ACE Inhibitors Raise Risk of Renal Crisis in Some SSc Patients, Study Says

Systemic sclerosis (SSc) patients with elevated protein in their urine (proteinuria) who are using angiotensin-converting enzyme (ACE) inhibitors (ACEi) are at higher risk of developing scleroderma renal crisis (SRC), a retrospective study shows.

The study, “Systemic sclerosis mediations and risk of scleroderma renal crisis,” was published in the journal BMC Nephrology.

SRC is a serious complication of SSc associated with high mortality. The risk of developing SRC is linked to several factors, but evidence suggests that medications commonly used in SSc may also pose a risk. These include prednisone, a corticosteroid that reduces inflammation, and ACE inhibitors (ACEi).

In SSc, blood levels of the hormone angiotensin 2 are usually higher than normal, which can contribute to renal crisis, generally preceded by a sudden increase in blood pressure. While ACEi are expected to improve SSc patients’ kidney function, studies so far have found no beneficial effect of ACEi on preventing SRC.

Researchers therefore investigated the effects of common SSc therapies on the risk of developing SRC.

The team conducted a retrospective analysis of electronic medical records from a U.S. military database, selecting cases between 2005 and 2016. From 749 potential SSc patients, they evaluated 353 cases with a confirmed diagnosis of SSc, of which 31 patients ended up developing SRC. Researchers then analyzed these patients’ medications, including ACEi, and their potential correlation with SRC development.

Results showed that ACEi use was associated with an increased risk of SRC, and that older and African-American SSc patients were more likely to develop SRC. This group also had more cardiac and pulmonary manifestations, such as pulmonary hypertension.

The majority of SRC cases within five years after SSc diagnosis had been prescribed ACEi (77%), compared to those without SRC who also received the therapy (33%).

Importantly, ACEi therapy was identified as a significant predictor for SRC development, specifically in patients with proteinuria (excessive protein in urine).

“Our study showed that ACEi use was associated with SRC in SSc patients with proteinuria, but not those without proteinuria,” researchers said.

Researchers also found that more than half of SRC cases (61%) received almost double the ACEi dose compared with controls, and reached the treatment maximum dose more often.

Regarding other common therapies used in SSc, including nasal fluticasone and oral non-steroidal anti-inflammatory drugs (NSAIDs), researchers found that these “seem not to add additional risk for developing SRC.”

The team concluded that “ACEi use at SSC diagnosis was associated with an increased risk for SRC,” and suggested that “SSC patients that require ACEi should be more closely monitored for SRC.”