bluuebunny/crossref_metadata_2025_split huggingface dataset:
#409 Correlation between ha factor concentration and urinary syndrome in patients with chronic glomerulonephritis when using rivaroxaban
Authors: Abduvakhitova Asalya 
Published: May 2024

Abstract

Background and Aims
Considering the pathogenetic role of factor X of the coagulation system in the formation and progression of chronic glomerulonephritis (CGN), as well as the mechanism of action of rivaroxaban, this study examined the concentration of coagulation factor X in peripheral blood. Aim of our study to reveal the pathogenetic relationship between the concentration of Xa factor and the severity of urinary syndrome in patients with CGN on the background of basic therapy with the inclusion of rivaroxaban.

Method
108 CGN patients, on the background of 3-month baseline therapy with inclusion of rivaroxaban (AC+ group, 55 patients) and without anticoagulant (AC- group, 53 patients). Initially and after 3 months of the study the concentration of coagulation factor Xa in peripheral blood was studied.

Results
In CGN patients the concentration of Xa factor was significantly higher than in CG (122.17 ± 2.23% vs. 104.28 ± 6.54% in CG, p &lt; 0.05). On the background of 3-month therapy including antiaggregant, corticosteroid hormone and cytostatic, the concentration of Xa factor decreased by 18.82 ± 0.64% (p &lt; 0.001 reliability of difference with initial data). The use of rivaroxaban, as expected, was associated with a more significant decrease in Xa factor level—by 38.76 ± 1.40% (p &lt; 0.001 significance of difference with baseline data; significance of difference in relative dynamics of Xa factor concentration between groups depending on anticoagulant use, p &lt; 0.001). Correlation analysis revealed a significant positive strong correlation between the initial concentration of Xa factor in peripheral blood of CGN patients and the severity of hematuria (r = 0.83, p &lt; 0.01) and a positive weak correlation between the concentration of Xa factor and cylindruria as a manifestation of proteinuria (r = 0.30, p &lt; 0.01), as well as a positive weak correlation between the concentration of Xa factor and cylindruria at the end of the 3rd month of observation (r = 0.33, p &lt; 0.01). There was also found a significant negative weak correlation between the initial concentration of Xa factor and the relative dynamics of hematuria (r = −0.48, p &lt; 0.01) and cylindruria (r = −0.33, p &lt; 0.01).

Conclusion
The study confirmed the pathogenetic relationship between the concentration of Xa factor and the severity of urinary syndrome in CGN patients. It was also found that initially high concentration of Xa factor is associated with less positive dynamics of urinary syndrome parameters.
#1577 Rituximab in patients with primary podocytopathies: case series
Authors: Costa Cláudia S , Antunes Amélia , Oliveira João , Pereira Marta Sofia Henriques , Godinho Iolanda , Fernandes Paulo , Jorge Sofia , Lopes José António , Gameiro Joana 
Published: May 2024

Abstract

Background and Aims
Rituximab (RTX) has been reported as an effective treatment alternative in primary forms of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) associated with steroid dependence and frequent relapses. However, the optimal RTX regimen and the outcomes of further doses of RTX remain unclear. This study aimed to evaluate the use of induction and maintenance RTX therapy for adults with primary podocytopathies.

Method
We performed a retrospective case series on adult patients with steroid-dependent podocytopathies who received an induction RTX therapy. Maintenance therapy was performed at physician's discretion. Remission and relapse rates, concomitant corticosteroids and immunosuppressants use, B-cell depletion and adverse events were analyzed.

Results
Fourteen patients (mean age at start of RTX 29.1 ± 21.9 years) with MCD (n = 7) or FSGS (n = 7) were treated with 2 doses of 1000 mg 2 weeks apart (n = 13) or four doses of 375 mg/m2 (n = 1) of RTX. At last follow-up (mean 47.3 ± 101.7 months) ten patients were in complete remission and two remained in partial remission. A reduction in the number of relapses, number of patients under corticosteroids and immunosuppressants, and dose of prednisolone was observed when compared to baseline [14 (100%) vs 5 (35.7%); 8/14 (57.1%) vs 4/12 (33.3%); 13/14 (92.9%) vs 7/12 (58.3%); 20 mg/day vs 5.25 mg/day, respectively]. Maintenance RTX therapy was used in six patients, with sustained complete remission. Infusion reactions were observed in four patients (one required treatment withdrawal).

Conclusion
Our findings support the use of RTX for a steroid-free remission in podocytopathies and suggest that maintenance RTX is well-tolerated and associated with prolonged remission. Further studies are needed to confirm its efficacy and safety and establish the optimal induction and maintenance RTX regimen in steroid-dependent podocytopathies.
#2565 Urine amino acid profiles enlighten new prediction models for renal Fanconi syndrome and its association with eGFR level
Authors: Chen Limeng , Dong Yuan , Shi Xiaoxiao , Hou Zuoxian , Xia Peng , Qiu Ling 
Published: May 2024

Abstract

Background and Aims
Renal Fanconi syndrome (FS) presented dysfunctions of renal proximal tubular (PT) transport with or without excessive urine amino acids (AAs) excretion, which might contribute to the progression of eGFR decline. This study aimed to explore the clinical benefit of 21 urinary AAs excretion patterns in renal FS and eGFR decline.

Method
Liquid chromatography-tandem Mass spectrometry (LC-MS-MS) is currently quantitative and detects over 21 types of amino acids in 157 patients with renal proximal tubular dysfunctions. To evaluate the diagnostic values of urine AAs in renal FS, we established a machine learning algorithm to perform binary classification using Random Forest Regressor in Python (version 3.8.8) with a training set and a testing set (8:2). We used Randomized search to find out the best model hyperparameters, calculated feature importance for contribution evaluation, and Receiver Operating Characteristic (ROC) curves to evaluate the performance of classification algorithms.

Results
A model based on a machine learning algorithm of all urine AAs to diagnose renal FS established with sensitivity = 0.71, specificity = 0.73, and AUC = 0.83 (95% CI 0.648-0.957) (Fig. 1), with similar performance in combined six urine AAs (citrulline, asparagine, threonine, phenylalanine, ornithine, and proline) models. The urine proline level independently correlated with eGFR &lt; 60 ml/min/1.73 m2 (bias regression coefficient 0.84, P = 0.001, OR = 2.31, 95% CI 1.41-3.80) when adjusted by age, etiology, gender, and blood urea nitrogen level. For the primary diseased diagnosis, the most susceptible urine AAs were citrulline (56.7%), proline (56.0%,) threonine (52.2%), and ornithine (45.9%) and the less susceptible ones were histidine (24.8%), aspartate (16.6%), and arginine (13.4%). Accordingly, the most common affected AA transporters were SLC6A19 (B0AT1) and etiology-specific urine AA atlas major in the eight urine AAs (isoleucine, glutamine, methionine, proline, alanine, ornithine, lysine, and arginine). Different from primary Sjӧgren syndrome patients (n = 26) with less susceptible, the patients with plasmacyte diseases (n = 8) showed elevations of almost all the urine AAs except glycine and aspartate. The connection between urine AAs excretion and hypouricemia showed gender differences, with 20 urine AAs significantly negatively correlating with serum uric acid levels in males but only five in females.

Conclusion
We first established a model based on the urine AA atlas detected by (LC-MS-MS) which contributed to differentiating the etiologies of renal tubular dysfunctions and associated well with eGFR. It shed light on the clinical practice in precision evaluation of tubule injury.
#1276 Clinical practice of complement inhibitor use in hemolytic uremic syndrome: findings from the European rare kidney disease registry
Authors: Vujovic Aleksandra 
Published: May 2024

Abstract

Background and Aims
Over the last decade, significant advancements have emerged in the field of rare kidney diseases, notably the introduction of C5 inhibitor therapy. The C5 inhibition has transformed the prognosis for atypical Hemolytic Uremic Syndrome (aHUS), offering improved clinical outcomes. However, despite these advancements, the utilization of C5 inhibitor therapy varies significantly, with disparities in treatment duration, reasons for discontinuation, and consideration of extending treatment to patients with infectious HUS (iHUS). This variability is further compounded by the considerable cost associated with C5 inhibitor treatment.

Method
This retrospective cohort study utilized data from the ERKNet Registry. The study cohort comprised 608 HUS patients enrolled in the ERKNet Registry between November 2018 and September 2023. The dataset encompassed patient demographics, disease and diagnostic records, medication profiles, dialysis or transplantation requirements, kidney function monitoring at the last visit, and clinical outcomes.

Results
Among 230 aHUS patients, 23 underwent kidney transplantation. 11 received C5 inhibitor therapy before kidney failure. The majority of these patients had genetic aHUS with various mutations (3 CFH, 2 CFI, and 1 CD46). The only death in the study was from this group of patients, unresponsive to C5 Inhibition. Out of 175 aHUS patients treated with Eculizumab, 23 (13%) transitioned to Ravulizumab. Among 104 patients who discontinued C5 inhibitors, 14 (14%) had to resume treatment, half of them with genetic aHUS, with 3 cases of CD46 mutations, 2 cases CFHR5 mutations, and one each involving mutations in CFI and C3. Only two patients required dialysis.. Among 371 iHUS patients, 82 (22%) received C5 Inhibitor treatment.

Conclusion
In the context of aHUS, we found that discontinuing C5 inhibitors is generally safe, with a slightly higher relapse rate in patients with complement gene variants, though most relapses were mild, requiring dialysis in only a few cases. Long-term follow-up revealed a return to normal kidney function following TMA relapses. Transitioning from Eculizumab to Ravulizumab exhibited promising outcomes, with no relapses or kidney failures in 23 patients. Our analysis of C5 inhibitor use in iHUS emphasized its association with more severe disease progression. While some studies question C5 inhibitors' acute-phase efficacy, others report remarkable improvements in patients unresponsive to other treatments. Overall, our findings underscore the safety of discontinuation practices, the potential benefits of Ravulizumab, and the ongoing need for further research on C5 inhibitor treatment in iHUS.
#689 Obinutuzumab in patients with previously untreated primary membranous nephropathy
Authors: Du Xuanyi , Lin Xiaojing , Fu Rao 
Published: May 2024

Abstract

Background and Aims
Primary membranous nephropathy (PMN) is the most common cause of nephrotic syndrome (NS) in adults and is currently considered an autoimmune-related disease. B cell depleting treatments, currently the most commonly used is rituximab, are usually effective in treating membranous nephropathy (MN). However, about 35% of patients treated with rituximab fail to respond, and relapses after RTX-induced remission are frequent. Among the new anti-B cell therapeutics, obinutuzumab has shown significant efficacy in treating refractory MN, including those that have failed treatment with RTX. The literature on the clinical efficacy of obinutuzumab as an initial treatment for MN is very limited. This study aimed to evaluate the efficacy and safety of obinutuzumab as an initial treatment for PMN.

Method
We reviewed all patients (n = 6) with PMN diagnosed by renal biopsy who were followed up for ≥3 months and received obinutuzumab as initial therapy at our center. We analyzed the trend of changes in related indicators such as urine protein, serum albumin, serum creatinine, serum PLA2R antibody, B lymphocyte count, and the response time and remission rate.

Results
After obinutuzumab therapy, all patients achieved remission at a median follow-up of 3 months (IQR, 2.5–3.25 months). The remission rate at three months was 83.3%. Two patients experienced adverse reactions in our study: one had interstitial pneumonia and eczema, and one had transient leukopenia.

Conclusion
As the initial treatment for primary membranous nephropathy, obinutuzumab induces a safe and rapid response. Large prospective studies are needed to provide more evidence.
#2988 Use of rivaroxaban for prevention of thrombotic events in patients with nephrotic syndrome
Authors: Rapetskaya Nadzeya , Komissarov Kirill , Kalachyk Aleh 
Published: May 2024

Abstract

Background and Aims
Patients with nephrotic syndrome are at increased risk of thrombotic events. The risk of thromboembolism is particularly high in patients with primary membranous nephropathy, elderly patients and patients with severe hypoalbuminemia. Although increased incidence of thrombosis is a well reported complication associated with nephrotic syndrome, management strategies are not well established. Use of aspirin seems to be insufficient to prevent venous thromboembolism. Use of warfarin and low-molecular-weight heparins is inconvenient for outpatients.
The aim of the trial was to evaluate effectiveness and safety of rivaroxaban in venous thromboembolism prophylaxis in patients with nephrotic syndrome.

Method
The randomized single-center trial was performed from October 2020 to November 2023. 30 adult patients with nephrotic syndrome due to primary glomerular diseases and glomerular filtration rate more than 60 ml/min were divided into two groups. The treatment group (n = 15) received 10-20 mg of rivaroxaban daily. The control group (n = 15) had no anticoagulation therapy. Thrombotic events and bleedings were recorded.

Results
Patients in both groups received immunosuppressive treatment of nephrotic syndrome according to primary disease. Rivaroxaban was prescribed for the entire treatment period until the onset of remission. Patients with membranous nephropathy were equally represented in both study groups (4 per group). No thromboembolic events were recorded in both groups. As well as there were no bleeding complications in patients who received rivaroxaban.

Conclusion
Rivaroxaban might be a possible alternative to warfarin and low-molecular-weight heparins in prevention of thrombosis in nephrotic syndrome. However, indications for anticoagulant prophylaxis, its duration and discontinuation are still not clear. Future studies should address the question regarding the utility of primary thromboprophylaxis.
#1609 Effect of dapagliflozin in proteinuria reduction and glomerular filtration rate in a group of Alport syndrome patients
Authors: Gomes Ana Marta , Malheiro Jorge , Lemos Carolina , Dias Joana Pereira , Lopes Daniela , Almeida Clara , Beirão Idalina 
Published: May 2024

Abstract

Background and Aims
Alport syndrome (AS) is the most common cause of inherited chronic kidney disease. This disorder is caused by deleterious variants on COL4A3, COL4A4 or COL4A5 genes. These genes codify the proteins that constitute collagen type IV of the glomerular basement membrane (GBM). Alterations in any of collagen type IV constituents cause disruption of the GMB structure, allowing the leakage of red blood cells and proteins, mainly albumin, into the urine resulting in kidney damage and loss of renal function.
In AS progressive kidney impairment can be delayed or possibly prevented by timely initiation of renin angiotensin aldosterone inhibitors (RAAi): in males with X-linked AS and in autosomal recessive AS ARAS at diagnosis and in females with XLAS and autosomal dominant AS at the onset of microalbuminuria. Recently, it was showed that sodium-cotransporter-2 inhibitors (SGLT2i) reduce proteinuria and slow the progression of kidney disease in many glomerular diseases. Thus, also in AS, SGLT2i could be promising in renal disease progression control.
The aim of this study was to determine the proteinuria reduction and the effect on the glomerular filtration rate (GFR) in a group of AS patients with persistent proteinuria besides the use of RAAi in maximum tolerated doses after adding SGLT2i to the treatment.

Method
This study was single-center, observational and prospective study evolving 8 AS adult patients, without a diagnosis of diabetes, with persistent proteinuria besides the use of RAAi in maximum tolerated doses. All patients were prescribed wit dapagliflozin 10 mg daily. We determine the changes from baseline of urinary protein/creatine (Up/cr) and glomerular filtration rate (based on epiGFR formula).

Results
Eight AS patients were included in this study. All were male patients. One patient has XLAS and the other 7 patients have ADAS. No patient was diabetic, and all were under RAAi in maximum tolerated doses. We determine de Up/cr and epiGFR at baseline and median time of 213.5 days (IQR 208.3-259) after SGLT2i initiation. At baseline, the median of Up/cr was 1.4 (IQR 0.8-2.1) and after SGLT2i Up/cr was 1.5 (0.8-2.6), p = 0.727. Up/cr, after SGLT2i treatment, reduced in 3 patients and worsened in 5. Median epiGFR at baseline was 80.3 ml/min (IQR 40.9-109.5) and after SGLT2i initiation was 74.7 ml/min (40.4-112.0), p = 0.727.

Conclusion
In this study, we did not observe an improvement in Up/cr of AS patients with SGLT2i treatment. A slight decrease in GFR was observed that may be due to the well know hemodynamic effects of SGLT2i. The small cohort and short time of the study are factors that can interfere in these results and should not discourage the treatment of AS patients with SGLT2i.
#2187 Rare disease, novel approach: C3GN and Iptacopan case report
Authors: Groome Ciaran , Padmanabhan Neal , Wong Edwin , Yule Ailson , Fairweather Jack 
Published: May 2024

Abstract

Background and Aims
C3 glomerulonephritis (C3GN) is a rare disease characterised on biopsy by proliferative lesions of predominant C3 deposition on immunofluorescence, particularly deposits within the mesangium and capillary walls. Dysregulation of the alternative complement pathway is thought to be the underlying mechanism [1]. There are no approved treatments for C3G and prognosis is poor, with 50% progression to kidney failure over 10 years and similar rates of transplant loss due to disease recurrence. Iptacopan (a selective Factor B complement inhibitor) is proposed to suppress key enzymes involved in the alternative pathway cascade [2]. It is being studied in clinical trials of C3G [3].
We sought to describe our experience in diagnosing and managing a 25-year-old with C3GN who presents with nephrotic syndrome, hypertension, and a reduction in his estimated glomerular filtration rate (eGFR) with a novel small molecule therapeutic.

Method
This report charts the clinical course of one male patient over 11 months from presentation with C3GN, to the introduction of immunosuppression and of Iptacopan, and the assessment of his response to the foregoing. The patient consented to the publication of his case.

Results
A 25-year-old male with a background of autism spectrum disorder was referred to his regional nephrology service due to reduction in his eGFR and proteinuria. His creatinine was 158 µmol/L with an eGFR was 51.8 ml/ml/1.73 m2 (CKD-EPI equation); urinary protein creatinine ratio (uPCR) 500 mg/mmol; urinary albumin creatinine ratio (uACR) 400.2 mg/mmol. Serum album 32g/L. His C3 0.22 (normal range 0.82–1.85 g/L); C4 0.27 (normal 0.15–0.53 g/L). A renal biopsy was performed which demonstrated diffuse MPGN dominant C3 staining; cholesterol crystals; and moderate to severe chronic tubulointerstitial damage.
1 mg/kg oral prednisolone with mycophenolate mofetil (MMF) titrated up to a dose of 1g twice a day was initiated. As he was established on the therapy his eGFR rose back to 57.9 ml/min over approximately 8 weeks from a nadir of 33.8 ml/min. Following initial weaning of his prednisolone dose, his eGFR dropped back down to 29.7 ml/min with a creatinine of 250 µmol/L.
With involvement and clinical support from the National Renal Complement Therapeutics Centre an application was made to Novartis for the compassionate use of Iptacopan which was commenced early August 2023 (he would not have been eligible for recruitment into any current clinical trials). His latest eGFR is 47.5 ml/ml/1.73 m2 with a uACR of 9.1 mg/mmol and normal C3 and C5b-9 levels after 5 months of Iptacopan.
His prednisolone dose is 10 mg. MMF continues at 2g total dose.

Conclusion
Iptacopan has so far resulted in the normalisation of serum C3 levels, reduction of uACR and stabilisation of serum creatinine as we have reduced the prednisolone dose.
#2349 Lysyl oxidase-like 2 inhibitor ameliorates tubulointerstitial fibrosis and albuminuria in cyclosporine induced nephropathy
Authors: Park Hyeong Cheon , Kim Hyo Jeong , Choi Hoon Young , Lee Jung Eun 
Published: May 2024

Abstract

Background and Aims
Lysyl oxidase-like 2 (LOXL2), an amine oxidase, contributes to fibrotic scarring in the tissue by facilitating collagen cross-linking. Recent data demonstrated upregulation of lysyl oxidase and LOXL2 in the fibrotic kidneys after administration of cylosporine A (CsA). Thus, inhibition of LOXL2 may render therapeutic effects against CsA-induced nephropathy by ameliorating tubulointerstitial fibrosis.

Method
Low salt fed CD-1 mice were administered saline or CsA (15 mg/kg/day, intraperitoneally) for 8 weeks. At 4 weeks, CsA-treated animals were divided into 2 groups respectively and treated with: (1) vehicle, (2) LOXL2 inhibitor (10 mg/kg/day, gavage feeding) for another 4 weeks up to 8 weeks. We explored the reduction of tubulointerstitial fibrosis as well as albuminuria with administration of LOXL2 inhibitor in CsA nephropathy mouse model.

Results
CsA administration significantly increased the levels of serum creatinine (10.0 ± 1.2 vs. 28.4 ± 4.3, p = 0.02), tubular injury scores (0.1 ± 0.2 vs. 3.6 ± 1.3, p = 0.03), tubulointerstitial fibrosis (Sirius red positive area, 14 ± 6% vs. 204 ± 43%, p = 0.01), F4/80 positive inflammatory cell infiltration in mouse kidney (2 ± 1 vs. 21 ± 4, p = 0.001). These changes were associated with upregulated mRNA expression of LOXL2, TGF-β1, and monocyte chemoattractant protein-1 (MCP-1). Administration of LOXL2 inhibitor significantly suppressed the expression of alpha-SMA and collagen 1A, intrarenal F4/80 positive inflammatory cell infiltrations (21 ± 4 vs. 14 ± 2, p = 0.001) and improved tubular injury scores (3.6 ± 1.3 vs. 1.6 ± 1.1, p = 0.02). Moreover, LOXL2 inhibitor effectively reduced albuminuria excretion (46 ± 4 vs. 22 ± 6, p = 0.02).

Conclusion
Our results suggest that LOXL2 inhibitor treatment can attenuate CsA nephropathy progression and LOXL2 may be a potential therapeutic target in CsA nephropathy.