scholarly journals Enyhe szövettani eltérések ellenére gyors progressziójú proliferativ glomerulonephritis monoklonális immunglobulin-G-depozitumokkal

2018 ◽  
Vol 159 (38) ◽  
pp. 1567-1572
Author(s):  
Dóra Bajcsi ◽  
Kypros Constantinou ◽  
László Krenács ◽  
Zsolt Barabás ◽  
Szabolcs Molnár ◽  
...  
Keyword(s):  
Kidney Failure ◽  
Interstitial Fibrosis ◽  
Rapidly Progressive Glomerulonephritis ◽  
Proliferative Glomerulonephritis ◽  
Caucasian Woman ◽  
Tubular Atrophy ◽  
Nephritic Syndrome ◽  
Dense Deposits ◽  
Tubulointerstitial Lesions ◽  
First Time

Abstract: Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits is characterized by granular deposits of monoclonal IgG; histologically it has typically a membranoproliferative or endocapillary pattern, and seen electronmicroscopically there are dense deposits without substructure. Here, we present the case of a 62-year-old Caucasian woman who was admitted with rapidly progressive kidney failure. The patient’s status, the laboratory and imaging examinations did not support prerenal, postrenal and – among the intrinsic causes – vascular and tubulointerstitial origin. The proteinuria and dysmorphic microhematuria suggested rapidly progressive glomerulonephritis. Tests for anti-neutrophil cytoplasmic antibodies, anti-glomerular basement membrane, antinuclear antibodies and cryoglobulins were negative, the C3 and C4 levels were normal. The biopsy evaluation diagnosed proliferative glomerulonephritis with monoclonal IgG deposits because of mesangial granular deposits of IgG3-kappa, C3, and C1q, and ultrastructurally electron-dense deposits (incidence in our adult native kidney biopsy series: 0.18%). 31 glomeruli were assessed histologically. 29 glomeruli displayed mild mesangial hypercellularity, 2 glomeruli were globally sclerotic. Crescents were not observed. Mild arteriolar hyalinosis, interstitial fibrosis and tubular atrophy accompanied the glomerular alterations. In the postbiopsy evaluation, paraprotein or multiple myeloma was not detected. Despite the mild histological findings, the kidney failure progressed, and hemodialysis had to be started two weeks after the biopsy. Steroids, cyclophosphamide and rituximab did not affect her kidney function, and she remained on hemodialysis during the follow-up of 39 months. This report presents for the first time proliferative glomerulonephritis with monoclonal IgG deposits as the possible cause of rapidly progressive nephritic syndrome in the absence of pronounced glomerular proliferative, sclerotic or tubulointerstitial lesions. Orv Hetil. 2018; 159(38): 1567–1572.

scholarly journals Rapidly progressive glomerulonephritis and acute kidney injury associated with cocaine use - Case report

2020 ◽  
Author(s):  
Paulo Vitor de Souza Pimentel ◽  
Hermany Capistrano Freitas ◽  
Marcos Diógenes Braga Leite ◽  
Rafael Siqueira Athayde Lima ◽  
Dulce Maria Sousa Barreto ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Wide Spectrum ◽  
Rapidly Progressive Glomerulonephritis ◽  
Kidney Injury ◽  
Percutaneous Biopsy ◽  
Pulse Therapy ◽  
Tubular Atrophy ◽  
Anca Vasculitis ◽  
Nephritic Syndrome

ABSTRACT A wide spectrum of renal complications can occur with acute and chronic use of cocaine. Most cases are related to rhabdomyolysis, but other mechanisms are malignant hypertension, renal ischemia, and rapidly progressive glomerulonephritis (RPGN) associated-ANCA vasculitis. In recent years, the use of cocaine adulterated with levamisole has been associated with ANCA vasculitis and pauci-immune RPGN. RPGN is clinically manifested as a nephritic syndrome with a rapid and progressive decline in renal function, and its histopathological finding is the presence of crescents in more than 50% of the glomeruli. We report a case of a 38-year-old man chronic user of cocaine, alcohol, and cigarettes who had red urine, oliguria, swollen legs and eyelids, as well as the uremic symptoms anorexia, emesis, and mental confusion. He was admitted with acute kidney injury and performed six hemodialysis sessions during the first 16 days of hospitalization and then was transferred to a tertiary hospital for diagnostic investigation. Tests of ANF (antinuclear factor), ANCA, anti-DNA, serology for hepatitis B, C, and HIV virus were negative. A renal percutaneous biopsy revealed crescentic glomerulonephritis with mild tubular atrophy. The patient underwent pulse therapy with methylprednisolone (for 3 days) and cyclophosphamide. Then he maintained daily prednisone and monthly intravenous cyclophosphamide and evolved with progressive improvement of renal function.

scholarly journals Comparative Histological Subtyping of Immune Cell Infiltrates in MPO-ANCA and PR3-ANCA Glomerulonephritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Samy Hakroush ◽  
Désirée Tampe ◽  
Philipp Ströbel ◽  
Peter Korsten ◽  
Björn Tampe
Keyword(s):  
Mononuclear Cell ◽  
Plasma Cells ◽  
Immune Cell ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Tubular Atrophy ◽  
Interstitial Inflammation ◽  
Tubulointerstitial Lesions ◽  
Mononuclear Cell Infiltrates ◽  
Immune Cell Infiltrates

BackgroundAcute kidney injury (AKI) is a common and severe complication of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), potentially leading to chronic kidney disease (CKD), end-stage renal disease (ESRD), or death. Pathogenic ANCAs, in particular proteinase 3 (PR3) and myeloperoxidase (MPO), trigger a deleterious immune response with intrarenal immune cell infiltration resulting in a pauci-immune necrotizing and crescentic glomerulonephritis (GN). However, a systematic analysis of intrarenal immune cell subtypes concerning neutrophils, eosinophils, plasma cells, and mononuclear cell infiltrates (macrophages, lymphocytes) in ANCA GN remains elusive. Therefore, we aimed to compare distinct immune cell infiltrates in association with clinicopathological findings in ANCA GN.MethodsA total of 53 kidney biopsies with ANCA GN at the University Medical Center Göttingen were retrospectively analyzed. Histological infiltrates of neutrophils, eosinophils, plasma cells, and mononucleated cells (macrophages, lymphocytes) were quantified as a fraction of the total area of inflammation.ResultsNeutrophilic infiltrates were associated with glomerular necrosis and severe kidney injury in ANCA GN. Among tubulointerstitial lesions, intrarenal neutrophils correlated with interstitial inflammation, tubulitis, and inflammation in areas of interstitial fibrosis/tubular atrophy (IFTA), representing active inflammatory lesions. Concerning eosinophils, infiltrates were associated with severe kidney injury, interstitial inflammation, and cellular casts independent of glomerular lesions, implicating a distinct role in inflammation and damage in ANCA GN. Plasma cell infiltrates correlated with tubulitis and interstitial fibrosis and were associated with renal replacement therapy during the short-term disease course. Finally, mononuclear cell infiltrates correlated with severe kidney injury and active histopathological lesions (glomerular crescents, interstitial inflammation, tubulitis, inflammation, and tubulitis in areas of IFTA) besides chronic lesions (interstitial fibrosis and tubular atrophy) in ANCA GN. Interestingly, intrarenal subtypes of immune cell infiltrates differed in MPO-ANCA versus PR3-ANCA GN and were associated with distinct glomerular and tubulointerstitial lesions, implicating different pathogenic mechanisms of kidney injury in ANCA subtypes.ConclusionOur observations imply distinct pathomechanisms contributing to inflammation and renal injury in MPO vs. PR3-associated ANCA GN and potentially contribute to new therapeutic targets in specific ANCA subtypes.

Uric Acid as a Predictor of Immunoglobulin A Nephropathy Progression: A Cohort Study of 1965 Cases

2018 ◽  
Vol 48 (2) ◽  
pp. 127-136 ◽  
Author(s):  
Bin Zhu ◽  
Dong-rong Yu ◽  
Ji-cheng Lv ◽  
Yi Lin ◽  
Qiang Li ◽  
...  
Keyword(s):  
Uric Acid ◽  
Kidney Failure ◽  
Regression Models ◽  
Primary Outcome ◽  
Interstitial Fibrosis ◽  
Immunoglobulin A ◽  
Immunoglobulin A Nephropathy ◽  
Tubular Atrophy ◽  
Increased Risk ◽  
All Cause Mortality

Background: The role of serum uric acid (SUA) level in the progression of Immunoglobulin A nephropathy (IgAN) remains controversial. Methods: In a cohort of 1,965 cases with biopsy-proven IgAN, we examined the associations of SUA concentration with the primary outcome of a composite of all-cause mortality or kidney failure (defined as a reduction of estimated glomerular filtration rate [eGFR] by 40% from baseline, requirements for dialysis and transplantation), or the outcome of kidney failure alone, assessed using Cox and logistic regression models, respectively, with adjustment for confounders. Results: At baseline, the mean age was 33.37 ± 11.07 years, eGFR was 101.30 ± 30.49 mL/min/1.73 m2, and mean uric acid level was 5.32 ± 1.76 mg/dL. During a median of 7-year follow-up, 317 cases reached the composite outcome of all-cause mortality (5 deaths) or kidney failure (36 cases of dialysis, 5 cases of renal transplantation, and 271 cases with reduction of eGFR by 40% from baseline). After adjustment for demographic and IgAN specific covariates and treatments, a higher quartile of uric acid was linearly associated with an increased risk of the primary outcome (highest versus lowest quartile, hazard ratio [HR] 2.39; 95% CI 1.52–3.75) and kidney failure (highest versus lowest quartile, HR 2.55; 95% CI 1.62–4.01) in the Cox proportional hazards regression models. In the continuous analysis, a 1 mg/dL greater uric acid level was associated with 16% increased risk of primary outcome (HR 1.16, 95% CI 1.07–1.25) and 17% increased risk of kidney failure (HR 1.17, 95% CI 1.08–1.27), respectively, in the fully adjusted model. The multivariate ­logistic regression analyses for the sensitive analyses drew consistent results. In the subgroup analyses, significant interactions were detected that patients with mean arterial pressure (MAP) < 90 mm Hg or mesangial hypercellularity had a higher association of SUA with the incidence of the primary outcome than those with MAP ≥90 mm Hg or those without mesangial hypercellularity respectively. Hyperuricemia was not significantly associated with the risk of developing the primary outcome in elder patients (≥32 years old), patients with eGFR < 90 mL/min or with tubular atrophy/interstitial fibrosis. Conclusions: SUA level may be positively associated with the progression of IgAN. It was noticeable that the association of hyperuricemia with IgAN progression was less significant in patients with elder age, lower eGFR, or tubular atrophy/interstitial fibrosis, which may be due to some more confounders in association with the IgA progression in these patients. Future prospective studies are warranted to confirm these findings and to investigate the underlying mechanisms.

scholarly journals Impact of the relationship between hemoglobin levels and renal interstitial fibrosis on long-term outcomes in type 2 diabetes with biopsy-proven diabetic nephropathy

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Miho Shimizu ◽  
Kengo Furuichi ◽  
Shinji Kitajima ◽  
Tadashi Toyama ◽  
Megumi Oshima ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Interstitial Fibrosis ◽  
Long Term Outcomes ◽  
Renal Interstitial Fibrosis ◽  
Tubular Atrophy ◽  
Tubulointerstitial Lesions ◽  
The Impact

Abstract Background Progression of renal anemia has been shown to be associated with advanced renal tubulointerstitial lesions. This retrospective study investigated the impact of lower hemoglobin (Hb) levels and renal interstitial fibrosis and tubular atrophy (IFTA) on long-term outcomes in type 2 diabetes with biopsy-proven diabetic nephropathy. Methods A total of 233 patients were enrolled. The severity of IFTA was scored according to the classification by the Renal Pathology Society. Patients were stratified according to baseline Hb tertiles by IFTA status. The outcomes were the first occurrence of renal events (requirement for dialysis or 50 % decline in estimated glomerular filtration rate from baseline) and all-cause mortality. Results At baseline, 151 patients had severe IFTA. There were no patients who have been received erythropoiesis-stimulating agents at the time of renal biopsy. The severity of IFTA was the independent pathological factor of lower Hb levels. During the mean follow-up period of 8.6 years (maximum, 32.4 years), 119 renal events and 42 deaths were observed. Compared with the combined influence of the highest tertile of Hb and mild IFTA, the risks of renal events were higher for the middle tertile and for the lowest tertile of Hb in severe IFTA, whereas the risk of renal events was higher for the lowest tertile of Hb in mild IFTA. The risk of mortality was higher for the lowest tertile of Hb only in severe IFTA. There were significant interactions of tertile of Hb and IFTA in renal events and mortality. Conclusions Impacts of lower Hb levels on long-term outcomes of diabetic nephropathy were greater in severe IFTA than in mild IFTA.

scholarly journals Diabetic Nephropathy Amelioration by a Low-Dose Sitagliptin in an Animal Model of Type 2 Diabetes (Zucker Diabetic Fatty Rat)

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Cristina Mega ◽  
Edite Teixeira de Lemos ◽  
Helena Vala ◽  
Rosa Fernandes ◽  
Jorge Oliveira ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Low Dose ◽  
Interstitial Fibrosis ◽  
Diabetic Rats ◽  
Vascular Lesions ◽  
Tubular Atrophy ◽  
Dipeptidyl Peptidase 4 ◽  
Renal Lesions ◽  
Tubulointerstitial Lesions

This study was performed to assess the effect of chronic low-dose sitagliptin, a dipeptidyl peptidase 4 inhibitor, on metabolic profile and on renal lesions aggravation in a rat model of type-2 diabetic nephropathy, the Zucker diabetic fatty (ZDF) rat. Diabetic and obese ZDF (fa/fa) rats and their controls ZDF (+/+) were treated for 6 weeks with vehicle (control) or sitagliptin (10 mg/kg/bw). Blood/serum glucose, HbA1c, insulin, Total-c, TGs, urea, and creatinine were assessed, as well as kidney glomerular and tubulointerstitial lesions (interstitial fibrosis/tubular atrophy), using a semiquantitative rating from 0 (absent/normal) to 3 (severe and extensive damage). Vascular lesions were scored from 0–2. Sitagliptin in the diabetic rats promoted an amelioration of glycemia, HbA1c, Total-c, and TGs, accompanied by a partial prevention of insulinopenia. Furthermore, together with urea increment prevention, renal lesions were ameliorated in the diabetic rats, including glomerular, tubulointerstitial, and vascular lesions, accompanied by reduced lipid peroxidation. In conclusion, chronic low-dose sitagliptin treatment was able to ameliorate diabetic nephropathy, which might represent a key step forward in the management of T2DM and this serious complication.

P0448CHARACTERISTICS OF PRIMARY GLOMERULAR DISEASE PATIENTS WITH HEMATURIA IN TURKEY: THE DATA FROM TSN-GOLD WORKING GROUP

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Abdullah Sumnu ◽  
Kultigin Turkmen ◽  
Egemen Cebeci ◽  
Aydin Turkmen ◽  
Necmi Eren ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Basal Membrane ◽  
National Database ◽  
Tubular Atrophy ◽  
Laboratory Findings ◽  
Glomerular Diseases ◽  
Nephritic Syndrome ◽  
Serum Blood Urea Nitrogen ◽  
Primary Glomerular Diseases ◽  
Primary Glomerular Disease

Abstract Background and Aims Hematuria is one of the most common laboratory findings in nephrology practice. In different regions of the world, the etiologic causes differ. To date, there is no enough data regarding the clinical and histopathologic characteristics of primary glomerular diseases (PGD) patients with hematuria in our country. Method Data were obtained from national multicenter (47 centers) data entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database between May 2009 and June 2019. The data of all PGD patients over the age of 16 years who were diagnosed with renal biopsy and had hematuria data were included in the study. The biopsy samples were processed using a light microscopy and immunofluorescence examination. Demographic characteristics such as age, sex, indications for biopsy, primary glomerular diseases, comorbidities, laboratory and biopsy findings of all patients were also recorded. Hematuria was defined as the presence of at least 5 red blood cells/hpf. Results Data of 3394 patients were included to the study after the exclusion of patients with secondary glomerulonephritis and patients with missing biopsy findings. While 1699 (50.1%) patients had hematuria, 1695 (49.9%) patients did not have hematuria. Demographic, laboratory, and histopathological characteristics of patients with and without hematuria are given in Table. Patients with hematuria had statistically higher systolic blood pressure (SBP), serum blood urea nitrogen, creatinine, albumin, levels and urine pyuria, however, these patients had statistically lower age, body mass index, presence of hypertension and diabetes, eGFR, 24-hour proteinuria, serum total, HDL and LDL-cholesterol and C3 levels when compared with patients without hematuria. Figure depicted the etiologic causes of patients with and without hematuria. According to histopathological findings, number of global sclerotic glomeruli, cellular and fibrocellular crescents, the levels of mesangial proliferation, endocapillary proliferation, exudative changes in glomeruli, severe tubular atrophy, interstitial inflammation, subendothelial deposition, moderate and severe IgA and C3 deposition were found to be significantly higher and the levels of basal membrane thickening, interstitial fibrosis, subepithelial deposition, severe IgG staining were found to be significantly lower in patients with hematuria. Conclusion This is the first multicenter national report regarding the demographic and histopathologic data of PGD patients with or without hematuria. Hematuria, a feature of nephritic syndrome, was found at a higher than expected in the PGDs presenting with nephrotic syndrome in our national database.

scholarly journals Should We Always Defer Treatment of Kidney Disease When There Is Extensive Interstitial Fibrosis on Biopsy?

2016 ◽  
Vol 44 (4) ◽  
pp. 286-288 ◽  
Author(s):  
Musab S. Hommos ◽  
Andrew D. Rule
Keyword(s):  
Kidney Disease ◽  
Prognostic Marker ◽  
Kidney Failure ◽  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Strong Predictor ◽  
Tubular Atrophy ◽  
Severe Fibrosis

Severity of interstitial fibrosis and tubular atrophy (IFTA) seen on kidney biopsy has been used by nephrologist as prognostic marker of kidney disease. While IFTA is a very strong predictor of kidney failure, some patients with severe fibrosis will still not progress to kidney failure within 5 years. Treatment of underlying kidney disease in select patients with severe IFTA should be considered when risks of treatment are reasonable despite the low potential for benefit.

scholarly journals P0113STANDARDIZED GRADING OF CHRONIC CHANGES IN MINIMAL CHANGE DISEASE: A VALIDATION STUDY IN NATIVE KIDNEY BIOPSY SPECIMENS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Gabriel Stefan ◽  
Simona Stancu ◽  
Madalina Hoinoiu ◽  
Nicoleta Petre ◽  
Adrian Dorin Zugravu ◽  
...  
Keyword(s):  
Minimal Change Disease ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Composite Endpoint ◽  
Minimal Change ◽  
Renal Outcome ◽  
Renal Survival ◽  
Tubular Atrophy ◽  
Cox Proportional Hazard ◽  
First Time

Abstract Background and Aims Recently, a group of pathologists and nephrologists devised a simple scoring system for chronic changes based on the grading of glomerulosclerosis (GS), tubular atrophy (TA), interstitial fibrosis (IF) and arteriosclerosis (AS). We aimed to validate for the first time this score in patients with minimal change disease. Method We included 79 adult patients (age 50.3 (46.3, 54.3) years, 57% male, eGFR 54.7 (44.2, 63.5) mL/min) with biopsy proven MCD between 2010-2015 who were followed up until January 1, 2017. The extent of GS, TA and AS was scored from 0 to 3, 0 to 3 and 0 to 1, respectively. The scores were then added (total renal chronicity score) to grade the overall severity of the chronic lesions into minimal (0–1 total score), mild (2–4 total score), moderate (5–7 total score) and severe (&gt;8 total score). The outcomes were: patient survival; kidney survival defined as doubling of serum creatinine or ESRD; partial (proteinuria 0.3 to 3.5g/24h) or complete remission (proteinuria &lt;0.3g/24h) - whichever came first. Variables related to renal outcome were further evaluated in a multivariate Cox proportional hazard (CPH) model. Results Minimal chronic lesions were found in 77%, mild in 18% and moderate in 5% of the studied patients. Fifty percent had a null score of chronicity; they were younger (44 (29-53) versus 62 (44-66) years, p&lt;0.001), had higher eGFR (65.0 (42.1-83.2) versus 43.4 (25.8-63.9) mL/min, p&lt;0.01) but similar proteinuria (4.8 (1.9-8.2) versus 4.5 (1.1-6.7) g/g, p=0.3). Patients with a score higher than one had higher mortality (18% versus 0%, p&lt;0.001) and started RRT more often (15% versus 0%, p=0.01). There were no differences regarding the presentation as acute kidney injury, and in reaching complete or partial remission. Moreover, there were no clinical or pathology features that predicted remission. 17% of the patients reached the composite endpoint of kidney survival; mean kidney survival time was 5.7 (5.2, 6.3) years. In the CPH analysis the only independent predictors of decreased renal survival were elevated chronicity score (HR 1.56 (95%CI 1.14-2.14), p&lt;0.01), lower serum albumin (HR 0.27 (95%CI 0.08-0.88), p=0.03) and the presence of hypertension (HR 0.18 (95%CI 0.03-0.93), p=0.04). Conclusion To the best of our knowledge, this is the first study to validate the standardized grading of chronic changes as an independent predictor of renal survival in patients with minimal change disease.

Reproducibility of the Oxford classification of immunoglobulin A nephropathy, impact of biopsy scoring on treatment allocation and clinical relevance of disagreements: evidence from the VALidation of IGA study cohort

2018 ◽  
Vol 34 (10) ◽  
pp. 1681-1690 ◽  
Author(s):  
Shubha S Bellur ◽  
Ian S D Roberts ◽  
Stéphan Troyanov ◽  
Virginie Royal ◽  
Rosanna Coppo ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Immunoglobulin A ◽  
Study Cohort ◽  
Immunoglobulin A Nephropathy ◽  
Oxford Classification ◽  
Tubular Atrophy ◽  
Tubulointerstitial Lesions ◽  
The Oxford Classification ◽  
The Impact

Abstract Background The VALidation of IGA (VALIGA) study investigated the utility of the Oxford Classification of immunoglobulin A nephropathy (IgAN) in 1147 patients from 13 European countries. Methods. Biopsies were scored by local pathologists followed by central review in Oxford. We had two distinct objectives: to assess how closely pathology findings were associated with the decision to give corticosteroid/immunosuppressive (CS/IS) treatments, and to determine the impact of differences in MEST-C scoring between central and local pathologists on the clinical value of the Oxford Classification. We tested for each lesion the associations between the type of agreement (local and central pathologists scoring absent, local present and central absent, local absent and central present, both scoring present) with the initial clinical assessment, as well as long-term outcomes in those patients who did not receive CS/IS. Results All glomerular lesions (M, E, C and S) assessed by local pathologists were independently associated with the decision to administer CS/IS therapy, while the severity of tubulointerstitial lesions was not. Reproducibility between local and central pathologists was moderate for S (segmental sclerosis) and T (tubular atrophy/interstitial fibrosis), and poor for M (mesangial hypercellularity), E (endocapillary hypercellularity) and C (crescents). Local pathologists found statistically more of each lesion, except for the S lesion, which was more frequent with central review. Disagreements were more likely to occur when the proportion of glomeruli affected was low. The M lesion, assessed by central pathologists, correlated better with the severity of the disease at presentation and discriminated better with outcomes. In contrast, the E lesion, evaluated by local pathologists, correlated better with the clinical presentation and outcomes when compared with central review. Both C and S lesions, when discordant between local and central pathologists, had a clinical phenotype intermediate to double absent lesions (milder disease) and double present (more severe). Conclusion We conclude that differences in the scoring of MEST-C criteria between local pathologists and a central reviewer have a significant impact on the prognostic value of the Oxford Classification. Since the decision to offer immunosuppressive therapy in this cohort was intimately associated with the MEST-C score, this study indicates a need for a more detailed guidance for pathologists in the scoring of IgAN biopsies.

scholarly journals POS0247 INTERSTITIAL ANCA-ASSOCIATED VASCULITIS ASSOCIATES WITH SEVERE KIDNEY INJURY INDEPENDENT OF GLOMERULONEPHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 345.2-345
Author(s):  
S. Hakroush ◽  
B. Tampe
Keyword(s):  
Kidney Function ◽  
Current Knowledge ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Small Vessel ◽  
Small Vessel Vasculitis ◽  
Tubular Atrophy ◽  
Anca Associated Vasculitis ◽  
Tubulointerstitial Lesions ◽  
Peritubular Capillaritis

Background:Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a small vessel vasculitis affecting multiple organ systems, including the kidney. Small vessels in the kidney include small-sized arteries (interlobular artery, afferent and efferent arteriole), capillaries (glomerular and peritubular capillary) and venules.Objectives:Although crescentic ANCA glomerulonephritis (GN) is a common histological finding reflecting glomerular small vessel vasculitis, it is reasonable that manifestation of AAV could also contribute to interstitial small vessel vasculitis. Therefore, we here aimed to expand our current knowledge focusing on interstitial vasculitis in ANCA GN by systematic histological scoring of vascular lesions analogous to Banff.Methods:A total number of 49 kidney biopsies with confirmed renal involvement of AAV at the University Medical Center Göttingen were retrospectively included between 2015 till 2020. A renal pathologist (SH) evaluated all biopsies and was blinded to clinical data collection and analysis. A detailed methological section is provided in the Supplementary material and methods section.Results:Since previous studies established that crescentic ANCA GN associates with severe kidney injury and acute deterioration of kidney function in AAV, we first systematically scored interstitial vasculitis in association with requirement of renal replacement therapy (RRT). Among all active and chronic tubulointerstitial lesions analogous to the Banff scoring system, the only association between severe kidney injury requiring RRT was observed for interstitial vasculitis in AAV reflected by peritubular capillaritis (ptc, p=0.0002) and arteritis (v, p=0.0069), affecting 5/49 (10.2%) and 11/49 (22.4%) of renal biopsies, respectively. Since it is known that severe deterioration of kidney function also correlates with crescentic ANCA GN, we next directly compared glomerular and tubulointerstitial lesions. The fraction of normal glomeruli was inversely associated with interstitial fibrosis (ci), total (ti) and inflammation in IFTA (i-IFTA), whereas glomerular crescents were associated with interstitial inflammation (i), tubulitis (t) and total inflammation (ti). In contrast, global glomerular sclerosis associated with less interstitial inflammation (i) but correlated with interstitial fibrosis (ci) and tubular atrophy (ct), confirming established mechansim that chronic glomerular injury leads to tubular atrophy and interstitial fibrosis. Interestingly, no association between interstitial vasculitis (ptc and v correlating with severe kidney injury) and any glomerular lesion in ANCA GN (also correlating with severe kidney injury) was observed, thereby confirming that interstitial vasculitis contributes to severe kidney injury independent of ANCA GN. By contrast, short-term renal recovery from RRT was equal in both groups, suggesting a distinct association with acute decline of kidney function at disease onset.Conclusion:Taken together, by using the Banff scoring system we here expand our current knowledge of renal interstitial lesions in AAV revealing peritubular capillaritis and arteritis as important histological alterations associated with severe kidney injury in a considerable subset of AAV. Furthermore, our findings that interstitial vasculitis did not correlate with crescentic ANCA GN implicate that the characteristics of each vasculitis manifestation are independent and could further improve our understanding of mechanisms contributing to renal injury. These observations suggest that interstitial vasculitis in AAV may also affect long-term prognosis requiring further investigation.Disclosure of Interests:None declared

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