bluuebunny/crossref_metadata_2025_split huggingface dataset:
#2427 A multi-targeted treatment approach to induce early remission in high-risk primary membranous nephropathy
Authors: Dobronravov Vladimir , Kochoyan Zinaida 
Published: May 2024

Abstract

Background and Aims
A considerable proportion of primary membranous nephropathy (PMN) patients do not achieve early clinical remission with current immunosuppression regimens. The goal of the study was to evaluate efficacy and safety of the multi-targeted treatment regimen including rituximab, cyclophosphamide, and corticosteroids (all administered at low cumulative doses) (RCP) in PMN with antibodies to the phospholipase A2 receptor (anti-PLA2R).

Method
The study enrolled 30 high- or very-high risk PMN patients with persistent nephrotic syndrome (NS) and elevated anti-PLA2R in a prospective single-arm study of RCP treatment. The experimental protocol consisted of a single intravenous infusion of RTX (375 mg/m2) and methylprednisolone (500 mg), followed by oral prednisolone (1 mg/kg) tapered rapidly at 10 mg per week and discontinued at week 49. An additional RTX infusion at the same dose was given during weeks 8-12, 20-24, and 32-36 if complete remission was not achieved and peripheral CD19+ cell exceeded 5 cells/μl. Four intravenous infusions of CYC were administered at a dose of 7.5 mg/kg every other week, in weeks 1, 3, 5, and 7.
The effectiveness of RCP was compared to that of historic controls who received either rituximab-based therapy (RTX, n = 15) or cyclosporine+corticosteroids (CSA, n = 42). The primary outcomes measured were complete clinical remission (CR), overall remission (OR, which combines complete and partial remission) at month 12 after treatment initiation, and the time to clinical remission. Cox regression models were used to analyse the effect of RCP therapy on the probability of remission. Furthermore, we conducted comparative time-to-remission analyses in the RCP group and controls after propensity score (PS) matching.

Results
The RCP group exhibited higher OR and CR rates at 12 months (97% and 60%) compared to the RTX group (60% and 7%, P≤0.009) and the CSA group (50% and 24%, P≤0.003) (Fig. 1A,B). The median time to OR was shorter in the RCP group (2.8 (1.6–3.9) months) than in the RTX group (7.1 (3.4–17.5) months, P = 0.008) and the CSA group (7.3 (6.0–13.6) months, P &lt; 0.001) (Fig. 1A). In the adjusted Cox regression, the hazard ratios for OR and CR attainment for RCP compared to other treatments were 5.2 (95% CI: 2.8–9.6) and 4.8 (95% CI: 2.2–10.3), respectively. These results were confirmed by comparative analyses of propensity score-matched groups. Only one serious adverse event (SAE) occurred in the RCP group during the 56 patient-year follow-up.

Conclusion
RCP therapy is considered effective and safe for inducing early remission in high-risk PMN patients.
#971 Effects of arsenic trioxide on MMP9/IL-17A expression in lupus nephritis—results from bioinformatics analysis and in vitro studies
Authors: Xie Ruiyan , Zhang Danting , Jason Sher Ka Ho , Zhu Litong , Yap Desmond 
Published: May 2024

Abstract

Background and Aims
Previous research has indicated that ATO treatment at low doses may decrease the likelihood of flares in active systemic lupus erythematosus (SLE) patients, but the pharmacological mechanisms of such effect have not been studied.

Method
Machine learning and network pharmacology analysis were employed to explore the potential targets from differentially expressed genes (DEGs) of human SLE and LN peripheral blood mononuclear cells (PBMCs) microarray datasets and pharmacological databases. GO and KEGG analyses were performed, and the protein-protein interaction (PPI) network was constructed. The association of these characteristic genes and immune cells were further examined and validated.

Results
Three machine learning models (RF, SVM, and XGB) were utilized to identify five immunoregulatory genes in SLE among twelve intersection DEGs. Among these genes, MMP9 exhibited the highest ROC AUC (0.92) in predicting disease development. KEGG analysis revealed significant associations with the IL-17 signaling pathway (p = 1.67E-18). Furthermore, ssGSEA analysis indicated positive correlations between MMP9 and macrophages (correlation coefficient 0.88) as well as neutrophils (correlation coefficient 0.66). In vitro treatment of PBMCs from lupus nephritis (LN) patients with ATO resulted in downregulation of MMP9 and IL-17A, validating our bioinformatics findings.

Conclusion
ATO has the potential to mitigate the MMP/IL-17A pathways in PBMCs in LN patients, and hence maybe a promising and innovative therapeutic alternative.
#2800 AL amyloidosis with renal involvement: TAPSE and new therapies
Authors: Moreno Fernando Bertomeu , Molina Águeda López de la Torre , Garcia Fabiola Alonso , De la Prada Francisco José , Lazo Mercedes Salguiera 
Published: May 2024

Abstract

Background and Aims
Light chain (LA) deposition amyloidosis is the most common type of renal amyloidosis. It may be associated with monoclonal gammopathy of uncertain significance (MGUS), meeting criteria for monoclonal gammopathy of renal significance (MGRS), or present in the course of multiple myeloma.
The therapy of choice is autologous hematopoietic stem cell transplantation (TAPSE), although given the associated risks, not all patients are considered candidates, and different therapeutic regimens may be used as an alternative or induction prior to TAPSE (Bortezomib/dexamethasone, daratumumab/bortezomib, cyclophosphamide-bortezomib-Dexamethasone (CyBorD).

Method
Retrospective observational study of a cohort of patients with AL amyloidosis evidenced by renal biopsy by spectrometry or immunohistochemistry.
Data extracted from the HUVM biopsy registry (2017-2022).

Results
12 patients. Median age: 64 years. 6 women and 6 men.
Mean creatinine 1.14 ± 0.6 mg/dl and proteinuria 3.8 ± 2.9 g/24 h.
Median monoclonal peak 0.348 g/dl. Light chain involved: 7 Lambda and 5 Kappa. 2 patients met criteria for MM. 2 Bence-Jones positive.
The 4 patients who did not have a renal response achieved a renal response, while of the 6 who did have a response, only 3 had a response (p = 0.091), 2 of them with previous induction with DARATUMUMAB, representing 100% of the total number of patients with this scheme.
3 patients died, with a median from diagnosis of 508 days. 1 of them had previously received TAPSE, out of a total of 6, while among the 5 patients who did not undergo this therapy, we found 2 exitus (p = 0.387).

Conclusion
The most common form of presentation in our sample was as MSG, with only 2 patients with MM criteria at the time of diagnosis. It also associated a reduced monoclonal component, and the Bence-Jones study was mostly negative.
We did not find significant prognostic differences between the different therapeutic groups, although it is worth noting the worse renal response in the TAPSE group (p = 0.091) and the better data associated with the DARATUMUMAB group.
#1960 Incidence of cancer in ANCA associated vasculitis (AAV)
Authors: File Ibolya , Trinn Csilla , Bidiga László , Markóth Csilla , Ujhelyi László , Balla József , Mátyus János 
Published: May 2024

Abstract

Background and Aims
We investigated the incidence rate and type of cancer in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in our Institute.

Method
We retrospectively included 210 patients with AAV [106 patients with microscopic polyangiitis (MPA), 93 with granulomatosis with polyangiitis (GPA) and 11 patients with eosinophilic GPA (EGPA)], and reviewed their medical records. We collected demographic, clinical and laboratory data. We selected patients with history of cancer, patients diagnosed with paraneoplastic AAV and patients who developed malignant disease after AAV. We reviewed the use of glucocorticoid and immunosuppressive drugs.

Results
Between 1993-2024 there were 16 patients with AAV who had cancer during their life in our Department.
There were eight patients with malignancy-associated AAV. Two patients were simultaneously diagnosed with kidney carcinoma and vasculitis. One patient's serum was positive for cytoplasmatic ANCA, the other patient's for pANCA. Complete resection of cancer and renal biopsy was performed, they got steroid monotherapy. Five patients were diagnosed with pANCA vasculitis a few months (1-5) after the diagnosis of malignancies (two pts with breast carcinoma, two pts with ovarium carcinoma, one patient with ventricular carcinoma). In one case the pAAV was established after 5 months of oropharyngeal tumor's resection.
Two patients had history of malignancy (one pts had colon carcinoma 4 ys before the appearance of AAV, the other patient had breast carcinoma 10 ys before the AAV). In both cases there were examinations for malignancy with negative results. In these cases the vasculitis was not associated with carcinoma. The therapeutic approach included the use of corticosteroids, plasmapheresis, and cyclophosphamide or rituximab.
Six patients were observed malignancy 0.5-10 years after the diagnosis of AAV. There was one pancreas, one ventricular, two lung and two bladder carcinoma.

Conclusion
In our study we focused on the relationship of malignancy and AAV. Between the 210 patients with AAV eight cases (3.8%) were malignancy-associated, in one case cANCA associated, the other cases pANCA was presented. Treating paraneoplastic vasculitis can be challenging. Individualized treatment strategy tailored to patients' needs is crucial. Six patients were diagnosed with solid tumor during the follow-up. The cumulative overall cancer incidence rates were 1.4% and 2.8% at 5 and 10 years, respectively. Only in one patient with bladder cancer was treated with the cumulative CYC doses ≥ 36 g. No leukemia or non melanotic skin cancer (NMSC) was represented contrary to other studies.
#1584 Development and validation of risk prediction models according to different clinical settings of IgA nephropathy: nationwide multicenter cohort study
Authors: Hirano Keita , Ikenoue Tatsuyoshi , Yasuda Takashi , Yasuda Yoshinari , Maruyama Shoichi , Yokoo Takashi , Suzuki Hitoshi , Suzuki Yusuke , Fukuma Shingo 
Published: May 2024

Abstract

Background and Aims
IgA nephropathy (IgAN) is the most common glomerulonephritis with a high risk of progression to end-stage renal disease (ESRD). Because machine learning models developed for research have limited use in clinical settings, this study developed and validated prediction models for IgAN according to different clinical settings.

Method
In this study, we analyzed data from 1,174 patients in the Japanese Nationwide Retrospective Cohort Study in IgAN, focusing on a 10-year observation period. We defined the derivation data from January 2002 to April 2004, and temporal validation data from May 2004 to December 2004. The composite renal outcome was defined as a 1.5-fold increase in creatinine or progression to ESRD. We developed and evaluated the three prediction models according to the different clinical settings: the primary care model for general physicians in primary care settings, the tertiary care model for specialists in tertiary care hospitals, and the research institute model, a machine learning-based approach for academic research institute settings.

Results
After excluding 82 patients for missing data, 114 and 14 patients experienced the composite renal outcome in the derivation (n = 874) and validation (n = 218) cohorts, respectively. The primary care model identified three variables—eGFR &lt;45 mL/min/1.73 m², proteinuria ≥0.5 g/day, and non-use of corticosteroids—as significant predictors (C-statistic: 0.796; 95% CI: 0.686-0.895). The tertiary care model composed of three variables including glomerular number, histological severity and tubular/interstitial severity showed a slightly higher C-statistic (0.807; 95% CI: 0.713-0.886). When stratifying patients into risk groups, the primary care model showed a higher incidence of composite renal events in high-risk patients, and the tertiary care model effectively discriminated outcomes in all groups. The research institute model, which included 38 variables including proteinuria level, hypertension, eGFR, and non-use of corticosteroids as key predictors, showed comparable performance (C-statistic: 0.808; 95% CI: 0.689-0.886).

Conclusion
The primary care and tertiary care models provide simple yet effective predictive tools, competitive with the machine learning-based research institution model. These models are critical for predicting renal outcomes in patients with IgA nephropathy and for patient management according to different clinical settings.
#1968 IgA nephropathy and impact of proteinuria and kidney function decline on healthcare resource utilisation among adults in the United Kingdom
Authors: Baxter Garth , de Arellano Antonio Ramirez , Schaufler Thilo , Csomor Philipp , Dasgupta Sonali , Imperato Joseph 
Published: May 2024

Abstract

Background and Aims
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and can result in kidney failure, especially if left untreated. Proteinuria ≥1.0 g/day is a major risk factor for IgAN progression and rapid kidney function decline. This study describes the characteristics of patients with IgAN in the United Kingdom (UK) and the impact of proteinuria and chronic kidney disease (CKD) stage on healthcare resource utilisation (HRU) and costs.

Method
In this retrospective, descriptive analysis, eligible patients had at least one code among ICD-9 583.9, ICD-10 N02.8, and ICD-10 N02.9 between 1 October 2015 and 1 October 2022. They were stratified by CKD stage and proteinuria level. CKD stage was defined by ICD-10 N18 code and estimated glomerular filtration rate. Proteinuria level was grouped as low or high by protein excretion rate (&lt;1 g/day vs ≥1 g/day), protein/creatinine ratio (&lt;0.88 g/g vs ≥0.88 g/g), or albumin/creatinine ratio (&lt;100 mg/mmol vs ≥100 mg/mmol). HRU data for 1 year from the index date were obtained from electronic medical records, and costs were obtained from the National Schedule of the National Health Service 2021/22. Weighted average costs were calculated for inpatient, outpatient, and emergency visits.

Results
We identified 6 940 patients with IgAN. The mean age was 62 years, and most patients (n = 3 980; 57%) were male. For all visit types, HRU (Fig.) and costs (Table) increased with advancing CKD. For all visit types combined, the mean total cost per patient was &gt;23 times higher for CKD stage 5 than stage 1 (£60 259 vs £2 609). Of 2 080 patients with proteinuria data, 560 (27%) had high proteinuria. Annual costs per patient (Table) and the numbers of all visit types (Figure) were higher for patients with a protein excretion rate ≥1 g/day than those with a rate &lt;1 g/day (£12 622 vs £2 822).

Conclusion
In patients with IgAN in the UK, elevated proteinuria and advanced CKD stage were associated with higher HRU and costs across visit types. Treatments that reduce proteinuria can slow disease progression and prevent rapid decline in kidney function while potentially reducing IgAN-related resource utilisation and costs.
#622 Baseline inflammatory indexes and clinicopathological features to predict the outcome of acute interstitial nephritis
Authors: Dirim Ahmet Burak , Namazova Nazrin , Dirim Merve Guzel , Oto Ozgur Akin , Artan Ayse Serra , Hurdogan Ozge , Ozluk Yasemin , Yazici Halil 
Published: May 2024

Abstract

Backgrounds-and-aims
Acute tubulointerstitial nephritis(AIN) is a rare cause of acute kidney injury(AKI). We aimed to investigate the characteristics of AIN patients and predictive factors for treatment response.

Method
31 patients diagnosed with AIN by biopsy between 2006-2021 were included in this retrospective study. Baseline clinical, pathological, and laboratory findings, including CBC(complete blood count), creatinine, serum-immune-inflammation-index(SII), neutrophil-to-lymphocyte ratio(NLR), and platelet-to-lymphocyte ratio(PLR) were evaluated. Also, treatment response and creatinine levels at the last follow-up were noted.

Results
Median age was 46 years, and 80.6% of the patients were female. Median baseline creatinine and proteinuria levels were 4.1 mg/dL and 0.84 g/g or g/day. Median follow-up was 14 months. 93.5% of patients received immunosuppressives. End-stage-kidney-disease(ESKD) developed in five patients. Renal recovery(creatinine &lt; 1.4 mg/dL) was observed in 17 (54.8%) patients. Global glomerulosclerosis percentage, interstitial fibrosis(IF), tubular atrophy(TA), granuloma formation, and higher baseline hemoglobin levels were associated with poor renal outcomes(non-responder). Also, ESKD-developed patients had higher baseline hemoglobin(p = 0.033) and lymphocyte(p = 0.044) and lower PLR levels(p = 0.016), as well as higher degrees of global glomerulosclerosis(p = 0.014), IF(p = 0.042), and TA(p = 0.030).

Conclusion
Treatment rates are low for AIN, which may lead to ESKD. Besides chronicity in pathology specimens, higher baseline hemoglobin levels and lower PLR might be prognostic for AIN. Further studies should be conducted on new markers for AIN.
#1346 Inpatient and outpatient service review of a Greek reference centre for glomerular diseases
Authors: Chalkia Aglaia , Koutsianas Christos , Bora Margarita , Giannou Panagiota , Tsalapaki Christina , Gakiopoulou Harikleia , Tsioufis Konstantinos , Vassilopoulos Dimitrios , Petras Dimitrios 
Published: May 2024

Abstract

Background and Aims
The glomerulonephritis (GN) is a rare and complicated disease with high demand of hospital resources while the chronic kidney disease and end-stage renal disease present increased prevalence in these patients.

Method
We retrospectively assessed the inpatient and outpatient service of a Greek reference centre for glomerular diseases during the pre-Covid-19 period 2018-2020.

Results
267 patients (38% female, median age 65 ± 23 years) included. All patients underwent a kidney biopsy by the nephrologist without complications. ANCA associated GN (18%), Focal Segmental Glomerulosclerosis/Minimal Change Disease (17.5%), IgA nephropathy (17%), Membranous Nephropathy (12.6%), Lupus Nephritis (5%), Membranoproliferative GN (3%), Fibrillary GN (3%), Monoclonal Gammopathy of Renal Significance (3.3%) and IgG4-related disease (2%.) are encompassed. We reported median 75 new patients per year. Regarding the inpatient service, we observed an increasing trend to the hospitalizations during this period (274, 452, 461 hospitalizations in 2018, 2019, 2020 respectively). The AAGN was the most common disease of hospitalizations through this period (53% in 2018, 33% in 2019, 39% in 2020), whereas the second most common was the FSGS/MCD (28% in 2018, 13% in 2019, 23.8% in 2020). The outpatient's service review also revealed an increasing number of visits per person per year (279, 456 and 464 total visits in 2018, 2019 and 2020 respectively). The disease with the highest number of visits per person was reported the AAV (median 3.25 visits per patient per year). All the patients were managed in adherence to the latest guidelines for GN in collaboration with a multidisciplinary team, consisting of nephrologist, rheumatologist, cardiologist, and pathologist. Finally, we reported complete response at 76% of the patients and in terms of renal improvement, 46% presented eGFR≥60 ml/min/1.73 m2, 45% eGFR&lt;60 ml/min/1.73 m2 and only 9% progressed to ESRD after the first year of treatment.

Conclusion
Patients with GN present an increased need for hospitalization and regular outpatient visits. Addressing these diseases necessitates the expertise of a multidisciplinary team to provide comprehensive care that maximizes the potential for sustained positive long-term outcomes.
#368 Matching-Adjusted Indirect Comparisons of eGFR slopes in the PROTECT study with UK RaDaR IgA nephropathy population and the control arm of NefIgArd
Authors: Gong Wu , Diva Ulysses , Bensink Mark , Chai Xinglei , Xie Yanwen , Gao Sophie , Hendry Bruce , Mercer Alex , Zhou Zheng-Yi , Rovin Brad , Barratt Jonathan 
Published: May 2024

Abstract

Background and Aims
Immunoglobulin A nephropathy (IgAN) is a rare kidney disorder characterized by deposition of IgA in the glomeruli leading to an increased risk of kidney failure. The PROTECT clinical trial in IgAN was designed to determine the long-term (approximately 2 year) nephroprotective potential of treatment with sparsentan compared to a blinded active control angiotensin receptor blocker (ARB) irbesartan, titrated to the maximum labelled dose after randomization (achieved in 97% of patients). To understand PROTECT clinical trial results relative to delivery of standard of care (SoC) treatment for IgAN in other clinical settings, this study compared two-year eGFR total slope outcomes between the two arms of PROTECT and delivery of SoC in two populations applying similar eligibility criteria:

Method
Using individual patient data (IPD) from PROTECT, unanchored matching-adjusted indirect comparisons (MAICs) were performed. Patients in both arms of PROTECT were weighted to match key baseline characteristics of the two comparator populations. Matching was based on published clinical characteristics using the method of moments. After weighting, two-year eGFR total slopes were calculated using random coefficients models. Two-tailed z-tests with pooled standard errors were used for indirect comparison.

Results
Based on assessment of cross-data source characteristics, populations were found to be sufficiently comparable for unanchored MAIC. After weighting IPD from PROTECT, all matched baseline patient characteristics were well-balanced between data sources. Comparative results showed that patients treated with maximally titrated irbesartan or sparsentan in PROTECT exhibited a slower decline in kidney function compared to SoC delivered in a real-world setting (RaDaR), with differences of:
Similar results were observed compared to SoC delivered in a clinical trial (NefIgArd), with differences of:

Conclusion
Both “maximally tolerated dose of ARB” (as recommended in the KDIGO guideline for IgAN) using irbesartan in PROTECT and sparsentan were associated with significantly slower decline in kidney function compared to real-world SoC treatment for IgAN (RaDaR) and delivery of physician defined, optimized SoC (& placebo) in the context of a clinical trial (NefIgArd). 2-year eGFR slope differences between clinical trials in IgAN need to be considered in the context of what is achieved in current clinical practice. With existing real-world and emerging clinical trial data in IgAN, MAIC is an approach that can be applied to compare outcomes between relevant, sufficiently aligned data sources.