Males Not at Higher Risk for Kidney Failure, Death Due to AAV

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Males are not at a greater risk than females of experiencing kidney failure or death due to ANCA-associated vasculitis (AAV), regardless of the kind of kidney damage they have, a study found.

These new findings counter the results of a 2018 study that had reported an increased risk of advanced kidney disease among male Norwegian patients with AAV.

“In our international, multi-centre study, we did not find a significant sex-specific difference in … outcomes,” the researchers wrote, contrasting their results with those of the earlier study.

“There was no difference between males and females” in kidney failure or death, they wrote.

The study, “A cohort study to investigate sex-specific differences in ANCA-associated glomerulonephritis outcomes,” was published in Scientific Reports.

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AAV, a group of autoimmune diseases, is caused by an abnormal immune response against the small blood vessels in the body, leading to inflammation and damage.

When inflammation hits the kidneys, it may injure the tiny clusters of looping blood vessels — known as glomeruli — responsible for filtering and removing waste products and extra water out the body. As a result, the kidneys may stop working properly.

A previous study, from Norway, had found that males may be more than twice as likely as females to develop end-stage kidney disease related to AAV. Of note, end-stage kidney disease occurs when loss of function reaches an advanced state, and the kidneys can no longer function on their own.

That study had used data collected between 1991 and 2012, when oral cyclophosphamide — an immunosuppressive medicine — was the standard of care. The researchers at that time had hypothesized that the gender difference they found could be attributed to “a higher effective immunosuppression dose in women, due to lower lean body mass.”

Now, to test this idea, a team in Ireland examined the medical records of 332 patients who were either part of the Irish Rare Kidney Disease Registry or were followed at the Royal Free Hospital in London, in the U.K., between 2012 and 2020. The patients were mainly Caucasian (92.2%) and had a mean age of 62; a majority (58%) were male.

The most common AAV subtype was microscopic polyangiitis (65%), followed granulomatosis with polyangiitis (28%) and eosinophilic granulomatosis with polyangiitis (2%).  The remaining 16 patients (5%) had unclassified AAV.

About 60% of patients had anti-neutrophil cytoplasmic autoantibodies against the protein myeloperoxidase, which are a known risk factor for end-stage kidney disease. These antibodies were significantly more common in females, who also were older (65.0 vs. 60.7 years) and weighed less. The women also had worse kidney function than men at the beginning of follow-up.

Over a median follow-up time of 40.2 months, 73 patients (22%) developed end-stage kidney disease — defined as a need for kidney replacement therapy, including dialysis or kidney transplant — and 47 (14%) died.

The percentage of patients who were still alive at one year was 84%. At five years, it was 79%. These percentages were not significantly different in males and females.

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Although there were more males than females with end-stage kidney disease in the first half-year after diagnosis, males were not at an increased risk of developing kidney failure, even after accounting for factors such as age, ANCA antibodies, initial kidney function, and kind of kidney damage. A composite measure of time to either end-stage kidney disease or death also revealed no increased risk for males.

“This observation probably reflects the improvement in overall AAV care over the last few decades, which may have eliminated the sex-specific discrepancy in renal outcome seen prior to 2012,” the researchers wrote.

To test if the previously observed differences could be attributed to the use of standardized doses of immunosuppressive therapy, the researchers examined weight-based doses of immunosuppressive treatments.

They found no differences between sexes in the cumulative dose per kilogram for oral cyclophosphamide, intravenous (into-the-vein) cyclophosphamide, or rituximab.

“We found no evidence to support that any difference is due to sex-dependent variation in cumulative immunosuppression dosing,” the researchers concluded. “On the contrary, we found that weight-based dosing regimens are now standard practice in Ireland, and treatment intensity does not vary by sex.”