Plasma exchange improves early kidney recovery in AAV: Study
Early kidney function improves when treatment added to immunosuppressants
Plasma exchange added to standard immunosuppressive treatments helps improve early kidney function in people with ANCA-associated vasculitis (AAV) who have glomerulonephritis, an inflammation of the kidneys’ filtering units, reducing the risk of kidney failure within the first year.
That’s according to a new analysis of data from the PEXIVAS Phase 3 trial (NCT00987389).
No differences in kidney function outcomes were found comparing reduced-dose with standard-dose glucocorticoids. “The use of reduced-dose [glucocorticoids] does not negatively impact kidney function at any time point in the first year,” the researchers wrote. Overall, the findings suggest that “rapidly effective therapies beyond early and prompt diagnosis may improve long-term outcomes,” they wrote.
The study, “The effects of plasma exchange and glucocorticoids on early kidney function among patients with ANCA-associated vasculitis in the PEXIVAS trial” was published in Kidney International.
AAV refers to a group of autoimmune diseases marked by inflammation and damage to small blood vessels, typically driven by the production of self-reactive antibodies known as antineutrophil cytoplasmic antibodies (ANCAs). The most common ANCAs target one of two enzymes: PR3 or myeloperoxidase (MPO).
Therapeutic approaches
Symptoms of AAV vary depending on the organs affected. Commonly involved systems include the kidneys, lungs, upper respiratory tract, skin, and nervous system.
Immunosuppressive therapies are among the main strategies to achieve disease remission. Common treatments include cyclophosphamide, rituximab (marketed as Rituxan in the U.S., with biosimilars available), and glucocorticoids.
An additional therapeutic approach is plasma exchange, or PLEX, a blood-cleaning procedure that removes and replaces plasma, the liquid portion of blood containing antibodies, water, and salts. While PLEX has been used in AAV cases for decades, it remains to be determined whether the approach may affect the rate of kidney failure and whether its effects on kidney function change over time.
An international team of researchers looked into kidney function changes over one year, and compared low-dose and standard glucocorticoid regimens.
The PEXIVAS trial involved participants with severe new or relapsing AAV and pulmonary bleeding and/or kidney disease.
A total of 691 patients had ANCA-associated glomerulonephritis, and about half of them underwent PLEX. Their median age was 65. The group was also divided into patients receiving a reduced dose (346 patients) and standard dose of glucocorticoids (345 patients).
The main goals of the analysis included changes in estimated glomerular filtration rate (eGFR) within the first year of treatment, and recovery of kidney function, which was defined as an eGFR increase of at least 15 ml per minute per 1.73 square meters after four, 26, and 52 weeks. eGFR is a standard assessment of kidney function and kidney disease.
Kidney function recovery
Mean eGFR was similar in the PLEX and no-PLEX groups at the start of the study. The mean improvements in eGFR at two, four, and eight weeks after initiation of therapy were greater in the PLEX group than in the no-PLEX group. No differences were observed at later intervals.
Participants given PLEX were significantly more likely to recover kidney function after four and 52 weeks than their no-PLEX counterparts. In contrast, the risk of an eGFR decline of at least 5 ml/min per 1.73 m2 did not differ between the two groups at week four.
“In this analysis, we found that the addition of PLEX to standard immunosuppressive therapy increased early recovery of kidney function,” the investigators wrote.
Results showed that a greater increase in eGFR at week four was significantly associated with a lower risk of end-stage kidney disease at the end of the analysis. Having a sustained low eGFR showed the opposite correlation, a higher risk of end-stage kidney disease.
As for the comparison between reduced versus standard-dose glucocorticoid regimens, no significant differences were seen in eGFR change from baseline nor in recovery of kidney function.
Improvement in eGFR was higher in patients with ANCAs against PR3 compared with those with antibodies against MPO from week four. This was accompanied by a significantly higher kidney function recovery across all time points in the PR3-positive group. These patients also had a lower risk for low sustained eGFR.
“These findings might help to individualize treatment decisions when treating patients with AAV with kidney involvement and might improve longer-term kidney outcomes,” the researchers wrote.
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