Blood GDF15 levels at diagnosis seen as predicting outcomes
Associations also found with AAV symptoms and activity in South Korean study
Blood levels of a signaling molecule called growth differentiation factor 15 (GDF15) at diagnosis may help predict poor outcomes, including kidney failure and death, in people with ANCA-associated vasculitis (AAV), according to a study in South Korea.
Data also showed that GDF15 levels were significantly associated with AAV symptoms and activity, assessed using the standard Birmingham Vasculitis Activity Score (BVAS).
Future studies “including more patients with AAV … through multicentre or multinational cooperation and serial measurements of circulating GDF15 will provide more reliable and dynamic information on its clinical usefulness in patients with AAV,” the researchers wrote.
The study, “Circulating GDF15 May Estimate Vasculitis Activity and Predict Poor Outcomes During the Disease Course of ANCA-Associated Vasculitis,” was published in the Journal of Clinical Medicine.
AAV is a group of autoimmune diseases characterized by inflammation and damage to small blood vessels, most commonly the lungs and kidneys. The disease is typically caused by ANCAs, self-reactive antibodies that bind and activate neutrophils, a type of immune cell.
Blood levels of GDF15, known to regulate inflammatory processes, may indicate chronic inflammation and be used as a prognostic factor of chronic inflammatory diseases.
“Therefore, it could be theoretically speculated that circulating GDF15 might have clinical implications not only at diagnosis but also during the disease course of AAV,” the researchers wrote.
The study and its findings
To learn more, the team of researchers in South Korea assessed whether blood GDF15 levels at the time of AAV diagnosis could be used to estimate AAV activity and outcomes during follow-up.
For that, they randomly selected 79 AAV patients who were not on immunosuppressive medications up to one month before their diagnosis and who were enrolled in an observational study at the Severance Hospital in Seoul, South Korea.
Participants had a mean age of 64 years and were most commonly women (59.5%). In terms of AAV types, nearly half had microscopic polyangiitis, 30.4% had granulomatosis with polyangiitis, and 20.3% eosinophilic granulomatosis with polyangiitis.
Additionally, most (57%) had ANCAs against the myeloperoxidase (MPO) enzyme, while 15.2% had ANCAs targeting the proteinase 3 (PR3) enzyme, and about a third (31.6%) had none.
According to the BVAS, patients most commonly had lung symptoms (62%), followed by throat, ear, and nose symptoms (51.9%), and kidney issues (48.1%).
During a follow-up of a little over two years, 7.6% of the patients died, and a quarter (25.3%) developed kidney failure. Nearly all patients received glucocorticoids (98.7%), with the most commonly used immunosuppressive drugs being cyclophosphamide (65.8%) and azathioprine (60.8%).
The researchers found that higher blood GDF15 levels at diagnosis were significantly associated with higher BVAS, indicating more severe disease. Additionally, higher GDF15 levels were significantly associated with older age, high levels of blood cells, C-reactive protein (an inflammation marker), and creatinine (a marker of kidney damage).
In turn, higher blood levels of GDF15 were significantly associated with lower levels of hemoglobin, the protein that carries oxygen in red blood cells, and albumin, a protein whose low levels are a marker of inflammation and kidney damage.
Further analyses indicated that using a cutoff value of GDF15 at 3,350.5 picograms (pg) per mL at diagnosis allowed researchers to discriminate patients with the most severe disease from those with less severe disease with an accuracy of 70.7%.
Specifically, patients with blood GDF15 levels at the cutoff value or higher were significantly more likely to have more severe disease than those with levels below the cutoff (78.6% vs. 24.6%). That corresponded to a 11 times higher risk of having more severe disease.
Similarly, a GDF15 cutoff value of 2,239.5 pg/mL at diagnosis was able to predict death of any cause, or all-cause death, with an accuracy of 74.9%, while a cutoff value of 2,208.5 pg/mL predicted progression to kidney failure with 68.9% accuracy.
Patients with GDF15 levels of 2,239.5 pg/mL or higher were nearly eight times more likely to die from any cause, and those with levels of 2,208.5 pg/mL or higher were about seven times more likely to develop kidney failure.
However, in statistical models adjusted for potential influencing factors, blood GDF15 levels were not independently associated with either all-cause death or kidney failure.
Notably, blood GDF15 levels of at least 2,208.5 pg/mL “showed a tendency toward independent association with progression to ESKD [kidney failure] during the disease course,” the team wrote.
“This study has merit in that this is the first to demonstrate that circulating GDF15 at diagnosis could estimate BVAS and potentially foresee all-cause mortality [and] progression to ESKD [kidney failure] during the disease course in patients with AAV,” the researchers wrote.
They emphasized, however, that larger studies are needed to confirm the predictive potential of blood GDF15 levels in AAV patients.
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