bluuebunny/crossref_metadata_2025 huggingface dataset:
P0297CHANGES OF CD4CD28NULL AND CD8CD28NULL T CELLS IN CHRONIC KIDNEY DISEASE AND THE IMPACT OF DIFFERENT DIALYSIS MODALITIES
Authors: Sampani Erasmia , STANGOU MARIA , Daikidou Dimitra Vasileia , Nikolaidou Vasiliki , Asouchidou Despoina , Dimitriadis Chrysostomos , Faitatzidou Danai , Fylaktou Asimina , Papagianni Aikaterini
Published: June 2020

Background and Aims

Chronic Kidney Disease (CKD) affects both the innate and adaptive immunity, although clinical consequences, and the effect of different renal replacement methods on those alterations remain unclear. The purpose of this prospective observational study was to investigate the alterations of T cell immunity in CKD patients, as well as the effect of different dialysis methods on T lymphocyte subtypes.

Method

T cell subpopulations namely CD3+CD4+, CD3+CD8+, CD4+CD28- and CD8CD28- cells, were isolated from whole blood samples using flow cytometry in 40 CKD patients at predialysis state (ESRD-T0). The immunological profile was repeated six months later after initiation of renal replacement therapy (hemodialysis (HD) or peritoneal dialysis (CAPD)). Fifteen age and gender matched healthy individuals served as controls.

Results

Both CD4+ and CD8+ T cells were significantly reduced in ERSD-T0 patients compared to controls, 604(105-3551) vs. 943(584-1867) μ/L, p=0.001, and 352(103-1561) vs. 422.4(263-1453) μ/L, p=0.05. The percentage of both CD4+CD28null and CD8+CD28null cells, 6.4(0.3-30) % vs. 2.7(0.1-7.8) %, p=0.04 and 58.2(12.8-85.4) % vs. 39(7.8-57.1) %, p=0.01 was increased in ERSD-T0 patients comparing to controls. Furthermore the percentage of CD4+CD28null cells correlated with CRP (r=0.4, p=0.04) and serum albumin levels (r=-0.5, p=0.007), while, significant differences were noticed between patients with and without cardiovascular disease, regarding both, CD4+CD28null and CD8+CD28null cells, 8.6(1-30) % vs. 2.1(0.1-19.8) %, p=0.04 and 62.5(12.8-85.4) vs. 45.5(5.7-73.7), p=0.02, respectively.

Changes in the population of CD4+CD28null after 6 months on dialysis showed significant differences between HD and CAPD methods, 110.11(-27.1 to 311.4)% vs. -28.1(-100 to 30)%, respectively, p=0.003, as were in CD8+CD28null cells, 55.23(-29.06 to 197.93)% vs. -8.34(-54.99 to 66.72)%, respectively, p=0.05.

Conclusion

CKD seem to affect specific T cell subtypes, at a pre-dialysis stage, and levels correlate with chronic inflammatory markers and the presence of CVD. These disturbances are further enhanced in HD, while they are alleviated in CAPD.
P0299EVALUATION OF THE CORRELATION BETWEEN VITAMIN D LEVELS AND THROMBOCYTE MARKERS IN PATIENTS WITH DİALYSİS, CHRONIC RENAL DISEASE AND RENAL TRANSPLANTATION PATIENTS
Authors: AHMEDOVA KÖNÜL , SAHIN Garip , Bal Cengiz , Mutluay Rüya
Published: June 2020

Background and Aims

25(OH)D3 levels are known to be lower in patients with chronic renal disease (CRD). Vitamin D supplementation has been shown to have beneficial effects on mortality in these patients. In our study, we have evaluated the pleiotropic effect of vitamin D on thrombocyte markers, which is known very little by most.

Method

The main thrombocyte function markers (MPV, PDW and PCT) were obtained in patients which underwent dialysis, renal transplantation and patients with grade 3-4 CRD before and after vitamin D supplementation. 40 healthy individuals were chosen as control group and 24 patients underwent renal transplantation, 25 patients underwent dialysis for at least 3 months, 32 patients were diagnosed as Grade 3-4 CRD. All of the patients above had 25(OH)D3 levels <20ng/mL (<50nmol/L). Thrombocyte markers were evaluated before and after vitamin D supplementation (which was given 50.000 IU orally once a week for 8 weeks).

Results

Statistically no significant difference were found between MPV values in- and across- group comparison before and after vitamin D supplementation. After the correlation analyses were reviewed, statistically significant negative correlation was found (r=-0,422 p<0.05) between ΔMPV and ΔVitamin D in renal transplantation group. Also statistically significant positive correlation was found between ΔPDW and ΔVitamin D. In the control group with healty participants, a statistically significant negative correlation was found (r=-0,493 p<0.05) between ΔVitamin D and ΔThrombocyte count. In the dialysis group a statistically significant negative correlation was found (r=-0,422 p<0.05) between ΔVitamin D and ΔMPV.

Conclusion

A significant correlation was found particularly between Vitamin D and MPV in dialysis and renal transplantation patients. In order to prevent cardiovascular events due to thrombosis caused by Vitamin D deficiency which increases MPV, it has been thought that Vitamin D supplementation and antiaggregant therapy might be beneficial.
P0317EARLY MARKERS OF RENAL INJURY AND ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH METABOLIC SYNDROME
Authors: Abdullaev Sherzod
Published: June 2020

Background and Aims

The definition of subclinical renal damage markers in patients with metabolic syndrome (MS) and evaluation the relations between the indicators of subclinical renal injury and endothelial dysfunction.

Method

The study included 62 patients with MS, 32 (51.6%) men and 30 (48.4%) women aged 51.2±5.4 years. The control group included 25 practically healthy individuals, 13 (52.0%) men and 12 (48.0%) women, aged 47.3±6.1 years. All patients were underwent clinical and laboratory examination, calculation of glomerular filtration rate (GFR) using the formula CKD-EPI, ultrasound of the carotid arteries, determination of the insulin resistance index (IR) (HOMA-IR), as well as determination of the content of endothelin-1 (ET-1) in serum and albumin excretion in a single portion of urine by IFA.

Results

When calculating GFR, hyperfiltration was detected in 10 (16.1%), optimal filtration - in 23 (37.1%), slightly reduced - in 29 (46.8%). At the same time, in patients with MS, a statistically significant excess of urinary albumin excretion (UAE) in a single dose was revealed compared with the control group (26.6±5.8 mcg/ml and 9.2±3.4 mcg/ml, respectively; p <0.001).

Based on the increase in level (ET-1) in patients of the main group, compared with the control (6.3±3.2 fmol/ml and 3.4±1.0 fmol/ml, respectively; p=0.03) may indicate the development in patients of the main group of endothelial dysfunction. A correlation analysis revealed a direct correlation between the level of UAE and ET-1 (R = 0.45; p = 0.005).

A direct correlation was found between UAE and IR-HOMA (R = 0.68; p <0.007), interventricular septum thickness (R = 0.71; p <0.001), and intima–media thickness (IMT) (R = 0.49; p <0.008) and systolic blood pressure (R = 0.47; p = 0.026). Similar associations were noted also for the ET-1 level: IR-HOMA2 (R = 0.78; p <0.001), with the thickness of the interventricular septum (R = 0.76; p = 0.001), IMT (R = 0.46; p <0.033) and systolic blood pressure (R = 0.45; p = 0.035).

Conclusion

In patients with metabolic syndrome, in addition to the well-known manifestations, in the early stages, may be a violation of renal function and endothelium, manifested by the change of glomerular filtration rate, increased levels of UAE and increased concentration of ET-1 in the blood. Direct correlation of the level of UAE and ET-1 level, and the coincidence of the correlation relationships of these indicators with a number of clinical and laboratory indicators of the metabolic syndrome will make it possible to consider an increasing of the level of UAE as one of the markers of endothelial dysfunction.
P0318HYPERKALEMIA: EPIDEMIOLOGY AND MANAGEMENT
Authors: Felah Eya , Samia Barbouch , Mariem Hajji , Ben amor Shedha , Chargui Soumaya , Amiri Mohamed lotfi , Trabelsi Raja , Goucha Rym , Ben Hmida Fethi , Ounissi Mondher , Ben abdallah Taieb
Published: June 2020

Background and Aims

Hyperkalemia is a dreadful biological event that can immediately compromise the vital prognosis. Etiologies are many and varied. The aim of our study is to better characterize the epidemiological and clinical aspects of this disorder in order to establish adequate diagnostic and therapeutic strategies in order to intervene effectively and in the shortest possible time.

Methods

Cross-sectional study carried out over a period of 12 months [January-December 2017] including all emergency calls for hyperkalemia greater than 5.5 mmol / l and undergoing hemodialysis in the nephrology department.

Results

We collected 185 patients (Sex ratio= 1.43) aged on average 61.8 ± 16.1 years [18-94 years].

70.3% had serum potassium between 5.5 and 7 mmol / l and 29.7% greater than 7. Patients mainly came from emergencies in 71.4% of cases. Main symptoms consisted in oligoanuria, vomiting, chest pain, and febrile syndrome in 38.9%, 10.8%, %, and 5.9% of cases, respectively. Of these patients, 76.2% are known to be chronic renal failure whose 29.7% are in chronic dialysis. Acute renal failure (ARF) was diagnosed in 30.3% of patients. Of these, 39.4% were functional AKI, 41% were obstructive and organic AKI in 19.6% of cases. Mean serum potassium was 6.7 ± 0.9mmol / l [5.5-11] associated with metabolic acidosis in 52.4% of cases. Mean serum creatinine was 988umol /l[184-3270]. The electrical signs of hyperkalemia were noted in 40% (n = 74) of patients: large T in 28.6% of cases, atrioventricular block (AVB) in 3.8% of cases including a 3rd BAV degree in 1.6% of cases, QRS wide in 11.4% of cases and sinus bradycardia in 7% of cases, Ventricular Extrasystoles and a branch block found respectively in 3.2% of cases. 30.8% (n = 57) of the patients were under hyperkalaemic treatment. In fact, 27 % of patients took a blocker of the renin-angiotensin system, 7% were on aldoactone, 13.5% of patients on þetabloquant,1.6 % of whom were on kaleoride and / or admitted to intensive care and infused with KCl. Medical treatment was started urgently in 42.7 % of cases and included the administration of twenty ml 10% ca gluconate that was given intravenously over 5-10minutes, insulin with glucose ,sodium polystyrene sulfate (Kayexalete) and salbutamol, sodium bicarbonate indicated for severe metabolic acidosis (pH<7.20). Overall mortality was 21.1% of cases .

Conclusion

Hyperkalemia remains a frequent metabolic disorder. Renal failure and acidosis were the main factors associated to hyperkalemia in our study. The clinical and therapeutic subtleties must be known by any caregiver in order to effectively mitigate the harmful effects of this disorder, mainly in the cardiac function.
P0352P-SELECTIN BLOCKADE AMELIORATES RENAL HYPOXIA OF LUPUS NEPHRITIS IN MRI/LPR MICE
Authors: Li Xiao
Published: June 2020

Background and Aims

Lupus nephritis is one of the most common and severe complications of systemic lupus erythematosus, of which poor prognosis is indicated by aggravated renal hypoxia and tubulointerstitial fibrosis. Cell adhesion molecules play a key role in the progression of lupus nephritis tubulointerstitial lesion, including P-selectin, which mediates the rolling of leukocytes and subsequent adhesion and infiltration and then initiates the inflammatory immune response and ischemia and hypoxia injury. However, the effects and mechanisms of P-selectin in lupus nephritis remain to be investigated, and a noninvasive measurement of lupus nephritis tubulointerstitial hypoxia and fibrosis remains to be explored.

Method

Thirty-four MRL/lpr mice were randomly divided into the following three groups: MRL/lpr, saline, and anti–P-selectin, which consisted of no treatment, treatment with normal saline, and treatment with anti–P-selectin monoclonal antibody (mAb) from 12 to 16 weeks of age, respectively. Ten male C57BL/6 mice of the same age served as normal controls. Twenty-four-hour urinary protein, urinary albumin–creatinine ratio, and periodic acid–Schiff were used to assess kidney damage; Western blot or immunohistochemical staining of the hypoxia probe HypoxyprobeTM-1, hypoxia-inducible factor 1α (HIF-1α), and CD31 were used to evaluate hypoxia in renal tissue; and NADPH oxidase subunit gp91phox and p22phox were used to examine renal oxidative stress. The correlation between kidney injury and blood oxygen level–dependent magnetic resonance imaging (BOLD-MRI) was calculated to assess the clinical value of BOLD-MRI.

Results

P-selectin is upregulated in lupus nephritis. Blocking P-selectin with mAb alleviated renal tubulointerstitial fibrosis, renal hypoxia, and peritubular capillary loss, without alteration of the levels of lupus activity indicators, anti-dsDNA antibody, or complement C3. BOLD-MRI showed that the reduced R2* values in the renal cortex and medulla of lupus mice were increased when treated with anti–P-selectin mAb as compared with those treated with normal saline, which were negatively correlated with HypoxyprobeTM-1 hypoxia probe and the expression of HIF-1α.

Conclusion

Early intervention of lupus nephritis with anti–P-selectin mAb can significantly improve the hypoxic state of the kidney and reduce the severity of tubulointerstitial lesions. BOLD-MRI techniques are noninvasive and can dynamically evaluate the changes in renal lesions and intrarenal oxygenation levels before and after treatment in lupus nephritis.
P0364A NOVEL INTERPLAY BETWEEN INTESTINAL BACTERIA AND METABOLITES IN IGA NEPHROPATHY IDENTIFIED VIA INTEGRATED MICROBIOME AND METABOLOME APPROACHES
Authors: Wu Hongwei , Dai Yong , Liu Fanna , Yin Lianghong
Published: June 2020

Background and Aims

Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis. Intestinal bacteria and their metabolites have been implicated in various diseases. Improved understanding of the gut microbiota and its metabolic capabilities will facilitate development of diagnostic, therapeutic, and prognostic methods for IgAN

Method

We identified gut microbiota and metabolite biomarkers of IgAN by analyzing microbiomes and metabolomes of fecal and serum samples of IgAN patients and healthy controls using 16s ribosomal RNA gene sequencing and liquid chromatography-tandem mass spectrometry, respectively, and bioinformatics approaches

Results

We found that relative abundances of Streptococcus and Enterococcus were higher in IgAN patients, whereas Bacteroidetes and Bacteroides were lower. The changes in gut microbiota affected metabolism and absorbance of microbiota-associated metabolites of IgAN patients, in particular polyunsaturated fatty acids, free amino acids and oligopeptides, and activated the phenylalanine metabolism pathway. Also, 5-hydroxyeicosatetraenoic acid and 5-hydroxy-6E,8Z,11Z-eicosatrienoic acid were proved to be associated with the classification of segmental glomerular sclerosis but not 24h urine protein and estimated glomerular filtration rate.

Conclusion

Our findings demonstrate an interplay between intestinal bacteria and metabolites in IgAN. The identified metabolites may have diagnostic and therapeutic applications.
P0390THERAPEUTIC EFFECTS AND SERUM METABOLOMIC VARIATIONS IN FOCAL SEGMENTAL GLOMERULOSCLEROSIS MICE ON TREATMENT WITH HUMAN UMBILICAL MESENCHYMAL STEM CELLS
Authors: Wang Caili
Published: June 2020

Background and Aims

Focal segmental glomerulosclerosis (FSGS) mediates the kidney podocyte dysfunction and leads to chronic renal diseases worldwide. Current treatment options are limited, owing to the poor understanding of the metabolic pathologic variations and regeneration of FSGS. Mesenchymal stem cells (MSC) offer the better insights to prevent renal injury and could promote the recovery of renal structure and function through complex mechanisms. Due to the safe, feasible, and therapeutic features, we first designed to investigate the role of human umbilical mesenchymal stem cells (HUMSCs) on FSGS mice and explored the potential serum metabolomic variations.

Method

Nephropathy was induced by adriamycin (ADR) in male Balb/C mice to study FSGS via intravenous administration. 2*106 HUMSCs are provided to treat FSGS model for 3 times. Renal function was measured by urine protein, serum urea nitrogen (BUN) and serum creatinine (SCr) in the study. Serum metabolic profiles from three groups of Balb/C mice were analysed using ultra- performance liquid chromatography coupled with a triple quadrupole-linear ion trap mass spectrometer and a novel mass spectrometry (UPLC-MS/MS) data collection technique.

Results

The concentrations of SCr and BUN were apparently decreased after HUMSCs injection for three times compared with the FSGS model and body weight from HUMSCs group was improved significantly. A total of 532 differential metabolites were identified between FSGS group and the normal control group. Bile acid dysregulation and valine/leucine/ isoleucine metabolism pathway, especially, N-acetylvaline and L-valine, were positively associated to ADR-induced FSGS. A panel of identified specific metabolites (pyrrole-2- carboxylic acid, urocanic acid and 6-hydroxynicotinic acid) as well as valine/leucine/isoleucine metabolism pathway rather than bile acid metabolism were related to the renal repair after HUMSCs treatment.

Conclusion

The administration of HUMSCs in FSGS induced ADR provides the promising protection owing to the improvement of metabolomics.

Figure 2. The distribution of DiR-HUMSCs in vivo.

Figure 3. Kidney pathology using periodic acid-Schiff (PAS) and Masson staining.

Figure 4. Metabolome profiling analysis and Venn diagram for comparisons of numbers from each group.

Figure 5. Metabolic pathway analysis results from FSGS + Saline and FSGS + HUMSCs groups.

Figure S1. The quality control (QC) of serum metabolomics was designed and performed as follows.

Figure S2. Metabolic pathway analysis results from FSGS + Saline and Normal + Saline groups.

Figure S3. Metabolic pathway analysis results from FSGS + HUMSCs and Normal + Saline groups.
P0401RITUXIMAB VESUS CYCLOPHOSPHAMIDE AS FIRST STEROID SPARING AGENT IN CHILDHOOD FREQUENTLY RELAPSING OR STEROID DEPENDENT NEPHROTIC SYNDROME
Authors: Kari Jameela , Albanna Amr , Alhassan Khalid , Safdar Osama , Shalaby Mohamed , Bockenhauer Detlef , El-Desoky Sherif
Published: June 2020

Background and Aims

Approximately 50% of children with steroid sensitive nephrotic syndrome (SSNS) will suffer from frequent relapses or steroid dependency, prompting the use of so-called steroid-sparing drugs. In this pilot study, we compare the efficacy and safety of rituximab to oral cyclophosphamide as first-line steroid-sparing medications

Method

A prospective open label randomized study of children with frequent relapsing or steroid-dependant SSNS. Exclusion criteria were steroid-resistant disease, prescription of immunosuppressive agents other than prednisolone or levamisole, evidence of impaired kidney function, leucopenia or active infection. The recruited children were allocated either to the oral cyclophosphamide (3mg/kg/day for 8 weeks) or intravenous rituximab treatment (two doses of 375 mg/m2/dose, 2 weeks apart) and were monitored for relapses and side effects for 12 months

Results

46 subjects were included from two centers; 27 received cyclophosphamide and 19 received rituximab. One-year relapse-free survival was reached in 17 (58.6%) patients treated with cyclophosphamide compared to 16 (84.2%) with rituximab (adjusted HR: 0.36; 95% CI: 0.09 – 1.45; p=0.151). The mean interval to relapse was 6.9 months in the cyclophosphamide group (N=10) and 6.3 months in the rituximab group (N=3). Both treatments were associated with a significant (p=?) reduction in prescribed dose of oral alternate days steroid from 1.02 to 0.36mg/kg (Cyclophoshamide) and 0.86 to 0.08mg/kg (Rituximab). Importantly, a significantly (P = 0.003) higher percentage of patients achieved complete withdrawal of steroid within 3 months of commencing study treatment in the rituximab (73.7%) versus cyclophosphamide (29.6%) group.

Transient leucopenia was the most frequent adverse effect observed in the cyclophosphamide group (18.5%) and one patient (3.4%) had acute hepatotoxicity beside severe leucopenia and neutropenia on the 7th week of treatment although she showed complete recovery with withdrawal of cyclophosphamide and maintained remission. A minor infusion related reaction was observed in 1 patient (5%) in the rituximab group.

Conclusion

Rituximab is non-inferior to cyclophosphamide and safe as a first-line steroid-sparing agent in children with SSNS. A larger multicenter study is required to assess superiority over cyclophosphamide
P0411PREDICTORS OF RENAL AND PATIENT OUTCOME IN PATIENTS WITH IDIOPATHIC MEMBRANOUS NEPHROPATHY: FROM KOGNET DATA
Authors: Choi Ji-Young , Kim Ji Hye , Lee Ga Young , Noh Hee Won , Jeon Soojee , Lim Jeong-Hoon , Jung Hee-Yeon , Cho Jang-Hee , Kim Chan Duck , Kim Yong-Lim , Park Sun-Hee
Published: June 2020

Background and Aims

Idiopathic membranous nephropathy (iMN) is a leading cause of nephrotic syndrome and one of the major causes of end-stage renal disease (ESRD). Various factors can affect renal and patient outcome in patients with iMN. In this study, we analyzed the predictors of renal and patient survival in patients with iMN.

Method

We analyzed 1,776 patients diagnosed with iMN in Korean GlomeruloNEphritis STudy (KoGNET), a retrospective database of patients with renal biopsy from 1979 to 2018 from 18 centers in Korea. Student t-test for continuous variables and Chi-square test for categorical variables were performed for analyses. Cox proportional hazard regression was used to determine risk factors affecting renal and patient survival.

Results

The mean age of patients was 53.0 ± 14.7 years old and 1,075 (60.5%) were male. At the time of renal biopsy, 755 (46.0%) and 266 (16.2%) had hypertension and diabetes, respectively. Serum albumin level was 2.7 ± 0.8 g/dL and 871 (49.0%) had nephrotic range of proteinuria. When analyzed by dividing over 65 and under, the hemoglobin and serum albumin level were lower, more patients showed nephrotic ranged proteinuria, and higher prevalence of comorbidities such as hypertension, diabetes, coronary heart disease and cerebrovascular disease in the group over 65 than in the group under 65. Median duration of follow-up was 88.0 (38.0 – 115.1) months. Complete or partial remission rates were 48.5%, 63.8%, and 68.0% at 6 months, 12months after biopsy, and last follow-up, respectively. In Cox proportional hazard regression, high hemoglobin [HR 0.66 (0.47 – 0.93), p=0.017], high serum albumin level [HR 0.41 (0.18 – 0.94), p=0.034], and high estimated GFR by CKD-EPI equation [HR 0.94 (0.91 – 0.96), p<0.001] at biopsy were good predictors for renal outcome, whereas presence of cerebrovascular disease at biopsy [HR 6.45 (1.16 – 35.71), p=0.033] were poor prognostic factors for ESRD. Age 65 and older [HR 3.26 (1.53 – 6.95), p=0.002] and presence of hypertension at biopsy [HR 2.45 (1.09 – 5.54), p=0.031] were significant risk factors for patient survival in multivariate Cox proportional regression analysis.

Conclusion

High hemoglobin and serum albumin, and good renal function at biopsy were good predictors for renal survival. Older age and hypertension at biopsy were poor prognostic factors for patient survival in iMN patients. Prognostic information of outcomes in this study might be helpful to optimize management in iMN patients.
P0415MONOCLONAL GAMMOPATHY-RELATED RENAL DISEASES: NEW CLINICAL AND HISTOLOGICAL PATTERNS
Authors: Schiavone Giulia , Santostefano Marisa , Fabbrizio Benedetta , Mancini Elena
Published: June 2020

Background and Aims

In the last few years new clinical-histopathological forms of paraproteinemia associated kidney disease have emerged: light chain proximal tubulopathies, proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) and C3-glomerulopathy.

It is now widely recognized that the pathogenic role of the monoclonal protein depends on the free light chain chemical-physical features, even in the case of “dangerous small B cell clones”.

Thus MGRS (monoclonal gammopathy of renal significance) associated disease is now considered a different entity from monoclonal gammopathy of undetermined significance (MGUS).

Method

We retrospectively evaluated the clinical-histopathological features of the biopsies performed in our Nephrological Unit on patients with MGUS in 2008-2018, in order to re-classify them in accordance with the recent scientific literature.

Results

Nine patients (7 M/2 F; age 46-77 y) were analyzed: five of them suffering from CKD stage 2, four of them with AKI or rapidly progressive CKD, 7 with proteinuria > 1 g/day, 2 with physiological proteinuria. Bone marrow biopsy: 7 patients with MGUS, 2 with smoldering multiple myeloma. Renal biopsy: 4 glomerulopathies (monoclonal fibrillary glomerulonephritis, cryoglobulinaemic (type I) glomerulonephritis, C3 glomerulonephritis, PGNMID), 5 proximal tubulopathies (2 LCPT with Fanconi syndrome, 1 LCPT without cytoplasmic inclusions and with interstitial inflammatory reaction, 2 LCPT with acute tubular necrosis) Table 1, Table 2, Light microscopy and IF of PGNMID.

Conclusion

MGRS is responsible for the pathogenesis of new histopathological renal lesions, based on new pathogenetic pathways. The clinical and histological features of the different disease states are dependent on the structure of FLCs. Our retrospective analysis of MGRS biopsies confirms how difficult and complex the diagnostic challenge of monoclonal renal injury really is.

The differentiation between MGUS and MGRS is based on renal biopsy and demonstration of monoclonality on kidney tissue even if serum/urine immunofixation is negative.

Early biomarkers of the pathogenetic role of monoclonal FLC should be identified both for diagnosis and therapeutical monitoring.
P0419AUTOANTIGEN-SPECIFIC TH17 AND TH22 INFLAME THE KIDNEY IN ANCA-VASCULITIS
Authors: Boschmann Erika , Hinkeldein Tanja , Kribben Andreas , Dolff Sebastian , Van Paassen Pieter , Witzke Oliver , Wilde Benjamin
Published: June 2020

Background and Aims

Anti-neutrophil-cytoplasmic-antibody (ANCA)-associated-vasculitis (AAV) is an autoimmune small-vessel-vasculitis. T-cells play a pivotal role in pathogenesis as drivers of autoantibody formation and vasculitic damage. However, the involvement of T-cells in renal vasculitis is understood poorly. IL-17C is secreted by epithelial parenchymal cells enhancing the pathogenicity of Th17 cells. Furthermore, IL-17C is a chemotactic factor for Th17 cells. The aim of this study was to assess the role of Th17 cells and IL-17C in the pathogenesis of ANCA-vasculitis in an animal model of AAV.

Method

Wistar-Kyoto-rats were immunized with myeloperoxidase (MPO) in Freunds Adjuvant to induce AAV. Control rats were immunized with Freunds Adjuvant only. Albuminuria was determined weekly and rats were culled after two, four and six weeks. At the time of harvest, renal T-cells were isolated and characterized by flow cytometry. Antigen-specificity was determined by ELiSPOT. Petechial bleedings on the lung surface reflecting pulmonary vasculitis were quantified after harvest. Gene expression in spleen, kidneys and lungs was studied by PCR and is expressed as fold change over controls. IL-17C levels were measured in sera by ELISA.

Results

MPO-rats developed detectable titres of anti-MPO by week two. By week six, all MPO-animals developed renal vasculitis with significant albuminuria and pulmonary vasculitis. Accordingly, MPO animals showed significant crescent formation as compared to the controls (% of affected glomeruli: 11.4 ±10.5% vs. 0.4 ±0.7%, p<0.005). The petechial bleeding score on the lung surface was higher in MPO-immunized rats than in controls at week six (68 ±13 vs. 2 ±1, p<0.05). From week two on, Th17 and Th22 cells inflamed the kidney as determined by PCR and/or flow cytometry in MPO-rats. The Th17 and Th22 infiltrate was heaviest at week six post-immunization. The intra-renal T-cell response was skewed towards Th17 as compared to the frequency of splenic Th17 cells in MPO-rats (9.1 ±4.3% vs. 1.9 ±0.6%, p<0.005). The majority of intra-renal Th17 and Th22 cells was MPO-specific. Control rats did not show renal T-cell infiltration. Renal transcripts for IL-17C were slightly decreased in week 2 (0.88 ±0.1 fold), unchanged in week four (1.0 ±0.2) and slightly increased in week six after immunization (1.7 ±0.7 fold). Pulmonary IL-17C mRNA transcripts were decreased during weeks two and four after disease induction as compared to controls (0.29 ±0.07 fold, 0.98 ±0.2 fold). During week six, pulmonary IL-17C mRNA transcripts were slightly increased over controls (1.9 ±0.4 fold). Serum levels of IL17C were unchanged during weeks two to six after disease induction comparing MPO-immunized rats and controls.

Conclusion

Th17 and Th22 cells are drivers of renal inflammation in ANCA-vasculitis. The role of IL-17C in this cascade needs to be determined.
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

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

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<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

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

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

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<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

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 <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<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

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.