The clinical course of ANCA small-vessel vasculitis on chronic dialysis

Division of Nephrology and Hypertension, UNC Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Kidney International (Impact Factor: 8.52). 07/2009; 76(6):644-51. DOI: 10.1038/ki.2009.218
Source: PubMed

ABSTRACT Antineutrophil cytoplasmic autoantibody (ANCA)-associated small-vessel vasculitis frequently affects the kidney. Here we describe the rates of infection, disease relapse, and death in patients with ANCA small-vessel vasculitis before and after end-stage renal disease (ESRD) in an inception cohort study and compare them to those of patients with preserved renal function. All patients had biopsy-proven ANCA small-vessel vasculitis. Fisher's exact tests and Wilcoxon rank sum tests were used to compare the characteristics by ESRD status. ESRD follow-up included time on dialysis with transplants censored. Over a median follow-up time of 40 months, 136 of 523 patients reached ESRD. ESRD was associated with new-onset ANCA small-vessel vasculitis in 51% of patients, progressive chronic kidney disease without active vasculitis in 43%, and renal relapse in 6% of patients. Relapse rates of ANCA small-vessel vasculitis, reported as episodes/person-year, were significantly lower on chronic dialysis (0.08 episodes) compared with the rate of the same patients before ESRD (0.20 episodes) or with patients with preserved renal function (0.16 episodes). Infections were almost twice as frequent among patients with ESRD on maintenance immunosuppressants and were an important cause of death. Given the lower risk of relapse and higher risk of infection and death, we suggest that immunosuppression be geared to patients with ESRD who present with active vasculitis.

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Available from: Sofia Lionaki, Jul 28, 2014
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    Advances in the Diagnosis and Treatment of Vasculitis, 11/2011; , ISBN: 978-953-307-786-4
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    ABSTRACT: Background Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides are potentially life-threatening disorders. Materials and methods Even though immunosuppressive therapy improves the prognosis, adverse events, either attributable to persistent disease activity or side effects of treatment remain a challenge. Infectious complications are the leading cause of death in the first year after diagnosis and a major cause of morbidity and mortality thereafter. Results Their incidence in clinical trials varies considerably but opportunistic and life-threatening infections, such as Pneumocystis jirovecii pneumonia or systemic cytomegalovirus infections, are frequent and thus predisposing/risk factors need to be defined. Pneumocystis jirovecii pneumonia has been associated with a lymphocyte count below 300/mm3. Additionally, besides the aggressiveness of the immunosuppressive regimen administered (especially the cumulative dose of steroids and cyclophosphamide), an elevated serum creatinine or dialysis dependency, older age and pulmonary involvement increase the rate of infectious omplications. Conclusions We suggest to routinely prescribe trimethoprim–sulfamethoxazole or antimicrobial agents such as pentamidine in case of intolerance or contraindication in the early phase of induction therapy irrespective of the immunosuppressive strategy used and to continue therapy, together with other targeted measures (antiviral, antimycotic or antibiotic) in the presence of risk factors for a prolonged period of time. Finally, there is an urgent need to standardize the reporting of infectious complications in clinical trials to enable comparing the adverse event spectrum of distinct treatment approaches more appropriately. Keywords ANCA-associated vasculitis, granulomatosis with polyangiitis, immunosuppression, infections, Pneumocystis jirovecii, trimethoprim–sulfamethoxazole.
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    ABSTRACT: In ANCA-associated GN, severe renal dysfunction portends a poor prognosis for renal recovery and patient survival. This study evaluated the prognostic factors affecting renal and patient outcomes in patients presenting with severe kidney failure to guide immunosuppressive therapy. This study retrospectively evaluated clinical and histopathologic characteristics of 155 patients who underwent biopsy between October 1985 and February 2011 (median eGFR at presentation, 7.1 ml/min per 1.73 m(2); 87% required hemodialysis), all treated with immunosuppressive medications. Three outcomes of interest were measured: patient survival, renal survival, and treatment response (defined as dialysis-free survival without active vasculitis by 4 months after biopsy). Competing risk, Cox, and logistic regression analyses were conducted for each outcome measure. Within 4 months after biopsy, treatment response was attained in 51% of patients, 35% remained on dialysis, and 14% died. In a competing risk analysis, estimated cumulative incidence rates of ESRD and disease-related mortality were 26% and 17% at 1 year and 32% and 28% at 5 years, respectively. Cyclophosphamide therapy and treatment response by 4 months were independently associated with patient and renal survival, adjusting for the percentage of normal glomeruli, histopathologic chronicity index score, and baseline clinical characteristics. Only 5% of patients still dialysis dependent at 4 months subsequently recovered renal function. Low chronicity index score (odds ratio [OR], 1.16; 95% confidence interval [95% CI], 1.04 to 1.30, per unit decrease) and baseline eGFR>10 ml/min per 1.73 m(2) (OR, 2.77; 95% CI, 1.09 to 7.01) were significantly associated with treatment response by 4 months. Among cyclophosphamide-treated patients, the likelihood of treatment response was >14% even with highest chronicity index score and eGFR<10 ml/min per 1.73 m(2). Although low baseline renal function and severe renal scarring are associated with lower treatment response rate, no "futility" threshold could be identified. Conversely, continued immunosuppressive therapy beyond 4 months is unlikely to benefit patients who remain dialysis dependent.
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