Plasma Exchange Risk: Lower for Kidney Failure, Higher for Infection

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Adding plasma exchange to standard treatment reduces the risk of kidney failure after one year, but does not improve survival in people with ANCA-associated vasculitis (AAV), a review study reports.

Plasma exchange was also associated with an increased risk of serious infections — a previously unrecognized effect that may explain the lack of a significant survival benefit, the researchers noted.

These findings, highlighting a relevant and complex trade-off between efficacy and safety, may help inform treatment decisions in this patient population.

The review study, “The effects of plasma exchange in patients with ANCA-associated vasculitis: an updated systematic review and meta-analysis,” was published in The BMJ.

AAV is characterized by inflammation and destruction of small blood vessels due to the production of antibodies called anti-neutrophil cytoplasmic autoantibodies (ANCAs).

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While standard treatment with immunosuppressive therapy and glucocorticoids “improve the outcomes of patients with AAV, they remain at high risk of death, end stage kidney disease (ESKD), and serious infections, particularly in the first year of treatment,” the researchers wrote.

ESKD, or kidney failure, happens when kidney function is lost to the point it can no longer sustain the body’s needs. Patients in this stage require frequent dialysis or a kidney transplant.

Plasma exchange involves removing and replacing a person’s plasma – the liquid portion of blood that contains water, salts, and proteins such as antibodies. Since this can remove ANCAs, it’s been used for decades in AAV patients to try to reduce small blood vessel inflammation and organ damage.

“However, the removal of antibodies, as well as the use of blood products and the potential need for central venous access [placement of a catheter in a large vein], may also increase the risk of harms, particularly serious infections, the most common cause of death for patients with AAV,” the researchers wrote.

An international team of researchers sought to better understand the potential benefits and risks of plasma exchange for AAV patients.

They systematically reviewed published studies up to July 2020 reporting at least one-year results from randomized controlled trials on plasma exchange in people with AAV or a similar condition, called rapidly progressive glomerulonephritis.

Nine trials — covering 1,060 patients followed for a median of three years — were analyzed.

Date of publication ranged from 1980 to 2020, and the trials included between 14 and 704 patients. Participants were randomly assigned to receive either plasma exchange (with varying regimens), in addition to standard therapy, or standard treatment alone (the control group).

The meta-analysis’ goals were to assess changes in the rates of all-cause mortality and kidney failure (reported in nine trials), serious infections (seven studies), other serious side effects (four trials), relapse (three trials), and remission and quality of life (one study each).

Results showed that all-cause mortality rates at both one year and at longer term were similar between patients in the control group and those given additional plasma exchange.

This lack of significant group differences in terms of survival were observed regardless of kidney function at treatment start (baseline) and the presence or absence of pulmonary hemorrhage, a potentially life-threatening condition wherein blood builds up in the lungs.

Plasma exchange was associated with a 38% reduced risk of kidney failure at one year, irrespective of baseline kidney function. There was also a trend toward benefits in the long term.

Patients at high risk of kidney failure showed stronger risk reductions than low-risk patients (16% vs. 0.08%).

While this brought patients some benefits, researchers found that plasma exchange-treated patients had a 27% greater risk of serious infections at one year and 13% at longer-term follow-up.

The effects of plasma exchange in the other outcomes “were uncertain or considered unimportant to patients,” the researchers wrote.

These findings highlight that plasma exchange “has no important effect on mortality, reduces the 12-month risk of ESKD, but increases the risk of serious infections,” in people with AAV, the research team wrote.

“The discordant effects of PLEX [plasma exchange] on ESKD compared with all-cause mortality noted in previous trials and reviews, and attributed to random error, are now more precisely estimated and a potential explanation has become evident — a previously unidentified, concomitant increase in the risk of serious infection,” they added.

The data also suggest that the treatment effects on both kidney failure and serious infection risks “diminish over time,” further emphasizing “the complicated trade-off between ESKD and serious infections,” the researchers wrote.

These findings are expected to “help healthcare providers, patients, and family members engage in shared decision making” regarding treatment for AAV, they added.

Among the study’s limitations, the researchers noted the moderate degree of variability across studies, including potentially different diagnoses, distinct plasma exchange regimens, and different therapies within standard care.