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

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.

Slo-Mo anti-neutrophil cytoplasmic antibody-associated renal vasculitis

“…Trivioli et al . report that 5% of a large multicentre series of 856 patients with AAV had slowly progressive renal AAV, corresponding to 11% of the microscopic polyangiitis (MPA) cases and 17% of AAV cases whose pre-diagnostic kidney function course could be ascertained ( Figure 2 ) [ 1 ]. Although it has been claimed that up to 30% of AAV patients with renal involvement present slow progression, we did not find full reports as sources for this claim which was present in abstracts, book chapters or review manuscripts without detailed patient characterization [ 2 ].…”

“… Slowly progressive AAV in the general context of AAV: frequency, clinical presentation and kidney biopsy patterns [ 1 ]. ( A ) Relative frequency of different forms of AAV.…”

“…In the report by Trivioli et al ., eGFR at diagnosis was low [23 mL/min/1.73 m 2 , interquartile range (IQR) 15–35] and 37% of patients were considered to have end-stage kidney disease (ESKD), including some requiring renal replacement therapy (RRT), implying that diagnosis was late [ 1 ]. Indeed, renal abnormalities had been present and observed for a median (IQR) of 13 months (6–35) before diagnosis and this was longer among patients with end stage renal disease (ESRD) at diagnosis (38 months, IQR 13–52).…”

“…Fear of immunosuppression-related complications in elderly patients with chronic features in the kidney biopsy may be the main reason why patients with slowly progressive AAV often receive only supportive therapy and/or low-level immunosuppression. In the report by Trivioli et al ., however, 56% of patients received steroids without (12%) or with immunosuppressants (44%: cyclophosphamide, mycophenolate or azathioprine) and 34% received a rituximab-based regimen, while only 10% were not treated with immune suppressants as renal recovery was considered unlikely [ 1 ]. Within 6 months, 73% of treated patients had an improved eGFR.…”

“…In this issue of Clinical Kidney Journal , Trivioli et al . report a retrospective European case series of 41 patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) with slowly progressive renal involvement not attributable to other causes, defined as a reduction in estimated glomerular filtration rate (eGFR) of 25–50% in the 6 months prior to diagnosis since rapidly progressive glomerulonephritis usually implies a eGFR reduction >50% in up to 3 months ( Figure 1 ) [ 1 ]. Given the few published studies, mostly consisting of case reports or small case series and mainly from Asia [ 2–5 ], the present report, the largest and first systematic assessment to date in slowly progressive renal AAV, provides several key insights.…”