bluuebunny/crossref_metadata_2025 huggingface dataset:
MO275RARE VARIANTS OF COMPLEMENT FACTOR H AND THROMBOMODULIN ARE OVER-REPRESENTED IN A COHORT OF SEVERE IGA NEPHROPATHY PATIENTS
Authors: Maillard Nicolas , Fremeaux Bacchi Veronique , Vieira-Martins Paula , Jullien Perrine , Alamartine Eric , Mariat Christophe
Published: May 2021

Background and Aims

IgA nephropathy is the most frequent primary glomerulonephritis leading to end stage renal disease (ESRD) in about 30% of cases within 20 years after diagnosis. Complement activation through alternative and lectin pathways has been described to impact the pathogeny of the disease. We hypothesized in this study that rare variants of alternative pathways regulatory genes could be overrepresented and could play a role at initiating the disease and could harm the prognosis of IgA Nephropathy.

Method

Patients with biopsy proven IgA nephropathy with markers of severity comprising an evolution through ESRD and/or a proteinuria >0.5g/day with available DNA sample were included. All coding sequences of CFH, CFI, MCP, C3, Factor B THBD and CFHR5 genes were analyzed by next generation sequencing. We defined a variant as rare when its minor allele frequency was below 0.1% in the general population. Frequencies were compared to a French volonteers cohort (n=80) and a European large cohort (n=503)

Results

We screened 128 patients with IgA N, with following characteristics at diagnosis: median age 42.4 yo, proteinuria (median) 1.4g/day, hypertension 66%, median eGFR 48.7 mL/min/1.73m². The median follow-up was 99 months and 58% of patients progressed to ESRD.

We identified rare variants with MAF<0.1% in 10.2 % (n=13) including 1 patient with two rare variants. The functional consequences of the 12 out the 14 variants are unknown. Two variants in CFH are located in function domains and are pathogenic.

Patients with IgA N have high rates of rare variants in CFH (n=9/128 ; 7 %) versus normal controls (n=9/503 ; 1.8%) (p=0.004); Pathogenic Variants with minor allele frequency <0.1% in CFH were found in 2 IgA N (2 out of 128, 1.5%) versus 1 European controls (1 out of 503)

In total, 11 % (14/128), 3.8 % (5/128) and 0.8 % (1/128) of the 128 patients were homozygous for the at-risk haplotype MCP ggaac, CFH tgtgt or both, respectively (versus 6.2 % (5/80), 3.8 % (3/80) and 0% in the controls)

6 patients carried the pathogenic variant in THDM gene p.Ala43Thr (6/128) versus 5 in 508 controls population (p=0.01).

No difference in term of hypertension, proteinuria, eGFR, Oxford classification, vascular score at diagnosis was noticed between patients without any rare variant compared to patients with at least one rare variant. The progression through ESRD was not different between groups.

Conclusion

In this cohort of Caucasian IgA nephropathy patients, rare variants of CFH and THBD were found significantly overrepresented compared to a French and European control cohort. Rare variants of alternative pathway regulatory genes were not associated with particular severity or prognosis.
MO280VALIDATION OF AN ANCA ASSOCIATED VASCULITIS RENAL RISK SCORE IN THE SOUTH WEST OF ENGLAND
Authors: Nimmo Ailish , Singh Arvind , Hopkins Jena , Rixon Anna , Sreerama Spoorthy , Tran Christina , Risdale Saira
Published: May 2021

Background and Aims

Determining the renal prognosis for patients with ANCA associated vasculitis (AAV) is important in guiding treatment decisions, including balancing the risks and benefits of aggressive immunosuppression, and informing patients of their likely trajectory. We examined the performance of the clinicopathologic risk stratification tool developed by Brix et al. 1 in determining renal outcomes in a cohort of AAV patients in the South West of England.

Method

A retrospective review of case notes of patients diagnosed with AAV between 2010 and 2020 from two renal units (Bristol and Plymouth) was performed. Patients were followed up until 1st August 2020. Demographic details, kidney function at presentation and initial treatment regime were collected alongside kidney biopsy data.

The renal risk score divides patients into three groups determined as being at low, medium and high risk of adverse renal outcomes based on (1) the percentage of normal glomeruli on kidney biopsy, (2) the percentage of tubular atrophy and interstitial fibrosis on kidney biopsy and (3) eGFR at diagnosis.

The outcome of interest was the development of end stage kidney disease (ESKD), defined as a dialysis requirement >3months or kidney transplantation. Patients were censored for death.

Results

In total 93 individuals were diagnosed with AAV over the study period; 51% were female and the median age at diagnosis was 69 years [IQR 60-78]. ANCA subclass was MPO positive in 73% of cases, PR3 positive in 19% and ANCA negative in 8%. At presentation, 42% had an eGFR below 15ml/min/1.73m2. With respect to risk scores, 17% of individuals were low risk (n=16), 52% were medium risk (n=48) and 31% were high risk (n=29).

Median follow up was 3.2 years [IQR 1.3-5.9], over which time 18% of patients developed ESKD (1 in the low risk group, 7 in the medium risk group and 9 in the high risk group). A further 20% of patients died. A Kaplan-Meier survival curve (Figure 1) demonstrated worsening renal survival with rising risk group (Log-rank test, p=0.05). At 1 year, 74 patients (80%) were alive and in these individuals renal survival was 100% in the low risk group, 91% in medium risk group and 75% in the high risk group.

Conclusion

Overall, 18% of patients developed ESKD over a median follow up of 3.2 years. The renal risk score developed by Brix et al. helps prognosticate renal survival and may assist in shared decision making with patients regarding treatment options. The score demonstrates the importance of the degree of chronicity in determining renal survival. Further work in larger cohorts to compare the performance of the risk score in different subgroups of patients with AAV would be informative.
MO281THE EVALUATION OF TEST EFFICIENCY ON LOW TITER SERUM PHOSPHOLIPASE A2 RECEPTOR ANTIBODY
Authors: Cui Haoyuan , Li Chao , Li Hang , Duan Lin , Li Yan , Chen Limeng , Li Xuemei
Published: May 2021

Background and Aims

Antibody to phospholipase A2 receptor (PLA2R) was widely detected for a decade as a diagnostic marker of idiopathic membranous nephropathy. Recently, several studies reported that a lower cut-off of serum PLA2R antibody (PLA2RsAb) could improve diagnostic efficacy. The recommend cut-off ranged from 2.0 to 2.7 RU/ml which was considered largely improving the sensitivity of the assay. Other reported that although sensitivity of the measurement might loss to some extent cut-off at 14 RU/ml might of the best clinical performance. However, the lower cut-off was slightly higher than the minimum detection limit, that was 2.0 RU/ml. There was no study evaluated the test efficiency of low titer antibody of the measurement.

Method

The reference range of PLA2RsAb was validated by testing 40 serum from health volunteer, male/female ratio was 20/20. The samples for intra and inter-batch precision test were prepared by mixing low titer PLA2RsAb serum. The intra-batch precision was performed by repeating six times of the validation sample in one plate. The inter-batch precision was performed by repeating four times of validation samples in one plate on five days.

Results

The medium age of male was 34 (31, 53) and 46 (31, 54) for female, respectively. PLA2RsAb was ranged from 2.0 to 4.3 RU/ml for male and 2.0 to 4.0 RU/ml for female. The average of intra-batch validation sample was 8.1 ± 1.2 RU/ml. The intra-batch precision was presented by coefficient of variation, that was 15%. The average of inter-batch validation samples were 4.0 ± 0.4 RU/ml and 5.2 ± 0.5 RU/ml, respectively. The inter-batch precision was 10% for both validation serum.

Conclusion

Healthy population showed low titer PLA2RsAb positive according to a lower cut-off. The validation showed relative high coefficient of variation on intra and inter-batch precision of low titer PLA2RsAb.
MO246ESTIMATING DELAY IN TIME TO ESKD FOR TREATMENT EFFECTS ON PROTEINURIA IN IGA NEPHROPATHY AND FSGS*
Authors: Carroll Kevin , Conley Leah , Mercer Alex , Saleem Moin A , Barratt Jonathan
Published: May 2021

Background and Aims

Reduction in proteinuria is associated with lower risk of end-stage kidney disease (ESKD) in IgA nephropathy (Thompson et al, 2019) and focal segmental glomerulosclerosis (FSGS) (Troost et al, 2017). Sparsentan, a dual endothelin receptor and angiotensin II receptor antagonist, is in phase 3 clinical trials in IgA nephropathy (PROTECT) and FSGS (DUPLEX), that are powered to detect a treatment benefit on proteinuria-based endpoints versus standard of care angiotensin receptor blockade (irbesartan). In this study, we aim to estimate the delay in time to ESKD conferred by the hypothesized treatment effect of sparsentan on proteinuria in these phase 3 trials; for PROTECT, a 30% reduction in urine protein to creatine ratio (UP/C) vs irbesartan in IgA nephropathy patients, and for DUPLEX, 30% more patients achieving the new FSGS Partial Remission Endpoint (UP/C <1.5 g/g associated with a 40% reduction in UP/C) versus irbesartan.

Methods

We analysed individual patient level data from two UK registries: the first is provided by Leicester General Hospital, UK and consists of IgAN patients, and the second is the UK National Registry of Rare Kidney Disease (RaDaR) Nephrotic Syndrome cohort, with access provided by the University of Bristol, UK, including FSGS patients. IgAN patients with urine total protein value ≥1.0 g/day or UP/C ≥1.0 g/g and eGFR >30 mL/min at the initiation of renin-angiotensin system blockade (RASB) were identified, as were patients with primary or genetic FSGS with UP/C ≥1.5 g/g and eGFR ≥30 mL/min. The time to ESKD (eGFR <15 mL/min, initiation of dialysis, transplantation) or death from any cause over the patient follow-up period was analysed using accelerated failure time modelling; Weibull, Log Logistic and Log Normal distributions were applied with the fitted survivor function reported from the model with the lowest AIC. The time gained for a given reduction in risk in ESKD/death and 5-year survival was estimated under proportional hazards.

Results

A 30% reduction in proteinuria in IgAN patients confers a 50% lower risk of ESKD, extending the median time to ESKD by 10.7 years, from 12.4 to 23.1 years; 5-year ESKD free survival rate is also increased, from 77.7% to 88.1%. Similarly, ongoing analysis in FSGS patients indicates 30% more patients achieving the FSGS Partial Remission Endpoint confers lower risk for ESKD and increase in 5-year ESKD free survival.

Conclusion

The data from the Leicester General Hospital, UK and RaDaR provide invaluable insight into the longer-term natural history of IgAN and FSGS patients and time to ESKD. Therapeutic interventions that reduce proteinuria and the risk of ESKD can confer important and clinically meaningful extensions in the time patients are alive and free from ESKD.
MO282EARLY RENAL RECOVERY AFTER A FIRST FLARE OF PAUCI IMMUNE GLOMERULONEPHRITIS
Authors: Zaworski Jeremy , Vandenbussche Cyrille , Bataille Pierre , Hachulla Eric , Glowacki Francois , Gibier Jean baptiste , Daroux Maïté , Rastimbazafy Anderson , Bitton Laura , Humez Sarah , Guincestre Thomas , Azar Raymond , Hoffmann Maxime , Bourdon Franck , Lemoine Corinne , Cardon Gerard , Behal Helene , Gnemmi Viviane , Quemeneur Thomas
Published: May 2021

Background and Aims

Renal involvement is a severe manifestation of ANCA-associated vasculitis. Patients often progress to end-stage renal disease. The potential for renal recovery after a first flare has seldom been studied. Our objectives were to describe the evolution of the estimated glomerular filtration rate (eGFR) and identify factors associated with the change in eGFR between diagnosis and follow-up at 3 months (ΔeGFRM0–M3) in a cohort of patients with a first flare of pauci-immune glomerulonephritis.

Methods

This was a retrospective study over the period 2003–2018 of incident patients in the Nord-Pas-de-Calais (France). Patients were recruited if they had a first histologically-proven flare of pauci immune glomerulonephritis with at least 1 year of follow up. Kidney function was estimated with MDRD-equation and analysed at diagnosis, 3rd, 6th and 12th months. The primary outcome was ΔeGFRM0–M3. Factors evaluated were histological (Berden classification, interstitial fibrosis, percentage of crescents), clinical (extra-renal manifestations, sex, age) or biological (severity of acute kidney injury, dialysis, ANCA subtype).

Results

One hundred and seventy-seven patients were included. The eGFR at 3 months was significantly higher than at diagnosis (mean ± standard deviation, 40 ± 24 vs 28 ± 26 ml/min/1.73 m2, p < 0.001), with a ΔeGFRM0–M3 of 12 ± 19 ml/min/1.73 m2. The eGFR at 12 months was higher than at 3 months (44 ± 13 vs 40 ± 24 ml/min/1.73m2, p = 0.003). The factors significantly associated with ΔeGFRM0–M3 in univariate analysis were: sclerotic class according to Berden classification, percentage of interstitial fibrosis, percentage of cellular crescents, acute tubular necrosis, neurological involvement. The factors associated with ΔeGFRM0–M3 in multivariate analysis were the percentage of cellular crescents and neurological involvement. The mean increase in eGFR was 2.90 ± 0.06 ml/min/1.73m2 for every 10-point gain in the percentage of cellular crescents. ΔeGFRM0–M3 was not associated with the risks of end-stage renal disease or death in long-term follow-up.

Conclusions

Early renal recovery after a first flare of pauci-immune glomerulonephritis occurred mainly in the first three months of treatment. The percentage of cellular crescents was the main independent predictor of early renal recovery.
MO284UTILITY OF SERUM IGA/C3 RATIO IN PREDICTING RENAL DISEASE PROGRESSION IN IGA NEPHROPATHY
Authors: Mohammed Sophia , Chinnadurai Rajkumar , Ponnusamy Arvind
Published: May 2021

Background and Aims:

IgA nephropathy is the most prevalent and predominantly slow progressing glomerular disease. Risk prediction tools like the international IgAN help to guide the prognosis in this group of patients. The IgA/C3 ratio has been shown to be a useful predictor of poor outcomes in Chinese cohort but such a study is lacking in the Caucasians. The study aims to investigate the utility of IgA/C3 score in predicting renal outcome in 5 years (50% decline in five years or reaching ESRD) in a Caucasian cohort.

Method

All available patients with biopsy-proven IgA nephropathy in our centre between January 2001 and December 2013 were included in this observational study (115 patients). Baseline (biopsy date) data relevant to the scores including demographics, laboratory and the histopathological features were collated at the time of biopsy. Follow up data on renal functions and renal outcome (50% decline in eGFR at 5 years) were collected until an arbitrary end date 31/12/2018. IgA/C3 ratio was available in 46 (40%) of the patients and this cohort wase split into two groups based on IgA/C3 ratio (A- ratio </=3 and B- ratio >3) and analysed.

Results

We had a total of 115 patients recorded over this 13-year period. The median age of our cohort at time of biopsy was 41 years with a predominance of male gender (71%). At baseline 84% were hypertensive and 11% diabetic. 77% were on a renin-angiotensin blocker, with 53% being on a statin.

At 2 years follow-up the median decline in estimated glomerular filtration (eGFR) between the groups was similar (Group- A 2.65 ml/min vs Group- B 2 ml/min, p=0.557). At 5 years, the median decline in eGFR was higher in Group B though not statistically significant (9.3ml/min vs 4.6ml/min, p=0.475) (Table-1). At 5 years a higher IGA/C3 ratio was showing appositive corelation to the decline in eGFR (Figure–2).

Conclusion

Patients with higher IgA/C3 ratio had a higher drop in estimated glomerular filtration rate at five years of follow-up. Validation in a larger sample is warranted before this can be used clinically.
MO285CLINICAL PRESENTATION OF IGA NEPHROPATHY AND LONG-TERM RENAL OUTCOME
Authors: Stefan Gabriel , Stancu Simona , Zugravu Adrian Dorin , Petre Nicoleta , Mircescu Gabriel
Published: May 2021

Background and Aims

There is a wide range of clinical presentation of IgA nephropathy (IgAN), from asymptomatic microscopic hematuria to rapidly progressive glomerulonephritis. However, there is little epidemiologic data on the relationship between the clinical pattern at diagnosis and long-term renal outcome.

Method

We performed a unicentric retrospective study on 299 consecutive IgAN patients (age 43 [35-56] years, 71% male, eGFR 42.1 [25.2-62.8] mL/min, proteinuria 1.3 [0.6-2.6] g/g creatinine) - kidney biopsy proven - between 2010-2017. Patients were followed until composite endpoint (doubling of serum creatinine, ESKD (dialysis or renal transplant) or death, whichever came first) or end of study (May 2018).

Results

Patients were followed for a mean of 41 (95%CI 38, 44) months, and 80 (27%) patients experienced the composite endpoint.

The most frequent clinical presentation at diagnosis regardless of age was nephritic syndrome (68%), followed by asymptomatic urinary abnormalities (AUA) (19%), macroscopic hematuria (15%), acute kidney injury (AKI) (14%) and nephrotic syndrome (10%).

The clinical pattern varied in frequency with age: macroscopic hematuria had a bimodal distribution in the 20- and 60-years groups, AKI was more frequent in the 50 to70 years groups, AUA was more often present in the 30 to 50 years groups (Figure 1).

Mean renal survival time for the entire cohort was 70 (95%CI 65, 75) months; patients with AKI (40 (95%CI 27, 54) vs 75 (95%CI 69, 80) months, p<0.001), nephrotic syndrome (42 (95%CI 26, 57) vs 73 (95%CI 67,78 months, p<0.001)) at diagnosis had significantly shorter renal survival time.

In multivariate Cox regression analysis adjusted for IgAN progression factors, presence of nephritic syndrome at diagnosis was associated with good renal outcome, while clinical presentation as AKI or nephrotic syndrome were associated with poor renal survival (Table 1).

Conclusion

Although AKI and nephrotic syndrome are uncommon in IgAN at diagnosis, their presence seems to be associated with poor renal survival.
MO289IS THERE A ROLE OF INTERSTITIAL CHANGES ON THERAPY OUTCOME AMONG PATIENTS WITH FOCAL-SEGMENTAL GLOMERULAR SCLEROSIS AND MINIMAL CHANGE DISEASE?
Authors: Jankovic Aleksandar , Djuric Petar , Bulatovic Ana , Markovic Dragana , Pešić Snezana , Dimkovic Nada , Naumovic Radomir
Published: May 2021

Background and Aims

It is well-known that interstitial changes in patients with focal-segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) are linked with disease chronicity and progression. The aim of this study was to analyze is there any connection between interstitial changes and outcome after “first line” therapy in patients with FSGS/MCD.

Method

From 2014 till 2019, biopsy proven diagnosis of FSGS/MCD was established in 40 patients. Interstitial changes were classified in three groups as following: 0-w/o changes; 1-mild changes; 2-severe changes. Patients with nephrotic syndrome (No=29) were treated with prednisolone (1mg/kg) and after six months we have registered therapy outcome as: CR-complete remission; PR-partial remission; EX-death; NO-no effect.

Results

Among treated patients (age 50.4±15.3 years, 15 men), CR was achieved in 10 patients (34.5%) and 6 out of these 10 (60%) had no interstitial changes. Partial remission was observed in 11 patients (37.9%), in 4 patients (13.8%) therapy did not have any effect, and 4 patients (13.8%) deceased (table 1). All patients in EX and NO group had interstitial changes. There were no significant difference in age, gender, proteinuria, albuminaemia, creatinine and glycaemia levels between groups except for hemoglobin levels that were significantly lower in EX group than in others (∑ 15.144; p=0.002) and urea levels that were significantly higher in EX group (∑ 138.057; p=0.024).

Conclusion

Patients with FSGS/MCD respond well on standard immunosuppressive protocol, particularly in absence of interstitial changes what may increase the chance for achieving complete remission.
MO247NOVEL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES REVEAL CHANGED METABOLOMIC PROFILE IN RECURRENT FOCAL SEGMENTAL GLOMERULOSCLEROSIS*
Authors: Müller-Deile Janina , Sarau George , Kotb Ahmed , Daniel Christoph , Kalkhof Stefan , Christiansen Silke , Schiffer Mario
Published: May 2021

Background and Aims

Idiopathic forms of Focal Segmental Glomerulosclerosis (FSGS) are caused by circulating permeability factors, which can lead early recurrence of FSGS and kidney failure after kidney transplantation. In the past three decades, many research endeavors were undertaken to identify these unknown factors. Even though some potential candidates have been recently discussed in the literature, “the” actual factor remains elusive. Therefore, there is an increased demand in FSGS research for the use of novel technologies that can allow us to study FSGS from a yet unexplored angle.

Method

We used novel treatment options, a personalized in vitro and in vivo assay as well as Raman spectroscopy and mass spectrometry for recurrent FSGS.

Results

Here, we report the successful treatment of recurrent FSGS in a patient after living related kidney transplantation by removal of circulating factors with CytoSorb apheresis (Fig. 1). Interestingly, the classical published circulating factors were all in normal range in this patient but early disease recurrence in the transplant kidney and immediate response to CytoSorb apheresis were still suggestive for pathogenic circulating factors. To proof the functional effects of the patient’s serum on podocytes and the glomerular filtration barrier we used a podocyte cell culture model and a proteinuria model in zebrafish to detect pathogenic effects on the podocyte’s actin cytoskeleton inducing a functional phenotype (Fig. 2, Fig. 3). We then performed Raman spectroscopy in the <50 kD serum fraction (Fig. 4), on cultured podocytes treated with the FSGS serum (Fig. 5), and in kidney biopsies of the same patient at the time of transplantation and at the time of disease recurrence (Fig. 6). The analysis revealed metabolomic changes in podocytes induced by the FSGS serum as well as in focal glomerular and parietal epithelial cell regions in the FSGS biopsy. Several disturbed Raman spectra were identified in the fractionated serum and metabolome analysis by mass spectrometry detected lipid profiles in the FSGS serum, which corresponded to disturbances in the Raman spectra.

Conclusion

Our novel innovative analysis reveals changed lipid metabolome profiles associated with idiopathic FSGS that might reflect a new subtype of the disease.
MO294COMPARISON OF TIP AND CELLULAR VARIANT OF PRIMARY FOCAL SEGMENTAL GLOMERULOSCLEROSIS
Authors: Zagorec Nikola , Horvatić Ivica , Kasumović Dino , Šenjug Petar , Horaček Matija , Pražetina Marko , Lucijanić Marko , Galešić Ljubanović Danica , Galesic Kresimir
Published: May 2021

Background and Aims

After membranous nephropathy, focal segmental glomerulosclerosis (FSGS) is the most common cause of nephrotic syndrome in European population. According to Columbia classification, there are five histological variants of FSGS defined on light microscopy (tip, cellular, perihilar, collapsing and not otherwise specified - NOS) and this classification has a prognostic significance. The aim is to compare features and outcomes of tip and cellular variant of primary FSGS.

Method

All patients with FSGS were identified by a retrospective review of the Registry of kidney biopsies at the Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb, from 2003 until 2020. Each kidney specimen was analyzed by light, immunofluorescent and electron microscopy and Columbia classification was applied by experienced nephropathologist. Patients with primary FSGS met following criteria: full nephrotic syndrome and diffuse podocyte foot process effacement in absence of secondary causes of FSGS. Laboratory findings were obtained for every patient at the time of biopsy and following outpatient visits. Complete remission was defined as proteinuria < 0.3 g/day with normal kidney function and partial remission as proteinuria 0.3 - 3.5 g/day. Variables are expressed as median ± IQR (interquartile range) and frequencies. Statistical comparison between groups of patients with tip and cellular variant of primary FSGS and disease outcome analysis were done.

Results

Out of 200 patients with FSGS, 59 (29.5 %) had primary form of disease. Tip variant was the most common form of primary FSGS (22 patients, 37 %) followed by NOS (20, 34 %), cellular (13, 22 %), perihilar (2, 3.5 %) and collapsing (2, 3.5 %) variant. Demographic and clinical features with initial laboratory findings are shown in Table 1. There were no significant differences between two groups in all analyzed variables in Figure 1. All patients were treated by anti-RAAS agents and steroids. Median follow-up was 55 months (range 1 – 196 months), and followup data were unavailable for three patients. Figure 2 shows treatment regimens in both patient grouos with treatment outcomes. Remission rate was significantly higher in tip variant (90 % vs. 41 %, p = 0.002). There was no difference in relapse rate between the two groups (p = 0.717).

Conclusion

There were no significant differences in clinical features and laboratory findings at the time of clinical presentation between tip and cellular variant of primary FSGS. Patients with tip variant had significantly higher remission rate than patients with cellular variant.
MO295RESULTS OF 30 YEARS OF RENAL BIOPSIES IN THE GENERAL HOSPITAL OF CIUDAD REAL. WHAT HAS CHANGED?
Authors: Moral Berrio Esperanza , Vozmediano Poyatos Carmen , Arambarri Segura Minerva , González López Lucía , Carreño Parrilla Agustín , Castro Fernández Paz , Ferrer García Guillermo , García Conejo Gloria , Anaya Fernández Sara , Olazo Gutierrez Eliana , Piccone Saponara Luis Guillermo
Published: May 2021

Background and Aims

The renal biopsy (RB) has been performed in the General Hospital of Ciudad Real (HGUCR) since the year 1989. It allows kidney diseases to be diagnosed and treated and pronostics to be made. We will analyse the results of these 30 years as well as the evolution of the various parameters studied.

Method

Descriptive study of the RB carried out in the HGUCR between 1989 and 2019. Age, sex, clinical syndrome (CS) at the time of the RB, number of glomeruli and histological diagnosis will be analysed. The patients are divided into 3 groups according to age: children (<15), adults (15-65) and the elderly (>65). We will establish three periods of 10 years: period A (1989-1998), period B (1999-2008) and period C (2009-2019). The categorical variables are expressed as percentages and the quantitative variables average ± standard deviation. Statistical analysis with SPSS 25.0.

Results

898 RB have been performed, average number of glomeruli 16, 70% of the RB with more than 10 glomeruli. The average age of the patients was 53±19 years old, 58% male. The most frequent CS was acute kidney failure (AKF) (35%), followed by nephrotic syndrome (NS) (30.5%), asymptomatic urinary disorders (19%), chronic kidney disease (11%), nephritic syndrome (3.6%), haematuria (0.7%) and arterial hypertension (0.7%). The most common in children were asymptomatic urinary disorders (50%), in adults NS (34%) and in the elderly AKF (55.5%). The predominant primary glomerulonephritis (GN): IgA nephropathy (IgAN) (15%), followed by membranous nephropathy (MN) (12%) and focal segmental glomerulosclerosis (FSGS) (11%). The most frequent secondary GN: vasculitis (11%) and lupus nephropathy (10%). 164 RB were performed in period A, 370 in period B and 346 in period C. In all three periods the predominant sex was male and the average age increased: 48 years old in A, 51 years old in B and 56 years old in C. Together with the increase in age, the indication of RB changes: NS in the first two periods and AKF in period C. The most frequent pathology in period A: FSGS (17%), IgAN (16%) in period B and IgAN (15%) followed by vasculitis (11%) in period C.

Conclusion

In the HGUCR the most common biopsied kidney pathology is IgAN, followed by MN. There has been an increase in the age of the patients as well as an increase in AKF and vasculitis. The KB constitutes a highly useful diagnostic test that allows us to establish prognostics and appropriate treatments.
MO296MEAN PLATELET VOLUME IN FAMILIAL MEDITERRANEAN FEVER RELATED AMYLOIDOSIS AND COMPARISON WITH COMMON PRIMARY GLOMERULAR DISEASES
Authors: Yildirim Tolga , Kutahya Berranur , Is Fatma , Erdevir Mehmet , Uzerk Kibar Muge , Koc Neriman Sila , Saglam Arzu , Yilmaz Seref Rahmi , Erdem Yunus
Published: May 2021

Background and Aims

Compared to healthy controls, mean platelet volume (MPV) is frequently higher in patients with Familial Mediterranean fever (FMF) but lower in amyloidosis patients. The cause of differing MPV levels in FMF patients with and without amyloidosis is not clear. We hypothesized that severe proteinuria and renal dysfunction in amyloidosis could be responsible from low MPV in contrast to FMF patients without amyloidosis. We aimed to compare MPV levels of FMF patients with amyloidosis and MPV values of patients with different glomerular diseases to understand if low MPV is unique to amyloidosis or MPV is similar in all glomerular diseases indicating that it is a consequence of proteinuria and/or renal dysfunction.

Method

We compared pre-biopsy MPV levels of patients with amyloidosis secondary to FMF, to MPV levels of patients with membranous glomerulonephritis, focal segmental glomerulosclerosis (FSGS) and IgA nephropathy that all present with proteinuria and renal dysfunction. Factors affecting MPV were also determined.

Results

703 patients (411 male, 292 female) were included in the study. Mean age was 42.6±14.3 years. There were 124 patients with amyloidosis, 224 patients with IgA nephropathy, 188 patients with membranous glomerulonephritis and 167 patients with FSGS. Patients with amyloidosis had lower MPV compared to patients without amyloidosis (7.9±1.2 fL vs. 8.2±0.9 fL respectively, p=0.008). Patients with amyloidosis had also significantly lower MPV compared to patients with each of the other diagnoses. MPV was negatively correlated with platelet count (r = - 0.351, p <0.001). There was no significant correlation of MPV with serum creatinine and proteinuria.

Conclusion

This study is the largest study of MPV in patients with biopsy proven amyloidosis and confirms previous studies reporting low MPV in amyloidosis. This study indicates that low MPV in amyloidosis cannot be explained with severe proteinuria and renal dysfunction.
MO299RELATIONSHIP BETWEEN LOW-TITER PHOSPHOLIPASE A2 RECEPTOR ANTIBODY AND TREATMENT RESPONSE OF IDIOPATHIC MEMBRANOUS NEPHROPATHY
Authors: Cui Haoyuan , Li Chao , Li Hang , Wen Yu-bing , Chen Limeng , Li Xuemei
Published: May 2021

Background and Aims

The circulating anti-Phospholipase A2 receptor (PLA2R) antibody has been widely detected since its discovery in 2009. It was suggested that the cut-off of serum PLA2R antibody (PLA2RsAb) should be reset at below 20 RU/mL to prove diagnostic efficacy. The correlation between low titer PLA2RsAb and treatment response has not been discussed. In this study, we focused on the low titer PLA2RsAb during follow-up of PLA2R-related IMN.

Method

We retrospectively enrolled 43 Chinese patients with biopsy-proved PLA2R-related IMN from March 2017 to October 2019. Baseline data were collected including age, gender, serum creatinine (Scr), albumin (Alb), 24h urine protein (24hUP), and PLA2RsAb at biopsy. PLA2RsAb was detected at one month, three months, six months and one year. The patients were stratified into three groups by the lowest PLA2RsAb titer during follow up. Low titer group was defined as anti-PLA2R antibody ＜2RU/mL (53.5%, n=23). Median titer group was defined as anti-PLA2R antibody >2 but ＜20RU/mL (32.6%, n=14). High titer group was defined as anti-PLA2R antibody >20RU/mL (13.9%, n=6). Complete remission (CR) was defined as 24hUP ＜0.3g/d. Partial remission (PR) was defined as 24hUP at the range of 0.3-3.5g/d and a reduction >50% of the baseline proteinuria. No remission (NR) was defined as absence of CR or PR at one-year.

Results

In the entire cohort, patients were 49 ± 16 years old with 28/15 male/female ratio. Baseline data of low, mid and high titer group were as follows: the median PLA2RsAb were 34.3(22.1, 314), 103(55.8, 361), 73.6(53.0, 215)RU/mL, P = 0.305; the median 24hUP were 6.8(3.5, 12.4), 6.4(5.6, 8.9), 4.9(3.4, 7.2)g/d, P = 0.493; the average Scr were 100.4 ± 60.0, 92.3 ± 29.2, 82.0 ± 21.9 umol/L, P = 0.681; the median Alb were 27.0 ± 5.7, 23.8 ± 5.8, 30.2 ± 3.3 g/L, P = 0.054. The rate of CR, PR, NR were 34.8% (8/23), 34.8% (8/23), 30.4% (7/23) in low titer group, 7.1% (1/14), 71.4% (10/14), 21.4% (3/14) in mid titer group, 0% (0/6), 66.7% (4/6), 33.3% (2/6) in high titer group, P = 0.119

Conclusion

The correlation between low titer PLA2RsAb and treatment response showed no statistical significance.
MO301RITUXIMAB FOR RELAPSING MEMBRANOUS NEPHROPATHY: A SPANISH HOSPITAL EXPERIENCE
Authors: Fernandez Lorente Loreto , Manrique Joaquin , Visus Maria Teresa , Izquierdo Diana , Castaño Itziar , Slon Roblero Maria Fernanda , Gomez Nerea , Romero Gregorio , Purroy Iruzun Carolina
Published: May 2021

Background and Aims

B cell targeting agent Rituximab has been proven to be effective and safe for the treatment of idiopathic membranous nephropathy (iMN) in previous studies with nearly 75% achievement of partial or complete remission of nephrotic syndrome. The aim of this study was to evaluate this treatment in a cohort of patients at Complejo Hospitalario de Navarra with relapsing disease.

Method

This is a retrospective, cross sectional study including 12 patients with membranous nephropathy diagnosed by means of a kidney biopsy. All of them were treated before with different immunosuppressive regimens and had a relapse at the time of the inclusion. All of them were treated with two iv infusions of Rituximab. In this study we report patient clinical and immunological baseline characteristics and treatment response at 12 months of follow up.

Results

Between 2015-20 a total of 12 patients (41,6% women and 58,3% men) were treated with two iv infusions of Rituximab with a total mean dose of 2gr. All of them diagnosed previously of iMN, and 10/12 were PLA2r positive. Baseline laboratory data showed serum creatinine levels 1,3±0,9 mg/dl, serum albumin 29±9 g/L, 24 hour- urinary protein excretion of 6,8±3,2 and serum PLA2R levels of 50,54±63,2 RU/ml. Either complete or partial response (CR and PR) were achieved in 83,3% of the cases, however only 3/12 (25%) patients had a complete response at 12 months follow up. All patients who responded had also a significative decrease PLA2r antibodies. Three of the patients who did a PR were treated with an incomplete dose of iv Rituximab (two infusions of 500mg).

Conclusion

Rituximab was effective in our cohort of patients with iMN with achievement of 83,3% response at 12 months of follow up, however only 25% of patients had complete response maybe due to incomplete dosing. Immunological response was seen in all patients. Still, a longer follow up of these patients is needed in order to evaluate Rituximab response.
MO303URINARY ALBUMIN-TO-CREATININE RATIO INDICATES NECROTIZING AND CRESCENTIC GLOMERULONEPHRITIS IN ANCA-ASSOCIATED VASCULITIS
Authors: Hakroush Samy , Tampe Björn
Published: May 2021

Background and Aims

Renal involvement is a common and severe complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) as it can cause acute kidney injury (AKI), end-stage renal disease (ESRD) or death. We have previously reported that elevated urinary albumin-to-creatinine ratio (uACR) correlates with rapid deterioration of kidney function in ANCA GN. Therefore, we here aimed to describe the association between proteinuric findings and histopathological diagnosis of necrotizing and crescentic ANCA GN in 50 urinary samples at admission and corresponding renal biopsies of patients with AAV.

Method

A total number of 50 urinary samples at admission and corresponding renal biopsies with confirmed renal involvement of AAV were retrospectively included between 2015 till 2020 in a single-center observational study.

Results

Renal involvement of AAV revealed variable proteinuria ranging from low-range to nephrotic syndromes, however most patients presented with subnephrotic proteinuria predominated by albumin (uACR). Severely increased uACR levels >300 mg/g correlated with reduction of normal glomeruli (P<0.001), attributed to increased glomerular crescents (P<0.001) and necrosis (P=0.008). By contrast, no such association was observed for global sclerotic glomeruli (P=0.58), revealing that uACR reflects necrotizing and crescentic ANCA GN rather than adaptive glomerular hyperfilitration in chronic sclerosing stage. These findings were additionnaly bolstered by histopathological subgrouping and ARRS: patients with uACR levels >300 mg/g were classified either into Berden’s crescentic class (P=0.002) or ANCA renal risk score (ARRS) high/intermediate risk (P=0.003). No association between uACR levels and extrarenal manifestation of AAV disease could be observered, suggesting that uACR levels reflected specific renal involvement with ANCA GN and further confirmed by survival analysis for cumulative incidence of RRT during the short-term course of disease. In summary, uACR measurements at admission were associated with renal biopsy findings thereafter. Levels of uACR >300 mg/g were more frequently observed in necrotizing and crescentic ANCA GN with classification either into Berden’s crescentic class or ARRS high/intermediate risk and specific for renal involvement in AAV.

Conclusion

Early identification of patients who mostly benefit from aggressive immunosuppressive therapy is of clinical importance. Our observation that uACR levels at disease onset predict necrotizing and crescentic ANCA GN requires further investigation for therapeutic decision especially in patients with severe deterioration of kidney function.
MO304COMPLEMENT INHIBITION FOR REFRACTORY GLOMERULONEPHRITIS IN SYSTEMIC VASCULITIS
Authors: Uriol Miguel , Obrador Mulet Aina , Arrufat Gemma , Escriva Ana , Lado Fuentes Mario , Garcia José Luis , Pallares Lucio
Published: May 2021

Background and Aims

Systemic vasculitis(SV) is a life-threatening disease and, in some cases, refractory to intensive multi-immunosuppressant drugs. Complement hyperactivation has gained interest in the pathogenesis of the SV. We report the efficacy of the short course of C5-inhibitor (eculizumab) in refractory cases of lupus nephritis (r-LN) and refractory ANCA-associated glomerulonephritis (r-AGN).

Method

In this retrospective study, eight consecutive patients were assessed (r-LN:n=3 and r-AGN:n=5). All patients were previously treated with three or more drugs included: corticosteroids (n=8), mycophenolate (n=8), rituximab (n=7), immunoglobulins (n=5), therapeutic plasma exchange (n=4), cyclophosphamide (n=1), and belimumab (n=1). Eculizumab was considered for use in off-label indication in patients with progressive renal deterioration (worsening creatinine, protein-to-creatinine ratio) or developing a high-risk lethal complication after the induction immunosuppressive therapy. The histologic lesson observed were: a) r-LN: Type VI (n=1), Type V(n=1), and type IV(n=1), and b) r-AGN: sclerotic (n=3), and malignant hypertension+/-thrombotic microangiopathy (n=1), in one patient who developed pulmonary hemorrhage no renal biopsy was performed.

Results

Mean age (SD): 51(17)years. Median (p25-p75) of follow-up: 19(12-28) months. Overall, 2(25%) of the patients needed chronic renal replacement therapy (one r-AGN patient who required urgent haemodialysis at presentation and one r-LN within 12 months after the onset eculizumab). During the follow-up the eGFR(mean(95%CI) changed from 28(16-40) to 30(20-41)mil/min/1.73m2(P = 0.51) and the median(p25-p75) protein-to-creatinine ratio decreased from 2.3(1.5-6.4) to 0.6(0.3-1.7) mg/mg(P= 0.028). The mean eculizumab cycle dose number was 5(95%CI:3-6), four patients required two cycles. Overall, the mean eculizumab dosage required was 7162 mg (95%CI: 2969-11355). No major side effects were recorded.

Conclusion

The coadyuvant complement inhibition with eculizumab stabilized renal function and decreased proteinuria in six out of the eight previously refractory patients and represents a promising tool in treating lupus and ANCA vasculitis nephritis.
MO306IGA NEPHROPATHY: A 20 YEAR RETROSPECTIVE SINGLE CENTRE EXPERIENCE
Authors: Storrar Josh , Mannan Fahmida , Roy Reuben , Chinnadurai Rajkumar , Sinha Smeeta , Kalra Philip A
Published: May 2021

Background and Aims

IgA nephropathy is the most common glomerulonephritis worldwide. The clinical course is heterogeneous and not always easy to predict. As such, determining which patients to treat with immunosuppression has been the cause of much debate. Over recent years there has been a focus on risk prediction to help with treatment decisions (such as the widely validated International IgA Risk Prediction Tool). Here, we present a 20 year retrospective study from a single centre with the following aims: to describe the epidemiology of our cohort, to assess outcomes (such as progression to ESKD requiring RRT, mortality), and to determine if treatment choices have changed over time.

Method

We collected all cases of IgA nephropathy from our biopsy database between January 2020 and December 2019. This totalled 525 biopsies. Of these, a number were excluded from analysis, including transplant biopsies and repeat biopsies in the same patient. After exclusion, the original 525 biopsies were narrowed down to 452 patients for analysis. We collected demographic data for each patient, along with creatinine and proteinuria values over time, MEST-C scores, progression to ESKD, mortality, use of RAAS blockade and immunosuppressants. Initial analysis was performed using Excel. We plan to perform further multivariate Cox regression analysis to determine if there are associations with progression to ESKD such as degree of proteinuria, MEST-C scores and immunosuppression treatment.

Results

We identified 452 patients with biopsy confirmed IgA nephropathy at our centre between January 2000 and December 2019. 138 (30.5%) were female and 314 (69.4%) were male. The average age at time of biopsy was 45.7 years. Mortality over this period was 19.2% (87 patients). 126 (27.9%) progressed to ESKD requiring RRT, 6 (1.3%) required temporary dialysis whilst 313 (69.2%) did not require RRT. With regards to treatment, 329 (72.8%) were treated with RAAS blockade in comparison to 85 (18.8%) who were not (in 38 patients this was unclear). No immunosuppression was used in 349 (77.2%), whilst a combination of prednisolone; IV cyclophosphamide and prednisolone; and MMF and prednisolone was used in 97 (21.5%).

Conclusion

We present here a large single centre dataset of IgA nephropathy patients over a 20 year period. We show that there remains a significant risk of progression to ESKD over time. It is important to identify those patients most at risk of progression early on in their disease course so that optimal treatment can be initiated. Further analysis of this dataset will allow us to assess whether treatment strategies in recent years has had a beneficial effect on outcomes, and also to assess the correlation between MEST-C scores and treatment decisions.
MO308COULD THE PRESENCE OF ANCAS IN IGA NEPHROPATHY WITH CRESCENTS HAVE A CLINICAL IMPLICATION?
Authors: Castañeda Amado Zaira , Gabaldon Alejandra , Sanz María Teresa , Bury Roxana , Baldallo Cinthia , Zuñiga Jose , León Juan Carlos , Sanchez Cesar , Vergara Ander , Bermejo Sheila , Soler María José , Seron Micas Daniel , Agraz Irene
Published: May 2021

Background and Aims

IgA nephropathy (IgAN) is the most common glomerulonephritis. The presence of ANCAs in this pathology represents a rare coincidence. However, it is not clear if the presence of IgA or IgG ANCAs in these patients could have clinical significance.

We aim to describe the presence of IgA and IgG ANCAs in patients diagnosed with IgAN with crescents, and its possible clinical implications.

Method

Retrospective study from 2013 to 2020, it included all patients diagnosed by kidney biopsy of IgAN with extracapillary proliferation. Outpatient follow-up time was up to 24 months. Demographics and clinicopathologic data, ANCAs subtype, characteristics of the biopsy and treatment at the time of diagnosis/follow up was recollected.

Results

From 2013 to 2020, 17 adults were diagnosed with IgAN and extracapillary proliferation. 5 patients presented ANCAs, 3 (17%) were IgA ANCAs and 2 (11%) were IgG ANCAs. At diagnosis, the median age was 48 years old (27-75 years, sd. 15), with 9 women (52%). At the time of diagnosis, the most common clinical presentation was hypertension (71%). The laboratory analysis showed that median hemoglobin was 11.7 mg/dl (8.4-14.9 mg/dL, sd. 1.5), median creatinine was 2.2 mg/dL (0.55-5.7 mg/dL, sd. 1.4) and median proteinuria was 3.5 g/mgCr (0.1-12 g/mgCr, sd. 3.5). 7 patients (41%) presented extracapillary proliferation less than 25%, 7 patients presented it between 25% and 50%, and 3 patients (17%) had it in more than 50%. 5 (30%) patients presented fibrinoid necrosis. 1 (6%) patient needed renal replacement therapy upon admission. In terms of treatment, all patients with ANCAs IgAN received endovenous steroids and cyclophosphamide. The mean follow-up time was 6 months. Oral steroids (59%) and mycophenolate (41%) were the most frequent treatments. At six months, the median creatinine was 1.9 mg/dL (0.4-7, sd. 1.78) and the median proteinuria was 1.45 g/gCr (0.12-5.9, sd. 1.84 g/gCr). 3 patients developed end-stage chronic kidney disease and requiring substitute renal therapy; 4 patients died. Statistical analysis did not show differences in clinical characteristics, demographics, kidney function, proteinuria, need for renal therapy replacement or mortality according to the presence or subtype of ANCA. ANCA negative patients presented less than 25% of extracapillary proliferation in renal biopsy (p = 0.04). ANCA positive patients presented more fibrinoid necrosis than ANCA negative patients (p=0.01).

Conclusion

Given the limited size of our sample, our results do not allow us to be conclusive, showing no significant differences between the ANCA subtypes. However, from the point of renal biopsy, it is observed that patients with negative ANCAs present less extracapillary proliferation; and that patients ANCA positive presented more fibrinoid necrosis.