bluuebunny/crossref_metadata_2025_split huggingface dataset:
#1777 Proteomic profiling of laser capture microdissection kidneys from diabetic nephropathy patients
Authors: Yang Ziqian , Liu Fanna , Tang Donge 
Published: May 2024

Abstract

Background and Aims
Diabetes nephropathy (DN) remains the primary cause of end-stage renal disease (ESRD), warranting equal attention and separate analysis of glomerular, tubular, and interstitial lesions in its diagnosis and intervention. This study aims to identify the specific proteomics characteristics of DN, and assess changes in the biological processes associated with DN.

Method
5 patients with DN and 5 healthy kidney transplant donor control individuals were selected for analysis. The proteomic characteristics of glomeruli, renal tubules, and renal interstitial tissue obtained through laser capture microscopy (LCM) were studied using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).

Results
The expression of multiple heat shock proteins, tubulin, and heterogeneous ribonucleoprotein particle in glomeruli and tubules was significantly reduced. Differentially expressed proteins (DEPs) in the glomerulus showed significant enrichment in pathways related to cell junctions and cell movement, including the regulation of actin cytoskeleton and tight junction. DEPs in renal tubules were significantly enriched in glucose metabolism-related pathways, such as glucose metabolism, glycolysis/gluconeogenesis, and the citric acid cycle. Moreover, the glycolysis/gluconeogenesis pathway was a co-enrichment pathway in both DN glomeruli and tubules. Notably, ACTB emerged as the most crucial protein in the PPI analysis of DEPs in both glomeruli and renal tubules.

Conclusion
By using LCM and the proteomics analysis, we provide insights into the distinctive characteristics of each sub-region of renal tissue, shedding light on the impact of glycolysis metabolic disorder in DN and the potential role of the glomerular cytoskeleton and cell junction.
#400 A new notable compression source of left renal vein entrapment: the Right Renal Artery
Authors: Du Xuanyi , Sun Zhanfeng , Wang Haitao 
Published: May 2024

Abstract

Background and Aims
Clinically, left renal vein (LRV) entrapment is almost equivalent to the nutcracker phenomenon (NCP). However, there is still much uncertainty and debate about the prevalence of NCP and its diagnostic criteria. As a particular type of LRV entrapment, the LRV compression by the right renal artery (RRA) was primarily reported as case reports. The study was designed to investigate the RRA-sourced LRV compression in two selected patient cohorts.

Method
The cross-sectional study consecutively selected 38 hospitalized kidney patients diagnosed with membranous nephropathy (Renal group) and 305 peripheral vascular inpatients or outpatients (Non-renal group) in the Second Affiliated Hospital of Harbin Medical University in China from November 2018 to March 2023. The patients with computed tomography (CT) of renal veins or abdominal aorta were included in both groups if axial CT imaging could visualize the renal vessels and was with regular and adequate layer thinness to perform multiplanar reconstruction analysis. Any potential situations that might cause positional or course changes in proximal RRA or LRV due to pathological reasons were excluded from the study. The CT data of LRV compression by different anatomical sources, including but not limited to RRA, was analyzed.

Results
With other anatomical compression sources excluded, there were 22.58% (7/31) and 20.00% (5/25) LRVs compressed by the RRAs in the Renal and Non-renal groups, respectively, with no significant difference (p = 1.0). The distal segments of the LRVs compressed by RRAs have a significantly larger lumen area than those of non-compressed veins (p &lt; 0.01 in both groups). The overall incidence of NCP was calculated as 10.71% (6/56). Complex compressions, namely those LRV compressions by another adjacent structure besides RRA, coincided in 7.14% of the total cases (4/56).

Conclusion
Our study showed that it was not rare for the proximal RRA to compress the end of LRV. The detected incidence of RRA-sourced LRV compression was twice that of the entrapment related to the superior mesenteric artery, the mainstay of NCP. Though this finding came from two relatively small subject populations, it challenged the present connotation of LRV entrapment. Further repetitive studies are needed to test if such a phenomenon prevails in different populations, including healthy individuals.
Legends for all figures: Green thick arrows, RRA; green arrowheads, superior mesenteric artery (SMA); red-edged white arrows, left renal artery (LRA); white short-shafted arrows, LRV; white long-shafted arrows, inferior vena cava (IVC); transparent or white arrowheads, compressed sites.
#565 Renal involvement in solid cancers: epidemiological, clinical and histological characteristics study of 154 onconephrology patients
Authors: Gueutin Victor , Cardineau Aurore , Mathian Alexis , Lanot Antoine , Comoz Francois , Brocheriou Isabelle , Izzedine Hassan 
Published: May 2024

Abstract

Background and Aims
Onconephrology is a growing discipline that aims to improve the management of patients with cancer and kidney disease. If renal histology is an essential key, the anatomopathological data remain weak. We propose an analysis of real-life data from patients managed in onconephrology consultations and had renal biopsy.

Method
Patients with active cancer who had a renal biopsy (RB) between 2015 and 2020 were included, and their clinicobiological and histological data were retrospectively analyzed. Our cohort consisted of 154 patients (83 women) with a mean age of 58 years who went for onconephrology care.

Results
One hundred twelve patients presented with proteinuria, 95 with acute renal failure, and 59 with arterial hypertension. Histologically, interstitial fibrosis was found in 74% of RBs, tubular atrophy in 55.1%, arteriolar hyalinosis in 58.4%, and fibrous endarteritis in 54.4%. Regarding the main acute lesions, thrombotic microangiopathy (TMA) was found in 29.9% of biopsies, acute tubular necrosis (ATN) in 51.3%, and acute interstitial nephritis in 24.8%. The etiological diagnosis most often made was the nephrotoxicity of anticancer drugs (87 patients), followed by a functional cause (15 patients) and renal disease unrelated to cancer (13 patients). Sixty-seven patients presented with at least 2 associated diagnoses. Different clusters were found, highlighting that anti-PD1 and anti-VEGF therapy were the most commonly involved drugs.

Conclusion
The nephrotoxicity of anticancer drugs was the etiology most often determined following RB this a onconephrology population, predominantly with diagnoses of TMA and ATN. Chronic histological lesions were very common. The etiological diagnoses were sometimes mixed, and primary or paraneoplastic glomerulopathies were detected mainly through histology.
#1643 Long-term cohort study on the prognostic impact of mesangial IgM deposition in IgA nephropathy
Authors: Stefan Gabriel , Stancu Simona , Zugravu Adrian Dorin , Terinte-Balcan George 
Published: May 2024

Abstract

Background and Aims
The prognostic importance of mesangial immunoglobulin (Ig) M deposition in IgA nephropathy (IgAN) is not well-understood and is subject to ongoing debate. Moreover, mesangial IgM deposition could also reflect lectin complement system activation. Thus, our study sought to examine the long-term prognostic implications of mesangial IgM deposition in a cohort of IgAN patients.

Method
We carried out a single-center retrospective study involving 93 consecutive IgAN patients (median age 41 years, 68% male, eGFR 48.7 mL/min, proteinuria 1.1 g/g) from 2010 to 2015. The follow-up period extended until the onset of end-stage kidney disease (ESKD), death, or January 2021, with a median duration of 7 years. An independent pathologist assessed the IgM immunofluorescence pattern, Oxford MEST-C score, and transmission electron microscopy (TEM) lesions using a detailed protocol.

Results
In our study, 70% (n = 65) of patients exhibited mesangial IgM-positive deposits, while 30% (n = 28) did not show IgM deposition. Both IgM-positive and IgM-negative groups were comparable in terms of age (40 vs 43 years, p 0.6), sex (69 vs 64% male, p 0.6), arterial hypertension prevalence (69 vs 64%, p 0.6), Charlson comorbidity scores (2 vs 1, p 0.3), kidney function (eGFR 46 vs 55 mL/min, p 0.1 and proteinuria 1.2 vs 0.7, p 0.1), pathology findings (including Oxford MEST-C score, IgG and C3 immune deposition), TEM analysis, as well as in their treatment with renin-angiotensin-system inhibitors (63 vs 71%, p 0.4) and immunosuppression (39 vs 39%, p 0.9), and mortality rates (11 vs 7%, p 0.5). However, a notable difference emerged in the progression to ESKD, with 37% of IgM-positive patients advancing to this stage compared to only 11% of those in the IgM-negative group (p 0.01). The multivariate Cox proportional hazards regression analysis identified lower eGFR (HR 0.94, 95% CI: 0.92, 0.97), higher Oxford MEST-C score (HR 1.53, 95% CI: 1.16, 2.02), and mesangial IgM deposits (HR 4.75, 95% CI: 1.25, 17.99) as independent predictors of reduced kidney survival.

Conclusion
Our study identifies mesangial IgM deposition as a potential risk factor for ESKD in advanced IgAN, suggesting a need for further investigation. Future research should explore whether IgM's activation of the lectin complement pathway and resultant damage, as proven in ischemia-reperfusion injury models, are applicable to IgAN.
#2543 Complement receptor C5aR1 correlates with inflammatory responses driven by glomerular uPAR upregulation in renal vasculitides
Authors: Zeisberg Michael , Tampe Björn 
Published: May 2024

Abstract

Background and Aims
Avacopan is a novel promising treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) targeting the complement system by blocking C5a receptor C5aR1. We here pursued a transcriptome array-based approach to dissect molecular signatures associated with C5aR1 in renal vasculitis.

Method
C5aR1 mRNA expression levels (reporter ID: 210845_s_at, platform: Affymetrix Human Genome U133 Plus 2.0 Array, altCDF v10) were extracted from microdissected samples of renal vasculitis (glomerular: n = 23, tubulointerstitial: n = 21). Pathway analysis was performed for gene enrichment associated with PLAUR mRNA expression with a correlation threshold of ≥0.5 by using reactome (http://reactome.org), pathways with a predefined entities value of p≤0.001 were included.

Results
We here identified a predominant glomerular expression of C5aR1 in renal vasculitis as compared to the tubulointerstitial compartment (p &lt; 0.0001). Furthermore, glomerular C5aR1 induction correlated with impaired kidney function (eGFR: 0.0193). Gene set enrichment identified various inflammatory signatures including neutrophil degranulation and innate immunity, and particularly enrichment of urokinase plasminogen activator receptor (uPAR). uPAR itself also correlated with impairment of kidney function in renal vasculitis and particularly active glomerular lesions (cellular crescents and necrosis, p &lt; 0.0001).

Conclusion
The therapeutic implications of targeting uPAR in renal vasculitis are promising, and ongoing research endeavors are aimed at unraveling the complexities of uPAR as a potential diagnostic marker and therapeutic target for this challenging renal pathology. We here expand our current knowledge and link C5aR1 to inflammatory responses driven by glomerular uPAR upregulation in renal vasculitis.
#1804 Long-term outcomes of CKD patients with lupus nephritis: a nationwide cohort study
Authors: Chrysostomou Charikleia , Faustini Francesca , Gunnarsson Iva , Carrero Juan-Jesus , Barany Franz Peter , Evans Marie , Faucon Anne-Laure 
Published: May 2024

Abstract

Background and Aims
Health trajectories of patients with lupus nephritis (LN) are poorly understood in the setting of moderate and advanced chronic kidney disease (CKD). Furthermore, data on comparison of outcomes of LN to other forms of CKD are scarce. Therefore, the aim of this study was to compare long-term outcomes between LN and CKD from other etiologies.

Method
Using data from the Swedish Renal Registry (2006-2021), we compared clinical outcomes between patients with moderate and advanced CKD related to LN (LN-CKD), and patients with CKD due to primary glomerular diseases (PGD-CKD, i.e. IgA nephropathy, focal segmental glomerulosclerosis, membranous nephropathy), and due to other common CKD etiologies with high cardiovascular risk (Other-CKD, mostly diabetes and nephrosclerosis). Cox proportional hazard models were used to estimate the adjusted hazard ratios of mortality, major cardiovascular events (MACE), heart failure (HF), kidney replacement therapy (KRT) and acute kidney injury (AKI). Models were adjusted for age, sex, comorbidities, clinical and biological data including kidney function, medications and healthcare utilization.

Results
At baseline, patients with LN-CKD (N = 317, 61 years, 76% women, median eGFR 30 mL/min per 1.73 m²) and PGD-CKD (N = 2296, 57 years, 30% women, eGFR 29 mL/min per 1.73 m²), were younger and had lower prevalence of cardiovascular disease than patients with Other-CKD (N = 34778, 75 years, 36% women, eGFR 25 mL/min per 1.73 m²).
Over a median follow-up of 6.2 [3.3; 9.8] years, 19029 deaths (51%), 15768 (42%) MACE and 8390 (22%) KRT events occurred. The unadjusted 5-year absolute risks of death and MACE were high both in patients with LN-CKD (27% and 25%) and Other-CKD (50% and 44%), but lower in those with PGD-CKD (16% and 14%), whereas the 5-year absolute KRT risk was higher in patients with PGD-CKD (PGD-CKD: 37%, LN-CKD: 23%, Other-CKD: 23%).
In multivariable analyses and as compared to PGD-CKD, patients with LN-CKD had a higher risk of death (adjusted HR: 1.63 [95% CI: 1.32-2.02]), MACE (1.65 [1.31-2.08]), HF (1.68 [1.31-2.14]) and AKI (1.45 [1.02-2.05]) and showed a lower risk of KRT (HR: 0.81 [0.64-1.02]), although the 95% CI slightly overlapped (Figure, panel A).
In contrast, the risks of adverse events were similar between patients with LN-CKD and those with Other-CKD (Figure, panel B).

Conclusion
While LN-CKD had a lower risk of KRT than PGD-CKD, they exhibited a higher risk of death, MACE, KRT, HF and AKI, reaching the risk magnitude of patients with high cardiovascular burden (Other-CKD). Our findings may inform decisions for care planning in patients with advanced CKD and LN.
#953 Preliminary results of the peripheral T follicular cells and their subsets in ANCA associated glomerulonephritis
Authors: Christodoulou Michalis , Moysidou Eleni , Stai Stamatia , Bantis Konstantinos , Fylaktou Asimina , Sarafidis Pantelis , Stangou Maria 
Published: May 2024

Abstract

Background and Aims
T cells play crucial role in the pathogenesis of autoimmune diseases such as ANCA associated vasculitis-glomerulonephritis (AAV/GN) by secreting immune mediators and helping B cell-mediated long-lived humoral immunity development. Specific T and B cells subsets can be used as biomarkers of patients with AAV/GN. We aimed to prospectively compare the predictive ability of such subpopulations in patients with active AAV/GN.

Method
Flow cytometry was applied in the peripheral blood of 29 subjects. 15 AAV/GN patients (M/F 6/9), age: 62.1(28-82)years, MPO/PR3/Negative ANCA: 10/4/1) and 14 healthy controls (HC), to estimate T-cells subsets: CD4, T-folicular cells (Tfol), T-regulatory cells (Tregs), Tfh, Tfh1, Tfh2, Tfh17, and T-folicular regulatory cells(Tfr) and B-cells subsets: CD19, IgD(+)CD127(-), IgD(+)CD127(+), IgD(-)CD127(+) and IgD(-)CD127(-).

Results
Compared to HC, AAV/GN patients had reduced CD4 (698.8 Vs 368.8, p = 0.04) but increased proportion of Tfol, and both Tfh1 and Tfh2 cells (7% vs 12%, p = 0.05, 8.4 vs 11.2, p = 0.03, 13.3 vs. 45.9, p = 0.09, respectively). Both Tfr (p = 0.048) and Tfh (p = 0.023) were also significantly higher in group A, compared to group HC.
CD19 levels were lower in AAV/GN compared to HC, with reduced all subpopulation, though of not-statistical significance.

Conclusion
Specific T-cells subsets can be measured in AAV/GN patients’ peripheral blood. Subpopulations such as Tfh and Tfr can be used as biomarkers to diagnose patients with active disease and their role in the pathogenesis of AAV/GN must be studied in detail to determine if they can become targets for new therapies in the future.
#3068 Fibrosis and CD-163+ macrophages: making a difference between MPO-AAV and PR3-AAV
Authors: Benito-García Silvia , Vilardell Jordi , Arce Yolanda , Barros Xoana , Marco Helena , Guirado Lluis , Encarnacion Montserrat Mercedes Diaz 
Published: May 2024

Abstract

Background and Aims
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis characterized by inflammation of small blood vessels, with the kidney being one of the most affected organs. Its pathogenesis is a complex, multifactorial process involving inflammation and fibrosis in which macrophages play a crucial role. Macrophages are plastic cells that can change their phenotype in response to their environment. Infiltration of CD163+ macrophages (anti-inflammatory) in the interstitium and glomeruli is observed in AAV patients. Clinical and demographic differences between PR3-AAV and MPO-AAV were observed. We observed that interstitial fibrosis (IFTA) is more pronounced in MPO-AAV than in PR3-AAV.
We aimed to investigate the differences in CD163+ macrophage infiltration and interstitial fibrosis between PR3-AAV and MPO-AAV.

Method
Retrospective single-center study of 80 AAV patients (66 MPO-AAV and 14 PR3-AAV) diagnosed by renal biopsy with at least 1 year of follow-up. Clinical and laboratory variables, ANCA type and renal/patient survival were evaluated. 26 human kidney tissue samples (13 MPO-AAV and 13 PR3-AAV) were stained for CD163+ by immunohistochemistry and immunofluorescence, and trichrome-stained biopsy slides were used to measure the degree of fibrosis. Histomorphometric quantification was performed using MetaMorph® software in both cases. Data analysis was performed under standard conditions. Statistical significance was defined as P values less than 0.05. All P values were 2-sided.

Results
CD163+ macrophages infiltration in the interstitial space was greater in MPO-AAV than PR3-AAV with statistical significance (p &lt; 0.001), observing an average infiltration area of 0.333% in MPO-AAV than 0.116% in PR3-AAV. Furthermore, IFTA was higher at diagnosis in MPO-AAV (35.35%) than in PR3-AAV (31.21%) at the diagnosis with a p = 0.03. However, a correlation between IF and CD163+ macrophages infiltration was not possible to stablish.

Conclusion
We have observed an increased macrophage infiltrate with an anti-inflammatory and reparative phenotype that is higher at diagnosis in ANCAS-MPO compared to ANCAS-PR3, the same difference occurs with respect to interstitial fibrosis. Since the study population is small, no correlations between fibrosis and CD163 macrophage infiltration have yet been found.
#627 C3 glomerulonephritis and C3-dominant infection related glomerulonephritis—are they similar?
Authors: Shankar Mythri , Siddalingappa Ranjitha , C.G. Sreedhara , A. Kishan , Tenannkore Karthik 
Published: May 2024

Abstract

Background
C3 glomerulonephritis (C3GN) and C3 dominant infection related glomerulonephritis (C3-IRGN) comprise two important immune complex mediated diseases. C3GN is caused by dysregulation of the alternate pathway by congenital or acquired abnormalities in the complement pathway. C3-IRGN is often preceded by infection followed by recovery after the infection resolves. Although kidney biopsy findings may be similar in both conditions, the clinical course and treatment differs. We aimed to compare the demographic, clinical and lab parameters of C3GN and C3-IRGN.

Methods
All kidney biopsies conducted at Institute of Nephrourology, Bengaluru with dominant C3 on immunofluorescence from Jan. 2019-Dec. 2022 were included. The diagnosis of C3-IRGN was established using established criteria. Patients with C3GN had persistently low C3 for more than 12 weeks and no identifiable source of infection. Patients with C3GN were treated with steroids and cyclophosphamide, while those with C3-IRGN received antibiotics along with supportive medical management (including renin-angiotensin-aldosterone inhibition). Demographic, clinical and lab parameters were recorded and compared.

Results
23 cases of C3-IRGN and 19 cases of C3GN were included in the study. The mean duration of follow-up was 2.79 ± 0.92 years for those with C3GN and 2.78 ± 0.90 years for those with C3-IRGN. C3GN was common in younger patients (second decade of life) while C3-IRGN was common in the fourth and fifth decades of life. C3GN (57.9%) and C3-IRGN (73.9%) were both common in males. Previous infection (26.1% vs 5.3%) and present infection (39.1% vs 15.8%) were significantly more common in C3-IRGN. Hematuria (52.6% vs 34.8%), patient reported “frothy” urine (47.4% vs 21.7%) was significantly more common in C3GN compared to C3-IRGN. 36.8% of patients with C3GN had IFTA of &gt;50% compared to only 8.7% in C3-IRGN. Patients with both conditions most commonly presented with either acute nephritic syndrome or rapidly progressive glomerulonephritis. In contrast, presentation with CKD was significantly more common in C3GN (36.8% vs 0%, P = 0.002) compared to C3-IRGN, and patients with C3GN were more likely to require kidney replacement therapy (47.4% vs 21.7%, P = 0.002). At the end of follow up, 65.2% of patients with C3-IRGN attained complete recovery, compared with only 47.4% of C3GN patients.

Conclusion
There are characteristic differences between individuals with C3-IRGN and C3GN that may help to better ascertain diagnosis at presentation. Patients with C3GN tend to have worse prognosis, emphasizing the importance of treatments to slow CKD progression and avoid the need for kidney replacement therapy.