bluuebunny/crossref_metadata_2025 huggingface dataset:
P0412VALUE OF INTERNATIONAL RISK-PREDICTION TOOL IN IGA NEPHROAPTHY : A SINGLE CENTRE STUDY
Authors: Arora Dhawal , Kanigicherla Durga , Hamilton Patrick
Published: June 2020

Background and Aims

A new International Risk-Prediction Tool in IgA Nephropathy developed was recently developed to help predict disease progression over a 5-7 year period1. We tested use of this Risk-Prediction Calculator in patients diagnosed with IgA Nephropathy to stratify the risk and predict outcomes during follow up.

Method

All adult patients (aged ≥18years) with biopsy proven IgA Nephropathy diagnosed between 2011 and 2016 at Manchester University NHS Foundation Trust were included in the study. Exclusion criteria included patients with secondary causes, prior exposure to immunosuppression, or presentation eGFR of less that 15ml/min. Demographic, clinical phenotypic & renal histological characteristics (MEST score) at baseline were used to calculate the individual risk scores. These risk scores were compared with outcomes seen during subsequent follow up. Primary outcome was a composite of first ESRD or reduction in eGFR to below 50% of value at biopsy. Patients were censored at last follow visit for primary outcome or death. Renal outcomes were analysed using Kaplan Meier survival plots of subgroups based on predicted risk (<16th percentile, 16-50th percentile, 50-84th percentile or >84th percentile).

Results

121 patients were included in the analyses. 45 other patients were excluded based on exclusion criteria. 84 patients (69%) were males, mean age was 42±16 years, eGFR was 63±34ml/min and uPCR was 151±42mg/mmol. Mean follow up was 51.4±28 months.

87% were on RAS inhibition at or within 6 weeks of kidney biopsy diagnosis. During the follow up period 23 patients (19%) developed the primary outcome. Outcomes were significantly worse in patients with higher risk-prediction scores (Fig 1 log rank p<0.01).

Conclusion

This single centre study confirms that the International IgA Nephropathy Risk-Prediction Model for kidney outcomes can be a valuable tool for prognostication in Primary IgA Nephropathy in routine clinical practice.
P0428CYTOMEGALOVIRUS INFECTION IN PATIENTS WITH GLOMERÜLER DISEASE TREATED WITH CYCLOPHOSPHAMIDE: A SINGLE-CENTER EXPERIENCE
Authors: Kumru Şahin Gizem , Eyüpoğlu Şahin , Eren Sadioğlu Rezzan , Çınar Güle , Ateş Kenan , Ertürk Şehsuvar , Nergizoğlu Gökhan , Şengül Şule , Kutlay Sim , Keven Kenan
Published: June 2020

Background and Aims

Cytomegalovirus (CMV) infection is an important complication in immunocompomised patients. Although approach to CMV infection is well-defined in stem cell and solid organ transplant recipients, less is known about the frequency and risk factors of CMV disease in patients with glomerulonephritis (GN). As few studies have shown that cyclophosphamide (CYC) treatment is a risk factor for CMV infection in GN patients, we aimed to describe the frequency and risk factors of CMV infection in GN patients treated with CYC.

Method

268 patients diagnosed GN between January 2017 and November 2019 in Ankara University İbni Sina Hospital, Nephrology Department. We recruited 43 GN patients who were treated with CYC and screened all patients for viral DNA monthly. CMV infection defined by CMV DNA detected >500 copies/µl. Patients developed CMV and no-CMV infection were compared for age, sex, glomerular pathology, renal function and clinical status before and after treatment.

Results

CMV infection was detected in 10 (23,3%) patients at 2±1 (min:1 max:3) months of CYC treatment (Table-1). 7 patients were treated for CMV infection with parenteral ganciclovir, while the other 3 patients with low CMV DNA level (509, 538 and 540 copies/ml) and no disease symptoms were monitored without antiviral treatment. Patients with CMV infection had higher serum creatinine (4,2±3,2 vs. 1,9±1,8 mg/dl, p=0,006), lower estimated glomerular filtration rate (29±11 vs. 65±8 (ml/min/1.73 m2, p=0.016), lower low-density lipoprotein (144±71 vs. 221±83 mg/dl, p=0,012) at diagnosis compared with no-CMV infection patients (Table-2). Also more patients were diagnosed with rapidly proggressive GN (80,0% vs. 27.3%, p=0,007), and secondary GN was the most common GN diagnosis (80,0% vs. 27.3%, p=0.007) in CMV infection group.

Conclusion

CMV infection is a common complication in GN patients treated with CYC. Routine monitoring and prophylaxis should be considered for the patients who have risk factors for CMV infection.
P0430EFFECT OF CORTICOSTEROIDS THERAPY FOR PATIENTS OF IGA NEPHROPATHY WITH CRESCENTS
Authors: Liang Mengjun , Li Aihua , Jiang Zongpei
Published: June 2020

Background and Aims

Patients with IgA nephropathy (IgAN) presented proteinuria≥1g/d and eGFR≥50ml/min/1.73m2 after supportive treatment had been advised 6-month course of corticosteroids therapy. Update of Oxford classification of IgAN had recommended crescents be added to the MEST score for they were predictive of outcome. Whether we should take some more positive therapy for crescents?

Method

We conducted a single-center, retrospective cohort study enrolling 46 patients from 2017.01 to 2018.06, diagnosed with IgAN by renal biopsy. Eligible patients had proteinuria of 0.5∼3.5g/d, eGFR≥30ml/min/1.73m2 and crescent proportion <50%. Patients were divided into two groups, one for classical steroid treatment (intravenous methylprednisolone 0.25g/d for 3 days at the beginning of months 1, 3 and 5, plus oral prednisone 0.5 mg/kg/d for 6 months, called 1-3-5 Group) and the other assigned an optimized steroid therapy (intravenous methylprednisolone 0.25g/d for 3 days at the beginning of months 1, 2 and 3, plus oral prednisone 0.5 mg/kg/d for 6 months, called 1-2-3 Group). The primary endpoint was remission of proteinuria, secondary endpoint was deterioration in renal function.

Results

There were 23 patients in each group and no significant differences in age, gentle, baseline proteinuria and eGFR between the two groups, except for the proportion of crescents (for Oxford C1 and C2: 52.5% and 13% in 1-3-5 Group vs. 95.7% and 4.3% in 1-2-3 Group respectively, p=0.001). After 6 months therapy, proteinuria in 1-3-5 Group was 0.5(0.2,0.8)g/d (vs. 1.2(0.8,2.6)g/d at baseline, p <0.001) and that in 1-2-3 Group was 0.3(0.2,0.6)g/d (vs. 1.5(0.7,2.6)g/d at baseline, p <0.001). 78.3% of patients in 1-3-5 Group had got remission of proteinuria, while 95.7% in 1-2-3 Group (p=0.187). The 6th month eGFR in 1-3-5 Group was 80.7(59.8,116.2)ml/min/1.73m2 (vs. 77.5(54.8,104.6)ml/min/1.73m2 at baseline, p=0.212), while that in 1-2-3 Group was 97.8(68.6,130.9)ml/min/1.73m2 (vs. 79.5(52.9,108.7)ml/min/1.73m2 at baseline, p=0.002). The slope of eGFR in 1-3-5 Group was 0.7(-1.7,3.3)ml/min/1.73m2/month, while that in 1-2-3 Group was 3(1.2,5.4)ml/min/1.73m2/month, p=0.027. For side effects, two patients in 1-2-3 Group had met bronchitis during the 2nd and 3rh therapy-month respectively; in 1-3-5 Group, one patient had got glaucoma during the 2nd therapy-month and the other had happened steroid-induced diabetes mellitus during the 3rd therapy-month.

Conclusion

Our preliminary results had indicated that optimized steroid therapy had equal effect on reducing proteinuria but more significant advantage to protect against renal function deterioration in IgAN with crescents. 1-2-3 month-steroid pulse therapy had not increase the morbidity of irreversible or severe side effects.
P0453BIOSIMILAR RITUXIMAB AND BRAND RITUXIMAB: RELAPSES AND PROTEINURIA IN THE GLOMERULAR PRYMARY DISEASES
Authors: Bury Roxana , Agraz Irene , Soler Romeo Maria Jose , Garcia Carro Clara , Espinel Eugenia , Seron Micas Daniel , Montoro Bruno , Varon Carlota
Published: June 2020

Background and Aims

Biosimilar drugs need to prove similar effectiveness to the brand name drug, in order to have their authorization from regulatory agencies. Rituximab initially developed as a treatment for non-Hodgkin lymphoma, is used as a therapeutic alternative to several autoimmune diseases, including primary glomerular diseases.

The objective of this study is to observe if there were differences in terms of effects measured in proteinuria and relapse episodes between rituximab brand versus biosimilar in primary glomerular diseases

Method

This is a retrospective descriptive study that included patients receiving rituximab brand or biosimilar for the first time between March 2018 to March 2019, collecting information from the reported medical records with primary glomerulopathy were included. The collected laboratory data included creatinine, proteinuria, leukocyte and lymphocyte count before (0-60 days before) and after (0-60 days after) administration of rituximab.

Results

A total of 19 patients with primary glomerulopathy were included. Six patients (59-years-old (26-74); 50% female) with baseline 6.52±2.00x10^9/L leucocyte count, 2.28±1.10x10^9/L lymphocyte count, 1.63±1.04 mg/dL creatinine and 6.84±3.36g/24h proteinuria, were treated with biosimilar-rituximab. Thirteen patients (58-years-old (25-81); 30% female) with baseline 9.80±4.62x10^9/L leucocyte count, 1.92±1.13 x10^9/L lymphocyte count, 1.61±0.85 mg/dL creatinine and 5.81±4.55 g/24h proteinuria, were treated with brand-rituximab. After the rituximab administration, these values were 6.13±1.94x10^9/L leucocyte count, 1.30±0.59x10^9/L lymphocyte count, 1.16±1.19 mg/dL creatinine, 3.29±0.58g/24h and proteinuria for the biosimilar group; and 8.77±3.78x10^9/L leucocyte count, 1.67±1.13x10^9/L lymphocyte count, 1.56±1.19 mg/dL creatinine and 3.36±2.20g/24h proteinuria for the brand group. After rituximab administration CD19+ lymphocytes become negative in both groups (5/5 for the biosimilar group; 6/6 for the brand group). There were 2 total remissions, 1 partial remission and 3 without response with the biosimilar and 1 total remission, 5 partial remissions and 7 without response with the rituximab brand. Biosimilar was well tolerated in 6/6 patients and Rituximab brand infection did not develop was well tolerated in 11/13 patients and 4/13 patients showed an episode of infection. No statistically significant results were observed for the response to treatment between both groups.

Conclusion

The biosimilar shows a similar profile in terms of proteinuria and remissions against rituximab mark in the reported follow-up period, however our study is limited since it has a small sample, so a larger study is necessary to demonstrate these results with statistical significance
P0458ADVERSE EVENTS AND INFECTIONS, POTENTIALLY RELATED TO GLUCOCORTICOIDS, REMAIN COMMON DURING MAINTENANCE TREATMENT OF ANCA ASSOCIATED VASCULITIS AND ADD TO CLINICAL AND HEALTHCARE RESOURCE USE BURDEN IN EUROPEAN PATIENTS
Authors: Rutherford Peter , Götte Dieter
Published: June 2020

Background and Aims

ANCA associated vasculitis (AAV) treatment aims to quickly control vasculitis activity and then prevent relapse during the maintenance phase of this long term condition. Patients are at risk from disease and treatment related complications with high dose and/or long term glucocorticoid use being a major concern. This retrospective study examined adverse events, infections and healthcare resource use in patients managed in routine practice.

Method

1478 AAV patients (France, Germany, Italy, Spain and UK) managed by 493 physicians (61% Nephrologists) who completed induction therapy for new or relapsing organ or life threatening AAV and initiated maintenance therapy between 2014-16 were studied. Data were collected at the time maintenance was determined to begin by the physician and then at 6, 12, 18 and 36 months. 51% had microscopic polyangiitis, mean age 54.2 years with 56% male. BVAS was not used routinely but 56% had moderate systemic disease and 44% severe systemic disease at the time of start of induction remission treatment.

Results

78% patients had comorbidity (48% hypertension, 20% dylipidaemia, 17% type 2 diabetes mellitus, 14% depression, 13% COPD/asthma and 9% had BMI > 35) at induction treatment start. Maintenance was defined by physicians as starting approximately 6 months into treatment. AEs potentially linked to GCs were common (values are %, bp = hypertension, DM = diabetes mellitus) during the maintenance phase and many patients remained on long term glucocortioids. Infections were also common, in particular upper (URTI) and lower respiratory tract (LRTI) infection and urinary tract infections (UTI). Hospitilisations still occurred during maintenance period, in particular these are due to infections. Maintenance treatment varied and was changed over follow up (in 13-19% patients at each time point) and in a proportion of patients the change in treatment was precipitated by an adverse event or infection (6 months 21%, 12 months 22%, 18 months 23%, 38 months 26%).

Conclusion

Comorbidity is common in AAV patients and needs to be considered carefully when making treatment decisions. Patients receiving maintenance therapy frequently experience potentially GC related AEs and infections are also common. Healthcare resource use continues in the maintenance phase and this is on the background of comorbidity, less then complete remission rates and high use of long term steroids. New approaches are required to reduce clinical and healthcare system burdens during the maintenance treatment phase of AAV.
P0460ASSOCIATION BETWEEN CAUSATIVE MICROORGANISMS OF INFECTIVE ENDOCARDITIS AND CLINICAL SPECTRUM OF RENAL LESIONS
Authors: Pisaruk Alexandra , Povalyaev Nikita , Sorokina Maria , Domonova Elvira , Kotova Elizaveta , Safarova Nargiz , Karaulova Yulia , Balatsky Alexandr , Efremovtseva Marina , Kobalava Zhanna
Published: June 2020

Background and Aims

The relation between microorganisms and renal lesions in IE has bilateral nature: urinary tract infections may be source of systemic invasion that will cause IE, IE causative microorganisms may cause inflammatory changes in glomeruli or be disseminated in renal parenchyma gematogenously with the formation of the abscesses in case of fragmentation or migration of the vegetations. IE-associated GN - is an immune-mediated GN caused by bacterial infection. More commonly GN presented in cases of streptococcal and staphylococcal IE. For renal embolism is typical association with staphylococcal infection, and there are documented cases of renal infarctions in IE caused by S. pneumonia, and C. burnetti. The effect of microorganisms on other clinical manifestations of kidney damage in IE has not been studied.

Method

The study included 209 patients with verified IE. All patients were performed bacteriological and 81(38,8%) parallel one-moment biomolecular (PCR or PCR with follow-up sequenition) tests. In case of death or cardiac surgery, affected valves (n=15) were tested with the same technique. To asses renal function we calculated glomerular filtration rate with CKD-EPI formula. AKI, AKD and CKD were diagnosed in accordance with present guidelines [KDIGO, 2012].

Results

Renal ivolvement into the pathological process trended higher in patients with Gr- (p=0,016) and few causative microorganisms (p=0,039). There are significant differences in incidence of different renal syndromes in patients with MRSA, Gr- and few causative microorganisms - these patients more often had acute nephritic syndrome (respectively p=0,036; p=0,005; p=0,003) (tab. 1). Impairment in the renal function was significantly associated with MRSA (p=0,012), Gr- (p=0,01) and few causative microorganisms (p=0,003). In addition long-lasting renal impairment was observed: patients with MRSA had median time of worsening of the renal function 9 days (IQR 4-14), with Gram-negative microorganisms median time was 9 days (IQR 5-12), with polyflora 10 days (IQR 7-14). But there were no significant differences in median time of renal function worsening in patients with other causative microorganisms. Incidence of AKI and AKD depending on causative organism did not significantly differ.

Conclusion

Kidney lesions in IE significantly associated with Gr- microorganisms, MRSA and with the presence of 2 or more causative microorganisms. Clinical spectrum of renal lesions is diverse: from the changes in the urine sediment to longstanding kidney dysfunction.
P0472RENAL OUTCOMES OF IDIOPATHIC MEMBRANOUS NEPHROPATHY IN ELDERLY
Authors: Breik Nessrine , Jerbi Mouna , Aoudia Raja , Chargui Soumaya , Guaied Hanen , Gorsane Imen , Goucha Rim , Benabdallah Taieb
Published: June 2020

Background and Aims

Idiopathic membranous nephropathy (IMN) is increasingly seen in older patients but little is known about its treatment and outcomes at long term follow up. The objective of this work is to study the renal survival of IMN in elderly as well as prognostic factors.

Method

We conducted a retrospective descriptive study in the nephrology department at Charles Nicolle hospital over a period of 44 years. All older patients (≥65 years) with histologically proven MN were included in this study. Data collected included demographic, clinical and biological parameters in each patient. Data were entered and analyzed using SPSS software. Chi-squared test with a level of significance of 0.05 was used for the qualitative variables.

Results

Twenty-eight patients were collected. The mean age was 67.03 years (65-78 years) with a male predominance (sex ratio: 2.3) and low socio-economic level in 82.5% of cases. Sixteen patients were smokers (57.14%), 5 ethyl patients (17.8%), diabetes was present in 3 patients (10.7%) and hypertension in 11 patients (39.28%). The clinico-biological picture was dominated by high systolic blood pressure in 21 cases (75%), anasarca in 7 cases (25%), proteinuria in all cases and hematuria in 20 cases (71.14%). Biology revealed nephrotic syndrome (NS) in all cases, hypercholesterolemia in 23 cases (82.14%), high serum creatinine in 14 cases (50%) with an average creatinine level of 127,95 µmol/l, anemia in 17 cases (60.7%) and anti-neutrophil cytoplasmic antibodies were positive in one case. MN was confirmed by a kidney biopsy in all cases. Symptomatic treatment was indicated in all patients. Immunosuppressive therapy was started early in 12 patients (40%) because of the severe NS and the deterioration of renal function. Eight patients (26.6%) received corticosteroids alone, three patients received corticosteroid with mycofenolate mofetil and one patient received corticosteroid with ciclosporin. Fourteen patients received only symptomatic treatment. We noted complete remission in 6 patients (21.42%) and end renal stage disease in 5 patients (17.85%). Our study showed that treatment with angiotensin receptors blockers was associated with better renal survival with a statistically significant difference, (p = 0.011). A reduced kidney function at presentation, tubule-interstitial disease and interstitial fibrosis and tubular atrophy were associated with poor survival with a statistically significant result (p = 0.012) (p=0,011) respectively.

Conclusion

IMN is the most common cause of nephrotic syndrome in elderly patients and it has the same risk for progression as in younger individuals. Decrements in glomerular filtration rate, increased risk for comorbidities, vascular disease and change in pharmacokinetics justify special attention to treatment decisions in elderly individuals with IMN.
P0476THE ABSENCE OF REMISSION PREDICTS MORTALITY IN RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS
Authors: Gil Giraldo Leydy Yohana , Muñoz Ramos Patricia , Fernández Perpen Antonio Carlos , Quiroga Borja
Published: June 2020

Background and Aims

Rapidly progressive glomerulonephritis (RPGN) encompasses a group of diseases with a common histology in which the absence of treatment progress to end-stage renal disease. Induction treatment includes the use of immunosuppressants, and in certain cases, plasmapheresis. The final objective of this study was to determine the long-term prognosis of the RPGN.

Method

A retrospective observational study was conducted, including patients diagnosed with RPGN between 2004 and 2019. Baseline epidemiological data and comorbidities were collected, as well as renal function and treatment at the time of diagnosis. During the follow up [median of 42 (5-101 months)], we analyzed the evolution of renal function, mortality and associated factors.

Results

Forty-three patients (65% women) were included, with a mean age of 70 ± 16 years. At the time of diagnosis, mean creatinine was 4.8 ± 2.6 mg/dl, proteinuria 1094 ± 856 mg/day and 37 patients (86%) presented hematuria Thirty-one patients (72%) presented positivity for antibodies against the neutrophil cytoplasm, 7 (16%) for antibodies against the glomerular basement membrane and 5 (12%) for both. Regarding the induction treatment, 41 patients received cyclophosphamide and corticoids and two patients received rituximab. Seventeen (31%) plasmapheresis were performed with a median of 7 (6-7 sessions).

At 6 months, 55% of the patients presented remission (15 patients complete remission and 8 patients partial remission). The median creatinine was 1.9 (1.2-3.1) mg/dl and the proteinuria was 380 (85 -542) mg/day (p<0.0001 compared to the initial data). At that time, 21% (9) of the patients needed dialysis. Associated factors with the absence of remission were diabetes mellitus (p= 0.016), creatinine at diagnosis (p= 0.002) and the need for hemodialysis at admission (p<0.0001). The only independent predictor of remission was initial creatinine (HR 0.5 [0.3-0.9], p= 0.048). During follow up, renal function improved with a median of creatinine at 18 months of 1.6 (1.2 – 2.9) mg/dl and 1.5 (0.8-2.4) mg/dl at the end. Twelve (28%) patients died during follow up. Associated factors with mortality were age (p=0.02), the need for hemodialysis (p=0.015) and the absence of remission at 6 months (p=0.012) (figure 1). An adjusted model using Cox regression demonstrated that the absence of remission was an independent predictor of mortality (HR 0.2 [0.5-0.8], p= 0.032).

Conclusion

Initial renal function and 6-month remission predicts mortality in the RPGN.
P0480LENALIDOMIDE PLUS DEXAMETHASONE FOR PROLIFERATIVE GLOMERULONEPHRITIS WITH MONOCLONAL IG DEPOSITS
Authors: Zhou Houan , Li Manna , Wang Xia , Zeng Caihong , Huang Xianghua , Chen Zhaohong , Cheng Zhen
Published: June 2020

Background and Aims

To evaluate the efficacy and safety of lenalidomide plus dexamethasone (LD) in patients with proliferative glomerulonephritis with monoclonal Ig deposits (PGNMID).

Method

Retrospectively analyzed the clinicopathological data of 6 PGNMID patients who treated with LD protocol from January 2010 to October 2019.

Results

All of the patients received LD treatment for ≥3 months after renal biopsy. 3 patients achieved renal remission. The renal remission rate was 50%. Light microscopy showed membranoproliferative glomerulonephritis and immunofluorescence showed single kappa type IgG3 was deposited in the mesangial region and the vascular loop. Before taking LD scheme, the median urinary protein were 7.76 (1.27,14.57) g/24h, the median serum creatinine 1.34 (0.8,3.27) mg/dL, the median albumin 34.5 (22.4,37.5) g/L. In 5 patients the concentration of serum free kappa and lambda light chain increased, but no patients with abnormal serum free light chain ratio. Complement C3 deteriorated in 2 patients, 2 cases of patients with monoclonal plasma cells, 0.7% and 0.5%, respectively. Immunofixation electrophoresis suggested that 1 patient had positive serum M protein for kappa type IgG3. At the last follow-up, median urine protein was 3.33 (0.33,11.23) g/24h, median serum creatinine was 1.23 (0.91,1.82) mg/dL, and median albumin was 35.9 (24.5,45.6) g/L. The concentration of 4 patients with elevated serum free light chain was lower than that before taking the drug. Two patients with decreased complement C3 increased to normal concentration at the last follow-up. However, the other two patients had a slight decrease in complement C3. The M spike did not turn negative during the follow-up in one patients. Adverse events included anemia, neutropenia, limb numbness, upper respiratory tract infection.

Conclusion

This study reported that lenalidomide plus dexamethasone may be effective in treating proliferative glomerulonephritis with monoclonal Ig deposits for the first time. More attention needs to be paid to the hematological adverse events during lenalidomide treatment.
P0487ROLE OF THERAPEUTIC PLASMAPHERESIS IN ANCA-ASSOCIATED VASCULITIS
Authors: CHALKIA AGLAIA , GIANNOU PANAGIOTA , Damianaki Katerina , KAPOTA ATHANASIA , THOMAS KONSTANTINOS , TSALAPAKI CHRISTINA , VASILOPOULOS DIMITRIOS , PETRAS DIMITRIOS
Published: June 2020

Background and Aims

The role of plasmapheresis in the overall and renal survival of patients with ANCA-associated vasculitis (AAV) has not been fully elucidated. The aim of this study is to address whether plasmapheresis is associated with improvement in renal function and survival at 12 months in patients with severe manifestations of AAV and to record the indications, adverse events and treatment characteristics.

Method

Retrospective, descriptive study of 28 patients with AAV diagnosed over the last five years in a tertiary center. Patients were included if they had received therapeutic plasmapheresis adjunctive to conventional therapy (steroids and immunosuppressants) for the first episode of AAV or in relapse.

Results

12 patients (75% male) were enrolled with average age at diagnosis 78.5±6.14 years. The patients were followed for a median period of 20 months. In 75% of the patients MPO-ANCA was positive, in 17% ANCA negative and in 8% double positive anti-GBM/ANCA. On admission, all patients had abnormal renal function with average serum creatinine 5mg/dl±2.12 and the majority of patients (9/12) were dialysis dependent. Indications for plasmapheresis were: alveolar hemorrhage in 33%, renal impairment in 25% and combination of the two above in 42%. 11 patients received plasmapheresis for the first episode of AAV and 1 patient for relapse. Plasmapheresis was performed using filtration and fresh frozen plasma as replacement fluid. The mean number of plasmapheresis treatment was 8 (range 1 to 19 days) and the average internal time between admission and first plasmapheresis treatment was 3 days. One patient had a severe allergic reaction resulting in early discontinuation and no episodes of severe infection or death were recorded during plasmapheresis. As far as treatment all patients received concomitant immunosuppressive therapy with cyclophosphamide (CYC) and corticosteroids while Rituximab (RTX) was added in 3 patients (3/12). Alveolar hemorrhage was resolved in all patients (100%). After one year, 75% of the patients had renal recovery (cre=5mg/dl±2.12 vs cre=2.6mg/dl±1.6, p=0.06) and 67% of the patients who required hemodialysis at the time of diagnosis, during the first year became independent of dialysis (75% vs 33%, p=0.5). Finally, survival at the end of the first year was 83% with cancer and ischaemic heart disease being the cause of death.

Conclusion

Plasmapheresis is quite often used in daily clinical practice with remarkable results in dialysis independence and survival, without serious complications. The actual role of plasmapheresis in ANCA-vasculitis therapeutic algorithm will be determined shortly with the expected results of a randomized multicenter study.
P0492ICAM-1 AND VEGF AS BIOMARKERS FOR PREDICTION LUPUS NEPHRITIS FLARE
Authors: Chyzh Konstantin , Ryabceva Tatyana , Soroka Nikolay , Viarshynin Pavel
Published: June 2020

Background and Aims

Systemic lupus erythematosus (SLE) is autoimmune systemic disease of the connective tissue and characterized by the development of severe complications associated with damage to vital organs, in particular the kidneys. One of the important issues is an adequate assessment of the current activity and the objective prediction of the lupus nephritis (LN) flare. For this purpose molecular biomarkers are being searched. The work aim is the analyzing role of the intercellular adhesion molecule (ICAM-1) and vascular endothelial growth factor (VEGF) in the serum and urine of patients with SLE as a biomarker for lupus nephritis flare.

Method

The study group consisted of patients with SLE with LN (n = 23). The control group included patients with SLE without renal pathology (n = 13). The concentration of ICAM-1 and VEGF molecules was determined in blood serum and urine by enzyme-linked immunosorbent assay.

Results

The median concentration of ICAM-1in serum in patients with LN is 822.41 (580.50; 1300.95) ng/ml. That is two times higher than this indicator in the control group (378.97 (356.47; 439.52) ng/ml). The concentration of the VEGF molecule in serum in the group of LN is 91.99 (74.18; 132.58) ng/ml. That is three times higher than in the control group (31.13 (22.32; 132.58) ng/ml). An increase in the blood serum concentration of patients with SLE ICAM ≥577.7 ng/ml will indicate the presence of LN with a sensitivity of 82.61% and a specificity of 83.33%. ROC analysis showed the AUC coefficient is 0.927 (p = 0.0001). An increase in the blood serum in VEGF concentration of ≥66.43 ng/ml in patients with SLE will indicate the presence of LN with a sensitivity of 80.00% and a specificity of 83.33%. ROC analysis showed that the AUC coefficient is 0.916 (p = 0.006).

Conclusion

The results allow to conclude that it is possible to use the ICAM and VEGF concentration in serum and urine as early molecular markers of the LN and LN flare in patients with SLE.
P0504FACTORS ASSOCIATED WITH THE LONG-TERM RENAL OUTCOME OF IDIOPATHIC FOCAL SEGMENTAL GLOMERULOSCLEROSIS WITH NEPHROTIC SYNDROME
Authors: TANAKA HIROAKI , Fujii Takayuki , KOSHIZAKA JUNYA , YAMAUCHI NOBUAKI , MORIMOTO MAYU , TERASAKI NORIKO , SUZUKI SATOSHI
Published: June 2020

Background and Aims

In the treatment of idiopathic focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome, the remission of proteinuria is considered to be an important goal. The partial remission of proteinuria improves renal survival, whereas it may progressively reduce the renal function. A study searched for a novel partial remission more accurately reflecting the long-term renal outcome. The goal of proteinuria reduction for improving the renal prognosis remains to be clarified.

We examined factors associated with the long-term renal outcome of idiopathic FSGS.

Method

Of 148 patients with FSGS diagnosed based on kidney biopsy between 1981 and 2018, a retrospective cohort study was conducted involving 33 who had undergone immunosuppressive therapy for nephrotic syndrome, and had been followed-up for ≥1 year, excluding those with secondary FSGS. We examined the renal prognosis, regarding a 50% decrease in the estimated glomerular filtration rate (eGFR) as an outcome. We calculated the rate of decrease in the urinary protein level 4 and 8 months after the start of treatment, and estimated the rate of decrease associated with renal hypofunction using ROC analysis. Based on the results of ROC analysis, Cox’s proportional hazard analysis was performed using factors contributing to renal hypofunction as covariates.

Results

Concerning the background of the 33 patients, the mean follow-up period was 11.4 years, and there were 24 males. The mean age was 49.8 years, and the mean blood pressure was 100.5 mmHg. The mean urinary protein level, albumin (Alb) level, eGFR, and total cholesterol (TCho) level were 7.4 g/day, 2.1 g/dL, 44.3 mL/min/1.73 m2, and 369 mg/dL, respectively. Corticosteroid therapy was selected in 21 patients, whereas it was combined with steroid pulse therapy in 12. The daily dose of prednisolone was 37.3 mg.

On ROC analysis, the rate of decrease in the urinary protein level after 4 months was 83.1% (AUC: 0.74, sensitivity: 0.80, specificity: 0.74), and that after 8 months was 85.7% (AUC: 0.78, sensitivity: 0.90, specificity: 0.65).

Cox’s proportional hazard analysis, in which the data were adjusted with the sex, blood pressure, urinary protein level at the start of treatment, Alb level, eGFR, and treatment methods, showed that the rate of decrease in the urinary protein level after 4 months was significantly correlated with renal hypofunction: after 4 months: hazard ratio, 0.19 (95%CI: 0.04-0.77); p=0.0202; after 8 months: hazard ratio, 0.34 (95%CI: 0.05-1.37); p=0.1359.

Conclusion

In the treatment of idiopathic FSGS with nephrotic syndrome, the rate of decrease in the urinary protein level 4 months after the start of treatment was correlated with the long-term renal outcome.
P0505COST ANALYSIS OF SCREENING FOR IGA NEPHROPATHY USING NOVEL BIOMARKERS
Authors: Ishida Mami , Matsuzaki Keiichi , Ikai Hiroshi , Suzuki Hitoshi , Suzuki Yusuke
Published: June 2020

Background and Aims

IgA nephropathy (IgAN) is the most common primary chronic glomerulonephritis and a major cause of end-stage kidney disease worldwide. Recently, novel biomarkers including aberrantly glycosylated IgA1 and the glycan-specific antibodies can be measured and will predict the IgAN. However, little is known about the cost-effectiveness of this screening method from the societal perspective. This is the cost analysis of additional novel biomarkers to the conventional IgAN screening strategy.

Method

Cost analysis was carried out to compare the two diagnostic strategies with or without biomarkers. We developed an analytical decision model to estimate the lifetime medical expense of each strategy. The decision tree was started at forty years old with first time hematuria, and simulated the clinical strategy after the screening using the novel biomarkers (Group N: N), and conventional strategy (Group C: C). The result of the analysis is presented as the lifetime medical expenses from societal perspective. Discount was not considered.

Results

Lifetime medical expenses per person during forty years were calculated as 31.6 million JPY (≈287,270 USD) for using the novel biomarkers, 33.9 million JPY (≈307,903 USD) for conventional strategy. They were lower by 2.3 million JPY (≈20,633 USD) in Group N. Moreover, by using the novel biomarkers, the expected value of IgAN led to increase by 5.67 percent points (N: 48.44%, C: 42.77%), and the expected value of the dialysis led to decrease by 0.85 percent points (N: 19.91%, C: 19.06%). One-way sensitive analysis showed that the prevalence of IgAN was the most influential variable. In the sensitivity analysis, the rate of tonsillectomy with steroid pulse therapy and achieved clinical remission was higher, the expected lifetime expenses were reduced by 3.3 million JPY (≈30,355 USD) and the expected value of the dialysis led to decrease by 1.76 percent points (N: 11.80%, C: 13.56%).

Conclusion

Screening for IgAN using novel biomarkers is expected to reduce the lifetime medical expenses.
P0506PATTERNS AND OUTCOMES OF GLOMERULAR DISEASES IN ADULTS PRESENTING TO MANSOURA UNIVERSITY HOSPITAL: A SINGLE-CENTER PROSPECTIVE STUDY
Authors: M. M. Abd-Elaziz Hoda , Nassar Mohammed Kamal , Abdallah Ibrahim Dina , Sayed-Ahmed Nagy
Published: June 2020

Background and Aims

Glomerular diseases (GDs) impose a substantial burden on patients and health care systems, and they are considered a major cause of end-stage renal disease (ESRD) worldwide. Morbidity and mortality have shown to be substantially higher in patients with GDs than in the general population. In Egypt, there is yet no available national registry for GDs, and GDs outcome is not adequately studied. Therefore, it is of considerable interest to study patterns and outcomes of GDs in our locality.

Method

Patients with features suggesting GDs presenting to Mansoura nephrology and dialysis unit (MNDU) were recruited in this study between 1 July 2017 and 30 June 2018, and those with biopsy-proven GDs were prospectively followed up for a minimum of 6 months or until either death or reaching ESRD. ESRD was defined as initiation of long-term dialysis or eGFR persistently <15 ml/min per 1.73 m2 during follow up visits. Enrolled patients were subjected to through history taking and clinical examination. Biopsies were independently examined by two pathologists blinded to the clinical data. The study outcomes were to identify the GDs subtype frequencies, and to identify the frequency of those achieving either renal recovery, progression to ESRD or death from all-cause mortality. Logistic regression analysis was carried out to identify the potential predictors for renal recovery.

Results

Sixty-six patients (21 males and 45 females) with biopsy-proven GDs were included and completed the required period of follow up. The median age of the studied patients was 32 years (IQR 23 - 46.45). Fifty percent of the cases had hypertension and only one patient had was diabetic. The main indications for renal biopsy were unexplained kidney function decline (62%) followed by subnephrotic (23%) and nephrotic presentation (15%). Diffuse proliferative GN followed by MPGN and sclerosing GN were the most frequently encountered histopathological patterns. Primary and secondary GDs constituted 30.3% and 69.7% respectively. Lupus nephritis (LN) was the most common cause of secondary GDs and class IV LN was the most frequently encountered class accounting for 16 cases (51.6%) of patients with lupus. By the end of 6-month follow up, renal recovery was achieved in 30 patients (45.5%), 21 patients (31.8%) progressed to ESRD and 7 patients (10.6%) had died. Urban residency and total renal chronicity score were the most significant predictors of renal recovery.

Conclusion

Diffuse proliferative GN is the most common histopathological pattern, and secondary GDs, particularly those related to lupus, are more frequently encountered than primary GDs in our center. Unfortunately, quick complete recovery is not the rule and is possibly predictable by less chronic changes in biopsy.
P0507ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE. ABOUT 32 CASES
Authors: Amiri Mohamed lotfi , Trabelsi Raja , Ounissi Mondher , Chargui Soumaya , Jerbi Mouna , Gaied Hanene , Hedri Hafedh , Gorsane Imen , Ben abdallah Taieb , Goucha Rim
Published: June 2020

Background and Aims

Anti-Glomerular basement membrane disease « anti-GBM » is a rare autoimmune disease. It most often results in a rapidly progressive glomerulonephritis syndrome associated with intra-alveolar hemorrhage. The diagnostic confirmation is histological, by the demonstration of linear deposits of immunoglobulins (IgG) along the glomerular basement membrane. The aim of our study was to describe its epidemiological, clinical, biological, immunological, histological, and evolutionary characteristics and to identify the different prognostic factors for predicting patient survival and renal survival.

Method

It was a retrospective, descriptive and analytical study including patients over 16 years old with anti-GBM disease proved by kidney biopsy and followed up over a period of 32 years (January 1985 to July 2017), in Internal Medicine Department of Charles Nicolle Hospital of Tunis.

Results

We collected 32 patients with a sex ratio H/F = 1.13. The mean age at diagnosis was 42 years old with extremes of 18 to 81 years old. The most frequent extra-renal manifestations were pulmonary (53%), neurological (12.5%) and ocular (6%) manifestations. Hematuria associated with proteinuria was constantly found.

The latter was nephritic in 31% of patients. All patients had renal insufficiency on admission, oligo-anuric in 60% of cases. The use of extra-renal treatment at admission was necessary in 75% of patients. On the immunological level, the search for anti-MBG antibodies, performed in 20 patients, was positive in 65% of cases. All our patients had undergone a renal biopsy puncture with direct immunofluorescence study.

Diffuse extra-capillary glomerulonephritis was observed in 93% of patients.

Corticotherapy was initiated in 27 cases, associated with plasma exchange in 21 cases and cyclophosphamide in 17 cases. Nine of our patients died in the first year. Renal outcome was marked by partial remission in 2 cases and end-stage renal failure in 19 cases. In univariate analysis, an age greater than 60 years and the occurrence of respiratory distress were predictors of death.

Oligo-anuria and need dialysis on admission were predictive factors for progression to end-stage renal failure.

Conclusion

Anti-GBM disease is a serious illness. Current therapeutic modalities have significantly improved patient survival. These must be intensive and rapid in order to hope for a favorable renal evolution whose prognosis remains reserved.
P0519HEXARELIN PROTECTS ISCHEMIA REPERFUSION INDUCED ACUTE KIDNEY INJURY BY TARGETING 14-3-3Σ
Authors: Guan Chen , Xu Yan
Published: June 2020

Background and Aims

Acute kidney injury (AKI), manifested as a sudden decline in renal function on the order of days or a week, is one of the most common complications and is strongly associated with renal prognosis, medical expenses and length of stay of hospitalized patients. However, incidence of AKI can be reduced by early intervention. Hexarelin is a synthetic analogue of ghrelin with a potent GH releasing activity, which is also found to exhibited a significant protectant activity against postischemic ventricular dysfunction in isolated perfused hearts subjected to low flow ischemia and reperfusion. This study aims to explore the effects of hexarelin on ischemia reperfusion induced acute kidney injury (I/R-AKI) and the underlying mechanism of it.

Method

Thirty healthy male SPF SD aged at 8 weeks weighing 250-300g rats were divided into 5 groups including normal group, sham operation group, acute kidney injury (AKI) group, acute kidney injury group after hexarelin (HEX + AKI), and acute kidney injury group after saline (Saline + AKI). Bilateral kidney artery clamping was applied for 50 min to induce AKI. The drug-administered group and the saline-controlled group rats were treated with intraperitoneal injections 7 days before modelling and the Hex + AKI group and the saline + AKI group were given Hexarelin (dose 100 μg/kg. d) and equal volume of saline, respectively. To explore the underlying mechanism of HEX on I/R-AKI, gene expression profiling of AKI samples were searched from Pubmed, GEO dataset. Differential expression genes were used to predict canonical signal transduction pathways and signalling networks. Molecular docking was used to predict the combination of hub proteins and HEX.

Results

1) Renal function in HEX-pretreated rats was significantly improved compared with control group: HE results showed that renal tubules were less dilated and rebuilt after pretreatment, and the infiltration area was significantly reduced; serum creatinine (P = 0.0005 <0.05), urea nitrogen (P <0.0001) concentration were significantly reduced; RT-qPCR showed that relative expression of Kim-1 (P<0.0001), caspase3 (P = 0.007), Bax (P <0.0001), Bad (P = 0.0168 <0.05) in HEX+AKI group were significantly decreased while the relative expression of Bcl-2 (P <0.05) was significantly increased compared with saline treated rats;

2) Microarray data analysis showed that 63 differential expression genes including SFN, Cyr61, Kim-1 were hub genes in the development of I/R-AKI;

3) Three-dimensional structure of the hub proteins HEX were obtained from the SWISS-MODEL database and the PubChem compound database, and Autodock software was used to calculate the molecular docking between proteins and HEX. Results showed that HEX and the protein that encoded by the gene SFN (SFN, 14-3-3σ) binding stably with a binding energy of -8.51;

Conclusion

Hexarelin protects ischemia reperfusion induced acute kidney injury by targeting 14-3-3σ.
P0521TICAGRELOR PROTECTS KIDNEY FROM SEPSIS INDUCED ACUTE KIDNEY INJURY THROUGH ADENOSINE DEPENDENT WAY
Authors: Cao Yuhan , Xu Qiancheng , Wang Yuwei , Fu Cong
Published: June 2020

Background and Aims

Sepsis induced acute kidney injury (AKI) is common in intensive care unit in multiple organ failure patients. Ticagrelor is an anti-platelet drug that widely applied in coronary artery disease. In addition, ticagrelor can increase the level of adenosine. Recent study had indicated that ticagrelor can protect renal function in sepsis induced AKI. However, the detailed mechanism was still unknown. Accordingly, we designed this trial to investigate if the ticagrelor alleviated sepsis induced AKI and demonstrated the potential mechanism that how ticagrelor works.

Method

C57BL6J mouse received oral ticagrelor (20mg/kg and 50mg/kg) for 7 days and caecum ligation and puncture (CLP) were performed. Adenosine-receptor antagonist was administered (10mg/kg, intraperitoneal injection) to block the adenosine pathway 2h before CLP. After 24h, serum creatinine was measured. PAS staining was used and TUNEL staining was applied to determine the pathological changes and cell apoptosis. Plasma concentrations of TNF-α and IL-1β were detected. Kidney tissue level of TNF-α and IL-1β were determined via qRT-PCR. Western blot was used to determine the expression of signal molecular in kidney.

Results

In ticagrelor group, PAS staining (fig. 1) showed that less swelling of renal tubules and TUNEL staining (fig. 2) showed the less cell apoptosis compared to CLP. Serum creatinine was significantly lower in ticagrelor group. Plasma TNF-α and IL-1β and kidney expression of TNF-α and IL-1β were significantly lower in ticagrelor group. Adenosine-receptor antagonist significantly blocked the effect of ticagrelor (fig. 3 ang 4). Western blot showed that ticagrelor activate the phosphorylation of AKT and mTOR in kidney. Adenosine-receptor antagonist inhibited the activation of AKT and mTOR (fig. 5).

Conclusion

The protective effect of ticagrelor was dependent on adenosine-receptor activation with downstream upregulation of phosphorylation of AKT and mTOR in sepsis induced AKI.