scholarly journals Plasma Exchange in ANCA-Associated Vasculitis: A Narrative Review

2021 ◽  
Vol 10 (21) ◽  
pp. 5154
Author(s):  
Stathis Tsiakas ◽  
Smaragdi Marinaki ◽  
Sophia Lionaki ◽  
John Boletis
Keyword(s):  
Plasma Exchange ◽  
Renal Involvement ◽  
Rapidly Progressive Glomerulonephritis ◽  
Standard Of Care ◽  
Medical Community ◽  
Anca Associated Vasculitis ◽  
Increased Risk ◽  
Life Threatening ◽  
End Stage ◽  
Potential Pathogenicity

Therapeutic plasma exchange (TPE) is an adjunctive intervention to immunosuppression for the treatment of severe renal involvement or lung hemorrhage in patients with ANCA-associated vasculitis (AAV). Patients with AAV have an increased risk for progression to end-stage kidney disease (ESKD) or death despite advances in immunosuppressive therapy. The potential pathogenicity of ANCA makes TPE a reasonable treatment approach for the life-threatening complications of AAV. The efficacy of intensive TPE in rapidly progressive glomerulonephritis was originally described in small studies almost four decades ago. Further randomized trials examined the addition of TPE to standard of care, exhibiting mixed results in both patient and renal survival. The largest clinical trial to date, PEXIVAS, failed to demonstrate a clear benefit for TPE in severe AAV. In light of new evidence, the role of TPE remains controversial across the vasculitis medical community. The purpose of this review is to summarize the clinical indications and the current available data for the use of TPE in patients with severe AAV.

scholarly journals Plasma exchange in ANCA-associated vasculitis: the pro position

2020 ◽  
Author(s):  
Andreas Kronbichler ◽  
Jae Il Shin ◽  
Chia-Shi Wang ◽  
Wladimir M Szpirt ◽  
Mårten Segelmark ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Rapidly Progressive Glomerulonephritis ◽  
Pulmonary Haemorrhage ◽  
Alveolar Haemorrhage ◽  
Anca Associated Vasculitis ◽  
Routine Administration ◽  
Function Impairment ◽  
Circulating Antibodies ◽  
End Stage

Abstract Plasma exchange (PLEX) is capable of removing significant amounts of circulating antibodies. In anti-neutrophil cytoplasmic antibody-associated vasculitis, PLEX was reserved for patients with severe presentation forms such as rapidly progressive glomerulonephritis and pulmonary haemorrhage. The Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis (PEXIVAS) trial included all comers with a glomerular filtration rate <50 mL/min/1.73 m2 and thus aimed to answer the question of whether PLEX is an option for patients with no relevant kidney function impairment or not. PEXIVAS revealed that after a follow-up of almost 3 years, routine administration of PLEX does not provide an additional benefit to reduce the rate of a composite comprising end-stage kidney disease or death. In the absence of histological parameters, it is tempting to speculate whether PLEX is effective or not in those with a potential for renal recovery. A subset of patients presented with alveolar haemorrhage, and there was a trend towards a better outcome of such cases receiving PLEX. This would be in line with observational studies reporting a recovery of alveolar haemorrhage following extracorporeal treatment. In this PRO part of the debate, we highlight the shortcomings of the PEXIVAS trial and stimulate further research paths, which in our eyes are necessary before abandoning PLEX from the therapeutic armamentarium.

scholarly journals AB0820 INFLUENCE OF ANCA ANTIBODIES ON DEMOGRAPHIC AND CLINICAL CHARACTERISTIC OF AAV

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1434.1-1434
Author(s):  
K. Wójcik ◽  
A. Masiak ◽  
Z. Zdrojewski ◽  
R. Jeleniewicz ◽  
M. Majdan ◽  
...  
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Clinical Characteristics ◽  
Renal Involvement ◽  
Organ Involvement ◽  
Unknown Etiology ◽  
Anca Associated Vasculitis ◽  
Stage Renal Disease ◽  
End Stage ◽  
Male To Female

Background:ANCA associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown etiology and the broad clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Unfortunately the clinical classification, ANCA specificity or genetic characteristics alone is not able to categorize AAV patients in a satisfactory manner. As a consequence advanced statistical techniques were used to identify and stratify AAV subphenotypes [1, 2]. Here we have analyzed influence of the ANCA type on clinical manifestations and demographic characteristics in various types of AAV, based on data from the POLVAS registryObjectives:We decided to retrospectively analyze a large cohort of Polish AAV patients deriving from several referral centers – members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS) – and concentrate on demographic and clinical characteristics of anti-PR3 and anti-MPO positive patients regardless of their clinical diagnosis.Methods:We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016. Patients were enrolled by 9 referral centers. We analyzed dichotomous variables: gender; ANCA status – anti-PR3+ or anti-MPO+, ANCA negative; organ involvement - skin, eye, ENT, respiratory, heart, GI, renal, urinary, CNS, peripheral nerves and polytomous variable (number of relapses), supported by quantitative covariates (e.g., age at diagnosis, CRP at diagnosis, maximal serum creatinine concentration ever)[3].Results:MPO-positive patients (both GPA and EGPA phenotype) were older at the time of diagnosis with a substantial percentage diagnosed > 65 years of age, and with high rate of renal involvement. Interestingly, while in the whole group of patients diagnosed with EGPA male to female ratio was 1:2, the MPO+ EGPA patients showed M:F ratio of 1:1.The analysis of ANCA negative AAV reveled significant differences in GPA, ANCA negative group is characterized with significantly lower frequency of renal involvement compared to rest GPA (11,5% vs 63,7%) p<0,05 what should be emphasized ANCA negative AAV never lead to ESRD (end stage renal disease) or even transient dialysis.Conclusion:ANCA specificity is indispensable as a separate variable in any clinically relevant analysis of AAV subcategories. MPO+ group is characterized by older age at time of diagnosis, male to female ration 1:1, kidney involvement, and shows more homogenous clinical phenotype than PR3+ AAV patients. In our group ANCA negative AAV never lead to ESRD (end stage renal disease) or even transient dialysis.References:[1]Mahr A, Specks U, Jayne D. Subclassifying ANCA-associated vasculitis: a unifying view of disease spectrum. Rheumatol Oxf Engl 2019;58:1707–9. https://doi.org/10.1093/rheumatology/kez148.[2]Wójcik K, Biedroń G, Wawrzycka-Adamczyk K, Bazan-Socha S, Ćmiel A, Zdrojewski Z et al. Subphenotypes of ANCA-associated vasculitis identified by latent class analysis. Clin Exp Rheumatol. 2020 Sep 1. Epub PMID: 32896241.[3]Wójcik K, Wawrzycka-Adamczyk K, Włudarczyk A, Sznajd J, Zdrojewski Z, Masiak A, et al. Clinical characteristics of Polish patients with ANCA-associated vasculitides—retrospective analysis of POLVAS registry. Clinical Rheumatology. 1 wrzesień 2019;38(9):2553–63.Disclosure of Interests:None declared

Staphylococcus-induced glomerulonephritis: potential role for corticosteroids

2021 ◽  
Vol 14 (1) ◽  
pp. e237011
Author(s):  
Rui Filipe Nogueira ◽  
Nuno Oliveira ◽  
Vítor Sousa ◽  
Rui Alves
Keyword(s):  
Kidney Function ◽  
Potential Role ◽  
Graft Infection ◽  
Clinical Manifestations ◽  
Rapidly Progressive Glomerulonephritis ◽  
Vascular Graft Infection ◽  
Systemic Corticosteroids ◽  
Life Threatening ◽  
Stage Renal Disease ◽  
End Stage

Staphylococcus aureus is a troublesome pathogen, responsible for a broad range of clinical manifestations, ranging from benign skin infections to life-threatening conditions such as endocarditis and osteomyelitis. The kidney can be affected through a rapidly progressive glomerulonephritis mediated by an inflammatory reaction against a superantigen deposited in the glomerulus during the infection’s course. This glomerulopathy has a poor prognosis, often leading to chronically impaired kidney function, eventually progressing to end-stage renal disease. Treatment rests on antibiotherapy. Despite the inflammatory role in this disease’s pathophysiology, most authors discourage a simultaneous immunosuppressive approach given the concomitant infection. However, there are some reports of success after administration of systemic corticosteroids in these patients. We present a 66-year-old man with a staphylococcus-induced glomerulonephritis brought on by a vascular graft infection, with rapidly deteriorating kidney function despite extraction of the infected graft and 3 weeks of antibiotherapy with achievement of infection control. Kidney function improved after the introduction of corticosteroids. This case highlights the potential role of corticosteroids in selected cases of staphylococcus-induced glomerulonephritis, particularly those in which the infection is under control.

scholarly journals P20 Scleritis as initial presenting feature in ANCA-associated vasculitis

2021 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Subrahmanyam Peddasomayajula ◽  
VenkateshwarRao Kesharaju ◽  
Anisur Rahman
Keyword(s):  
Case Report ◽  
Plasma Exchange ◽  
Immune Therapy ◽  
Pulmonary Haemorrhage ◽  
Ocular Manifestations ◽  
Anca Associated Vasculitis ◽  
Life Threatening ◽  
Collaborative Working ◽  
Systemic Manifestations ◽  
Systemic Symptoms

Abstract Case report - Introduction ANCA-associated vasculitis (AAV) encompasses the clinical entities of GPA, MPA, renal-limited vasculitis and eGPA. Even though well recognised and described in the medical literature, ocular manifestations in AAV are relatively uncommon (&lt;20%) and may precede, present concomitantly with, or follow systemic manifestations. Our patient developed scleritis as the first manifestation of AAV and presented to the ophthalmology department. Within a few days, he developed systemic symptoms and subsequently severe and potentially life-threatening pulmonary haemorrhage. With collaborative working, he received appropriate treatments and made a good recovery. Case report - Case description Our patient is a 36-year-old Indian gentleman, who presented to Broomfield Hospital ophthalmology department in February 2021 with a 1-week history of pain and redness involving the left eye. Diagnosis of anterior scleritis was made and he received dexamethasone 0.1% eye drops and later switched to prednisolone 60mg/day. Investigations are shown below (Table 1). Diagnosis of AAV was made and he came under the care of the rheumatology. By this time, he noticed fleeting but severe arthralgia. He received three pulses of I.V. methyl prednisolone and received first dose of 1000mg of rituximab and one pulse of IV cyclophosphamide. His haemoglobin dropped with reduced oxygen saturation of 88% on air. Repeat CT chest showed extensive pulmonary haemorrhage and he was admitted to ITU. He did not need intubation and was transferred to University College London Hospital. Following five plasma exchanges and high-dose prednisolone, CRP fell from 113 to 6.6 and saturation improved to 98% on air. He completed four rituximab infusions. By June 2021 his chest X-ray returned to normal. 1. Table of Investigations Case report - Discussion This patient’s story highlights multiple clinical aspects of AAV. Published literature states that ocular manifestations as “initial” presentation of AAV are very uncommon (about 6%). The ophthalmologist requested the correct investigations including ANCA which helped to establish the diagnosis. Within a few weeks, the patient went on to develop other systemic manifestations which necessitated stepping-up the immune therapy. Rituximab was chosen for remission induction as it is now established as an alternative to cyclophosphamide. We discussed the case at virtual MDT of ENRAD (Eastern Network for Rare Autoimmune Disease) and got swift approval to use rituximab. Unfortunately, his clinical course was complicated with development of pulmonary haemorrhage which is potentially life-threatening. The PEXIVAS trial (Walsh et al NEJM 382; 622-31 (2020)) compared groups randomised to plasma exchange or no plasma exchange in addition to corticosteroids and either rituximab or cyclophosphamide. Outcomes were not different between the groups. However, Kronbichler et al (Nephrol Dial Transplantation 36; 227-31 [2021]) have argued that there was a trend towards better outcomes in a subgroup with alveolar haemorrhage and that plasma exchange may still have a role in such patients. Following five cycles of plasma exchange our patient made an excellent recovery from pulmonary haemorrhage which is very rewarding. Case report - Key learning points Scleritis is an uncommon presenting feature of AAV and should prompt the physician to look for systemic symptoms and check for ANCA serology. To recognise pulmonary haemorrhage as a potential life-threatening manifestation in a patient with AAV who drops haemoglobin. Despite lack of strong clinical trial evidence, plasma exchange can be a very useful therapeutic tool. Early recognition and initiation of immune therapy is crucial to induce remission. Collaborative working with clinicians from different medical specialities is the key for improved patient outcomes.

scholarly journals Clinical implication of plasma exchange on life-threatening antineutrophil cytoplasmic antibody-associated vasculitis

2020 ◽  
Author(s):  
Pil Gyu Park ◽  
Byung-Woo Yoo ◽  
Jason Jungsik Song ◽  
Yong-Beom Park ◽  
Sang-Won Lee
Keyword(s):  
Plasma Exchange ◽  
Survival Benefit ◽  
Laboratory Data ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Alveolar Haemorrhage ◽  
Anca Associated Vasculitis ◽  
Kaplan Meier ◽  
All Cause Mortality ◽  
Life Threatening

Abstract Background: We assessed the rate of and the predictor for all-cause mortality in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients receiving plasma exchange (PLEX) and evaluated the survival-benefit of PLEX for diffuse alveolar haemorrhage (DAH) between AAV patients receiving PLEX and those not receiving. Methods: We retrospectively reviewed the medical records of 212 AAV patients. Demographic, clinical and laboratory data at the time of PLEX was collected from both 9 patients receiving PLEX and 10 AAV patients with DAH. The follow-up duration was defined as the period from the time of PLEX or DAH occurrence to death for the deceased patients and as that to the last visit for the survived patients. Results: The median age of 9 AAV patients receiving PLEX was 71.0 years and 5 patients were men. Four of 9 patients receiving PLEX died at a median follow-up duration of 92.0 days. Three died of sepsis and one died of no response to PLEX. When patients with DAH receiving PLEX and those not receiving were compared, there were no significant differences in variables between the two groups. The cumulative patients’ survival rate between patients with DAH receiving PLEX and those not receiving were also compared using the Kaplan-Meier survival analysis but no survival-benefit of PLEX for DAH was observed. Conclusion: The rate of all-cause mortality in 9 AAV patients receiving PLEX was assessed as 44.4% and it was controversial that PLEX is beneficial for the improvement of prognosis of AAV-related DAH.

scholarly journals Slo-Mo anti-neutrophil cytoplasmic antibody-associated renal vasculitis

2020 ◽  
Author(s):  
Alejandro Avello ◽  
Raul Fernandez-Prado ◽  
Begoña Santos-Sanchez-Rey ◽  
Jorge Rojas-Rivera ◽  
Alberto Ortiz
Keyword(s):  
Renal Involvement ◽  
Unmet Need ◽  
Rapidly Progressive Glomerulonephritis ◽  
Response To Therapy ◽  
Systematic Assessment ◽  
Uncommon Presentation ◽  
Physician Awareness ◽  
Renal Vasculitis ◽  
End Stage ◽  
Renal Phenotype

Abstract Nephrologists are familiar with severe cases of anti-neutrophil cytoplasmic antibodies-associated vasculitis (AAV) presenting as rapidly progressive glomerulonephritis. However, less is known about AAV with slowly progressive renal involvement. While its existence is acknowledged in textbooks, much remains unknown regarding its relative frequency versus more aggressive cases as well as about the optimal therapeutic approach and response to therapy. Moreover, this uncommon presentation may be underdiagnosed, given the scarce familiarity of physicians. In this issue of Clinical Kidney Journal, Trivioli et al. report the largest series to date and first systematic assessment of patients with AAV and slowly progressive renal involvement, defined as a reduction in estimated glomerular filtration rate (eGFR) of 25–50% in the 6 months prior to diagnosis after excluding secondary causes. Key findings are that slowly progressive AAV may be less common than previously thought, although it still represents the second most common presentation of renal AAV, it usually has a microscopic polyangiitis, anti-myeloperoxidase, mainly renal phenotype in elderly individuals, diagnosis may be late (over one-third of patients had end-stage kidney disease at diagnosis), clearly identifying an unmet need for physician awareness about this presentation, but those not needing renal replacement therapy at diagnosis still responded to immunosuppression.

scholarly journals Efficacy of Rituximab and Plasma Exchange in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis with Severe Kidney Disease

2020 ◽  
Vol 31 (11) ◽  
pp. 2688-2704 ◽  
Author(s):  
Marta Casal Moura ◽  
Maria V. Irazabal ◽  
Alfonso Eirin ◽  
Ladan Zand ◽  
Sanjeev Sethi ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Kidney Disease ◽  
Plasma Exchange ◽  
Retrospective Cohort ◽  
Controlled Trial ◽  
Renal Involvement ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Remission Induction ◽  
Randomized Controlled ◽  
Anca Associated Vasculitis

BackgroundTreatment of patients with ANCA-associated vasculitis (AAV) and severe renal involvement is not established. We describe outcomes in response to rituximab (RTX) versus cyclophosphamide (CYC) and plasma exchange (PLEX).MethodsA retrospective cohort study of MPO- or PR3-ANCA–positive patients with AAV (MPA and GPA) and severe kidney disease (eGFR <30 ml/min per 1.73 m2). Remission, relapse, ESKD and death after remission-induction with CYC or RTX, with or without the use of PLEX, were compared.ResultsOf 467 patients with active renal involvement, 251 had severe kidney disease. Patients received CYC (n=161) or RTX (n=64) for remission-induction, and 51 were also treated with PLEX. Predictors for ESKD and/or death at 18 months were eGFR <15 ml/min per 1.73 m2 at diagnosis (IRR 3.09 [95% CI 1.49 to 6.40], P=0.002), renal recovery (IRR 0.27 [95% CI 0.12 to 0.64], P=0.003) and renal remission at 6 months (IRR 0.40 [95% CI 0.18 to 0.90], P=0.027). RTX was comparable to CYC in remission-induction (BVAS/WG=0) at 6 months (IRR 1.37 [95% CI 0.91 to 2.08], P=0.132). Addition of PLEX showed no benefit on remission-induction at 6 months (IRR 0.73 [95% CI 0.44 to 1.22], P=0.230), the rate of ESKD and/or death at 18 months (IRR 1.05 [95% CI 0.51 to 2.18], P=0.891), progression to ESKD (IRR 1.06 [95% CI 0.50 to 2.25], P=0.887), and survival at 24 months (IRR 0.54 [95% CI 0.16 to 1.85], P=0.330).ConclusionsThe apparent benefits and risks of using CYC or RTX for the treatment of patients with AAV and severe kidney disease are balanced. The addition of PLEX to standard remission-induction therapy showed no benefit in our cohort. A randomized controlled trial is the only satisfactory means to evaluate efficacy of remission-induction treatments in AAV with severe renal involvement.

Nierenbeteiligung bei ANCA-assoziierten Vaskulitiden

2018 ◽  
Vol 143 (02) ◽  
pp. 79-88 ◽  
Author(s):  
Marion Haubitz
Keyword(s):  
Renal Function ◽  
Maintenance Treatment ◽  
Renal Involvement ◽  
Young Patients ◽  
Induction Treatment ◽  
Renal Manifestation ◽  
Increased Risk ◽  
Stage Renal Disease ◽  
End Stage

AbstractIn patients with ANCA-associated vasculitis renal involvement is frequently seen and the severity of renal manifestation is very important for therapeutic strategies and prognosis. Clinically rapid loss of renal function, nephritic sediment and proteinuria in a non-nephrotic range are characterizing a focal segmental necrotizing pauci-immune glomerulonephritis with extrarenal proliferations. Induction treatment depends on the severity of manifestations. With a normal renal function methotrexate can be used in combination with steroids. In patients with organ threatening involvement but creatinine below 500 µmol/l cyclophosphamide pulses or Rituximab should be used together with steroids, initially with i. v. pulses. Rituximab is more effective in PR3-ANCA vasculitis and should be used in relapsing disease, in young patients to avoid gonadal toxicity and in patients with an increased risk of malignancies. In patients on dialysis or with creatinine > 500 µmol/l plasma exchange should be added. Maintenance treatment (mainly with azathioprine) is necessary as at least 50 % of the patients develop relapses. Rituximab seems more effective, however it is not approved for maintenance treatment and no long-term data are available. Adjuvant treatment, long-term side effects and the increased incidence of cardiovascular events have to be included in the follow-up of vasculitis patients. In end-stage renal disease patients relapses occur but are more difficult to diagnose and treat with higher incidence of infections. Transplantation should be offered as patient and transplant survival is good.

Antiglomerular basement membrane disease

2018 ◽  
Author(s):  
Zhao Cui ◽  
Neil Turner ◽  
Ming-hui Zhao
Keyword(s):  
Basement Membrane ◽  
Plasma Exchange ◽  
Rapidly Progressive Glomerulonephritis ◽  
Standard Of Care ◽  
Experimental Models ◽  
Pulmonary Haemorrhage ◽  
Small Vessel Vasculitis ◽  
Mediated Effects ◽  
Early Peak ◽  
Pathogenic Antibodies

Cyclophosphamide and plasma exchange are the standard of care in rapidly progressive glomerulonephritis or lung haemorrhage caused by antiglomerular basement membrane (anti-GBM) disease, and it is unusual to encounter patients at earlier stages. Steroids are universally used in addition. There is some evidence that plasma exchange may not be a critical part of treatment at an earlier stage. There is no more than anecdotal evidence for other therapies. Slower-onset therapies such as antibodies to B cells are rarely appropriate. If untreated, patients with severe anti-GBM disease will not recover renal function and are at risk of pulmonary haemorrhage. Evidence for the pathogenicity of circulating anti-GBM antibodies provides rationale for removal of circulating antibodies as rapidly as possible, whilst simultaneously inhibiting their synthesis. This was behind the introduction of the combination of plasma exchange with immunosuppressive therapy in mid 1970s, which revolutionized outcomes. Plasmapheresis aims to remove circulating pathogenic antibodies against GBM and possibly other mediators; cyclophosphamide prevents further synthesis of autoantibodies; and steroids act as anti-inflammatory agents to attenuate the glomerular inflammatory response initiated by anti-GBM antibodies. It is clear from experimental models and occasional observations in man that the anti-cell mediated effects of current therapies are important too. Outcomes vary, but in general patient survival is now good, while renal survival remains poor, in many series less than 50% at 1 year. Treatment is toxic and after an early peak in deaths due to pulmonary haemorrhage, secondary infections are the next threat. It may therefore be best not to immunosuppress patients with a very poor renal prognosis who appear to be at low risk of pulmonary haemorrhage. Treatment can usually be curtailed after 3 months without recurrence. ANCA and anti-GBM antibodies occur together in some patients. This is typically an older group which often has features of vasculitis, and the anti-GBM response may often be secondary. Longer treatment as for small vessel vasculitis is usually indicated.

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