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      Comparing outcomes of biopsy-proven anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis patients treated with cyclophosphamide in the 20th and 21st centuries: a 23-year study

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          Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disorder associated with significant morbidity and mortality. Approximately 80–90% of patients have circulating ANCAs. Long-term outcomes appear to be improving. This retrospective study analyses the incidence and patient outcomes over a period of 23 years at a single tertiary centre.


          Outcomes of patients diagnosed with AAV between 1 January 1988 and 31 December 2010 were collected retrospectively. Data including patient demographics, age of diagnosis, dates of starting renal replacement therapy, death and biochemistry results were collected. Patients were divided into two cohorts (1988–99 and 2000–10) and analysed using Stata software (StataCorp, College Station, TX, USA).


          A complete dataset was obtained for 273 patients. Of these patients, 101 were diagnosed between 1988 and 1999 while 172 were diagnosed between 2000 and 2010. The number of patients diagnosed with AAV increased from 2.2/million in 1988 to 10.3/million in 2010. A higher proportion of patients (56.4%) in the earlier cohort presented with creatinine >500 μmol/L compared with the later cohort (30.2%; P < 0.001). Overall patient survival improved significantly between the two cohorts. Cohort 1 had a median survival of 59 months compared with 125 months for Cohort 2 (P = 0.003).


          This study shows that AAV is being diagnosed at an earlier stage, resulting in improved outcomes. This may be because of improvements in the management of AAV and chronic kidney disease.

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          Most cited references 26

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          Long-term patient survival in ANCA-associated vasculitis.

          Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain. To describe the long-term patient survival and possible prognostic factors at presentation in an international, multicentre, prospectively recruited representative patient cohort who were treated according to strictly defined protocols at presentation and included the full spectrum of ANCA-associated vasculitis disease. Outcome data were collected for 535 patients who had been recruited at the time of diagnosis to four randomised controlled trials between 1995 and 2002. Trial eligibility was defined by disease severity and extent, covered the spectrum of severity of ANCA-associated vasculitis and used consistent diagnostic criteria. Demographic, clinical and laboratory parameters at trial entry were tested as potential prognostic factors in multivariable models. The median duration of follow-up was 5.2 years and 133 (25%) deaths were recorded. Compared with an age- and sex-matched general population there was a mortality ratio of 2.6 (95% CI 2.2 to 3.1). Main causes of death within the first year were infection (48%) and active vasculitis (19%). After the first year the major causes of death were cardiovascular disease (26%), malignancy (22%) and infection (20%). Multivariable analysis showed an estimated glomerular filtration rate <15 ml/min, advancing age, higher Birmingham Vasculitis Activity Score, lower haemoglobin and higher white cell count were significant negative prognostic factors for patient survival. Patients with ANCA-associated vasculitis treated with conventional regimens are at increased risk of death compared with an age- and sex-matched population.
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            Histopathologic classification of ANCA-associated glomerulonephritis.

            Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is the most common cause of rapidly progressive glomerulonephritis worldwide, and the renal biopsy is the gold standard for establishing the diagnosis. Although the prognostic value of the renal biopsy in ANCA-associated glomerulonephritis is widely recognized, there is no consensus regarding its pathologic classification. We present here such a pathologic classification developed by an international working group of renal pathologists. Our classification proposes four general categories of lesions: Focal, crescentic, mixed, and sclerotic. To determine whether these lesions have predictive value for renal outcome, we performed a validation study on 100 biopsies from patients with clinically and histologically confirmed ANCA-associated glomerulonephritis. Two independent pathologists, blinded to patient data, scored all biopsies according to a standardized protocol. Results show that the proposed classification system is of prognostic value for 1- and 5-year renal outcomes. We believe this pathologic classification will aid in the prognostication of patients at the time of diagnosis and facilitate uniform reporting between centers. This classification at some point might also provide means to guide therapy.
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              Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial.

              Current therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are limited by toxicity. To compare pulse cyclophosphamide with daily oral cyclophosphamide for induction of remission. Randomized, controlled trial. Random assignments were computer-generated; allocation was concealed by faxing centralized treatment assignment to providers at the time of enrollment. Patients, investigators, and assessors of outcomes were not blinded to assignment. 42 centers in 12 European countries. 149 patients who had newly diagnosed generalized ANCA-associated vasculitis with renal involvement but not immediately life-threatening disease. Pulse cyclophosphamide, 15 mg/kg every 2 to 3 weeks (76 patients), or daily oral cyclophosphamide, 2 mg/kg per day (73 patients), plus prednisolone. Time to remission (primary outcome); change in renal function, adverse events, and cumulative dose of cyclophosphamide (secondary outcomes). Groups did not differ in time to remission (hazard ratio, 1.098 [95% CI, 0.78 to 1.55]; P = 0.59) or proportion of patients who achieved remission at 9 months (88.1% vs. 87.7%). Thirteen patients in the pulse group and 6 in the daily oral group achieved remission by 9 months and subsequently had relapse. Absolute cumulative cyclophosphamide dose in the daily oral group was greater than that in the pulse group (15.9 g [interquartile range, 11 to 22.5 g] vs. 8.2 g [interquartile range, 5.95 to 10.55 g]; P < 0.001). The pulse group had a lower rate of leukopenia (hazard ratio, 0.41 [CI, 0.23 to 0.71]). The study was not powered to detect a difference in relapse rates between the 2 groups. Duration of follow-up was limited. The pulse cyclophosphamide regimen induced remission of ANCA-associated vasculitis as well as the daily oral regimen at a reduced cumulative cyclophosphamide dose and caused fewer cases of leukopenia. The European Union.

                Author and article information

                Clin Kidney J
                Clin Kidney J
                Clinical Kidney Journal
                Oxford University Press
                February 2019
                11 September 2018
                11 September 2018
                : 12
                : 1
                : 42-48
                [1 ]Renal Department, Royal Preston Hospital, Preston, UK
                [2 ]Faculty of Health and Wellbeing, University of Central Lancashire, Preston, UK
                Author notes
                Correspondence and offprint requests to: Steven Whatmough; E-mail: steven.whatmough@
                © The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact

                Page count
                Pages: 7


                anca, epidemiology, survival, vasculitis


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