IgA vasculitis (IgAV) in adults has been relatively under-investigated. Since outcomes are worse in other forms of vasculitis with increasing age, we investigated the outcomes of IgAV comparing ...younger adults (18-34), middle aged adults (35-64) and elderly patients (≥64 years) focusing on kidney outcomes.
We identified patients with renal biopsy confirmed IgAV nephritis and collected data regarding clinical features and progression to end stage kidney disease (ESKD). The relationship between patient factors and ESKD was analysed by regression.
We identified 202 cases, 34% aged 18-34, 43% aged 35-64 and 23% were elderly (>64 years). Median follow up was 44 months. Elderly patients were more likely to present with ESKD (23.9%) compared with middle aged (13.7%) and younger adults (2.9%)(χ2 11.6, p= 0.002). In patients with independent kidney function at biopsy, there was no difference in outcomes between age groups. Male gender, Black ethnicity, diabetes, histological evidence of chronic renal damage and eGFR < 30mls/min were risk factors for development of ESKD. In this observational study 68.3% of patients received glucocorticoids and 56.9% additional immunosuppression.
Elderly patients with IgAV are more likely to have ESKD at presentation, but there is no difference in renal survival between age groups, among those presenting with independent renal function. Renal impairment at biopsy is an independent risk factor for subsequent development of ESKD. There is significant variability in the timing of kidney biopsy and management of these patients among specialist centres. Young adults have outcomes more in keeping with childhood IgAV.
To perform a literature review and develop recommendations for the use of rituximab in ANCA-associated vasculitis.
A committee of experts (five rheumatologists, five nephrologists and one ...paediatrician) conducted a modified Delphi exercise to identify five topics for a systematic literature search. The evidence was then reviewed, categorized according to international criteria and assimilated to form five recommendations statements and a research agenda.
Forty-three studies met the review criteria. These included two randomized controlled trials and a predominance of small, uncontrolled series. In refractory ANCA-associated vasculitis, remission rates of >80% are obtained with rituximab. In newly diagnosed disease, rituximab is at least as effective as conventional therapy. Fifteen recommendations were made. Their strength was restricted by the low quality of the evidence. Six areas for future research were identified.
On the basis of the available evidence and expert consensus, recommendations have been made for the use of rituximab as a treatment of ANCA-associated vasculitis. Further questions, in particular regarding long-term outcomes, remain to be explored.
Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical ...practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange–treated patients was not adopted due to concerns over treatment-associated complications. Without immunosuppression, the relapse rate was high (five of seven). However, reintroduction of treatment resulted in recovery of renal function. All patients treated with eculizumab achieved sustained remission. Five patients received renal transplants without specific factor H autoantibody–targeted treatment with recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate eculizumab therapy for treatment of factor H autoantibody–mediated atypical hemolytic uremic syndrome rather than plasma exchange with or without immunosuppression. Based on this retrospective analysis we see no suggestion of inferior treatment, albeit the strength of our conclusions is limited by the small sample size.
Patients receiving in-center hemodialysis treatment face unique challenges during the coronavirus disease 2019 (COVID-19) pandemic, specifically the need to attend for treatment that prevents ...self-isolation. Dialysis unit attributes and isolation strategies that might reduce dialysis center COVID-19 infection rates have not been previously examined.
We explored the role of variables, including community disease burden, dialysis unit attributes (size and layout), and infection control strategies, on rates of COVID-19 among patients receiving in-center hemodialysis in London, United Kingdom, between March 2, 2020 and May 31, 2020. The two outcomes were defined as (
) a positive test for infection or admission with suspected COVID-19 and (
) admission to the hospital with suspected infection. Associations were examined using a discrete time multilevel time-to-event analysis.
Data on 5755 patients dialyzing in 51 units were analyzed; 990 (17%) tested positive and 465 (8%) were admitted with suspected COVID-19 between March 2 and May 31, 2020. Outcomes were associated with age, diabetes, local community COVID-19 rates, and dialysis unit size. A greater number of available side rooms and the introduction of mask policies for asymptomatic patients were inversely associated with outcomes. No association was seen with sex, ethnicity, or deprivation indices, nor with any of the different isolation strategies.
Rates of COVID-19 in the in-center hemodialysis population relate to individual factors, underlying community transmission, unit size, and layout.
Rituximab, a monoclonal antibody directed against the CD20 molecule found on pre-B cells and mature B cells (but not on plasma cells), was introduced in the late 1990s for the treatment of ...non-Hodgkin's lymphoma. Recently, this antibody has been used to treat autoimmune diseases, especially those associated with a prominent humoral component and with potentially pathogenic autoantibodies. Small cohort studies have indicated that rituximab could have an important role in the management of these disorders. Rituximab has also been utilized in the transplant setting, to diminish levels of alloreactive antibodies in highly sensitized patients, to manage ABO-incompatible transplants, and to treat rejection associated with B cells and antibodies. The exact mechanism by which rituximab exerts its effects in autoimmunity and transplantation remains unclear, as specific autoantibody or alloantibody levels often seem not to diminish in parallel with clinical improvement. A role for rituximab in depleting B cells and compromising their antigen-presenting function seems likely; rituximab might also inhibit T-cell activation. A synergistic effect has been noted in vitro following administration of corticosteroids to B-cell lines, with accentuation of B-cell cytotoxicity; this observation might be relevant to certain studies, as some regimens have utilized both agents simultaneously. This article reviews the current use of rituximab in renal disease and transplantation, and includes discussion of the drug's potential role in novel therapeutic protocols.
Abstract
Objectives
Relapses affect 30–50% of patients with ANCA-associated vasculitis (AAV) over 5 years, necessitating long-term treatment. Although there have been studies looking at predictors of ...relapse in AAV, this research has yet to translate clinically into guidance on tailored therapy. The aim of this systematic review was to identify and meta-analyse existing risk factors from the literature and produce a model to calculate individualised patient risk of relapse.
Method
A search strategy was developed to include all studies identifying predictors of AAV relapse using multivariate analysis. Individual risk factors were extracted and pooled hazard ratios (HRs) calculated. A model to predict the time to first relapse based on identified risk factors was tested retrospectively using a cohort of patients with AAV.
Results
The review of 2674 abstracts identified 117 papers for full text review, with 16 eligible for inclusion. Pooled HRs were calculated from significant risk factors, including anti-PR3 ANCA positivity HR 1.69 (95% CI 1.46, 1.94), cardiovascular involvement HR 1.78 (95% CI 1.26, 2.53), creatinine >200 µmol/l (relative to creatinine ≤100) HR 0.39 (95% CI 0.22, 0.69) and creatinine 101–200 µmol/l HR 0.81 (95% CI 0.77, 0.85). Using data from 182 AAV patients to validate the model gave a C-statistic of 0.61.
Conclusion
Anti-PR3 ANCA positivity, lower serum creatinine and cardiovascular system involvement are all associated with an increased risk of relapse, and a combination of these risk factors can be used to predict the individualised risk of relapse. In order to produce a clinically useful model to stratify risk, we need to identify more risk factors, with a focus on robust biomarkers.
Up to one third of patients on renal replacement programmes have an unknown cause of kidney disease, and the diagnosis may only be established following renal transplantation when the disease recurs ...or if new extra-renal symptoms develop.
We present two patients who presented with progressive chronic kidney disease of unknown cause. Both patients underwent successful renal transplantation but subsequently developed multisystem abnormalities, and were ultimately diagnosed with mitochondrial cytopathy 10-15 years following transplantation.
Mitochondrial cytopathies are rare inborn errors of metabolism that should be considered in adults with renal impairment, especially in those with a family history of kidney or other multisystem disease. The widespread availability of genetic testing provides the potential for earlier diagnoses, thereby enhancing management decisions, anticipation of complications, avoidance of mitotoxic drugs, and informed prognosis prediction.
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