Factors Predicting Serious AAV Infections Found to Vary Over Time

The risk factors that predict serious infections in people with ANCA-associated vasculitis (AAV) vary with time, a study found.

Factors associated with early infection include age and admission to an intensive care unit, whereas kidney function is the most important risk factor for late infections, the investigators said.

The findings were published in Kidney International Reports, in a study titled “Incidence and Temporal Trend in Risk Factors of Severe Infections in ANCA-Glomerulonephritis Patients.”

Infections are a major cause of death among individuals with AAV. Identifying which AAV patients are at the highest risk of infection can help guide treatment decisions, such as the use of preventative (prophylactic) antibiotics.

Prior research has suggested that some factors, like older age, poorer kidney function, and reduced white blood cell count, are predictive of serious infections in people with AAV.

“However, to date, no study has addressed whether risk factors of infection [in AAV patients] vary over time,” the researchers wrote. “Thus, the aim of this study was to analyze time-dependent variations in risk factors for severe infections.”

To that end, investigators at multiple centers in France analyzed data for 168 people with AAV-associated kidney inflammation, called glomerulonephritis. Here, it is referred to as ANCA-GN. The patients’ median age at symptom onset was 68 years, and most (61.9%) were male. ANCAs targeting myeloperoxidase (MPO) were detected in 114 patients (67.9%) while those targeting proteinase 3 (PR3) were found in 52 individuals (31.0%). Two patients were ANCA-negative.

All of the patients had at least three months of follow-up — the median follow-up time was about four years. Over the course of follow-up, 43 of the patients died. Infections accounted for about a third of these deaths.

Overall, 90 of the patients experienced a total of 235 serious infections. Most of the infections (79.6%) were caused by bacteria, and the most commonly affected body part was the lungs, in 40.6% of infections.

“We are able to confirm that severe infections are very common in ANCA-GN patients,” the researchers wrote.

In initial analyses, older age, ICU admission, and the need for kidney replacement therapy — for example, dialysis — at diagnosis were significantly associated with a higher risk of infection at any time. Preventive antibiotic treatment was significantly associated with a lower infection risk at any time.

Then, the researchers analyzed risk factors associated with early infections — those within the first six months of follow-up — or late infections, or those occurring after six months of follow-up.

In multivariate analyses, or examinations that mathematically account for potential confounding factors, the only significantly predictive factors for early infection were older age and ICU admission.

In contrast, for late infections, the only factor that was significant in multivariate analyses was reduced kidney function. Age and preventive antibiotic treatment showed some indications of associations with late infections; however, these did not reach statistical significance.

Of note, different immunosuppressive treatments were not associated with higher or lower infection risks.

“To the best of our knowledge, this study is the first to address the risk factors of infection in ANCA-GN patients by performing a temporal [time-based] trend analysis. The major finding is that risk factors vary over time,” the researchers concluded.

“This suggests that renal [kidney] function becomes the main risk factor for [late] infection, moreso than other classic risk factors, such as age,” they added.

The main limitations of this study are its retrospective and observational design, as well as the lack of vaccination data, according to the researchers.

They also added that, while ICU admissions were predictive of early infections in a statistical sense, “we cannot exclude that infection was in fact the cause of ICU admission at least in some patients.”