Severe Infection in Anti-Glomerular Basement Membrane Disease: A Retrospective Multicenter French Study

Abstract

In patients presenting with anti-glomerular basement membrane (GBM) disease with advanced isolated kidney involvement, the benefit of intensive therapy remains controversial due to adverse events, particularly infection. We aim to describe the burden of severe infections (SI) (requiring hospitalization or intravenous antibiotics) and identify predictive factors of SI in a large cohort of patients with anti-GBM disease. Among the 201 patients (median [IQR] age, 53 [30–71] years) included, 74 had pulmonary involvement and 127 isolated glomerulonephritis. A total of 161 SI occurred in 116 patients during the first year after diagnosis. These infections occurred during the early stage of care (median [IQR] time, 13 [8–19] days after diagnosis) with mainly pulmonary (45%), catheter-associated bacteremia (22%) and urinary tract (21%) infections. In multivariable analysis, positive ANCA (HR [95% CI] 1.62 [1.07−2.44]; p = 0.02) and age at diagnosis (HR [95% CI] 1.10 [1.00–1.21]; p = 0.047) remained independently associated with SI. Age-adjusted severe infection during the first three months was associated with an increased three-year mortality rate (HR [95% CI] 3.13 [1.24–7.88]; p = 0.01). Thus, SI is a common early complication in anti-GBM disease, particularly in the elderly and those with positive anti-neutrophil cytoplasmic antibodies (ANCA). No significant association was observed between immunosuppressive strategy and occurrence of SI.

Disease activity prediction and prognosis of anti-GBM nephritis based on T lymphocyte subset ratios

“…23 In our study, the incidence of lung infection was 31%, which was lower than Caillard et al's study. 23 There's no serious infection reported in the course of disease, besides at disease onset or after aggressive therapy. It also has been reported that for patients with clinical features, such as high SCr, oliguria, or anuria, a delayed diagnosis results in a poor renal prognosis.…”

“…The 5-year renal survival rate in this study was 18.5%, which was lower than that reported by Levy et al 22 but in line with that by Cui et al 7 Severe infection is a common early complication and very important for prognosis in anti-GBM disease. 23 In our study, the incidence of lung infection was 31%, which was lower than Caillard et al's study. 23 There's no serious infection reported in the course of disease, besides at disease onset or after aggressive therapy.…”

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

“…This predisposed the patient to unusual and opportunistic infections, in this case disseminated adenoviral disease manifesting as necrotizing pneumonia and hepatitis, ultimately inducing multi‐organ collapse. The consequence of infection in the setting of therapy for anti‐GBM disease is not unusual, as studies suggest more than half of patients may develop severe infections, typically with Gram‐positive (eg, Staphylococcus aureus ) or Gram‐negative (eg, Escherichia coli ) bacteria 9,10 . However, disseminated disease due to adenovirus is significantly less common, as disseminated adenoviral infections are uncommon outside of the transplant population 11 .…”

“…Thus, the patient theoretically could have been at greater risk for disseminated adenovirus given her asplenia. Additionally, a large retrospective, multicenter study found that a positive ANCA was independently associated with severe infection in patients with anti‐GBM disease, 9 suggesting underlying disease factors likely influence the propensity for development of infections. Other factors that could potentially increase a patient's risk of developing infection during therapy, such as HIV/AIDS and various congenital or acquired immunodeficiencies, should be taken into consideration when treating these patients.…”

Pneumocystis pneumonia secondary to intensive immunosuppression treatment for anti-GBM disease complicated with IgA nephropathy

“…Severe infections were frequent during the early phase of the disease and were associated with substantial morbidity and a reduced 3-year survival rate. The lungs, the urinary tract, and catheters were the main sites of infection [21] . Pneumocystis pneumonia (PCP) is a severe opportunistic pulmonary infection of pneumocystis jiroveci in immunocompromised patients, which mortality is as high as 29% to 50% [22,23] .…”