bluuebunny/crossref_metadata_2025 huggingface dataset:
P0329CLINICAL SIGNIFICANCE OF CREATININE VARIABILITY AND ITS IMPACT ON CARDIOVASCULAR OUTCOMES
Authors: Lee Soojin , Lee Yeonhee , Park Sehoon , Han Kyungdo , Kim Yaerim , Kim Jung-Hyun , Joo Kwon Wook , Kim Dong Ki
Published: June 2020

Background and Aims

Linear decline of glomerular filtration rate (GFR) is associated with aggravating the patient outcomes. Serum creatinine, which is commonly used for estimating GFR, often fluctuates throughout the serial measurement. The clinical significance of creatinine fluctuation among the general population whose renal function is prior to chronic kidney disease (CKD) development had not been demonstrated yet. Thus, we investigated the study to evaluate the impact of creatinine variability on patient outcomes.

Method

A nationwide retrospective cohort study was performed usaing the database of Korean National Health Insurance System. Adult patients who received national health screening program and measured creatinine for ≥3 times between 2012 and 2016 were considered. Those who previously developed CKD were excluded. The variability of creatinine values were presented with variability independent of mean (VIM). The patients were classified into quartiles of the VIM and Q4 presented highest variability of creatinine. Then, the risks of myocardial infarction (MI), stroke and death were assessed according to the extent of variability.

Results

During the median follow up of 3.27 years, 3,509,899 participants were examined for association of creatinine variability and cardiovascular outcomes. Participants with higher creatinine variability were significantly associated with elevated risk of MI (hazard ratio (HR) (95% confidence interval (95% CI)) 1.11 (1.04-1.18), stroke (HR (95%CI) 1.06 (1.00-1.13)) and death (HR (95%CI) 1.15 (1.09-1.21)), compared to those with the lowest quartile of creatinine variability.

Conclusion

Increased creatinine variability exhibited association with elevated risk of MI, stroke and death. In general population, whose renal function is prior to CKD development, monitoring of creatinine variability needs to be considered as the parameter of predicting the adverse outcomes, in addition to the decline of GFR.
P0342A STUDY OF TREATMENT WITH RITUXIMAB IN REFRACTORY LUPUS NEPHRITIS
Authors: Mahanta Pranab Jyoti , Sharma Manjuri , Alam Shahzad , Doley Prodip Kumar , Pegu Gayatri , MAZUMDER MASTAKIM AHMED
Published: June 2020

Background and Aims

SLE patients have 40% to 70% life time risk of developing lupus nephritis (LN). In LN patients rate of end-stage renal disease is 10%, remaining constant in the last 30 years, even after the emergence of various immunosuppressive therapy.

SLE is an example of classical antibody-mediated disease and hence treatment with B cell depleting agent (like the use of Rituximab ) appears to be a promising approach for this unwinnable disease from the Roman era.

The aim of this study was to analyze the outcome in terms of - no renal response (NRR), complete renal response (CRR) or partial renal response (PRR) at week 24 after rituximab treatment initiation in refractory LN.

CRR considered, if serum creatinine (S Cr) level returned to baseline, with a decline in the 24 hour urinary protein to < 500 mg/day. PRR defined as stabilization (+/-25%), or improvement of S Cr, plus a 50% decrease in 24 hour urinary protein (which was < 3.5 gm/day). NRR considered, if participant did not achieve either a CRR or PRR.

Method

It is a single center prospective observational study, comparing short term (24 week) outcomes in resistant lupus nephritis patients of >18 year age group with weekly (total 4) dose of rituximab therapy.

The study was conducted on 25 refractory lupus nephritis patients admitted in Nephrology Department (not responding to conventional immunosuppressive drugs like cyclophosphamide, MMF). Repeat renal biopsy was performed, all baseline investigations were done.

Injection Rituximab 375 mg/m2 weekly 0,1,2,3 week along with premedication treatment were given to every patient. The clinical outcome was assessed monthly post-treatment.

Results

In the study maximum patients were of class IV, n=21 (84 %). Sustained (6 months post treatment) CRR was achieved in n=6 (24%) patients, n=7 (28%) patients achieved PRR, rest n=12 (48%) patients had NRR. Mean blood absolute CD-19 count was significantly negatively correlated with response to rituximab treatment ( p< 0.001) .Mean absolute CD-19 count was 2.33/microliter in CRR, 2.14/microliter in PRR group and 21.25 / microliter in NRR group . No significant side effects of rituximab were observed.

Limitations –Small sample size, single center study, long term follow up not considered.

Conclusion

In refractory LN patients, 24 weeks after Rituximab treatment
P0343RISK PREDICTION MODELS FOR PREDICTING PROGRESSION OF IGA NEPHROLOGY:A VALIDATION STUDY
Authors: Xie Jingyuan
Published: June 2020

Background and Aims

Risk prediction models for IgA nephropathy (IgAN) containing clinical variables (clinical model) or clinical plus pathological variables (full model) have been established based on a large international collaborative study recently, but external validation of these models are still required before clinical application. The aim of this study is to externally validate previously reported risk prediction models based on our multi-center IgAN cohort.

Method

Biopsy-proven IgAN patients with eGFR ≥15 ml/min/1.73 m2 at baseline and a minimum follow-up of 6 months were enrolled. Primary outcome was defined as end-stage kidney disease (ESRD). Cox proportional hazards models were built to validate risk models. R2, Akaike information criterion (AIC) and C statistic were calculated to evaluate model accuracy.

Results

A total of 2300 IgAN patients with a median follow-up of 30 months were enrolled, and 214(9.3%) ESRD occurred during the follow-up period. The median age was 35(interquartile range, 28-44) years, and 1106 cases (48.1%) were men. Our cohort successfully validated the clinical model and the full model based on C statistic (0.90 and 0.91) and R2 (0.32 and 0.32). Our results showed limited improvement in model performance after adding the Oxford classification parameters to clinical parameters. However, both two models performed better than the model consisting only pathological parameters(C statistic 0.83, R2 0.24). We also validated other risk prediction models, including CLIN model (C statistic 0.90, R2 0.32) and CLINPATH model (C statistic 0.91, R2 0.31) derived from Chinese IgAN patients or CKD model (C statistic 0.90, R2 0.32) derived from Canadian CKD patients. It was found that clinical models based on different combinations of clinical parameters performed similarly.

Conclusion

In summary, we successfully validated a recently reported IgAN risk model and we found that clinical parameters alone could accurately predict ESRD risk in IgAN patients.
P0344NEFECON® (BUDESONIDE) SELECTIVELY REDUCES CIRCULATING LEVELS OF BAFF (BLYS) AND SOLUBLE BCMA AND TACI IN IGA NEPHROPATHY
Authors: Molyneux Karen , Wimbury David , Barratt Jonathan
Published: June 2020

Background and Aims

There is increasing evidence to support a pivotal role for the gut-associated lymphoid tissue (GALT) as a major source of the poorly O-galactosylated immunoglobulin A1 (IgA1) that triggers the formation of nephritogenic immune complexes in IgA nephropathy (IgAN). Critical to the regulation of IgA synthesis in GALT are two cytokines, which regulate B-cell maturation, function and survival: BAFF (B-cell activating factor [also known as BLyS (B-lymphocyte stimulator)]) and APRIL (A PRoliferation-inducing ligand). BAFF and APRIL bind to specific cell-surface receptors: TACI (transmembrane activator and calcium modulator and cyclophilin-ligand interactor), BCMA (B-cell maturation antigen) and the BAFF receptor. Several studies have shown elevated levels of BAFF and APRIL in IgAN linked to worse clinical outcomes. The therapeutic potential of selectively targeting GALT was demonstrated in the NEFIGAN trial (NCT01738035), which assessed the safety and efficacy of a novel targeted-release formulation of budesonide (NEFECON®), designed to deliver budesonide to the GALT-rich distal ileum in patients with IgAN. The trial comprised a 6-month run-in, 9-month treatment and 3-month follow-up phase: 48 patients received NEFECON® 16 mg/day, 51 patients received NEFECON® 8 mg/day and 50 patients received placebo. The headline result of the study was that NEFECON® 16 mg/day, added to optimised renin–angiotensin system blockade, reduced proteinuria and stabilised estimated glomerular filtration rate in patients with IgAN. In this study, we aimed to determine whether NEFECON® treatment altered synthesis of the BAFF and APRIL B-cell maturation modulators.

Method

Serum levels of BAFF, APRIL, BCMA and TACI were measured using Luminex technology. Changes in the levels of each biomarker between randomisation (T0), end of treatment (T1) and the end of study (T2) and between treatments arms were compared using a one-way analysis of variance. Significance was set at p<0.05.

Results

A significant, dose-dependent reduction in serum BAFF levels was seen with NEFECON®, which reversed on cessation of NEFECON®. There were similar significant reductions in the levels of soluble BCMA and TACI with treatment but no effect was seen on circulating levels of APRIL. These changes were mirrored by parallel changes in soluble CD27 levels and are consistent with our previous reports describing a dose-dependent reduction in circulating IgA–IgG immune complexes, secretory IgA and galactose-deficient IgA levels with NEFECON®.

Conclusion

Delivering budesonide to the GALT-rich distal ileum modulates key regulators of GALT B-cell maturation in IgAN. Although the samples available are not sufficient to determine that the observed changes in serum BAFF, BCMA and TACI levels are due to a direct action on GALT, it is intriguing to note that BAFF-transgenic mice develop an IgAN-like disease, principally due to IgA overexpression in the intestinal lamina propria.
P0351IMPACT OF APOL1 POLYMORPHISM ON LUPUS NEPHRITIS
Authors: Burger Carole , Alexandre KARRAS
Published: June 2020

Background and Aims

African ancestry is associated with more severe kidney involvement and end stage renal disease (ESRD) in lupus nephritis (LN). Two polymorphisms of the apolipoprotein L1 gene (APOL1), defining the risk allels (RA) G1 and G2, particularly frequent among subjects of African ancestry, markedly increase the risk of ESRD and the occurrence of collapsing glomerulopathy (CG) in the general population. The aim of this study was to assess the impact of ApoL1 RA on clinical, biological, and histological presentation of LN, and its prognosis.

Method

Patients of African ancestry with biopsy-proven LN were included between January 2017 and September 2018. Clinical, laboratory and pathology datas were retrospectively collected and ApoL1 genotyping was performed.

Results

Among the 53 included patients, 31 had no RA, 16 were heterozygous with only one RA and 6 had 2 RA (G1/G1 or G2/G2 or G1/G2). The population was divided in 2 groups: low risk polymorphism (LRP) group defined by the presence of 0 or 1 RA, and high risk polymorphism (HRP) group with 2 RA. At presentation, hypertension (OR 25,4 [1,3-510,3]) and acute renal failure (OR: 9,3 [1,3-65,2]), were more frequent in the HRP group when compared to the LRP group. Initial median serum creatinine was respectively 363 μmol/l (IQR 119-594) vs 64 μmol/l (IQR 55-127). After 2-year follow-up, median eGFR was 59mL/min (IQR 41-91) in the HRP group and 117mL/min (IQR 92-124mL/min) in the LRP group. Patients in the HRP group were more likely to have an impaired renal function with an estimated glomerular filtration rate (eGFR) <60mL/min compared to patients in the LRP group (OR: 13,5 [2,1-86,5]). Moreover, ESRD-free survival was worse in the HRP group (Hazard ratio: 78,8 [5,3-1124,0]) despite similar chronicity indexes on initial kidney biopsy and comparable therapeutic strategies. As for histological findings, CG was observed in 67% of patient’s kidney biopsy in the HRP group whereas it only concerned 12% of patient’s kidney biopsy in the LRP group (OR: 14,8 [2,4-84,8]).

Conclusion

The ApoL1 polymorphism strongly affects LN prognosis in patients with African ancestry, resulting in more severe inaugural presentation, higher risk of subsequent severe chronic kidney disease and development of collapsing glomerulopathy for subjects with 2 RA.
P0354MATRIX ASSISTED LASER DESORPTION/IONIZATION MASS SPECTROMETRY IN PROTEIN ALTERATIONS ASSOCIATED WITH THE PROGRESSION OF IGA NEPHROPATHY DISCOVERY
Authors: Ivanova Mariia , Dyadyk Olena , Ivanov Dmytro , Clerici Francesca , Smith Andrew , Magni Fulvio
Published: June 2020

Background and Aims

IgA nephropathy (IgAN) is one of the most diffuse glomerulonephrites worldwide, but there are still many issues regarding its prognosis and pathogenesis understanding. Although the diagnosis is established by renal biopsy examination, there are still remaining pitfalls in primary origin discrimination, and therefore for prognosis and outcome for the patient.

Method

In this pilot study we performed matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) with a high spatial resolution (raster sampling of 20 μm) on formalin fixed paraffin embedded renal biopsies obtained from patients with IgAN (n=11) and other mesangioproliferative glomerulonephrites (MesPGN, n=6) attempting to enlighten proteomic alterations that may be associated with the progression of IgAN. The patients in both disease groups were separated according to their CKD stage (CKDI, CKDII, CKDIII and more). After MALDI-MSI analysis, all biopsies were stained with hematoxylin and eosin, scanned and overlaid with molecular image in order to verify the signals’ spatial distribution.

Results

Using MALDI-MSI we detected clear differences in the proteomic profiles of IgAN and other MesPGN tissues. Fourteen signals (AUC ≥ 0.8) were observed to have an altered intensity among the different CKD stages within the IgAN group. In particular, large increases in the intensity of these signals could be observed at CKD stages II and above. Putatively identified, these signals primarily corresponded to proteins involved in inflammatory and healing pathways and their increased intensity was localised within regions of tissue with large amounts of inflammatory cells or sclerosis (Figure 1), verified by immunohistochemical staining (Figure 2).

Conclusion

The capability of MALDI-MSI to provide highly spatially resolved proteomics analysis of complex renal tissue demonstrates it a useful additional diagnostic and prognostic tool and a promising approach in the search for prognostic or predictive markers in glomerular diseases.
P0355FAMILY HISTORY OF COMPLEX TRAITS IN THE CUREGN COHORT: ASSOCIATIONS WITH RENAL FUNCTION, COMORBIDITY BURDEN AND DISEASE PROGRESSION
Authors: Zanoni Francesca , Verbitsky Miguel , Carlassara Lucrezia , Marasa Maddalena , Kiryluk Krzysztof , Gharavi Ali
Published: June 2020

Background and Aims

Family history (FHx) of complex traits may reflect shared genetic/environmental risk. Few studies suggest associations with increased risk of comorbidities and worsening renal function, but this has not been examined in primary glomerulopathies (GNs). Herein, we studied the association of FHx of complex traits with presentation patterns, comorbidities and disease progression in a prospective cohort of patients with primary GN.

Method

The Cure Glomerulopathy Networ (CureGN) is a prospective multi-center observational study of GN patients (N=2474) affected by biopsy-proven Focal Segmental Glomerulosclerosis (FSGS), Minimal Change Disease (MCD), Membranous Nephropathy (MN) and IgA Nephropathy/Vasculitis (IgAN/V). Associations of self-reported FHx of diabetes (DM), coronary artery disease (CAD), cancer (C), clotting disorders (CD), and autoimmune diseases (AD) with eGFR, UPCR at diagnosis, and comorbidities prevalence were studied using linear and logistic regression models adjusted for age, sex, ethnicity, race, BMI and other relevant clinical covariates. Associations between FHx and ESRD/40%eGFR reduction were investigated with multivariate Cox models.

Results

FHx of DM was associated with lower eGFR and higher UPCR at diagnosis in the entire cohort (p=0.006 and p=0.03), lower eGFR in FSGS (p=0.02) and higher UPCR in IgAN/V (p=0.01). Regarding comorbidity burden (Table 1), FHx of DM was associated with higher prevalence of DM, heart failure and infections requiring hospitalization, FHx of C with cancer, FHx of CD with higher prevalence of thrombosis and FHx of AD with inflammatory bowel, celiac diseases, asthma and drug allergies. At the survival analysis adjusted for age, sex, ethnicity, race, BMI, diagnosis group, eGFR and UPCR at diagnosis, DM, hypertension, use of immunosuppressants and RAAS-inhibitors, FHx of DM was associated with higher risk of the composite outcome of ESRD/40%eGFR reduction in the entire cohort (HR 1.39, 95%CI 1.07-1.81, p=0.01), and specifically in FSGS (HR 1.76, 95%CI 1.08-2.85, p=0.02) and in the paediatric subgroup (HR 1.98, 95%CI 1.04-3.80, p=0.04).

Conclusion

FHx of complex traits are associated with higher prevalence of specific comorbidities. FHx of DM identifies patients with lower eGFR at diagnosis, higher prevalence of infections and higher risk of renal disease progression. These findings, which need to be confirmed in other cohorts, suggest that FHx could be an additional useful parameter for risk stratification and management of primary GN.
P0369MINOR GLOMERULAR ABNORMALITIES ARE ASSOCIATED WITH DETERIORATION OF LONG-TERM KIDNEY FUNCTION AND MITOCHONDRIAL INJURY
Authors: Park Mooyong , Yu Byung Chul , Park Su Jung , Park Jin Hoon , Lee Kyung Ho , Moon Ahrim , Choi Soo Jeong , Kim Jin Kuk , Hwang Seung Duk
Published: June 2020

Background and Aims

Minor glomerular abnormalities (MGAs) are unclassified glomerular lesions indicated by the presence of minor structural abnormalities that are insufficient for a specific pathological diagnosis. The long-term clinical outcomes and pathogenesis have not been examined. We hypothesized that MGAs would be associated with the deterioration of long-term kidney function and increased urinary mitochondrial DNA (mtDNA) copy numbers.

Method

We retrospectively enrolled patients with MGAs, age-/sex-/estimated glomerular filtration rate (eGFR)-matched patients with IgA nephropathy (IgAN), and similarly matched healthy controls (MHCs; n = 49 each). We analyzed the time×group interaction effects of the eGFR and compared mean annual eGFR decline rates between the groups. We prospectively enrolled patients with MGAs, age- and sex-matched patients with IgAN, and MHCs (n = 15 each) and compared their urinary mtDNA copy numbers.

Results

Compared to the MHC group, the MGA and IgAN groups displayed differences in the time×group effects of eGFR (Figure 1), higher mean annual rates of eGFR decline (Table), and higher urinary mtDNA copy numbers (Figure 2); however, these groups did not significantly differ from each other.

Conclusion

The results indicate that MGAs are associated with deteriorating long-term kidney function, and mitochondrial injury, despite few additional pathological changes. We suggest that clinicians conduct close long-term follow-up of patients with MGAs.
P0375URINARY DICKKOPF-3 PREDICTS RENAL SURVIVAL IN ANCA-ASSOCIATED VASCULITIS
Authors: Diaz Enamorado Yunayka , Shabaka Amir , Garcia Iñigo Francisco Jose , Villacorta Javier , Cases Corona Clara Maria , Dominguez Torres Patricia , Fernandez Juarez Gema Maria
Published: June 2020

Background and Aims

Urinary Dickkopf-related protein-3 (DKK3), a stress-induced renal tubular glycoprotein, has been identified as a novel biomarker for chronic kidney disease patients at risk of kidney disease progression. The aim of our study was to assess urinary DKK3 as a diagnostic biomarker for predicting GFR loss and renal survival in a cohort of patients with ANCA-associated vasculitis

Method

We measured baseline urinary DKK3 levels in a cohort of patients diagnosed with ANCA-associated vasculitis (AAV), and repeated measurements at 1 and 3 months of diagnosis. Urinary DKK3 levels were normalized to urinary creatinine concentrations to account for dilution of the urine. The association between baseline uDKK3/creatinine levels and the rate of GFR loss was measured. The primary composite outcome was defined as an increase of >50% in baseline serum creatinine, initiation of renal replacement therapy or death.

Results

We included 36 AAV patients with a mean age 71.2 ±12.0 years, 55.6% males, with baseline eGFR at diagnosis 22.3 ±14.1 ml/min. There was a correlation between baseline DKK3-creatinine levels and age (r=0.48, p=0.003) and baseline eGFR (r=-0.327, p=0.051). Ten patients (27.8%) reached the primary composite outcome. Patients were then stratified into two groups according to baseline uDKK3 levels. The group of patients with baseline uDKK3-Creatinine >16000 pg/mg were older (76±12.5 vs 66.4 years, p=0.014), presented a lower baseline eGFR (16.2±10.8 vs 28.5±14.5 ml/min, p=0.007) and had higher baseline uCD163 levels (1135.1 [312.4-2537.5] vs 397.2 [146-809.4], p=0.089]). There were no differences in baseline proteinuria, microhematuria or histological class across the groups. After a median follow-up of three years, 44.4% of the patients in the highest DKK3 group reached the primary composite outcome, whereas only 11.1% of those with lower DKK3 levels reached the endpoint at the end of follow-up (p=0.026) . The area under the time-dependent curve for predicting the primary composite outcome according to uDKK3 was 0,677, with a sensibility of 80% and specificity of 61.5% at the cutoff 16056 pg/mg. Additionally, patients who had a >30% increase in uDKK3 levels after one month reached the primary composite outcome more often (40%) than those who remained with a stable or decreasing DKK3 levels (0%, p=0.04). There were no differences in the rate of change in DKK3 and the different treatment regimens.

Conclusion

Elevated urinary DKK3 levels help identify those patients who are at a higher risk of kidney disease progression and dialysis dependency over the next three years in ANCA-associated vasculitis. DKK3 monitoring could be considered in the follow-up of these patients to assess the effect of treatment and predict the long-term response.
P0381THE UTILITY OF LOW DOSE RITUXIMAB FOR INDUCTION AND MAINTENANCE TREATMENT IN ELDERLY PATIENTS WITH ANCA-ASSOCIATED VASCULITIS: A SINGLE CENTRE EXPERIENCE
Authors: Metraiah El Hakem , Dospinescu Paula , Fluck Nicholas , Basu Neil , Kidder Dana
Published: June 2020

Background and Aims

Elderly patients with Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) tend to have higher rates of mortality and treatment-related adverse events. Rituximab is now widely used in the treatment of patients with AAV based on the results of remission induction (RITUXVAS and RAVE) and remission maintenance (MAINRITSAN) randomized controlled trials. Elderly patients were relatively under-represented in these trials. In this observational study we aimed to examine the outcome of elderly patients who received Rituximab (either as low dose Rituximab (LDR) or standard dose Rituximab (SDR)) for remission induction and maintenance.

Method

We investigated the outcome of three treatment strategies in elderly (age>65 years) patients who presented with AAV to our Vasculitis clinic from 1 July 2007 to 9 of July 2017. These strategies included: LDR (17 patients), SDR (14 patients) and Cyclophosphamide/Azathioprine (Cyc/A) 26 patients. LDR patients received two dose of 500mg Rituximab fortnightly followed by six monthly 500mg doses for 2 years. SDR patients received 1g Rituximab fortnightly followed by six monthly 1g doses for 2 years. Cyc/A patients received 1.5mg/kg oral Cyclophosphamide for 3 months followed by 18 months of Azathioprine.

Results

Among 57 AAV patients, 56% were females and mean age of 79.6 +/- 4 (LDR), 72.4 +/- 7.2 (SDR), and 71.1 +/- 5 (Cyc/A) (p=0.001). The distribution of MPA and GPA was 11/6 in LDR, 7/7 in SDR and 18/8 in Cyc, respectively. Relapsing GPA was significantly higher in SDR 12/2 compared to LDR 3/14, and Cyc/A 0/26 (p=0.0001). There were no significant differences in serum creatinine, BVAS scores or CRP between groups at initiation of treatment. Patients survival at 24 months was 88% (LDR), 92% (SDR), and 77% (Cyc), p=0.3. The mean corticosteroids dose at 3 months from onset of treatment was significantly lower in the LDR (7.6 +/- 1.7) and SDR (8.6 +/- 3.1) compared with Cyc/A (12.5 +/- 3.6), p=0.001. 1 patients relapsed in the SDR group and 4 patients in the Cyc/A group. Hospitalization for infections were significantly lower in the LDR (3 episodes) compared to Cyc/A (17 episodes), p=0.004. The number of patients with hypogammaglobulinemia was not significantly different between LDR and SDR.

Conclusion

In this single centre observational study, we found that low dose Rituximab for remission induction and maintenance associated with similar patient outcome to SDR. The findings of this study needs to be replicated with longer duration of follow-up.
P0385CLINICAL DIFFERENCES OF MEMBRANOPROLIFERATIVE GLOMERULONEPHROPATHY (MPGN) ACCORDING TO PRESENCE OF HEPATITIS B VIRUS INFECTION
Authors: Kim Hea Eun , CHIN HO JUN
Published: June 2020

Background and Aims

Traditional definition of MPGN by morphologic changes on light microscopic examination was reclassified into MPGN caused by immunoglobulin/immune complex injury and C3 glomerulopathy (C3G) with alternative complement pathway abnormality based on immunofluorescence staining. MPGN might be caused by various causes such as malignancy, infection, autoimmune diseases, etc. It was rarely known the clinical characteristics of MPGN according to the possible causes excluding C3G.

Method

We enrolled 20,481 adult patients having native kidney biopsy for diagnosis of nephritis between 1979 and 2018, retrospectively. Among them, there were 553 patients with MPGN whom we reclassified into 18 patients with C3G and 535 MPGN patients. We excluded patients with cancer, autoimmune disease, hepatitis C virus infection, C3G, or combined pathologic diagnosis other than MPGN. Finally, we enrolled 156 patients without hepatitis B surface antigen (HBsAg)[MPGN] and 48 patients with HBsAg [MPGN_HBV]. The final outcomes were incidences of end stage renal disease (ESRD) and death.

Results

Patients with MPGN_HBV are younger than MPGN (45.5 ± 15.8 years vs 54.6 ± 15.7 years, p=0.001) and included more males (43 (89.6%) vs 97 (62.2%), p<0.001). The systolic blood pressure was not different between groups but the diastolic blood pressure was higher in MPGN_HBV (85.4 ± 10.4 mmHg vs 80.7 ± 13.4 mmHg, p=0.018). The level of urine protein to creatinine ratio was not different between groups but the level of glomerular filtration rate (GFR) was higher in patients with MPGN_HBV compared to patients with MPGN (65.8 ± 29.0 ml/min/1.73 m2 vs 57.5 ± 34.8 ml/min/1.73 m2, p=0.039). Mortality was observed in 2 patients with MPGN_HBV (4.2 %) and 9 patients with MPGN (5.8%)(p=1.000) during 64.9 months (median). Incident ESRD was notified in 6 patients with MPGN_HBV (13.3 %) and 39 patients with MPGN (26.5 %)(p=0.067) during 47.8 months (median). HBV positivity was not a risk factor to mortality (p=0.847) and was not a risk factor to incident ESRD (p=0.108), either, by Cox’s hazard proportional model adjusted with related factors to mortality. The most important risk factor was hemoglobin and GFR at renal biopsy.

Conclusion

The clinical characteristics of MPGN according to presence of HBsAg were different, however, the prognosis was not dependent on HBsAg positivity, which suggested the severity of renal injury was more important than the cause of renal injury.
P0388ABC-R ANCA STUDY ESTABLISHMENT OF AN ANATOMOPATHOLOGICAL BIOLOGICAL AND CLINICAL PROGNOSTIC SCORE IN THE MANAGEMENT OF ANCA VASCULITIS WITH RENAL IMPAIRMENT
Authors: HODIQUE Florine , NOUVIER Mathilde , PICARD Cecile , RABEYRIN Maud , Juillard Laurent , DIJOUD Frederique , FABIEN Nicole , Fouque Denis , BARBA Thomas , HOT Arnaud
Published: June 2020

Background and Aims

Glomerulonephritis is common in ANCA associated vasculitis (GN-AAV). There is extensive published data on the renal prognosis of these conditions. However, few authors have described predictive factors for end-stage renal disease (ESRD) in patients with GN-AAV. Many authors suggest that renal biopsy should be abandoned in patients whose diagnosis would be established by antibody positivity alone.

The aim of the study was to establish a prognostic score for renal damage during ANCA vasculitis and demonstrate need for prognostic renal biopsy.

Method

One Hundred and eighteen patients referred to 2 french nephrology departments in Lyon between January 2003 and January 2019 were retrospectively analysed. Patients were randomly divided in 2 cohorts at a ratio of 70/30: training and validation cohorts. ESRD was defined as glomerular filtration rate (eGFR) ≤ 15mL/min/1.73m2,need of chronic dialysis or renal transplantation.

Results

Of the 118 patients, 38 (32.20%) developed ESRD. We identified 3 criteria associated with development of ESRD in patients with GN-AAV. One point was assigned to each criterion according to a threshold value: eGFR at the time of renal biopsy ≤ 15 mL/min; percentage of sclerotic glomeruli ≥ 11% and percentage of normal glomeruli < 20%. A new prognostic renal score was established in patients with GN-AAV. It classifies patients into 3 categories at risk of developing ESRD: low (≤ 1 point), moderate (2 points) and high (3 points).

Conclusion

Two of the three criteria of our score are histological. Biopsy remains, when possible, an essential tool for diagnosis and especially to predict renal prognosis of ANCA vasculitis with renal impairment.
P0396THE NEPHRITIC SYNDROME IN JAPAN AND EUROPE
Authors: Weiner Maria , Fujimoto Shouichi , Suzuki Yusuke , Skrunes Rannveig , Goritschan Anna , Crnogorac Matija , Geddes Colin C , Turkmen Kultigin , Galesic Kresimir , Rosenkranz Alexander , Kaname Shinya , Sugiyama Hitoshi , Segelmark Mårten
Published: June 2020

Background and Aims

The combination of new onset haematuria, proteinuria and declining GFR, often referred to as the nephritic syndrome, constitute a strong indication for renal biopsy. Several different disease entities can underlie these findings, many of them requiring prompt treatment. Epidemiological studies of glomerular diseases are in general hampered by the strong influence of differences in biopsy practices. However, there is reason to believe that such differences are less pronounced in cases of acute/subacute nephritic syndrome. The aim of the present study is to compare the frequencies of diseases causing the nephritic syndrome in Japan and Europe using data from renal biopsy registries.

Method

Data were retrieved from national or regional renal biopsy registries in Japan, Sweden, Norway, Scotland, Austria, Croatia and Turkey from 2007-01-01 to 2018-12-31. Only patients biopsied due to acute or subacute nephritic syndrome, defined as a combination of new onset haematuria, sub-nephrotic proteinuria and reduced GFR, were included. Demographic, clinical and laboratory data were collected from the time of renal biopsy.

Results

A total number of 2789 patients from Japan and 1202 patients from Europe were included. Among the Japanese patients, 46% were women, median age was 67 years (IQR 54-74) and median creatinine concentration at the time of renal biopsy was 198 µmol/L (IQR 109-343). In Europe, 43% were women, median age was 58 years (IQR 42-70) and median creatinine concentration was 210 µmol/L (IQR 127-390). Figures from the different European countries are presented in Table 1. The most common diagnosis in both Japan and Europe was ANCA-associated nephritis (44% in Japan, 34% in Europe), followed by IgA nephritis (8.5% in Japan, 18.6% in Europe) and acute tubulointerstitial nephritis (6.2% in Japan and 7.1% in Europe).

Conclusion

We describe preliminary data from a large multicenter cohort of patients presenting with the nephritic syndrome. This clinical presentation is most often encountered in the 6th and 7th decade of life and the distribution between men and women is fairly equal. The most common underlying cause of the nephritic syndrome in both Japan and Europe is ANCA-associated nephritis.
P0406ASSOCIATION OF MICROHEMATURIA WITH OUTCOMES IN ADULT PATIENTS WITH IGA NEPHROPATHY
Authors: Mirioglu Safak , Gurel Erdem , Guzel-Dirim Merve , Kara Asli , Ozluk Yasemin , Aktar Irem , Dirim Ahmet Burak , Ciftkaya Aylin , Oto Ozgur Akin , Caliskan Yasar Kerem , Kilicaslan Isin , Yazici Halil , Turkmen Aydin , Sever Mehmet Sukru
Published: June 2020

Background and Aims

Although hematuria is the cardinal symptom of IgA nephropathy (IgAN), its effects on the outcome have not been studied extensively. We, therefore, aimed to analyze the association between microhematuria and clinicopathological features as well as outcome parameters in adult patients with IgAN.

Method

129 adults with IgAN, diagnosed by kidney biopsy, and followed up for a median duration of 54.5 (IQR: 24.25-92.75) months, were included in this retrospective study. Urinary sediment analyses during the bouts of macrohematuria were not taken into consideration. For the purpose of this analysis, microhematuria was described as ≥5 red blood cells per high-power field (RBCs/hpf) and classified as mild (5-9 RBCs/hpf), moderate (10-19 RBCs/hpf), or severe (≥20 RBCs/hpf). Study outcome (event) was defined as at least a 50% reduction in baseline eGFR or development of stage 5 chronic kidney disease (eGFR <15 ml/min/1.73 m2). eGFRs of the patients were calculated by using CKD-EPI formula.

Results

Demographic, clinical, laboratory and histopathological features of patients at the time of diagnosis are summarized in the table. Usage of ACEi/ARBs [75/81 (92.5%) vs 45/48 (93.75%), p=0.803], fish oil [30/81 (37%) vs 19/48 (39.5%), p=0.773], azathioprine [16/81 (19.7%) vs 10/48 (20.8%), p=0.882] and mycophenolic acid derivatives [14/81 (17.2%) vs 11/48 (22.9%), p=0.434] were comparable among the patients with and without microhematuria. Corticosteroids were more frequently used in patients with microhematuria [41/81 (50.6%) vs 17/48 (35.4%)], although this difference was not statistically significant (p=0.093). Overall 30 patients (23.2%) reached the study outcome, and there were no differences between patients with (19, 23.4%) and without (11, 22.9%) microhematuria (p=0.944). Kaplan-Meier analysis revealed that event free survival rates were similar across study groups: 77.1% for patients without microhematuria; while 80% for mild, 77.3% for moderate, and 72.7% for severe microhematuria (p=0.436) (Figure). Microhematuria did not predict the study outcome when multivariable Cox regression analyses were performed [HR: 1.847 (95% CI: 0.696-4.904), p=0.218]. Throughout the follow-up, microhematuria disappeared (dropped below 5 RBCs/hpf) in 43 patients (53%), 8 of whom (18.6%) reached the study outcome as compared to 11 patients (28.9%) with persistent microhematuria (p=0.273). Disappearance of microhematuria was not a predictor of study outcome, as well [HR: 0.386 (95% CI: 0.068-2.180), p=0.281].

Conclusion

Microhematuria is not associated with renal outcomes of adult patients with IgAN.
P0418LUPUS NEPHRITIS: A MONOCENTRIC STUDY
Authors: Omrane Marwa , Aoudia Raja , Ounissi Mondher , Chargui Soumaya , Jerbi Mouna , Gaied Hanene , Hidri Hafedh , Harzallah Amel , Ben Abdallah Taieb , Goucha Rim
Published: June 2020

Background and Aims

Systemic lupus erythematosus is a multi-visceral autoimmune disease. Renal involvement is one of the most common and serious manifestations of this disease. The histological lesions are highly polymorphic and the renal biopsy remains crucial for the therapeutic management of lupus nephritis (LN). The aim of our investigation was to study the epidemiological, clinical, biological and histological characteristics, outcomes and to evaluate the therapeutic protocols used for lupus nephritis’ treatment and to identify predictive factors of renal prognosis in patients with lupus nephritis.

Method

It was a retrospective study including patients over 16 years old with lupus nephritis proved by kidney biopsy and followed up over a period of 17 years in our department.

Results

We collected 155 women and 19 men with a sex ratio F / H of 8.2. The mean age at the time of the discovery of LN was 32.6 years with a maximum between 15 years and 45 years. The most frequent extra-renal manifestations were articular and dermatological manifestations (79%). Renal symptomatology was dominated by proteinuria noted in all patients, associated to a nephrotic syndrome in 68% of patients. At the time of diagnosis of LN, hematuria was present in 69% of patients and renal failure was present in half of cases. Immunologically, antinuclear antibody were positive in 89.1% of cases, anti DNA positive in 73.4% of cases, anti Sm positive in 79.8% of cases and Antiphospholipids were positive in 50% of cases, associated with an antiphospholipid syndrome in 14.9% of cases. We performed 243 renal biopsies with 174 initial and 69 iterative biopsies. The histological lesions were polymorphic dominated by LN class IV (36.6%) isolated or associated with LN class V (17.7%). All patients received a corticosteroid for induction or maintenance treatment. It was associated with immunosuppressive treatment according to different treatment regimens. The median duration of follow-up was 81.2 months. Renal outcome was marked by complete and sustained remission in 36.7% of cases, incomplete remission with chronic kidney disease in 34.5% of cases, chronic renal failure in 28.7% of cases. At univariate analysis, we identified the young age below 35 years at the time of the discovery of LN, the male sex, increased serum creatinine at the time of biopsy, proliferative forms, the presence of histological signs of chronicity and lesions of thrombotic microangiopathy as predictive factors of poor renal outcomes.

Conclusion

Lupus nephritis is one of the most common and serious manifestations of Systemic lupus erythematosus. The generalization of renal biopsy, the use of early codified therapeutic protocols and regular monitoring and evaluation of disease activity according to the appropriate scores can improve management and survival of patients with renal impairment.
P0429OUTCOMES OF LUPUS NEPHRITIS OVER AN ERA OF EVOLVING IMMUNOSUPPRESSION
Authors: McMinn Jason , Geddes Colin C , McQuarrie Emily
Published: June 2020

Background and Aims

The reported incidence of lupus nephritis (LN) is approximately 6.1 cases per million population per year in Scotland based on Scottish Renal Registry biopsy data. Despite immunosuppressive treatment, approximately 10-30% of patients will progress to established renal failure (ERF) within 15 years. In December 2007, our unit moved from a protocol of Cyclophosphamide/ steroid induction with Azathioprine/ Prednisolone maintenance to Mycophenolate/ steroid induction and maintenance. We undertook this study to compare remission rates before and after this change.

Method

A retrospective electronic patient record analysis was performed for all patients in our centre with a documented native renal biopsy showing a histopathological diagnosis of LN, between 1 July 1993 and 31 December 2017. Repeat biopsies were excluded. Baseline demographics, histopathological class and first and second line induction and maintenance therapies were recorded. Endpoints analysed were; partial and complete response (as defined in KDIGO Clinical Practice Guideline for Glomerulonephritis 2012), time to achieve this response, relapse, progression to ERF and death.

Results

120 patients who underwent a biopsy during the 24.5-year period received a diagnosis of lupus nephritis. 82.5% of patients were Caucasian. Median duration of follow-up was 72 months. 15% of patients died and 5% developed ERF within the follow-up period, representing one death per 56 patient years and one incident case of ERF per 168 patient years.

There were 40 patients in the pre-December 2007 group and 80 in the post-December 2007 group. Those in the earlier group were younger, with a mean age of 35.4 years versus 44.8 years in the later group (p=0.002). 23% had class V in the earlier group compared to 15% in the later group (p=0.31). Proportions of female patients were 80% and 75% in the early and late groups respectively (p=0.54). Median creatinine was 106µmol/L in the pre-December 2007 group and 89.5 µmol/L in the post-December 2007 group (p=0.96).

Patients in the pre- and post- December 2007 groups had comparable rates of complete response, at 72% and 71% respectively. However, those diagnosed before December 2007 were slower to respond, with a median time to achieve complete response of 10.5 months, compared to 6 months in those diagnosed after 1 December 2007 (p=0.007).

Conclusion

Following a change in our immunosuppressive induction regimen from Cyclophosphamide/ steroids to Mycophenolate/ steroids, our response rates have remained similar, however speed of attaining remission has improved.
P0431TRENDS OF PRIMARY GLOMERULAR DISEASE IN TURKEY FROM 2009 TO 2017: A REGIONAL REGISTRY REPORT FROM TSN-GOLD WORKING GROUP
Authors: Gul Cuma Bulent , Kucuk Mehmet , Ozturk Savas , Demir Erol , Eren Necmi , Sumnu Abdullah , Seyahi Nurhan , Gullulu Mustafa , Dede Fatih , Derici Ülver , Koc Yener , SAHIN Garip , Oymak Oktay , Manga Sahin Gulizar , Tatar Erhan , Dursun Belda , Dheir Hamad , Apaydin Süheyla , Suleymanlar Gultekin , Ulu Memnune Sena , Altunoren Orcun , Kutlay Sim , Mese Meral , Sahin İdris , Ustundag Sedat , Turkmen Kultigin , Yilmaz Mehmet Emin , Turan Kazancioglu Rumeyza , Uzun Ozcan , Candan Ferhan , Aydin Zeki , Oygar Deren , Aktas Nimet , Erdem Yunus , Paydas Saime , Guven Taymez Dilek , Can Basak , Kıykım Ahmet , Koc Leyla , Sezer Siren , Duranay Murat , Bardak Simge , Altintepe Luftullah , Kaya Burcu , Azak Alper , Alisir Ecder Sabahat , Cavdar Caner , Selcuk Nedim Yılmaz
Published: June 2020

Background and Aims

Several glomerular disease registries in Europe, and they shared their data; however, there was a lack of current data on trends of primary glomerulopathy in Turkey. Glomerular disease patterns can change geographical areas and populations decade by decade. Our aim is to present Turkey's primary glomerular disease pattern from 2009 to 2017.

Method

3878 native kidney biopsy records were assessed in the Turkish Society of Nephrology Glomerulopathy (TSN-GOLD) Working Group Registry. Secondary disease (lupus, etc.) and transplant biopsies do not enroll in the registry. These records divided into four periods, before 2009, 2009 to 2013, 2013 to 2017, and 2017 to current.

Results

A total of 3858 patients (M = 2173, K = 1685) were examined. There was no difference in the distribution of number of patients according to periods (Q1 = 968, Q2 = 960, Q3 = 968, Q4 = 962). Nephrotic syndrome was the most common biopsy indication in all quarters (58.6%, 53%, 44.1%, 51.6%, respectively). Glomerulopathy types; Membranous GN (29.9%, n = 290) was the first in Q1 and IgA nephropathy (17.7%, n = 172) was the second. IgA nephropathy (28.5%, n = 274) was the most common glomerulopathy in Q2, while Membranous GN (25.5%, n = 245) was the second most common. IgA nephropathy (29.9%, n = 285) was the most common glomerulopathy in Q3, followed by FSGS (22.9%, n = 222) and Membranous GN. In Q4, FSGS (26.8, n = 258) was the most common glomerulopathy, followed by IgA nephropathy (26.7%, n = 257) and Membranous GN (24.5%, n = 236) (Figure 1).

Conclusion

While biopsy indications did not change over the years, the incidence of FSGS and IgA nephropathy gradually increased.
P0434COST-EFFECTIVENESS OF MAINTANCE THERAPY WITH AZATHIOPRIME VERSUS RITUXIMAB (TAILORED OR FIXED-SCHEDULE) IN ADULTS WITH GENERALIZED ANCA VASCULITIS IN COLOMBIA
Authors: Contreras Kateir Mariel , Orozco Ortiz Viviana , Puche Eduardo José , Garcia Paola Karina , Gonzalez Camilo Alberto , Rodriguez Martha Patricia , Rosselli Diego
Published: June 2020

Background and Aims

Azathioprine has been for decades the drug of choice for maintenance therapy in patients with generalized ANCA vasculitis in remission. However, recent studies show that rituximab, a high-cost biological agent, which can be administrated in two different schedules, might be more effective, so it is necessary to know the cost- effectiveness.

Our goal was to compare the cost-effectiveness of the 3 maintenance schemes: standard therapy with azathioprine; fixed-dose rituximab and rituximab tailored according to CD19 lymphocyte level and ANCA titres, from the perspective of the Colombian healthcare system.

Method

We designed a 5-year annual cycle Markov model with the following stages: remission, minor relapse, mayor relapse and death. Transition probabilities were obtained from a systematic review of the literature (Scopus and Pubmed). Following national guidelines for economic studies, costs (in 2018, 1 euro = 3489 Colombian pesos) were estimated based on national drug registries, and official tariff manuals for procedures and other resources. Main outcome was quality-adjusted life years (QALY), using lupus nephropathy as a proxy; values were obtained from Tufts CEA Registry and validated by local expert panel through a modified Delphi technique. Cost-effectiveness threshold was three-times per capita GDP (16.872 euros). Discount rate was 5%. Univariate and probabilistic sensitivity analyses were performed.

Results

Overall discounted 5-years costs were € 1149 for azathioprine; € 4025 for tailored rituximab and € 5221 for fixed rituximab. QALY gains were 2.94, 3.63 and 3.64, respectively. Both tailored and fixed rituximab were cost-effective (cost per QALY gained: € 4168 and € 5817 respectively), but tailored dosing was preferable due to its lower cost. Sensitivity analyses did not modify these results significantly.

Conclusion

To our knowledge this is the first economic evaluation that compare azathioprine with tailored and fixed rituximab regimens as a vasculitis maintenance treatment in adults with ANCA generalized. Due to its lower effectiveness azathioprine should not be the first line of treatment. Tailored rituximab should be a better option than fixed schedule due to its lower cost with similar effectiveness.