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ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse.

ABSTRACT: 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.

SUBMITTER: Goceroglu A

PROVIDER: S-EPMC5156375 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse.

Göçeroğlu Arda A Berden Annelies E AE Fiocco Marta M Floßmann Oliver O Westman Kerstin W KW Ferrario Franco F Gaskin Gill G Pusey Charles D CD Hagen E Christiaan EC Noël Laure-Hélène LH Rasmussen Niels N Waldherr Rüdiger R Walsh Michael M Bruijn Jan A JA Jayne David R W DR Bajema Ingeborg M IM

PloS one 20161214 12

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 Eur ...[more]

PMID: 27973575

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Project description:BackgroundRapidly progressive glomerulonephritis caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is typically characterized as pauci-immune glomerulonephritis. However, immune complex (IC) deposition in the glomerulus has been reported in a growing number of studies. Here, we assess the presence of glomerular immune deposits alongside renal outcome in myeloperoxidase (MPO)-ANCA associated glomerulonephritis (MPO-ANCA GN).MethodsClinical and histopathologic characteristics of 97 patients with MPO-ANCA GN classified by renal biopsy from January 2008 to December 2019 were extracted retrospectively from electronic medical records. The extent of immune deposits in the kidney (C3, C4, C1q, IgA, IgG, IgM) at diagnosis were analyzed by immunofluorescence (IF). Patients were followed up for a median period of 15 months. The response to treatment and outcomes of renal and histological lesion changes were also assessed.ResultsIn our study, 41% (40/97) of patients showed positive IF (≥2+) for at least one of the six immunoglobulin or complement components tested. Patients with IC deposits showed higher levels of serum creatinine (p=0.025), lower platelet counts (p=0.009), lower serum complement C3 (sC3) (≤790 ml/L) (p=0.013) and serum IgG (p=0.018) than patients with pauci-immune (PI) deposition at diagnosis. End-stage renal disease was negatively associated with eGFR (HR 0.885, 95% CI 0.837 to 0.935, p<0.0001), platelet count (HR 0.996, 95% CI 0.992 to 1.000, p=0.046) and serum globulin (HR 0.905, 95% CI 0.854 to 0.959, p=0.001). Patients with lower sC3 levels showed a worse renal outcome than the patients with normal sC3 at diagnosis (p=0.003). Analysis of the components of the renal deposits found that patients with IgG deposits exhibited a poorer renal outcome compared to patients that were IgG negative (p=0.028). Moreover, Bowman's capsule rupture occurred less frequently in patients with IgM deposition compared with IgM negative counterparts (p=0.028). Vascular lesions and granuloma-like lesions had been seen more frequently in cases with IgA deposition than those without IgA deposition (p=0.03 and 0.015, respectively).ConclusionIn conclusion, patients with immune complex deposits in the kidney showed less platelet count, lower sC3 and sIgG levels, and higher serum creatinine levels. Patients with low sC3 at initial and with continued low sC3 during the treatment displayed a trend toward poorer kidney survival. Moreover, the IC group showed a worse renal outcome than the PI group, further enforcing the present strategy of introducing complement targeted therapies in AAV.

Project description:The prognosis of antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) is unfavorable despite immunosuppressive therapy. It has been suggested that the loss of podocytes is a hallmark of progressive kidney disease. However, it is unclear about podocyte injuries and their predictive values on the prognosis in ANCA-GN. Therefore, the current study aimed to investigate the podocyte injury in renal histopathology and its association with renal prognosis of patients with ANCA-GN. A total of 170 patients with ANCA-GN were recruited in this study. Morphometric investigation of podocytes by electron microscopy including foot process width (FPW), podocyte density per glomerulus (Nv), and glomerular basement membrane (GBM) width were measured and calculated in ANCA-GN patients. Cox regression analysis was used to analyze the association between podocyte injuries and prognosis of patients with ANCA-GN. Foot processes broadening, podocyte detachment, and GBM thickening could be observed in electron micrographs in the specimens of 158/170 (92.9%), 142/170 (83.5%), and 150/170 (88.2%) patients, respectively. Compared with normal controls, FPW and GBM width in ANCA-GN patients was significantly higher (1269.39?±?680.19 vs 585.81?±?77.16, P?=?0.004; 668.23?±?208.73 vs 354.23?±?52.70, P?=?0.000, respectively), while the podocyte density was significantly lower (55.90?±?36.32 vs 255.23?±?47.29, P?=?0.000). The podocyte density was independently associated with the recovery of renal function in logistic regression analysis (OR, 1.083; 95% CI, 1.025-1.440; P?=?0.005). Furthermore, multivariate analysis revealed that podocyte density was an independent predictor of end-stage renal disease (ESRD) (model A: HR, 0.950; 95% CI, 0.919-1.982; P?=?0.002; model B: HR, 0.953; 95% CI, 0.922-0.985; P?=?0.004). Podocyte structural damage and detachment occurred frequently in patients with ANCA-GN. Moreover, podocyte detachment was an independent predictor of renal outcomes.

Project description:Background and objectivesThe histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes were ordered by severity of kidney function loss as follows: focal, crescentic, mixed, and sclerotic. Subsequent validation studies disagreed on outcomes in the crescentic and mixed classes. This study, driven by the original investigators, provides several analyses in order to determine the current position of the histopathologic classification of ANCA-associated GN.Design, setting, participants, & measurementsA validation study was performed with newly collected data from 145 patients from ten centers worldwide, including an analysis of interobserver agreement on the histopathologic evaluation of the kidney biopsies. This study also included a meta-analysis on previous validation studies and a validation of the recently proposed ANCA kidney risk score.ResultsThe validation study showed that kidney failure at 10-year follow-up was significantly different between the histopathologic classes (P<0.001). Kidney failure at 10-year follow-up was 14% in the crescentic class versus 20% in the mixed class (P=0.98). In the meta-analysis, no significant difference in kidney failure was also observed when crescentic class was compared with mixed class (relative risk, 1.15; 95% confidence interval, 0.94 to 1.41). When we applied the ANCA kidney risk score to our cohort, kidney survival at 3 years was 100%, 96%, and 77% in the low-, medium-, and high-risk groups, respectively (P<0.001). These survival percentages are higher compared with the percentages in the original study.ConclusionsThe crescentic and mixed classes seem to have a similar prognosis, also after adjusting for differences in patient populations, treatment, and interobserver agreement. However, at this stage, we are not inclined to merge the crescentic and mixed classes because the reported confidence intervals do not exclude important differences in prognosis and because an important histopathologic distinction would be lost.

Dataset Information

ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse.

Publications

ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse.

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