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

2021 ◽  
Vol 1 (1) ◽  
pp. 61-73
Author(s):  
Elena Zakharova ◽  
Anastasiia Zykova ◽  
Tatyana Makarova ◽  
Eugenia Leonova ◽  
Ekaterina Stolyarevich

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.

Author(s):  
Elena Zakharova ◽  
Anastasiia Zykova ◽  
Tatyana Makarova ◽  
Eugenia Leonova ◽  
Ekaterina Stolyarevich

ANCA-associated vasculitis (AAV) pose a significant risk of kidney failure, kidney biopsy remains a key prognostic tool. Pathology classification of the 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 2000-2020. Primary outcome was kidney survival at the end of 18 [5; 66] months follow-up, kidney death considered as CKD stage 5. We found significant difference in the 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, median and low risk ARRS groups respectively (p&amp;lt;0.001); TA/IF analysis showed kidney survival 49.6% vs 87.7% for widespread and mild TA/IF respectively (р=0.003). Kidney survival was significantly lower in anti-MPO-ANCA versus anti-PR3-ANCA carriers (50.3% and 78.1% respectively, р=0.045). We conclude that unfavorable AAV kidney outcomes associated with sclerotic GN class by Berden&rsquo;s classification, ARRS high risk group, and anti-MPO-ANCA subtype.


2021 ◽  
pp. ASN.2020081181 ◽  
Author(s):  
Aishwarya Ravindran ◽  
Marta Casal Moura ◽  
Fernando C. Fervenza ◽  
Samih H. Nasr ◽  
Mariam P. Alexander ◽  
...  

BackgroundIn patients with secondary (autoimmune) membranous nephropathy, two novel proteins, Exostosin 1 and Exostosin 2 (EXT1/EXT2), are potential disease antigens, biomarkers, or both. In this study, we validate the EXT1/EXT2 findings in a large cohort of membranous lupus nephritis.MethodsWe conducted a retrospective cohort study of patients with membranous lupus nephritis, and performed immunohistochemistry studies on the kidney biopsy specimens against EXT1 and EXT2. Clinicopathologic features and outcomes of EXT1/EXT2-positive versus EXT1/EXT2-negative patients were compared.ResultsOur study cohort included 374 biopsy-proven membranous lupus nephritis cases, of which 122 (32.6%) were EXT1/EXT2-positive and 252 (67.4%) were EXT1/EXT2-negative. EXT1/EXT2-positive patients were significantly younger (P=0.01), had significantly lower serum creatinine levels (P=0.02), were significantly more likely to present with proteinuria ≥3.5 g/24 h (P=0.009), and had significantly less chronicity features (glomerulosclerosis, P=0.001 or interstitial fibrosis and tubular atrophy, P<0.001) on kidney biopsy. Clinical follow-up data were available for 160 patients, of which 64 (40%) biopsy results were EXT1/EXT2-positive and 96 (60%) were EXT1/EXT2-negative. The proportion of patients with class 3/4 lupus nephritis coexisting with membranous lupus nephritis was not different between the EXT1/EXT2-positive and EXT1/EXT2-negative groups (25.0% versus 32.3%; P=0.32). The patients who were EXT1/EXT2-negative evolved to ESKD faster and more frequently compared with EXT1/EXT2-positive patients (18.8% versus 3.1%; P=0.003).ConclusionsThe prevalence of EXT1/EXT2 positivity was 32.6% in our cohort of membranous lupus nephritis. Compared with EXT1/EXT2-negative membranous lupus nephritis, EXT1/EXT2-positive disease appears to represent a subgroup with favorable kidney biopsy findings with respect to chronicity indices. Cases of membranous lupus nephritis that are EXT1/EXT2-negative are more likely to progress to ESKD compared with those that are EXT1/EXT2-positive.


2021 ◽  
Vol 10 (18) ◽  
pp. 4191
Author(s):  
Yura Chae ◽  
Hye Eun Yoon ◽  
Yoon Kyung Chang ◽  
Young Soo Kim ◽  
Hyung Wook Kim ◽  
...  

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulonephritis characterized by diffuse deposits of IgM in the glomerular mesangium. However, its renal prognosis remains unknown. We compared renal outcomes of IgMN patients with those of patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), or mesangial proliferative glomerulonephritis (MsPGN) from a prospective observational cohort, with 1791 patients undergoing native kidney biopsy in eight hospitals affiliated with The Catholic University of Korea between December 2014 and October 2020. IgMN had more mesangial proliferation and matrix expansion than MsPGN and more tubular atrophy and interstitial fibrosis than MCD. IgMN patients had decreased eGFR than MCD patients in the earlier follow-up. However, there was no significant difference in urine protein or eGFR among all patients at the last follow-up. When IgMN was divided into three subtypes, patients with FSGS-like IgMN tended to have lower eGFR than those with MCD-like or MsPGN-like IgMN but higher proteinuria than MsPGN-like IgMN without showing a significant difference. The presence of hypertension at the time of kidney biopsy predicted ≥20% decline of eGFR over two years in IgMN patients. Our data indicate that IgMN would have a clinical course and renal prognosis similar to MCD, FSGS, and MsPGN


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Ailish Nimmo ◽  
Arvind Singh ◽  
Jena Hopkins ◽  
Anna Rixon ◽  
Spoorthy Sreerama ◽  
...  

Abstract Background and Aims Determining the renal prognosis for patients with ANCA associated vasculitis (AAV) is important in guiding treatment decisions, including balancing the risks and benefits of aggressive immunosuppression, and informing patients of their likely trajectory. We examined the performance of the clinicopathologic risk stratification tool developed by Brix et al. 1 in determining renal outcomes in a cohort of AAV patients in the South West of England. Method A retrospective review of case notes of patients diagnosed with AAV between 2010 and 2020 from two renal units (Bristol and Plymouth) was performed. Patients were followed up until 1st August 2020. Demographic details, kidney function at presentation and initial treatment regime were collected alongside kidney biopsy data. The renal risk score divides patients into three groups determined as being at low, medium and high risk of adverse renal outcomes based on (1) the percentage of normal glomeruli on kidney biopsy, (2) the percentage of tubular atrophy and interstitial fibrosis on kidney biopsy and (3) eGFR at diagnosis. The outcome of interest was the development of end stage kidney disease (ESKD), defined as a dialysis requirement &gt;3months or kidney transplantation. Patients were censored for death. Results In total 93 individuals were diagnosed with AAV over the study period; 51% were female and the median age at diagnosis was 69 years [IQR 60-78]. ANCA subclass was MPO positive in 73% of cases, PR3 positive in 19% and ANCA negative in 8%. At presentation, 42% had an eGFR below 15ml/min/1.73m2. With respect to risk scores, 17% of individuals were low risk (n=16), 52% were medium risk (n=48) and 31% were high risk (n=29). Median follow up was 3.2 years [IQR 1.3-5.9], over which time 18% of patients developed ESKD (1 in the low risk group, 7 in the medium risk group and 9 in the high risk group). A further 20% of patients died. A Kaplan-Meier survival curve (Figure 1) demonstrated worsening renal survival with rising risk group (Log-rank test, p=0.05). At 1 year, 74 patients (80%) were alive and in these individuals renal survival was 100% in the low risk group, 91% in medium risk group and 75% in the high risk group. Conclusion Overall, 18% of patients developed ESKD over a median follow up of 3.2 years. The renal risk score developed by Brix et al. helps prognosticate renal survival and may assist in shared decision making with patients regarding treatment options. The score demonstrates the importance of the degree of chronicity in determining renal survival. Further work in larger cohorts to compare the performance of the risk score in different subgroups of patients with AAV would be informative.


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249592
Author(s):  
Rozita Mohd ◽  
Nur Ezzaty Mohammad Kazmin ◽  
Rizna Abdul Cader ◽  
Nordashima Abd Shukor ◽  
Yin Ping Wong ◽  
...  

Introduction IgA nephropathy (IgAN) has a heterogeneous presentation and the progression to end stage renal disease (ESRD) is often influenced by demographics, ethnicity, as well as choice of treatment regimen. In this study, we investigated the long term survival of IgAN patients in our center and the factors affecting it. Methods This study included all biopsy-proven IgAN patients with ≥ 1year follow-up. Patients with diabetes mellitus at diagnosis and secondary IgAN were excluded. Medical records were reviewed for demographics, clinical presentation, blood pressure, 24-hour urine protein, serum creatinine, renal biopsy and treatment received. The primary outcome was defined as combined event of 50% estimated glomerular filtration rate (eGFR) reduction or ESRD. Results We included 130 (74 females; 56 males) patients of mean age 38.0 ± 14.0 years and median eGFR of 75.2 (interquartile range (IQR) 49.3–101.4) ml/min/1.73m2. Eighty-four (64.6%) were hypertensive at presentation, 35 (26.9%) had nephrotic syndrome and 57 (43.8%) had nephrotic range proteinuria (NRP). Median follow-up duration was 7.5 (IQR 4.0–13.0) years. It was noted that 18 (13.8%) developed ESRD and 34 (26.2%) reached the primary outcome. Annual eGFR decline was -2.1 (IQR -5.3 to -0.1) ml/min/1.73m2/year, with median survival of 20 years. Survival rates from the combined event (50% decrease in eGFR or ESRD) at 10, 20 and 30 years were 80%, 53% and 25%, while survival from ESRD were 87%, 73% and 65%, respectively. In the univariate analysis, time-average proteinuria (hazard ratio (HR) = 2.41, 95% CI 1.77–3.30), eGFR <45ml/min/1.73m2 at biopsy (HR = 2.35, 95% CI 1.03–5.32), hypertension (HR = 2.81, 95% CI 1.16–6.80), mean arterial pressure (HR = 1.02, 95% CI 1.01–1.04), tubular atrophy/interstitial fibrosis score (HR = 3.77, 95% CI 1.84–7.73), and cellular/fibrocellular crescent score (HR = 2.44, 95% CI 1.19–5.00) were found to be significant. Whereas only time-average proteinuria (TA-proteinuria) remained as a significant predictor in the multivariate analysis (HR = 2.23, 95% CI 1.57–3.16). Conclusion In our cohort, TA-proteinuria was the most important predictor in the progression of IgAN, irrespective of degree of proteinuria at presentation.


2021 ◽  
pp. 239936932110319
Author(s):  
Yihe Yang ◽  
Zachary Kozel ◽  
Purva Sharma ◽  
Oksana Yaskiv ◽  
Jose Torres ◽  
...  

Introduction: The prevalence of chronic kidney disease (CKD) is high among kidney neoplasm patients because of the overlapping risk factors. Our purpose is to identify kidney cancer survivors with higher CKD risk. Methods: We studied a retrospective cohort of 361 kidney tumor patients with partial or radical nephrectomy. Linear mixed model was performed. Results: Of patients with follow-up >3 months, 84% were identified retrospectively to fulfill criteria for CKD diagnosis, although CKD was documented in only 15%. Urinalysis was performed in 205 (57%) patients at the time of nephrectomy. Multivariate analysis showed interstitial fibrosis and tubular atrophy (IFTA) >25% ( p = 0.005), severe arteriolar sclerosis ( p = 0.013), female gender ( p = 0.024), older age ( p = 0.012), BMI ⩾ 25 kg/m2 ( p < 0.001), documented CKD ( p < 0.001), baseline eGFR ⩽ 60 ml/min/1.73 m2 ( p < 0.001), and radical nephrectomy ( p < 0.001) were independent risk factors of lower eGFR at baseline and during follow-up. Average eGFR decreased within 3 months post nephrectomy. However, patients with different risk levels showed different eGFR time trend pattern at longer follow-ups. Multivariate analysis of time × risk factor interaction showed BMI, radical nephrectomy and baseline eGFR had time-dependent impact. BMI ⩾ 25 kg/m2 and radical nephrectomy were associated with steeper eGFR decrease slope. In baseline eGFR > 90 ml/min/1.73 m2 group, eGFR rebounded to pre-nephrectomy levels during extended follow-up. In partial nephrectomy patients with baseline eGFR ⩾ 90 ml/min/1.73 m2 ( n = 61), proteinuria ( p < 0.001) and BMI ( p < 0.001) were independent risk factors of decreased eGFR during follow up. Conclusions: As have been suggested by others and confirmed by our study, proteinuria and CKD are greatly under-recognized. Although self-evident as a minimum workup for nephrectomy patients to include SCr, eGFR, urinalysis, and proteinuria, the need for uniform applications of this practice should be reinforced. Non-neoplastic histology evaluation is valuable and should include an estimate of global sclerosis% (GS) and IFTA%. Patients with any proteinuria and/or eGFR ⩽ 60 at the time of nephrectomy or in follow-up with urologists, and/or >25% GS or IFTA, should be referred for early nephrology consultation.


2018 ◽  
Vol 16 ◽  
pp. 205873921880268
Author(s):  
Qijun Wan ◽  
Yongcheng He ◽  
Hongtao Chen ◽  
Hongping Liu ◽  
Saodong Luan ◽  
...  

IgA nephropathy (IgAN) is now widely recognized as the most common primary glomerulonephritis worldwide, especially in China. The immunosuppressive treatment option for IgAN is still controversial. Previously, we proved that mycophenolate mofetil (MMF; Shanghai Roche, China) combined with low-dose prednisone was an effective and safe option for biopsy-proven mild to moderate IgAN patients in a short term of follow-up. This article we first reported the safety and efficacy of this regimen in a 42-year-old male biopsy-proven advanced 10-year follow-up IgAN case (Lee’s Class V; the patient was biopsied 10 years ago, so the Oxford Mesangial hypercellularity Endocapillary hypercellularity Segmental glomerulosclerosis Tubular atrophy/interstitial fibrosis (MEST) classification was not used). The mycophenolate and prednisone were only given for a limited time. The other main medications included calcium channel blockers and antiplatelet agents. Clinical and laboratory indexes were aperiodic assessed during the 10-year follow-up. The serum creatinine decreased from 356 to around 210 μmol/L and urine excretion protein reduced from 3.4 g/d to about 0.5 g/d after 6 months of the initiation of this regimen, respectively. These perfect treatment effects could maintain well during the whole follow-up period. No obvious complications were observed.


2013 ◽  
Vol 137 (4) ◽  
pp. 531-540 ◽  
Author(s):  
Steven P. Salvatore ◽  
Eugene K. Cha ◽  
James S. Rosoff ◽  
Surya V. Seshan

Context.—Evaluating nontumor portions of tumor nephrectomies is useful to diagnose nonneoplastic renal disease. Objective.—To determine the medical renal disease frequency and to assess the prognostic significance of the various renal pathologic variables with long-term follow-up in tumor nephrectomy patients. Design.—We reviewed nonneoplastic kidney sections of 456 consecutive cases from 1998 to 2008. Seventy-five cases were excluded (19 tumor compression, 25 no nonneoplastic tissue, 22 embolized kidneys, 9 end stage). Special staining, immunofluorescence, and/or electron microscopy was performed where appropriate. Vascular sclerosis was scored from mild to severe; interstitial fibrosis/tubular atrophy and global glomerulosclerosis (GS) were expressed as percentages. Follow-up, minimum 12 months, was evaluated in 156 cases. All renal pathologic variables were compared with regard to change in creatinine level from preoperative assessment to follow-up. Results.—Of 381 cases, 57 had additional medical renal disease (15%), most frequently diabetic nephropathy (28) and hypertensive nephropathy (11). Postoperative creatinine levels increased significantly in patients with severe arteriosclerosis or arteriolosclerosis, &gt;5% GS, and &gt;10% interstitial fibrosis/tubular atrophy. Seventy-four percent of cases with additional nonneoplastic diagnoses showed severe arteriolosclerosis. Higher corresponding GS was seen in the more affected vascular cases: mean, 5.56% GS for mild versus 23% GS for severe. Three patients progressed to renal failure 1 to 4 years after nephrectomy, 2 with hypertensive nephrosclerosis and 1 with diabetic nephropathy. Conclusions.—Medical renal disease was identified in 15% of tumor nephrectomy specimens. The degrees of vascular sclerosis, GS, and interstitial fibrosis/tubular atrophy are predictive of elevated creatinine levels in postnephrectomy patients. Prognostic implications of the nontumor pathology are important in nephrectomized patients.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Cristina Rabasco ◽  
Ana Martínez ◽  
Rosa Ortega ◽  
Mario Espinosa

Abstract Background and Aims Membranous nephropathy (MN) is the most common cause of biopsied nephrotic syndrome in adults. Recently, it has been reported that the pathogenesis of MN may be associated with an activation of the complement system. The pathway of activation is not clearly established. The intensity of C3 deposition could be a good marker of this activation in MN as has been shown in other diseases (IgA nephropathy, crescentic GN). The aim of this study is to evaluate clinical-pathological data in a cohort of patients with MN and the significance of glomerular C3 staining as a possible predictor of renal outcomes. Method We analysed patients with idiopathic MN biopsied in our department between January 2000 and December 2019, excluding those who had no material for IF (n = 115). The patients were divided into positive (87 cases) and negative (28 cases) based on glomerular C3 deposition. We assessed the clinical and histological characteristics and the percentage of spontaneous remission (SR) and end-stage renal disease (ESRD). Results A total of 115 patients with MN were followed with a median follow-up of 65 (25-161) months. We found no differences in baseline characteristics between both groups, with the exception that patients with C3 deposit had less albumin at the time of biopsy that negative patients [2.4 (2-2.9) vs 2.8 (2.3-3.1) g/dl, P=0.011)]. Patients with C3-negative had a higher percentage of SR than patients with C3-positive (75 vs 24%, P = 0.000) and less need for immunosuppressive treatment (18 vs 56%, P =0.001). At the most recent follow-up, C3-positive group had higher creatinine [1.42 (0.8-1.7) vs 0.97 (0.71-1) mg/dl, P=0.045] and proteinuria [1.64 (0.08-3.2) vs. 0.62 (0.05-0.79) g / 24h, P = 0.039]. Regarding histology, we found no differences in glomerular sclerosis, tubular atrophy and interstitial fibrosis. The renal survival analysis showed no statistically significant differences between both groups (P = 0.091). We analysed a subgroup of patients (n = 23) with antibodies against the phospholipase receptor on blood at the time of the biopsy (13/23 were positive). 84% of this positive group presented C3-positive in the renal biopsy vs 25% of the C3-negative group (P =0.008). Conclusion Patients without C3 staining show a higher rate of SR and less need for immunosuppressive treatment than patients with C3-positive. These results would support the theory that complement activation in this entity can play an important role. It is possible that these patients with negative C3 deposit represent a MN with evolution to SR and in these patients and that these patients do not need immunosuppressive treatment.


Lupus ◽  
2021 ◽  
pp. 096120332098453
Author(s):  
Bahar Bagheri ◽  
Seyed Mohammad Owji ◽  
Simin Torabinezhad ◽  
Hadi Raeisi Shahraki ◽  
Amirhossein Kamalinia ◽  
...  

Introduction Renal involvement is seen in about 40-82% of systemic lupus erythematosus (SLE) Asian patients. The exact diagnosis and classification of lupus nephritis are important for treatment and prognosis. This study aimed to investigate the value of electron microscopy (EM) in the diagnosis and classification of lupus nephritis compared with light microscopy. Method In this cross-sectional referral-center 16-year study of lupus nephritis, the final diagnosis was based on the EM study. Primary light microscopy findings were compared with EM diagnosis. Moreover, Immunofluorescence patterns distribution was assessed. Results From 496 patients diagnosed with lupus nephritis based on EM, 225(45.4%) of patients were categorized in class IV, followed by 98(19.7%), 93(18.8%), 46(9.3%), and 14(2.8%) who were categorized into classes of II, III, V, and VI respectively. Only 1(0.2%) patient belonged to class I, and 19(3.8%) cases were diagnosed with mixed two classes. Using EM was essential for diagnosing 25.6% of cases taking the correct classification by light microscopy into account; however, disregarding correct classification, this could change to a 7.4% contribution rate of EM. The most common cause of misdiagnosis, disregarding incorrect classification, was inadequate or wrong tissue. Positive associations were detected between tubular atrophy and interstitial fibrosis of both electron and light microscopy with different classes (P < 0.001). Conclusion While light microscopy is highly accurate for diagnosing lupus nephritis regardless of correct classification, EM contributes substantially to the correct classification of lupus nephritis types.


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