Kidney biopsy chronicity grading in antineutrophil cytoplasmic antibody-associated vasculitis

2021 ◽  
Author(s):  
Marta Casal Moura ◽  
Fernando C Fervenza ◽  
Ulrich Specks ◽  
Sanjeev Sethi
Keyword(s):  
Renal Function ◽  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Response To Treatment ◽  
Remission Induction ◽  
Induction Treatment ◽  
Tubular Atrophy ◽  
Renal Outcomes ◽  
The Impact

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.

scholarly journals In Patients with Membranous Lupus Nephritis, Exostosin-Positivity and Exostosin-Negativity Represent Two Different Phenotypes

2021 ◽  
pp. ASN.2020081181 ◽  
Author(s):  
Aishwarya Ravindran ◽  
Marta Casal Moura ◽  
Fernando C. Fervenza ◽  
Samih H. Nasr ◽  
Mariam P. Alexander ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Study Cohort ◽  
Lower Serum ◽  
Tubular Atrophy ◽  
Novel Proteins ◽  
Biopsy Specimens ◽  
Membranous Lupus Nephritis

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.

scholarly journals The Impact of Endovascular Aneurysm Repair on Long Term Renal Function Based on Hard Renal Outcomes

2019 ◽  
Vol 70 (4) ◽  
pp. 1380
Author(s):  
E.R. Charles ◽  
D. Lui ◽  
J. Delf ◽  
R.D. Sayers ◽  
M.J. Bown ◽  
...  
Keyword(s):  
Renal Function ◽  
Endovascular Aneurysm Repair ◽  
Renal Outcomes ◽  
Aneurysm Repair ◽  
The Impact

Cellular pharmacokinetics of daunorubicin: relationships with the response to treatment in patients with acute myeloid leukemia.

1988 ◽  
Vol 6 (5) ◽  
pp. 802-812 ◽  
Author(s):  
E Kokenberg ◽  
P Sonneveld ◽  
W Sizoo ◽  
A Hagenbeek ◽  
B Löwenberg
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Response To Treatment ◽  
Remission Induction ◽  
Pharmacokinetic Parameters ◽  
Induction Treatment ◽  
Blast Cells ◽  
Acute Myeloid

In an attempt to identify pharmacokinetic factors that determine the response of acute myeloid leukemia (AML) patients to induction chemotherapy, we determined the concentrations of daunorubicin (DNR) and the main metabolite daunorubicinol (DOL) in vivo and particularly evaluated the concentrations in blood and bone marrow nucleated cells. Cell measurements were obtained in 37 evaluable patients during their first remission induction treatment with DNR and cytarabine (ara-C) and directly compared with the plasma distribution kinetics of DNR. We show that (1) plasma DNR concentrations do not correlate with DNR concentrations in bone marrow nucleated cells; but (2) plasma area under the curve (AUC) values of DNR correlate inversely (P less than .01) with AUC values of DNR in WBCs; (3) concentrations of DNR in WBCs correlate positively (P less than .01) with DNR concentrations in bone marrow nucleated cells; and (4) the concentrations of DNR in WBCs show a negative correlation (P less than .01) with the numbers of peripheral blast cells at diagnosis. We then tested whether the pharmacokinetic parameters had predictive value for the clinical outcome of therapy, but none of the plasma levels or WBC and bone marrow concentrations of DNR predicted treatment outcome. The inverse correlation between the concentrations of DNR in WBC and the numbers of peripheral blast cells suggests that the effective DNR concentrations achieved intracellularly are mainly a function of the tumor load so that lesser amounts of DNR accumulate intracellularly when the AML cell numbers in blood are higher.

Propylthiouracil-induced Antineutrophil Cytoplasmic Antibody (ANCA)-associated Renal Vasculitis Versus Primary ANCA-associated Renal Vasculitis: A Comparative Study

2012 ◽  
Vol 39 (3) ◽  
pp. 558-563 ◽  
Author(s):  
YONG-XI CHEN ◽  
WEN ZHANG ◽  
XIAO-NONG CHEN ◽  
HAI-JIN YU ◽  
LI-YAN NI ◽  
...  
Keyword(s):  
Estimated Glomerular Filtration Rate ◽  
Interstitial Fibrosis ◽  
Renal Involvement ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Good Prognosis ◽  
Small Vessel Vasculitis ◽  
Renal Survival ◽  
Tubular Atrophy ◽  
Renal Vasculitis ◽  
Immunological Abnormalities

Objective.Renal involvement is frequently present in primary antineutrophil cytoplasmic antibody-associated small-vessel vasculitis (AAV) as well as propylthiouracil (PTU)-induced AAV. We analyzed the characteristics of patients with PTU-induced AAV with renal involvement and investigated the differences of the 2 diseases.Methods.Thirty-six patients with PTU-induced AAV, diagnosed from 1997 to 2010, were enrolled for study. Their data were compared with those of 174 patients with primary AAV diagnosed at the same time. Renal involvement was present in all patients.Results.There was a prominent proportion of young women with PTU-induced AAV (p < 0.01). They had lower levels of proteinuria and serum creatinine and higher estimated glomerular filtration rate (p < 0.01, p < 0.01, and p < 0.01, respectively). Clinical immunological abnormalities were less severe in patients with PTU-induced AAV. Patients with PTU-induced AAV had less organ involvement and lower Birmingham Vasculitis Assessment Score than patients with primary AAV (p < 0.01). Renal biopsies showed a lower proportion of glomeruli with crescents (p < 0.01). Interstitial inflammation was less severe in patients with PTU-induced AAV (p < 0.05). Similarly, interstitial fibrosis and tubular atrophy were less severe in patients with PTU-induced AAV (p < 0.01, p < 0.05, respectively). Renal survival and total survival were better in patients with PTU-associated vasculitis (p < 0.05, p = 0.01).Conclusion.Clinical and histopathological abnormalities were less severe in patients with PTU-induced AAV and most of them had a good prognosis.

Retrospective analysis of nephritis response and renal outcome in a cohort of 928 Egyptian lupus nephritis patients: a university hospital experience

Lupus ◽  
2017 ◽  
Vol 26 (14) ◽  
pp. 1564-1570 ◽  
Author(s):  
M Momtaz ◽  
A Fayed ◽  
M Wadie ◽  
S M Gamal ◽  
S A Ghoniem ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lupus Nephritis ◽  
Serum Creatinine ◽  
Lupus Erythematosus ◽  
Interstitial Fibrosis ◽  
University Hospital ◽  
Response To Treatment ◽  
Renal Outcome ◽  
Induction Treatment ◽  
Baseline Serum

Aim We aim to describe the pattern of response to treatment in a cohort of Egyptian lupus nephritis (LN) patients and to define variable prognostic factors. Methods We retrospectively analyzed records of 928 systemic lupus erythematosus (SLE) patients (898 females, 30 males) with biopsy-confirmed LN seen between 2006 and 2012 at Cairo University hospitals. Results Our study involved 928 SLE patients with a mean age of 26.25 ± 6.487 years, mean LN duration at time of renal biopsy 6.48 ± 4.27 months, mean SLEDAI 28.22 ± 11.7, and mean follow-up duration of 44.14 ± 17.34 months. Induction treatment achieved remission in 683 patients. Remission was achieved in all 32 patients with class II LN, compared to 651/896 (72.7%) patients in classes III, IV, and V. Induction by intravenous (IV) cyclophosphamide achieved response in 435/575 (75.7%) patients, while induction by mycophenolate mofetil (MMF) resulted in response in 216/321 (67.3%) patients ( p = 0.0068). Nephritic flares were least observed when MMF was used for maintenance (30/239 (12.6%) patients), compared to 71/365 patients (19.5%) ( p = 0.0266) when azathioprine (AZA) was used, and 22/79 patients (27.8%) ( p = 0.002) with IV cyclophosphamide. Class IV LN, high chronicity index, presence of crescents, and interstitial fibrosis in biopsies were all associated with chronic kidney disease (CKD) development eventually ( p < 0.001, p = 0.005, p = 0.012, and p = 0.031, respectively). By the end of the study duration, 305 (32.7%) patients had CKD. Logistic regression detected that high baseline serum creatinine, failure to achieve remission, hypertension, and nephritic flare were the main risk factors for poor renal outcome ( p < 0.001, p < 0.001, p = 0.004, and p < 0.001, respectively). The 5 years’ mortality was 69 (7.4%) patients with sepsis being the main cause of death. Conclusion IV cyclophosphamide superseded as induction treatment, while MMF was the best maintenance treatment. High serum creatinine, hypertension, and nephritic flare were the main risk factors for poor renal outcome.

scholarly journals Rhubarb Enema Decreases Circulating Trimethylamine N-Oxide Level and Improves Renal Fibrosis Accompanied With Gut Microbiota Change in Chronic Kidney Disease Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunlan Ji ◽  
Yin Li ◽  
Yenan Mo ◽  
Zhaoyu Lu ◽  
Fuhua Lu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intestinal Microbiota ◽  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Underlying Mechanism ◽  
Uremic Toxins ◽  
16S Rrna Sequence ◽  
Tubular Atrophy ◽  
The Impact

Objectives: Trimethylamine N-oxide (TMAO), a metabolic product of gut flora, is increased in chronic kidney disease (CKD) subjects and is recognized as one type of uremic toxins which is associated with poor cardiovascular outcomes and kidney function loss. Previous studies have suggested that rhubarb enema could reduce circulating uremic toxins such as urea, creatinine, and indoxyl sulfate and also regulate the intestinal microbiota. However, whether rhubarb enema retards kidney dysfunction by reducing circulating TMAO and its underlying mechanism, are still unclear. The present study aims to investigate the impact of rhubarb enema on TMAO and its precursors, as well as on the intestinal microbiota in 5/6 nephrectomized (5/6Nx) CKD rats.Design: Rats in the treatment groups were given rhubarb enema after modeling. At the end of the study, blood, feces, and kidney tissues were collected and processed for biochemical analyses, histological and western blot analyses, 16S rRNA sequence and untargeted metabolomic analyses.Results: Rhubarb enema reduced serum TMAO and trimethylamine (TMA) levels, inhibited the expression of inflammatory markers (interleukin-6, tumor necrosis factor α and Interferon-γ) and alleviated tubular atrophy, monocyte infiltration and interstitial fibrosis in 5/6Nx CKD rats. Moreover, rhubarb enema significantly increased the abundance of some symbiotic bacteria and probiotics, while reduced the abundance of some potential pathogens at the genus level. In addition, Spearman’s correlation analysis revealed that lachnospiraceae and romboutsia were positively correlated with TMAO.Conclusion: Rhubarb enema decreases circulating TMAO level and improves renal fibrosis in 5/6Nx CKD rats, which may be related to the regulation of intestinal microbial community.

scholarly journals MO003DISTAL RENAL TUBULAR ACIDOSIS IN PATIENTS WITH AUTOIMMUNE DISEASES

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Oana Ion ◽  
Valentina-Georgiana Fratila ◽  
Andreea Gabriella Andronesi ◽  
Camelia Achim ◽  
Elena Georgia Micu ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Renal Tubular Acidosis ◽  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Sjögren Syndrome ◽  
Sjogren Syndrome ◽  
Cryoglobulinemic Vasculitis ◽  
Urinary Ph ◽  
Tubular Atrophy ◽  
Renal Tubular

Abstract Background and Aims Distal renal tubular acidosis (DRTA) is characterized by hyperchloremic metabolic acidosis, with normal anion gap and with the inability to acidify the urine to a pH lower than 5.3. DRTA can evolve without symptoms and systemic acidosis, this form being defined as incomplete DRTA, that necessitates the use of a urinary acidification test like the Furosemide and Fludrocortisone test for establishing the diagnosis. There are several cases of type 1 DRTA reported in patients with autoimmune diseases, especially Sjögren syndrome and systemic lupus erythematosus (SLE), most of them being diagnosed due to severe symptoms caused by the associated hypokalemia. The prevalence of the DRTA in patients with autoimmune diseases is unknown, especially if we refer to the incomplete form. Method We conducted an observational prospective study in a selected cohort of 21 patients diagnosed with autoimmune diseases, who presented for evaluation in our clinic during December, 2020 and January, 2021. We included patients diagnosed with SLE, Sjögren syndrome, ANCA vasculitis, cryoglobulinemic vasculitis, who were submitted to Furosemide/Fludrocortisone test in our nephrology department. The urinary pH was evaluated hourly for 6 hours after the test began.  The test was considered positive if the urinary pH did not decrease &lt; 5.3. Results The study included 21 patients (16 females, 5 males, mean age 41.52 ± 17.58 years), diagnosed with SLE (13 patients, mean age 30.23 ± 10.34 years, eGFR 81.61±20.39 ml/min/1.73 m2), pANCA vasculitis (6 patients, mean age 60.83 ± 6.14, eGFR 40 ± 12.64 ml/min/1.73 m2), Sjogren syndrome (one 44 year-old patient, eGFR 39 ml/min/1.73 m2) and cryoglobulinemic vasculitis (one 69 year-old patient, eGFR 31 ml/min/1.73 m2). The test was positive for 4 patients out of 21 (3 females, one male; one with SLE, one with pANCA vasculitis, one with Sjogren syndrome and one with cryoglobulinemic vasculitis). Although 2 patients developed hypokalemia defined as a level of serum potassium lower than 3.5 mmol/l after the test and 1 patient augmented previous hypokalemia, there was not a significant change in kalemia (3.93 ± 0.32 mmol/l before the test vs 3.95 ± 0.49 mmol/l after the test, p=0.835). Although none of the patients developed metabolic alkalosis after the test, there was a significant increase in the level of serum bicarbonate (26.6 (2.2) mmol/l before the test vs 28.2 (2.7) mmol/l after the test, p=0.005) and also in the level of serum pH (7.36 ± 0.04 before the test vs 7.38 ± 0.04 after the test, p=0.018). None of the patients reported digestive or allergic side effects. It was interesting that the patients with vasculitis responded with delay to the treatment and urinary acidification under the pH of 5.3 occurred after a mean period of 3.2 hours in comparison to 1.5 hours in patients with SLE (p=0.014). Regarding the histological data, both the patients with vasculitis were elders, with an altered kidney function (both with a eGFR of 31 ml/min/1.73 m2) and severe tubular atrophy and interstitial fibrosis on kidney biopsy. The female patient with cryoglobulinemic vasculitis also had positive titers for antinuclear antibody, anti Ro-antibodies and anti-La antibodies. The patient with Sjögren syndrome was diagnosed with nephrocalcinosis and the kidney biopsy was not effectuated. The youngest patient with a positive test had preserved renal function, without tubular or interstitial lesions on kidney biopsy, but with a pattern of membranous lupus nephritis and with intense immunological activity (ANA, anti ds-DNA antibodies, anti RNP and Sm antibodies, antiphospholipid syndrome). Conclusion Incomplete DRTA was found in 4 out of 21 patients with autoimmune diseases, one with Sjogren syndrome and nephrocalcinosis, two with pANCA and cryoglobulinemic vasculitis with decreased eGFR and severe tubular atrophy and interstitial fibrosis and one young female with SLE.

A Validation of the 2018 Revision of International Society of Nephrology/Renal Pathology Society Classification for Lupus Nephritis: A Cohort Study from China

2020 ◽  
Vol 51 (6) ◽  
pp. 483-492 ◽  
Author(s):  
Juan Tao ◽  
Hui Wang ◽  
Xiao-Juan Yu ◽  
Ying Tan ◽  
Feng Yu ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Renal Biopsy ◽  
International Society ◽  
Interstitial Fibrosis ◽  
Activity Index ◽  
Renal Pathology ◽  
Tubular Atrophy ◽  
Female Ratio ◽  
Renal Outcomes

Background: A revision of the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification for lupus nephritis has been published in 2018. The current study aimed to verify the utility of this system. Materials and Methods: A total of 101 lupus nephritis patients from a large Chinese cohort who underwent renal biopsy in Peking University First Hospital were reevaluated by 2 renal pathologists, who had no knowledge of the clinical findings. The association between clinical data at the time of initial renal biopsy and follow-up and pathological features were further analyzed on all patients selected. Results: The mean age of the cohort was 33 years with a male/female ratio of 1:9, and a median follow-up period of 128 months. The presence and extent of mesangial hypercellularity, endocapillary hypercellularity, global and segmental glomerulosclerosis, neutrophil exudation/karyorrhexis, glomerular hyaline deposits, extracapillary proliferation (crescents), tubular atrophy/interstitial fibrosis, and interstitial inflammation were significantly correlated with several clinical renal injury indices (systemic lupus erythematosus disease activity index, serum creatinine value, proteinuria, and C3 level) at the time of biopsy. By multivariable Cox hazard analysis, fibrous crescents, tubular atrophy/interstitial fibrosis, and the modified National Institutes of Health chronicity index were independent risk factors for patients’ composite renal outcomes (hazard ratio [HR] 4.100 [95% CI 1.544–10.890], p = 0.005; HR 8.584 [95% CI 2.509–29.367], p = 0.001; and HR 3.218 [95% CI 1.138–9.099], p = 0.028; respectively). Conclusions: The 2018 revision of the ISN/RPS classification for lupus nephritis has utility for prediction of clinical renal outcomes.

What is the value of repeat kidney biopsies in patients with lupus nephritis?

Lupus ◽  
2020 ◽  
Vol 30 (1) ◽  
pp. 25-34
Author(s):  
Enrique Morales ◽  
Hernando Trujillo ◽  
Teresa Bada ◽  
Marina Alonso ◽  
Eduardo Gutiérrez ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Lupus Nephritis ◽  
Disease Progression ◽  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Repeat Biopsy ◽  
Vascular Lesions ◽  
Clinical Indication ◽  
Tubular Atrophy ◽  
Kidney Disease Progression

Introduction Recent studies with protocol biopsies have shown a mismatch between clinical and histological remission in lupus nephritis (LN). We aimed to evaluate histological changes in repeat kidney biopsies by clinical indication in patients with LN. Methods We analyzed 107 patients with LN in which a kidney biopsy was performed between 2008 and 2018. Of those, we included 26 (24.2%) who had ≥2 kidney biopsies. Classification was done according to the International Society of Nephrology/Renal Pathology Society. Results Mean time between biopsies was 71.5 ± 10.7 months. 73.1% of patients presented a change of class at repeat biopsy; 38.4% to a higher class and 34.6% to a lower class. A significant increase in glomerulosclerosis (% GS) (3.8% vs 18.7%, p = 0.006), interstitial fibrosis (3.8% vs 26.9%, p = 0.021), tubular atrophy (15.4% vs 57.7%, p = 0.001) and chronicity index (CI) (1 vs 3, p < 0.001) was observed at repeat biopsy. Subjects who developed chronic kidney disease progression had a lower rate of complete remission at 12 months (0% vs 37.5%, p = 0.02), higher % GS at first biopsy (7.9% vs 1.2%, p = 0.02) and higher CI (4 vs 2, p = 0.006), tubular atrophy (90% vs 37.6%, p = 0.008), interstitial fibrosis (50% vs 12.5%, p = 0.036) and vascular lesions (60% vs 18.8%, p = 0.031) at second biopsy. Conclusions Our major finding was that patients with LN showed a significant increase in % GS, interstitial fibrosis, tubular atrophy and vascular lesions in repeat biopsies performed by clinical indication. This suggest that a second kidney biopsy may provide valuable and useful information regarding kidney disease progression.

scholarly journals P0456LONG TERM PATIENT SURVIVAL AND RELAPSE RATE IN ANCA ASSOCIATED PATIENTS WITH RENAL INVOLVMENET - DATA FROM CROATIAN REFERRAL CENTER

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Matija Crnogorac ◽  
Ana Brechelmacher ◽  
Ivica Horvatić ◽  
Patricia Kacinari ◽  
Miroslav Tišljar ◽  
...  
Keyword(s):  
Relapse Rate ◽  
Interstitial Fibrosis ◽  
Renal Involvement ◽  
Induction Treatment ◽  
Tubular Atrophy ◽  
Free Survival ◽  
Acute Dialysis ◽  
Significant Difference ◽  
Stage Renal Disease

Abstract Background and Aims The aim of the research was to evaluate patient and renal as well as relapse free survival in ANCA associated vasculitis (AAV) patients in our center. Despite the advances in understanding pathogenesis of AAVs and advances in treatment, the outcomes of AAV patient differ in various centers. Method This study included 106 consecutive AAV patients with renal involvement in the period from 2007-2017. We performed renal biopsy on patients using automatic 16 Gauge needle. Light, immunofluorescent and electronic microscopy were performed. All the patients were treated with cyclophosphamide and steroids in induction treatment with adjuvant PLEX and dialysis depending on renal function and lung manifestations. Primary outcomes were combined outcome progression to end-stage renal disease, defined as persistent (more than three months) need for renal replacement therapy or permanent reduction of EGFR to &lt;15ml/minute (according to CKD EPI formula) and/or death (ESRDD), death (D) and ESRD alone, and disease relapse. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between phenotypes and finding significant predictors regarding outcomes. Out of 106 patients (55,6% female, median age 61; IQR 51-70) there were 66 (61,1%) microscopic poliangitiis (MPA), 20 (18,5%) granulomatosis with angitiis and 20 (18,5%) with renal limited vasculitis (RLV),There were 14 (13%) PR3-ANCA positive patients, 57 (52,8%) MPO ANCA positive, 5 (4,6%) PR3-ANCA+MPO-ANCA positive and 32 (29,6%) ANCA negative patients. Histologically (Berden classification) 43 (39,8%) patients had crescentic, 19 (17,6%) focal, 34 (31,5%) mixed and 12 (11,1%) sclerotic class. Follow up time ranged from 1 to 127 months. Median follow up time was 21 months (IQR = 7-44). Median time to diagnosis was 3 months (IQR 2,0-6,0). Results During follow up 21 (19,8%) patients died, 26 (24,5%) patients reached ESRD and 10 (9,4%) patients relapsed. There was no significant difference in outcomes between clinical, serological or histological phenotypes. In multivariant analysis independent predictors for death were age (HR = 1,059, 95% CI =1,001-1,120; p = 0,046), anemia (HR = 0,952, 95% CI =0,908-0,998; p = 0,040) and BVAS (HR = 1,093, 95% CI =1,030-1,159; p = 0,003), for ESRD. the need for acute dialysis (HR = 4,674, 95% CI =1,996-10,946; p = &lt; 0,001), and interstitial fibrosis and tubular atrophy (IFTA) percentage over 50% (HR = 2,652, 95% CI =1,157-6,081; p = 0,021). and for relapse rate younger age (HR = 0,924, 95% CI = 0,870-0,981; p =0,010), lower serum creatinine levels (HR = 0,996, 95% CI = 0,992-1,000; p = 0,033), and the need for acute dialysis (HR = 59,545, 95% CI =3,467-1022,665; p = 0,005). Event free survival after 12, 24, 36 and 60 months was for death 83,9, 81,2, 79 and 74,7%, for ESRD 80,6, 77,9, 76,1 and 71% and for relapse 95,3, 88,4, 88,4 and 85%. Conclusion Timely diagnosis and treatment can ensure better outcomes in AAV patients. Though there is an overlap in predictive factors between different cohorts, there are still distinctive differences especially between cohorts from clinical trials and those from observational studies. Our study is among few to show significance of anemia as clinical predictor and IFTA percentage as pathohistological predictor.

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