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      Kidney biopsy chronicity grading in antineutrophil cytoplasmic antibody-associated vasculitis

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          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 m 2, 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.

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          Most cited references55

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          A new equation to estimate glomerular filtration rate.

          Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.
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            2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides.

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              Rituximab versus cyclophosphamide for ANCA-associated vasculitis.

              Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. Nine centers enrolled 197 ANCA-positive patients with either Wegener's granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P=0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.) 2010 Massachusetts Medical Society
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                Author and article information

                Contributors
                Journal
                Nephrol Dial Transplant
                Nephrol Dial Transplant
                ndt
                Nephrology Dialysis Transplantation
                Oxford University Press
                0931-0509
                1460-2385
                September 2022
                26 August 2021
                26 August 2021
                : 37
                : 9
                : 1710-1721
                Affiliations
                Department of Medicine, Division of Pulmonary and Critical Care, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
                Department of Medicine, Division of Nephrology and Hypertension, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
                Department of Medicine, Division of Pulmonary and Critical Care, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
                Department of Laboratory Medicine and Pathology, Division of Anatomic Pathology, Mayo Clinic College of Medicine and Science , Rochester, MN, USA
                Author notes
                Correspondence to: Sanjeev Sethi; E-mail: sethi.sanjeev@ 123456mayo.edu
                Author information
                https://orcid.org/0000-0002-4536-7709
                Article
                gfab250
                10.1093/ndt/gfab250
                9395375
                34436585
                5c3326a1-165a-4276-b845-951a5bab350c
                © The Author(s) 2021. Published by Oxford University Press on behalf of ERA.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 11 May 2021
                : 06 August 2021
                Page count
                Pages: 12
                Categories
                Original Article
                AcademicSubjects/MED00340

                Nephrology
                anca,glomerulonephritis,kidney biopsy,mayo clinic chronicity score
                Nephrology
                anca, glomerulonephritis, kidney biopsy, mayo clinic chronicity score

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