Kidney tissue patterns may influence treatment response in AAV
Study finds similar outcomes, with differences in some biopsy groups
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In most people with kidney damage due to ANCA-associated vasculitis (AAV), outcomes from initial treatment to bring the disease under control are similar across commonly used immunosuppressive therapies, including cyclophosphamide and rituximab.
That’s according to a study analyzing data from hundreds of patients at several European centers.
Kidney biopsy patterns may affect treatment response
However, patients with a specific pattern of tissue damage seen on kidney biopsy, known as the crescentic pattern, may have better outcomes from initial induction treatment with cyclophosphamide than from rituximab, the data showed.
“These findings, if replicated, may provide a solid basis to use kidney [tissue features] as a guide to personalize immunosuppressive treatment,” the researchers wrote.
The study, “Kidney Outcomes in ANCA-Glomerulonephritis According to Induction Immunosuppression and Histopathology,” was published in Kidney International Reports.
AAV is a group of rare disorders marked by inflammation and damage of small blood vessels. It is often associated with the production of self-reactive antibodies called ANCAs. Glomerulonephritis — inflammation of the glomeruli, the kidneys’ filtering units — is a common complication of AAV.
In 2010, scientists proposed a classification system for ANCA-related glomerulonephritis based on biopsy findings, meaning analyses of kidney tissue under the microscope. The system divides ANCA-related kidney damage into four classes based on glomerular injury.
These classes are focal, where most glomeruli look normal; sclerotic, where most glomeruli are scarred; crescentic, where most have cellular crescents — abnormal cell growth in response to damage; and mixed, which includes patients who do not fit neatly into the other categories.
How AAV is treated to bring the disease under control
The goal of initial AAV treatment is to induce remission, meaning to bring the disease under control so symptoms and disease activity are reduced or absent. This initial, or induction, treatment typically involves immunosuppressive medications such as cyclophosphamide and rituximab, along with glucocorticoids, which help reduce inflammation and immune activity.
Cyclophosphamide — available as Cytoxan and others, with generics available — is used off-label in AAV. Rituximab, which is approved for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the two most common types of AAV, is sold as Rituxan in the U.S. and MabThera in Europe, with biosimilars available.
“Although [rituximab] has become established as first line treatment for induction of remission in most scenarios, it remains unclear whether [cyclophosphamide] may remain preferable in some specific contexts,” the researchers wrote. “Previous studies on kidney outcomes did not examine whether histopathology [disease-associated tissue] lesions may influence the efficacy of different immunosuppressive therapies.”
Study examines treatment response across biopsy groups
To address this question, an international team of researchers across Europe examined whether responses to induction treatment with cyclophosphamide or rituximab differ across the different kidney biopsy classes in AAV.
The study included 304 GPA and MPA patients who had kidney involvement and available biopsy data, treated at 11 European expert centers. Of the kidney biopsies, 23.4% were classified as focal, 11.8% as sclerotic, 31.6% as crescentic, and 33.2% as mixed.
More than half of the participants (58.6%) received cyclophosphamide alone as induction therapy, while 17.1% received rituximab alone, and 24.3% received both medications. Most were also treated with glucocorticoids.
The researchers used statistical analyses to compare how many patients in each treatment group showed recovery in kidney function within six months of starting therapy.
Among patients in the crescentic class, those treated with rituximab alone were significantly less likely, by about 77%, to achieve recovery of kidney function than those treated with cyclophosphamide alone. They were also significantly more likely to experience kidney failure.
For patients in the other biopsy classes, outcomes were generally similar regardless of which induction treatment was used. The researchers noted the findings support previous research suggesting that biopsy-based classifications can help predict outcomes.
Some biopsy patterns linked to worse kidney outcomes
For example, regardless of the induction treatment used, patients in the sclerotic class generally showed the least improvement in kidney function and the highest risk of kidney failure, a pattern that has been reported in previous studies.
The scientists stressed that “although these results are intriguing, they should be interpreted with great caution,” noting that this analysis was exploratory and had several limitations. For example, many patients received different combinations of medications beyond rituximab and cyclophosphamide.
The researchers said further studies are needed to better understand how biopsy findings can be used to guide treatment and improve patient outcomes.
“Future work will be needed to better understand how to personalize treatment based on kidney histopathology and, ideally, other noninvasive biomarkers and clinical features,” the team wrote.
