Abstract
Background and Aims
Infections remain an important contributor to the morbidity and mortality of immunosuppressive (IS) therapy in aggressive glomerulonephritis. We sought to investigate the infection profile and associated risk factors in a compiled cohort of patients with lupus nephritis (LN), cryoglobulinemic vasculitis (CryoVas) and ANCA-associated vasculitis (AAV) treated with induction and maintenance IS regimens.
Method
A total of 162 patients (101 with LN, 24 with CryoVas and 37 with AAV) were retrospectively reviewed for any infection that occurred from initiation of induction therapy. Infections were graded (1-5) according to the Common Terminology Criteria for Adverse Events. Infection site and type of microorganism were also recorded. Univariate and multivariate Cox proportional hazard regression analysis were performed in order to identify independent risk factors for infection.
Results
Eighty-two patients (50.6%) had at least one infection with a total 179 episodes of infection occurring during a median follow-up of 12 months (IQR:4-36.25 months). The majority of patients (64 of 82) had infections during the first 24 months since IS treatment initiation with a 24-month infection-free rate of 55%. The most common site was lung infection (in 32.7% of patients), while 39.5% of patients had bacterial infections (1.8% with Mycobacterium tuberculosis). 36.7% of patients had severe infections (grade 3 or higher) with 4.4% of infection-related deaths (8 patients). The most common induction regimen was cyclophosphamide in addition to corticosteroids (62%), while 43% received either mycophenolate mofetil or azathioprine in addition to corticosteroids as a maintenance regimen. In univariate Cox regression analysis, chronic obstructive pulmonary disease (HR 3.91; 95% CI, 1.76-8.68, p=0.001), pulmonary involvement in the setting of systemic disease (HR 2.35; 95% CI, 1.26-4.37, p=0.007), pulse methylprednisolone (HR 2.7; 95% CI, 1.7-4.31, p=0.001) and high-dose (≥30 mg/day) oral corticosteroids (HR 3.38; 95% CI, 2.11-5.43, p=0.001) were risk factors for infection. In multivariate Cox regression analysis, high-dose oral corticosteroids (HR 2.67; 95% CI, 1.5-4.76, p=0.001) remained an independent predictor of infection risk. Of the risk factors associated with severe infections (grade 3 or higher), in univariate analysis we identified pulmonary involvement in the setting of systemic disease (HR 3.65; 95% CI, 1.72-7.77, p=0.001), pulse methylprednisolone (HR 3.56; 95% CI, 1.7-7.3, p=0.001), high-dose (≥30 mg/day) oral corticosteroids (HR 3.56; 95% CI, 1.77-7.16, p=0.001), estimated GFR (HR 0.98; 95% CI, 0.98-0.99, p=0.01) and AAV (by comparison to CryoVas and LN) (HR 2.81; 95% CI, 1.39-5.66, p=0.004) as risk factors for infection. After multivariate adjustment, pulmonary involvement in the setting of systemic disease (HR 2.38; 95% CI, 1.01-5.73, p=0.05) and high-dose oral corticosteroids (HR 2.44; 95% CI, 1.04-5.72, p=0.04) were identified as independent predictors of infection risk.
Conclusion
Infections occur frequently with current immunosuppressive regimens in aggressive glomerulonephritis. In addition to pulmonary involvement in the setting of systemic disease, a high dose corticosteroid regimen was the most significant risk factor for infection.
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