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Article

Kidney Pathology and Outcomes in ANCA-Associated Vasculitis: Retrospective Analysis of 85 Patients

1
Nephrology, Botkin Hospital, 125284 Moscow, Russia
2
Nephrology, Moscow State University of Medicine and Dentistry, 127473 Moscow, Russia
3
Faculty of Medicine, Lomonosov Moscow State University, 119991 Moscow, Russia
4
Pathology, Moscow City Nephrology Center, 123182 Moscow, Russia
*
Author to whom correspondence should be addressed.
Kidney Dial. 2021, 1(1), 61-73; https://doi.org/10.3390/kidneydial1010010
Received: 26 June 2021 / Revised: 8 August 2021 / Accepted: 12 August 2021 / Published: 22 August 2021

Abstract

:
ANCA-associated vasculitis (AAV) poses a significant risk of kidney failure; kidney biopsy remains a key prognostic tool. The histopathologic classification of AAV glomerulonephritis (GN) developed by Berden et al. showed correlation between GN classes and kidney outcomes; ANCA Renal Risk Score (ARRS) included tubular atrophy and interstitial fibrosis (TA/IF) as an additional parameter for risk assessment. We aimed to evaluate kidney survival across AAV GN classes and ARRS groups. A single-center retrospective study included 85 adult patients with biopsy-proven AAV kidney disease followed in the period of 2000–2020. Primary outcome was kidney survival at the end of 18 (5; 66) months follow-up, and kidney death was considered as stage 5 CKD. We found significant differences in kidney survival for sclerotic, mixed, crescentic and focal AAV GN classes: 19%, 76.2%, 91.7% and 100%, respectively (p = 0.009). Kidney survival was 0%, 75.6% and 100% for the high-, medium- and low-risk ARRS groups, respectively (p < 0.001); TA/IF analysis showed kidney survival at 49.6% vs. 87.7% for widespread and mild TA/IF, respectively (p = 0.003). Kidney survival was significantly lower in anti-MPO-ANCA versus anti-PR3-ANCA carriers (50.3% and 78.1%, respectively, p = 0.045). We conclude that unfavorable AAV kidney outcomes are associated with sclerotic GN class by Berden’s classification, ARRS high risk group, and anti-MPO-ANCA subtype.

1. Introduction

ANCA-associated vasculitis (AAV) poses a significant risk of kidney failure; frequency of kidney involvement in AAV varies from 90% in Microscopic Polyangiitis (MPA) and 80% in Granulomatosis with Polyangiitis (GPA) to 45% in Eosinophilic Granulomatosis with Polyangiitis (EGPA) [1,2]. Therefore, kidney survival remains one of the most important outcomes in AAV. A systematic review of 44 studies, performed in 2008 by the European Vasculitis Study Group, found valuable data for GPA only, with kidney survival at 93% and 85% for 1 year and 5 years, respectively; the data for MPA and EGPA were scarce. [3]. Eight years later, a multicenter study of 144 patients with MPA managed according to the EULAR recommendations [4] showed that stage 5 chronic kidney disease (CKD) developed in 7.6% of patients with median follow-up of 33.5 months [5]. However, another study, including 80% of patients with MPA or renal-limited AAV, demonstrated less optimistic results—47% of patients reached stage 5 CKD by the end of the 5-year follow-up period [6]. A study of the Asian population confirmed unfavorable kidney outcomes for MPA—30.1% of patients reached a composite end-point (doubling of serum creatinine or stage 5 CKD) in 17 months, regardless of the immunosuppressive treatment [7]. In contrast, the most recent data concerning kidney survival in EGPA, provided by the retrospective study of 63 patients, show that just 17% of patients reached stage 5 CKD, with median follow-up of 48 months [8].
Evaluation of ANCA titers in association with kidney outcomes did not show a direct correlation between clinical remission and decrease in ANCA levels [9]; the role of ANCA subtype remains controversial. A review, published in 2016, concluded that the anti-proteinase3 (anti-PR3) subtype of ANCA was associated with higher risk of relapses [10]. Later, a single-center study of 85 patients with AAV confirmed that the anti-myeloperoxidase (anti-MPO) subtype of ANCA was associated with a lower risk for relapse, but with the worst patients and kidney survival rate; additional unfavorable prognostic factors included older age at the disease onset and male gender [11]. The most recent publication of a long-term observation of patients with AAV demonstrated that recurrent or persistent ANCA-positivity was associated with worst kidney outcomes, and a recurrent pattern of anti-MPO-AAV was associated with worsening kidney function [12].
Patients with AAV, especially those with severe kidney disease, remain at high risk of unfavorable outcomes, despite currently available effective treatments [2,9,13,14,15,16]. Even though the prognostic value of ANCA titer and subtype and several other biomarkers, as well as the role of treatment and therapeutic strategies, have been extensively studied in association with kidney outcomes over the last few decades, kidney biopsy remains a key diagnostic and prognostic tool, in particular for ANCA-negative and renal-limited AAV [17]. The characteristic kidney lesion in AAV is pauci-immune focal and segmental necrotizing and crescentic glomerulonephritis (GN); however, pathology features vary from mild focal segmental extracapillary proliferation to diffuse crescentic GN and interstitial granulomas or infiltrates [18,19]. Moreover, differential diagnosis between GPA, EGPA and MPA is based, above all, on the presence or absence of the granulomatous inflammation, as it is stressed in the statements of the Chapel-Hill Consensus Conference 2012 [20] as well as in the algorithms of the European Medical Agency (EMA) [21].
The histopathologic classification of AAV GN, proposed by Berden et al., demonstrated a correlation between GN classes and kidney outcomes [22]. This classification distinguishes four classes: focal (≥50% of normal glomeruli), extracapillary or crescentic (≥50% of the glomeruli with cellular crescents), sclerotic (≥50% of totally sclerosed glomeruli), and mixed; interstitial damage did not show significant influence on the kidney failure rate, which initially led to the conclusion that glomerular damage plays a key role [22]. However, later, the same group showed that tubular atrophy and necrosis were significant predictors of the decline in kidney function [23]. In the last decade, several other histological classifications for renal AAV were proposed and validated [24,25,26,27]. Thus, the recently developed clinicopathologic ANCA Renal Risk Score (ARRS) for prediction of renal outcome in AAV GN includes tubular atrophy and interstitial fibrosis (TA/IF) as one of the parameters for the risk assessment. Proposed and validated parameters are the percentage of normal glomeruli (N: 0–4–6 points), percentage of TA/IF (T: 0–2 points), and glomerular filtration rate (GFR) (G: 0–3 points); the calculated sum of points distinguishes three risk groups: low (0 points), medium (2–7 points), and high (8–11 points) [28]. In addition, a higher percentage of normal glomeruli was found in the biopsies of patients with a comparable GFR level at the time of kidney biopsy and anti-PR3 subtype versus anti-MPO subtype. Anti-MPO-ANCA was also associated with the higher extent of fibrotic lesions—both glomerulosclerosis and interstitial fibrosis [29,30].
In this retrospective study of AAV kidney outcomes, we aimed to evaluate kidney survival in association with GN class according to Berden’s classification, with the ARRS group, and with the ANCA subtypes.

2. Materials and Methods

A single-center retrospective study, using an electronic database, identified 121 patients ≥18 years old with AAV, diagnosed in our center in the period of 2000–2020 according to the ACR [31] criteria and EMA algorithm [21]. For the purpose of this study, the main data retrieved were age, gender, main diagnosis, systemic signs and symptoms and serum creatinine at presentation, disease activity, ANCA levels and subtype, date of kidney biopsy, kidney pathology findings, initial and subsequent treatment regimens, follow-up duration, and eGFR at the end of the follow-up.
Ultrasound-guided kidney biopsy was performed according to the standard in-hospital protocol, with specimen handling and pathology evaluation in the dedicated kidney pathology unit. For light microscopy, sections of formalin-fixed paraffin-embedded tissue were stained with H&E, Masson’s trichrome, periodic acid-Schiff and Congo Red. Immunofluorescence was performed on frozen sections with FITS-conjugated antibodies to IgA, IgG, IgM, C1q, C3, fibrinogen, lambda and kappa light chains. ANCA levels were tested using immunoenzyme assay or indirect immunofluorescence. Disease activity was scored at the time of diagnosis, based on the Birmingham Vasculitis Activity Index (BVAS v.3) [32]. Pattern and severity of kidney disease were evaluated according to Berden’s classification and ARRS [22,28].
After evaluation of clinical, serology and pathology findings, 36 patients with dual phenotype (both ANCA and anti-GBM positivity) or with AAV, superimposed on IgA-vasculitis, and cases without adequate kidney pathology data (less than 5 glomeruli in the biopsy specimen) were excluded from further analysis (Figure 1). The median number of glomeruli per specimen in the study group was 13 (12; 19); 82 out of 85 cores contained ≥10 glomeruli, and only 3 cores contained 7 and 6 glomeruli, respectively. The study group comprised 85 patients with pathology-proven AAV kidney disease, including 51 (60%) females and 34 (40%) males, with a median age of 55.5 (41; 61.7) years. GPA was diagnosed in 34 (40%) patients, MPA in 44 (51.8%) patients, and EGPA in 7 (8.2%) patients.
Initial treatment regimens included glucocorticoids plus intravenous cyclophosphamide in 57 (67%) cases, glucocorticoids plus rituximab in 12 (14.1%) cases, and glucocorticoids plus cyclophosphamide followed by rituximab in 16 (18.8%) cases. Seven patients presented with pulmonary hemorrhage and received plasma exchanges. Subsequent treatment regimens included low doses of glucocorticoids combined with azathioprine or methotrexate for patients who initially received cyclophosphamide. Patients who received rituximab for initial treatment continued on rituximab.
Primary outcome was kidney death at the end of follow-up. The end of follow-up was defined as the date of the last visit or the date of the patient’s death. Kidney death was considered as stage 5 CKD (eGFR < 15 mL/min/1.73 m2 CKD-EPI equation), regardless of the demand for kidney replacement therapy.
The data were presented as number (percentage) for categorical variables and median (interquartile range (IQR)) for continuous variables. Spearman’s rank correlation coefficient was used for statistical correlations. Kidney survival rate was assessed using the Kaplan–Meier method. Differences between categories were assessed using the log-rank test; p value < 0.05 was considered as significant. The data analysis was performed on a personal computer using the statistical package IBM SPSS Statistics v 23.

3. Results

3.1. Main Disease Characteristics

Elevated ANCA levels found in 77 (90.6%) of patients, 42 of which had anti-MPO-ANCA and 25—anti-PR3-ANCA; in 10 cases, a screening test for ANCA using indirect immunofluorescence was performed without identification of ANCA subtype; 8 patients (9.4%) had seronegative AAV. All patients had severe disease with a median BVAS score of 15 (12.3; 19.8) at the time of diagnosis. Systemic features and kidney pathology are shown in Table 1.
Median serum creatinine at presentation was 257.0 (171; 528.5) µmol/L. According to Berden’s classification, 20 patients had focal GN, 22—crescentic GN, 18—mixed GN, and 24—sclerotic GN class; a single patient with severe kidney and lung involvement had interstitial nephritis without glomerular damage. Median ARRS in the main study group was 4 points (2.0; 6.0), while 21 patients had high risk, 42 patients—medium risk, and 22—low risk according to the ARRS.
Follow-up duration did not differ significantly between patients with GPA, MPA and EGPA. By the end of the follow-up period, 66 (77.6%) patients achieved remission, 12 (14.1%) patients with remission of extrarenal manifestations developed ESKD and received dialysis treatment, and 7 (8.2%) patients did not achieve remission and died from extrarenal complications.

3.2. Kidney Survival Analysis in the Main Study Group

At the end of the follow-up with the median of 18 (5; 66) months, patient survival was 89.5%, and kidney survival—75.4%. Patients of more advanced age at disease onset had more advanced CKD stages by the end of the follow-up period (r = 0.303; p = 0.011). Comparison of kidney outcomes in 2000–2010 and 2011–2020 did not show significant differences; kidney death occurred in 26.6% and 23.6% of cases, respectively (χ2 = 0.098, p = 0.754).
Analysis of the outcomes for AAV GN classes defined according to Berden’s classification showed significant difference in the kidney survival between all four classes: 19%, 76.2%, 91.7% and 100% for sclerotic, mixed, crescentic and focal classes, respectively (p = 0.009) (Figure 2).
Among 57 patients who received cyclophosphamide followed by azathioprine or methotrexate, kidney survival was 33%, 75%, 86.7% and 100% for sclerotic, mixed, crescentic and focal classes, respectively (p = 0.004). In 12 patients who received rituximab only, kidney survival was 0% for sclerotic class and 100% for mixed, crescentic and focal classes (p = 0.015). In the patients switched from cyclophosphamide to rituximab, kidney survival was 62% for the sclerotic class, 0% for the mixed class, and 100% for the focal and crescentic classes (p = 0.033).
We found a statistically significant correlation between median ARRS at presentation and CKD stage at the end of follow-up (r = 0.490, p < 0.001). The high ARRS group demonstrated unfavorable kidney outcome—kidney survival was 0%, 75.6% and 100% for the high, medium and low groups, respectively (p < 0.001) (Figure 3).
In addition, kidney survival was 0% and 100% for the low- and high-risk group, respectively, regardless of the treatment regimen. In the medium-risk group, kidney survival was 100% in the patients who received rituximab only or were switched from cyclophosphamide to rituximab and continued on rituximab, and 81.8% in the patients who received cyclophosphamide followed by azathioprine or methotrexate (p = 0.438).
Using ARRS parameters, we evaluated the degree of TA/IF and of glomerular damage separately, and found that the patients with widespread TA/IF reached stage 5 CKD significantly more often compared to those with mild TA/IF: kidney survival was 49.6% vs. 87.7% for T2 and T0 points, respectively (p = 0.003) (Figure 4).
Similarly, the patients with a higher number of damaged glomeruli reached stage 5 CKD significantly more often, compared to those with a lower number of damaged glomeruli: kidney survival 30%, 43.2% and 78.1% for N6, N4 and N0 points, respectively (p = 0.001) (Figure 5).
Finally, kidney survival was significantly lower in patients anti-MPO-ANCA compared to those with anti-PR3-ANCA (50.3% vs. 78.1%, respectively, p = 0.045) (Figure 6).

3.3. Kidney Survival Analysis in the Anti-PR3-ANCA and Anti-MPO-ANCA Subgroups

Given the different renal outcomes in the patients with anti-PR3 and anti-MPO-ANCA in the main group, we divided patients with available ANCA subtype data into two subgroups—anti-MPO and anti-PR3 ANCA carriers. The results of analysis according to Berden’s classification in the subgroups tend to be close to the general study group; however, we did not find statistically significant differences for all four classes in the particular subgroups. Kidney survival in the anti-PR3-ANCA subgroup was similarly high (100%) for the crescentic and focal classes, and in the anti-MPO-ANCA subgroup—almost similarly low (24.3% and 31%) for the sclerotic and mixed classes, respectively.
In contrast, analysis according to the ARRS showed statistically significant differences within the ANCA subtypes’ subgroups. In the anti-PR3-ANCA subgroup, kidney survival was 0%, 82.5% and 100% (p = 0.019) (Figure 7), and in the anti-MPO-ANCA subgroup, it was 0%, 41.8% and 100% (p = 0.028) for the high, medium and low risk, respectively (Figure 8).
Kidney survival in the low- and high-ARRS risk groups did not differ significantly in both ANCA subtypes subgroups. However, the patients with medium ARRS risk and anti-MPO-ANCA had worse kidney survival compared to medium ARRS risk and anti-PR3-ANCA (41.8% vs. 82.5%, respectively), even though the differences did not reach statistical significance (p = 0.13).

4. Discussion

Patients with AAV remain at high risk of unfavorable outcomes despite currently available effective treatments [2,3,4,5,6,7,8]; evaluation of the prognostic factors for kidney outcomes at the time of diagnosis plays a key role. Kidney pathology not only confirms the diagnosis, but also predicts kidney survival and thus, guides the treatment strategy. Even though Berden’s classification of the AAV GN clearly distinguishes focal and active lesions from diffuse and chronic, and demonstrates the impact of glomerular sclerosis on the kidney outcome, this classification does not accommodate TA/IF. However, the degree of tubulointerstitial damage and its role in CKD progression for glomerular diseases is well established [33,34,35] and the ARRS score’s main advantage is incorporation of both glomerular and tubulointerstitial lesions.
In our study group, kidney survival by the end of the follow-up of 18 (5; 66) months was 75.4%, which is comparable to the most recent data [16]. We used both Berden’s classification and ARRS to evaluate the prognostic value of kidney pathology. Our results are consistent with Berden’s original publication data [22]: in our study group, the focal class, as expected, had the best outcome, and sclerotic class—the worst outcome. Of note, not all validation studies confirmed the difference between crescentic and mixed classes; thus, a large meta-analysis, including 1601 patients, did not show significant differences in the progression to stage 5 CKD between these classes (RR 1.14, 95% CI 0.91–1.43, p = 0.27) [36]. In our study, kidney survival in the crescentic class turned out significantly better compared to the mixed class in the general group, confirmed by the analysis in the anti-MPO-ANCA and anti-PR3 subgroups. Importantly, we found significantly worse kidney survival in the anti-MPO-ANCA carriers, regardless of kidney pathology findings, which confirms the negative impact of anti-MPO-ANCA on kidney outcomes [18,19,29,30,37]. Comparison of kidney survival across Berden’s classification and according to treatment regimens did not show significant differences between the main study group and the group of patients who received initial treatment with cyclophosphamide. The results showed 19%, 76.2%, 91.7% and 100% for the sclerotic, mixed, crescentic and focal classes, respectively, for the main group and 33%, 75%, 86.7% and 100% for the sclerotic, mixed, crescentic and focal classes, respectively, for the cyclophosphamide subgroup. However, the patients who received rituximab or were switched from cyclophosphamide to rituximab due to a lack of cyclophosphamide efficacy demonstrated 100% kidney survival not only for the focal, but also for the crescentic class, which means that rituximab may be more effective than cyclophosphamide for the treatment of active lesions.
The results of ARRS analysis in our study are also consistent with the original publication [28] data; we found that kidney survival in the high ARRS group was not surprisingly the worst. It is worth noting that the separate evaluation of glomerular and tubulointerstitial lesions confirmed significant differences in kidney survival depending on both N (percentage of normal glomeruli) and T (percentage of TA/IF) parameters. There are some data concerning isolated tubulointerstitial damage in AAV [38]; however, in our group, just one patient did not have glomerular lesions, which did not allow for analysis of this pattern. An additional finding in our study was the worse kidney survival within the medium ARRS risk group in the anti-MPO-ANCA carriers versus anti-PR3-ANCA carriers. The difference did not reach statistical significance, and the possible explanation refers to the data indicating that severe active lesions at the disease onset in anti-PR3 AAV may flatten the differences in prognostic value of ANCA subtypes [39,40]. However, summarizing the available data, Kronbichler and Jane [41] stressed the association of the anti-MPO-ANCA subtype with TA/IF, tubular necrosis, and glomerulosclerosis. Importantly, kidney survival in our study did not depend on the treatment regimen across the ARRS groups, confirming that ARRS, which includes tubulointerstitial damage and eGFR, is the most effective tool for prediction of kidney outcomes.

5. Conclusions

Our study confirms that unfavorable renal outcomes for AAV kidney disease are associated with sclerotic class according to Berden’s classification of AAV GN, high ARRS risk group, and the presence of anti-MPO-ANCA; and demonstrates the strength of ARRS for selected groups of patients.

Author Contributions

Conceptualization, E.Z. and A.Z.; methodology, E.Z. and A.Z.; software, A.Z.; formal analysis, A.Z.; investigation, E.Z., T.M., E.L. and E.S.; resources, E.Z., E.S., T.M. and E.L.; data curation, E.Z. and A.Z.; writing—original draft preparation, A.Z.; writing—review and editing, E.Z.; visualization, A.Z.; supervision, E.Z. and E.S. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Ethical review and approval were waived for this study, due to the retrospective nature of the study, not implying any prospective interventions.

Informed Consent Statement

Informed consent for kidney biopsy was obtained from all the patients prior to the procedure according to the in-hospital protocol. Patient consent for participation in this particular study was waived due to the retrospective nature of the study, not including any personal data.

Data Availability Statement

The data source is the patients’ electronic records in the nephrology and kidney pathology units’ databases, which contain personal information and thus cannot be shared.

Acknowledgments

We thank Elena Tareeva, Olga Vinogradova, Elena Nikitina, Alina Anilina, Evgeny Sgutov and Sergey Loginov for their help in the diagnosis and treatment of the patients.

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. Study group selection.
Figure 1. Study group selection.
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Figure 2. Kidney survival in the different classes of ANCA-associated glomerulonephritis according to Berden’s classification (p = 0.009).
Figure 2. Kidney survival in the different classes of ANCA-associated glomerulonephritis according to Berden’s classification (p = 0.009).
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Figure 3. Kidney survival according to the ARRS group (Low, 0–1 points: Medium, 2–7 points: High, 8–11 points) (p < 0.001).
Figure 3. Kidney survival according to the ARRS group (Low, 0–1 points: Medium, 2–7 points: High, 8–11 points) (p < 0.001).
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Figure 4. Kidney survival according to the tubular atrophy and interstitial fibrosis ARRS points (T0 < 25%; T2 > 25%) (p = 0.003).
Figure 4. Kidney survival according to the tubular atrophy and interstitial fibrosis ARRS points (T0 < 25%; T2 > 25%) (p = 0.003).
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Figure 5. Kidney survival according to the percentage of normal glomeruli ARRS points (N0 > 25%; N4 10–25%; N6 < 10%) (p = 0.001).
Figure 5. Kidney survival according to the percentage of normal glomeruli ARRS points (N0 > 25%; N4 10–25%; N6 < 10%) (p = 0.001).
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Figure 6. Kidney survival in the patients with anti-MPO-ANCA versus anti-PR3-ANCA (p = 0.045).
Figure 6. Kidney survival in the patients with anti-MPO-ANCA versus anti-PR3-ANCA (p = 0.045).
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Figure 7. Kidney survival according to the ARRS score in the anti-PR3 subgroup (p = 0.019).
Figure 7. Kidney survival according to the ARRS score in the anti-PR3 subgroup (p = 0.019).
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Figure 8. Kidney survival according to the ARRS score in the anti-MPO subgroup (p = 0.028).
Figure 8. Kidney survival according to the ARRS score in the anti-MPO subgroup (p = 0.028).
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Table 1. Clinical manifestations and kidney pathology.
Table 1. Clinical manifestations and kidney pathology.
Systemic FeaturesAll Patients (85)Anti-PR3-Positive (25)Anti-MPO-Positive (42)ANCA Screening Test-Positive (10)Sero-Negative (8)
Lungs, N (%)
Interstitial lung damage22 (25.9)8 (32)3 (30.9)2 (20)0 (0)
Infiltrates16 (18.8)3 (12)8 (19)4 (40)1 (12.5)
Cavities3 (3.5)3 (12)0 (0)2 (20)0 (0)
Nodular masses3 (3.5)2 (8)1 (2.4)01 (12.5)
Asthma7 (8.2)2 (8)4 (9.5)1 (10)2 (25)
Hemoptysis, pulmonary hemorrhage11 (12.9)3 (12)6 (14.3)1 (10)1 (12.5)
Skin, N (%)22 (25.8)6 (24)16 (38.1)2 (20)1 (12.5)
Joints, N (%)27 (31.7)11 (44)12 (28.6)2 (20)2 (25)
Gastrointestinal, N (%)6 (7.0)2 (8)3 (7.1)1 (10)1 (12.5)
Nervous system, N (%)12 (14.1)6 (24)5 (11.9)01 (12.5)
ENT, N (%)38 (44.7)19 (76)16 (38.1)2 (20)4 (50)
Eyes, N (%)13 (15.3)8 (32)4 (9.5)0 (0)1 (12.5)
BVAS v.3 at presentation15.0
(12.9; 19.8)
15
(14; 20)
15
(13; 20)
14
(13; 18.5)
18
(11; 20.5)
Median serum creatinine at presentation, µmol/L257.0
(171.0; 528.5)
203
(130; 311)
139
(120; 347)
250
(151.5; 576)
100
(73; 308.5)
Kidney pathology (Berden’s classification)
Focal, N (%)20 (23.5)3 (12)11 (26.2)3 (30)3 (37.5)
Crescentic, N (%)22 (25.9)8 (32)9 (21.4)3 (30)2 (25)
Mixed, N (%)18 (21.2)7 (28)9 (21.4)2 (20)0 (0)
Sclerotic, N (%)24 (28.2)7 (28)12 (28.6)2 (20)3 (37.5)
ARRS
Low, N (%)22 (25.9)7 (28)9 (21.4)2 (20)4 (25)
Medium, N (%)42 (49.4)12 (48)21 (50)6 (60)3 (37.5)
High, N (%)21 (24.7)6 (24)12 (28.6)2 (20)1 (12.5)
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Zakharova, E.; Zykova, A.; Makarova, T.; Leonova, E.; Stolyarevich, E. Kidney Pathology and Outcomes in ANCA-Associated Vasculitis: Retrospective Analysis of 85 Patients. Kidney Dial. 2021, 1, 61-73. https://doi.org/10.3390/kidneydial1010010

AMA Style

Zakharova E, Zykova A, Makarova T, Leonova E, Stolyarevich E. Kidney Pathology and Outcomes in ANCA-Associated Vasculitis: Retrospective Analysis of 85 Patients. Kidney and Dialysis. 2021; 1(1):61-73. https://doi.org/10.3390/kidneydial1010010

Chicago/Turabian Style

Zakharova, Elena, Anastasiia Zykova, Tatyana Makarova, Eugenia Leonova, and Ekaterina Stolyarevich. 2021. "Kidney Pathology and Outcomes in ANCA-Associated Vasculitis: Retrospective Analysis of 85 Patients" Kidney and Dialysis 1, no. 1: 61-73. https://doi.org/10.3390/kidneydial1010010

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