Calprotectin Blood Levels May Work as Biomarker for Tailoring Maintenance Treatments in AAV Patients

Levels of calprotectin in the blood correlate with markers of disease activity and a worsening in kidney function in ANCA-associated vasculitis patients, researchers in Spain report.

The study, “Calprotectin as a smoldering activity detection tool and renal prognosis biomarker in ANCA associated vasculitis,” was published in the journal PLOS One.

A significant proportion of people with ANCA-associated vasculitis (AAV) eventually show disease symptoms in their kidneys, and are at risk of kidney failure.

These patients are usually treated with immunosuppressants to induce remission, but the duration and dosage of subsequent treatments to maintain remission have not yet been defined. Researchers believe that biomarkers identifying patients at risk of relapse would help in better matching treatment to each patient’s needs.

Calprotectin, a protein produced by neutrophils – immune cells involved in tissue damage in AAV – plays a key role in amplifying inflammation, and has shown promise as a biomarker for certain autoimmune diseases. Its usefulness in AAV, however, is not known.

Researchers aimed to examine calprotectin as a potential biomarker for disease relapse in AAV patients. They included 42 patients and four control in their study.

Among patients, 27 (mean age, 66.1) were in remission and being treated with immunosuppressants, while the other 15 (mean age, 62.9) were in an acute disease phase — 10 had not yet started treatment and five experienced disease worsening. The study’s mean follow-up period was 50.4 months (four years and two months).

Blood and urine levels of calprotectin were measured at study start (baseline) and its end. The presence of blood or proteins in urine (hematuria and proteinuria), C-reactive protein (CRP) levels, and ANCA levels were monitored to assess disease activity.

Researchers found that patients in the acute phase had the highest blood and urine calprotectin levels, followed by those in remission and controls. However, no correlation was seen between the baseline blood and urine calprotectin levels.

During follow-up, levels of calprotectin decreased significantly compared to baseline, indicating that blood calprotectin levels are a good biomarker to monitor disease activity in patients in remission.

No statistically significant association was found between serum calprotectin and glomerular filtration rate — a measure of kidney function — or the impact of the disease on other organs, making it an independent measure, the researchers found.

“We consider that this is essential, given the fact that AAV is a chronic disease that frequently alters GFR, thus consolidating calprotectin as a solid biomarker in AAV,” investigators wrote.

Despite its promise as a biomarker of disease activity, blood calprotectin levels could not predict disease relapse. There was no significant difference in serum calprotectin levels between patients who relapsed and those who did not. A relapse history also did not influence serum calprotectin levels.

Researchers also found that the baseline serum calprotectin levels were significantly higher in patients who, at follow-up, also showed higher urine protein levels, and had non-decreasing ANCA levels. No marked difference was reported in baseline urine calprotectin levels in these patients.

Blood calprotectin levels were also indicative of kidney function. Indeed, patients with deteriorating kidney function at follow-up had markedly higher levels of serum calprotectin at baseline than those with stable kidney function.

Although urine calprotectin levels did not have a predictive value for disease activity, they had a significant association with the kidney damage, examined at the tissue level.

In the Berden Classification, kidney biopsies are divided into four categories – focal, crescentic, sclerotic and mixed – based on the appearance of lesions indicating the health of the glomeruli, the kidney’s filtering units.

Among patients in remission, those whose kidney biopsies were classified as sclerotic at the time of diagnosis had significantly lower urine calprotectin levels compared to all other classifications. A similar association was seen in patients in an acute disease phase.

Thus “calprotectin during remission in ANCA vasculitis may be useful to identify subclinical inflammation and worse renal prognosis patients,” investigators wrote.

“Altogether, we think that the information derived from serum and urine calprotectin quantification is helpful to individualize immunosuppressive maintenance therapy in AAV,” they concluded.