During acute AIP attacks, high levels seen for 2 compounds in urine: Study
Buildup may predict worse outcomes for porphyria patients
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Among people with acute intermittent porphyria (AIP), high levels of two compounds in urine are linked to increased odds of occasional or recurrent attacks, with levels of one, called aminolevulinic acid or ALA, also tied to a greater likelihood of hospitalization.
That’s according to the findings of a new study by an international team of researchers who sought to “describe disease burden across all clinical AIP states.”
The team found that, for those with AIP, living with the genetic disease can range from having no symptoms at all to experiencing acute attacks, typically marked by severe abdominal pain as well as gastrointestinal issues and urinary problems. Such attacks, whether occasional or recurrent, led to reduced work capacity for many AIP patients, limiting some to marginal tasks and leaving others unable to hold any jobs, resulting in unemployment, the data showed.
Nearly one-third of the more than 200 adults whose data were reported in the European Porphyria Registry and used in this study were admitted to the hospital for acute attacks, the team noted.
In a “Key Findings” section, the researchers wrote that the study’s results “can guide risk assessment, follow-up and counselling strategies for patients with AIP.”
The study, “Clinical Characteristics and Outcomes of Acute Intermittent Porphyria: Insights from the European Porphyria Registry,” was published in the journal Liver International.
With porphyria, the body cannot properly produce part of hemoglobin — the protein that carries oxygen in red blood cells — from compounds called porphyrins. As a result, porphyrins and their precursors build up in the body to toxic levels. Some patients never develop symptoms, while others have acute attacks, which are sudden episodes of severe symptoms.
Researchers note need to ID AIP patients at higher risk
AIP is the most common form of acute porphyrias, characterized by sudden and usually severe attacks in which symptoms develop over hours to days, and can last for days to weeks.
“The natural history of AIP varies greatly; however, there is limited knowledge on how to identify individuals at risk of developing more severe disease states and long-term complications,” the researchers wrote.
That information gap led the team to look at patients across Europe, hoping to better understand these different disease patterns.
Their study involved 239 adults diagnosed with AIP who were not treated with Givlaari (givosiran), a medication approved to treat this and other types of acute porphyria. The data was recorded in the patient registry for the years 2012 to 2018, the researchers noted.
The patients were grouped into five categories: individuals with occasional attacks; those with frequent, or recurrent, attacks; patients in remission, meaning they had no symptoms after treatment; individuals with signs but no symptoms of AIP; and those at risk but with no signs of disease.
High ALA levels linked to greater likelihood of hospitalization
On average, patients with occasional or recurrent attacks were younger. Most individuals who had experienced symptoms at some point, including those in remission, reported a family history of AIP. For many patients with recurrent attacks (61%) or occasional attacks (47%), work capacity was reduced, limited to marginal tasks, or not possible at all.
In addition to ALA, which is the first compound in the pathway for producing porphyrins, the researchers also measured porphobilinogen (PBG), another precursor of porphyrins. During acute attacks, patients had significantly higher levels of both ALA and PBG in urine compared with when they were not having attacks.
During the study period, 72 patients were admitted to the hospital for acute attacks, the data showed. Higher levels of ALA in urine were more strongly associated with hospitalization than PBG.
Specifically, those with higher levels of ALA in urine were more likely to be admitted, with each unit increase linked to a 42% jump in the odds when accounting for age and sex. This held true when also excluding patients with signs but no symptoms of AIP and those at risk for the disease.
Recurrent attacks were more likely in patients with high levels of PBG in urine — at least 10 times as high as the upper reference limit — and less likely in those with a known family history at diagnosis. This may suggest that patients diagnosed earlier through family screening are more likely to receive timely treatment, according to the researchers.
“Patients with a family history may benefit from earlier recognition, faster diagnosis and care from providers familiar with managing AIP within the family,” the researchers wrote.
Conversely, “absence of a family history of AIP … may lead to delayed diagnosis and treatment due to a reduced awareness of the condition, with a risk of prolonged exposure to precipitating factors,” the team noted.
Patients with recurrent attacks were seven times more likely than those not experiencing attacks to have impaired work capacity or to be unemployed. That risk was fivefold higher for those requiring treatment with heme, which reduces the body’s need to produce porphyrins during acute episodes.
Long-term issues seen for all AIP patients
Long-term complications such as high blood pressure, chronic kidney disease, and liver cancer were observed across all groups.
Indeed, “AIP’s impact … was evident” in many aspects of patients’ lives, the researchers noted.
“These findings identify factors associated with more severe disease states and outcomes which should be explored further,” the team concluded, while also noting the importance of monitoring patients closely, even those without symptoms of AIP, because long-term complications can still occur.
