Anti-glomerular Basement Membrane Glomerulonephritis: A Study in Real Life

Abstract

IntroductionAnti-glomerular basement membrane (anti-GBM) disease is a severe entity with few therapeutic options including plasma exchange and immunosuppressive agents. The aim of this study was to analyze the clinical and pathological features that predict the evolution of end-stage kidney disease (ESKD) and the kidney survival in a cohort of patients with anti-GBM disease with renal involvement in real life.MethodsA retrospective multicentre observational study including 72 patients from 18 nephrology departments with biopsy-proven anti-GBM disease from 1999 to 2019 was performed. Progression to ESKD in relation to clinical and histological variables was evaluated.ResultsCreatinine at admission was 8.6 (± 4) mg/dL and 61 patients (84.7%) required dialysis. Sixty-five patients (90.3%) underwent plasma exchange. Twenty-two patients (30.6%) presented pulmonary hemorrhage. Kidney survival was worse in patients with creatinine levels > 4.7 mg/dL (3 vs. 44% p < 0.01) and in patients with > 50% crescents (6 vs. 49%; p = 0.03). Dialysis dependence at admission and creatinine levels > 4.7 mg/dL remained independent significant predictors of ESKD in the multivariable analysis [HR (hazard ratio) 3.13 (1.25–7.84); HR 3 (1.01–9.14); p < 0.01]. The discrimination value for a creatinine level > 4.7 mg/dL and 50.5% crescents had an area under the curve (AUC) of 0.9 (95% CI 0.82–0.97; p < 0.001) and 0.77 (95% CI 0.56–0.98; p = 0.008), respectively. Kidney survival at 1 and 2 years was 13.5 and 11%, respectively. Patient survival at 5 years was 81%.ConclusionIn real life, patients with severe anti-GBM disease (creatinine > 4.7 mg/dL and > 50% crescents) remained with devastating renal prognosis despite plasma exchange and immunosuppressive treatment. New therapies for the treatment of this rare renal disease are urgently needed.

Immunity in the balance: Fatal disseminated adenovirus infection in a patient undergoing plasma exchange and immunosuppressive chemotherapy for anti‐glomerular basement membrane disease

“…This mortality historically approached 90%, 17 though contemporary estimates range from 8 to 20% at 1 year. 10,14,18 Importantly, some studies have suggested that patients with both ANCA and anti-GBM antibodies may be at higher risk of severe disease, and similar to the patient described here, this "double-positivity" may contribute to worse outcomes. [19][20][21] Nonetheless, we believe one consideration that warrants revisiting is the recommended frequency of TPE.…”

“…However, we suggest that aggressive therapy for those that fall into the former group should be considered in the context of the individual patient, as the considerable immunosuppression undoubtedly contributes to mortality in this condition. This mortality historically approached 90%, 17 though contemporary estimates range from 8 to 20% at 1 year 10,14,18 . Importantly, some studies have suggested that patients with both ANCA and anti‐GBM antibodies may be at higher risk of severe disease, and similar to the patient described here, this “double‐positivity” may contribute to worse outcomes 19‐21 .…”

Epidemiology and clinical characteristics of biopsy-confirmed adult-onset IgA vasculitis in southern Sweden

“…For comparison, kidney survival at 1 year after biopsy-confirmed anti-glomerular basement membrane disease may be as low as 13.5%. 28 A 30-year follow-up study of ANCA-associated glomerulonephritis reported an estimated 5-year renal survival of only 54%, not death-censored and as many as 14% of patients were on dialysis at time of the renal biopsy. 29 The same study also showed an improvement over the years, and suggested earlier diagnosis and better treatment as possible explanations.…”

Systemic vasculitis involving the kidney: the nephropathologist’s point of view

“…The formation of crescents in the absence of significant endocapillary/mesangial hypercellularity at LM is the histopathological hallmark of anti-GBM disease 59 . According to a large biopsy series, crescents are present in up to 95% of kidney biopsies with > 50% of glomeruli affected in the majority, and the degree of renal impairment at presentation correlating with the proportion of affected glomeruli 60 . Crescents are usually uniform and temporally homogeneous, showing the same stage of activity and chronicity, conversely to what happens in AAV showing mixture of cellular, fibrocellular, and fibrous crescents of varying ages and activity levels 61 .…”