#5028 CHANGING PATTERNS IN CLINICAL-HISTOLOGICAL PRESENTATION AND OUTCOMES OVER THE LAST FOUR DECADES IN PATIENTS WITH MICROSCOPIC POLYANGIITIS (MPA)
Authors: Uzzo Martina , Sala Filippo , Reggiani Francesco , L'imperio Vincenzo , Calatroni Marta , Maggiore Umberto , Moroni Gabriella Luisa , Sinico Renato Alberto 
Published: June 2023

Abstract

Background and Aims
Recent data seem to indicate an increasing age of patients affected by MPA over the last decades, which may result from the wider availability of anti-neutrophil cytoplasmic antibody (ANCA) testing and to a greater awareness of the disease. It is not known whether the changing MPA has been mirrored by a change in the pattern of clinical outcomes. We aimed at assessing the changes in demographic, clinical and histological presentation, and outcomes of MPA patients over a 42-year period.

Method
We performed a multicenter retrospective cohort study. Patients diagnosed with MPA between 1980 and the 31st of January 2022 were grouped in two periods (p), based on the year of diagnosis: p1980–2001 and p2002–2022. We tested the baseline differences using the Mann-Whitney test and the Fisher's exact. We estimated the crude patient survival using the Kaplan-Meier estimator and the cumulative incidence of competing events death/dialysis using Aalen-Johansen estimator. The probability of end-stage kidney disease (ESKD) and death at each time point since MPA diagnosis was estimated through a multistate model, which accounted for patients who died after starting dialysis. We used Cox proportional hazards, Fine-Gray regression, and multistate regression models to adjust for potential confounding factors such as age, kidney function and clinical symptoms at the time of diagnosis.

Results
Out of 201 patients, 187 had non-missing follow-up to ESKD and/or death and could be included in the study. There were 77 patients in p1980-2001, and 110 patients in p2002-2022. Compared to p1980-2001, patients in p2002-2022 were older (66.2 (14.0) vs 57.7 (15.8) vs; P&lt;0.001) and had better kidney function (eGFR (MDRD), mL/min/1.73m2 25.9 (24.8) vs 21.5 (28.2); P = 0.011). The prevalence of the sclerotic class according to the Berden histopathological classification was lower in p2002-2022 (4.8 vs 18.2%; P = 0.006). There were mild differences in the pattern of clinical symptoms, with a lower prevalence of constitutional symptoms (83.6 vs 94.8%; P = 0.021) and a higher prevalence of pulmonary disease (40 vs 20.8%; P = 0.040) and peripheral neuropathy (17.3 vs 5.2%; P = 0.013) in p2002-2022. Crude and adjusted patient survival was similar. However, the risk of ESKD decreased during p2002-2022 compared to p1980-2001 (Figure 1; crude Subhazard ratio of ESKD: 0.30 [95%CI: 0.16 to 0.57; P&lt;0.001]). The difference in the probability of ESKD remained significant even after accounting for death after ESKD (Figure 2), and after adjusting for potential confounders (Hazard ratio of ESKD since MPA diagnosis in multistate models: 0.33 [95%CI: 0.18 to 0.63; P&lt;0.001]).

Conclusion
Clinical presentation of MPA has become less severe in the last decades, leading to a reduced risk of ESKD, despite a comparable risk of death. Older age, changing clinical patterns and better kidney function at the time of diagnosis do not fully account for the reduction in ESKD, which may be instead related to new induction and maintenance therapies as well as to a greater awareness of the disease.