Immunosuppression Group Research Articles

Effects of immunosuppressive therapy on renal prognosis in primary membranous nephropathy

BackgroundImmunosuppressive therapy plays a crucial role in treating membranous nephropathy, with previous studies highlighting its benefits for patients with primary membranous nephropathy (PMN). Guidelines suggest that the management of membranous nephropathy should be tailored to individual risk levels. However, there is a lack of real-world studies examining the effects of immunosuppressive therapy on renal outcomes in PMN patients. This study aimed to investigate the relationship between immunosuppressive therapy and renal prognosis in PMN patients.MethodsThis was a real-world retrospective study including patients diagnosed with PMN in Shenzhen Second People’s Hospital and Hechi People’s Hospital. Univariate and multivariate Cox regression analysis and Kaplan-Meier survival analysis were used.ResultsAfter propensity score-matching, 464 PMN patients were included and they were assigned to conservative and immunosuppressive group in a 1:1 ratio. Immunosuppressive therapy was the protective factor of renal composite outcome (HR = 0.65, p < 0.01). Separately, the effect was significant in moderate- and high-risk but not in low-risk patients. Key influencing factors including age, blood pressure, albumin and total cholesterol levels, with slight differences among patients at different risk.ConclusionsThis study demonstrates the efficacy of immunosuppressive therapy in non-low-risk PMN patients. The key factors affecting renal prognosis in patients with different risk levels are emphasized to help provide individualized treatment.

Anti-Tumor Necrosis Factor Therapy and the Risk of Gestational Diabetes in Pregnant Women With Inflammatory Bowel Disease.

Anti-tumor necrosis factor (anti-TNF) therapy may improve insulin sensitivity, and its impact during pregnancy remains unclear. We aimed to assess the risk of gestational diabetes mellitus (GDM) associated with anti-TNF treatment among pregnant women with inflammatory bowel disease (IBD). This nationwide cohort study included patients with IBD in Korea from 2010 to 2021. Anti-TNF exposure was identified from the last menstrual period (LMP) to LMP + 140 days. The development of GDM was assessed from LMP + 141 days to delivery. We performed overlap weighting to balance the covariates and used a generalized linear mixed model to measure the risk ratio (RR) and 95% confidence intervals (CIs). The anti-TNF group was compared with the unexposed group, as well as with the immunosuppressant, 5-aminosalicylate, and untreated groups. A total of 3,695 pregnancies in women with IBD were identified, of which 338 (9.2%) were exposed to anti-TNFs. GDM was found in 7.1% of the pregnancies exposed to anti-TNFs as compared with 11.0% of those unexposed. The crude and weighted RRs for GDM risk were 0.64 (95% CI 0.43-0.96) and 0.68 (95% CI 0.55-0.84), respectively. The weighted RR when compared with the immunosuppressant, 5-aminosalicylate, and untreated groups was 0.70 (95% CI 0.41-1.18), 0.71 (95% CI 0.52-0.95), and 0.85 (95% CI 0.59-1.24), respectively. This nationwide cohort reported a decreased risk of GDM among patients who used anti-TNFs during early pregnancy compared with those unexposed. GDM risk may become a consideration in the decision-making process when choosing treatment options for pregnant women with a risk factor for GDM.

Efficacy and safety of telitacicept, a BLyS/APRIL dual inhibitor, in the treatment of IgA nephropathy: a retrospective case-control study.

Telitacicept, a B lymphocyte stimulator/A proliferation-inducing ligand dual-target fusion protein, has recently been used in autoimmune diseases. We assessed the efficacy and safety of telitacicept in immunoglobulin A nephropathy (IgAN) patients. This study included 42 IgAN patients who received telitacicept treatment, forming the 'whole telitacicept group'. Among them, 20 patients who had not previously received corticosteroid (CS) therapy or immunosuppressive (IS) agents were categorized as the 'newly treated telitacicept subgroup'. Additionally, 28 patients who were selected to match historical controls received conventional IS therapy (CS therapy with/without IS agents) and were classified as the 'conventional IS group'. Telitacicept was partially used in combination with conventional IS therapy, including initial CS in different doses. Various indicators were compared at 4-week intervals up to 24weeks among the three groups. After 24weeks of treatment, the 24-hour proteinuria decreased from 1.70g [interquartile range (IQR) 1.05-2.58] to 0.21g (IQR 0.39-0.13) (P=.043) in the newly treated telitacicept subgroup, from 1.78g (IQR 0.97-2.82) to 0.44g (IQR 1.48-0.16) (P=.001) in the conventional IS group and from 1.07g (IQR 0.66-1.99) to 0.26g (IQR 0.59-0.17) (P=.028) in the whole telitacicept group. The estimated glomerular filtration rate (eGFR) increased from 76.58±30.26ml/min/1.73m2 to 80.30±26.76ml/min/1.73m2 (P=.016) in the newly treated telitacicept subgroup, from 72.73±33.41ml/min/1.73m2 to 84.08±26.81ml/min/1.73m2 (P=.011) in the conventional IS group and from 70.10±32.88ml/min/1.73m2 to 71.21±31.49ml/min/1.73m2 (P=.065) in the whole telitacicept group. During follow-up periods, the efficacy rates of the three groups did not show statistically significant differences and no serious adverse events were observed. Telitacicept may be a safe and effective treatment for IgAN, offering reductions in proteinuria and increases in eGFR similar to conventional IS therapy. After a 24-week follow-up, the incidence of adverse events was lower for telitacicept than for conventional IS therapy.

Impact of Photobiomodulation and Melatonin on Periodontal Healing of Periodontitis in Immunosuppressed Rats.

Introduction: Periodontitis is an inflammatory disease due to bacterial origin; it has a chronic course and progresses by immunosuppressive therapy. However, adjuvant therapies such as photobiomodulation (PBM) and melatonin can reduce the severity of the inflammation and inhibit the progression of periodontitis. Therefore, the present study evaluated the effects of PBM (PBM) and melatonin, as adjuvant therapies, on periodontal healing in immunosuppressed rats with periodontitis. Methods: Random allocation was performed on 36 albino Wistar rats, divided into the following groups: control, periodontitis, immunosuppressant only, immunosuppressant+PBM, immunosuppressant+melatonin, and immunosuppressant+melatonin+PBM. Periodontitis caused by ligature in all groups, except for the control group. Subcutaneous administration of dexamethasone was performed in the immunosuppressant groups for immunosuppression. All the groups except the control group received scaling and root planning (SRP). Each group was subdivided into three equal subgroups according to the evaluation period: (A), one week, (B) two weeks (C), 4 weeks. Histological examination was done with haematoxylin & eosin and Masson's Trichrome for inflammation and periodontal healing. Statistical Analysis of the data was done by using the chi-square test. The significance level was set at P≤0.05. Results: Regarding the inflammatory response and periodontal healing, histological examination revealed statistically significant difference in all treated groups in comparison with the control untreated immunosuppressed group (P<0.001). The combined application of melatonin and PBM resulted in a best histological response presented by lower inflammatory response and better periodontal healing, when compared with all other treated groups (P<0.001). Conclusion: After considering the circumstances of this research, the combination of melatonin and PBM by a 650 nm diode laser with output power of 100 mw for one minute for three sessions appeared to be a beneficial adjunct in periodontal healing in immunosuppressed rats with periodontitis.

Clinical features of flare in Japanese patients with new-onset SLE and risk factors for SLE flare in daily clinical practice: a single-center cohort study

This study aimed to elucidate the clinical features, outcomes and risk factors of flares in patients with systemic lupus erythematosus (SLE). Data were collected from patients with newly diagnosed SLE at the Fukushima Medical University Hospital between 2011 and 2022. Patients who experienced a flare during the study period constituted the flare group, and their clinical features were compared with those of the no-flare group. The cumulative flare-free survival regarding several clinical items was compared between the two groups using Kaplan–Meier’s curves. Among 387 patients with SLE, 83 patients with newly diagnosed SLE were included. Their mean age was 37.9 years, and 29 patients experienced flares during the study period. The general characteristics were similar between the two groups, with the exception of the observation period and anti-SS-A antibody positivity. Regarding therapy, a significantly increased frequency of hydroxychloroquine intake and combination with immunosuppressive agents were observed in the no-flare group. The Kaplan–Meier analysis revealed a significantly higher cumulative flare-free survival in the anti-SS-A negative group and combination immunosuppressive therapy group. In conclusion, anti-SS-A positivity may be a risk factor for SLE flare. In turn, combination immunosuppressive therapy may be beneficial for SLE treatment in daily clinical practice.

#1170 Efficacy and safety of telitacicept in IgA nephropathy: a real-world study

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary glomerular disease in the world, and the specific therapeutic methods are limited in IgAN. Telitacicept is a humanized fusion protein composed of a transmembrane activator and calcium-modulating cyclophilin ligand interactor receptor and human IgG. This study was designed to evaluate the efficacy and safety of telitacicept in adult patients with IgAN in a real-world study. Method Biopsy-proven IgAN patients with 24-hour proteinuria greater than 0.5 g/day who received telitacicept 240 mg once a week were recruited in this study and 1:1 matched with patients who received supportive treatment only or immunosuppressive treatment by propensity score matching. The primary outcome was the change from baseline in 24-hour proteinuria over the 3-month follow-up. Results Twenty-one patients in each group were enrolled. The mean eGFR was 80.1 ml/min/1.73 m2, and the median 24-hour urine protein level was 1.48 g/day. At the end of the 3-month follow-up period, telitacicept reduced median proteinuria by 0.72 g/d (54.6%) from baseline, compared with a reduction of 0.18 g/d (20%) in the supportive treatment group (P &amp;lt; 0.001), and 1.12 g/d (72.1%) in the immunosuppressive treatment group (P = 0.814). Preserved eGFR levels were observed in the telitacicept group (1.9 ml/min/1.73 m2 [4.3%]), while the eGFR level declined in the supportive treatment group (- 2.9 ml/min/1.73 m2 [- 5.8%]) and immunosuppression group (- 6.1 ml/min/1.73 m2 [- 8.4%]). No serious adverse events were observed in the telitacicept treatment group. Injection site reactions were more prevalent in the telitacicept group (8/21 [38.1%]), meanwhile immunosuppression group had more respiratory tract infections (7/21, [33.3%]). Conclusion Telitacicept can reduce proteinuria in patients with IgAN and showed a favourable safety profile in patients with IgAN.

Immunosuppressant Agents as Add-On Therapy Failed to Improve the Outcome of Immunoglobulin A Nephropathy with Crescent Score C1

Introduction: The renoprotective benefits of adding immunosuppressant therapy to corticosteroid (CS) treatment for immunoglobulin A nephropathy (IgAN) patients with less than 25% crescent formation (C1) remain uncertain, warranting further research. Methods: A retrospective study was conducted on IgAN patients with crescent C1 lesions confirmed by renal biopsy at Xinqiao Hospital between May 1, 2017, and May 1, 2020. Patients were stratified into either the CS treatment group or the CS combined with an additional immunosuppressant therapy group. Follow-up assessments were conducted within 24 months. Propensity score analysis was used to match patients receiving CS and CS + immunosuppressant drug treatment in a 1:1 ratio. Primary outcomes included changes in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Subgroup analyses were performed to evaluate the benefits of different populations. Composite endpoint outcomes comprised a 30% eGFR decrease, end-stage kidney disease (ESKD) necessitating dialysis or transplant, or kidney disease-related mortality. Adverse events were also compared between the two groups. Results: 296 IgAN patients with C1 lesions were included in the analysis. Baseline characteristics indicated that IgAN patients in the CS + immunosuppressant group exhibited poorer renal function and higher UACR levels. Propensity score analysis effectively minimized the influence of baseline clinical characteristics, including age, serum creatinine, initial eGFR, UACR, and 24-h proteinuria. Both treatment groups demonstrated continuous eGFR improvement and significant UACR reduction during follow-up, especially at 6 months. However, no significant differences in eGFR and UACR reduction rates were observed between the two groups throughout the entire follow-up period, both before and after matching. Subgroup analysis revealed improved eGFR in both treatment groups, notably among patients with an initial eGFR below 90 mL/min/1.73 m2. Conversely, IgAN patients with C1 lesions and a cellular crescent ratio exceeding 50% treated with CS and immunosuppressant therapy experienced a significant improvement in renal function and a decline in urinary protein creatinine ratio. Composite endpoint outcomes did not significantly differ between the two groups, while the incidence of adverse events was comparable. Conclusion: Our findings suggest that the addition of immunosuppressant therapy to corticosteroid monotherapy did not confer significant therapeutic advantages in patients with C1 lesions compared to CS monotherapy, although some specific patient populations appeared to derive modest benefits from this combined approach.

Anti-intercellular adhesion molecule 1 monomaintenance therapy induced long-term liver allograft survival without chronic rejection

Calcineurin inhibitors (CNIs) are essential in liver transplantation (LT); however, their long-term use leads to various adverse effects. The anti–intercellular adhesion molecule (ICAM)-1 monoclonal antibody MD3 is a potential alternative to CNI. Despite its promising results with short-term therapy, overcoming the challenge of chronic rejection remains important. Thus, we aimed to investigate the outcomes of long-term MD3 therapy with monthly MD3 monomaintenance in nonhuman primate LT models. Rhesus macaques underwent major histocompatibility complex–mismatched allogeneic LT. The conventional immunosuppression group (Con-IS, n = 4) received steroid, tacrolimus, and sirolimus by 4 months posttransplantation. The induction MD3 group (IN-MD3, n = 5) received short-term MD3 therapy for 3 months with Con-IS. The maintenance MD3 group (MA-MD3, n = 4) received MD3 for 3 months, monthly doses by 2 years, and then quarterly. The MA-MD3 group exhibited stable liver function without overt infection and had significantly better liver allograft survival than the IN-MD3 group. Development of donor-specific antibody and chronic rejection were suppressed in the MA-MD3 group but not in the IN-MD3 group. Donor-specific T cell responses were attenuated in the MA-MD3 group. In conclusion, MD3 monomaintenance therapy without maintenance CNI provides long-term liver allograft survival by suppressing chronic rejection, offering a potential breakthrough for future human trials.

P766 No difference in progression of disability 2 years after stopping infliximab or immunosuppressant vs. continuing combination therapy in patients with CD in sustained steroid-free remission: a subanalysis of SPARE

Abstract Background In the SPARE trial, the discontinuation of infliximab (IFX) in patients with Crohn’s disease (CD) in sustained remission under combination therapy (IFX and immunosuppressant therapy), was associated with a significantly higher relapse rate than when continuing combination therapy or discontinuing immunosuppressant therapy. However, a high proportion of patients rapidly recover remission when resuming treatment. The impact of this treatment strategy on functional disability, a major endpoint in assessing CD progression, has been poorly studied. We aimed to compare the evolution of the IBD-disability index (IBD-DI) in patients continuing combination therapy, discontinuing IFX or immunosuppressant therapy. Methods The study of the evolution of the IBD-DI in the 3 groups (combination, IFX withdrawal, immunosuppressant withdrawal), between baseline and the end of study (2 years), was a pre-defined secondary endpoint of the trial. Changes in scores (between baseline and the end of study) were compared using Wilcoxon tests between the arms “combination group” versus “IFX withdrawal group” and between “immunosuppressant withdrawal group” versus “IFX withdrawal group”. Results IBD-DI was available at baseline and at the end of study for 153 patients out of the 211 randomised in the SPARE trial between November 2015 and April 2019 (46 in the combination group, 55 in the IFX withdrawal group, and 52 in the immunosuppressant withdrawal group) and those were included in the analysis. Table 1 summarizes baseline characteristics of these patients. 30 patients had a relapse (6 [13%] of 46 in the combination group, 19 [34.5%] of 55 in the IFX withdrawal group, 5 [9.6%] of 52 in the immunosuppressant withdrawal group). Of 23 patients who had a relapse and were retreated or optimised according to protocol, remission was achieved in 21 patients (1 of 2 in the combination group, 18 of 19 in the IFX withdrawal group, and 2 of 2 in the immunosuppressant withdrawal group). The median IBD-DI at baseline was 12.5 (IQR, 5.36-21.43), without significant differences between the 3 groups. Figure 1 shows changes in the IBD-DI between baseline and the end of study in the 3 groups. There was no significant difference in terms of changes in IBD-DI between the arms "combination group" and "IFX withdrawal group" (p=0.56), or between the arms "immunosuppressant withdrawal group” and "IFX withdrawal group" (p=0.29). Conclusion In patients with CD in sustained steroid-free remission under combination therapy with IFX and immunosuppressant therapy, there was no difference in progression of disability over 2 years between those who continued combination therapy, stopped IFX or stopped the immunosuppressant with the possibility of recycling the medication after a relapse.

Efficacy of prednisone combined with mycophenolate mofetil for immunoglobulin A nephropathy with moderate-to-severe renal dysfunction.

Immunoglobulin A nephropathy (IgAN) is a common form of chronic glomerulonephritis. Currently, IgAN is one of the main causes of chronic renal failure in China; its prognosis varies greatly between patients, with renal function at the time of diagnosis and prognosis being strongly correlated. Mycophenolate mofetil (MMF) is a drug with a good immunomodulatory effect and is commonly used clinically. However, its effects in IgAN have not yet been clearly demonstrated. Therefore, herein, we retrospectively compared the effectiveness and safety of prednisone alone or combined with MMF for the treatment of primary IgAN with moderate-to-severe renal impairment. To evaluate the effectiveness and safety of prednisone and MMF in treating IgAN with moderate-to-severe renal dysfunction. Between January 2011 and December 2020, 200 patients with moderate-to-severe IgAN were included in this study, all of whom were admitted to Wuxi People's Hospital affiliated with Nanjing Medical University. All patients underwent a renal puncture biopsy, which revealed primary IgAN with a glomerular filtration rate (GFR) of 30-60 mL/min. The patients were divided into a glucocorticoid therapy group (GTG) and an immunosuppressive therapy group (ITG) according to the different treatment regimens, with 100 patients in each group. Based on general treatments, such as angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers, patients in the GTG were administered prednisone 0.5-0.8 mg/ (kg·d-1) for 4-8 wk, which was reduced by 5 mg every two weeks until the maintenance(30 mg/d) dose was reached and maintained for 12 mo. In the ITG, MMF was administered at 1.0 g/d for 6-12 mo, followed by a maintenance dosage of 0.5 g/d for 12 mo. Age, sex, blood pressure, 24-h urinary egg white measurement, serum creatinine (Scr), blood uric acid, blood albumin, blood potassium (K), hemoglobin, GFR, alanine aminotransferase, total cholesterol (T-CHO), fasting blood glucose, and body mass index were recorded. The 24-h urinary protein, Scr, and GFR levels were recorded 3, 6, 9, and 12 mo after treatment. Follow-up data were also collected. No discernible differences existed between the two groups in terms of age, sex, blood pressure, creatinine, 24-h urinary protein level, GFR, or other biochemical indicators at the time of enrollment. Both regimens significantly reduced the 24-h urinary protein quantitation and stabilized renal function. Nine months after treatment, the 24-h urinary protein and Scr of the ITG decreased more significantly than those of the GTG. By the 12th month of treatment, the 24-h urinary protein and Scr in both groups continued to decrease compared to those by the 9th month. In addition, the overall response rate in the ITG was significantly higher than that in the GTG. The occurrence of side effects did not vary significantly between the two regimens; however, endpoint events were significantly more common in the GTG than in the ITG. The follow-up time for the GTG was noticeably lower than that for the ITG. Prednisone combined with MMF was effective for the treatment of IgAN with moderate-to-severe renal dysfunction.

Impact of COVID-19 in Thalassemia Patients Undergoing Hematopoietic Stem Cell Transplant Recipients

Objective: This article primarily examines the clinical attributes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in transplant recipients with thalassemia, offering significant insights into the treatment and care of this patient population. Method: The present study retrospectively analyzed the data of all thalassemia patients who underwent Hematopoietic stem cell transplantation (HSCT) at the First Affiliated Hospital of Guangxi Medical University between December 2019 and December 2022. A total of 280 patients were included, of which 81 had confirmed coronavirus disease 2019 (COVID-19). The study collected information on patient demographics, transplantation type and timing, graft-versus-host disease (GVHD), use of immunosuppressive agents, onset time and severity of COVID-19, and prognosis. Follow-up was conducted until March 31, 2023.Univariate analysis was performed using SPSS v25.0, and GraphPad Prism was used for the cumulative incidence comparisons. Results: The median age was 3.6(2-19) years.The main type of thalassemia was β type (93.9%). Identical sibling donors accounted for 40%, haploidentical donors accounted for 25.4%, and identical unrelated donors accounted for 34.6% (10/10). The main source of hematopoietic stem cells was bone marrow combined with peripheral blood (85%).There were no significant differences in age, gender, diagnosis, donor type, graft type, use of immunosuppressive agents, GVHD, and pneumonia of pro-COVID-19 between infected patients and non-infected patients with SARS-CoV-2. Most of the patients were mild (74 cases, 91.3%) in terms of the severity of COVID-19 infection, only 8.6% of the moderate cases, and none severe and died. 74 cases were cured without drug treatment. Of the seven patients treated with medications, four were azvudine and three were nematasvir. The median number of days (IQR) of treatment for COVID-19 was 5(5) days. The cumulative incidence in the immunosuppressive group was higher than that in the non-immunosuppressive group over the same time frame. There was no significant difference in the final infection rate of COVID-19 among patients receiving transplantation in different years(2020,2021,2022), which was 24.7 26.8 36.5 ( p=0.368), respectively. Conclusion: The low infection rate and no severe cases may be due to scientific protection and timely medication. There are no special risk factors for COVID-19 infection in thalassemia patients after transplantation.

Mimicking Clinical Rejection Patterns in a Rat Osteomyocutaneous Flap Model of Vascularized Composite Allotransplantation

IntroductionGraft loss in vascularized composite allotransplantation (VCA) is more often associated with vasculopathy and chronic rejection (CR) than acute cellular rejection (ACR). We present a rat osteomyocutaneous flap model using titrated tacrolimus administration that mimics the graft rejection patterns in our clinical hand transplant program. Comparison of outcomes in these models support a role for ischemia reperfusion injury (IRI) and microvascular changes in CR of skin and large-vessel vasculopathy. The potential of the surgical models for investigating mechanisms of rejection and vasculopathy in VCA and treatment interventions is presented. Materials and MethodsFour rodent groups were evaluated: syngeneic controls (Group 1), allogeneic transient immunosuppression (Group 2), allogeneic suboptimal immunosuppression (Group 3), and allogeneic standard immunosuppression (Group 4). Animals were monitored for ACR, vasculopathy, and CR of the skin. ResultsTransient immunosuppression resulted in severe ACR within 2 wk of tacrolimus discontinuation. Standard immunosuppression resulted in minimal rejection but subclinical microvascular changes, including capillary thrombosis and luminal narrowing in arterioles in the donor skin. Further reduction in tacrolimus dose led to femoral vasculopathy and CR of the skin. Surprisingly, femoral vasculopathy was also observed in the syngeneic control group. ConclusionsTitration of tacrolimus in the allogeneic VCA model resulted in presentations of rejection and vasculopathy similar to those in patients and suggests vasculopathy starts at the microvascular level. This adjustable experimental model will allow the study of variables and interventions, such as external trauma or complement blockade, that may initiate or mitigate vasculopathy and CR in VCA.

Assessment of off-label prescribing: profile, evidence and evolution

ObjectiveThe objectives of the study were to describe the extent and profile of off-label prescriptions, to evaluate the level of evidence supporting these indications, to assess the research activity in these conditions, and to determine to what extent these were authorized as new indications five years after the application. MethodsA cross-sectional study including all applications conducted in the Hospital Universitario Reina Sofía in Córdoba during 2010. Analysis: level of evidence according to the criteria by SIGN-NICE (Scottish Intercollegiate Guidelines Network, National Institute for Health and Care Excellence) and CEBM (Centre for Evidence-based Medicine), registered clinical trials (source: ClinicalTrials.gov), and review of product specifications and monthly newsletters from the Spanish Agency of Medicines and Medical Devices. ResultsThere were 190 applications for off-label prescription for 82 different indications. The most requested medications were: tacrolimus, mycophenolate, colistimethate and everolimus; the immunosuppressant group had the highest number of uses for non-approved indications. Out of the applications, 52.4% were based on some clinical trial, while the rest had a low level of evidence (observational studies and case reports). We have found on-going clinical trials for 67% of the indications, but new indications in their product specifications have only been authorized for nine drugs (bevacizumab, deferasirox, everolimus, lenalidomide, methotrexate, sildenafil, sorafenib, raltegravir and tenofovir). ConclusionsWe have detected a major volume of off-label prescription without good supporting evidence, which identifies these indications and medications as interesting research lines, but that require follow-up in terms of effectiveness and costs.

Rhodotorula mucilaginosa ZTHY2 Attenuates Cyclophosphamide-Induced Immunosuppression in Mice.

Rhodotorula mucilaginosa (R. mucilaginosa) can enhance the immune and antioxidant function of the body. However, whether R. mucilaginosa has an immunoregulatory effect on cyclophosphamide (CTX)-induced immunosuppressed animals remains to be clarified. In this study, the R. mucilaginosa ZTHY2 that we isolated from the coastal waters of the South China Sea previously was prepared in order to investigate its immunoprotective effect on CTX-induced immunosuppression in mice, and the effects were compared to those of Lactobacillus acidophilus (LA) (a well-known probiotic). Seventy-two male SPF mice were divided into six groups: The C group (control); IM group (immunosuppressive model group) (+CTX); Rl, Rm, and Rh groups (+CTX+low, medium, and high concentration of R. mucilaginosa, respectively); and PC (positive control) group (+CTX+LA). After a 28-day feeding trial, blood samples were taken for biochemical and serum immunological analysis, and the thymus and spleen were collected to analyze the organ index, lymphocyte proliferation and differentiation, and antioxidant capacity. The findings showed that R. mucilaginosa ZTHY2 improved the spleen and thymus indices, effectively attenuated immune organ atrophy caused by CTX, and enhanced the proliferation of T and B lymphocytes induced by ConA and LPS. R. mucilaginosa ZTHY2 promoted the secretion of cytokines and immunoglobulins and significantly increased the contents of IL-2, IL-4, IL-6, TNF-α, IFN-γ, IgA, IgG, IgM, CD4, CD8, CD19, and CD20 in serum. The proportion of CD4+, CD8+, CD19+, and CD20+ lymphocytes in spleen, thymus, and mesenteric lymph nodes were increased. In addition, R. mucilaginosa ZTHY2 reduced the reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increased glutathione (GSH), total superoxide dismutase (SOD), and catalase (CAT) levels. Our results indicated that R. mucilaginosa ZTHY2 can significantly enhance the immune function of immunosuppressed mice, and improving antioxidant capacity thus attenuates CTX-induced immunosuppression and immune organ atrophy.

Effect of immunosuppressive agents on clinical outcomes in idiopathic membranous nephropathy.

Few comparative studies on the effects of immunosuppressants in patients with idiopathic membranous nephropathy have been conducted. Data from 489 patients who received conservative treatment or immunosuppressants were retrospectively analyzed by propensity score matching. Primary outcomes were complete or partial remission (CR or PR) of proteinuria, and secondary outcomes were renal survival and infection. Of the 489 patients, 357 (73.0%) received immunosuppressants. Propensity score matching identified 82 patients from the conservative group and 82 patients in the immunosuppressant group. CR or PR at 12 months was significantly higher in the immunosuppressant group compared with the conservative group for the total population (p = 0.002) and the propensity score-matched population (p = 0.02). The use of immunosuppressants was significantly more effective with respect to achieving a CR or PR at 12 months in patients who were aged <65 years or female, or who had a proteinuria level of ≥4.0 g/g or an estimated glomerular filtration rate of ≥60 mL/min/1.73 m2 (p < 0.05). Renal survival was similar between patients receiving immunosuppressants and conservative treatment in both the total and matched populations. The immunosuppressant group (21.8%) had a significantly higher incidence of infections compared with the conservative group (13.6%) for the total population (p = 0.03), but statistical significance disappeared in the matched population (p > 0.99). The remission rate was significantly higher in the immunosuppressant group than in the conservative group, particularly in the subgroup of patients who were young or female, or those with heavy proteinuria loads or good renal function.

Comparison of anti-spike IgG, anti-spike IgA levels and neutralizing antibody activity induced by CoronaVac and BNT162b2 vaccines in patients with inflammatory rheumatic diseases receiving immunosuppressive therapy

BackgroundThe importance of COVID-19 vaccination for patients on immunosuppressive (IS) medication has increased due to the high risk of severe disease or mortality. Different vaccines have varying efficacy rates against symptomatic COVID-19, ranging from 46.8% to 95%. The objective of this study was to examine the differences in anti-Spike IgG, anti-Spike IgA, and neutralizing antibody (NAb) activity between the inactive CoronaVac vaccine and the mRNA-based BNT162b2 vaccine in IS patients.MethodA total of 441 volunteers, including 104 IS patients, 263 healthy controls (HC), who received two doses of CoronaVac or BNT162b2, and 74 unvaccinated patients with a history of SARS-CoV-2 infection, were included in the study. Anti-spike IgG, IgA, and NAb activity were investigated.ResultsImmunogenicity with BNT162b2 was higher than with CoronaVac, but in IS groups, it was lower than HC (CoronaVac-IS: 79.3%, CoronaVac-HC: 96.5%, p < 0.001; BNT162b2-IS: 91.3%, BNT162b2-HC: 100%, p = 0.005). With CoronaVac, anti-Spike IgG levels were significantly lower than BNT162b2 (CoronaVac-IS: 234.5AU/mL, CoronaVac-HC: 457.85AU/mL; BNT162b2-IS: 5311.2AU/mL, BNT162b2-HC: 8842.8AU/mL). NAb activity in the BNT162b2 group was significantly higher. NAb and anti-Spike IgG levels were found to be correlated. Among the IS group, a significantly lower response to the vaccines was observed when using rituximab. IgA levels were found to be lower with CoronaVac.ConclusionsAlthough immunogenicity was lower in IS patients, an acceptable response was obtained with both vaccines, and significantly higher anti-Spike IgG, anti-Spike IgA, and NAb activity levels were obtained with BNT162b2.

Efficacy of Selective Laser Trabeculoplasty in Patients on Systemic Immunosuppressive Therapy.

When comparing patients on systemic immunosuppressive therapy to those without, there was no difference in intraocular pressure (IOP) early after SLT; however, at 1 year following SLT, IOP was higher in the immunosuppression group compared with controls. To determine whether patients taking systemic immunosuppressive medications have a different IOP-lowering response to selective laser trabeculoplasty (SLT) compared with a control group of patients. All patients who underwent SLT at Mayo Clinic 2017-2021 were identified. Patients on systemic immunosuppressive medications at the time of SLT were compared with control patients not receiving systemic immunosuppressive medications. The primary endpoints of this study were the percentage IOP reduction at 1 to 2, 3 to 6, and 12 months. Additional analyses included the percentage of patients who did not require additional therapy at each time point. There were 108 eyes of 72 patients that underwent SLT in the immunosuppressed group and 1997 eyes of 1417 patients in the control group. There was no significant difference in age-adjusted change in IOP between groups at the first postoperative visit 1 to 2 months following SLT (-18.8±20.7% vs. -16.0±16.5%, P =0.256) or 3-6 months following SLT (-15.2±21.6% vs. -18.3±23.2%, P =0.062). However, at 12 months following SLT, the IOP reduction in the immunosuppressive therapy group was significantly less compared with the control group (-15.1±21.2% vs. -20.3±22.9%, P =0.045). There was no difference between groups in the number of additional treatments during the study intervals. Patients in the systemic immunosuppressive therapy group showed equivalent early IOP-lowering after SLT compared with a control group, but the treatment response was diminished at 1 year. Further studies investigating IOP regulation after SLT in immunosuppressed patients are needed.

#3269 EPIDEMIOLOGY OF PRIMARY FSGS INCLUDING CLUSTER ANALYSIS OVER A 20-YEAR PERIOD

Abstract Background and Aims Focal segmental glomerulosclerosis (FSGS) is one of the leading causes of nephrotic syndrome (NS) in adults. This epidemiological study describes a renal centre's 20 year ‘real world' experience of patients with primary FSGS including cluster analysis. Method This retrospective analysis was conducted on patients diagnosed with primary FSGS at a tertiary renal centre with a catchment population of 1.55 million, over 2 decades. Data collection included baseline demographics, laboratory results, immunosuppression (IS) and outcomes: Complete &amp; partial remission, relapse, progression to renal replacement therapy (RRT) and mortality. A two-step cluster analysis was used to reveal groupings to aid prognostication and treatment decisions. Pre-specified cluster variables were: Serum albumin (sAlb), urine protein: creatinine ratio (uPCR) &amp; estimated glomerular filtration rate (eGFR). Results 87 patients were identified with primary FSGS after exclusion of secondary causes. Mean age was 49.3 years, 60.9% male, 86.2% white with median eGFR 46 ml/min, uPCR 573 mg/mmol, sAlb 33g/l (Table 1). Rates of partial and complete remission were 23% &amp; 49.4% respectively. Progression to RRT occurred in 27.4%, death in 27.4%. Comparing those receiving IS vs not: sAlb was lower 23 g/L vs 40 g/L (p&amp;lt;0.001), uPCR was higher 795 mg/mmol vs 318 mg/mmol (p &amp;lt;0.001). The IS group was more likely to achieve complete remission (62% vs 40%, p = 0.041), but relapsed more 48.6% vs 22% (p&amp;lt;0.027). There were no statistically significant differences between mortality or RRT. The 2-step cluster analysis separated the cohort into 3 clusters, see Fig. 1: Cluster 1 (n = 26) with ‘nephrotic range proteinuria’ mean sAlb 30 g/L, uPCR 778 mg/mmol and eGFR 72 ml/min; Cluster 2 (n = 43) with ‘non-nephrotic range proteinuria’, mean sAlb 39 g/L, uPCR 284 mg/mmol and eGFR 46 ml/min; Cluster 3 (n = 18) ‘NS’ sAlb 20 g/L, uPCR 1117 mg/mmol and eGFR 25 ml/min. IS use was comparable in the NS (cluster 3) and nephrotic range proteinuria (cluster 1) cohorts, but lower in cluster 2 (non-nephrotic range proteinuria) 77.8% &amp; 69.2% vs 11.6% p &amp;lt;0.001. Rates of complete remission were greatest in clusters 1 &amp; 3 vs cluster 2: 57.7% &amp;66.7% vs 37.2% though this did not achieve statistical significance (p 0.067). Conclusion Although there have been several recent US &amp; Asian reviews of primary FSGS, this study provides a review of the epidemiology of FSGS over a 20-year period in a predominantly white cohort in the UK. In general, the patients who received IS had lower sAlb and achieved remission more frequently. Although the aetiology of primary FSGS is unknown, it is hypothesised that it is due to an undiscovered circulating permeability factor. After the exclusion of secondary causes, KDIGO suggests only making the diagnosis in the presence of NS. Despite this the average sAlb in most epidemiological studies of primary FSGS have been above 30g/l. This is likely because of the inclusion of undiagnosed genetic or adaptive FSGS, but it may also be true that NS phenotype alone is too insensitive to diagnose primary ‘antibody driven’ FSGS. Our cluster analysis highlighted 3 potential FSGS phenotypes: A nephrotic cluster that clearly require IS; a cohort with preserved sAlb and non-nephrotic range proteinuria who will benefit from supportive care; lastly a cluster with heavy proteinuria but a sAlb &amp;gt; 30g/l. This group may still have antibody driven disease and thus benefit from immunosuppression and potentially genetic testing. The study received grant support from CSL Vifor

Immunosuppression versus Supportive Care on Kidney Outcomes in IgA Nephropathy in the Real-World Setting.

The efficacy of immunosuppression in the management of immunoglobulin A (IgA) nephropathy remains highly controversial. The study was conducted to assess the effect of immunosuppression, compared with supportive care, in the real-world setting of IgA nephropathy. A cohort of 3946 patients with IgA nephropathy, including 1973 new users of immunosuppressive agents and 1973 propensity score-matched recipients of supportive care, in a nationwide register data from January 2019 to May 2022 in China was analyzed. The primary outcome was a composite of 40% eGFR decrease of the baseline, kidney failure, and all-cause mortality. A Cox proportional hazard model was used to estimate the effects of immunosuppression on the composite outcomes and its components in the propensity score-matched cohort. Among 3946 individuals (mean [SD] age 36 [10] years, mean [SD] eGFR 85 [28] ml/min per 1.73 m 2 , and mean [SD] proteinuria 1.4 [1.7] g/24 hours), 396 primary composite outcome events were observed, of which 156 (8%) were in the immunosuppression group and 240 (12%) in the supportive care group. Compared with supportive care, immunosuppression treatment was associated with 40% lower risk of the primary outcome events (adjusted hazard ratio, 0.60; 95% confidence interval, 0.48 to 0.75). Comparable effect size was observed for glucocorticoid monotherapy and mycophenolate mofetil alone. In the prespecified subgroup analysis, the treatment effects of immunosuppression were consistent across ages, sexes, levels of proteinuria, and values of eGFR at baseline. Serious adverse events were more frequent in the immunosuppression group compared with the supportive care group. Immunosuppressive therapy, compared with supportive care, was associated with a 40% lower risk of clinically important kidney outcomes in patients with IgA nephropathy.

Clinicopathological features and outcome in elderly patients with idiopathic membranous nephropathy

Background Idiopathic membranous nephropathy (IMN) is the leading cause of nephrotic syndrome in the elderly. The treatment of idiopathic membranous nephropathy is quite challenging due to the particularity of elderly patients. This study intends to investigate the clinicopathological characteristics and initial therapeutic effect of idiopathic membranous nephropathy among elderly patients. Methods A retrospective study of 67 elderly patients (58.2% male, median age 69.0 years, range, 65–83 years) with biopsy-proven membranous nephropathy was conducted at Guangdong Provincial People’s Hospital from 2016 to 2020. Data on clinicopathological characteristics and initial therapeutic effects were analyzed. Results Of the 67 patients, the mean eGFR of overall patients was 66.49 mL/min/1.73m2 while the median urine protein-to-creatinine ratio (uPCR) and urine albumin-to-creatinine ratio (uACR) was 5676.73 mg/g and 2951.56 mg/g, respectively. Pathological data revealed that the membranous Churg’s stage II was the most frequent (71.64%). Moreover, glomerular PLA2R antigen fluorescence intensity of (+) and IgG4 antigen fluorescence intensity of (++) were detected in 63.6% and 86.4% of all patients, respectively. Overall, 44 patients, accounting for 65.7%, achieved remission including complete remission and partial remission within 1 year after renal biopsy. Compared with a non-remission group, the levels of uPCR (6274.6 vs. 3235.6 mg/g, p = 0.007) and uACR (3433.6 vs. 1773.2 mg/g, p = 0.017) were significantly higher in remission group. The proportion of immunosuppressive therapy in the remission group was also higher (86.4% vs. 30.4%, p < 0.01). Compared with conservative treatment, patients with combined treatment with glucocorticoid and cyclophosphamide (CTX) or glucocorticoid and calcineurin inhibitor (CNIs) achieved higher remission rate (glucocorticoid plus cyclophosphamide vs. conservative treatment, 84.6% vs. 27.3%, p = 0.001; glucocorticoid plus calcineurin inhibitor vs. conservative treatment, 88.0% vs. 27.3%, p < 0.001). Further analysis showed that compared with patients who underwent conservative treatment, the proportion of males, the levels of uPCR, uACR, BUN, Scr, CysC and PLA2R antigen-positive staining rate in kidney biopsy were higher in those who underwent combined treatment with glucocorticoid and CTX, while the levels of eGFR, TP and ALB were lower (p < 0.05). In addition, patients who received combined treatment with glucocorticoid and CNIs had higher levels of uPCR, uACR, TC and lower levels of TP, ALB than those who received conservative treatment (p < 0.05). Moreover, there were no statistically significant differences in the 1-year progression rate in eGFR between the immunosuppressive treatment group and conservative treatment group (3.3 vs. 0.2 ml/min/1.73m2, p = 0.852). Conclusions Most elderly patients diagnosed with IMN had multiple comorbidities, and the membranous Churg’s stage II was most common. The glomerular PLA2R and IgG4 antigen deposition were frequently detected accompanied by glomerulosclerosis and severe tubulointerstitial injury. For high-risk elderly patients with severe proteinuria, early initial immunosuppressive therapy could achieve a higher urinary protein remission rate. Therefore, it is crucial for clinicians to balance the risks and benefits of immunosuppressive therapy based on clinical and pathological characteristics and develop individualized treatment regimens for elderly patients with IMN.