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David Jayne - One of the best experts on this subject based on the ideXlab platform.
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management of alveolar hemorrhage in lung vasculitides
Seminars in Respiratory and Critical Care Medicine, 2011Co-Authors: Alina Casian, David JayneAbstract:Alveolar hemorrhage (AH) is an important pulmonary manifestation of small vessel Vasculitis because severe presentations are the most common vasculitic cause of early death. Renal Vasculitis is usually present with AH; the combination is known as pulmonary-Renal syndrome. Early diagnosis and intensive therapy are of particular importance to reduce early mortality and improve longer-term outcomes. The commonest immune-mediated cause of AH is anti-neutrophil cytoplasmic antibody (ANCA)-associated Vasculitis (AAV) (80%), with other vasculitides, including systemic lupus erythematosus and anti-glomerular basement membrane disease accounting for 20%. One quarter of AAV patients develop AH, which when mild is associated with a good outcome, but mortality rises to 50% for cases with respiratory failure requiring ventilator support. The prognosis of AH in the other vasculitides is generally favorable, but cases are rare and experience is limited. Treatment follows similar regimens to those for other AAV presentations, although when severe there is widespread use of parenteral glucocorticoids together with plasma exchange. These interventions have developed empirically supported by a theoretical rationale but have not been validated by randomized clinical trials. Sepsis and cardiovascular and thromboembolic events are important early complications. and long-term follow-up is required to monitor for and prevent relapse and manage disease-related damage. A minority of cases develop on a background of pulmonary fibrosis, or progressive pulmonary fibrosis develops after Vasculitis has gone into remission.
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plasma exchange for Renal Vasculitis and idiopathic rapidly progressive glomerulonephritis a meta analysis
American Journal of Kidney Diseases, 2011Co-Authors: Michael Walsh, L. Guillevin, Charles D. Pusey, Fausta Catapano, Wladimir Szpirt, Kristian Thorlund, Annette Bruchfeld, Marion Haubitz, Peter A Merkel, David JayneAbstract:Background Plasma exchange may be effective adjunctive treatment for Renal Vasculitis. We performed a systematic review and meta-analysis of randomized controlled trials of plasma exchange for Renal Vasculitis. Study Design Systematic review and meta-analysis of articles identified from electronic databases, bibliographies, and studies identified by experts. Data were abstracted in parallel by 2 reviewers. Setting & Population Adults with idiopathic Renal Vasculitis or rapidly progressive glomerulonephritis. Selection Criteria for Studies Randomized controlled trials that compared standard care with standard care plus adjuvant plasma exchange in adult patients with either Renal Vasculitis or idiopathic rapidly progressive glomerulonephritis. Intervention Adjuvant plasma exchange. Outcome Composite of end-stage Renal disease or death. Results We identified 9 trials including 387 patients. In a fixed-effects model, the pooled RR for end-stage Renal disease or death was 0.80 for patients treated with adjunctive plasma exchange compared with standard care alone (95% CI, 0.65-0.99; P = 0.04). No significant heterogeneity was detected (P = 0.5; I2 = 0%). The effect of plasma exchange did not differ significantly across the range of baseline serum creatinine values (P = 0.7) or number of plasma exchange treatments (P = 0.8). The RR for end-stage Renal disease was 0.64 (95% CI, 0.47-0.88; P = 0.006), whereas the RR for death alone was 1.01 (95% CI, 0.71-1.4; P = 0.9). Limitations Although the primary result was statistically significant, there is insufficient statistical information to reliably determine whether plasma exchange decreases the composite of end-stage Renal disease or death. Conclusions Plasma exchange may decrease the composite end point of end-stage Renal disease or death in patients with Renal Vasculitis. Additional trials are required given the limited data available.
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Renal Vasculitis in japan and the uk are there differences in epidemiology and clinical phenotype
Nephrology Dialysis Transplantation, 2008Co-Authors: Richard A Watts, David Jayne, David G I Scott, Eri Muso, Toshiko Itoihara, Shouichi Fujimoto, Yasuki Harabuchi, Shigeto Kobayashi, Kazuo Suzuki, Hiroshi HashimotoAbstract:Background. The epidemiology of Renal Vasculitis in different populations is poorly understood. A recent study fromJapansuggeststhatwhilsttheoverallincidenceissimilar to that reported from Europe, the clinical phenotype is different, with Wegener’s granulomatosis being very much less common. The aim of this study was to compare the incidence of Renal Vasculitis in the UK with recent data from a Japanese population. Methods. Incident patients with Renal Vasculitis were identified prospectively between 2000 and 2004 from a well-defined UK population. The case notes were reviewed and clinical features extracted. Classification between Wegener’s granulomatosis, microscopic polyangiitis and Churg Strauss syndrome was performed using a predetermined algorithm. Inclusion criteria were (i) new patients with Vasculitis with or without histological confirmation, (ii) Renal involvement and (iii) positive serology for antineutrophil cytoplasmic antibody (ANCA). Results. We identified 27 cases of Renal Vasculitis (Wegener’sgranulomatosis13,microscopicpolyangiitis11, Churg Strauss syndrome 3) fulfilling the case definition. The overall average age was 63.5 years which is less than those of the Japanese patients. The overall annual incidence of Renal Vasculitis was 12.2/million similar to Japan. The annual incidence of Wegener’s granulomatosis was 5.8/million,microscopicpolyangiitis4.9/millionandChurg Strauss syndrome 1.4/million. ENT and neurological involvement were much less common in Japan. No patients
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randomized trial of plasma exchange or high dosage methylprednisolone as adjunctive therapy for severe Renal Vasculitis
Journal of The American Society of Nephrology, 2007Co-Authors: David Jayne, Loïc Guillevin, Caroline O S Savage, Gill Gaskin, Franco Ferrario, Niels Rasmussen, Daniel Abramowicz, Eduardo Mirapeix, Renato Alberto Sinico, Coen A StegemanAbstract:Systemic Vasculitis associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA) is the most frequent cause of rapidly progressive glomerulonephritis. Renal failure at presentation carries an increased risk for ESRD and death despite immunosuppressive therapy. This study investigated whether the addition of plasma exchange was more effective than intravenous methylprednisolone in the achievement of Renal recovery in those who presented with a serum creatinine >500 micromol/L (5.8 mg/dl). A total of 137 patients with a new diagnosis of ANCA-associated systemic Vasculitis confirmed by Renal biopsy and serum creatinine >500 micromol/L (5.8 mg/dl) were randomly assigned to receive seven plasma exchanges (n = 70) or 3000 mg of intravenous methylprednisolone (n = 67). Both groups received oral cyclophosphamide and oral prednisolone. The primary end point was dialysis independence at 3 mo. Secondary end points included Renal and patient survival at 1 yr and severe adverse event rates. At 3 mo, 33 (49%) of 67 after intravenous methylprednisolone compared with 48 (69%) or 70 after plasma exchange were alive and independent of dialysis (95% confidence interval for the difference 18 to 35%; P = 0.02). As compared with intravenous methylprednisolone, plasma exchange was associated with a reduction in risk for progression to ESRD of 24% (95% confidence interval 6.1 to 41%), from 43 to 19%, at 12 mo. Patient survival and severe adverse event rates at 1 yr were 51 (76%) of 67 and 32 of 67 (48%) in the intravenous methylprednisolone group and 51 (73%) of 70 and 35 of (50%) 70 in the plasma exchange group, respectively. Plasma exchange increased the rate of Renal recovery in ANCA-associated systemic Vasculitis that presented with Renal failure when compared with intravenous methylprednisolone. Patient survival and severe adverse event rates were similar in both groups.
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outcome of anca associated Renal Vasculitis a 5 year retrospective study
American Journal of Kidney Diseases, 2003Co-Authors: Anthony D Booth, Charles D. Pusey, Gill Gaskin, Michael Almond, Aine Burns, Peter Ellis, Guy H Neild, Martin Plaisance, David JayneAbstract:Abstract Background: Renal involvement is frequently present in antineutrophil cytoplasmic autoantibody (ANCA)-associated systemic Vasculitis and is an important cause of end-stage Renal failure (ESRF). Methods: This retrospective, multicenter, sequential cohort study reports presenting features and outcome of 246 new patients diagnosed in London, UK, between 1995 and 2000. Results: Diagnostic subgroups were microscopic polyangiitis, 120 patients (49%); Wegener's granulomatosis (WG), 82 patients (33%); Renal-limited Vasculitis, 33 patients (13.5%); and Churg-Strauss angiitis, 11 patients (4.5%). Median age was 66 years, 57% were men, and median creatinine level at presentation was 3.87 mg/dL (342 μmol/L). ANCA was present in 92%. Cumulative patient survival at 1 and 5 years was 82% and 76%, respectively. Mortality was associated with age older than 60 years ( P P P = 0.01), and sepsis ( P P = 0.048) and proteinase 3-ANCA ( P = 0.034). Leukopenia occurred in 41% and was associated with sepsis ( P
Ala Abudayyeh - One of the best experts on this subject based on the ideXlab platform.
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checkpoint inhibitor related Renal Vasculitis and use of rituximab
Journal for ImmunoTherapy of Cancer, 2020Co-Authors: Omar Mamlouk, Jamie S Lin, Maen Abdelrahim, Amanda Tchakarov, William F Glass, Umut Selamet, Maryam Buni, Noha Abdelwahab, Ala AbudayyehAbstract:The percentage of patients with cancer eligible for checkpoint inhibitor (CPI) therapy has increased rapidly over the past few years and approaches 45%. As a result, more cases of CPI-related nephrotoxicity, including a rare subset with Vasculitis, are being reported. To elucidate the clinical presentation of CPI-associated Renal Vasculitis and its possible mechanisms, treatment options and prognosis, we describe cases from a comprehensive cancer center and reviewed the literature for similar cases. We retrospectively reviewed the charts of all patients with cancer from 2014 to 2020 who were diagnosed with CPI-related nephrotoxicity and underwent a kidney biopsy. We identified five cases of Renal Vasculitis: three patients were diagnosed with seronegative antineutrophil cytoplasm antibody (ANCA)-associated Vasculitis, one case with seropositive ANCA-associated Vasculitis and one case was diagnosed with IgA Vasculitis. Of these cases, four patients were receiving nivolumab, and one patient was receiving tremelimumab. All patients had microscopic hematuria, four out of five patients had negative ANCA serology, one patient had concurrent lung involvement and positive ANCA serology, and all had severe acute kidney injury with creatinine >4.50 mg/dL on diagnosis. All patients were treated by discontinuing CPI and initiating corticosteroids and rituximab. Three patients received plasmapheresis; two of these required Renal replacement therapy including the patient with lung involvement. All patients after rituximab had a partial or complete Renal response. Two patients died within 8 months of diagnosis due to malignancy progression. None of the patients had a relapse of Vasculitis. We demonstrated that CPI can be associated with different types of Renal Vasculitis that are predominantly ANCA negative and manifest as severe acute kidney injury. Despite the lack of strong evidence, treatment similar to treatment of primary seropositive ANCA-associated Vasculitis with corticosteroids and rituximab is well tolerated with favorable Renal outcomes.
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checkpoint inhibitors related Renal Vasculitis and use of rituximab
Journal of Clinical Oncology, 2020Co-Authors: Omar Mamlouk, Jamie S Lin, Maen Abdelrahim, Amanda Tchakarov, William F Glass, Umut Selamet, Maryam Buni, Noha Abdelwahab, Ala AbudayyehAbstract:e15145Background: As the percentage of cancer patients eligible for checkpoint inhibitor therapy (CPI) is increasing rapidly over the past couple years and approaching 45%, more cases of CPI relate...
Vladimir Tesar - One of the best experts on this subject based on the ideXlab platform.
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rituximab versus cyclophosphamide in anca associated Renal Vasculitis 2 year results of a randomised trial
Annals of the Rheumatic Diseases, 2015Co-Authors: Rachel B Jones, Shunsuke Furuta, Jan Willem Cohen Tervaert, Thomas H Hauser, Raashid Luqmani, Matthew D Morgan, Chen Au Peh, Caroline O S Savage, Marten Segelmark, Vladimir TesarAbstract:Objectives The RITUXVAS trial reported similar remission induction rates and safety between rituximab and cyclophosphamide based regimens for antineutrophil cytoplasm antibody (ANCA)-associated Vasculitis at 12months; however, immunosuppression maintenance requirements and longer-term outcomes after rituximab in ANCA-associated Renal Vasculitis are unknown. Methods Forty-four patients with newly diagnosed ANCA-associated Vasculitis and Renal involvement were randomised, 3:1, to glucocorticoids plus either rituximab (375mg/m(2)/weekx4) with two intravenous cyclophosphamide pulses (n=33, rituximab group), or intravenous cyclophosphamide for 3-6months followed by azathioprine (n=11, control group). Results The primary end point at 24months was a composite of death, end-stage Renal disease and relapse, which occurred in 14/33 in the rituximab group (42%) and 4/11 in the control group (36%) (p=1.00). After remission induction treatment all patients in the rituximab group achieved complete B cell depletion and during subsequent follow-up, 23/33 (70%) had B cell return. Relapses occurred in seven in the rituximab group (21%) and two in the control group (18%) (p=1.00). All relapses in the rituximab group occurred after B cell return. Conclusions At 24months, rates of the composite outcome of death, end-stage Renal disease and relapse did not differ between groups. In the rituximab group, B cell return was associated with relapse. Trial registration number ISRCTN28528813.
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rituximab versus cyclophosphamide in anca associated Renal Vasculitis
The New England Journal of Medicine, 2010Co-Authors: Rachel B Jones, Jan Willem Cohen Tervaert, Thomas H Hauser, Raashid Luqmani, Matthew D Morgan, Caroline O S Savage, Marten Segelmark, Vladimir Tesar, Pieter Van Paassen, D WalshAbstract:BackgroundCyclophosphamide induction regimens for antineutrophil cytoplasmic antibody (ANCA)–associated Vasculitis are effective in 70 to 90% of patients, but they are associated with high rates of ...
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long term outcome of patients with antineutrophil cytoplasmic autoantibody associated Vasculitis with Renal involvement
Kidney & Blood Pressure Research, 2005Co-Authors: Zuzana Rihova, M Merta, J Zabka, Eva Jancova, Romana Rysava, Jana Reiterova, Vladimir TesarAbstract:Background: Despite treatment, Renal involvement in antineutrophil cytoplasmic autoantibody (ANCA)-positive Vasculitis is still associated with significant long-term mortality and remains an important cause of end-stage Renal failure. Methods: We retrospectively analyzed a series of 61 consecutive patients with newly diagnosed ANCA-associated Renal Vasculitis (54.1% Wegener’s granulomatosis, 23% Renal-limited Vasculitis, 16.4% microscopic polyangiitis, 4.9% Churg-Strauss syndrome) diagnosed between 1986 and 1997. Results: The median creatinine level at diagnosis was 221.5 (63–762) µmol/l, i.e. 2.5 (0.7–8.6) mg/dl, 32.8% were dialysis-dependent. All patients were treated with cyclophosphamide. Remission was achieved in 87% of patients. Relapses occurred in 44.7%. The median Renal disease-free interval was 62.5 (0–138) months. The estimated patient survival at 5 and 10 years was 78.3 and 62.2%, respectively. Mortality was associated with age (p = 0.04 when age limit 50 years) and advanced Renal failure (p = 0.038 when compared dialysis-dependent and independent patients). Estimated Renal survival time at 5 and 10 years was 69.2 and 55.8%, respectively. At the end of follow-up, 50.8% of patients were in complete remission, 31% had died. The median serum creatinine level was 137.5 (77–469) µmol/l, i.e. 1.56 (0.87–5.3) mg/dl, 24.6% of patients were on regular dialysis treatment. Conclusion: Patient survival, relapse rate and mortality were comparable to similar reports. In view of the severity of the Renal disease and the length of follow-up, Renal survival was very good. Despite effective treatment, the long-term outcome of patients with ANCA-associated Renal Vasculitis remains unsatisfactory.
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cytokines and adhesion molecules in Renal Vasculitis and lupus nephritis
Nephrology Dialysis Transplantation, 1998Co-Authors: Vladimir Tesar, Z Masek, Ivan Rychlik, M Merta, J Bartůnkova, A Stejskalova, J Zabka, I Janatkova, T Fucikova, C DostalAbstract:BACKGROUND Plasma levels of some pro-inflammatory cytokines and soluble adhesion molecules have been suggested to be useful parameters to assess the activity of antineutrophil cytoplasmic antibody (ANCA)-positive Vasculitis and lupus nephritis. We hypothesized that the Renal activity of these diseases is better reflected by the urinary excretion and fractional excretion of these molecules. METHODS Plasma levels and urinary excretion of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, and the soluble cell adhesion molecules sICAM-1 and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 14 patients with ANCA-positive Renal Vasculitis (eight active, ANCA-A; six in remission, ANCA-R), six patients with active lupus nephritis (LN), 15 patients with IgA nephropathy (IgAN) and nine healthy subjects. Fractional excretion of selected cytokines and adhesion molecules was also calculated. RESULTS Patients with ANCA-A had increased urinary excretion and fractional excretion of TNF-alpha (9.27 +/- 3.19% vs 0.58 +/- 0.02%, P < 0.01), IL-6 (120.79 +/- 65.83% vs 1.89 +/- 0.34%, P < 0.01) and increased fractional excretion of IL-8 (23.34 +/- 6.38% vs 2.56 +/- 1.07%, P < 0.01) and sVCAM-1 (0.81 +/- 0.33% vs 0.03 +/- 0.02%, P < 0.01) compared with controls. Urinary excretion of TNF-alpha and IL-6 and fractional excretion of TNFalpha, IL-6 and IL-8 were higher in ANCA-A than in ANCA-R. Patients with LN had increased plasma TNF-alpha (20.52 +/- 2.01 pg/ml vs 12.33 +/- 0.23 pg/ml, P < 0.05) and sVCAM-1 (1537.88 +/- 276.36 ng/ml vs 692.26 +/- 44.42 ng/ml, P < 0.05) and increased urinary excretion of TNF-alpha (2.81 +/- 0.51 microg/mol creat vs 0.98 +/- 0.05 microg/mol creat, P < 0.01), IL-8 (35.78 +/- 14.03 microg/mol creat vs 12.46 +/- 5.19 microg/mol creat, P < 0.05) and sVCAM-1 (48.98 +/- 20.20 microg/mol creat vs 2.92 +/- 1.35 microg/mol creat, P < 0.01) compared with controls. Patients with IgAN had, in comparison with controls only increased plasma TNF-alpha (18.10 +/- 0.57 pg/ml vs 12.33 +/- 0.23 pg/ml, P < 0.05). CONCLUSIONS Urinary excretion and fractional excretion, but not plasma levels, of selected pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-8) were increased in patients with active ANCA-positive Renal Vasculitis, but not in ANCA positive Vasculitis in remission. These parameters may be useful to monitor the activity of this disease.
Caroline O S Savage - One of the best experts on this subject based on the ideXlab platform.
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rituximab versus cyclophosphamide in anca associated Renal Vasculitis 2 year results of a randomised trial
Annals of the Rheumatic Diseases, 2015Co-Authors: Rachel B Jones, Shunsuke Furuta, Jan Willem Cohen Tervaert, Thomas H Hauser, Raashid Luqmani, Matthew D Morgan, Chen Au Peh, Caroline O S Savage, Marten Segelmark, Vladimir TesarAbstract:Objectives The RITUXVAS trial reported similar remission induction rates and safety between rituximab and cyclophosphamide based regimens for antineutrophil cytoplasm antibody (ANCA)-associated Vasculitis at 12months; however, immunosuppression maintenance requirements and longer-term outcomes after rituximab in ANCA-associated Renal Vasculitis are unknown. Methods Forty-four patients with newly diagnosed ANCA-associated Vasculitis and Renal involvement were randomised, 3:1, to glucocorticoids plus either rituximab (375mg/m(2)/weekx4) with two intravenous cyclophosphamide pulses (n=33, rituximab group), or intravenous cyclophosphamide for 3-6months followed by azathioprine (n=11, control group). Results The primary end point at 24months was a composite of death, end-stage Renal disease and relapse, which occurred in 14/33 in the rituximab group (42%) and 4/11 in the control group (36%) (p=1.00). After remission induction treatment all patients in the rituximab group achieved complete B cell depletion and during subsequent follow-up, 23/33 (70%) had B cell return. Relapses occurred in seven in the rituximab group (21%) and two in the control group (18%) (p=1.00). All relapses in the rituximab group occurred after B cell return. Conclusions At 24months, rates of the composite outcome of death, end-stage Renal disease and relapse did not differ between groups. In the rituximab group, B cell return was associated with relapse. Trial registration number ISRCTN28528813.
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rituximab versus cyclophosphamide in anca associated Renal Vasculitis
The New England Journal of Medicine, 2010Co-Authors: Rachel B Jones, Jan Willem Cohen Tervaert, Thomas H Hauser, Raashid Luqmani, Matthew D Morgan, Caroline O S Savage, Marten Segelmark, Vladimir Tesar, Pieter Van Paassen, D WalshAbstract:BackgroundCyclophosphamide induction regimens for antineutrophil cytoplasmic antibody (ANCA)–associated Vasculitis are effective in 70 to 90% of patients, but they are associated with high rates of ...
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randomized trial of plasma exchange or high dosage methylprednisolone as adjunctive therapy for severe Renal Vasculitis
Journal of The American Society of Nephrology, 2007Co-Authors: David Jayne, Loïc Guillevin, Caroline O S Savage, Gill Gaskin, Franco Ferrario, Niels Rasmussen, Daniel Abramowicz, Eduardo Mirapeix, Renato Alberto Sinico, Coen A StegemanAbstract:Systemic Vasculitis associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA) is the most frequent cause of rapidly progressive glomerulonephritis. Renal failure at presentation carries an increased risk for ESRD and death despite immunosuppressive therapy. This study investigated whether the addition of plasma exchange was more effective than intravenous methylprednisolone in the achievement of Renal recovery in those who presented with a serum creatinine >500 micromol/L (5.8 mg/dl). A total of 137 patients with a new diagnosis of ANCA-associated systemic Vasculitis confirmed by Renal biopsy and serum creatinine >500 micromol/L (5.8 mg/dl) were randomly assigned to receive seven plasma exchanges (n = 70) or 3000 mg of intravenous methylprednisolone (n = 67). Both groups received oral cyclophosphamide and oral prednisolone. The primary end point was dialysis independence at 3 mo. Secondary end points included Renal and patient survival at 1 yr and severe adverse event rates. At 3 mo, 33 (49%) of 67 after intravenous methylprednisolone compared with 48 (69%) or 70 after plasma exchange were alive and independent of dialysis (95% confidence interval for the difference 18 to 35%; P = 0.02). As compared with intravenous methylprednisolone, plasma exchange was associated with a reduction in risk for progression to ESRD of 24% (95% confidence interval 6.1 to 41%), from 43 to 19%, at 12 mo. Patient survival and severe adverse event rates at 1 yr were 51 (76%) of 67 and 32 of 67 (48%) in the intravenous methylprednisolone group and 51 (73%) of 70 and 35 of (50%) 70 in the plasma exchange group, respectively. Plasma exchange increased the rate of Renal recovery in ANCA-associated systemic Vasculitis that presented with Renal failure when compared with intravenous methylprednisolone. Patient survival and severe adverse event rates were similar in both groups.
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anca associated Renal Vasculitis at the end of the twentieth century a disease of older patients
Rheumatology, 2005Co-Authors: Lorraine Harper, Caroline O S SavageAbstract:Objective. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are increasingly recognized in older patients. However, it is unknown whether disease presentation and response to treatment differs from younger patients. We aimed to examine the presentation, response to treatment and outcome of patients over 65 yr of age compared with a younger cohort. Methods. This retrospective, single centre, sequential cohort study reports presenting features and outcome of 233 consecutive new patients with ANCA-associated Vasculitis between 1990 and 2000. Results. The median age of all patients was 65 yr (range 16–90 yr). Older patients (>65 yr) presented with more severe Renal involvement at presentation (P 400lmol/l), infection and low serum albumin. Leucopenia was associated with severe Renal impairment (P ¼ 0.0048) and increased risk of infection (P ¼ 0.0006). Multivariate analysis determined that serum creatinine >400lmol/l and age were independent risk factors for poor prognosis. Conclusion. ANCA-associated Vasculitis occurs frequently in older patients and physicians should maintain a high index of suspicion. Older patients have a poorer prognosis due to more severe Renal involvement and increased sensitivity to adverse effects of treatment. This study highlights the importance of careful dosing of cyclophosphamide: in those aged over 65 yr a 25% dose reduction is safe and reduces the risk of leucopenia. This study further highlights the importance of Renal function on prognosis and the need for less toxic treatment regimens.
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anca associated Renal Vasculitis
Kidney International, 2001Co-Authors: Caroline O S SavageAbstract:The hemoglobin level was 8.8 g/dL with normal indices. The CASE PRESENTATION erythrocyte sedimentation rate was 70 mm/hr. C-reactive proA 62-year-old white woman presented to another hospital tein was 30 mg/L (normal 10 mg/L), and she had a positive with a five-week history of profound malaise and small joint antineutrophil cytoplasmic antibody (ANCA) test to a titer of arthralgia. Initially she had noticed a mild sore throat that set1:400 serum dilution by indirect immunofluorescence with a tled spontaneously. She had transient redness of her left conperinuclear pattern. Subsequent antigen-specific ELISA conjunctiva. One week after the onset of symptoms, she had a firmed reactivity to myeloperoxidase (MPO), denoting MPOsingle episode of macroscopic hematuria for which she received ANCA (Fig. 1). The ANA, anti-DNA, and anti-GBM antibody antibiotics from her family doctor. She denied dysuria or uritests were negative. Complement C3 and C4 levels were nornary frequency. For one week prior to admission, she had mal, and cryoglobulins were not detectable. Hepatitis B and suffered nausea and vomiting without abdominal pain or bowel C serologies were negative. After control of blood pressure, a disturbance. She had lost one stone (14 pounds) in weight. She Renal biopsy was performed; the tissue contained eight glomerhad been hypertensive five years previously, but she had had uli. Of these, one was globally sclerosed, three were normal, no other antecedent illnesses. There was no family history of and four contained acute segmental lesions of various sizes Renal disease, hypertension, or rheumatic complaints. She had with thrombosis, tuft disruption, and a few cells in Bowman’s four adult children, all of whom were well. Medication on space (Fig. 2). Tubules were acutely damaged, with blood in admission comprised a beta blocker (atenolol, 100 mg daily) a few. A patchy infiltrate of chronic inflammatory cells was for hypertension. She did not smoke cigarettes and drank less present. Small arteries and arterioles appeared virtually northan three units (24 g) of alcohol per week. She was a poultry mal. Immunoperoxidase study revealed no significant immunofarmer and lived in a rural setting. protein deposition within glomeruli. Clinical examination revealed that she was pale and dehyThe clinical history, Renal biopsy findings, and blood serology drated. She had no rash, no active synovitis, and no lymphadewere consistent with an acute vasculitic (pauci-immune) glonopathy. Her temperature was 37.2 C; pulse, 70 beats/min; merulonephritis of the microscopic polyangiitis type. An assessand blood pressure, 160/90 mm Hg lying and 145/80 mm Hg ment of vasculitic activity showed a Birmingham Vasculitis Acstanding. Her jugular venous pressure was not elevated and she tivity Score (BVAS) of 13 and a Vasculitis Damage Index (VDI) had no sacral or ankle edema. The heart sounds were normal score of 0. Therapy with prednisolone, 1 mg/kg/day, and oral
Omar Mamlouk - One of the best experts on this subject based on the ideXlab platform.
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checkpoint inhibitor related Renal Vasculitis and use of rituximab
Journal for ImmunoTherapy of Cancer, 2020Co-Authors: Omar Mamlouk, Jamie S Lin, Maen Abdelrahim, Amanda Tchakarov, William F Glass, Umut Selamet, Maryam Buni, Noha Abdelwahab, Ala AbudayyehAbstract:The percentage of patients with cancer eligible for checkpoint inhibitor (CPI) therapy has increased rapidly over the past few years and approaches 45%. As a result, more cases of CPI-related nephrotoxicity, including a rare subset with Vasculitis, are being reported. To elucidate the clinical presentation of CPI-associated Renal Vasculitis and its possible mechanisms, treatment options and prognosis, we describe cases from a comprehensive cancer center and reviewed the literature for similar cases. We retrospectively reviewed the charts of all patients with cancer from 2014 to 2020 who were diagnosed with CPI-related nephrotoxicity and underwent a kidney biopsy. We identified five cases of Renal Vasculitis: three patients were diagnosed with seronegative antineutrophil cytoplasm antibody (ANCA)-associated Vasculitis, one case with seropositive ANCA-associated Vasculitis and one case was diagnosed with IgA Vasculitis. Of these cases, four patients were receiving nivolumab, and one patient was receiving tremelimumab. All patients had microscopic hematuria, four out of five patients had negative ANCA serology, one patient had concurrent lung involvement and positive ANCA serology, and all had severe acute kidney injury with creatinine >4.50 mg/dL on diagnosis. All patients were treated by discontinuing CPI and initiating corticosteroids and rituximab. Three patients received plasmapheresis; two of these required Renal replacement therapy including the patient with lung involvement. All patients after rituximab had a partial or complete Renal response. Two patients died within 8 months of diagnosis due to malignancy progression. None of the patients had a relapse of Vasculitis. We demonstrated that CPI can be associated with different types of Renal Vasculitis that are predominantly ANCA negative and manifest as severe acute kidney injury. Despite the lack of strong evidence, treatment similar to treatment of primary seropositive ANCA-associated Vasculitis with corticosteroids and rituximab is well tolerated with favorable Renal outcomes.
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checkpoint inhibitors related Renal Vasculitis and use of rituximab
Journal of Clinical Oncology, 2020Co-Authors: Omar Mamlouk, Jamie S Lin, Maen Abdelrahim, Amanda Tchakarov, William F Glass, Umut Selamet, Maryam Buni, Noha Abdelwahab, Ala AbudayyehAbstract:e15145Background: As the percentage of cancer patients eligible for checkpoint inhibitor therapy (CPI) is increasing rapidly over the past couple years and approaching 45%, more cases of CPI relate...