Discussion
In this study we have defined four time-course ANCA patterns and we observed an increased risk of clinical relapse in patients with a recurrent or persistent ANCA pattern, independently of the clinical diagnosis or the antigenic specificity.
The presence of anti-PR3 antibodies has long been associated with an increased risk of clinical relapse (1,10,11). However, in our cohort, the recurrent or persistent ANCA patterns were associated with an increased risk of relapse, regardless of the ANCA antigenic specificity. These results are in keeping with other studies showing that patients with AAV and recurrent high anti-MPO antibodies are also at increased risk of clinical relapse (12,13), and by the observation of Kemna et al showing that the association of an ANCA rise with a relapse was influenced by persistence of ANCA and not by ANCA antigenic specificity (14). Our results do not support the opinion of some authors claiming that there is no need in routinely monitoring ANCA titres in patients with ANCA-associated vasculitis (7).
We have also found that patients with anti-MPO vasculitis and a recurrent ANCA pattern were more prone to worsening renal function. It is generally accepted that patients with anti-MPO antibodies have a worse renal prognosis and a higher risk of progression to ESRD than patients with anti-PR3 antibodies (11,15-21), although not all studies have confirmed this association (22-24). Patients with anti-MPO antibodies usually have more glomerulosclerosis and interstitial fibrosis on renal biopsies than patients with anti-PR3 antibodies (18,20,22,24). Some authors have suggested that these chronic lesions could result from a more protracted course and a greater diagnostic delay in anti-MPO AAV patients, meaning that on starting treatment they would have more irreversible chronic renal lesions than anti-PR3 AAV patients (18,20,22). Our results, showing a lower decline of renal function in anti-PR3 patients despite being immunologically active, do not support this hypothesis. Conversely, it is likely that inflammatory lesions of patients with anti-MPO antibodies would have a greater tendency to residual fibrosis, as suggested both in experimental studies (25), and in clinical observations showing an increased risk of lung fibrosis in patients with anti-MPO antibodies (26,27).
Other factors that have been associated with renal prognosis in AAV are advanced age (16), renal failure at disease onset (16,19), and presence of tubular atrophy (16). The importance of the longitudinal ANCA patterns on renal survival has been scarcely investigated. A small retrospective study by Franssen et al (28) found similar results to ours, with persistently high anti-MPO levels leading to chronic renal failure. Our series, with a larger number of patients with anti-MPO AAV, provides original data in this regard, showing a worse renal prognosis in patients with recurrent or persistent high anti-MPO-antibody levels.
The present study provides new information on the prognosis of AAV according to ANCA patterns, but several limitations should be mentioned. This is a retrospective observational study, so the clinical follow-up and treatments administered were not uniform. However, we performed a multivariate analyses and none of the administered treatments had a significant impact on the associations that have been described.
In conclusion, our study suggests that patients with a recurrent or persistent ANCA pattern have a higher risk of clinical relapse than patients with a monophasic or remitting pattern. In addition, patients with anti-MPO antibodies and a recurrent ANCA pattern had worse renal prognosis. Our results would suggest that a more aggressive treatment may be needed in these patients in order to preserve their renal function.