Colocalization of ANCA-antigens and fibrinoid necrosis in ANCA-associated vasculitis

Colocalization of ANCA-antigens and fibrinoid necrosis in ANCA-associated vasculitis. A variety of antineutrophil cytoplasmic auto-antibodies (ANCAs) are known to be associated with small vessel vasculitides such as Wegener's granulomatosis and microscopic polyangiitis. To visualize colocalization patterns of the fibrinoid necrotic lesions and ANCA-antigens more accurately, we have developed a double staining technique in which an immunohistochemical staining is followed by a histological staining. Instead of using sequential biopsy slides of histologically and immunohistochemically stained sections, which may lead to an underestimation of the number and size of the lesions, our technique permits the visualization of the colocalized patterns of fibrinoid necrosis with an ANCA-antigen in a single slide. The double staining procedure is presented in this Technical Note

ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse.

Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild-moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray's regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8-14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray's model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different

ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse.

Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild-moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray's regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8-14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray's model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different

Renal relapse in antineutrophil cytoplasmic autoantibody-associated vasculitis : unpredictable, but predictive of renal outcome

Objectives: To determine predictors of renal relapse and end-stage renal failure (ESRF) in patients with ANCA-associated vasculitis. Methods: Data from four European Vasculitis Society randomized controlled trials, conducted roughly simultaneously between 15 March 1995 and 30 September 2002, was pooled to determine predictors of long-term renal outcome. The respective trial inclusion criteria covered the entire spectrum of disease severity. Baseline predictors of time to first renal relapse and time to ESRF were assessed by competing events analysis and Cox proportional hazards regression. The effect of renal relapse on time to ESRF was assessed by adding renal relapses to the competing events analysis as a time-varying covariate. Results: The number of patients participating was 535; mean serum creatinine (±s.d.) at entry was 341 ± 321 µmol/l and 19.7% developed ESRF. One or more renal relapse(s) was experienced by 101 patients. Multivariable regression analysis demonstrated that, in addition to impaired baseline renal function, developing ⩾1 renal relapse was an independent risk factor for ESRF (subhazard ratio 9; 95% CI 4, 19; P < 0.001). No predictive factors for renal relapse were found. Conclusion: In addition to baseline renal function, the occurrence of renal relapses is an important determinant of ESRF in patients with ANCA-associated vasculitis. We did not find any clinical predictors for renal relapse itself, including disease activity elsewhere. In light of the silent nature of renal relapse in ANCA-associated vasculitis, we stress the need for long-term vigilant monitoring for early signs of renal relapse and propose performing 3-monthly urinalysis. This will enable timely treatment and help further improve renal outcome

Revisiting the classification of clinical phenotypes of anti-neutrophil cytoplasmic antibody-associated vasculitis: a cluster analysis

Background Granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA) are subgroups of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) defined historically by clinical and histological features. GPA and MPA are heterogeneous entities with overlapping phenotypes. To identify novel subgroupings, cluster analysis was used to explore the phenotypic spectrum of AAV. Methods This study used a dataset of patients newly diagnosed as having GPA and MPA enrolled in five clinical trials. One cluster model included nine clinical baseline variables as input variables, and a second cluster model additionally included ANCA specificities. The clustering process involved multiple correspondence analyses followed by hierarchical ascendant cluster analysis. The clinical relevance of the generated clusters was analysed by their summary characteristics and outcomes. Results The analyses involved data for 673 subjects: 396 (59%) with GPA and 277 (41%) with MPA. Both cluster models resulted in five partially redundant clusters of subjects, and the model including ANCA resulted in more pertinent separations. These clusters were named 'renal AAV with proteinase 3 (PR3)-ANCA' (40% of subjects), 'renal AAV without PR3-ANCA' (32%) and 'non-renal AAV' (12%), 'cardiovascular AAV' (9%) and 'gastrointestinal AAV' (7%). The five clusters had distinct death and relapse rates. On the basis of 4 variables, 651 subjects (97%) could be accurately allocated to 1 of the 5 classes. Conclusions This analysis suggests that AAV encompasses five classes associated with different outcomes. As compared with the traditional GPA-MPA separation, this classification system may better reflect the phenotypic spectrum of AAV

Key elements in selection of pre-dialysis patients for home dialysis

Background: Most pre-dialysis patients are medically eligible for home dialysis, and home dialysis has several advantages over incentre dialysis. However, accurately selecting patients for home dialysis appears to be difficult, since uptake of home dialysis remains low. The aim of this study was to investigate which medical or psychosocial elements contribute most to the selection of patients eligible for home dialysis. Methods: All patients from a Dutch teaching hospital, who received treatment modality education and subsequently started dialysis treatment, were included. The pre-dialysis programme consisted of questionnaires for the patient, nephrologist and social worker, followed by an assessment of eligibility for home dialysis by a multidisciplinary team. Clinimetric assessment and logistic regression were used to identify domains and questions associated with home dialysis treatment. Results: A total of 135 patients were included, of whom 40 were treated with home dialysis and 95 with incentre haemodialysis. The key elements associated with long-term home dialysis treatment were part of the domains ‘suitability of the housing’, ‘self-care’, ‘social support’ and ‘patient capacity’, with adjusted odds ratios ranging from 0.13 for negative to 18.3 for positive associations. Conclusion: The assessment of contraindications by a nephrologist followed by the assessment of possibilities by a social worker or dialysis nurse who investigates four key elements, ideally during a home visit, and subsequent detailed education offered by specialized nurses is an optimal way to select patients for home dialysis

Key elements in selection of pre-dialysis patients for home dialysis

Background: Most pre-dialysis patients are medically eligible for home dialysis, and home dialysis has several advantages over incentre dialysis. However, accurately selecting patients for home dialysis appears to be difficult, since uptake of home dialysis remains low. The aim of this study was to investigate which medical or psychosocial elements contribute most to the selection of patients eligible for home dialysis. Methods: All patients from a Dutch teaching hospital, who received treatment modality education and subsequently started dialysis treatment, were included. The pre-dialysis programme consisted of questionnaires for the patient, nephrologist and social worker, followed by an assessment of eligibility for home dialysis by a multidisciplinary team. Clinimetric assessment and logistic regression were used to identify domains and questions associated with home dialysis treatment. Results: A total of 135 patients were included, of whom 40 were treated with home dialysis and 95 with incentre haemodialysis. The key elements associated with long-term home dialysis treatment were part of the domains ‘suitability of the housing’, ‘self-care’, ‘social support’ and ‘patient capacity’, with adjusted odds ratios ranging from 0.13 for negative to 18.3 for positive associations. Conclusion: The assessment of contraindications by a nephrologist followed by the assessment of possibilities by a social worker or dialysis nurse who investigates four key elements, ideally during a home visit, and subsequent detailed education offered by specialized nurses is an optimal way to select patients for home dialysis