Kidney biopsy chronicity grading in antineutrophil cytoplasmic antibody-associated vasculitis

Abstract

Background: Kidney biopsy is valuable for prognostic assessment of renal outcomes in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with glomerulonephritis (AAV-GN) but the impact of chronic changes is not determined.

Methods: We conducted a retrospective cohort study of myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA-positive patients with AAV and active renal disease. We applied the Mayo Clinic Chronicity Score (MCCS) and validated and evaluated its implications on outcome prediction in AAV-GN.

Results: We analyzed 329 patients with kidney biopsies available to score. The extent of chronicity was graded by MCCS as minimal [102 (31.0%)], mild [106 (32.2%)], moderate [86 (26.1%)] and severe [35 (10.6%)]. The MCCS grades correlated with the degree of renal function impairment at presentation [mean estimated glomerular filtration rate (eGFR) 48.3 versus 29.2 versus 23.7 versus 18.5 mL/min/1.73 m2, respectively; P < 0.0001]. Higher degrees of the individual components of the MCCS (glomerulosclerosis, interstitial fibrosis, tubular atrophy and arteriosclerosis) were associated with lower median eGFR (P < 0.0001) and decreased event-free [kidney failure (KF) and death] survival (P = 0.002, P < 0.0001, P < 0.0001 and P = 0.017, respectively). Patients with lower MCCS grades recovered renal function more frequently (P < 0.0001). Increasing MCCS grades were associated with decreased renal recovery (P = 0.001), more frequent events and shorter time to KF (P < 0.0001), KF and death (P < 0.0001) and death (P = 0.042), independent of the remission induction treatment used (cyclophosphamide or rituximab). The MCCS stratified renal outcomes for each MCCS grade and can be used in clinical practice as a cutoff for KF prediction (MCCS ≥4).

Conclusions: Chronic changes on kidney histology independently predict renal function, outcomes and response to treatment in AAV-GN.

Keywords: ANCA; Mayo Clinic Chronicity Score; glomerulonephritis; kidney biopsy.

FIGURE 1

Strengthening the Reporting of Observational Studies in Epidemiology flowchart for the selection of the patient with active renal involvement in AAV-GN. Active renal involvement was defined by the presence of active, biopsy-proven, pauci-immune glomerulonephritis; red blood cell casts on urine microscopy or an increase in serum creatinine (SCr) >30% (or a >25% decrease in creatinine clearance) attributed to active vasculitis. Kidney biopsies were scored for chronicity based on the MCCS grading system into minimal, mild, moderate and severe.

FIGURE 2

Light microscopy of kidney biopsy findings in AAV-GN according with the MCCS grading and Berden classification: (A) minimal, focal; (B) mild, crescentic; (C) moderate, mixed; (D) severe, sclerotic. Arrows point to cellular crescents.

FIGURE 3

The categories of each histologic component of the MCCS are strongly and independently correlated with (A) renal function at baseline and (B) are associated with kidney disease progression and decreased event-free survival (KF and/or death).

FIGURE 4

Kaplan–Meier plots of renal outcomes. (A) Renal recovery (with minimal eGFR ≥30 mL/min/1.73 m²) and remission for 12 months: 61 versus 50 versus 33 versus 10, mean time to event 4.6 versus 5.9 versus 6.7 versus 7.9 months; P = 0.001. (B) KF at 12 months (minimal versus mild versus moderate versus severe): 4 versus 13 versus 19 versus 13 events, mean time to event 11.7 versus 10.7 versus 9.9 versus 8.7 months; P < 0.0001. (C) Combined events of KF and/or death over 24 months (minimal versus mild versus moderate versus severe): 12 versus 19 versus 23 versus 15 events, mean time to event 22.1 versus 20.6 versus 18.7 versus 14.8 months; P < 0.0001.