bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0424CLINICO-PATHOLOGICAL CHARACTERISTICS AND OUTCOMES OF PATIENTS WITH DNAJB9 POSITIVE FIBRILLARY GLOMERULONEPHRITIS
Authors: Liang Shaoshan , Liang Dandan , Xu Feng , Zhang Mingchao , Yang Fan , Li Ping , Zeng Caihong 
Published: June 2020

Abstract

Background and Aims
To investigate the clinicopathological features and prognosis of DNAJB9 positive fibrillary glomerulonephritis (FGN) in a single center in China.

Method
Cases diagnosed as FGN by renal biopsy from January 2011 to December 2019 in Jinling Hospital were stained with anti-DNAJB9 by immunohistochemistry. The patients with DNAJB9 positive FGN were retrospective analyzed.

Results
DNAJB9 staining of glomerular deposits was seen in 6 cases of FGN. 1 man and 5 women with a median age of 26 years (range, 21 to 49 years) were studied. Underlying autoimmune disease of Sjogren's syndrome and Hashimoto thyroiditis was in 1 case. None of them had dysproteinemia, malignancy, hepatitis C, hepatitis B, cryoglobulinemia, or diabetes. The patients presented with hypertension and edema in 5 cases, renal insufficiency in 1 case, and proteinuria in 6 cases with the median 24-hour urine protein 2.58 g (range, 1.66 to 9.57 g), nephrotic syndrome in 3 cases, and microscopic hematuria in 2 cases. The histologic pattern was mesangial proliferative glomerulonephritis (GN) and membranoproliferative GN. A mean of 9.7% of glomeruli were globally sclerotic. Crescents were present in 1 case (10%). The degree of tubular atrophy and interstitial fibrosis were absent (2 cases) and mild (4 cases), and severe acute tubular injury was in 1 case. All 6 cases showed glomerular positivity for IgG, C3 and C1q, 5 of which were positive for IgM, and 4 of which were positive for IgA. The glomerular deposits stained for polyclonal IgG subclasses and both kappa and lambda light chains in 3 cases. In 1 case, it stained for polyclonal IgG subclasses without kappa or lambda. IgG subclasses were IgG4 dominant in 3 cases and IgG1 dominant in 1 case. In 2 cases, they stained for monoclonal IgG1-kappa and IgG1-lambda. On electron microscopy (EM), the fibrillary deposits were seen infiltrating the mesangium, subendothelial, subepithelial area in all 6 cases, and the lamina densa of the GBMs in 5 cases with diameter of 7-40nm. Combined with observation of DNAJB9 staining, immunofluorescence microscopy and EM, extraglomerular deposits were identified in vessel walls in 5 cases, tubular basement membranes in 3 cases, peritubular capillaries in 3 cases. Congo red positivity was in 4 cases. At a median time of 32.9 months (range, 1 to 68.3 months) after biopsy, 3 cases were stable, 1 case had partial renal function recovery, and 2 cases had partial remission of proteinuria.

Conclusion
DNAJB9 immunohistochemistry is sensitive and specific for FGN. Monoclonal IgG and light chain was observed in young patients. Extraglomerular deposits were common. Prognosis was good in this young patient’s series.
P0436REFRACTORY IGA NEPHROPATHY. A MULTICYTOKINE NORMALIZED LEVELS THERAPY FOR T CELLS IMBALANCE
Authors: URIOL MIGUEL , Obrador Mulet Aina , Tugores Ana , Daza Vanessa , Gomez Ana , Gasco Joan 
Published: June 2020

Abstract

Background and Aims
Interleukine-17(IL-17) is a pro-inflammatory cytokine which influences in glomerulonephritis (GN) in animal models. IgA nephropathy (IgAN) is a primary GN with auto-inflammatory and autoimmune features. Imbalances in Th1/Th17 and Treg/Th17 have been associated with the pathogenesis of the IgAN. We evaluated the effect of sequential treatment with a selective vitamin D receptor activator and with an IL-17 blocker in patients with refractory IgA GN (r-IgAN).

Method
Five patients with r-IgAN (previously treated with steroids, mycophenolate, tacrolimus and a renin-angiotensin-aldosterone system inhibitor) were treated initially with paricalcitol and six months later with secukinumab (IL-17A blocker) with the objective to improve anti-inflammatory and subsequentially inhibit pro-inflammatory milieu, respectively. We evaluate the evolution of the proteinuria, haematuria, plasma creatinine and urinary N-acetyl-beta-D-glucosaminidase: u-NAG, as a measure of lysosomal activity during the first month of treatment (induction phase) and at month 3 after treatment. We also evaluate the evolution of the evolution of the Th1/Th17 and Treg/Th17 ratio in whole blood. We evaluated the changes at month (M) 0, 1 and 3.

Results
Five males were included. Age: 43±11 years. Proteinuria (24h-collected) decreased along the study from 3.5, 2.1 to 1.6g (P&lt;0.01) at M0, M1 and M3 respectively. Four (80%) patients who presented haematuria at month 0 disappeared at month 3. Creatinine did not show changes over time (1.84, 1.88 and 1.95 mg/dl for M0, M1 and M3, P=0.44). uNAG increased after induction phase from 7.2 to 9.8(P= 0.01) and finally decreased to 8.3 at month 3(P=1, respect to month1). Uric acid decreased but not significantly from 8.0, 7.1 and 7.6g/dl at any time point. The ratio Th1/Th17 and Treg/TH17 changed from the month 0 to month 3, from 1.8 to 2.6 (P =0.25) and 0.23 to 0.32 (P=0.16), respectively.

Conclusion
Sequential treatment was associated with a reduction in proteinuria and haematuria was well controlled.
The changes in u-NAG suggest and intensive initial effect on the lysosomal activity since no changes in renal function was observed.
The theoretical benefit of the Th1/Th17 and Treg/Th17 ratio represents a new modality of treatment that need to be rigorously evaluated for its clinical implication in r-IgAN patients.
P0443ONE YEAR AFTER PROTEINURIA IN LUPUS NEPHRITIS: EURO LUPUS VS MYCOPHENOLATE, A SINGLE-CENTER EXPERIENCE
Authors: Calderaro Alessandra , Cernaro Valeria , Cordiano Raffaele , Vienna Federica giada , Laudani Alfredo , Siligato Rossella , Gembillo Guido , AMATRUDA MICHELA , LA BARBERA GIULIA , Conti Giovanni , Santoro Domenico 
Published: June 2020

Abstract

Background and Aims
Lupus nephritis (LN) develops in about 50% of patients affected by Systemic Lupus Erythematosus (SLE) and it is associated with higher morbidity and mortality risk. Approximately 10 % of LN patients is expected to reach end stage renal disease (ESRD). Proteinuria at 1 year has been demonstrated as the best predictor factor of long-term renal outcome. We compared the effects of two different induction therapies (Euro Lupus protocol [EL] vs Mycophenolate [MMF]) in terms of eGFR, proteinuria, serum albumin and complement activation in LN patients related to our centre.

Method
We retrospectively reviewed the records of 34 adult patients with LN from 2011 to 2019. Patients were divided in two groups according to therapeutic strategy chosen: EL (n=21 patients, group 1) and MMF (n=13, group 2). Data with normal distribution are expressed as average ± standard deviation, while data with non normal distribution are referred to as median and interquartile range [IQR]. Basal values of eGFR, proteinuria, albumin and complement were compared to 1 year values with Student t-test for normal variables or with Wilcoxon test for non normal variables.

Results
The mean age of the patients was 41.27±17.43 years, there was a predominance of female (85,3%) LN was diagnosed at 32±16 years old. According to LN classification, 88.2% of them was affected by III, IV, V and mixed LN class Basal values of eGFR (estimated with CKD-EPI method) were similar between groups 1 and 2 (86.12±52.86 vs 73.75±30.35, P=0.4890) as well as proteinuria (2.00 [0.48-4.57] vs 0.71 [0.28-1.39] g/24h, P=0.3284). After one year of follow up, eGFR did not show significant differences between two groups, while proteinuria was significantly lower in group 1 (2.)). 00 [0.48-4.57] vs 0.44 [0.19-0.91] g/24h, P=0.0034) than in group 2 (0.71 [0.28-1.39] vs 0.15 [0.08-0.77] g/24h, P=0.4687) (fig.1). Moreover, we recorded in group 1 higher values of albumin after one year of follow up (3.20 [2.52-3.94] vs 4.33 [3.99-4.57] g/dl, P=0.0195) (fig.2) and C3 consumption (35.00 [1.00-81.25] vs 89.00 [2.00-112.50] mg/dl, P=0.0067) (fig.3), while group 2 did not show any statistically significant differences.

Conclusion
In patients affected by LN, EL protocol demonstrated to be more effective than MMF in reducing one year after proteinuria, thus improving albumin and C3 serum titer.
P0455CLINICAL PROFILE OF C3 GLOMERULOPATHY AT A TERTIARY CARE CENTRE
Authors: Lingaraj Umesh 
Published: June 2020

Abstract

Background and Aims
To study the clinico-pathological profile of patients with C3 glomerulonephritis at a tertiary care entre.

Method
A prospective observational study of all cases of C3 glomerulonephritis was done between August 2016 and December 2017. C3 glomerulonephritis was defined by predominant glomerular C3 fragment deposition with electron-dense deposits on EM

Results
Total of the 1190 patients under went biopsy during the study period. C3 glomerulonephritis was present in 32 cases (2.68%). The mean age was 35±2 years. Out of the 32 patients, 18 were male ( 56.25% ) and 14 were female (43.75% ). Hypertension was present in 30 out of 32 patients (93.7%) while diabetes was present in 7 patients (21.8%). Most common presentation was with RPGN (72%). 100% patients had active urinary sediments. The mean serum creatinine at admission was 5.15mg/dl while it was 3.18mg/dl at discharge. The mean serum C3 was 83.8 mg/dl with 18 patients (56.25%) having low serum C3 levels in our study. All patients had normal serum C4 levels with mean being 29.34 mg/dl. Anti CFH antibody titres were measured in 6 patients of with it was elevated in 2 patients (33.3%). On LM, 14 out of 32 had crescentic GN (43.75%), 12 had diffuse exudative pattern (37.5%), 4 had diffuse mesangioproliferative pattern (12.5%), 3 had MPGN pattern (9.37%), 3 had focal exudative pattern (9.37%), 1 patient had glomerular TMA (3.15%) and 1had chronic sclerosing pattern ( 3.15%). On IF, all patients had dominant C3 staining. Also 3 (9.37%) patients had IgG staining of 1+ intensity. EM study was done in two patients and was suggestive of DDD in one patient (3.15%). All patients were managed with pulse steroids followed by oral steroids. IV Cyclophosphamide was used monthly for 6 doses in 14 patients ( 43.7%) while oral cyclophosphamide was used in 2 patients (6.25%). Plasmapharesis was done in 11 patients (34.37%) and 11 patients required haemodialysis (34.37%)

Conclusion
C3 glomerulonephritis has emerged as a new entity in the recent past with significant percentage of our patients presenting with RPGN. Hypertension was present in most patients. On light microscopy, the most common presentation was crescentic glomerulonephritis, One third of our patients had advanced renal failure requiring haemodialysis. Plasmapharesis was done in one third of patients.
P0464HEALTH ADN ECONOMIC BURDEN OF THROMBOTIC MICROANGIOPATHY. A NEED FOR A MULTIDISCIPLINARY TEAM
Authors: URIOL MIGUEL , Obrador Mulet Aina , Escriva Ana , Tugores Ana , Perez Albert , Mas Antonio , Garcia José Luis , Gasco Joan 
Published: June 2020

Abstract

Background and Aims
Thrombotic microangiopathy (TMA) is a life-threatening and rare disease associated with a higher risk of dead and chronic renal replacement therapy (CRRT). Eculizumab is highly effective but also expensive. We evaluate the direct economic burden of the TMA, the cost of CRRT, Eculizumab, and the impact of a multidisciplinary team (MDT) after two years of its implementation.

Method
It is a retrospective study, conducted in a 3rd level hospital. We evaluate the risk of i) dead and ii) CRRT need. The number of patients no treated under futility consideration. The cost (euros) for hospitalization at the floor and intensive care unit admission, CRRT and Eculizumab at the pre-MDT implementation (from January 2008 to May 2016) in comparison with the post-MDT period (from May 2018 to Dec 2018). Clinical outcomes: i) risk of death and ii) risk of CRRT need. To determine the cost per patient-year, we calculated the total number of days of hospitalization, the entire months on dialysis or in kidney transplant program (KTx) and the milligrams of Eculizumab used at any period. The total amount divided by the whole years of observation and finally and by the mean number of patients per year diagnosed at any period. The number of patients-year we determined considering the incidence density (ID: cases/1,000,000 person-year). Patients with ADAMTS-13 deficiency were excluded.

Results
Forty-two patients were included. ID increased from 2.3 cases/1,000,000 person-years (n=20) to 11.7 cases/1,000,000 person-year (n=22). Comparing with the pre-MDT period, the number of patients who died increased from 3(15%) to 7(32%), P=0.20; while the risk for CRRT decreased from 9(45%) to 0, P&lt;0.01 [relative risk (95%CI) for no CRRT requirements: 0.55 (0.37 to 0.81)]. One (5%) and three (14%) patients died under futility consideration at the pre- and post-MDT period, respectively (P=0.60). From all the patients who died, only one was in acute dialysis program while 7 showed neurologic damage. The mean cost per patient-year changed from 319,931 to 150,878 euros from the pre- to post-MDT period.

Conclusion
The implementation of an MDT shows a change in the natural history of the disease, where neurological damage emerges as a risk factor associated with mortality instead of CRRT needs.
TMA patients represent a remarkable economic burden, representing an essential challenge for the health system sustainability that could be improved by an MDT.
P0482INTERSTITIAL HSP70 EXPRESSION AT DIAGNOSIS ASSOCIATES WITH LONG TERM RENAL SURVIVAL IN AN ANCA VASCULITIS COHORT
Authors: Petrakis Ioannis , Androvitsanea Ariadni , Stratakis Stavros , Daphnis Eugene , Stylianou Kostas 
Published: June 2020

Abstract

Background and Aims
Heat shock proteins(HSP) present an evolving role in immune response. ANCA associated vasculitis(AAV) is often associated with kidney injury and progression to chronic kidney disease(CKD)

Method
Twenty nine patients with biopsy proven renal AAV were followed(1995-2015). Study end point was renal death. Renal tissue at diagnosis was stained with monoclonal antibodies against HSP60 and HSP70. Interstitial inflammatory cells and interstitial fibrosis graded were evaluated as mild(0-50%) or severe(≥50%). Healthy renal tissue served as control. Survival analysis(Kaplan-Meier), Fisher’s exact test, or Test Chi-Square and bivariate analysis were performed. Statistical significance was set at &lt;0,05.

Results
Mean age and mean eGFR at baseline was 57,8±19.2 years and 24,47 ml/min/1,73m2 BSA respectively. Interstitial inflammatory infiltrates were present in most patients. Interstitial fibrosis was present in 10,3% of patients. Control biopsies showed a weak HSP expression. AAV-patients presented significantly higher HSP expression within crescents, proximal tubule, distal tubule and renal interstitium. Renal fibrosis associated with intense interstitial HSP70 expression(Pearson´s-R=0.521 p=0,004). Interstitial inflammatory infiltrates associated with increased distal tubular HSP60 expression(Pearson´s-R=0.672 p&lt;0,001). Renal fibrosis associated with renal function loss(Mean time to renal replacement therapy 2.6 years, 95%CI 1.2-4.1 years, Log-Rank Chi-Square=4.33,p=0.038). Strong interstitial HSP70 expression associated with worsened renal survival in AAV-patients even in the absence of severe renal fibrosis(Mean time to renal replacement therapy initiation 0 years ; 95%CI 0, Log-Rank Chi-Square=11.45, p=0.001).

Conclusion
Interstitial HSP70 overexpression is associated with worse renal outcomes in renal AAV. To our knowledge this is the first study that shows an association of renal heat shock protein expression and renal outcomes in an AAV cohort.
P0488IG A NEPHROPATHY: ANALYSIS OF 501 BIOPSY
Authors: Omrane Marwa , Aoudia Raja , Ounissi Mondher , Chargui Soumaya , Jerbi Mouna , Gaied Hanene , Hidri Hafedh , Gorsane Imen , Ben Abdallah Taieb , Goucha Rim 
Published: June 2020

Abstract

Background and Aims
Mesangial deposits Ig A was described the first time in 1968 by Berger and Hinglais. It remains the most common primary glomerulonephritis worldwide. It is often idiopathic but can also be secondary. The aim of our study is to describe the epidemiologic characteristics, the incidence and the anatomopathological features of 501 IgA nephropathy (IgA N) patients.

Method
It is a retrospective mono-centric study including patients having IgA N in the renal biopsy done in our department among a period of 17 years.

Results
We analyzed data of 8427 patients who underwent renal biopsy. 81% had glomerular nephropathy with 7.3% (501) IgA N. A male-to-female ratio of 2.27. The average age was 28.7 years. IgA N was primary in 80.2% cases and secondary in 17.8% cases. The most frequent secondary IgA N was rheumatoid purpura (74.8%). There was a male predominance in Berger‘s disease as well as in rheumatoid purpura. Berger’s disease was more common in adults, whereas rheumatoid purpura was more common in children. The main indication of renal biopsy was proteinuria with hematuria in 23.2% of cases and nephrotic syndrome in 23.8%. The association of non-nephrotic proteinuria, hematuria, arterial hypertension and renal injury was found in 9.3% whereas isolated macroscopic hematuria only in 6.4% of cases. According to HAAS classification, HAAS 3 was the most frequent. OXFORD classification used only from 2010, and M1, S1, E0, T0 and M1, S1, E0, T2 were the most frequent. Glomerular lesions were associated to tubulo interstitial and vascular lesions in 48.2% of cases.

Conclusion
IgA nephropathy is the most common glomerular disease and a frequent cause of end stage renal disease. Because of a clear increase of it’s incidence in our country and the delay in the diagnosis, a systematic screening of urines is needed in our country as it’s done in Singapore and Japan.
P0508NEPHROTIC SYNDROME DUE TO HEAVY AND LIGHT CHAIN (AHL) AMYLOIDOSIS
Authors: Markóth Csilla , Bidiga László , Pettendi Piroska , Rékasi Éva , Ujhelyi László , Balla Jozsef , Mátyus János 
Published: June 2020

Abstract

Background and Aims
Kidney diseases with heavy chain deposition are rare, including AHL amyloidosis also. The mutation/deletion of the constant domain (CH1/CH2) of the heavy chain causing high tissue affinity seems most likely in its pathogenesis. The very low serum level is responsible for the difficult diagnosis, which is often based on kidney biopsy or laser microdissection / mass spectrometry.

Method
Case study of a 76-year-old male patient, examined in January, 2019.

Results
Besides treatment for Ménière syndrome and benign prostatic hyperplasia there was no other important event in patient’s history. Significant proteinuria and microscopic haematuria were observed from May 2016, but eGFR was 70 ml/min/1,73 m2 at that time. By April, 2018 nephrotic range proteinuria (10 g/day) with full nephrotic syndrome developed. Screening tests for cancer were negative. Despite symptomatic treatment, half year later eGFR decreased to 27 ml/min/1,73 m2, therefore he was referred to nephrology. Serum protein electrophoresis verified IgG lambda (8,1 g/l) and free lambda (0,5 g/l) monoclonal light chains, and in addition the possibility of IgG heavy chain accumulation. Urine electrophoresis showed also IgG lambda (1720,1 mg/l), and free lambda light chain (552,1 mg/l) monoclonality. Serum free lambda and kappa light chain ratio was 0,06, complement serology was normal. Kidney biopsy was done, which showed IgG heavy and light chain restriction, Congo red stain positivity and apple green birefringence under the polarized microscope in the expanded mesangium, in the interstitium and along the tubular basement membrane and the blood vessels. The electron microscope detected fibrillary deposits (10 nm) in the same structures, therefore diagnosis of AHL amyloidosis was established. He had no extrarenal symptoms. Bone marrow aspiration flow cytometry verified 1,11% plasma cell accumulation, 93% of them had pathological immunphenotype. Bone marrow morphology assay showed 30-40% plasma cell infiltration, and chromosome assay detected monoallelic deletion of IgH and MAF and gains of 1q region, suggesting myeloma multiplex in the background of AHL amyloidosis. VCD (bortezomib-cyclophosphamide-dexamethason) treatment was started, so far he has received 8 cycles. He is asymptomatic, proteinuria decreased, kidney function stabilized, eGFR 23 ml/min/1,73 m2.

Conclusion
only about 20 cases of AHL amyloidosis have been reported in the literature so far. In the context of longstanding kidney failure with nephrotic syndrome, we should consider renal disease associated with plasma cell dyscrasia also. If case of an AHL amyloidosis caused by myeloma multiplex, effective anti-plasma cell therapy can improve the hematological and the renal outcome.
P0539NICOTIFLORIN ATTENUATES RENAL ISCHEMIA/REPERFUSION INJURY THROUGH REDUCING CELL APOPTOSIS
Authors: Wang Lin , Xu Yan 
Published: June 2020

Abstract

Background and Aims
Renal ischemia/reperfusion (I/R) is the main cause for acute kidney injury, Nicotiflorin can ameliorate ischemia/reperfusion injury in other organs, just like in cerebral ischemic damage. Therefore, this article intends to explore whether Nicotiflorin has protective effects on renal tubular epithelial cell after ischemia-reperfusion. On the one hand, We use C57 mice to establish the Nicotiflorin group, DMSO group, AKI group, sham group and control group to investigate whether Nicotiflorin can ameliorate ischemia-reperfusion injury of kidney. In other hand, we use CCK8 to explore the optimal concentration of Nicotiflorin in renal tubular epithelial cells and find optimal hypoxia oxygenation time, in order to analysis the influence of Nicotiflorin. The results indicate that Nicotiflorin can alleviate ischemia-reperfusion injury by reducing apoptosis of renal tubular epithelial cells.

Method
In this study, we investigated the protective mechanism of Nicotiflorin on ischemic acute kidney injury by analyzing gene chip in patients with acute kidney injury and proving in vitro and in vivo experiments. The main methods are as follows: (1) Multiple nucleus ischemia-reperfusion model transcriptase data were selected from the NCBI GEO Datasets database and analyzed to screen out related proteins that may be involved in ischemia-reperfusion kidney injury; (2) The tertiary structure of Nicotiflorin and related proteins was obtained from the SWISS-MODEL database and the PubChem compound database. The molecular docking between protein and Nicotiflorin was performed using Autodock software, and the binding energy between Nicotiflorin and the selected protein was analyzed to determine Nicotiflorin binds to each other; (3) We set different groups, such as control group, sham group, AKI group, Nicotiflorin group and DMSO group in animals. The blood function was used to detect renal injury related function indicators 24 hours after modeling. Renal tissue samples were collected for real-time fluorescent RT-PCR, Western blotting and histopathological analysis; (4)Renal tubular epithelial cells were treated with different concentrations of Nicotiflorin, CCK8 was screened for the most appropriate concentration, and the hypoxic and reoxygenated cells were intervened at the concentration to explore the interaction between Nicotiflorin and the docking protein, and to observe the protective mechanism of Nicotiflorin on the kidney

Results

Conclusion
Nicotiflorin binds to ATF3 and promotes the expression of Cyr61 through protein interactions to improve renal ischemia-reperfusion injury.