Plasma exchange seen to help in scleroderma renal crises

Blood pressure was reduced in patients, but kidneys still impaired

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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Plasma exchange helped reduce high blood pressure linked to scleroderma renal crisis (SRC) — a potentially life-threatening complication marked by abrupt blood pressure changes and acute kidney failure — in patients unresponsive to standard treatment, a case series study reported.

Despite these successes, most patients still had impaired kidney function that required dialysis.

Researchers suggested that plasma exchange works to remove self-reactive antibodies associated with SRC that trigger the narrowing of blood vessels and the elevation of blood pressure.

The case series study, “Intensive receptor blockade and plasma exchange to treat refractory scleroderma renal crisis in patients with agonistic autoantibodies targeting the angiotensin II type 1 and endothelin-1 type A receptors,” was published in the Journal of Scleroderma and Related Disorders.

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Scleroderma, or systemic sclerosis (SSc), is a chronic disease marked by excess scar formation on the skin and potentially the internal organs, including the heart and blood vessels, the lungs, the stomach, and the kidneys.

A scleroderma renal crisis, known as an SRC, occurs in about 5% of cases and is marked by a rapid decline in kidney function and an abrupt rise in blood pressure. Such crises are a life-threatening complication for systemic scleroderma patients.

First-line treatments for SRC are medications like angiotensin-converting enzyme (ACE) inhibitors that help dilate or widen blood vessels and lower blood pressure. They’re also called vasodilators.

Despite the benefits of such treatment, however, many patients require dialysis or, eventually, a kidney transplant.

Studies suggest an increased risk of SRC is related to elevated levels of self-reactive antibodies, or autoantibodies, that target the angiotensin II type 1 receptor (AT1R) and the endothelin-1 type A receptor (ETAR) in blood vessels. These autoantibodies are thought to stimulate receptor activity, which narrows blood vessels and increases blood pressure.

With this in mind, researchers in Germany described how they treated 10 patients with scleroderma renal crisis who had unsuccessfully received ACE inhibitors or AT1R blockers.

When first treated, six patients had moderate to severe high blood pressure, and all had signs of kidney scarring as assessed by biopsy. Overall, the median bloodstream level of anti-AT1R antibodies was 22.1 Units per mL (U/mL), and anti-ETAR levels reached a median of 21.0 U/mL.

The researchers noted that previous reports indicated an anti-AT1R level above 15.8 U/mL was associated with an 11.6 times increase in the risk of SRC. For anti-ETAR, levels above 16.5 U/mL were linked to an eightfold elevated SRC risk.

To reduce the levels of these autoantibodies, plasma exchange was started. This treatment involves removing blood from the body, separating cells from the noncellular part (plasma), then mixing cells with a plasma substitute and infusing them back into the body. The goal of the procedure is to filter out the autoantibodies.

Blood vessel narrowing was addressed with vasodilators, including ACE inhibitors and/or endothelial receptor antagonists and Ventavis (iloprost). Five patients also received intravenous (into-the-vein) immunoglobulins after plasma exchange — a type of treatment intended to normalize a compromised immune system.

Patients were treated with immunosuppressive agents to limit autoantibody production. Treatments were adjusted depending on each patient’s needs, and dialysis was started and stopped as necessary.

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Kidney function recovered in two individuals (patients 2 and 3) and improved in one (patient 1), who still required dialysis after nearly two years. Patient 6 was still undergoing dialysis 20 months, or more than 1.5 years, after SRC onset, which improved urination levels. Meanwhile, patient 7 needed dialysis after two months but was lost to follow-up two months later.

Patient 8 underwent transient or on and off dialysis between seven and 21 months but still had severely impaired kidney function. The remaining patients — 4, 5, 9, and 10 — showed no improved kidney function with treatment. Overall, median dialysis-free survival was 23 months, or nearly two years.

While several different medications were used to treat high blood pressure before plasma exchange, all of these medicines were stopped after the first treatment session. Plasma exchange reduced the median anti-AT1R level from 22.1 to 13.4 U/mL and median anti-ETAR levels from 21.0 to 14.0 U/mL.

The researchers noted that this immediate response to highly elevated blood pressure levels to plasma exchange was best explained by eliminating autoantibodies and their effects on blood vessel narrowing.

This report demonstrates that intensive multimodal therapy … provides a salvage option for patients with refractory [hard-to-treat] scleroderma renal crisis.

Three patients were classified as responders and six as non-responders based on kidney function. The only significant difference between responders and non-responders referred to damage in the inside lining of small blood vessels. Both of these groups had similar levels of autoantibodies before and after treatment.

“This report demonstrates that intensive multimodal therapy taking account of potentially pathogenic [disease-related] antiangiotensin II type 1 receptor and anti-endothelin-1 type A receptor autoantibodies in concert with other vasodilatory interventions provides a salvage option for patients with refractory scleroderma renal crisis,” the researchers wrote.