Slowly progressive anti-neutrophil cytoplasmic antibody-associated renal vasculitis: clinico-pathological characterization and outcome

Giorgio Trivioli; Seerapani Gopaluni; Maria L Urban; Davide Gianfreda; Matthias A Cassia; Paolo G Vercelloni; Marta Calatroni; Alessandra Bettiol; Pasquale Esposito; Corrado Murtas; Federico Alberici; Federica Maritati; Lucio Manenti; Alessandra Palmisano; Giacomo Emmi; Paola Romagnani; Gabriella Moroni; Gina Gregorini; Renato A Sinico; David R W Jayne; Augusto Vaglio

doi:10.1093/ckj/sfaa139

Slowly progressive anti-neutrophil cytoplasmic antibody-associated renal vasculitis: clinico-pathological characterization and outcome

Clin Kidney J. 2020 Sep 6;14(1):332-340. doi: 10.1093/ckj/sfaa139. eCollection 2021 Jan.

Authors

Giorgio Trivioli¹, Seerapani Gopaluni², Maria L Urban³, Davide Gianfreda⁴, Matthias A Cassia⁵, Paolo G Vercelloni⁶, Marta Calatroni⁷, Alessandra Bettiol⁸, Pasquale Esposito⁹, Corrado Murtas¹⁰, Federico Alberici^{11

12}, Federica Maritati¹³, Lucio Manenti¹⁴, Alessandra Palmisano¹⁴, Giacomo Emmi³, Paola Romagnani¹, Gabriella Moroni¹⁵, Gina Gregorini¹⁶, Renato A Sinico⁶, David R W Jayne², Augusto Vaglio¹

Affiliations

¹ Department of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Firenze, and Nephrology Unit, Meyer Children's Hospital, Firenze, Italy.
² Department of Medicine, University of Cambridge, Cambridge, UK.
³ Department of Experimental and Clinical Sciences, University of Firenze, Firenze, Italy.
⁴ Nephrology Unit, Fondazione Panico Hospital, Tricase, Italy.
⁵ Department of Health Science, University of Milan, Italy.
⁶ Nephrology Unit, University Milano Bicocca, Monza, Italy.
⁷ Nephrology Unit, Humanitas Hospital, Rozzano, Italy.
⁸ Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Firenze, Firenze, Italy.
⁹ Department of Internal Medicine and Medical Specialties, University of Genova, Genova, Italy.
¹⁰ Nephrology Unit, Nephrology Unit, ASSL Oristano, ATS Sardegna, Oristano, Italy.
¹¹ Nephrology Unit, ASST Spedali Civili, Brescia, Italy.
¹² Department of Medical and Surgical Specialities, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
¹³ Nephrology, Dialysis and Transplant Unit, Ospedali Riuniti, Ancona, Italy.
¹⁴ Nephrology Unit, Parma University Hospital, Parma, Italy.
¹⁵ Nephrology Unit, Policlinico Hospital, Milano, Italy.
¹⁶ Nephrology Unit, Spedali Civili, Brescia, Italy.

Abstract

Background: Although rapidly progressive glomerulonephritis is the main renal phenotype of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), slow renal disease progression is sometimes observed. These forms have been rarely discussed; we analysed their prevalence, clinico-pathological characteristics and outcome.

Methods: We screened patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis followed at seven referral centres and selected those with estimated glomerular filtration rate (eGFR) reduction <50% over a 6-month period preceding diagnosis. Data regarding patient features and response to treatment were retrieved.

Results: Of 856 patients, 41 (5%) had slowly progressive renal AAV. All had MPA and all but one was P-ANCA/myeloperoxidase (MPO) ANCA-positive. At diagnosis, the median age was 70 years [interquartile range (IQR) 64-78] and extra-renal manifestations were absent or subclinical (interstitial lung lesions in 10, 24%). The median (IQR) eGFR was 23 mL/min/1.73 m² (15-35); six patients (15%) had started renal replacement therapy (RRT). All had proteinuria (median 1180 mg/24 h, IQR 670-2600) and micro-haematuria. Main histologic findings were extracapillary proliferation at chronic stages and glomerulosclerosis; following Berden's classification, 6/28 biopsies (21%) were 'focal', 1/28 (4%) 'crescentic', 9/28 (32%) 'mixed' and 12/28 (43%) 'sclerotic'. At last follow-up (median 32 months, IQR 12-52), 20/34 patients (59%) treated with immunosuppression had eGFR improvement >25% as compared with diagnosis, while 4/34 (12%) had started RRT.

Conclusions: AAV may present with slow renal disease progression; this subset is hallmarked by advanced age at diagnosis, positive MPO-ANCA, subclinical interstitial lung lesions and chronic damage at kidney biopsy. Partial renal recovery may occur following immunosuppression.

Keywords: ANCA; end-stage renal disease; glomerulonephritis; microscopic polyangiitis; rituximab; vasculitis.