Treatment Of IgA Nephropathy Research Articles

Network Pharmacological Analysis of Hydroxychloroquine Intervention in the Treatment of Iga Nephropathy.

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally and has a high propensity to develop into end-stage renal disease (ESRD). Hydroxychloroquine has been proven to reduce proteinuria in IgAN patients, but the precise mechanism remains unclear. Therefore, network pharmacology was used to investigate the mechanism. PubChem and SwissADME databases were utilized to acquire the structure of hydroxychloroquine. The SwissTargetPrediction, PharmMapper, DrugBank, TargetNet, and BATMAN-TCM databases were then utilized to obtain the targets. The target genes related to IgAN were then gathered from the databases, which included GeneCards, PHARMGKB, DrugBank, OMIM, and DisGeNET. Common targets were obtained by UniProt. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to define the main molecular mechanisms and pathways. Furthermore, a protein-protein interaction (PPI) network was constructed using the STRING tool, and the core targets were obtained by Cytoscape. Finally, molecular docking between the core targets and hydroxychloroquine was performed. 167 common target genes were acquired by overlapping. The core targets were TNF, ALB, IL1B, JUN, FOS, SRC, and MMP9. The GO and KEGG results showed the targets to be related to the production of inflammatory cytokines and chemokines and were engaged in the toll-like receptor (TLR) signaling pathway. At the same time, the molecular docking results showed that the core targets all combined with hydroxychloroquine closely. This study proved that hydroxychloroquine may treat IgAN through the TLR signaling pathway, and the restraint of TNF, TLR, IL1B, and JUN may be essential for the treatment.

Therapeutic Profile of IgA Nephropathy Regarding Pharyngeal Kidney Theory

IgA nephropathy (IgAN) is the most common glomerular disease, which is one of the main causes of chronic kidney disease. The course of this disease is prolonged, and the condition is often recurrent, and most of the disease changes after respiratory, gastrointestinal, and urinary infections, and respiratory infections are the most common of the three, which makes the treatment more difficult. In Chinese medicine, there is no direct name for this disease, but according to its symptoms, it can be categorized as "hematuria", "edema", "urolithiasis", "slow kidney wind" and other diseases. The disease is often caused by the recurrence of exogenous infections. For the recurrence of this disease due to exogenous infection, Chinese medicine treats IgA nephropathy from the pharynx according to the theory of "pharyngeal and renal correlation", which has achieved good clinical efficacy, and this point of view has received more and more attention nowadays. This article focuses on the treatment of IgA nephropathy from the pharyngeal-renal theory.

From Despair to Promise: The Dawn of Novel Treatment in IgA Nephropathy.

From Despair to Promise: The Dawn of Novel Treatment in IgA Nephropathy.

Integrative multi-omics and network pharmacology reveal the mechanisms of Fangji Huangqi Decoction in treating IgA nephropathy

Ethnopharmacological relevanceFangji Huangqi Decoction (FJHQD), a classical Chinese herbal formulation, has demonstrated significant clinical efficacy in the treatment of IgA nephropathy (IgAN), although its mechanisms remain poorly understood. Aim of the studyThis study aims to investigate the renal protective mechanisms of FJHQD using an integrated approach that combines transcriptomics, proteomics, and network pharmacology. MethodsRenal glomerular structure changes were assessed via hematoxylin and eosin (H&E) and Masson staining. IgA expression in the glomeruli was quantified using immunofluorescence. Furthermore, the potential mechanisms underlying the effects of FJHQD were explored through a combined strategy of network pharmacology, transcriptomics, and proteomics. The expression of signaling pathway-related proteins was detected using Western blot. ResultsFJHQD inhibited mesangial cell proliferation and renal interstitial fibrosis, and significantly reduced excessive IgA deposition in the glomerular mesangium. Network pharmacology identified 113 important active components and 8 common active components in FJHQD, with quercetin, isorhamnetin, jaranol, and kaempferol having the highest number of target interactions. Integration of network pharmacology with multi-omics approaches revealed that 44 active components regulated numerous immune and inflammatory signaling pathways through 17 hub targets. These pathways include the Calcium signaling pathway, cAMP signaling pathway, Ras signaling pathway, MAPK signaling pathway, and PI3K-AKT signaling pathway. Subsequent in vivo experiments demonstrated that FJHQD effectively regulates the identified pathways in IgAN mice. Ultimately, molecular docking results further validated the reliability of the network pharmacology combined with multi-omics analyses. ConclusionThe findings suggest that FJHQD exerts a renal protective effect, potentially through modulation of the Calcium signaling pathway, cAMP signaling pathway, Ras signaling pathway, MAPK signaling pathway, and PI3K-AKT signaling pathway. These insights offer valuable support for the clinical use of FJHQD and open new avenues for exploring the active compounds and molecular mechanisms of Traditional Chinese Medicines (TCMs).

Combination treatment with telitacicept, mycophenolate mofetil and glucocorticoids for immunoglobulin A nephropathy: A case report

BACKGROUND Telitacicept reduces B cell activation and abnormal immunoglobulin A (IgA) antibody production by inhibiting the activity of B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), thereby decreasing IgA deposition in the glomeruli and local inflammatory response. This ultimately protects the kidneys from damage. This mechanism suggests that Telitacicept has potential efficacy in the treatment of IgA nephropathy. CASE SUMMARY We present the case of a 24-year-old female who was diagnosed with IgA nephropathy due to significant proteinuria and mild renal impairment. Pathologically, she exhibited focal proliferative glomerulonephritis. Treatment with angiotensin II receptor blocker, hormones, and mycophenolate mofetil did not lead to a significant improvement in her condition. However, upon the addition of telitacicept, the patient’s renal function recovered and her proteinuria rapidly reduced. Hormones were swiftly tapered and discontinued, with no occurrence of severe infections or related complications. CONCLUSION Telitacicept combined with hormones and mycophenolate mofetil may be a safe and effective induction therapy for IgA nephropathy.

Follow-Up Kidney Biopsy Might Be a Mandatory Procedure after Treatment in IgA Nephropathy

Follow-Up Kidney Biopsy Might Be a Mandatory Procedure after Treatment in IgA Nephropathy

New Insights and Future Perspectives of APRIL in IgA Nephropathy.

IgA nephropathy (IgAN) is characterized by immune-mediated glomerulonephritis, with the accumulation of galactose-deficient IgA1 (Gd-IgA1) in the glomeruli and increased levels of circulating Gd-IgA1 and Gd-IgA1-containing immune complexes. An incomplete understanding of the underlying mechanisms and differences in clinical and pathological features between individuals and ethnicities has contributed to the lack of established treatments for IgAN. A tumor necrosis factor (TNF) family member, a proliferation-inducing ligand (APRIL), is a crucial cytokine essential for the generation and survival of plasma cells. Recent studies demonstrated that APRIL is a pivotal mediator in the production of Gd-IgA1 in IgAN. As our understanding of the autoimmune pathogenesis underlying IgAN has improved, various pharmacological therapeutic targets, including APRIL antagonists, have emerged. Preliminary results showed that APRIL-targeting agents effectively reduced proteinuria and Gd-IgA1 levels without significantly increasing adverse events, indicating their potential as novel therapeutic agents for IgAN. In the present review, we discuss the current understanding of the role of APRIL in the pathogenesis of IgAN and novel therapeutic strategies focusing on APRIL-targeting agents for IgAN. APRIL inhibitors may offer new hope to patients with IgAN.

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.

IgA Nephropathy – Current and Future Perspectives in Treatment

Abstract Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulopathy in our adult population and is associated with a high lifetime risk of kidney failure. Recent years have succeeded in describing the pathogenesis of IgAN at the molecular level, where immune complexes containing specific galactose deficient IgA1 play an essential role. The gold standard in the diagnosis of IgAN remains renal biopsy followed by determination of a prognostic score using the Oxford classification. A fundamental goal in the management of patients with IgAN is to optimize supportive therapy involving active lifestyle modification and renoprotective medications. The reno-protective drug menu has recently been expanded to include effective sodium-glucose cotransporter 2 inhibitors (SGLT2i), and additional agents are on the way. However, despite maximal supportive therapy, a wide range of patients remain at high risk of disease progression and require the deployment of immunomodulatory drugs. To date, however, we do not have high potency agents that are well tolerated and safe. This has led to the initiation of many studies to target the inflammatory process at different pathogenetic levels. In this article, we summarize the current standards in the treatment of IgAN and present new promising options in the management of this disease.

IgA Nephropathy: Significance of IgA1-Containing Immune Complexes in Clinical Settings.

IgA nephropathy (IgAN) is considered to be an autoimmune disease characterized by the formation of IgA1-containing immune complexes in the circulation and glomerular immunodeposits. Extensive research has identified multiple genetic, immunological, and environmental factors contributing to disease development and progression. The pathogenesis of IgAN is considered a multifactorial process involving the formation of immune complexes wherein aberrantly O-glycosylated IgA1 is recognized as an autoantigen. Consequently, the clinical presentation of IgAN is highly variable, with a wide spectrum of manifestations ranging from isolated microscopic hematuria or episodic macroscopic hematuria to nephrotic-range proteinuria. Whereas some patients may exhibit a slowly progressive form of IgAN, others may present with a rapidly progressive glomerulonephritis leading to kidney failure. Development of the treatment for IgAN requires an understanding of the characteristics of the pathogenic IgA1-containing immune complexes that enter the glomerular mesangium and induce kidney injury. However, not all details of the mechanisms involved in the production of galactose-deficient IgA1 and immune-complex formation are fully understood. Here, we review what we have learned about the characteristics of nephritogenic IgA1 in the half-century since the first description of IgAN in 1968.

Advances in primary glomerulonephritis.

Primary glomerulonephritis comprises several renal-limited diseases that can cause haematoproteinuria, chronic kidney disease, nephrosis and end stage kidney disease. The most common of these are IgA nephropathy (IgAN), primary membranous nephropathy (PMN), Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD). Although rare, these diseases cause a significant burden to health care systems, given the high cost of treating End Stage Kidney Disease (ESKD) with dialysis or transplantation. Until recently, the pathogenesis of primary gloerulonephritis has remained obscure. However, recent advances in understanding of how these diseases evolve has led to the introduction of novel therapeutic agents. Trials are underway or have recently completed that have huge implications for the standard of care for the primary glomerulonephritidies, and should dramatically reduce the number of patients who progress onto end stage kidney disease. This article reviews the international Kidney Disease Improving Global Outcomes (KDIGO) guidelines for the treatment of IgAN, PMN, FSGS and MCD, as well as recent research on pathogenesis and treatment.

Current understanding and new insights in the treatment of IgA nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, and almost all patients are at risk of progression to end-stage kidney disease within their lifetime. The mechanisms responsible for the presentation and development of IgAN are required for the development of highly targeted therapies for this disease. In this review, we first demonstrate the current treatment strategy of IgAN recommended by the 2021 KDIGO guideline. Then, we update the new insights into disease pathogenesis based on the well acknowledged 'multiple-hit hypothesis' and provide the potential therapeutic targets involved in the upstream production of pathogenic IgA1 and the downstream complement activation. Finally, the recent large randomized controlled trials focusing on these novel targets have been summarized, among which Nefecon and Sparsentan have received approval and Telitacicept have been used off-label for IgAN. In the future, emerging treatment approaches for IgAN is likely to evolve, which will signify a shift in the management of the IgAN from traditional immunosuppressive approaches to an era of targeted treatment based on the understanding of the pathogenic mechanisms.

Research Progress of Traditional Chinese Medicine in the Treatment of IgA Nephropathy

The treatment of IgA nephropathy (IgAN) is difficult, and modern medicine is still not clear about its etiology and pathogenesis. Traditional Chinese medicine(TCM) plays an important role in the treatment of IgAN, the use of "poison damage of renal collaterals", from the wind treatment, general use, "mediation trijiao", treating IgAN from the pharynx, spleen and kidney, intelligent door as well as five zang-organs make , the selection of Zhuling decoction, Banxia-xiexin decoction, Shenqi-Dihuang Decoction, Guben-Tongluo Decoction and other classic and experience prescriptions, trijiao acupuncture, invigorating spleen and kidney acupuncture treatment, etc. TCM such as diet therapy can control clinical symptoms such as hematuria, proteinuria and hypertension caused by IgAN, and further control and delay the progress of IgAN.

Immunosuppressive therapy for IgA nephropathy in children.

IgA nephropathy (IgAN) is the most common cause of primary glomerulonephritis. It is a heterogeneous disease with different presentations and high morbidity. Thirty per cent of adults and 20% of children (followed into adulthood) will have a 50% decline in kidney function or develop kidney failure after 10 years. To determine the benefits and harms of immunosuppressive therapy for the treatment of IgAN in children. We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 03 October 2023 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. We included randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) investigating the treatment of IgAN in children with immunosuppressive therapies compared to placebo, no treatment, supportive care, standard therapy (Japanese protocol), other immunosuppressive therapies or non-immunosuppressive therapies. Two authors independently extracted data and assessed the risk of bias. Random effects meta-analyses were used to summarise estimates of treatment effects. Treatment effects were expressed as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes, and the mean difference (MD) and 95% CI for continuous outcomes. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs and the ROBIN-I tool for NRSIs. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). This review included 13 studies with 686 participants. Ten RCTs included 334 children and 191 adults, and three NRSIs included 151 participants, all children. Most participants had mild kidney disease. The risk of bias was unclear for most of the domains relating to allocation concealment, blinding of participants, personnel, and outcome assessment. In children with IgAN, it is uncertain if corticosteroid (steroid) therapy, compared to placebo reduces proteinuria (1 study, 64 children and young adults: RR 0.47, 95% CI 0.13 to 1.72; low certainty evidence) or the decline in estimated glomerular filtration rate (eGFR) (1 study, 64 children and young adults: RR 0.47, 95% CI 0.09 to 2.39; low certainty evidence). It is uncertain if steroids reduce proteinuria compared to supportive care (2 studies, 61 children: RR 0.04, 95% CI -0.83 to 0.72; low certainty evidence). Adverse events associated with steroid therapy were not assessed due to heterogeneity in steroid protocols, including dose and duration, and lack of systematic assessment for adverse events in the included studies. Azathioprine, mycophenolate mofetil, mizoribine, or cyclophosphamide alone or in combination with steroid therapy had uncertain effects on improving proteinuria or preventing eGFR decline in children with IgAN. Fish oil, vitamin E and tonsillectomy had uncertain effects on improving proteinuria or preventing eGFR decline. Effects of other immunosuppressive therapies, secondary outcomes and adverse events were not assessed due to insufficient data. There is a lack of high-quality evidence to guide the management of IgAN in children. There is no evidence to indicate that steroids, other immunosuppressive therapies, or tonsillectomy, when added to optimal supportive care, prevent a decline in eGFR or proteinuria in children with IgAN. Available studies were few, with small numbers, low-quality evidence, high or uncertain risk of bias, did not systematically assess harms associated with treatment, or report net benefits or harms. Severe cases and atypical presentations of IgAN were not included in the reviewed studies, and our findings cannot be generalised to these situations.

#1063 Presentation, treatment, and outcome of IgA nephropathy in children: comprehensive characterization of a Croatian single centre cohort

Abstract Background and Aims IgA nephropathy (IgAN) is a complex disease diagnosed only upon evaluation of a kidney biopsy. Since the threshold to perform this invasive procedure is higher and symptoms usually more indolent in children, the true prevalence might be underestimated, with fewer studies examining the presentation, treatment, and outcome of IgAN in paediatric population. Moreover, there is a substantial heterogeneity of clinical presentation and pathological features between geographical locations, with fewer data available for region of central and southern Europe. We therefore aim to provide a conscientious description of a paediatric IgAN cohort followed for an extended period of time in a centre caring for most of the Croatian paediatric patients. Method Single centre retrospective study of children newly diagnosed as IgAN since 2011 and followed for >2 years in a tertiary referral centre for paediatric nephrology of the Republic of Croatia. Results Total of 15 paediatric (<18 years) patients were included, of which 11 (73%) were male, 14 Caucasians and 1 of Roma origin. All the patients had proteinuria (>150 mg/day) and hematuria (>5 RBC/mm3 in uncentrifuged urine) at the time of the biopsy, with the mean age of 12.2 ± 3.6 years. The median eGFR was 87 (69 – 111) mL/min/1.73m2 and the median value of proteinuria 260 (150 – 370) mg/day. More specifically, 2 patients had mild proteinuria (<20 mg/kg/day), 12 had moderate (20 – 50 mg/kg/day) and 1 had nephrotic range (>50 mg/kg/day). The results of biopsy in terms of MEST-C score showed M1 in 4, E1 in none, S1 in 3, T1 in 4, T2 in 0, C1 in 2 and C2 in none of the patients. The IF was positive for IgA and C3 in all patients, and in 1 for C1q. There was no significant correlation between C3 intensity values (0-4+) and 24 h proteinuria (r = 0.49, p = 0.06) or eGFR (r = −0.22, p = 0.43). Hypertension (≥95 percentile for age) was present in 2 (13%) patients. The median risk of a 30% decline in eGFR or progression to end-stage renal disease 5 years after renal biopsy calculated by International IgAN prediction tool for use in paediatric patents was 8.03% (4.58 – 11.27). Initial presenting episode was treated with ACEi in 7 (47%) and with glucocorticoids in 4 (27%) patients. There was no significant difference in proteinuria (p = 0.19) or risk of decline in eGFR or progression to ESRD (p = 0.16) among treated and untreated patients. In all of the treated patients proteinuria reached a target of <20 mg/kg during the median time of 11 (6 – 21) months. The median follow up was 6.5 (2.8 – 11.1) years. During the follow up 5 patients experienced first relapse of proteinuria, 3 had second and none had third relapse. None of the patients had adverse event related to medications. None were treated with renal replacement therapy or other immunomodulatory drugs. Tonsillectomy was performed in two patients with a substantial improvement of haematuria episodes reported by caregivers. Omega-3 polyunsaturated fatty acid was used in 1 patient. While none of the patients developed CKD during the follow up, none have reached complete renal remission defined as eGFR >90 ml/min/1.73m2, proteinuria <150 mg/day and RBC < 5/mm3 in urinalysis. Conclusion All the patients in our cohort had indolent disease with proteinuria, along with low risk of decline in eGFR or progression to ESRD after biopsy. Almost half of them were treated with ACEi, and a quarter with glucocorticoids, all with beneficial response. Nevertheless, none of the patients in the cohort achieved full renal remission due to the persistent hematuria. While there are few well performed studies on the treatment of IgAN in adult patients, to date, there are no high-quality randomised studies on immunosuppressing and other drugs, as well as nutritional and other interventions in children with IgAN, prompting a case-to-case decision regarding the use of various therapeutic modalities. Therefore, well characterized cohorts from around the globe might provide further reassurance for physicians taking care of children with this intricating disease, support when deciding to commence the intervention and inform while selecting the most appropriate form.

#2954 A comparative view of IgA nephropathy care across four global regions

Abstract Background and Aims IgA nephropathy (IgAN) is a chronic, rare, and slow progressing glomerular disease. IgAN treatment currently consists of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB), sodium-glucose co-transporter 2 (SGLT2) inhibitors, corticosteroids, and recently approved Nefecon and sparsentan in select markets. This research compares approaches to IgAN treatment in four regions of the world. Method Data was collected in partnership with 730 nephrologists submitting chart data from 1,570 of their most recently seen IgAN patients to create a representative sample across the US, EU5 (UK, Germany, Italy, France, and Spain), Japan, and China via parallel online surveys in 2023. Results Regardless of their geographic location, audited patient charts revealed that hypertension, hyperlipidemia, obesity, and diabetes were the leading comorbid conditions among IgAN patients. Across the four regions evaluated, Japanese patients were the healthiest (44% have no comorbid conditions vs. 28% EU5, 25% China, 18% US) and Japanese nephrologists perceived 79% of their IgAN patients to be in “excellent” overall health. Comparatively, patients in the US had the highest calculated body mass index (28.2) and the most comorbid conditions reported. Audited records also revealed that patients in Japan and China were referred to nephrology care earlier in their CKD progression as measured by eGFR levels, with over 50% of patients referred to their current nephrologist in CKD Stages 1 or 2, compared to approximately 35% of patients in the US and EU5. Chinese nephrologists (59%) and those in the US (53%) were most likely to agree that it is easy to identify IgAN patients who are likely to have rapid progression (vs. 43% EU5 and 40% Japan). When treating their IgAN patients, Japanese nephrologists ordered labs on a more frequent basis compared to those in the US, EU5, and China and on average, Japanese patients had blood work and urinalysis labs conducted six times within the past twelve months (versus four in the other countries.) Most audited patients had a calculated annual eGFR decline of 1 ml/year or more. Chinese patients (77%) were most notable for their IgAN progression, while those in Japan were least likely to be progressing in their disease (41%). Due to its chronic nature, most IgAN patients will eventually need dialysis, and while still representative of the majority of their audited patients, US nephrologists projected the lowest percentage of IgAN patients to eventually progress to end stage renal disease (66% vs. 73% Japan, 75% EU5, and 85% China). Most participating nephrologists reported that they closely adhere to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines when treating their IgAN patients. Nearly all audited IgAN patients were on baseline therapy of ACE inhibitors or ARBs, while the uptake of SGLT2 inhibitors has been notable in China (44%), the US (43%), and EU5 (43%), with Japan (33%) trailing in current treatment rates. Meanwhile, the use of corticosteroid was also higher in patients in Japan (65%) and China (59%) compared to those in the EU5 (51%) and US (43%). Of note, tonsillectomies are frequently used as a treatment approach for IgAN patients in Japan, with 45% of patients having received the procedure, whereas this approach is used much less often in the other regions. Following a tonsillectomy, nearly all Japanese patients received a pulse of steroids, leading to higher overall corticosteroid use compared to other regions. At the time of fielding, Nefecon was available to prescribe in the US and Germany with 9% and 7% of patients currently on treatment, respectfully; however, sparsentan had not been approved in any regions. Conclusion The comparison of patient chart data across various regions reveals differences in perspectives and IgAN treatment approaches among nephrologists. Prognostic and predictive tools are available and utilized globally, but the reliability and correlation between results, lab values, and disease progression calls for better education and alignment of global treatment guidelines.

#1894 Disappearance of proteinuria is not a surrogate marker of improvement in IgA nephropathy

Abstract Background and Aims IgA nephropathy is one of the most common chronic glomerulonephritis and 30-45% falls into chronic kidney disease over a period of 20 to 25 years. Lots of treatment regimens are tried such as RAAS blocker, corticosteroids, complement inhibitors, Nefecon, Atrasentan, SGLT2 inhibitor etc., however disappearance of proteinuria has been regarded as surrogate marker of improvement. We performed follow up renal biopsy to confirm the efficacy of disappearance of proteinuria. Method During last 10 years, our clinic performed 1,867 cases of renal biopsies at OPD level. Of which 585 cases (31.3%) were IgA nephropathy. We performed follow up renal biopsies in 149 cases, who showed improved proteinuria after methylprednisolone pulse therapy. Follow renal biopsy findings were divided into 3 groups: One cycle of methylprednisolone pulse therapy consists of methylprednisolone (20-30 mg/kg, max 1 gm/day) for 3 consecutive days. Depends on the pathological grade, we performed 3 to 17 cycles every 2 weeks. Results Male to female ratio was 0.96(73:76), Mean age was 38.4 years old. Of the 149 follow up biopsies, 75 cases (50%) showed improved pathology (Group A), 60 cases (40%) showed no pathological changes (Group B) and 14 cases (10%) showed aggravated pathology (Group C). Conclusion Normalized proteinuria could not be a surrogate marker of renal improvement, because only 50% showed pathological improvement. Follow up renal biopsy might be a mandatory procedure to define the efficacy of treatment in IgA nephropathy.

#1392 MEST-C score correlation with proteinuria reduction after SGLT2i treatment in patients with IgA nephropathy

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with better cardiovascular outcomes and with nephroprotection independent of diabetes status. Recent data suggest that SGLT2i significantly reduce proteinuria in patients with IgA nephropathy (IgAN). Data available for the use of the MEST-C score to determine if treatment would benefit IgAN patients is scarce. The aim of our study was to assess the degree of proteinuria reduction after SGLT2i treatment in IgAN and its possible association with the MEST-C score. Method 63 adult patients with biopsy-proven IgA nephropathy, eGFR ≥ 30 mL/min/1.73 m2 (CKD-epi), and total urine protein of >0.5 grams/day at screening were included. Patients with secondary IgAN and crescents were excluded. All receiving maximally tolerated RASi for at least 12 weeks. All patients started dapagliflozin 10 mg once per day after baseline data were registered. The total follow-up was 12 months. The main outcome was the decline in eGFR and the reduction in 24-hour proteinuria from SGLT2i initiation to 1,3, 6, 9, 12 months, end-stage renal disease, or kidney or cardiovascular death. Three repeated measurements of proteinuria (mg/24H) were performed, 90 days before SGLT2i treatment initiation, and only patients with stable proteinuria were enrolled in the study. Results 49 patients (35/14 M/F), with mean age of 41,9 ± 19,6 years, completed follow up. 8 patients discontinued treatment due to adverse events attributed to dapagliflozin. At baseline eGFR was 68.21±18,1 ml/min/1.73 m2 and Upr: 2196±1091 mg/24H. The MEST-C scores were correlated with the serum creatinine level, proteinuria, and hematuria. The mean serum creatinine level was higher in M1, E1, S1, and T1 compared with score “0”. It was statistically significant (p = 0.03) only in the T-score. The mean proteinuria level was again higher in M1, S1, and T1 but reached statistical significance (p = 0.037) in only the T1-score. E1 has higher hematuria. The Upr/24H difference for dapagliflozin was −24.7% (95% CI −27.5, −23.2; p < 0.001) at the end of follow-up (month 12). Proteinuria reduction was similar across all eGFRs, age, and baseline proteinuria. Among MEST-C score parameters, T1 had a negative impact on the antiproteinuric effect of dapagliflozin (p = 0.01) No hypoglycemic events were reported and no deaths occurred. Conclusion In the present study, the use of SGLT2i was associated with a significant reduction of proteinuria in patients with IgA nephropathy and maximally tolerated RASi. We analyzed renal outcomes in association with pathologic features. We established that the presence of the T1 score has a negative impact on proteinuria reduction after SGLT2i treatment. Further studies are needed to investigate the impact of the use of the Oxford Classification score for developing individual treatment therapies.

#1679 Relationship between initial eGFR DIP with proteinuria after SGLT2i treatment, in patients with IgA nephropathy. A real-world clinical study

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with better cardiovascular outcomes and with nephroprotection independent of diabetes status. Recent data suggest that SGLT2i significantly reduce proteinuria in patients with IgA nephropathy (IgAN). However, they often cause an initial decline in estimated glomerular filtration rate (eGFR). The aim of our study was to assess the degree of proteinuria reduction after SGLT2i treatment in IgAN and its possible association with the initial functional dip in eGFR. Method 63 adult patients with biopsy-proven IgA nephropathy, eGFR ≥ 30 mL/min/1.73 m2 (CKD-epi), and total urine protein of >0.5 grams/day at screening were included. Patients with secondary IgAN were excluded. All receiving maximally tolerated RASi for at least 12 weeks. All patients started dapagliflozin 10 mg once per day after baseline data were registered. The total follow-up was 12 months. The main outcome was the decline in eGFR and the reduction in 24-hour proteinuria from SGLT2i initiation to 1,3, 6, 9, 12 months, end-stage renal disease, or kidney or cardiovascular death. Results 55 patients (38/17 M/F), with mean age of 44,2±18,3 years, completed follow up. 8 patients discontinued treatment due to adverse events attributed to dapagliflozin. At baseline eGFR was 66.17±19,7 ml/min/1.73 m2 and Upr: 2356±1023 mg/24H. There was a transient decline in eGFR, 30 days after initiation of dapagliflozin (66.17±19,7 min/1.73 m2 at baseline to 57 ml/min/1.73 m2) but then, there was an improvement at month 3 from baseline. The Upr/24H difference for dapagliflozin was −25.1% (95% CI −27.5, −23.2; p < 0.001) at the end of follow-up (month 12). Proteinuria reduction was similar across all eGFRs. Notably, a significant correlation was found between the initial eGFR dip and percentage proteinuria reduction in the 12th month. (R = –0.23; p = 0.03). Consistent results of dapagliflozin treatment on proteinuria were found in all analysis subgroups including sex, baseline proteinuria, systolic blood pressure, and body mass index. No hypoglycaemic events were reported and no deaths occurred. Conclusion In the present study, the use of SGLT2i was associated with a significant reduction of proteinuria in patients with IgA nephropathy in patients with maximally tolerated RASi. Higher initial eGFR dip after treatment initiation was a predictor of a significantly higher reduction in proteinuria at the end of follow-up. The correlation between eGFR dip and proteinuria reduction perhaps reflects the intraglomerular pressure reduction, mediated by tubuloglomerular feedback, one of the numerous.

#1993 Analysis of the characteristics of IgA nephropathy patients using real-world data from five European countries

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally; it has a significant health burden and a highly variable disease course. As IgAN is a heterogeneous disease, it is important to appreciate the associated patient characteristics in order to understand disease progression and how best to implement individualised treatment regimens. To determine the patient characteristics associated with IgAN, a physician questionnaire and patient chart audit were conducted. Method From 21 December 2022 to 6 February 2023, physicians from five European countries (France, Germany, Spain, Italy and the UK) completed a questionnaire and patient chart review of their IgAN patients. Physicians were required to have ≥50 patients with stage 1–4 chronic kidney disease (CKD); at least four of these were required to be non-dialysis IgAN patients. Patients whose charts were included were required to be aged 12 years or older, non-dialysis IgAN patients and have an estimated glomerular filtration rate of ≥15 mL/min/1.72 m2. The charts included were required to be from patients who had seen a participating physician within the prior 6 months. Results 261 physicians answered the questionnaire and completed chart audits on 473 of their most recently seen patients. Patient charts audited were largely from male (71%) Caucasian (78%) patients from 31–49 years of age (38%). 22% of patients were referred to their current physician within the past year. Most patients (70%) were referred by a primary care physician and 9% by another nephrologist. Of those referred by a nephrologist, 32% were referred for specialised care. Participating physicians perceived that close to 30% of patients were referred to them late or extremely late, with contributing factors including lack of engagement from patients with annual follow-ups and patients remaining asymptomatic for a long time. At the most recent visit, 24.3% had CKD stage 1 or 2, 26.6% of patients had CKD stage 3a, 30.4% had stage 3b and 18.6% had stage 4 disease. Nephrologists characterised 53% of their CKD stage 4 patients as having severe IgAN. The symptoms reported with greatest frequency at the most recent visit included fatigue (59%), blood in the urine (41%) and increased weight gain (41%). In total, 71% of patients had proteinuria >0.5 g/day (8% had no values available) and 8% of patients had nephrotic syndrome (urine protein >3.5 g/day and low serum albumin). In total, 28% of patients had no co-morbid conditions. More than half (54%) of the patients whose charts were audited had comorbid hypertension. Other comorbidities included hyperlipidaemia (22%), obesity (17%), type 2 diabetes (15%) and peripheral oedema (7%). Counterintuitively, when asked about the overall health of their patients, physicians perceived the majority (98%) of patients to be in good or excellent overall health. Patients were prescribed five medications on average, with most (92%) taking an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, or both. The number of medications prescribed increased after the age of 50. Two-thirds (66%) of physicians felt that patients completely adhered to their treatment regimen. However, 54% of physicians reported some form of dissatisfaction with the response of their patients to their overall treatment regimen; though, levels of satisfaction varied between individual treatment options. Conclusion Despite high rates of proteinuria and patients often in late-stage CKD at referral, physicians perceived the majority of patients to be in good or excellent overall health, revealing a potential gap in physicians’ perceptions of patients’ health and their risk of progression to kidney failure. As a result, patients were often diagnosed or referred late and their perception of their own health may have led to a lack of engagement with physicians. These data indicate that there is an unmet need for early diagnosis and treatment of IgAN to ensure that patients receive appropriate care.