bluuebunny/crossref_metadata_2025 huggingface dataset:
#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

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 >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.
#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

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

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

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 < 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

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 <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 < 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

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>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

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

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 (< 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

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

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 < 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

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

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

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

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 <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

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 (<1 g/day vs ≥1 g/day), protein/creatinine ratio (<0.88 g/g vs ≥0.88 g/g), or albumin/creatinine ratio (<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 >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 <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

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 < 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

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<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

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.