion metrics in the treatment group (p < 0.05). The intervention was generally well-tolerated with manageable side effects. PE with albumin replacement is a promising therapeutic approach for AD, warranting further investigation to confirm its efficacy and safety across broader settings. https://osf.io/v6dez/?view_only=1cd9637e7e0347d39713bf19aac0dfe8.

A case report of plasma exchange in imidacloprid poisoning: A promising therapeutic approach for acute toxicity

Abstract: Imidacloprid, a neonicotinoid insecticide, is commonly used in agricultural and urban settings for pest control. However, its toxic effects on both target and nontarget organisms, including humans, have raised concerns. Imidacloprid poisoning can result in a wide range of symptoms, including neurological, gastrointestinal, and cardiovascular manifestations, and may even be fatal in severe cases. In recent years, plasma exchange has emerged as a potential therapeutic approach in cases of imidacloprid poisoning, with promising outcomes reported in a few published case reports. This article reviews the role of plasma exchange in imidacloprid poisoning, highlighting its mechanism of action, clinical indications, technical aspects, and potential benefits. The article also discusses the current evidence supporting the use of plasma exchange in imidacloprid poisoning, including relevant case reports and studies. While plasma exchange appears to be a promising adjunctive therapy in managing imidacloprid poisoning, further research and clinical experience are needed to establish its effectiveness and safety. This article emphasizes the importance of early recognition and management of imidacloprid poisoning, including considering plasma exchange as a potential treatment modality in severe cases.

#1475 Anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) in real world life

Abstract Background and Aims Anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) is a rare disease and the different treatment with plasma exchange are still controversial. We evaluate the AAV-GN outcomes of the last ten years in our centre. Method We retrospectively reviewed the clinical presentations and outcomes of AAV-GN patients in our centre between 2013-2022. We compared the presentation and prognosis according to the type of ANCA, serum creatinine (SCr) and the use of plasma exchange (PLEX). We included patients with AAV and kidney biopsy with at least 6 months of follow-up. Patients with positivity for both MPO and PR3, anti-GBM antibodies or did not meet inclusion criteria were excluded. Results Of 64 patients reviewed, 13 were excluded: 3 lack of follow-up, 3 absence of renal biopsy, 3 ANCA negative, and 4 concomitant anti-GBM antibodies. A total of 51 patients were included in the analysis (Table 1): 28 women (54.9%), age 66.75 ± 15.24 years, (64.7% over 65 years) and 44 (86.3%) with ANCA-MPO (+). Results comparing ANCA-MPO and PR3 in Table 1. The most frequent form of presentation was anaemia with haemoglobin 9.87 ± 2.04 mg/dL, acute kidney injury (AKI) AKIN III (39.2%), median SCr 2.78 (1.58-5.22) mg/dL, 41 (80.4%) with microhematuria, proteinuria 2.62 ± 2.7g/g, and 8 (15.7%) alveolar haemorrhage. 18 patients (25.3%) required hemodialysis, and 7 (13.5%) were transient (4 requiring &amp;lt;1 month). Rituximab was more used than cyclophosphamide (p &amp;lt; 0.001). Of the patients treated with plasma exchange (PLEX, n = 11), 6 (54.5%) had alveolar haemorrhage and/or 7 (63.6%) SCr&amp;gt;5.6 mg/dL, with no further infections or mortality at one year. Of the patients diagnosed with SCr&amp;gt;5.6 mg/dL, 9 (81.8%) were men (p = 0.008), 7 (63.6%) received PLEX (p &amp;lt; 0.001) and 6 (54.4%) died (p = 0.003). As expected, in the multivariate binary logistic regression SCr&amp;gt;5.6 at diagnosis was identified as independent risk factor for PLEX (p = 0.02, OR = 15.6 (95% CI 3.16-76.92). There were 13 deaths (25.5%), 6 in the first year after diagnosis. The most used maintenance treatment was MMF (52.9%), SCr and glomerular filtration rates at 2 years were 1.5 mg/dL and 45.36 mL/min/1.72 m² respectively. Conclusion The most common AAV-GN in our centre are ANCA-MPO+, and mainly affect people over 65 years of age, with rituximab being the most used treatment. ANCA-MPO+ patients have worse renal function at 18 months of follow-up. Mortality is higher in AAV-GN with serum creatinine greater than 5.6 mg/dL at diagnosis and in ANCA-MPO+. PLEX therapy is more used in cases of alveolar hemorrhage or severe renal involvement, without presenting an impact in our cohort in the incidence of infections or mortality at one year of follow-up.

#3076 A UK parallel cohort study on renal ANCA associated vasculitis outcomes for avacopan exposed and matched unexposed cohorts

Abstract Background and Aims Avacopan was approved in the UK for severe ANCA associated vasculitis (AAV) in December 2022. The ADVOCATE trial found the differential effect of avacopan on kidney function was greatest in patients with the lowest estimated glomerular filtration rate (eGFR), at highest risk of progression to end stage kidney disease (ESKD). Patients with an eGFR &amp;lt;15 ml/min/1.73 m2, pulmonary haemorrhage requiring invasive ventilation, under 12 months prognosis, use of plasma exchange and dual therapy with cyclophosphamide (CYC) and rituximab (RTX) were excluded from ADVOCATE; all common scenarios in real life practice. We aim to provide further information on these subgroups and evaluate 6 month renal outcome data in the UK. Method Parallel cohort study on renal AAV outcomes for avacopan exposed and matched unexposed cohorts, with severe, active GPA or MPA. 120 patients on avacopan from 7 UK centres have been recruited to date. Controls matched by renal function and age will be presented. Comparisons of ESKD, delta eGFR, eGFR recovery, reduction in proteinuria/haematuria, remission, relapse and mortality will be presented, with subgroup analyses for eGFR&amp;lt;15 ml/min/1.73 m2. Steroid exposure will be presented. Results Baseline characteristics of the avacopan cohort are below. Most received oral prednisolone at avacopan initiation (89%, n = 107) and 54% received intravenous methylprednisolone (n = 65). The majority received RTX alone (44%, n = 53) or RTX and CYC combination therapy (43%, n = 52). Fewer received CYC alone (9%, n = 11) and 3% were initiated on alternative immunosuppression (n = 4). 26% (n = 31) underwent plasma exchange and 13% required haemodialysis (n=16). 3% of patients have died. Excluding dialysis dependent patients at presentation, median eGFR was 22ml/min/1.73 m2 (IQR 10-36). eGFR at the time of avacopan initiation was 21ml/min/1.73 m2 (IQR 11-34). Conclusion Avacopan is commonly being used to treat nephritis in patients with a low eGFR, including haemodialysis dependent and elderly patients. Avacopan is frequently used with RTX and CYC combination therapy. 6 month outcome data will provide new data on important patient subgroups excluded from the ADVOCATE trial.

Risk of Relapse of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in a Randomized Controlled Trial of Plasma Exchange and Glucocorticoids.

Relapses of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are important events that can cause organ dysfunction and reduce quality of life. Understanding the effects of the initial treatments for ANCA-associated vasculitis on the subsequent risk of relapse may help guide monitoring and treatment. We performed a post hoc analysis of participants with severe ANCA-associated vasculitis enrolled in an international two-by-two factorial randomized controlled trial comparing the effects of plasma exchange (PLEX) to no PLEX and a regimen of reduced glucocorticoid exposure to a standard regimen. We estimated the effects of treatments on relapses of any severity using three competing risk time-to-event models adjusted for patient and disease characteristics and other treatments. Each model was adjusted for disease manifestations in different ways. Of 704 participants, 649 (92.2%) achieved remission and 147 (22.7%) experienced 204 relapses. The relapse rate was 10.3 (95% confidence interval [CI] 8.4-12.1) relapses per 100 patient-years. Neither the use of PLEX (subhazard ratio 0.91-0.94; 95% CIs range from 0.66 to 1.31) nor a glucocorticoid regimen (subhazard ratio 0.93-0.94; 95% CIs range from 0.67 to 1.35) appreciably changed the risk of relapse. Proteinase 3-ANCA and the presence of nonhemorrhagic respiratory manifestations of the disease at trial entry were associated with increased risks of relapse. Receiving dialysis at baseline and administration of oral cyclophosphamide as induction therapy were associated with lower risks of relapse. In patients with severe ANCA-associated vasculitis, relapses remain common; neither the use of PLEX nor an initial glucocorticoid tapering regimen impacted relapse risk.

Trends in Plasma Exchange Use in Optic Neuritis Hospitalizations in the United States

To report use trends of plasma exchange (PLEX) as well as sociodemographic and medical comorbidities associated with PLEX in the United States. Retrospective cross-sectional study. Adult patients (≥ 18 years) admitted for inpatient hospitalization with a primary diagnosis of optic neuritis (ON). Data from the National Inpatient Sample database was compiled to assess PLEX use rates between 2000 and 2020. The cohorts of patients receiving PLEX versus not receiving PLEX were analyzed between quarter 4 of 2015 through 2020 (International Classification of Diseases, Tenth Revision [ICD-10], only) for patient sociodemographic variables, medical diagnoses, insurance types, hospital characteristics, cause of disease, time to therapy, length of stay (LOS), and total charges incurred. Incidence of ON, incidence of PLEX, demographics, diagnoses associated with PLEX therapy, total charges, and LOS. From 2000 through 2020, 11 209 patients hospitalized with a primary diagnosis of ON were identified, with a significant majority managed at urban teaching hospitals. Use of PLEX increased steadily over 2 decades from 0.63% to 5.46%. Use was greatest in the western United States and least in the eastern United States. In the subset of ICD-10 cases, 3215 patients were identified. The median time to therapy of PLEX was 1 day after admission, and PLEX use was highest in patients with neuromyelitis optica spectrum disorder (NMOSD) (21.21%) and lowest in multiple sclerosis-associated ON (3.80%). Use of PLEX was associated with significantly longer LOS and higher total charges incurred. Medical comorbidities associated with PLEX included adverse reaction to glucocorticoids (adjusted odds ratio [aOR], 31.50), hemiplegia (aOR, 28.48), neuralgia (aOR, 4.81), optic atrophy (aOR, 3.74), paralytic strabismus (aOR, 2.36), and psoriasis (aOR, 1.76). Over the last 2 decades in the United States, PLEX therapy for ON has increased, with the highest use in the western United States and for patients with the diagnosis NMOSD ON. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Successful management of massive digoxin overdose using DIGIFab and therapeutic plasma exchange: a case report

BackgroundDespite the efficacy and safety of DIGIFab, it is relatively expensive and has limited availability. In addition, alternative interventions, such as therapeutic plasma exchange, may need to be considered in massive digoxin overdoses. Although few case reports describe its efficacy.Case presentationWe report a case of a 17-year-old white male patient brought by family members to our emergency department in Riyadh, Saudi Arabia. After intentionally ingesting 48 mg of digoxin tablets to commit suicide, the patient’s initial digoxin serum level was 8.04 ng/mL. The patient was resuscitated in the emergency department. After admission to the intensive care unit, the patient underwent therapeutic plasma exchange, because of insufficient DIGIFab doses. Afterward, the serum digoxin levels drastically decreased, and his symptoms reverted. The patient was successfully managed and discharged 7 days after admission.ConclusionDespite insufficient evidence and a limited number of case reports describing the use of extracorporeal treatment in digoxin overdose, we noted the significant impact of therapeutic plasma exchange on our patient. However, therapeutic plasma exchange’s use in routine treatment requires stronger evidence to confirm its benefits.

Treatment with plasma exchange of a pregnant woman with anti-PP1Pk alloimmunization: A case report

The histo-blood group antigens P, P1 and Pk are a closely related set of glycosphingolipid structures expressed by red blood cells and other tissues. None of these three characters is expressed on p cells, a null phenotype that arises in the context of homozygous mutation of the A4GALT gene. Subjects with p phenotype spontaneously develop a natural alloantibody named anti-PP1Pk, which is a mixture of IgG and IgM against P1, P and Pk. While anti-P1 is a weak cold antibody with poor clinical significance, anti-P and anti-Pk antibodies are potent haemolysins responsible for severe hemolytic transfusion reactions. The rare anti-PP1Pk alloantibodies are associated with recurrent spontaneous abortion in the first trimester of gestation. P and Pk antigens are expressed at high levels on the placenta and antibodies directed against both these structures are deleterious to placental trophoblasts. Here we describe the use of plasma exchange (PEX) in a nulliparous 39-year-old woman with anti-PP1Pk antibodies and a history of repeated spontaneous early abortions and hypofertility. The patient underwent apheresis starting from the third week throughout the pregnancy and a healthy child was delivered by cesarean section at 35 WG. The newborn required only phototherapy within a few days of life. We can state that an early treatment with the only PEX has proven to be effective and safe in the management of a fetomaternal P-incompatibility caused by a high anti-PP1Pk titer (256).

Plasma Exchange Reduces Aβ Levels in Plasma and Decreases Amyloid Plaques in the Brain in a Mouse Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common type of dementia, characterized by the abnormal accumulation of protein aggregates in the brain, known as neurofibrillary tangles and amyloid-β (Aβ) plaques. It is believed that an imbalance between cerebral and peripheral pools of Aβ may play a relevant role in the deposition of Aβ aggregates. Therefore, in this study, we aimed to evaluate the effect of the removal of Aβ from blood plasma on the accumulation of amyloid plaques in the brain. We performed monthly plasma exchange with a 5% mouse albumin solution in the APP/PS1 mouse model from 3 to 7 months old. At the endpoint, total Aβ levels were measured in the plasma, and soluble and insoluble brain fractions were analyzed using ELISA. Brains were also analyzed histologically for amyloid plaque burden, plaque size distributions, and gliosis. Our results showed a reduction in the levels of Aβ in the plasma and insoluble brain fractions. Interestingly, histological analysis showed a reduction in thioflavin-S (ThS) and amyloid immunoreactivity in the cortex and hippocampus, accompanied by a change in the size distribution of amyloid plaques, and a reduction in Iba1-positive cells. Our results provide preclinical evidence supporting the relevance of targeting Aβ in the periphery and reinforcing the potential use of plasma exchange as an alternative non-pharmacological strategy for slowing down AD pathogenesis.

Low ADAMTS13 Activity in Patients with Liver Disease- Thrombotic Thrombocytopenic Purpura or Not?

Introduction: Patients with liver injury have hemostatic defects including reduced ADAMTS13 (A disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13). Severe deficiency of ADAMTS13 (ADMS13) activity (&amp;lt; 10%) is pathognomonic for thrombotic thrombocytopenic purpura (TTP), a rare thrombotic microangiopathy (TMA). Differentiating TTP from severe liver injury is complex for multiple reasons including 1) low baseline ADMS13 2) concomitant coagulopathies complicating differentiation from disseminated intravascular coagulation (DIC) 3) ADMS13 activity (ADMS13:AC) assay interference (hyperbilirubinemia (&amp;gt;30mg/dL) can cause artifactual reduction of ADMS13:AC). Here we sought to characterize the clinical presentation, management, and outcomes of patients with liver injury presenting with thrombocytopenia (TCP), microangiopathic hemolytic anemia (MAHA) and low ADMS13:AC at our institution. Methods: In this retrospective study, after IRB approval, electronic medical records (EMR) of institutional patients who had ADMS13:AC and inhibitor profile performed in our special coagulation laboratory between 2018 and July 17, 2023, were reviewed. Eligible patients had ADMS13:AC ≤20% were ≥ 18 years and had evidence of liver injury at time of ADMS13. Liver injury was defined as ALT or AST elevations greater than two times the upper level of normal within one month prior to ADMS13:AC testing, history of end stage liver disease or cirrhosis, or liver transplant with evidence of graft dysfunction. Details regarding clinical presentation, management and outcomes were extracted from the EMR. PLASMIC and ISTH DIC scores were retrospectively calculated. Results: 70 patients had at least one ADMS13:AC &amp;lt; 20% during the study period. 28/70 patients met liver injury inclusion criteria and 20/28 had TCP and MAHA. Of those 20 patients, median age at initial ADMS13:AC was 56.5 years (29-85). Most patients (n=14) had ADMS13:AC of 10-20%. ADMS13:AC was &amp;lt; 5% and 5-10% in 3 patients each. Eleven patients had a positive inhibitor with a median Bethesda titer of 1.85 BU (0.5-3.9). Etiology of liver included: ischemic hepatopathy (n=8), liver graft failure (n=4), liver metastasis (n=3), cirrhosis (n=2), alcoholic hepatitis (n=1), unknown (n=2). Median hemoglobin and platelet (plt) count at time of ADMS13 was 7 g/dL (6.4-13.2) and 30 x10 9/L (3-98), respectively. 7/20 patients had a PLASMIC score of ≥5; PLASMIC score was ≥5, in 2/6 patients with ADMS13:AC &amp;lt;10%. 16/18 patients had an ISTH DIC score ≥5. 18/20 patients had a creatinine &amp;gt; 2 mg/dL or were receiving renal replacement therapy the time of ADMS13: AC. 7/20 patients had total or direct bilirubin of &amp;gt;30mg/dL. Eight/20 patients were treated with plasma exchange (PEX) for a median duration of 7 days (2-13). 66.7% of pts with ADMS13:AC &amp;lt;10% received PEX. Glucocorticoids and Rituximab were used with the intent to treat TTP in 7 and 3 patients, respectively. Caplacizumab was used in 2 patients. 3/8 (37.5%) patients receiving PEX demonstrated normalization of MAHA. One of these patients demonstrated improvement but not normalization of plts (Table 1B, case 5). All patients had recurrence of hematologic abnormalities after PEX was stopped. One patient was treated with plasma infusion with stabilization in plt count. There were 13 and 15 deaths within 1 and 6 months of first ADMTS13:AC, respectively. One death was potentially attributable to management of TTP (Table 1B, case 1). There was no difference in time to death or mortality with the use of PEX. Repeat ADMS13:AC remote from PEX, TCP and MAHA was available for 1/5 surviving patients. This patient (Table1, case 2) had normalization of ADMS:AC after undergoing liver transplant. Conclusion: The differential diagnosis of TCP and MAHA in patients with liver injury includes hepatic dysfunction, DIC and TMA. In the current cohort, 89% of evaluable patients met criteria for overt DIC per ISTH criteria. Due to a low ADMTS13:AC, 40% of patients underwent a trial of PEX with 37.5% demonstrating improvement in MAHA that was not sustained upon discontinuation of PEX due to persistent liver dysfunction. Six-month mortality was 75% and use of PEX did not affect mortality. Given the high mortality, further studies evaluating which patients with TMA and liver injury are more likely to benefit from therapies typically used to treat TTP are necessary.

Use of plasma exchange as therapeutic tool in clinical practice

ObjectiveTo descrive the use of therapeutic plasma exchange in several pathologies and its adjustment to international reference guides. MethodObservational, descriptive, retrospective study, of all the patients that received plasmapheresis between January 2014-December 2015. We analized the appropriate indication according to the bibliography consulted, and the therapeutic outcome. Indication, replaced volume of plasma, number of sessions and periodicity were established by the Hematology Service depending on the disease and its clinical course. Results10 patients (8 women), between 28-72 years old, received therapeutic plasma exchange. The pathologies treated were neurological (9 patients), Waldenstrom disease (1 patient). The technique used was continuous centrifugation with albumin 5% as replacement fluid. ConclusionsThe therapeutic plasma exchange in reviewed patients agreed to reference guides. There was not a direct relation between the recommendation grade and the response obtained. The reduced number of patients is a limitation to obtain conclusive results.

Clinical practice guidelines ofthe Japan Research Committee ofthe Ministry ofHealth, Labour, andWelfare forIntractableVasculitis forthe management ofmicroscopic polyangiitis andgranulomatosis with polyangiitis: The 2023 update - secondary publication.

To revise the 2017 clinical practice guidelines (CPG) for the management of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) to reflect advancements in the field. Similar to the 2017 CPG, the Grading of Recommendations, Assessment, Development, and Evaluation system was adopted for this revision. The intended users of this CPG include patients diagnosed with MPA or GPA in Japan and their families and healthcare professionals, including specialists and non-specialists. Based on a scoping review, four clinical questions (CQs) of the 2017 guidelines were modified, and six new CQs were added. We suggest a combination of glucocorticoid and cyclophosphamide or rituximab for remission induction therapy. In cases where cyclophosphamide or rituximab is used, we suggest the use of avacopan over high-dose glucocorticoid. Furthermore, we suggest against the use of plasma exchange in addition to the standard treatment in severe cases of MPA/GPA. Finally, we suggest the use of glucocorticoid and rituximab over glucocorticoid and azathioprine for remission maintenance therapy. The recommendations have been updated based on patient preference, certainty of evidence, benefit and risk balance, and cost.

Early Versus Late Acute AMR in Kidney Transplant Recipients-A Comparison of Treatment Approaches and Outcomes From the ANZDATA Registry.

Antibody-mediated rejection (AMR) is a major cause of kidney allograft failure and demonstrates different properties depending on whether it occurs early (<6 mo) or late (>6 mo) posttransplantation. We aimed to compare graft survival and treatment approaches for early and late AMR in Australia and New Zealand. Transplant characteristics were obtained for patients with an AMR episode reported to the Australia and New Zealand Dialysis and Transplant Registry from January 2003 to December 2019. The primary outcome of time to graft loss from AMR diagnosis, with death considered a competing risk, was compared between early and late AMR using flexible parametric survival models. Secondary outcomes included treatments used, response to treatment, and time from AMR diagnosis to death. After adjustment for other explanatory factors, late AMR was associated with twice the risk of graft loss relative to early AMR. The risk was nonproportional over time, with early AMR having an increased early risk. Late AMR was also associated with an increased risk of death. Early AMR was treated more aggressively than late with more frequent use of plasma exchange and monoclonal/polyclonal antibodies. There was substantial variation in treatments used by transplant centers. Early AMR was reported to be more responsive to treatment than late. Late AMR is associated with an increased risk of graft loss and death compared with early AMR. The marked heterogeneity in the treatment of AMR highlights the need for effective, new therapeutic options for these conditions.

Design and Rationale of the APPELHUS Phase 3 Open-Label Study of Factor B Inhibitor Iptacopan for Atypical Hemolytic Uremic Syndrome

Atypical hemolytic uremic syndrome (aHUS) is a rare, progressive, and life-threatening form of thrombotic microangiopathy (TMA) which is caused by dysregulation of the alternative complement pathway (AP). Complement inhibition is an effective therapeutic strategy in aHUS, though current therapies require intravenous administration and increase the risk of infection by encapsulated organisms, including meningococcal infection. Further studies are required to define the optimal duration of existing therapies, and to identify new agents that are convenient for long-term administration. Iptacopan (LNP023) is an oral, first-in-class, highly potent, proximal AP inhibitor that specifically binds factor B (FB). In phase 2 studies of IgA nephropathy, paroxysmal nocturnal hemoglobinuria, and C3 glomerulopathy, iptacopan inhibited the AP, showed clinically relevant benefits, and was well tolerated. Iptacopan thus has the potential to become an effective and safe treatment for aHUS, with the convenience of oral administration. Alternative Pathway Phase III to Evaluate LNP023 in aHUS (APPELHUS; NCT04889430) is a multicenter, single-arm, open-label, phase 3 study to evaluate the efficacy and safety of iptacopan in patients (N= 50) with primary complement-mediated aHUS naïve to complement inhibitor therapy (including anti-C5). Eligible patients must have evidence of TMA (platelet count<150× 109/l, lactate dehydrogenase≥1.5× upper limit of normal, hemoglobin≤ lower limit of normal, serum creatinine≥ upper limit of normal) and will receive iptacopan 200 mg twice daily. The primary objective is to assess the proportion of patients achieving complete TMA response without the use of plasma exchange or infusion or anti-C5 antibody during 26 weeks of iptacopan treatment. APPELHUS will determine if iptacopan is safe and efficacious in patients with aHUS.

Plasma Exchange for ANCA-Associated Vasculitis: An International Survey of Patient Preferences

We sought to elicit patient preferences regarding the use of plasma exchange in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and its tradeoffs of risk of kidney failure and risk of serious infection. Patient survey. The online survey was circulated to adults with AAV via kidney and vasculitis networks in Canada, the United Kingdom, and the United States. Respondents reviewed the estimated 1-year risks of kidney failure and serious infection in AAV with and without plasma exchange across 5 serum creatinine categories (150, 250, 350, 450, and 600μmol/L). For each scenario, participants indicated whether or not they would choose plasma exchange. Responses were assessed with multilevel multivariable logistic regression models to identify predictors of respondent choice regarding treatment with plasma exchange. The 470 respondents from the 13 countries (United States 61.7%, United Kingdom 20.0%, Canada 13.8%, and other countries 4.5%) had a mean age of 58.6 (SD 14.3) years, 70.2% women. Respondents were more likely to choose plasma exchange in scenarios at high risk of kidney failure and serious infection (creatinine level of 350 or 450μmol/L) compared with lower risk scenarios or the highest risk scenario. However, 145 (30.9%) chose plasma exchange across all scenarios, whereas 80 (17.0%) declined plasma exchange across all scenarios. Respondents from the United Kingdom (OR, 2.61; 95% CI, 1.09-6.22) who received previous dialysis (OR, 2.70; 95% CI, 1.12-6.52) or received previous plasma exchange (OR, 5.62; 95% CI, 2.72-11.61) were more likely to choose plasma exchange, whereas older respondents (OR, 0.98; 95% CI, 0.96-0.99 per 1 year increase) were less likely. Unclear generalizability to non-English-speaking, older, and less health literate adults, possible responder bias, survivor bias, lack of individualized risk assessments for kidney failure, and serious infection. Patients with AAV do not express a consistent choice for plasma exchange, which highlights the need for shared decision making.

Plasma exchange and COVID 19

Plasma exchange and COVID 19

Diagnosing and treating ANCA-associated vasculitis: an updated review for clinical practice.

ANCA-associated vasculitides (AAV) are a group of rare, primary, systemic necrotizing small-vessel vasculitides. Granulomatosis with polyangiitis and microscopic polyangiitis account for ∼80-90% of all AAV. Exposure to silica dust, farming and chronic nasal Staphylococcus aureus carriage are associated with increased risk of developing AAV. When a diagnosis of AAV is suspected, as in patients with multisystem organ dysfunction or those with features such as chronic recurrent rhinosinusitis, cavitated lung nodules, palpable purpura or acute kidney injury, then appropriate further investigations are needed, including ANCA testing. In this scenario, a structured clinical assessment should be conducted, evaluating all the organs possibly involved, and tissue biopsy may be necessary for confirmation of the diagnosis. Therapeutic algorithms vary based on the severity of AAV, the clinical diagnosis/ANCA specificity, and the patient's age, weight, comorbidities and prognosis. Recent data favour rituximab as a preferable option for both induction and maintenance of remission. In addition, regimens with less glucocorticoids are equally effective and safer in inducing remission compared with conventional regimens, and avacopan is an effective glucocorticoid-sparing option. In contrast, there is not compelling evidence to support the routine use of plasma exchange in addition to standard remission-induction therapy in AAV. ANCA and other biomarkers can be helpful in association with clinical assessment to guide diagnosis and treatment decisions. Patients should be frequently evaluated during follow-up for possible disease relapses or treatment-related morbidity, and for monitoring damage accrual, especially metabolic and cardiovascular damage.