Early treatment response tied to better outcomes in adults with TMA

Rapid response to treatment was associated with better outcomes among adults with biopsy-confirmed thrombotic microangiopathy (TMA), a group of conditions that includes atypical hemolytic uremic syndrome (aHUS), a small study suggested.

“These findings highlight the potential importance of timely recognition and close monitoring of treatment response in patients with biopsy-proven TMA,” the researchers wrote in the study, “Clinicopathologic spectrum and prognostic determinants in biopsy-proven thrombotic microangiopathy,” published in Medicina Clínica.

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aHUS was the most common cause of TMA in the study

aHUS is a type of TMA, a group of diseases marked by small blood clots that block blood flow and can damage organs, especially the kidneys.

TMA can be triggered by several conditions, including pregnancy complications, autoimmune diseases, severe high blood pressure and certain medications. aHUS, however, is caused by abnormal activation of the complement cascade, part of the immune system.

Because TMA can vary widely from one person to another, predicting outcomes can be challenging.

Researchers therefore aimed to describe the causes and outcomes of biopsy-confirmed kidney TMA at a single medical center in Turkey. They also examined whether early treatment response was associated with later outcomes.

In the retrospective study, researchers reviewed 1,432 people who underwent kidney biopsies. The analysis included 46 adults with biopsy-confirmed TMA and complete medical records; about 70% were women.

aHUS was the most common identified cause of TMA, accounting for 37% of cases, followed by pregnancy-related TMA at 26.1%. Other causes included autoimmune diseases such as lupus or antiphospholipid syndrome, certain medications, severe high blood pressure, transplant rejection, and other rare conditions.

By the end of follow-up, just under half of the patients, 20 of 46, or 43.5%, had experienced a serious outcome. Thirteen progressed to kidney failure requiring long-term dialysis, and seven died.

Acute kidney injury at diagnosis was more common among patients with an adverse outcome than among those with a more favorable outcome (90% vs. 57.7%). Patients with adverse outcomes also had higher serum creatinine levels and lower estimated glomerular filtration rate (eGFR) values, both signs of poorer kidney function.

Pregnancy-related TMA was significantly less common among those with adverse outcomes than among those with favorable outcomes (10% vs. 38.5%).

Early treatment response linked to better outcomes

Early treatment response was much more common among patients with favorable outcomes than among those with adverse outcomes (80.8% vs. 25%).

After accounting for other influencing factors in an exploratory statistical analysis, early treatment response remained strongly associated with better outcomes and about 85% lower odds of kidney failure or death. This finding came from the full TMA cohort and was not established specifically in the aHUS subgroup.

When kidney biopsy tissue was examined, researchers found small clots in the kidney’s blood vessels in 56.5% of cases, with similar rates among patients with favorable and adverse outcomes.

Clots in the small arteries, called arterioles, were more common among patients with adverse outcomes, but the difference was not statistically significant and may have been due to chance.

Genetic testing was performed in 10 patients, and complement-related gene variants were found in five. The affected genes included CFH, CFB, MCP, CFHR5 and PLG.

The authors noted several limitations, including the study’s small size, retrospective design and single-center setting. Also, not all patients underwent comprehensive genetic testing, which may mean some complement-related abnormalities went undetected.

“Early-onset treatment response was associated with more favorable outcomes and may represent a dynamic marker of the short-term disease trajectory,” the researchers concluded. “These findings should be interpreted with caution and require validation in larger, prospective multicenter studies.”