ANCA-Associated Glomerulonephritis: Risk Factors for Renal Relapse

Abstract

Relapse in ANCA-associated vasculitis (AAV) has been studied previously, but there are few studies on renal relapse in particular. Identifying patients at high risk of renal relapse may aid in optimizing clinical management. We investigated which clinical and histological parameters are risk factors for renal relapse in ANCA-associated glomerulonephritis (AAGN). Patients (n = 174) were newly diagnosed and had mild-moderate or severe renal involvement. Data were derived from two trials of the European Vasculitis Society: MEPEX and CYCAZAREM. The Cox regression model was used to identify parameters increasing the instantaneous risk (= rate) of renal relapse (useful for instant clinical decisions). For identifying predictors of renal relapse during follow-up, we used Fine & Gray's regression model. Competing events were end-stage renal failure and death. The cumulative incidence of renal relapse at 5 years was 9.5% (95% CI: 4.8-14.3%). In the Cox model, sclerotic class AAGN increased the instantaneous risk of renal relapse. In Fine & Gray's model, the absence of interstitial infiltrates at diagnosis was predictive for renal relapse. In this study we used two different models to identify possible relationships between clinical and histopathological parameters at time of diagnosis of AAV with the risk of experiencing renal relapse. Sclerotic class AAGN increased the instantaneous risk of renal relapse. This association is most likely due to the high proportion of sclerosed glomeruli reducing the compensatory capacity. The absence of interstitial infiltrates increased the risk of renal relapse which is a warning sign that patients with a relatively benign onset of disease may also be prone to renal relapse. Renal relapses occurring in patients with sclerotic class AAGN and renal relapses occurring in patients without interstitial infiltrates were mutually exclusive, which may indicate that they are essentially different.

Fig 1. Events.

Overview of different events experienced by 174 patients during follow-up. Twenty-five patients presented with ESRF at baseline. Nineteen of them died during follow-up. Thirty-one patients experienced renal relapse during follow-up; six of them developed ESRF, of whom four died, and three died without ESRF during follow-up. Nineteen patients developed ESRF without renal relapse (competing event 1), of whom 10 died at a later timepoint. Twenty-nine patients died without experiencing renal relapse or ESRF (competing event 2). Seventy patients experienced no event during follow-up. Abbreviations: DSF, disease-free survival; ESRF, end-stage renal failure; ESRF0, end-stage renal failure at baseline.

Fig 2. Cumulative incidence of renal relapse, end-stage renal failure or death.

Cumulative incidence of patients who experienced renal relapse (event of interest) and patients who developed ESRF or died (competing events). This figure illustrates the probability of experiencing a renal relapse and the probability of developing ESRF or dying without experiencing a renal relapse. Abbreviations: CI, cumulative incidence; ESRF, end-stage renal failure.

Fig 3. Events of the 113 patients with ≥7 glomeruli in their renal biopsy without end-stage renal failure at baseline.

Twenty-four patients experienced a renal relapse during follow-up. Of these 24 patients, four developed ESRF, of which three died, and four died without ESRF during follow-up. Fourteen patients developed ESRF without renal relapse (competing event 1), of whom 7 died at a later timepoint. Twenty patients died without renal relapse and without ESRF (competing event 2). Fifty-five patients experienced no event during follow-up. Abbreviations: DSF, disease-free survival; ESRF, end-stage renal failure.