bluuebunny/crossref_metadata_2025_split huggingface dataset:
#2890 Role of alternative pathway of complement system in membranous nephropathy: a study from STARMEN clinical trials
Authors: León-Machado Lina María , Maldonado Maria , Rivera Jorge Enrique Rojas , Ortega Esther , Praga Manuel , De Jorge Elena Goicoechea , Juarez Gema Maria Fernandez 
Published: May 2024

Abstract

Background and Aims
Membranous nephropathy (MN) is an antibody-mediated autoimmune disease characterized by glomerular immune complexes containing complement components. A recent animal model of PLA2r antibody-induced MN induced has demonstrated the crucial role of complement pathway, although is still unclear which complement pathway is most involved in its pathogenesis
This study aimed to explore the role of alternative pathway of complement cascade in a cohort of patients from STARMEN clinical trial.

Method
We analyzed longitudinal plasma samples from 51 patients from STARMENT cohort stored in a biobank. Samples were stored at enrollment and longitudinally throughout the follow up at 3, 6, 9, 12, 18 and 24 months. We measured the circulating plasma levels of C3, FB, FH, FHR1, FHR2 and FHR5 in every time.

Results
Fifty-two patients with a mean age of 56 ± 10 years and 60% male were included. 44% were treated with tacrolimus+Rituximab and 56% with ponticelli regimen. The basal creatinine was 0.9 ± 0.3 mg/dl, median proteinuria/day was 8.8 g/day (IQR 5.7-11.6 gr/day) and serum albumin of 2.6 g/dl (IQR 2.3-2.9 g/dl). All patients were followed-up for two years. Thirty-four patients achieved complete remission (CR), 11 patients partial remission (PR) and 15 did not respond (including relapse).
During active disease, the mean concentration of FH, FHR-1 and FHR-2 were significantly increased compared with remission status (complete or partial). We did not find different in other factors: FB or FHR-5. Moreover, a positive correlation was observed between FH and FB with C3. There were no differences according to treatment arm.
PLA2r antibodies tested positive in 68%. The median of baseline anti-PLA2R title levels was 80 RU/ml (IQR 43-141). Circulating plasma levels of FHR1 at baseline were significantly higher in PLA2r testing negative vs positive patients (199 ± 108 vs 249 ± 41 µg/ml, p = 0.021). This significant difference was present when remission was achieved (205 ± 97 vs 264 ± 49 µg/ml, p = 0.023). Similar tendency was observed for FB.

Conclusion
These data provide evidence of complement system activation through the alternative pathway in membranous nephropathy. We know that different subtypes of IgG are behind the different antibodies-induced MN induced, and that every subtype active different complement pathway. The results of this study lead to speculate that not all the antigens that induced MN active complement pathway in the same way.
#2006 CircMTND5 participated in tubulointerstitial fibrosis progression of lupus nephritis by binding with A1CF
Authors: Zhou Hua 
Published: May 2024

Abstract

Background and Aims
lupus nephritis (LN) is the most common and severe complication of systemic lupus erythematosus (SLE). CircRNA MTND5 participated in the pathogenesis of LN by sponging miR6812. However, it remains unclear what RNA binding role of circMTND5 play in LN. We aim to investigate whether circMTND5 can interact with RBP in the development and progression in LN, and to clarify the corresponding mechanisms.

Method
A1CF, a RNA binding protein, E-cadherin, α-SMA, TGF-β, and Fibronectin were analyzed by immunohistochemistry on paraffin-embedded section of LN patients and NC kidney tissues. The above parameters and circMTND5 were also examined in Fcgr2b-/- spontaneous LN mice kidneys by Western blotting and qPCR. In human kidney (HK) -2 cells, the binding of circMTND5 to A1CF protein was examined by RNA immunoprecipitation (RIP) assay. After knockdown in HK-2 cells and overexpression in hTGF-β stimulated HK-2 cells, we examined the all above indices.

Results
the expression of A1CF was down-regulated in the kidneys of LN patients and was localized in tubular epithelial cells. E-cadherin was down-regulated while α-SMA was up-regulated. The expression of circMTND5 was down-regulated in kidneys of Fcgr2b-/- spontaneous LN mice. In HK-2 cells, the binding of circMTND5 to A1CF was confirmed by RIP. A1CF and E-cadherin were down-regulated, while α-SMA, TGF-β and FN were up-regulated in HK-2 cells with knockdown of circMTND5. The overexpression of circMTND5 reverted the changes of the those above parametered induced by hTGF-β in both mRNA and proteins levels.

Conclusion
The expression level of circMTND5 in renal tissue of LN mice was downregulated. CircMTND5 might play an important role in tubulointerstitial fibrosis of lupus nephritis by binding with A1CF protein.
#1641 Assessing long-term prognosis in patients with glomerular disease: nephrotic syndrome versus nephrotic range proteinuria comparison
Authors: Stefan Gabriel , Stancu Simona , Zugravu Adrian Dorin , Petre Nicoleta 
Published: May 2024

Abstract

Background and Aims
Although there is considerable research on the role of proteinuria in the progression of chronic kidney disease, a direct comparison between biopsy-diagnosed glomerular disease (GD) patients presenting with nephrotic syndrome (NS) and those with nephrotic range proteinuria (NRP) is lacking. Our study aims to bridge this gap by comparing the long-term outcomes of patients with NS and NRP.

Method
We conducted a unicentric retrospective study on 240 kidney biopsy-proven GD patients (median age 50 years, 65% men, median eGFR 58 mL/min, median proteinuria 6.0 g/24 h), tracked from 2010-2015 until end-stage kidney disease (ESKD), death, or study end in January 2022.

Results
The median follow-up was 8.8 years. Diagnoses were predominantly nonproliferative (53%), proliferative (25%) nephropathies, diabetic nephropathy (12%), and paraprotein diseases (10%).
NS was observed in 141 (59%) patients, presenting more frequently with arterial hypertension (61 vs 43%, p 0.001), higher eGFR (64.9 vs 51.5 mL/min, p 0.001), increased proteinuria (6.4 vs 5.4g/24 h, p 0.01), and dyslipidemia (serum cholesterol 316 vs 251 mg/dL, p 0.001; serum triglycerides 226 vs 184 mg/dL, p 0.001) than NRP patients.
NRP patients more often had proliferative (30 vs 22%) GD and diabetic nephropathy (22 vs 5%) ; their renal chronicity score was higher (2 vs 0, p 0.001).
ESKD endpoint occurred in 35% NS and 39% NRP patients (p 0.4). The cohort's mean kidney survival time was 8.2 years. In multivariate analysis, NS (HR 1.79, 95% CI: 1.09, 2.94), lower eGFR (HR 0.97, 95% CI: 0.96, 0.98), higher renal chronicity score (HR 1.12, 95% CI: 1.02, 1.23), and diabetic nephropathy (Ref, p 0.001) were associated with ESKD.
64 patients (27%) died, 73% post-kidney replacement therapy initiation, mostly from cardiovascular disease (63%). Mortality between proteinuria forms showed no difference. Multivariate analysis found lower eGFR (HR 0.98, 95% CI: 0.97, 0.99), higher Charlson comorbidity score (HR 1.38, 95% CI: 1.17, 1.64), and diabetic nephropathy (Ref, p 0.01) associated with mortality.

Conclusion
Our study found no difference in all-cause mortality between NS and NRP in glomerular diseases. However, adjusted analysis revealed poorer kidney survival for NS patients, emphasizing the need for personalized management to improve renal prognosis.
#626 C3 glomerulonephritis and thrombotic microangiopathy—a prospective observational study
Authors: Shankar Mythri , Siddalingappa Ranjitha , C.G Sreedhara , A Kishan , Tenannkore Karthik 
Published: May 2024

Abstract

Background and Aims
Complement mediated TMA (cTMA) and complement component 3 glomerulonephritis (C3GN) are two distinct complement mediated kidney diseases. cTMA is characterized by acute kidney injury, thrombocytopenia and microangiopathic hemolytic anemia. C3GN results from uncontrolled activation of the alternative complement pathway leading to the deposition of C3 in the glomerulus. We sought to describe characteristic differences between these two conditions in a large cohort of patients from Bengaluru, India.

Method
All cases of cTMA and kidney biopsy proven C3GN from 2019-2022 at a tertiary care centre in India were included. Patients with C3GN had persistently low C3 for more than 12 weeks and no identifiable source of infection. All patients received protocolized medical therapy; patients with C3GN were treated with steroids and cyclophosphamide, while those with complement mediated TMA received plasmapheresis in addition to cyclophosphamide and steroids. Protocolised medical management (renin-angiotensin-aldosterone inhibition and diuretics) was provided in both the cases. Demographic, clinical and lab parameters were reported and compared.

Results
A total of 25 cTMA cases and 19 C3GN cases were included in the study. Both C3GN (52.7%) and cTMA (48%) were more common in males. Patients with C3GN typically presented in the third decade of life while cTMA cases presented in the fourth decade. Secondary hypertension was common in the cTMA group (92% vs 78.9%, compared to C3GN). 60% of patients with cTMA had either recent or current infection compared to 21.1% of C3GN patients (P = 0.04). The majority of cTMA cases had IFTA of &lt;25% (84%) compared to C3GN (57.9%) although this was not statistically significant. Both C3GN and cTMA most commonly presented as rapidly progressive kidney failure and acute kidney injury. A total of 76% of patients in the cTMA group required kidney replacement therapy as compared to 47.4% in the C3GN group (P = 0.009). 44% of cTMA cases had anti factor H antibody positivity compared to 15.8% of C3GN patients (P = 0.02). Finally, 44% of cases in cTMA group had complete recovery compared to 47.4% in C3GN group at the end of 2.8 years of followup.

Conclusion
Although both conditions result from dysregulation of the alternative pathway, there are several important clinical characteristic differences between patients with cTMA and C3GN including presence or absence of secondary hypertension, concurrent infection, anti-factor H positivity and requirement of kidney replacement therapy. This information may be helpful to inform both diagnosis and prognosis for patients presenting with a complement mediated kidney disease.
#1933 Urinary proteomics identifying the novel biomarker associated with crescentic glomerulonephritis
Authors: Zhang Shuo , Chen Xin , Xu Jiatong , Hu Yu-Ting , Wang Ying , Xia Peng , Qiu Bintao , Chen Limeng 
Published: May 2024

Abstract

Background and Aims
As a severe progressive acute renal injury, crescentic glomerulonephritis requires timely pathology diagnosis and treatment. New non-invasive biomarkers will be crucial when the renal biopsy is not available or unacceptable. Urinary proteomics, specifically data-independent acquisition (DIA) proteomics, might provide some potential indicators.

Method
Urine proteomics examination was on patients with crescentic glomerulonephritis(n = 15), chronic glomerulonephritis (n = 15), acute kidney injury (AKI) without glomerular crescentic(n = 10), and 15 healthy controls. The crescentic glomerulonephritis group is the patients with extensive glomerular crescents over 50%. We performed LC-MS/MS analysis to identify differentially expressed proteins (DEPs), Ingenuity Pathway Analysis (IPA), and the proteome map for significant pathways and crucial proteins among patients and controls. The signature proteins were validated using enzyme-linked immunosorbent assay (ELISA) analysis.

Results
A total of 55 population, males occupied 45.45%, with the average age being 53 ± 13 years old. A volcano plot among crescentic glomerulonephritis and control groups is in Fig. 1. IPA analysis showed that neutrophil degranulation and complement cascade were the top two pathways in crescentic glomerulonephritis but not in the healthy and nephritis groups. The activated neddylation pathway in patients with crescentic glomerulonephritis compared with AKI patients. After integrating the DEPs among three groups via the Venn plot, we observed eight DEPs significantly associated with the crescentic glomerulonephritis, among which Coagulation factor V (F5), Phospholipid transfer protein (PLTP), and Alcohol dehydrogenase 1C (ADH1C) were significant proteins. Biomarker analysis showed the area under the curve values for predicting crescentic glomerulonephritis were 0.867, 0.851, and 0.815, respectively (P &lt; 0.001).

Conclusion
Urine proteomics holds promise in identifying the crescentic glomerulonephritis patient, thus providing a potential value as a noninvasive biomarker.
#2645 Clinical features and outcomes of steroid resistant focal sclerosing glomerulosclerosis (FSGS) in a single tertiary nephrology centre in Malaysia
Authors: Arimuthu Durga Arinandini , Lim Christopher Thiam Seong , Ibrahim Fairol Huda , Goh Bak Leong 
Published: May 2024

Abstract

Background and Aims
Steroid resistant FSGS is defined as persistence of proteinuria with &lt;50% reduction from baseline despite prednisolone 1 mg/kg/d for at least 16 weeks. We aim to study the clinical presentations, treatment, treatment response and kidney survival among steroid resistant FSGS patients.

Method
This retrospective study included all patients who had undergone renal biopsy in HSIS and had documented diagnosis of steroid resistant FSGS from January 2007 until December 2022. Data was collected and analysed using SPSS version 17. Results are expressed in mean ± standard deviation (SD) unless stated otherwise.

Results
A total of 74 patients had primary FSGS out of which 15 were identified as steroid resistant. Median age was 33 years old with 53% being female. Median weight at diagnosis was 73.7kg with BMI of 28kg/m2. One third had no co-morbid disease while 4 patients had underlying diagnosis of minimal change disease. Proteinuria on presentation was 7.6g with albumin levels of 16 g/L. No difference was seen between steroid resistant and steroid sensitive cohort with regards to age, proteinuria, GFR and laboratory parameters. Median duration of steroid was 38.8 months with duration of high dose steroids were 5 months and complications often set in by 2 months of therapy. Steroid toxicity occurred in 13 patients with most common complication seen was Cushingoid features (8/13) followed by acne (2/13) and diabetes mellitus (2/13). There were more steroid complications in steroid resistant cohort compared to the steroid sensitive. Second line was initiated in all patients but one with cyclosporin A being the most common choice (11/14) followed by Azathioprine (2/14) and cyclophosphamide (3/14). The median duration of second line agent was 22 months with CNI specifically being for 18 months. 3 patients developed CNI toxicity and was given cyclophosphamide while one patient developed CNI resistance and was given IV Rituximab. 4 (%) patients went on to achieve complete remission, 8 had partial remission while the rest did not achieve remission. 9 patients had normal renal function, while 3 developed chronic kidney disease. One patient went on to become end stage renal disease while 2 patients died. There was no difference in terms of renal or patient outcome between steroid resistant and steroid sensitive FSGS.

Conclusion
Steroid resistant FSGS is a challenging entity of FSGS that warrants close monitoring for complications and management. The outcomes were not different between steroid sensitive and steroid resistant FSGS however, the steroid complications were more common in steroid resistant FSGS.
#2691 Treatment naive membranous nephropathy patients treated with rituximab in COVID19 era
Authors: Brinar Ivana Vukovic , Stanusic Ivana , Ivandic Ema , Prlic Margareta Fistrek , Bulimbasic Stela , Ćorić Marijana , Kurtov Karlo , Kos Jelena , Jelakovic Ana , Jelaković Bojan 
Published: May 2024

Abstract

Background and Aims
Standard of care of high-risk idiopathic membranous nephropathy patients is immunosuppressive treatment with cyclophosphamide and corticosteroids or rituximab. Our aim was to assess outcome and safety of rituximab therapy in COVID19 era in comparison to modified Ponticelli protocol.

Method
In this retrospective study all adult patients with biopsy proven membranous nephropathy treated with rituximab as a first line therapy from 2020 till 2022 were enrolled and compared with MN patients treated with modified Ponticelli protocol from 2013 till 2020. Renal outcome was defined as composite of partial and complete remission defined according KDIGO guidelines. Except otherwise stated, data are shown as N (%) or median with interquartile range (IQR) and accompanied p levels.

Results
During the COVID 19 era, between 2020 and 2022, 8 MN patients were treated with rituximab as a first line therapy. One was lost from follow up and one had allergic infusion reaction and therefore was excluded from further analysis. Ten patients were treated with modified Ponticelli protocol. There was no difference in age (60 vs. 59 years; p = 0.669), gender (M 57.1 vs. 60%), BMI (26.3 vs. 29.1cm/kg; p = 0.906), systolic (140. vs. 150 mmHg; p = 0.161) or diastolic (90 vs. 91.5 mmHg; p = 0.230) blood pressure between rituximab and cyclophosphamide treated group. Also, there was no difference in proteinuria between rituximab and cyclophosphamide treated group (16.2 (5.7–31.3) vs. 8.7 (6.5–12.5) g/dU; p = 0.201) Patients treated with cyclophosphamide had lower eGFR compared with patients treated with rituximab (51 (34-79) vs. 93 (72-98) ml/min/1,73 m²; p = 0.005). At 6 months follow up only 2 (28.6%) in rituximab group and 6 (60%) in cyclophosphamide group achieved outcome defined as composite of complete and partial remission. At one year follow up, there was no difference in outcome between groups and all patients from rituximab group compared to 8 patients (88.9%) from cyclophosphamide group accomplished composite favorable renal outcome (p = 398). At the end of follow up, one year after cyclophosphamide therapy eGFR was better (57 (43-96) vs. 51 (34-79) ml/min/1,73 m²). Rituximab was safe in our cohort. Three (50%) of patients acquired SARS CoV2 infection and there was no adverse outcome regarding COVID 19 disease.

Conclusion
Cyclophosphamide is faster than rituximab in accomplishing remission of nephrotic syndrome and improves deteriorated kidney function. Nevertheless, at 1 year follow up rituximab efficiency is proven to be excellent. Cyclophosphamide should be reserved for MN patients with nephrotic syndrome with reduced glomerular filtration rate.
#211 Low albumin levels are associated with intrarenal complement C4d deposits in critically ill patients with ANCA-associated renal vasculitides
Authors: Baier Eva , Kluge Ingmar , Korsten Peter , Hakroush Samy , Tampe Björn 
Published: May 2024

Abstract

Background and Aims
Despite serum albumin levels being predictive for clinical outcome in ANCA-associated renal vasculitis, implications providing a direct link between low serum albumin levels and intrarenal lesions remain elusive. Therefore, we here aimed to systematically assess the clinical relevance of low albumin levels and scrutinize clinicopathological correlations to expand our current knowledge.

Method
We here retrospectively enrolled biopsy-proven cases of ANCA-associated renal vasculitis between 2015 till 2020 in a single-center observational study. Survival-curve analyses on long-term renal survival and short-term clinical recovery were performed. Correlative analyses between serum albumin levels, laboratory parameters, proteinuria levels, and histopathological lesions including tubulointerstitial immune cell infiltrates, lesions analogous to the Banff score and intrarenal complement deposition of C3c and C4d were performed.

Results
We here show that hypoalbuminemia below the median of 2.4 g/dL impairs long-term renal survival especially in MPO-positive ANCA-associated renal vasculitis (p = 0.006, HR: 5.0, 95% CI: 1.2-21.5), while short-term clinical recovery particularly in critically ill patients is negatively affected by low serum albumin levels (p = 0.0082, HR: 3.6, 95% CI: 1.1-11.7). Low albumin levels are associated with the urinary marker of tubular damage in the total cohort (β = −0.5, p = 0.01), PR3-ANCA (β = −0.5, p = 0.04) and MPO-ANCA (p = 0.002, β = −0.8), but not in critically ill patients (β = −0.5, p = 0.07) implying hypoalbuminemia to occur by extrarenal causation in the state of critical illness. We identified plasmacytic infiltrates to correlate with low albumin levels in the total cohort (β = −0.6, p = 0.004) and in the subgroup of critically ill patients (β = −0.7, p = 0.005). Banff-scored interstitial inflammation (i) was further observed to inversely correlate with albumin levels (β = −0.7, p = 0.02). Intrarenal C4d deposition showed a significant correlation with low serum albumin levels in the glomerular tuft (β = −0.4, p = 0.04) and in interstitial arteries (β = −0.7, p = 0.01).

Conclusion
In conclusion, long-term renal outcome is significantly affected by low serum albumin levels especially in the setting of MPO-ANCA seropositivity. By contrast, short-term recovery was predicted by low albumin levels in critically ill patients with ANCA-associated renal vasculitis. We here provide evidence that low levels of serum albumin might directly affect tubulointerstitial inflammation as reflected by plasmacytic immune-cell infiltration, and intrarenal C4d complement deposition in ANCA-associated renal vasculitis.
#1425 Anemia in patients with IgA nephropathy: an impact on the prognosis of IgA nephropathy
Authors: Kim Kyu Yeun , Park Sun-Hee , Yoo Jieun , Kim Mingyu , Kim Yoon-Ju , Jeon You-Hyun , Lim Jeong-Hoon , Jung hee-Yeon , Choi Ji-Young , Cho Jang-Hee , Kim Chan Duck , Kim Yong-Lim 
Published: May 2024

Abstract

Background and Aims
Immunoglobulin A Nephropathy (IgAN) has several well-known predictors of renal outcomes, including persistent proteinuria, hypertension, and baseline eGFR at the time of diagnosis. However, the effect of hemoglobin (Hb) levels on the progression of IgAN is rarely reported. This study aims to evaluate the impact of Hb levels on the prognosis of IgAN and to identify risk factors for anemia in patients with IgAN.

Method
A retrospective analysis of the data of 855 patients diagnosed with IgAN at Kyungpook National University Hospital between January 2002 and December 2021 was performed. We obtained the data on clinical parameters and pathological findings according to the Oxford classification at the time of the kidney biopsy. Univariate and multivariate logistic regression analyses were used to evaluate the risk factors for anemia, and a Cox proportional hazard model was used to estimate the effects of anemia on the development of end-stage kidney disease (ESKD).

Results
Lower serum albumin, lower eGFR, severe interstitial fibrosis, and tubular atrophy were associated with anemia in patients with IgAN. The Kaplan-Meier survival curve revealed that patients with anemia had worse renal survival than those without anemia. The multivariable Cox analysis showed that anemia was an independent risk for the progression to ESKD (HR 2.86, confidence interval 1.58–5.17, p = 0.001). In a sex-specific analysis, only the female sex showed a significant and higher risk for ESKD (hazard ratio 4.07, confidence interval 1.53–10.8, p = 0.005).

Conclusion
A low Hb level at the time of biopsy, even if subclinical, was an independent risk factor for the development of ESKD in patients with IgAN. Therefore, it is necessary to monitor Hb levels at the time of diagnosis and take proactive measures to reduce the risk of disease progression.