Background Intravenous pulse methylprednisolone (MP) is commonly included in the management of severe ANCA associated vasculitis (AAV) despite limited evidence of benefit. We aimed to evaluate outcomes in patients who had, or had not received MP, along with standard therapy for remission induction in severe AAV. Methods We retrospectively studied 114 consecutive patients from five centres in Europe and the United States with a new diagnosis of severe AAV (creatinine > 500 μmol/L or dialysis dependency) and that received standard therapy (plasma exchange, cyclophosphamide and high-dose oral corticosteroids) for remission induction with or without pulse MP between 2000 and 2013. We evaluated survival, renal recovery, relapses, and adverse events over the first 12 months. Results Fifty-two patients received pulse MP in addition to standard therapy compared to 62 patients that did not. There was no difference in survival, renal recovery or relapses. Treatment with MP associated with higher risk of infection during the first 3 months (hazard ratio (HR) 2.7, 95%CI [1.4–5.3], p = 0.004) and higher incidence of diabetes (HR 6.33 [1.94–20.63], p = 0.002), after adjustment for confounding factors. Conclusions The results of this study suggest that addition of pulse intravenous MP to standard therapy for remission induction in severe AAV may not confer clinical benefit and may be associated with more episodes of infection and higher incidence of diabetes. Electronic supplementary material The online version of this article (10.1186/s12882-019-1226-0) contains supplementary material, which is available to authorized users.
Murine and human lupus nephritis are characterized by glomerular deposits of electron-dense structures (EDS). Dominant components of EDS are chromatin fragments and IgG antibodies. Whether glomerular EDS predispose for similar deposits in skin is unknown. We analysed (i) whether dermo-epidermal immune complex deposits have similar molecular composition as glomerular deposits, (ii) whether chromatin fragments bind dermo-epidermal structures, and (iii) whether deposits in nephritic glomeruli predispose for accumulation of similar deposits in skin. Paired skin and kidney biopsies from nephritic (NZBxNZW)F1 and MRL-lpr/lpr mice and from five patients with lupus nephritis were analysed by immunofluorescence, immune electron microscopy (IEM) and co-localization TUNEL IEM. Affinity of chromatin fragments for membrane structures was determined by surface plasmon resonance. Results demonstrated (i) presence of EDS containing chromatin fragments and IgG in both organs in nephritic patients, (ii) chromatin fragments possessed high affinity for dermo-epidermal laminins and collagens, (iii) glomerular immune complex deposits did not predict similar interstitial deposits in skin, although such complexes were present in capillary lumina in glomeruli and skin of all nephritic individuals. Thus, chromatin-IgG complexes accounting for lupus nephritis seem to reach skin through circulation, but other undetermined factors are required for these complexes to deposit within skin membranes.
Objectives This study aimed to characterize the association between HLA alleles and ANCA-associated vasculitis (AAV) in a genetically homogeneous population, and to analyse the contribution of specific HLA molecule amino acid sequences to the risk of AAV. Methods We included 187 Danish patients with AAV and 1070 healthy controls. All were HLA typed at two-field resolution. The association of HLA alleles to PR3- or MPO-AAV was analysed. The contribution of the dominant molecular motifs of the HLA-DPB1 molecule to the risk of AAV was investigated by association studies that included specific amino acid sequences of the hypervariable regions in exon 2. Results Ninety-four percent of patients with PR3-AAV were carriers of HLA-DPB1*04:01 while all patients with PR3-AAV were carriers of an HLA-DPB1*04 allele, and 85% were homozygous. This was significantly more than in the control group (P < 0.0001). The association was even stronger when HLA-DPB1*04:02 and -DPB1*23:01 were included. HLA-DPB1*04:01, -DPB1*04:02 and -DPB1*23:01 share amino acids in positions 8–9, 69, 76 and 84–87 within the hypervariable regions, but only positions 69 and 84–87 contributed significantly to the disease risk. HLA-DRB1*15 was associated with an increased risk of developing PR3-AAV, while HLA-DRB1*04, -DRB1*07 and -DQB1*03 were associated with a reduced risk of kidney involvement in PR3-AAV. MPO-AAV was only weakly associated with HLA class I alleles. Conclusion PR3-AAV is strongly associated with the HLA-DPB1 alleles HLA-DPB1*04:01, -DPB1*04:02 and -DPB1*23:01, which share amino acid sequences crucial for the peptide-binding groove.
Background Patients with stage 5 chronic kidney disease (CKD5) collaborate with their clinicians when choosing their future treatment modality. Most elderly patients with CKD5 may only have two treatment options: dialysis or conservative kidney management (CKM). The objective of this systematic review was to investigate whether CKM offers a quantity or quality of life benefit compared to dialysis for some patients with CKD5. Methods The databases MEDLINE, EMBASE, the Cochrane Library, and CINAHL were systematically searched for studies comparing patients with CKD5 who had chosen or were treated with either CKM or dialysis. The primary outcomes were mortality and quality of life (QoL). Hospitalization, symptom burden, and place of death were secondary outcomes. For studies reporting hazard ratios, pooled values were calculated, and forest plots conducted. Results Twenty-five primary studies, all observational, were identified. All studies reported an increased mortality in patients treated with CKM (pooled hazard ratio 0.47, 95 % confidence interval 0.34–0.65). For patients aged ≥ 80 years and for elderly individuals with comorbidities, results were ambiguous. In most studies, CKM seemed advantageous for QoL and secondary outcomes. Findings were limited by the heterogeneity of studies and biased outcomes favouring dialysis. Conclusions In general, patients with CKD5 who have chosen or are on CKM live for a shorter time than patients who have chosen or are on dialysis. In patients aged ≥ 80 years old, and in elderly individuals with comorbidities, the survival benefits of dialysis seem to be lost. Regarding QoL, symptom burden, hospitalization, and place of death, CKM may have advantages. Higher quality studies are needed to guide patients and clinicians in the decision-making process.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.