bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO210: Anti-Receptor Type M Antibodies of Phospholipase A2 in the Diagnosis of Primary Membrane Nephropathy
Authors: Daniel Diaz Garcia Juan 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Idiopathic membranous nephropathy (IMN) is one of the main causes of nephrotic syndrome in the adult population. Approximately between 20% and 40% of patients who suffer from it require replacement therapy in a period of 10–15 years. Recently, it has been reported that antibodies against the Type M phospholipase A2 receptor (APLA2R) are responsible for between 69% and 82% of cases with IMN in different parts of the world. Until now, the diagnosis and clinical follow-up of IMN requires the performance of a renal biopsy and proteinuria measurements.

METHOD
Diagnostic test study in a cohort of 106 patients who continued to be followed up in the nephrology outpatient clinic (EC), in the period from 1 January 2009 to 31 January 2017. Serum samples were taken and analyzed of patients with histological diagnosis of IMN with proteinuria &gt; and &lt;1 g in 24 h and other glomerular diseases other than IMN such as lupus nephritis, diabetic nephropathy, primary glomerular diseases and kidney donors (healthy subjects) with measurement of APLA2R by ELISA (EUROIMMUN ) concomitant with measurement of 24-h urine proteinuria.

RESULTS
In 22 of 106 patients, an APLA2R concentration &gt;9 RU/mL was found and all these cases had IMN (21 active IMN, Proteinuria &gt;1 g in 24 h and 1 inactive IMN, Proteinuria &lt; 1 g in 24 h). The prevalence of seropositivity in cases with active IMN was 78% (21/27). APLA2R concentrations were positively correlated with 24-h urine proteinuria (r = .68) and serum cholesterol (r = .42) and negative with serum albumin (r = −0.34). All these correlations were statistically significant with a P &lt; .001. The area under the ROC curve (AB-ROC) of APLA2R was 0.87 (95% CI 78–0.96). When comparing subjects with active IMN versus other subjects with glomerular diseases, with a cut-off point of 9 RU/mL, the sensitivity was 78% and the specificity 99%.

CONCLUSION
The APLA2Rs have an adequate diagnostic utility to diagnose IMN in the selected population; especially in subjects with proteinuria greater than 1 g/day, with a sensitivity of 78% with a specificity of 99%. The APLA2Rs are useful for the diagnosis of idiopathic membranous nephropathy, especially when there is proteinuria greater than 1 g in 24 h. The APLA2Rs measured by ELISA with titers greater than 9 RU/mL exclude other glomerular diseases and are highly specific for the diagnosis of IMN, which could prevent the performance of a renal biopsy.
MO213: Sars-COV-2 Vaccination DID Not Affect the Clinical Course of IGA Nephropathy in Latvian Adult Cohort
Authors: Rācenis Kārlis , Jana Saulīte Anna , Popova Anna , Saulīte Mikus , Kroiča Juta , Petersons Aivars , Cernevskis Harijs , Lejnieks Aivars , Oļeiņika Kristīne , Šlisere Baiba , Seilis Janis , Kuzema Viktorija 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The current strategy to fight against the COVID-19 pandemic involves active patient vaccination. Patients with renal and autoimmune diseases are in high risk for severe COVID-19 infection [1]. Therefore they should be prioritized for vaccination. Immunoglobulin A nephropathy (IgAN) is one of the most common primary glomerulonephritis triggered by mucous membrane alteration; however, there is a discussion about vaccination-caused IgA flare [2]. The immunological nature of IgAN and misleading information in public sources leaves patients skeptical about whether to get vaccinated [3]. The study aimed to investigate the impact of SARS-CoV-2 vaccination on the clinical course of IgA nephropathy.

METHOD
Adult patients treated in Pauls Stradins Clinical University Hospital with morphologically proven IgAN were included in the study. Patients with secondary IgAN were excluded. Evaluation of clinical and laboratory markers was performed on inclusion visit and on the second visit 6 months later. SARS-CoV-2 vaccination type and status were noted on both visits. Estimated GFR was calculated with CKD-EPI creatinine–cystatin equation. IBM SPSS Statistics version 27 and Microsoft Excel 10 were used for data analysis.

RESULTS
The study involved 54 patients, 36 were unvaccinated and 18 were fully vaccinated. A significant difference between the two groups was observed by baseline proteinuria. Other differences were not observed. Fourteen patients were vaccinated with mRNA vaccine, 13 with Comirnaty and 1 with Spikevax, and four patients were vaccinated with Vaxzevria vector vaccine. The differences between the two groups are shown in Table 1. During study period, two patients had COVID-19 infection; a patient in the vaccinated group had COVID-19 prior to vaccination.

CONCLUSION
SARS-CoV-2 vaccination did not affect the clinical course of IgA nephropathy. Our study results indicate that SARS-CoV-2 vaccination in IgA nephropathy patients was safe regarding renal function and disease activity markers.
MO229: Is Nodular Glomerulosclerosis Always Associated with Diabetic Nephropathy?
Authors: Nabil Hamouche , Chettati Mariam , Fadili Wafaa , Laouad Inass 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Nodular glomerulosclerosis (NGS) is a histological diagnosis that can be found in several etiologies. It corresponds to a particular form of expansion of the extracellular matrix within the mesangium.
Glomerulosclerosis is not very specific, its nodular form is on the other hand more interesting from an etiological point of view since only a few pathologies can take this aspect, the most frequent are diabetes (mainly), membranoproliferative glomerulonephritis (MPGN) and renal expression of gammopathies monoclonal.
In the absence of an identified etiology, NGS is said to be idiopathic. This entity, described 30 years ago, is very rare and therefore largely unrecognized. Some pathophysiological hypotheses have emerged in recent years, particularly involving smoking, high blood pressure or insulin resistance.
The aims of our study were as follows:

METHOD
Monocentric retrospective study of patients with NGS in renal biopsy, collected between January 2016 and December 2021 at Mohammed VI University hospital of Marrakech.
The epidemiological, clinical and etiological characteristics were studied.

RESULTS
We have collected 108 NGS. Of our patients, 47.22% presented with NGS of diabetic origin and 52.95% with non-diabetic NGS. For patients with NGS of diabetic origin, the indication for PBR was glomerular syndrome (19 patients), nephrotic syndrome (7 patients), rapidly progressive renal failure or severe renal failure (11 patients), recent diabetes (7 patients), absence of diabetic retinopathy (3 patients), presence of extra-renal signs (2 patients) and monoclonal peak (2 patients).
The diagnosis of idiopathic NGS was made after eliminating all the etiologies of NGS (normal complement dosage, no diabetes, no monoclonal peak, negative IFD, history of smoking and hypertension and dyslipidemia) and immunohistochemistry. Two patients were tested for deposits of the kappa and lambda chains, thus eliminating the myeloma.
Among the risk factors for idiopathic SNB detected in our work, we cite:

CONCLUSION
The most common etiology of NGS remains diabetes, but this lesion can be seen in other conditions such as MPGN, Randall disease, amyloidosis, monotypic immunoglobulin deposition, non-immunoglobulin and idiopathic glomerulopathies.
Idiopathic nodular glomerulosclerosis is a rare entity, frequent in most series in humans, which contrasts with the data of our study. On the other hand, a causal link between this histological entity and smoking, hypertension and Metabolic syndrome has been well established in several studies, which is consistent with the data from our work.
MO239: Clinical Evaluation of Immunological and Clinical Recurrence of Immune-Mediated Nephropathies after SARS-COV-2 Vaccine
Authors: Musetti Claudio , Fornara Laura , Cantaluppi Vincenzo 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The mass vaccination for COVID-19 has raised new concerns for patients with immune-mediated nephropathies: there is a small but growing literature of case-reports linking SARS-CoV-2 vaccines with heightened off-target immune responses leading to de novo or relapsing glomerular diseases [1, 2].
Aim of this study was to evaluate how many and how severe were the relapses of immune-mediated nephropathies after the SARS-CoV-2 vaccine in a single center.

METHOD
This is a retrospective study held in Italy from the start of the vaccination campaign (late December 2020) to December 31st 2021. We included all patients with an immune-mediated nephropathy (either on or off immunosuppressive therapy—IS), excluding patients with an end-stage renal disease or kidney transplant.
In Italy we used mRNA (Comirnaty by Pfizer-BioNTech or Spikevax by Moderna) or adenoviral vector vaccines (Vaxzevria by AstraZeneca or Janssen), without any preference for patients with kidney disease, but those on active IS were given preferentially an mRNA vaccine.
There was no active surveillance of lab tests after vaccination and post-vaccine tests were either concomitant to programmed visits or suggested on a patient by patient basis.
Recurrence was defined as relapse of nephrotic or nephritic syndrome, doubling of urinary proteins with a max value &gt; 1 g/24h, acute kidney injury with an active urinary sediment, or positivization or 5-fold increase of serological markers of disease activity (i.e.: ANCA in AAV).

RESULTS
A total of 38 patients (M: F 28:10, age at vaccine 45.9 ± 19.1 years) completed the vaccination protocol: among them, the most common nephropathy was membranous nephropathy (n = 12, 31.6%), followed by IgA nephropathy (n = 7, 18.4%), minimal change disease (n = 6, 15.8%) and ANCA-associated vasculitis (n = 6, 15.8%); 26 patients (68.4%) had at least one other comorbidity. We observed six relapses (4 MN, 1 IgA, 1 AAV), of which only one (MN) developed a mild oedema. The mean time from the first vaccine dose to the relapse was 101 ± 71 days (5–199 days) and only two episodes occurred within 4 weeks from a vaccine dose. We could not find an association between recurrences and maintenance IS at the time of vaccine or any other variable. The overall post-vaccine incidence rate of relapses was 35.8/100 patient-years, as compared with 14.0/100 patient-years historically observed in the same cohort [IRR 2.55, 95% confidence interval (CI) 0.89–5.97].

CONCLUSION
Relapses of immune-mediated nephropathies are not common after SARS-CoV-2 vaccine and we did not observe any clinically relevant relapse. However the overall rate of relapse seems to be a little higher than prior vaccination [3], but only 2/6 patients recurred soon after a vaccine dose. As these relapses seem to be self-limiting, a post-vaccine monitoring could be useful in patients at high risk of severe disease.
MO252: Complement 3 Deposits on Renal Tubule and Glomeruli in Phospholipase A2 Receptor-Related Idiopathic Membranous Nephropathy
Authors: Cui Haoyuan , LI Chao , LI Hang , Wen Yu-Bing , Chen Limeng 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Evidence shows galactose-deficient IgG4 is able to act complement system via lectin pathway in phospholipase A2 receptor (PLA2R) related idiopathic membranous nephropathy (IMN). However, the severity of PLA2R-related IMN runs parallel with neither the electron microscope stage nor the complement density in situ. We find positive complement factor 3 (C3) deposition on renal proximal tubule in some IMN patients and manage to analysis the relationship between it and the severity of the disease.

METHOD
We retrospectively involved 113 PLA2R related IMN patients from March 2017 to October 2019. The inclusion criteria were diagnosed by kidney biopsy with complete clinical and pathological data. The exclusion criteria were with any secondary causes such as lupus nephritis type V, Sjogren's syndrome, hepatitis B associated glomerulonephritis and atypical membranous nephropathy. We divided total patients into four subgroups according to the C3 deposition site. We defined no C3 deposition subgroup (40,35%) as C3 appeared in neither glomeruli nor tubule, C3 glomeruli deposition subgroup (32, 28%) as C3 deposited on glomeruli only, C3 tubule deposition subgroup (12, 11%) as C3 deposited on tubule only, C3 extensive deposition subgroup (29, 26%) as C3 deposited on both glomeruli and tubule.

RESULTS
Clinical data of four groups were as follows: Male/female ratio were 22/18, 23/9, 5/7, 16/13, P = .252; The median of age were 50 (33, 57), 51 (42, 57), 57 (49, 61), 51 (33, 57), P = .412; The median of were 24-h urine protein were 4.4 (2.0, 6.9), 5.0 (2.7, 8.3), 4.9 (2.5, 11.2), 5.5 (2.4, 10.2) g/L, P = .427. The average serum albumin were 28.6 ± 6.8, 27.2 ± 6.7, 24.6 ± 2.7, 25.5 ± 6.0 g/L, P = .046. The median of serum creatinine were 70 (57, 82), 77 (65, 92), 68 (57, 89), 69 (58, 80) μmol/L, P = .255. The median of serum C3 were 1.14 (1.0, 1.33), 1.17 (1.04, 1.36), 1.22 (1.0, 1.34), 1.11 (0.99, 1.23) g/L, P = .291. The median of anti-PLA2R antibody were 0 (0, 55), 29 (25, 33), 12 (0, 136), 35 (19, 131) RU/mL, P = .049.

CONCLUSION
There were differences in serum anti-PLA2R antibody and Alb in patients with different C3 deposition. Patients with extensive C3 deposition showed higher PLA2R antibody.
MO254: Baseline Characteristics of Patients Enrolled in the Ongoing Phase 3 Randomized, Double-Blind, Active-Control Trial of Sparsentan for the Treatment of Focal Segmental Glomerulosclerosis (DUPLEX)
Authors: Trachtman Howard , Radhakrishnan Jai , Komers Radko , Mercer Alex , Rosenberg Noah 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Uncontrolled focal segmental glomerulosclerosis (FSGS) often follows a progressive course to end-stage kidney disease and has a profound negative impact on patient quality of life and long-term survival. Treatments that reduce proteinuria and risk of kidney disease progression are urgently needed. Sparsentan is a novel dual endothelin angiotensin receptor antagonist (DEARA) being investigated for FSGS. The Phase 3 DUPLEX study is examining the potential long-term antiproteinuric and nephroprotective potential and safety of sparsentan compared with an active control, angiotensin receptor blocker (ARB) irbesartan in adults and pediatric patients with FSGS. Here we report the baseline characteristics for all patients enrolled in the DUPLEX trial.

METHOD
DUPLEX is an ongoing, global, Phase 3, multicenter, randomized, double-blind, active-controlled study designed to evaluate the efficacy and safety of sparsentan versus irbesartan in adult and pediatric patients (≥8–75 years old) with FSGS. The study duration is 268 weeks: a 112-week double-blind period followed by an open-label extension period of up to 156 weeks. The primary efficacy endpoint is the slope of eGFR over approximately 2 years of randomized treatment. Key inclusion and exclusion criteria are shown in Table 1. Patients receiving renin–angiotensin–aldosterone system (RAAS) inhibitors underwent a 2-week washout prior to randomization. Patients were randomized 1:1 to sparsentan or irbesartan (target dose 800 and 300 mg/day, respectively), stratified by screening eGFR and urine protein/creatinine ratio (UP/C). The blinded and aggregated baseline characteristics of all patients enrolled in the DUPLEX trial are summarized descriptively.

RESULTS
The DUPLEX study is fully enrolled with 371 patients (336 adult and 35 pediatric) across 179 study sites in 22 countries. Selected demographic and clinical characteristics in the total population are reported in Table 2.

CONCLUSION
DUPLEX is the largest randomized controlled trial to date in FSGS. Patients with FSGS enrolled in the DUPLEX trial display demographic and clinical characteristics consistent with the profile previously reported in the broader population of patients globally with FSGS not in remission.
MO267: Traditional and Disease-Related Cardiovascular Risk Factors in Anca-Associated Vasculitis: A Prospective, Two-Centre, Observational Cohort Study
Authors: Vegting Yosta , Lars Penne Erik , Hilhorst Marc , Pagnoux Christian , Houben Eline 
Published: May 2022

Abstract

BACKGROUND AND AIMS
ANCA-associated vasculitis (AAV) has been associated with increased risk of cardiovascular (CV) events. The purpose of the present study was to asses cardiovascular risk determinants and outcomes in a two-centre prospective cohort of AAV patients.

METHOD
Prevalent patients diagnosed with AAV ≥ 3 months were recruited over a period of 8 months from the Northwest Clinics in the Netherlands and 3 months from the Mount Sinai Hospital in Canada, and followed for 3–5 years. A comprehensive CV risk assessment was performed at inclusion. Subjects were followed up yearly until the first cardiovascular event, death or end of follow-up, whichever came first. Cardiovascular events were assessed by an independent outcome panel. Cox proportional hazards analyses were performed to relate baseline characteristics to the first CV event.

RESULTS
A total of 144 patients were included (median age 64.6 years, male sex 56%, median BVAS score 0, median Framingham risk score 14.3%). After a median follow-up of 2.91 years, 28 non-fatal and 4 fatal CV events were registered in 16 patients. Twelve patients died of non-cardiovascular causes. The incidence of fatal and non-fatal CV events was 5.5 per 100 patient-years. In a univariable analysis an association was found between traditional risk factors and risk of CV events [hazard ratio (HR) (95% confidence interval)], including age [HR 1.08 (95% CI 1.03–1.14)], HbA1c [HR 1.59 (95% CI 1.15–2.22)], systolic blood pressure [HR 1.04, 1.01–1.06), history of CV event [HR 3.47 (95% CI 1.29–9.32)] and Framingham risk score [HR 1.05 (95% CI 1.03–1.08)]. After adjusting for age and sex, HbA1c [HR 1.70 (95% CI 1.17–2.48)] and previous CV event [HR 2.90 (95% CI 1.02–8.21)] remained significantly associated with CV events. In a multivariable cox regression analysis (adjusted for Framingham risk score), a longer disease duration was associated with CV events [HR 1.08 (95% CI 1.01–1.16)].

CONCLUSION
The present study is the largest prospective study on CV risk in patients with AAV and showed that CV risk was driven by both traditional and disease-related risk factors. Disease duration is associated with increased risk of CVE, but which precise disease-related factors accounts for this finding, and whether it can be acted upon remain to be determined.
MO276: Renal Tubular CD24 Upregulation Aggravates Folic Acid-Induced Acute Kidney Injury Through Inhibition of Regulatory T Cells in Mice
Authors: Schwartz Doron , Grupper Ayelet , Zubkov Asia , Chernichovski Tamara , Arber Nadir , Shashar Moshe , Schwartz Edith 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Acute kidney injury (AKI) is characterized by cell death and inflammation. CD24 is a sialoglycoprotein which is induced during tissue damage and is not expressed in matured renal tissue. We explored the role of CD24 in the pathogenesis of folic acid-induced AKI (FA-AKI) in mice.

METHOD
A single i.p. injection of folic acid induced AKI in WT and CD24-/- mice. Renal function tests, histological analysis, immunohistochemistry, Western blot analysis and ELISA were performed to assess the severity of renal damage and the intensity of the inflammatory response.

RESULTS
FA-AKI induced the expression of CD24 in the distal tubular epithelial cells. Compared to WT mice, FA-AKI CD24-/- mice exhibited an attenuated reduction in renal function and histological injury, lower serum IL-10 and interferon γ, and decreased expression of renal TNFα. Renal and systemic IL-33 were upregulated in both groups. However, it was more pronounced in FA-AKI CD24-/- animals. FA-AKI CD24-animals exhibited increased splenic margination and renal infiltration of regulatory T cells (Tregs). At day 7, FA-AKI CD24-/- mice demonstrated increased expression of tubular pro-apoptotic (activated caspase 3) and decreased anti-apoptotic (Bcl-xL) proteins compared with WT animals. Administration of anti CD24 antibody to FA-AKI mice attenuated the decrease in renal function and ameliorated the histological injury in comparison with untreated animals.
Renal biopsies from patients with ATN stained strongly for CD24 in the distal tubules.

CONCLUSION
During AKI, upregulation of CD24 promotes renal inflammation through inhibition of Tregs infiltration and diversion of cell death towards necrosis rather than apoptosis. Neutralization of CD24 may prove as a target for future therapies in AKI.
MO279: Vitamin D Supplementation Attenuates Hyperandrogenemia-Associated Acute Kidney Injury in Female Sprague-Dawley Rats
Authors: Masjedi Fatemeh , Roozbeh Jamshid , Karimi Zeinab 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Polycystic ovary syndrome (PCOS) is closely related to the onset and development of metabolic abnormalities. However, the correlation between PCOS and kidney injury has not been clarified, and the underlying mechanism remains unknown. Vitamin D therapy has beneficial effects in women with PCOS and renal injuries. Therefore, this study was designed to explain the mechanisms responsible for kidney damages in a model of hyperandrogenic rats and the healing effects of vitamin D.

METHOD
Female Sprague-Dawley rats were randomly divided into five groups (n = 10): (i) control, (ii) sham, (iii) dehydroepiandrosterone (DHEA, 6 mg/100 g day-1 S.Q.), (iv) DHEA + vitamin D (1000 IU/Kg; 3 days/week), and (v) vitamin D. Plasma total testosterone, plasma creatinine (Cr), blood urea nitrogen (BUN), plasma and tissue levels of total oxidant status (TOS), total antioxidant capacity (TAC) and oxidative stress index (OSI), and histopathological changes of ovary and kidney were determined.

RESULTS
Plasma testosterone increased 9-fold in DHEA-treated rats compared with controls. They also had increased Cr, BUN, and severe renal tubular injury. Plasma and tissue TAC levels showed significant decreases, whereas TOS and OSI showed significant increases in the DHEA group. A significant injury in the glomerular and tubular parts of the kidney and ovarian follicular structure was observed in DHEA-administered rats. Vitamin D treatment attenuated TOS levels and significantly improved TAC levels. Kidneys and ovaries histopathological changes were significantly improved by vitamin D treatment.

CONCLUSION
Hyperandrogenemia causes systemic abnormalities through oxidative stress-related mechanisms, followed by obvious destruction to renal and ovarian tissues. Vitamin D supplementation attenuated these hyperandrogenemia-associated acute kidney injuries.