bluuebunny/crossref_metadata_2025_split huggingface dataset:
#1681 Efficacy and safety of combined treatment with rituximab and low doses of cyclophosphamide for ANCA associated renal vasculitis
Authors: León-Póo Mariana , Shabaka Amir , Ortega Esther , Maldonado Maria , Navarro Juan Antonio Martín , Rodriguez-Moreno Antolina , Roldan Deborah , Juarez Gema Maria Fernandez 
Published: May 2024

Abstract

Background and Aims
Current guidelines recommend the use of rituximab (RTX) or cyclophosphamide (CP) as induction treatment for ANCA-associated vasculitis (AAV) with renal involvement. Some authors have described the combination of CP and RTX in the treatment of severe AAV, and recently a regimen of 6 cycles of low-dose CP combined with RTX has been used with good results. The aim our study was to compare the efficacy and safety of combined treatment with even lower doses of intravenous CP (2-3 cycles) and RTX, compared to standard treatment with RTX.

Method
We conducted a retrospective study that included 14 patients with histologically confirmed AAV, treated with an induction treatment scheme of corticosteroids, RTX and 2-3 cycles of intravenous CP. A case-control analysis was performed with 16 patients who received only corticosteroids and RTX in the same period, matched by propensity score for age, creatinine at presentation and histological parameters (sclerosed glomeruli, epithelial crescents and normal glomeruli). We compared renal and overall survival, and complications from immunosuppression in both groups.

Results
At presentation, patients treated with the combined regimen had a mean age of 67 ± 12.1 years, a mean glomerular filtration rate estimated by CKD-EPI of 19.8 ± 11.1 ml/min/1.73 m2, proteinuria of 1.6 (0.81- 1.84) g/24 hours and initial BVAS score of 18.5 ± 6.9. 78.6% of the patients were anti-MPO positive and 21.4% were anti-PR3 positive. According to Berden's classification, 85.7% had a mixed variant, 7.1% crescentic and 7.1% sclerotic, in the renal biopsy. The mean dose of CP was 1445 ± 384 mg, and of RTX was 2g. 28.6% required dialysis at presentation, of which 75% recovered kidney function. The duration of steroid treatment was 8 (4.6-16.9) months. Remission rate at 6 months was 71.4%, and after a median follow-up of 20 (15-35) months, 92.9% had remitted. During follow-up, 50% had serious infections; and at the end, 7.1% progressed to end-stage chronic kidney disease (ESKD). 21.4% of the patients included ended up dying. In comparison with the control group, patients who received the combined treatment had a higher remission rate (92.9% vs. 75%), a lower relapse rate (15.4% vs. 35.7%), lower progression to ESKD (7.1% vs. 20%) and lower mortality (21.4% vs 37.5%), with no differences for serious infections.

Conclusion
The association of low doses of cyclophosphamide to rituximab induction treatment could improve the prognosis in patients with severe ANCA-associated renal vasculitis.
#1770 Clinical characteristics and outcomes in patients with ANCA-associated vasculitis (AAV) and kidney involvement—a Swedish single-center cohort
Authors: Voudouri Klytaimnistra , Marttala Kerstin , Eriksson Svensson Maria K 
Published: May 2024

Abstract

Background and Aims
Poor patient outcomes in ANCA-associated vasculitis (AAV) with kidney involvement is attributed to multiple factors such as delay in diagnosis, inadequate efficacy of treatments and long-term complications due to the disease as well as the toxic effects of immunosuppressive therapy. The aim of the present study was to evaluate the clinical characteristics of a Swedish cohort of patients with AAV (granulomatosis with polyangiitis; GPA and microscopic polyangiitis; MPA) and kidney involvement to study causes of death and predictors of all-cause mortality.

Method
This retrospective single-centre cohort study included 93 patients from the Uppsala region in mid-Sweden, diagnosed with AAV and kidney involvement between 1993 and 2023. Clinical and laboratory variables were obtained from review of electronic medical records as well as patient follow-up visits. Differences between groups were assessed using independent t-test and Chi-square test. Multivariable logistic regression analyses were performed to evaluate the influence of risk factors of interest on all-cause mortality.

Results
93 patients, 71 (76%) were clinically diagnosed with MPA, and 22 (24%) with GPA. The median age at diagnosis was 66.5 ± 13 years. eGFR at diagnosis was 29 ± 23.5 ml/min/1.73 m2 and 15% of patients were dialysis-dependent AAV at diagnosis. Patients with MPA and GPA received comparable induction therapy except for PLEX which was significantly more frequent in patients with GPA (52% vs 26% respectively, p = 0.041). 56 (60%) of patients died during follow up and survival time was 7.1 ± 6.9 years. Baseline clinical and biochemical characteristics are shown in Table 1. A multivariate logistic regression showed that older age at diagnosis (OR 95% CI 1.012-1.110; p = 0.013) and being dialysis-dependent at diagnosis (OR 95% CI 1.343-16.079; p = 0.015) significantly predicted all-cause mortality (Table 2). Causes of death are presented in Fig. 1. Infections was the most common cause of death (30%).

Conclusion
Long-term prognosis and patient survival were significantly associated with age and dialysis-dependency at diagnosis in this cohort of patients diagnosed with AAV and kidney involvement. Infections was the most common cause of death.
#1940 Plasma complement activation profile in kidney transplant recipients with IgAN supports the importance of the complement alternative pathway in IgAN
Authors: Duval Anna , Obrecht Augustin , Meuleman Marie-Sophie , Durey Marie-Agnes Dragon , Gautier-Vargas Gabriela , Cognard Noelle , Perrin Peggy , Chauvet Sophie , Roumenina Lubka , Moulin Bruno , Bacchi Veronique Fremeaux , Caillard Sophie 
Published: May 2024

Abstract

Background and Aims
The alternative complement and lectin pathways are key players in IgA nephropathy (IgAN). However, the precise dynamics of complement activation in IgAN remain poorly understood. Non-invasive complement biomarkers are urgently needed in view of the evolving landscape of complement-targeting therapies under evaluation in IgAN.

Method
We analyzed plasma complement activation biomarkers in a cohort of 87 kidney transplant recipients (KTR) with IgAN and 30 controls consisting of autosomal dominant polycystic kidney disease (ADPKD) KTR (NCT05234463, DC-2013-1990). Patients were excluded if 1) they had a biological inflammatory syndrome at the time of sampling or 2) they had experienced a cellular/humoral rejection in the year prior to or after sampling. We simultaneously measured a large panel of complement activation and regulation fragments (C3a, C5a, C4a, sC5b-9, Ba, Bb) and intact proteins (C3, C4, FI, FH, properdin) in plasma using multiplex ELISA (Quidel Ortho®, A900), nephelometry and in-house ELISA.

Results
There was no consumption of C3 and C4 proteins in IgAN patients. However, C3a and Bb concentrations were elevated in IgAN patients compared to ADPKD patients (161 [98-227] vs. 102 [66-172] ng/mL, p = 0.007; 3.0 [2.6-4.0] vs. 2.5 [2.0-2.8] µg/mL, p &lt; 0.0001). Overall, 70/87 IgAN patients (80.5%) had elevated Bb levels. The plasma concentration of C5a was elevated in IgAN patients compared to ADPKD patients (6.3 [3.8-9.2] vs. 4.9 [2.8-6.3] ng/mL, p = 0.0274), with values within the reference range in 92.0% of IgAN patients. There was no difference in plasma levels of sC5b-9 between the two groups (p = 0.186). The combined analysis of C3a, C5a and sC5b-9 allowed us to distinguish 4 clusters of patients (Fig. 1). A total of 48 patients (55.2%) show evidence of C3 convertase activity in plasma (clusters 3 and 4), including 16 patients (18.4%) with the highest plasma concentrations of sC5b-9, C3a and Bb. In contrast, 15 patients (17.2%, cluster 1) have no (or very low) complement activation. The last group (n = 32, 36.8%, cluster 2) shows an isolated increase in sC5b-9 without evidence of plasma C3 convertase activity. Proteinuria was significantly increased in groups 3 and 4, which had the highest C3a concentrations, compared to groups 1 and 2 (p = 0.0051).

Conclusion
This study provides insights into the mechanisms of complement activation in IgAN, with a pivotal role for the activity and regulation of the alternative C3 pathway convertase. In addition, the combined analysis of complement biomarkers identified, for the first time, clusters of patients who may benefit from complement targeting therapies.
#2090 Kidney Biopsy by Nephrologists in Patients with Severe Renal Impairment: Complications and histological Spectrum
Authors: Meena Priti , Panda Sandip , Das Paromita , Garg Anish 
Published: May 2024

Abstract

Background and Aims
Kidney biopsy is the gold standard test for assessing kidney disease and offers pivotal insights into the diagnosis, prognosis, and treatment of kidney disorders. However, its application in patients with a diminished glomerular filtration rate (GFR) poses a heightened risk of complications. In this study, we explored the safety and utility of kidney biopsy in patients with an estimated GFR &lt;15 ml/min/1.73 m2.

Method
In this prospective study, we enrolled consecutive adult patients with an eGFR below 15 ml/min/1.73 m2 who underwent a kidney biopsy and provided informed consent. Exclusions comprised patients with solitary or transplanted kidneys or acute kidney injury. All biopsies were performed under ultrasound guidance. Following the procedure, patients were observed for 24 hours to monitor complications, and an analysis of their associated risk factors was done.

Results
Among the 88 patients included in the study, 60% were male, 20% had diabetes, and 30% were hypertensive. Chronic glomerulonephritis (45%), with IGA nephropathy being the most prevalent), chronic tubulointerstitial disease (43%), and diabetic kidney disease (12%) were the predominant histological diagnoses in kidney biopsies. Peri-renal hematomas ≥2 cm were observed in 9 patients, with three requiring blood transfusions. A major complication necessitating angioembolization occurred in one patient. The biopsy sample was deemed adequate in 80% of patients (n = 70). The requirement of blood transfusion (p &lt; 0.04) and hemodialysis before biopsy (p = 0.05) was associated with an increased risk of complications. This study suggests the safety and necessity of kidney biopsy in CKD patients, underscoring its importance for accurate diagnosis and the initiation of appropriate therapeutic measures, irrespective of GFR

Conclusion
This study suggests the safety and necessity of kidney biopsy in CKD patients, underscoring its importance for accurate diagnosis and the initiation of appropriate therapeutic measures, irrespective of GFR
#2963 Light chain deposition in the kidney is more frequent in patients with proliferative lupus nephritis
Authors: Knežević Tamara , Ivkovic Vanja , Padjen Ivan , Laganovic Mario , Biloglav Zrinka , Bulimbasic Stela , Prlic Margareta Fistrek , Ćorić Marijana , Anić Branimir 
Published: May 2024

Abstract

Background and Aims
Light chain deposition in the kidney is an important histologic feature having a significant role in the pathogenesis of glomerular and autoimmune diseases, including lupus nephritis (LN). However, there is no study examining differences in light chain deposition profile between proliferative and non-proliferative LN.

Method
We have conducted a retrospective cohort study to evaluate the characteristics and prognostic significance of light chain deposition profile in the kidney of subjects with proliferative and non-proliferative LN. We have collected data on demographics, clinical and laboratory parameters and histopathology (light, immunofluorescent and electron microscopy). Lambda domination (LD) was defined as lambda intensity—kappa intensity ≥ +1. SLE was diagnosed using the American College of Rheumatology criteria and renal outcomes per KDIGO guidelines. Proliferative LN was defined as those containing classes III and IV, while all other classes comprised non-proliferative LN.

Results
A total of 56 patients with biopsy-proven LN were followed up for at least one year after kidney biopsy (79% women, mean age at biopsy 38 ± 13 years). A total of 71% of patients had proliferative LN. Mean number of glomeruli per biopsy sample was 26 ± 12. Mean immunofluorescent intensity was 1.6 ± 1.0 for lambda and 1.8 ± 1.0 for kappa light chain. A total of 42 (75%) patients had light chain deposition in the glomerulus with 4 (7%) having restricted lambda chain deposition and none had restricted kappa chain deposition. Patients with proliferative LN had more frequent light chain deposition in glomeruli than those with non-proliferative lupus (88% vs. 57%, p = 0.049) , with no difference in LD (24% vs. 14%, p = 0.71). There was no difference between frequency of restricted lambda chain deposition between proliferative and non-proliferative LN (5% vs. 17%, p = 0.60). A total of 12 (21%) patients had LD in the glomerulus. When examining renal outcomes at one year post-biopsy, 55% of patients achieved complete response (CR), 30% achieved partial response (PR) and 15% had no response. There were no differences in achievement of remission (CR or PR) between patients with proliferative and non-proliferative LN (87% vs. 90%, p = 0.93). We also found no difference in frequency of light chain deposition and achievement of remission in proliferative or non-proliferative LN (both p&gt;0.05).

Conclusion
Light chain deposition is prevalent in LN and is more frequent in patients with proliferative LN. Further studies examining their pathophysiologic properties and potential prognostic value are much warranted.
#2240 The complex fluctuation of circulating T follicular cells in patients with lupus nephritis (LN)
Authors: Moysidou Eleni , Christodoulou Michalis , Lioulios Georgios , Nikolaidou Vasiliki , Sarafidis Pantelis , Frangou Eleni , Fylaktou Asimina , Stangou Maria 
Published: May 2024

Abstract

Background and Aims
Follicular T (TF) cells constitute a subgroup of cells recently discovered, located in the germinal center (GC) of lymphoid follicles, where they mediate B lymphocyte development, maturation, and antibody production. Meanwhile, T cells with similar markers have also been detected in the peripheral blood, considered as a circulating memory compartment with unknown origin or function. TF cells seem to be implicated in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN) by assisting the selection of high-affinity B cells in germinal centers; nonetheless, research about their circulating regimen is lacking. Herein, we describe the population of circulating TF cells in patients with LN and their association with disease hallmarks.

Method
Flow cytometry was performed to identify cTF (CD4+CD45RA-CXCR5+) cells and their subsets, defined as cTF1 (CD4+CD45RA-CXCR5+CXCR3+CCR6-), cTF2 (CD4+CD45RA-CXCR5+CXCR3-CCR6-), cTF17 (CD4+CD45RA-CXCR5+CXCR3-CCR6+), and activated-cTF, cTF-ICOS+ (CD4+CD45RA-CXCR5+ICOS+), as well as cTF-Regulatory (cTFR) (CD4+CD45RA-CXCR5+CD127-CD25+FOXP3+). Peripheral blood was collected from 25 LN patients (LN) and 25 healthy controls (HC) of similar age.

Results
Here are presented preliminary results analyzed in 15 LN patients (age = 38 ± 8yrs) and compared to 9 HC (age = 31.5 ± 7yrs).
Although our findings were not significant in total and the percentage and total number of cTFH cells were similar between LN and HC [7.1 (0.6-22.4)% and 52.57 (3.38-412.7)cells/μL, vs. 6.6 (1.9-12.1)% and 45.65 (13.3-69.6)cells/μL, respectively], the fluctuation of the different subsets is interesting. cTF-ICOS+, cTF1, cTF2, and also surprisingly cTFR cells were upregulated in LN compared to HC [0.9 (0-5.2) vs 0.51 (0-1.45)cells/μL, 9.3 (0.2-31.6) vs. 3.02 (0.4-23.08)cells/μL, 10.89 (0-47.41) vs 3.37 (0.46-39.01)cells/μL, and 0.21 (0-12) vs 0.12 (0-1.53) cells/μL, respectively], while the cTF17 compartment was condensed [5.36 (0.79-213.8) vs 8.37 (0.22-29.2)cells/μL, respectively]. Clinical and laboratory markers of the disease were then assessed, resulting in a strong positive correlation of the SLEDAI score with the percentage of cTF2 and cTFR (r = 0.643 and 0.706, respectively) and of C3 levels with cTF percentage (r = 0.663) and cTF-ICOS (+) number (r = 0.719) while the correlation was negative between C4 levels with the percentage of cTF1 (r = −0.577) and cTF2 (r = −582) and between ANA antibody levels and cTF-ICOS (+) cells (r = −657). The analysis did not show any association between the anti-dsDNA antibody levels and the understudied subpopulations.

Conclusion
cTF cells tend towards 1 and 2 rather than the 17 phenotype in LN. From the various subsets, cTF2 appear to serve as a possible monitoring marker. Certainly, the complexity of the disease imposes further investigation.
#2622 Very late renal recovery in patient with light chain cast nephropathy: the prognostic value of renal biopsy
Authors: Gaudio Costanza , Cancila Glenda , Moscato Marco , Brucia Sofia , Cuello Seni Esmer Lebron , Becherelli Paola , Marcantonio Elio D I , Fani Filippo Maria , Spatoliatore Giuseppe , Scopetani Nicoletta , Fortunato Laura , Rosati Alberto 
Published: May 2024

Abstract

Background and Aims
Renal biopsy is not necessary to assess LCCN (Light Chain Cast Nephropathy) in patients with laboratory features suggestive of the disease. However, it has been shown that the histological picture often correlates with renal outcome.
We present the case of a 55-year-old man with no significant previous medical history that was evaluated in the emergency department for a stage 3 AKI (sCr 17.3 mg/dl, eGFR 3 ml/min/1.73 m2). Laboratory tests showed a Lambda Micromolecular Myeloma (K chains 44.6 mg/l, λ 4160 mg/l and K/ λ 0.01); Bence Jones not evaluable due to anuria. Bone marrow plasmacytosis was 70%.

Method
The patient started chemotherapy with Bortezomib and Dexamethasone and hemodialysis thrice a week with a PMMA hemofilter in order to improve the FLC (Free Light Chain) removal rate. After three months of treatment the patient achieved a complete hematologic response but he didn't reach any renal response. In order to assess a more precise renal prognosis a kidney biopsy was performed. The histopathological exam showed a Cast Nephropathy (&lt; 5 casts/mm2) associated with low grade interstitial fibrosis and tubular atrophy (IFTA +1).
After 5 cycles with Bortezomib and Dexamethasone, one year after onset, the patient underwent ASCT (Autologous Stem Cell Transplantation).

Results
In the following months, a progressive increase in renal function allowed us to perform a gradual reduction of dialysis rate, until discontinuation occurred 16 months after disease onset. To date, three years after onset, complete hematologic and renal remission persists with an eGFR of 20 ml/min/1.73 m2.

Conclusion
Renal biopsy, performed even several months after disease onset, could play a pivotal role in cases of LCCN with a discordance between hematologic and renal response. A low cast number and low IFTA grade are known to be positive prognostic factors for renal outcome and they can predict a renal recovery that sometimes could be exceptionally late.
#1833 Analysis of clinical and laboratory manifestations in different classes of lupus nephritis—a Serbian single center experience
Authors: Golubović Sonja , Đurović Vladimir , Glogonjac Nikola , Šajinović Slobodan , Veselinov Vladimir , Majstorović Gordana Stražmešter , Celic Dejan , Petrovic Lada 
Published: May 2024

Abstract

Background and Aims
Lupus nephritis represents one of the most serious manifestations of systemic lupus erythematosus. The gold standard for determining the class of lupus nephritis is percutaneous kidney biopsy and the histopathological analysis of the biopsy specimen. The aim of this study was to analyze the clinical and laboratory characteristics of different histopathological classes of lupus nephritis (LN) at the time of the systemic lupus diagnosis and onset of symptoms.

Method
This retrospective cross-sectional study included a total of 54 subjects who were hospitalized at the Clinic for Nephrology and Clinical Immunology of the University Clinical Center of Vojvodina from 2017 to 2022 and underwent percutaneous kidney biopsy. Available clinical and laboratory data, as well as the histopathological findings of kidney biopsies, were analyzed. Based on the histopathological classification, patients were divided into four groups (Class II, III, IV, and V), and the clinical and laboratory characteristics were analyzed for all subjects. Due to a low number of patients, no analysis of Class I and Class VI was made.

Results
The most prevalent class among the subjects was Class IV, in which the lowest values of the C3 complement component were recorded. Subjects in this LN class had higher blood pressure values, a higher frequency of clinical manifestations such as arthralgia, and joint swelling. Class IV LN was also associated with elevated anti-dsDNA antibody values with a significant statistical significance (p = 0.004), lower red blood cell parameters, and higher levels of nitrogenous substances compared to other classes. The lowest values of total serum proteins and albumins, as well as the highest values of total cholesterol, LDL cholesterol, and triglycerides, were observed in the group of subjects with Class V LN; C-reactive protein had the highest average values in Class III and IV, which showed a statistical significance (p = 0.007). The lowest values of total serum calcium and iron were in Class III, and 24-hour proteinuria was most pronounced in Class V (p = 0.001), whereas microscopic hematuria was most present in Class II LN (p = 0.03).

Conclusion
Patients with lupus nephritis exhibit different clinical and laboratory manifestations based on histopathological classification and the time of diagnosis. The results of this study suggest their potential use in diagnosis, assessment of histopathological classification, and the development of a targeted and personalized therapeutic approach. These parameters will be used to develop machine learning models which might help in further evaluation and treatment.