Can Erythrocyte Sedimentation Rate Predict Hypersensitivity Reactions to Rituximab Therapy in Kidney Diseases?

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Omer Faruk Akcay, Asil Demirezen, Yigit Kiran, Ulver Derici, Galip Guz, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5951214/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: This study investigates hypersensitivity reactions (HSRs) associated with rituximab therapy in nephrology patients, focusing on identifying potential risk factors. Methods Records of patients treated in our unit with rituximab for kidney diseases were reviewed between January 2019 and June 2024. Demographic, clinical, and laboratory data were evaluated to identify risk factors for HSRs. Patients were premedicated with paracetamol, diphenhydramine, and corticosteroids before rituximab infusions. Binary logistic regression analyses were performed to determine independent risk factors. Receiver operating characteristic (ROC) curve analysis were plotted to illustrate the best cut-off values of risk factors for HSRs estimation. Results 170 patients received rituximab therapy with 447 treatment doses for nephrological indications. Rituximab treatment was indicated for MN in 89/150 (57%) patients with native kidney disease. HSRs were observed in 14% of patients, including infusion-related reactions (IRRs, 10%) and rituximab-induced serum sickness (RISS, 4%). The majority of HSRs (61%) occurred during the first infusion. RISS cases were observed exclusively in patients with MN. Elevated erythrocyte sedimentation rate (ESR) was identified as an independent risk factor for HSRs (OR: 1.020, 95% CI: 1.002–1.038, p = 0.027). Besides, ESR demonstrated its predictive value for HSRs with an area under the curve (AUC) of 0.73 (95% CI: 0.637–0.826, p < 0.001), achieving a sensitivity of 74% and a specificity of 66% at a cutoff value of 38.5 mm/hour. Conclusion Elevated baseline ESR levels may serve as a predictive marker for HSRs in nephrology patients treated with rituximab. Premedication with corticosteroids may have resulted in a lower incidence of adverse events. Further prospective studies are needed to validate ESR as a biomarker for HSRs risk stratification. Hypersensitivity reactions Infusion related reactions Rituximab Erythrocyte Sedimentation Rate Serum Sickness Disease Figures Figure 1 Figure 2 Figure 3 Introduction Rituximab has established itself as a key therapeutic agent due to its efficacy and safety profile in diverse patient populations following its FDA approval in 1997. A monoclonal antibody targeting the CD20 antigen on B lymphocytes, rituximab has been widely utilized in treating B-cell lymphomas and several autoimmune conditions [ 1 ]. Despite its broad therapeutic utility, rituximab is associated with a spectrum of adverse reactions broadly categorized as immunodeficiency and hypersensitivity reactions (HSRs). While immunodeficiency is an expected outcome of its B-cell-depleting mechanism, HSRs are more complex and less predictable, often complicating patient management. HSRs to rituximab are typically categorized as infusion-related reactions (IRRs) or rituximab-induced serum sickness (RISS). IRRs are the most frequent, occurring during or shortly after infusion, and often manifest as fever, chills, and rigors, though severe cases may involve hypotension, bronchospasm, or angioedema [ 2 ]. Reported IRR incidence varies widely, from 25.7–85%, depending on factors such as underlying disease and premedication protocols [ 3 , 4 ]. In contrast, RISS, a delayed-type III hypersensitivity reaction, emerges 5 to 21 days post-infusion and is characterized by complement-fixing IgM and IgG antibodies targeting rituximab epitopes. Clinical manifestations include fever, rash, and polyarthritis, which, although less frequent than IRRs, may still present significant challenges to patient management [ 5 , 6 ]. Rituximab has become integral to treating diseases such as membranous nephropathy (MN), minimal change disease (MCD), and ANCA-associated vasculitis (AAV) [ 7 , 8 ]. While its efficacy is well-established, data on hypersensitivity reactions in nephrology remain limited, with most studies relying on small cohorts [ 9 ]. Existing research on rituximab hypersensitivity is predominantly derived from hematology, oncology, and rheumatology populations, leaving gaps in our understanding of these reactions in patients with renal conditions [ 3 , 4 ]. In this study, we aimed to address this gap by evaluating the incidence, clinical features, and risk factors for hypersensitivity reactions in a large cohort of patients with kidney disease. Materials and Methods Study Population This retrospective study evaluated adult patients (≥ 18 years) who underwent rituximab therapy for various nephrological conditions, including primary MN, MCD, AAV, focal segmental glomerulosclerosis (FSGS), or antibody-mediated rejection (ABMR) at our institution between January 2019 and June 2024. Exclusion criteria were applied to individuals who met any of the following conditions: (1) age under 18 years, (2) rituximab administration for conditions unrelated to nephrology, such as hematological malignancies, or (3) incomplete baseline demographic or clinical data. Data Collection Patient demographic, clinical, and laboratory data prior to rituximab treatment were retrospectively analyzed. Factors such as sex, age, body mass index (BMI), comorbidities such as diabetes mellitus (DM) and rheumatologic diseases, ongoing steroid therapy, and transplantation history were reviewed. Biochemical parameters assessed were serum albumin levels, estimated glomerular filtration rate (eGFR), hematocrit, neutrophil count, lymphocyte count, platelet count, 24-hour urine protein excretion, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Clinical and laboratory findings were evaluated to identify potential risk factors for HSRs. Our study exclusively used baseline laboratory values obtained before the first dose of rituximab to accurately assess the patients' initial status and avoid the confounding effects that could result from treatment-related changes in subsequent doses. Rituximab Administration Patients received an initial dose of 1000 mg of rituximab for the first and second administrations, given two weeks apart under KDIGO (Kidney Disease Improving Global Outcomes) guideline recommendations [ 7 ]. Premedication included 1 g of oral paracetamol, 50 mg of intravenous (IV) diphenhydramine hydrochloride, and 100 mg of intravenous methylprednisolone (MPZ). The required dose of rituximab was diluted in normal saline to achieve a final concentration of 1 mg/mL. The infusion began at 50 mL/h, with vital signs monitored every 15 minutes. If no adverse events, such as infusion-related reactions (IRRs), occurred, the infusion rate was increased by 50 mL/h every 30 minutes, up to a maximum rate of 400 mL/h. Classification and Severity of Hypersensitivity Reactions This study evaluated the occurrence of HSRs, including IRRs and RISS, in patients receiving rituximab. IRRs were identified when symptoms such as fever (> 38.0°C), chills, malaise, itching, headache, facial flushing, hypotension, nausea, or vomiting occurred within 24 h after rituximab infusion, as recorded by physicians or nurses. Hypotension was a systolic blood pressure below 90 mmHg or a 30% drop from baseline. IRRs were classified using the modified Brown criteria [ 10 ]: Grade I (mild) included skin-related symptoms; Grade II (moderate) involved multiple organ systems without vital sign changes; and Grade III (severe) featured vital sign changes, such as hypotension or oxygen desaturation. RISS is characterized by the hallmark symptoms of rash, fever, and polyarthralgia or polyarthritis, typically emerging 5–21 days after rituximab administration. Diagnoses of both IRRs and RISS were confirmed by two physicians, who reviewed hospital records independently. The confirmation process involved assessing documented symptoms, their timing, and the exclusion of alternative causes, such as infections or unrelated drug reactions. Statistical Analysis Numerical data were summarized using descriptive statistics by their distribution. Variables with normal distribution are presented as means with standard deviations, and variables without normal distribution as medians and interquartile ranges. Counts (n) and percentages (%) were used to define nominal data. Mann-Whitney U test was used for numerical variables without normal distribution, while the independent samples t-test was applied for normally distributed variables for group comparison. Chi-square or Fisher's exact tests were used in nominal variables to compare data. Binary logistic regression analyses were employed to identify independent risk factors associated with HSRs; variables with a p-value of less than 0.1 in the univariate analysis were chosen to include in the multivariate analysis. In addition, receiver operating characteristic (ROC) curve analysis were plotted to illustrate the best cut-off values of risk factors for HSRs estimation. p < 0.05 was determined as the threshold for statistical significance. SPSS software, version 20.0 (IBM Corp., Chicago, IL, USA), was operated to conduct all statistical analyses. Results This study included a total of 170 patients who received rituximab therapy for nephrological indications, with a total of 447 treatment doses. 14% (n = 23) of participants developed HSRs after rituximab administration. The study cohort comprised 42% female participants, with a median age of 48 (45–59). In patients with native kidney disease (n = 155), rituximab treatment was indicated for MN in 89 (57%) patients, MCD-FSGS in 30 (19%) patients, and AAV in 25 (17%) patients. In patients with kidney transplantation (n = 15), the most common indication for rituximab therapy was ABMR (73%). The median ESR was higher in patients with HSRs [48 (33–70) vs. 28 (15–46) mm/h; p < 0.001, respectively]. Other demographic characteristics were similar throughout the cohort, as outlined in Table 1 . Table 1 General characteristics of the patients who developed hypersensitivity reactions after rituximab treatment Total n: 170 No HSRs n: 147 (86%) HSRs n: 23 (14%) p value Age , years 48 (35–59) 49 (35–60) 48 (35–57) 0.84 Female , n (%) 72 (42%) 61 (42%) 11 (48%) 0.56 DM , n (%) 34 (20%) 30 (20%) 4 (18%) 1.00 Rheumatologic disease , n (%) 16 (9%) 15 (10%) 1 (4%) 0.70 BMI (kg/m 2 ) 24.6 (22.8–27.3) 24.6 (22.8–27.3) 24.4 (22.8–27.2) 0.92 Transplantation history , n (%) 15 (9%) 13 (9%) 2 (9%) 1.00 Current steroid therapy , n (%) 131 (77%) 113 (77%) 18 (78%) 0.88 RAAS inhibitors , n (%) 128 (75%) 111 (76%) 17 (74%) 0.92 Neutrophil count (/uL) 5190 (3700–7400) 5350 (3700–7500) 4600 (3500–6100) 0.93 Lymphocyte count (/uL) 1900 (1300–2600) 2000 (1300–2600) 1500 (800–2800) 0.22 Hematocrit (%) 38.6 (34.2–42.6) 38.8 (35-42.9) 37.7 (30.8–40.9) 0.14 eGFR (mL/min/1.73m²) 81 (44–106) 82 (44–107) 76 (37–96) 0.42 Albumin (g/dL) 3.4 (3-3.8) 3.4 (3-3.8) 3.6 (28 − 3.9) 0.83 CRP (mg/L) 3.1 (2-4.4) 3.1 (1.9-4) 3.6 (3-5.8) 0.07 ESR (mm/h) 29 (16–49) 28 (15–46) 48 (33–70) < 0.001 Serum LDL (mg/dL) 130 (112–179) 139 (111–183) 147 (126–158) 0.80 NLR (%) 2.7 (1.8–4.4) 2.8 (1.8–4.3) 2.3 (1.6–6.2) 0.75 PLR (%) 134 (93–187) 132 (93–186) 144 (86–279) 0.28 Proteinuria (mg/24h) 3475 (1872–7073) 3486 (1872–7308) 2972 (1638–6262) 0.57 Transplant indication (n = 15) Rejection Other 11 (73%) 4 (27%) 9 (69%) 4 (31%) 2 (100%) 0 (0%) NA Native indication (n = 155) Membranous MCD- FSGS AAV Other 89 (57%) 30 (19%) 25 (17%) 11 (7%) 75 (56%) 25 (19%) 23 (17%) 11 (8%) 14 (67%) 5 (24%) 2 (9%) 0 (0%) 0.55 AAV : ANCA-associated vasculitis, BMI : Body mass index, DM : Diabetes mellitus, eGFR : Estimated glomerular filtration rate, ESR : Erythrocyte sedimentation rate, FSGS : Focal segmental glomerulosclerosis, LDL : Low-density lipoprotein, MCD : Minimal change disease, NLR : Neutrophil- lymphocyte ratio, PLR : Platelet- lymphocyte ratio, RAAS : Renin-angiotensin-aldosterone system Among patients with HSRs, 17 (74%) experienced IRRs, while 6 (26%) developed RISS. Reactions occurred with the first therapy dose in 61% (n = 14), the second dose in 26% (n = 6), and the third or later in the remaining patients (Fig. 1 A-B). Of patients with IRRs, 53% (n = 9) had mild (grade I) reactions, 35% (n = 6) had moderate (grade II) reactions, and 12% (n = 2) had severe (grade III) reactions (Fig. 2 ). We also found that the treatment indication for all patients with RISS was primary MN. During follow-up, rituximab treatment was discontinued in 10/170 (6%) patients due to HSRs. Binary logistic regression identified several potential risk factors for HSRs in univariate analysis, including lower hematocrit (Odds Ratio [OR]: 0.942, 95% Confidence Interval [CI]: 0.882–1.005), higher ESR (OR: 1.024, 95% CI: 1.009–1.039), and elevated PLR (HR: 1.003, 95% CI: 1.000-1.006). In multivariate analysis, only higher ESR remained statistically significant (OR: 1.020, 95% CI: 1.002–1.038, p = 0.027) (Table 2 ). ESR levels of the patients with IRRs and RISS were comparable [53 (36–74) vs. 44.5 (23–54) mm/h, p = 0.3]. In addition, we plotted ROC curve to define the best cutoff values of ESR to predict rituximab-related HSRs (Fig. 3 ). We found that 35.5 mm/h was the best cutoff value for ESR with 74% sensitivity and 66% specificity (AUC:0.73, 95% CI: 0.637–0.826, p < 0.001). Table 2 Univariate and multivariate analysis of risk factors for the hypersensitivity reactions due to rituximab treatment Univariate, OR (%95 CI) p value Multivariate, OR (%95 CI) p value Age 1.000 (0.972–1.028) 0.988 Sex 0.774 (0.320–1.868) 0.569 Current steroid therapy 1.083 (0.374–3.134) 0.883 Hematocrit 0.942 (0.882–1.005) 0.071 0.984 (0.913–1.62) 0.684 eGFR 0.995 (0.983–1.008) 0.452 CRP 1.035 (0.985–1.088) 0.175 ESR 1.024 (1.009–1.039) 0.002 1.020 (1.002–1.038) 0.027 NLR 1.057 (0.958–1.166) 0.269 PLR 1.003 (1.000-1.006) 0.044 1.001 (0.997–1.004) 0.664 CRP : C-reactive protein, eGFR : Estimated glomerular filtration rate, ESR : Erythrocyte sedimentation rate, NLR : Neutrophil- lymphocyte ratio, PLR : Platelet- lymphocyte ratio Discussion In this study, the primary indication for rituximab therapy was primary MN, accounting for 57% of the cases with native kidney diseases. We observed that the prevalence of HSRs among our cohort was 14%, with IRRs typically presenting as mild to moderate in severity. Notably, patients who experienced HSRs exhibited significantly higher ESR levels prior to the administration of rituximab. In recent years, the use of rituximab in nephrology has significantly increased, with current KDIGO guidelines recommending it for various glomerular diseases [ 7 ]. Rituximab is indicated for AAV, primary MN, relapsing MCD, and select cases of lupus nephritis. It is as effective as cyclophosphamide in inducing remission in AAV, with superior efficacy in maintenance therapy and a lower risk of malignancy and treatment-related burdens [ 11 – 13 ]. In primary MN, rituximab demonstrates comparable efficacy to traditional therapies regarding survival and remission rates, establishing itself as a first-line treatment for patients with moderate to high risk of declining kidney function [ 7 , 14 ]. Despite its widespread use in nephrology for various indications, data on rituximab-associated HSRs in this population remain unclear. Rituximab has been linked to serious adverse events, including fatal infusion reactions and severe mucocutaneous reactions. We observed a significantly lower incidence of adverse events related to rituximab infusion. Specifically, only 10% of our patients experienced IRRs. Our premedication approach differs significantly from previous studies evaluating IRRs to rituximab. Moore et al. reported a prevalence of 65% in CLL patients, and Cho et al. reported a prevalence of 43.3% in NHL patients [ 15 , 16 ]. In those studies, patients typically received only paracetamol and an H1 receptor antagonist as premedication. However, our protocol includes the administration of corticosteroids prior to rituximab infusions. This practice may contribute to our patients' lower incidence of IRRs. Studies on rituximab in RA and lupus, where intravenous corticosteroids were also part of the premedication regimen, reported infusion reaction rates more comparable to our findings [ 16 , 17 ]. Patients in both studies were given MPZ 100 mg IV before rituximab infusion, similar to our daily practice. Besides, Jung et al. demonstrated that corticosteroid premedication reduced the incidence of IRRs during the first rituximab infusion fivefold (8.3% compared to 41.2%) [ 3 ]. While corticosteroid premedication has effectively reduced IRRs, further studies are needed to standardize protocols across nephrology practices. On the other hand, the true prevalence of RISS is unknown, but it may be around 10% in autoimmune disorders. A systematic review identified 33 cases of RISS from 25 articles, with a predominantly female patient population (77%) and a mean age of 39 years, likely due to the high association with autoimmune conditions (85%) [ 5 ]. In trials of rituximab for Sjogren's syndrome, 9.8% of patients developed RISS, while a prospective study also reported a prevalence of 9.1% RISS in hepatitis C virus-induced cryoglobulinemic vasculitis [ 18 , 19 ]. Autoimmune diseases, particularly lupus, appear to predispose patients to RISS, as evidenced by its higher prevalence in such cases compared to hematological malignancies. The mechanism behind this condition may involve B-cell lysis induced by rituximab leading to antigen-antibody complex formation, especially in patients with autoimmune disorders with elevated autoantibody production and reduced clearance of immune complexes [ 18 ]. Our study observed a 4% prevalence of RISS, with all affected patients having MN. Based on prior findings, producing M-type phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A antibodies in MN patients may be linked to this condition. Several risk factors for rituximab-related IRRs have been identified across different conditions, including bulky disease and low-grade disease in patients with B-cell lymphomas and higher actual body weight in malignant hematology patients [ 20 , 21 ]. D'Arena et al. demonstrated a model to predict adverse drug reactions in rituximab therapy, including the history of allergy, splenomegaly, female sex, and hb ≥ 13 g/dl [ 22 ]. However, these factors were not significant in our cohort, likely due to the distinct characteristics of nephrology patients compared to hematology populations. Our study found that elevated baseline ESR levels represent an independent risk factor for HSRs. A previous study has demonstrated that Stevens-Johnson syndrome, a delayed-type HSR that can occur after mycoplasma pneumonia infection, is associated with elevated ESR [ 23 ]. Researchers have linked this phenomenon to cold agglutinins during mycoplasma infections. Furthermore, a recent study reported that serum anti-PLA2R-IgG and -IgG4 levels correlated with high-density lipoprotein levels and ESR in patients with MN [ 24 ]. However, our study found no significant differences between the groups in hematocrit, proteinuria levels, or disease distribution. It is plausible that the elevated baseline ESR observed in our study is related to disease-associated autoantibodies that were not assessed, indirectly contributing to the development of HSRs. Although our data are retrospective and preliminary, pre-treatment ESR values exceeding 35.5 mm/h may be a potential marker for an increased risk of HSRs in nephrology patients. These findings highlight the necessity for further research to assess the clinical utility of ESR in risk stratification. As a retrospective study, our findings may underestimate the overall incidence of HSRs as some mild cases may have been missed. Our study's relatively low incidence of HSRs likely reflects the daily practice setting from which our data were derived and the liberal use of prophylactic corticosteroids in our center. Also, the lack of PLA2R antibody levels in some patients with MN prevented us from an additional analysis for HSRs in this subgroup of patients. Despite these limitations, our study is the first large-scale investigation involving over 150 patients with nephrological indications from a single center to identify risk factors for rituximab-related HSRs. In addition, to our knowledge, it is the only study that provides the frequency of the RISS in nephrology patients receiving rituximab treatment. Conclusion Our study highlights a 'real-world' clinical perspective, indicating an approximate 14% incidence of HSRs to rituximab in patients with nephrological conditions. Notably, elevated baseline ESR levels emerged as a potential predictive marker for these reactions. Given the reduced incidence of HSRs observed in our cohort and other populations receiving intravenous corticosteroid premedication, we advocate for the routine inclusion of corticosteroids in premedication protocols for nephrology patients undergoing rituximab therapy. While rituximab is generally well-tolerated, further research, specifically in a prospective manner, is needed to explore the utility of ESR and other biomarkers in predicting HSRs in nephrological indications. Abbreviations AAV ANCA-associated vasculitis ABMR Antibody-mediated rejection AUC Area under the curve BMI Body mass index CLL Chronic lymphocytic leukemia CRP C-reactive protein DM Diabetes mellitus eGFR Estimated glomerular filtration rate ESR Erythrocyte sedimentation rate FSGS Focal segmental glomerulosclerosis HSRs Hypersensitivity reactions IRRs Infusion-related reactions KDIGO Kidney Disease Improving Global Outcomes MCD Minimal change disease MN Membranous nephropathy MPZ Methylprednisolone NHL Non-Hodgkin lymphoma OR Odds Ratio PLA2R Phospholipase A2 receptor RA Rheumatoid arthritis RISS Rituximab-induced serum sickness ROC Receiver operating characteristic Declarations Author contributions Concept – OFA, OH; Design – OFA, OH, AD; Supervision –OFA, UD, GG, OH; Analysis and/or Interpretation –OFA, YK, OH; Literature Search –OFA, AD, YK; Writing –OFA; Critical Reviews – OFA, UD, GG, OH. Acknowledgements Not applicable. Funding The authors did not receive any funding. Data availability The data supporting the findings of this study are not publicly available due to the inclusion of information that may compromise the privacy of research participants. However, they can be obtained from the corresponding author (O.F.A.) upon reasonable request. Ethics Statement Gazi University Faculty of Medicine review board reviewed and approved the study protocol in compliance with the Declaration of Helsinki and ethical guidelines for human research. This retrospective study was based on standard clinical practice, so informed consent was not required. Consent for publication Not applicable. Conflict of Interest Statement The authors have no conflicts of interest to declare. Author details 1 Gazi University Faculty of Medicine, Department of Nephrology, Ankara, Türkiye 2 Gazi University Faculty of Medicine, Department of Internal Medicine, Ankara, Türkiye References Cerny T, Borisch B, Introna M, et al. Mechanism of action of rituximab. 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Review of the Role of Rituximab in the Management of Adult Minimal Change Disease and Immune-Mediated Focal and Segmental Glomerulosclerosis. Glomerular Dis. 2023;3(1):211–19. Nishiura H, Takahashi M, Mori K, et al. Patients with infusion-related reactions on fixed-dose rituximab treatment have higher body surface area than those without infusion-related reactions in adults with frequently relapsing minimal change nephrotic syndrome: a retrospective study. J Pharm Health Care Sci. 2024;10(1):12. Brown SG. Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol. 2004;114(2):371–6. Smith RM, Jones RB, Specks U, et al. Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis. Ann Rheum Dis. 2020;79(9):1243–49. Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221–32. van Daalen EE, Rizzo R, Kronbichler A, et al. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5951214","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":444596737,"identity":"7fb3825f-53c5-4e5e-bdb5-b785837fef3c","order_by":0,"name":"Omer Faruk Akcay","email":"data:image/png;base64,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","orcid":"","institution":"Gazi University","correspondingAuthor":true,"prefix":"","firstName":"Omer","middleName":"Faruk","lastName":"Akcay","suffix":""},{"id":444596741,"identity":"12608c5b-f3d6-4d54-9d2d-90db3fd2ebf6","order_by":1,"name":"Asil Demirezen","email":"","orcid":"","institution":"Gazi University","correspondingAuthor":false,"prefix":"","firstName":"Asil","middleName":"","lastName":"Demirezen","suffix":""},{"id":444596743,"identity":"b021c786-f702-4e42-84b8-a0a530980ee9","order_by":2,"name":"Yigit Kiran","email":"","orcid":"","institution":"Gazi University","correspondingAuthor":false,"prefix":"","firstName":"Yigit","middleName":"","lastName":"Kiran","suffix":""},{"id":444596744,"identity":"93607570-32e3-4cfc-b479-d0fa110d1308","order_by":3,"name":"Ulver Derici","email":"","orcid":"","institution":"Gazi University","correspondingAuthor":false,"prefix":"","firstName":"Ulver","middleName":"","lastName":"Derici","suffix":""},{"id":444596745,"identity":"e7641864-879b-4dba-a199-bacab3b72b7f","order_by":4,"name":"Galip Guz","email":"","orcid":"","institution":"Gazi University","correspondingAuthor":false,"prefix":"","firstName":"Galip","middleName":"","lastName":"Guz","suffix":""},{"id":444596746,"identity":"917a8917-5a27-4510-bba4-c2b72ede8a00","order_by":5,"name":"Ozant Helvaci","email":"","orcid":"","institution":"Gazi University","correspondingAuthor":false,"prefix":"","firstName":"Ozant","middleName":"","lastName":"Helvaci","suffix":""}],"badges":[],"createdAt":"2025-02-03 13:08:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5951214/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5951214/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":81542332,"identity":"5e98871d-51e5-483a-91f3-7d96c58bfaa0","added_by":"auto","created_at":"2025-04-28 11:19:49","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":60572,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA-B: \u003c/strong\u003eClinical Characteristics of Hypersensitivity Reactions with Rituximab Therapy\u003c/p\u003e","description":"","filename":"Figure1AB.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5951214/v1/45a969f51a4b11cfb353f5e2.jpg"},{"id":81543946,"identity":"1726df17-62b3-4af1-9896-8c7fdf596153","added_by":"auto","created_at":"2025-04-28 11:27:49","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":29752,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA-B: \u003c/strong\u003eSeverity of Infusion-Related Reactions due to Rituximab Therapy\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5951214/v1/c10abb282a40c89b48b8a6eb.jpg"},{"id":81542330,"identity":"ae3530a3-8f99-48f5-9d14-fafeb452950f","added_by":"auto","created_at":"2025-04-28 11:19:49","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":37766,"visible":true,"origin":"","legend":"\u003cp\u003eReceiving Operative Characteristic Curve to define the best cutoff value of erythrocyte sedimentation rate to predict hypersensitivity reactions with rituximab therapy\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5951214/v1/926e4ea91102c10bb6c10a81.jpg"},{"id":85973476,"identity":"b6eb6ae6-c36d-427f-b067-b26142c48eef","added_by":"auto","created_at":"2025-07-03 20:01:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":934239,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5951214/v1/75d64f37-96b2-4cd1-90e3-76ee4ac34a29.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Can Erythrocyte Sedimentation Rate Predict Hypersensitivity Reactions to Rituximab Therapy in Kidney Diseases?","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRituximab has established itself as a key therapeutic agent due to its efficacy and safety profile in diverse patient populations following its FDA approval in 1997. A monoclonal antibody targeting the CD20 antigen on B lymphocytes, rituximab has been widely utilized in treating B-cell lymphomas and several autoimmune conditions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Despite its broad therapeutic utility, rituximab is associated with a spectrum of adverse reactions broadly categorized as immunodeficiency and hypersensitivity reactions (HSRs). While immunodeficiency is an expected outcome of its B-cell-depleting mechanism, HSRs are more complex and less predictable, often complicating patient management.\u003c/p\u003e \u003cp\u003eHSRs to rituximab are typically categorized as infusion-related reactions (IRRs) or rituximab-induced serum sickness (RISS). IRRs are the most frequent, occurring during or shortly after infusion, and often manifest as fever, chills, and rigors, though severe cases may involve hypotension, bronchospasm, or angioedema [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Reported IRR incidence varies widely, from 25.7\u0026ndash;85%, depending on factors such as underlying disease and premedication protocols [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In contrast, RISS, a delayed-type III hypersensitivity reaction, emerges 5 to 21 days post-infusion and is characterized by complement-fixing IgM and IgG antibodies targeting rituximab epitopes. Clinical manifestations include fever, rash, and polyarthritis, which, although less frequent than IRRs, may still present significant challenges to patient management [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRituximab has become integral to treating diseases such as membranous nephropathy (MN), minimal change disease (MCD), and ANCA-associated vasculitis (AAV) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. While its efficacy is well-established, data on hypersensitivity reactions in nephrology remain limited, with most studies relying on small cohorts [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Existing research on rituximab hypersensitivity is predominantly derived from hematology, oncology, and rheumatology populations, leaving gaps in our understanding of these reactions in patients with renal conditions [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In this study, we aimed to address this gap by evaluating the incidence, clinical features, and risk factors for hypersensitivity reactions in a large cohort of patients with kidney disease.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eThis retrospective study evaluated adult patients (\u0026ge;\u0026thinsp;18 years) who underwent rituximab therapy for various nephrological conditions, including primary MN, MCD, AAV, focal segmental glomerulosclerosis (FSGS), or antibody-mediated rejection (ABMR) at our institution between January 2019 and June 2024.\u003c/p\u003e \u003cp\u003eExclusion criteria were applied to individuals who met any of the following conditions: (1) age under 18 years, (2) rituximab administration for conditions unrelated to nephrology, such as hematological malignancies, or (3) incomplete baseline demographic or clinical data.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003ePatient demographic, clinical, and laboratory data prior to rituximab treatment were retrospectively analyzed. Factors such as sex, age, body mass index (BMI), comorbidities such as diabetes mellitus (DM) and rheumatologic diseases, ongoing steroid therapy, and transplantation history were reviewed. Biochemical parameters assessed were serum albumin levels, estimated glomerular filtration rate (eGFR), hematocrit, neutrophil count, lymphocyte count, platelet count, 24-hour urine protein excretion, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Clinical and laboratory findings were evaluated to identify potential risk factors for HSRs. Our study exclusively used baseline laboratory values obtained before the first dose of rituximab to accurately assess the patients' initial status and avoid the confounding effects that could result from treatment-related changes in subsequent doses.\u003c/p\u003e\n\u003ch3\u003eRituximab Administration\u003c/h3\u003e\n\u003cp\u003ePatients received an initial dose of 1000 mg of rituximab for the first and second administrations, given two weeks apart under KDIGO (Kidney Disease Improving Global Outcomes) guideline recommendations [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Premedication included 1 g of oral paracetamol, 50 mg of intravenous (IV) diphenhydramine hydrochloride, and 100 mg of intravenous methylprednisolone (MPZ). The required dose of rituximab was diluted in normal saline to achieve a final concentration of 1 mg/mL. The infusion began at 50 mL/h, with vital signs monitored every 15 minutes. If no adverse events, such as infusion-related reactions (IRRs), occurred, the infusion rate was increased by 50 mL/h every 30 minutes, up to a maximum rate of 400 mL/h.\u003c/p\u003e\n\u003ch3\u003eClassification and Severity of Hypersensitivity Reactions\u003c/h3\u003e\n\u003cp\u003eThis study evaluated the occurrence of HSRs, including IRRs and RISS, in patients receiving rituximab. IRRs were identified when symptoms such as fever (\u0026gt;\u0026thinsp;38.0\u0026deg;C), chills, malaise, itching, headache, facial flushing, hypotension, nausea, or vomiting occurred within 24 h after rituximab infusion, as recorded by physicians or nurses. Hypotension was a systolic blood pressure below 90 mmHg or a 30% drop from baseline.\u003c/p\u003e \u003cp\u003eIRRs were classified using the modified Brown criteria [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]: Grade I (mild) included skin-related symptoms; Grade II (moderate) involved multiple organ systems without vital sign changes; and Grade III (severe) featured vital sign changes, such as hypotension or oxygen desaturation. RISS is characterized by the hallmark symptoms of rash, fever, and polyarthralgia or polyarthritis, typically emerging 5\u0026ndash;21 days after rituximab administration.\u003c/p\u003e \u003cp\u003eDiagnoses of both IRRs and RISS were confirmed by two physicians, who reviewed hospital records independently. The confirmation process involved assessing documented symptoms, their timing, and the exclusion of alternative causes, such as infections or unrelated drug reactions.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eNumerical data were summarized using descriptive statistics by their distribution. Variables with normal distribution are presented as means with standard deviations, and variables without normal distribution as medians and interquartile ranges. Counts (n) and percentages (%) were used to define nominal data. Mann-Whitney U test was used for numerical variables without normal distribution, while the independent samples t-test was applied for normally distributed variables for group comparison. Chi-square or Fisher's exact tests were used in nominal variables to compare data. Binary logistic regression analyses were employed to identify independent risk factors associated with HSRs; variables with a p-value of less than 0.1 in the univariate analysis were chosen to include in the multivariate analysis. In addition, receiver operating characteristic (ROC) curve analysis were plotted to illustrate the best cut-off values of risk factors for HSRs estimation. p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was determined as the threshold for statistical significance. SPSS software, version 20.0 (IBM Corp., Chicago, IL, USA), was operated to conduct all statistical analyses.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThis study included a total of 170 patients who received rituximab therapy for nephrological indications, with a total of 447 treatment doses. 14% (n\u0026thinsp;=\u0026thinsp;23) of participants developed HSRs after rituximab administration. The study cohort comprised 42% female participants, with a median age of 48 (45\u0026ndash;59). In patients with native kidney disease (n\u0026thinsp;=\u0026thinsp;155), rituximab treatment was indicated for MN in 89 (57%) patients, MCD-FSGS in 30 (19%) patients, and AAV in 25 (17%) patients. In patients with kidney transplantation (n\u0026thinsp;=\u0026thinsp;15), the most common indication for rituximab therapy was ABMR (73%). The median ESR was higher in patients with HSRs [48 (33\u0026ndash;70) vs. 28 (15\u0026ndash;46) mm/h; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, respectively]. Other demographic characteristics were similar throughout the cohort, as outlined in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGeneral characteristics of the patients who developed hypersensitivity reactions after rituximab treatment\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003en: 170\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo HSRs\u003c/p\u003e \u003cp\u003en: 147 (86%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHSRs\u003c/p\u003e \u003cp\u003en: 23 (14%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (35\u0026ndash;59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (35\u0026ndash;60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48 (35\u0026ndash;57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFemale\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 (42%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDM\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (18%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRheumatologic disease\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.70\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.6 (22.8\u0026ndash;27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.6 (22.8\u0026ndash;27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.4 (22.8\u0026ndash;27.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTransplantation history\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrent steroid therapy\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e131 (77%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e113 (77%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (78%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRAAS inhibitors\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128 (75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e111 (76%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.92\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNeutrophil count\u003c/b\u003e (/uL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5190 (3700\u0026ndash;7400)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5350 (3700\u0026ndash;7500)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4600 (3500\u0026ndash;6100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLymphocyte count\u003c/b\u003e (/uL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1900 (1300\u0026ndash;2600)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2000 (1300\u0026ndash;2600)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1500 (800\u0026ndash;2800)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHematocrit\u003c/b\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.6 (34.2\u0026ndash;42.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.8 (35-42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.7 (30.8\u0026ndash;40.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eeGFR\u003c/b\u003e (mL/min/1.73m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81 (44\u0026ndash;106)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82 (44\u0026ndash;107)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76 (37\u0026ndash;96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlbumin\u003c/b\u003e (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.4 (3-3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.4 (3-3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.6 (28\u0026thinsp;\u0026minus;\u0026thinsp;3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP\u003c/b\u003e (mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.1 (2-4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.1 (1.9-4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.6 (3-5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eESR\u003c/b\u003e (mm/h)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (16\u0026ndash;49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (15\u0026ndash;46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48 (33\u0026ndash;70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSerum LDL\u003c/b\u003e (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e130 (112\u0026ndash;179)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e139 (111\u0026ndash;183)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e147 (126\u0026ndash;158)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNLR\u003c/b\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.7 (1.8\u0026ndash;4.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.8 (1.8\u0026ndash;4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.3 (1.6\u0026ndash;6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePLR\u003c/b\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e134 (93\u0026ndash;187)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e132 (93\u0026ndash;186)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e144 (86\u0026ndash;279)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eProteinuria\u003c/b\u003e (mg/24h)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3475 (1872\u0026ndash;7073)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3486 (1872\u0026ndash;7308)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2972 (1638\u0026ndash;6262)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTransplant indication (n\u0026thinsp;=\u0026thinsp;15)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eRejection\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eOther\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (73%)\u003c/p\u003e \u003cp\u003e4 (27%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (69%)\u003c/p\u003e \u003cp\u003e4 (31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (100%)\u003c/p\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNative indication (n\u0026thinsp;=\u0026thinsp;155)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eMembranous\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eMCD- FSGS\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eAAV\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003eOther\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89 (57%)\u003c/p\u003e \u003cp\u003e30 (19%)\u003c/p\u003e \u003cp\u003e25 (17%)\u003c/p\u003e \u003cp\u003e11 (7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (56%)\u003c/p\u003e \u003cp\u003e25 (19%)\u003c/p\u003e \u003cp\u003e23 (17%)\u003c/p\u003e \u003cp\u003e11 (8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (67%)\u003c/p\u003e \u003cp\u003e5 (24%)\u003c/p\u003e \u003cp\u003e2 (9%)\u003c/p\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cb\u003eAAV\u003c/b\u003e: ANCA-associated vasculitis, \u003cb\u003eBMI\u003c/b\u003e: Body mass index, \u003cb\u003eDM\u003c/b\u003e: Diabetes mellitus, \u003cb\u003eeGFR\u003c/b\u003e: Estimated glomerular filtration rate, \u003cb\u003eESR\u003c/b\u003e: Erythrocyte sedimentation rate, \u003cb\u003eFSGS\u003c/b\u003e: Focal segmental glomerulosclerosis, \u003cb\u003eLDL\u003c/b\u003e: Low-density lipoprotein, \u003cb\u003eMCD\u003c/b\u003e: Minimal change disease, \u003cb\u003eNLR\u003c/b\u003e: Neutrophil- lymphocyte ratio, \u003cb\u003ePLR\u003c/b\u003e: Platelet- lymphocyte ratio, \u003cb\u003eRAAS\u003c/b\u003e: Renin-angiotensin-aldosterone system\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong patients with HSRs, 17 (74%) experienced IRRs, while 6 (26%) developed RISS. Reactions occurred with the first therapy dose in 61% (n\u0026thinsp;=\u0026thinsp;14), the second dose in 26% (n\u0026thinsp;=\u0026thinsp;6), and the third or later in the remaining patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA-B). Of patients with IRRs, 53% (n\u0026thinsp;=\u0026thinsp;9) had mild (grade I) reactions, 35% (n\u0026thinsp;=\u0026thinsp;6) had moderate (grade II) reactions, and 12% (n\u0026thinsp;=\u0026thinsp;2) had severe (grade III) reactions (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). We also found that the treatment indication for all patients with RISS was primary MN. During follow-up, rituximab treatment was discontinued in 10/170 (6%) patients due to HSRs.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBinary logistic regression identified several potential risk factors for HSRs in univariate analysis, including lower hematocrit (Odds Ratio [OR]: 0.942, 95% Confidence Interval [CI]: 0.882\u0026ndash;1.005), higher ESR (OR: 1.024, 95% CI: 1.009\u0026ndash;1.039), and elevated PLR (HR: 1.003, 95% CI: 1.000-1.006). In multivariate analysis, only higher ESR remained statistically significant (OR: 1.020, 95% CI: 1.002\u0026ndash;1.038, p\u0026thinsp;=\u0026thinsp;0.027) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). ESR levels of the patients with IRRs and RISS were comparable [53 (36\u0026ndash;74) vs. 44.5 (23\u0026ndash;54) mm/h, p\u0026thinsp;=\u0026thinsp;0.3]. In addition, we plotted ROC curve to define the best cutoff values of ESR to predict rituximab-related HSRs (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). We found that 35.5 mm/h was the best cutoff value for ESR with 74% sensitivity and 66% specificity (AUC:0.73, 95% CI: 0.637\u0026ndash;0.826, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and multivariate analysis of risk factors for the hypersensitivity reactions due to rituximab treatment\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnivariate, OR (%95 CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMultivariate, OR (%95 CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.000 (0.972\u0026ndash;1.028)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.988\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.774 (0.320\u0026ndash;1.868)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.569\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCurrent steroid therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.083 (0.374\u0026ndash;3.134)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.883\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHematocrit\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.942 (0.882\u0026ndash;1.005)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.071\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.984 (0.913\u0026ndash;1.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.684\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eeGFR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.995 (0.983\u0026ndash;1.008)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.452\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.035 (0.985\u0026ndash;1.088)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.175\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eESR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.024 (1.009\u0026ndash;1.039)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.020 (1.002\u0026ndash;1.038)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.027\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNLR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.057 (0.958\u0026ndash;1.166)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.269\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePLR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.003 (1.000-1.006)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.001 (0.997\u0026ndash;1.004)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.664\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cb\u003eCRP\u003c/b\u003e: C-reactive protein, \u003cb\u003eeGFR\u003c/b\u003e: Estimated glomerular filtration rate, \u003cb\u003eESR\u003c/b\u003e: Erythrocyte sedimentation rate, \u003cb\u003eNLR\u003c/b\u003e: Neutrophil- lymphocyte ratio, \u003cb\u003ePLR\u003c/b\u003e: Platelet- lymphocyte ratio\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, the primary indication for rituximab therapy was primary MN, accounting for 57% of the cases with native kidney diseases. We observed that the prevalence of HSRs among our cohort was 14%, with IRRs typically presenting as mild to moderate in severity. Notably, patients who experienced HSRs exhibited significantly higher ESR levels prior to the administration of rituximab.\u003c/p\u003e \u003cp\u003eIn recent years, the use of rituximab in nephrology has significantly increased, with current KDIGO guidelines recommending it for various glomerular diseases [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Rituximab is indicated for AAV, primary MN, relapsing MCD, and select cases of lupus nephritis. It is as effective as cyclophosphamide in inducing remission in AAV, with superior efficacy in maintenance therapy and a lower risk of malignancy and treatment-related burdens [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In primary MN, rituximab demonstrates comparable efficacy to traditional therapies regarding survival and remission rates, establishing itself as a first-line treatment for patients with moderate to high risk of declining kidney function [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Despite its widespread use in nephrology for various indications, data on rituximab-associated HSRs in this population remain unclear.\u003c/p\u003e \u003cp\u003eRituximab has been linked to serious adverse events, including fatal infusion reactions and severe mucocutaneous reactions. We observed a significantly lower incidence of adverse events related to rituximab infusion. Specifically, only 10% of our patients experienced IRRs. Our premedication approach differs significantly from previous studies evaluating IRRs to rituximab. Moore et al. reported a prevalence of 65% in CLL patients, and Cho et al. reported a prevalence of 43.3% in NHL patients [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In those studies, patients typically received only paracetamol and an H1 receptor antagonist as premedication. However, our protocol includes the administration of corticosteroids prior to rituximab infusions. This practice may contribute to our patients' lower incidence of IRRs. Studies on rituximab in RA and lupus, where intravenous corticosteroids were also part of the premedication regimen, reported infusion reaction rates more comparable to our findings [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Patients in both studies were given MPZ 100 mg IV before rituximab infusion, similar to our daily practice. Besides, Jung et al. demonstrated that corticosteroid premedication reduced the incidence of IRRs during the first rituximab infusion fivefold (8.3% compared to 41.2%) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. While corticosteroid premedication has effectively reduced IRRs, further studies are needed to standardize protocols across nephrology practices.\u003c/p\u003e \u003cp\u003eOn the other hand, the true prevalence of RISS is unknown, but it may be around 10% in autoimmune disorders. A systematic review identified 33 cases of RISS from 25 articles, with a predominantly female patient population (77%) and a mean age of 39 years, likely due to the high association with autoimmune conditions (85%) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In trials of rituximab for Sjogren's syndrome, 9.8% of patients developed RISS, while a prospective study also reported a prevalence of 9.1% RISS in hepatitis C virus-induced cryoglobulinemic vasculitis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Autoimmune diseases, particularly lupus, appear to predispose patients to RISS, as evidenced by its higher prevalence in such cases compared to hematological malignancies. The mechanism behind this condition may involve B-cell lysis induced by rituximab leading to antigen-antibody complex formation, especially in patients with autoimmune disorders with elevated autoantibody production and reduced clearance of immune complexes [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Our study observed a 4% prevalence of RISS, with all affected patients having MN. Based on prior findings, producing M-type phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A antibodies in MN patients may be linked to this condition.\u003c/p\u003e \u003cp\u003eSeveral risk factors for rituximab-related IRRs have been identified across different conditions, including bulky disease and low-grade disease in patients with B-cell lymphomas and higher actual body weight in malignant hematology patients [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. D'Arena et al. demonstrated a model to predict adverse drug reactions in rituximab therapy, including the history of allergy, splenomegaly, female sex, and hb\u0026thinsp;\u0026ge;\u0026thinsp;13 g/dl [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, these factors were not significant in our cohort, likely due to the distinct characteristics of nephrology patients compared to hematology populations.\u003c/p\u003e \u003cp\u003eOur study found that elevated baseline ESR levels represent an independent risk factor for HSRs. A previous study has demonstrated that Stevens-Johnson syndrome, a delayed-type HSR that can occur after mycoplasma pneumonia infection, is associated with elevated ESR [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Researchers have linked this phenomenon to cold agglutinins during mycoplasma infections. Furthermore, a recent study reported that serum anti-PLA2R-IgG and -IgG4 levels correlated with high-density lipoprotein levels and ESR in patients with MN [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. However, our study found no significant differences between the groups in hematocrit, proteinuria levels, or disease distribution. It is plausible that the elevated baseline ESR observed in our study is related to disease-associated autoantibodies that were not assessed, indirectly contributing to the development of HSRs. Although our data are retrospective and preliminary, pre-treatment ESR values exceeding 35.5 mm/h may be a potential marker for an increased risk of HSRs in nephrology patients. These findings highlight the necessity for further research to assess the clinical utility of ESR in risk stratification.\u003c/p\u003e \u003cp\u003eAs a retrospective study, our findings may underestimate the overall incidence of HSRs as some mild cases may have been missed. Our study's relatively low incidence of HSRs likely reflects the daily practice setting from which our data were derived and the liberal use of prophylactic corticosteroids in our center. Also, the lack of PLA2R antibody levels in some patients with MN prevented us from an additional analysis for HSRs in this subgroup of patients. Despite these limitations, our study is the first large-scale investigation involving over 150 patients with nephrological indications from a single center to identify risk factors for rituximab-related HSRs. In addition, to our knowledge, it is the only study that provides the frequency of the RISS in nephrology patients receiving rituximab treatment.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study highlights a 'real-world' clinical perspective, indicating an approximate 14% incidence of HSRs to rituximab in patients with nephrological conditions. Notably, elevated baseline ESR levels emerged as a potential predictive marker for these reactions. Given the reduced incidence of HSRs observed in our cohort and other populations receiving intravenous corticosteroid premedication, we advocate for the routine inclusion of corticosteroids in premedication protocols for nephrology patients undergoing rituximab therapy. While rituximab is generally well-tolerated, further research, specifically in a prospective manner, is needed to explore the utility of ESR and other biomarkers in predicting HSRs in nephrological indications.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAAV \u0026nbsp; ANCA-associated vasculitis\u003c/p\u003e\n\u003cp\u003eABMR \u0026nbsp;Antibody-mediated rejection\u003c/p\u003e\n\u003cp\u003eAUC \u0026nbsp; \u0026nbsp; Area under the curve\u003c/p\u003e\n\u003cp\u003eBMI \u0026nbsp; \u0026nbsp; Body mass index\u003c/p\u003e\n\u003cp\u003eCLL \u0026nbsp; \u0026nbsp; Chronic lymphocytic leukemia \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCRP \u0026nbsp; \u0026nbsp;C-reactive protein\u003c/p\u003e\n\u003cp\u003eDM \u0026nbsp; \u0026nbsp; \u0026nbsp;Diabetes mellitus\u003c/p\u003e\n\u003cp\u003eeGFR \u0026nbsp;Estimated glomerular filtration rate\u003c/p\u003e\n\u003cp\u003eESR \u0026nbsp; \u0026nbsp;Erythrocyte sedimentation rate\u003c/p\u003e\n\u003cp\u003eFSGS \u0026nbsp;Focal segmental glomerulosclerosis\u003c/p\u003e\n\u003cp\u003eHSRs \u0026nbsp; Hypersensitivity reactions\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIRRs \u0026nbsp; \u0026nbsp; Infusion-related reactions\u003c/p\u003e\n\u003cp\u003eKDIGO Kidney Disease Improving Global Outcomes\u003c/p\u003e\n\u003cp\u003eMCD \u0026nbsp; \u0026nbsp;Minimal change disease\u003c/p\u003e\n\u003cp\u003eMN \u0026nbsp; \u0026nbsp; \u0026nbsp; Membranous nephropathy\u003c/p\u003e\n\u003cp\u003eMPZ \u0026nbsp; \u0026nbsp; Methylprednisolone\u003c/p\u003e\n\u003cp\u003eNHL \u0026nbsp; \u0026nbsp;Non-Hodgkin lymphoma\u003c/p\u003e\n\u003cp\u003eOR \u0026nbsp; \u0026nbsp; \u0026nbsp; Odds Ratio\u003c/p\u003e\n\u003cp\u003ePLA2R \u0026nbsp;Phospholipase A2 receptor\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRA \u0026nbsp; \u0026nbsp; \u0026nbsp; Rheumatoid arthritis\u003c/p\u003e\n\u003cp\u003eRISS \u0026nbsp; \u0026nbsp;Rituximab-induced serum sickness\u003c/p\u003e\n\u003cp\u003eROC \u0026nbsp; Receiver operating characteristic\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConcept \u0026ndash; OFA, OH; Design \u0026ndash; OFA, OH, AD; Supervision \u0026ndash;OFA, UD, GG, OH; Analysis and/or Interpretation \u0026ndash;OFA, YK, OH; Literature Search \u0026ndash;OFA, AD, YK; Writing \u0026ndash;OFA; Critical Reviews \u0026ndash; OFA, UD, GG, OH.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors did not receive any funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study are not publicly available due to the inclusion of information that may compromise the privacy of research participants. However, they can be obtained from the corresponding author (O.F.A.) upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGazi University Faculty of Medicine review board reviewed and approved the study protocol in compliance with the Declaration of Helsinki and ethical guidelines for human research. This retrospective study was based on standard clinical practice, so informed consent was not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003e Gazi University Faculty of Medicine, Department of Nephrology, Ankara, T\u0026uuml;rkiye\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u003c/sup\u003e Gazi University Faculty of Medicine, Department of Internal Medicine, Ankara, T\u0026uuml;rkiye\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCerny T, Borisch B, Introna M, et al. Mechanism of action of rituximab. Anticancer Drugs. 2002;13(Suppl 2):S3\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLenz HJ. Management and preparedness for infusion and hypersensitivity reactions. Oncologist. 2007;12(5):601\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJung JW, Kang HR, Lee SH, et al. The incidence and risk factors of infusion-related reactions to rituximab for treating B cell malignancies in a single tertiary hospital. Oncology. 2014;86(3):127\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFouda GE, Bavbek S. Rituximab Hypersensitivity: From Clinical Presentation to Management. Front Pharmacol. 2020;11:572863.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarmacharya P, Poudel DR, Pathak R, et al. Rituximab-induced serum sickness: A systematic review. Semin Arthritis Rheum. 2015;45(3):334\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLe Guenno G, Ruivard M, Charra L, et al. Rituximab-induced serum sickness in refractory immune thrombocytopenic purpura. Intern Med J. 2011;41(2):202\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRovin BH, Adler SG, Barratt J, et al. Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100(4):753\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAslam A, Koirala A. Review of the Role of Rituximab in the Management of Adult Minimal Change Disease and Immune-Mediated Focal and Segmental Glomerulosclerosis. Glomerular Dis. 2023;3(1):211\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNishiura H, Takahashi M, Mori K, et al. Patients with infusion-related reactions on fixed-dose rituximab treatment have higher body surface area than those without infusion-related reactions in adults with frequently relapsing minimal change nephrotic syndrome: a retrospective study. J Pharm Health Care Sci. 2024;10(1):12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown SG. Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol. 2004;114(2):371\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith RM, Jones RB, Specks U, et al. Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis. Ann Rheum Dis. 2020;79(9):1243\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010;363(3):221\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Daalen EE, Rizzo R, Kronbichler A, et al. Effect of rituximab on malignancy risk in patients with ANCA-associated vasculitis. Ann Rheum Dis. 2017;76(6):1064\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGauckler P, Shin JI, Alberici F, et al. Rituximab in Membranous Nephropathy. Kidney Int Rep. 2021;6(4):881\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoore JE, Bloom PC, Chu CC, et al. Rituximab induced cytokine release with high serum IP-10 (CXCL10) concentrations is associated with infusion reactions. Leuk Res. 2023;129:107072.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCohen SB, Emery P, Greenwald MW, et al. 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Clin Lymphoma Myeloma Leuk. 2019;19(11):723\u0026ndash;28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eD'Arena G, Simeon V, Laurenti L, et al. Adverse drug reactions after intravenous rituximab infusion are more common in hematologic malignancies than in autoimmune disorders and can be predicted by the combination of few clinical and laboratory parameters: results from a retrospective, multicenter study of 374 patients. Leuk Lymphoma. 2017;58(11):2633\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlson D, Watkins LK, Demirjian A, et al. Outbreak of Mycoplasma pneumoniae-Associated Stevens-Johnson Syndrome. Pediatrics. 2015;136(2):e386\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang Y, Huang Y, Huang B, et al. Clinical Evaluation of Antiphospholipase A2 Receptor IgG4 level and Its IgG4-to-IgG Ratio Based on Quantitative Immunoassays in Idiopathic Membranous Nephropathy. Biomed Res Int. 2022;2022:9127520.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hypersensitivity reactions, Infusion related reactions, Rituximab, Erythrocyte Sedimentation Rate, Serum Sickness Disease","lastPublishedDoi":"10.21203/rs.3.rs-5951214/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5951214/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e \u003cp\u003eThis study investigates hypersensitivity reactions (HSRs) associated with rituximab therapy in nephrology patients, focusing on identifying potential risk factors.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eRecords of patients treated in our unit with rituximab for kidney diseases were reviewed between January 2019 and June 2024. Demographic, clinical, and laboratory data were evaluated to identify risk factors for HSRs. Patients were premedicated with paracetamol, diphenhydramine, and corticosteroids before rituximab infusions. Binary logistic regression analyses were performed to determine independent risk factors. Receiver operating characteristic (ROC) curve analysis were plotted to illustrate the best cut-off values of risk factors for HSRs estimation.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e170 patients received rituximab therapy with 447 treatment doses for nephrological indications. Rituximab treatment was indicated for MN in 89/150 (57%) patients with native kidney disease. HSRs were observed in 14% of patients, including infusion-related reactions (IRRs, 10%) and rituximab-induced serum sickness (RISS, 4%). The majority of HSRs (61%) occurred during the first infusion. RISS cases were observed exclusively in patients with MN. Elevated erythrocyte sedimentation rate (ESR) was identified as an independent risk factor for HSRs (OR: 1.020, 95% CI: 1.002\u0026ndash;1.038, p\u0026thinsp;=\u0026thinsp;0.027). Besides, ESR demonstrated its predictive value for HSRs with an area under the curve (AUC) of 0.73 (95% CI: 0.637\u0026ndash;0.826, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), achieving a sensitivity of 74% and a specificity of 66% at a cutoff value of 38.5 mm/hour.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eElevated baseline ESR levels may serve as a predictive marker for HSRs in nephrology patients treated with rituximab. Premedication with corticosteroids may have resulted in a lower incidence of adverse events. Further prospective studies are needed to validate ESR as a biomarker for HSRs risk stratification.\u003c/p\u003e","manuscriptTitle":"Can Erythrocyte Sedimentation Rate Predict Hypersensitivity Reactions to Rituximab Therapy in Kidney Diseases?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-28 11:19:44","doi":"10.21203/rs.3.rs-5951214/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9f636613-5285-438a-9784-01e1fd434ed5","owner":[],"postedDate":"April 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-03T19:53:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-28 11:19:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5951214","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5951214","identity":"rs-5951214","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}