Medullary sponge kidney with IgA nephropathy: a case report and literature review.

BACKGROUND: Medullary sponge kidney (MSK)is rare in association with glomerulonephritis. We report a patient with medullary sponge kidney, and the kidney biopsy revealed a diagnosis of IgA nephropathy. CASE PRESENTATION: A 27-year-old female presented with hematuria and proteinuria, and imaging studies indicated the presence of medullary spongy kidney. With appropriate preparation, a kidney biopsy was performed. Considering the patient's clinical and pathological characteristics, the final diagnosis was determined to be medullary sponge kidney associated by IgA nephropathy. The combination of corticosteroids and angiotensin receptor blockers (ARBs) proved to be significantly effective in reducing proteinuria in the current case. To the best of our knowledge, this is the first reported case that demonstrates the coexistence of MSK and IgA nephropathy. CONCLUSIONS: Administering precise therapy based on renal pathology can potentially enhance outcomes for patients with renal conditions, necessitating the need for clinicians to be vigilant about differential diagnosis in order to reduce the rates of missed diagnoses and misdiagnosis.

[Anti-Proteinuric Effect of GLP1-RA as Add-On to SGLT2-i and ACE-i in a Diabetic Patient with IgA Nephropathy].

Immunoglobulin A (IgA) nephropathy is a common glomerulonephritis, but its treatment remains matter of debate. Recommendation for corticosteroids has been supported, but renin-angiotensin inhibitors, RAAS, and sodium-glucose co-transporter 2 inhibitors (SGLT2i) are increasingly used because of a better benefit/safety balance in comparison with systemic steroids and immunosuppressive treatments. In this case report, a patient with type 2 diabetes (T2DM) and biopsy-proven nephrotic IgA-related nephropathy documented a rapid meaningful reduction of proteinuria and the effect was persistent for 2 years, after receiving the treatment with a GLP1-RA on top of the previous treatment with ACE-inhibitors and SGLT2-i. Considering the beneficial effects of GLP1-RA in diabetes related chronic kidney disease, the present case report supports the notion that these drugs could also represent a beneficial treatment option in IgA nephropathy.

Sinomenine Hydrochloride Protects IgA Nephropathy Through Regulating Cell Growth and Apoptosis of T and B Lymphocytes.

Purpose: Sinomenine hydrochloride (SH) is used to treat chronic inflammatory diseases such as rheumatoid arthritis and may also be efficacious against Immunoglobulin A nephropathy (IgAN). However, no trial has investigated the molecular mechanism of SH on IgAN. Therefore, this study aims to investigate the effect and mechanism of SH on IgAN. Methods: The pathological changes and IgA and C3 depositions in the kidney of an IgAN rat model were detected by periodic acid-Schiff (PAS) and direct immunofluorescence staining. After extracting T and B cells using immunomagnetic beads, we assessed their purity, cell cycle phase, and apoptosis stage through flow cytometry. Furthermore, we quantified cell cycle-related and apoptosis-associated proteins by Western blotting. Results: SH reduced IgA and C3 depositions in stage 4 IgAN, thereby decreasing inflammatory cellular infiltration and mesangial injury in an IgAN model induced using heteroproteins. Furthermore, SH arrested the cell cycle of lymphocytes T and B from the spleen of IgAN rats. Regarding the mechanism, our results demonstrated that SH regulated the Cyclin D1 and Cyclin E1 protein levels for arresting the cell cycle and it also regulated Bax and Bcl-2 protein levels, thus increasing Cleaved caspase-3 protein levels in Jurkat T and Ramos B cells. Conclusion: SH exerts a dual regulation on the cell cycle and apoptosis of T and B cells by controlling cell cycle-related and apoptosis-associated proteins; it also reduces inflammatory cellular infiltration and mesangial proliferation. These are the major mechanisms of SH in IgAN.

Immunosuppressive treatment results in patients with primary IgA nephropathy in Turkiye; the data from TSN-GOLD working group.

BACKGROUND: Immunoglobulin A (IgA) nephropathy (IgAN) treatment consists of maximal supportive care and, for high-risk individuals, immunosuppressive treatment (IST). There are conflicting results regarding IST. Therefore, we aimed to investigate IST results among IgAN patients in Turkiye. METHOD: The data of 1656 IgAN patients in the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases Study Group were analyzed. A total of 408 primary IgAN patients treated with IST (65.4% male, mean age 38.4 ± 12.5 years, follow-up 30 (3-218) months) were included and divided into two groups according to treatment protocols (isolated corticosteroid [CS] 70.6% and combined IST 29.4%). Treatment responses, associated factors were analyzed. RESULTS: Remission (66.7% partial, 33.7% complete) was achieved in 74.7% of patients. Baseline systolic blood pressure, mean arterial pressure, and proteinuria levels were lower in responsives. Remission was achieved at significantly higher rates in the CS group (78% vs. 66.7%, p = 0.016). Partial remission was the prominent remission type. The remission rate was significantly higher among patients with segmental sclerosis compared to those without (60.4% vs. 49%, p = 0.047). In the multivariate analysis, MEST-C S1 (HR 1.43, 95% CI 1.08-1.89, p = 0.013), MEST-C T1 (HR 0.68, 95% CI 0.51-0.91, p = 0.008) and combined IST (HR 0.66, 95% CI 0.49-0.91, p = 0.009) were found to be significant regarding remission. CONCLUSION: CS can significantly improve remission in high-risk Turkish IgAN patients, despite the reliance on non-quantitative endpoints for favorable renal outcomes. Key predictors of remission include baseline proteinuria and specific histological markers. It is crucial to carefully weigh the risks and benefits of immunosuppressive therapy for these patients.

Sparsentan ameliorates glomerular hypercellularity and inflammatory-gene networks induced by IgA1-IgG immune complexes in a mouse model of IgA nephropathy.

IgA nephropathy (IgAN) is characterized by glomerular deposition of immune complexes (ICs) consisting of IgA1 with O-glycans deficient in galactose (Gd-IgA1) and Gd-IgA1-specific IgG autoantibodies. These ICs induce kidney injury, and in the absence of disease-specific therapy, up to 40% of patients with IgAN progress to kidney failure. IgA1 with its clustered O-glycans is unique to humans, which hampered development of small-animal models of IgAN. Here, we used a model wherein engineered ICs (EICs) formed from human Gd-IgA1 and recombinant human IgG autoantibody are injected into nude mice to induce glomerular injury mimicking human IgAN. In this model, we assessed the protective effects of sparsentan, a single-molecule dual endothelin angiotensin receptor antagonist (DEARA) versus vehicle on EIC-induced glomerular proliferation and dysregulation of gene expression in the kidney. Oral administration of sparsentan (60 or 120 mg/kg daily) to mice intravenously injected with EIC attenuated the EIC-induced glomerular hypercellularity. Furthermore, analysis of changes in the whole kidney transcriptome revealed that key inflammatory and proliferative biological genes and pathways that are upregulated in this EIC model of IgAN were markedly reduced by sparsentan, including complement genes, integrin components, members of the mitogen-activated protein kinase family, and Fc receptor elements. Partial overlap between mouse and human differentially expressed genes in IgAN further supported the translational aspect of the immune and inflammatory components from our transcriptional findings. In conclusion, our data indicate that in the mouse model of IgAN, sparsentan targets immune and inflammatory processes leading to protection from mesangial hypercellularity.NEW & NOTEWORTHY The mechanisms by which deposited IgA1 immune complexes cause kidney injury during early phases of IgA nephropathy are poorly understood. We used an animal model we recently developed that involves IgA1-IgG immune complex injections and determined pathways related to the induced mesangioproliferative changes. Treatment with sparsentan, a dual inhibitor of endothelin type A and angiotensin II type 1 receptors, ameliorated the induced mesangioproliferative changes and the associated alterations in the expression of inflammatory genes and networks.

A Case Report of Kidney Transplantation in a Patient With Pre-existing Chronic Myeloid Leukemia: The Role of Achieving Molecular Response and Treatment-Free Remission.

BACKGROUND: Treatment-free remission (TFR) in chronic myeloid leukemia (CML) is achieved when a patient who has discontinued tyrosine-kinase inhibitor treatment sustains major molecular response (MMR) and does not require restarting therapy. The feasibility of kidney transplantation (KT), and achieving TFR post-transplantation in patients with a pre-existing CML, are currently not well-studied. METHODS: We describe the clinical course of a 39-year-old Filipino woman with IgA nephropathy who developed CML during treatment. She received nilotinib 600 mg daily and was able to achieve MMR after 5 months. Eight years later, the patient sustained MMR; however, she ultimately underwent KT due to advancing kidney disease. Before the transplant, she was able to achieve deep molecular response. In anticipation of possible drug-to-drug interaction of nilotinib with tacrolimus and everolimus, a shared decision was made to discontinue nilotinib despite not fulfilling the criteria for TFR. Twelve months post-transplant, the patient remains in MMR without nilotinib. Good renal allograft function was maintained, and there were no signs of allograft rejection. CONCLUSIONS: Attempting TFR may be feasible after KT in patients with low-risk chronic phase CML especially if good molecular response is obtained before the transplant. Data regarding the length at which TFR can be maintained after KT is still yet to be determined. In this regard, low-risk chronic phase CML in good disease control may not be considered a contraindication to KT.

Protective effect of modified Huangqi Chifeng decoction on immunoglobulin A nephropathy through toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B signaling pathway.

OBJECTIVE: To examine the nephroprotective mechanism of modified Huangqi Chifeng decoction (, MHCD) in immunoglobulin A nephropathy (IgAN) rats. METHODS: To establish the IgAN rat model, the bovine serum albumin, lipopolysaccharide, and carbon tetrachloride 4 method was employed. The rats were then randomly assigned to the control, model, telmisartan, and high-, medium-, and low-dose MHCD groups, and were administered the respective treatments via intragastric administration for 8 weeks. The levels of 24-h urinary protein, serum creatinine (CRE), and blood urea nitrogen (BUN) were measured in each group. Pathological alterations were detected. IgA deposition was visualized through the use of immunofluorescence staining. The ultrastructure of the kidney was observed using a transmission electron microscope. The expression levels of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-ß1 (TGF-ß1) were examined by immunohistochemistry and quantitative polymerase chain reaction. Levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB) P65, were examined by immunohistochemistry, Western blotting, and quantitative polymerase chain reaction. RESULTS: The 24-h urine protein level in each group increased significantly at week 6, and worsen from then on. But this process can be reversed by treatments of telmisartan, and high-, medium-, and low-dose of MHCD, and these treatments did not affect renal function. Telmisartan, and high-, and medium-dose of MHCD reduced IgA deposition. Renal histopathology demonstrated the protective effect of high-, medium-, and low-dose of MHCD against kidney injury. The expression levels of MCP-1, IL-6, and TGF-ß1 in kidney tissues were downregulated by low, medium and high doses of MHCD treatment. Additionally, treatment of low, medium and high doses of MHCD decreased the protein and mRNA levels of TLR4, MyD88, and NF-κB. CONCLUSIONS: MHCD exerted nephroprotective effects on IgAN rats, and MHCD regulated the expressions of key targets in TLR4/MyD88/NF-κB signaling pathway, thereby alleviating renal inflammation by inhibiting MCP-1, IL-6 expressions, and ameliorating renal fibrosis by inhibiting TGF-ß1 expression.

Efficacy and safety of biologic agents for IgA nephropathy: A protocol for systematic review and meta-analysis.

BACKGROUND: IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide and a leading cause of chronic kidney failure. There are currently no definitive therapeutic regimens to treat or prevent the progression of IgAN. However, biologic agents offer novel therapeutic approaches that target immunological mechanisms to slow or halt disease progression. The objective of this study is to evaluate the efficacy and safety of biologic agents in patients with IgA nephropathy. METHODS: We will systematically search PubMed, EMbase, Web of Science, Cochrane Library, and www.clinicaltrials.gov for randomized controlled trials of biologic agents for the treatment of IgA nephropathy. The search period will span from the establishment of each database until October 2023. The quality assessment of included studies will be performed individually using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2), and meta-analysis will be conducted using Revman 5.4.1 software. CONCLUSIONS: The results of this study will provide evidence-based medical evidence for the clinical application of biologic agents in patients with IgA nephropathy. PROSPERO REGISTRATION NUMBER: CRD42023400450.

Efficacy and safety of low-dose corticosteroids combined with leflunomide for progressive IgA nephropathy: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The effectiveness of immunosuppressive and corticosteroid treatments for Immunoglobulin A (IgA) nephropathy (IgAN) remains thoroughly evaluated. We undertook a meta-analysis to investigate the efficacy and safety of low-dose corticosteroids plus leflunomide for progressive IgA nephropathy. METHODS: Eligible studies were obtained from PubMed, Embase, and Cochrane Library databases. We also searched the references of the included studies. Our protocol followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Eligibility criteria were defined using a PICOS framework. RESULTS: Our study included three articles presenting 342 patient cases. Findings revealed that low-dose corticosteroids combined with the leflunomide group were effective in relieving urine protein excretion (UPE) [mean difference (MD) = -0.35, 95% confidence interval (CI): -0.41 to -0.30, P < 0.00001] compared with the full-dose corticosteroids group. Regarding serum creatinine (SCr), estimated glomerular filtration rate (eGFR), complete remission rate, and overall response rate, there was no difference between the groups (p > 0.05). Regarding safety, low-dose corticosteroids combined with leflunomide significantly reduced the risk of serious adverse events [odds ratio (OR): 0.11, 95% CI: 0.01 to 0.91, P = 0.04]. Besides, no significant differences were observed between the two groups in the incidence of respiratory infection, abnormal liver function, diarrhea, herpes zoster, alopecia, pruritus, insomnia, pneumonia, diabetes, and urinary tract infection (P > 0.05). CONCLUSIONS: Low-dose corticosteroids combined with leflunomide are a safe and effective treatment for progressive IgA nephropathy. TRIAL REGISTRATION: The PROSPERO registration number is CRD42022361883.

A cluster of type I interferon-regulated genes associates with disease activity and prognosis in patients with IgA nephropathy.

The exact pathogenesis of IgA nephropathy (IgAN) is complex and so far, not well defined. Since it has been shown that microbial infections could induce high levels of type I interferon (IFN-I) and there is an evident link between mucosal infection and gross hematuria in IgAN, we hypothesized that IFN-I may play a role in the pathogenic process. In this study, we investigated the type I interferon status in IgAN based on the expression of 17 IFN-regulated genes (IRGs) in whole blood from 59 IgAN patients in a cross-sectional study, of which 34 patients followed longitudinally. Analysis of the IFN-score showed that there was a significant elevated IFN-score in the IgAN patients compared with healthy controls (n = 28, p = 9.80 × 10-3), and we observed an elevated IFN-score in the group with less tubular atrophy/interstitial fibrosis (p = 1.07 × 10-2) and with a lower proportion of mesangial hypercellularity (p = 1.23 × 10-2). In the longitudinal analysis, Cox regression analysis revealed that a higher IFN level was associated with a better renal outcome in IgAN after adjustments for gender and age (hazard ratio, 0.90; 95 % confidence interval, 0.81 to 0.97; p = 4.20 × 10-2). In conclusion, our finding suggested that IFN score may represent a novel type of biomarker in IgAN, which requires further exploration on its mechanism and therapeutic targeting.

Unveiling biomarkers and therapeutic targets in IgA nephropathy through large-scale blood transcriptome analysis.

INTRODUCTION: IgA nephropathy (IgAN) is the most prevalent form of glomerulonephritis. Unfortunately, molecular biomarkers for IgAN derived from omics studies are still lacking. This research aims to identify critical genes associated with IgAN through large-scale blood transcriptome analysis. METHODS: We constructed novel blood transcriptome profiles from peripheral blood mononuclear cells (PBMCs) of 53 Chinese IgAN patients and 28 healthy individuals. Our analysis included GO, KEGG, and GSEA for biological pathways. We analyzed immune cell profiles with CIBERSORT and constructed PPI networks with STRING, visualized in Cytoscape. Key differentially expressed genes (DEGs) were identified using CytoHubba and MCODE. We assessed the correlation between gene expressions and clinical data to evaluate clinical significance and identified hub genes through machine learning, validated with an open-access dataset. Potential drugs were explored using the CMap database. RESULTS: We identified 333 DEGs between IgAN patients and healthy controls, mainly related to immune response and inflammation. Key pathways included NK cell mediated cytotoxicity, complement and coagulation cascades, antigen processing, and B cell receptor signaling. Cytoscape revealed 16 clinically significant genes (including KIR2DL1, KIR2DL3, VISIG4, C1QB, and C1QC, associated with sub-phenotype and prognosis). Machine learning identified two hub genes (KLRC1 and C1QB) for a diagnostic model of IgAN with 0.92 accuracy, validated at 1.00 against the GSE125818 dataset. Sirolimus, calcifediol, and efaproxiral were suggested as potential therapeutic agents. CONCLUSION: Key DEGs, particularly VISIG4, KLRC1, and C1QB, emerge as potential specific markers for IgAN, paving the way for future targeted personalized treatment options.

Non-immunosuppressive treatment for IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerular disease, with approximately 20% to 40% of patients progressing to kidney failure within 25 years. Non-immunosuppressive treatment has become a mainstay in the management of IgAN by improving blood pressure (BP) management, decreasing proteinuria, and avoiding the risks of long-term immunosuppressive management. Due to the slowly progressive nature of the disease, clinical trials are often underpowered, and conflicting information about management with non-immunosuppressive treatment is common. This is an update of a Cochrane review, first published in 2011. OBJECTIVES: To assess the benefits and harms of non-immunosuppressive treatment for treating IgAN in adults and children. We aimed to examine all non-immunosuppressive therapies (e.g. anticoagulants, antihypertensives, dietary restriction and supplementation, tonsillectomy, and herbal medicines) in the management of IgAN. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to December 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of non-immunosuppressive agents in adults and children with biopsy-proven IgAN were included. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed search results, extracted data and assessed study quality. Results were expressed as mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI) using random-effects meta-analysis. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: This review includes 80 studies (4856 participants), of which 24 new studies (2018 participants) were included in this review update. The risk of bias within the included studies was mostly high or unclear for many of the assessed methodological domains, with poor reporting of important key clinical trial methods in most studies. Antihypertensive therapies were the most examined non-immunosuppressive therapy (37 studies, 1799 participants). Compared to placebo or no treatment, renin-angiotensin system (RAS) inhibition probably decreases proteinuria (3 studies, 199 participants: MD - 0.71 g/24 h, 95% CI -1.04 to -0.39; moderate certainty evidence) but may result in little or no difference to kidney failure or doubling of serum creatinine (SCr), or complete remission of proteinuria (low certainty evidence). Death, remission of haematuria, relapse of proteinuria or > 50% increase in SCr were not reported. Compared to symptomatic treatment, RAS inhibition (3 studies, 168 participants) probably decreases proteinuria (MD -1.16 g/24 h, 95% CI -1.52 to -0.81) and SCr (MD -9.37 µmol/L, 95% CI -71.95 to -6.80) and probably increases creatinine clearance (2 studies, 127 participants: MD 23.26 mL/min, 95% CI 10.40 to 36.12) (all moderate certainty evidence); however, the risk of kidney failure is uncertain (1 study, 34 participants: RR 0.20, 95% CI 0.01 to 3.88; very low certainty evidence). Death, remission of proteinuria or haematuria, or relapse of proteinuria were not reported. The risk of adverse events may be no different with RAS inhibition compared to either placebo or symptomatic treatment (low certainty evidence). In low certainty evidence, tonsillectomy in people with IgAN in addition to standard care may increase remission of proteinuria compared to standard care alone (2 studies, 143 participants: RR 1.90, 95% CI 1.45 to 2.47) and remission of microscopic haematuria (2 studies, 143 participants: RR 1.93, 95% CI 1.47 to 2.53) and may decrease relapse of proteinuria (1 study, 73 participants: RR 0.70, 95% CI 0.57 to 0.85) and relapse of haematuria (1 study, 72 participants: RR 0.70, 95% CI 0.51 to 0.98). Death, kidney failure and a > 50% increase in SCr were not reported. These trials have only been conducted in Japanese people with IgAN, and the findings' generalisability is unclear. Anticoagulant therapy, fish oil, and traditional Chinese medicines exhibited small benefits to kidney function in patients with IgAN when compared to placebo or no treatment. However, compared to standard care, the kidney function benefits are no longer evident. Antimalarial therapy compared to placebo in one study reported an increase in a > 50% reduction of proteinuria (53 participants: RR 3.13 g/24 h, 95% CI 1.17 to 8.36; low certainty evidence). Although, there was uncertainty regarding adverse events from this study due to very few events. AUTHORS' CONCLUSIONS: Available RCTs focused on a diverse range of interventions. They were few, small, and of insufficient duration to determine potential long-term benefits on important kidney and cardiovascular outcomes and harms of treatment. Antihypertensive agents appear to be the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined were predominantly angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The benefits of RAS inhibition appear to outweigh the harms in patients with IgAN. The certainty of the evidence of RCTs demonstrating a benefit of tonsillectomy to patients with Japanese patients with IgAN was low. In addition, these findings are inconsistent across observational studies in people with IgAN of other ethnicities; hence, tonsillectomy is not widely recommended, given the potential harm of therapy. The RCT evidence is insufficiently robust to demonstrate efficacy for the other non-immunosuppressive treatments evaluated here.

IgA vasculitis nephritis: insights from kidney biopsies.

PURPOSE OF REVIEW: To present findings indicating the value of kidney biopsy in assessing prognosis and guiding clinical approach to patients with IgA vasculitis nephritis (IgAVN), including a recent international study examining the value of the Oxford (MEST-C) classification. RECENT FINDINGS: Historically, kidney biopsies with IgAVN are scored using the International Society for Kidney Diseases in Children (ISKDC) classification. However, this classification has limited prognostic value, and most biopsies fall into just two of the six ISKDC grades. There are few studies examining the clinical value of the Oxford classification, which is well documented to be predictive of kidney outcomes in IgA nephropathy, in IgAVN. However, a recent study of 361 biopsied patients with IgAVN showed that endocapillary hypercellularity (Oxford E1) predicted a subclass of patients showing initial improvement in kidney function with immunosuppressive treatment, followed by a later decline. SUMMARY: Kidney outcome in patients with biopsied IgAVN treated with immunosuppression is determined by clinical factors and endocapillary hypercellularity. The latter is not part of the ISKDC classification and supports including MEST-C scores in biopsy reports of IgAVN. Even patients showing a good initial response to immunosuppression require long-term follow-up due to risk of subsequent kidney function decline.

New therapies for immunoglobulin A nephropathy: what's the standard of care in 2023?

PURPOSE OF REVIEW: As the most common primary glomerulonephritis, immunoglobulin A (IgA) nephropathy (IgAN) is an important cause of kidney failure and mortality. Until recently, therapeutic options were limited. Fortunately, there have been numerous recent clinical trials demonstrating efficacy of new therapies in slowing chronic kidney disease (CKD) progression at varying stages of disease. RECENT FINDINGS: The TESTING trial has provided high-quality evidence for slowing estimated glomerular filtration rate (eGFR) decline with a reduced-dose glucocorticoid regimen, while demonstrating an improved safety profile. Targeted-release budesonide represents a well tolerated therapy for reducing eGFR decline. Mycophenolate mofetil may reduce CKD progression in some populations, while hydroxychloroquine is efficacious in reducing proteinuria. Sodium-glucose cotransporter (SGLT2) inhibitors and sparsentan are effective therapies for CKD due to IgAN, but should not be used in lieu of disease-modifying immunosuppressive therapy. Many new therapies are approaching readiness for clinical use. SUMMARY: Numerous therapeutic options now exist and include disease-modifying and nephroprotective drugs. Identifying the right treatment for the right patient is now the clinical challenge and, with new drugs on the horizon, represents the primary unmet research need in this rapidly-developing field.

Efficacy and Safety of Hydroxychloroquine in Patients with IgA Nephropathy: A Meta-Analysis.

AIM: The purpose of this study was to determine efficacy and safety of hydroxychloroquine (HCQ) for patients with IgA nephropathy (IgAN). METHODS: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, Wanfang database, Chinese National Knowledge Infrastructure and VIP database up to February 2023 were searched for associated studies comparing HCQ with any other nonHCQ for treating IgAN. The effects of proteinuria, a 50% decrease in proteinuria, estimated glomerular filtration rate (eGFR) and adverse events in patients with IgAN were examined in a meta-analysis. Data were extracted and pooled using RevMan 5.3. RESULTS: Three randomized controlled trials (RCTs), two retrospective and two prospective studies (675 patients) that matched our inclusion criteria were identified. Compared with a control group, HCQ significantly reduced proteinuria (mean difference (MD): -0.26, 95% confidence interval (CI): -0.44 to -0.08, p < 0.01). Patients receiving HCQ plus renin-angiotensin system inhibitors (RASSi) had a better efficacy in proteinuria alleviation and a 50% decrease in proteinuria compared with control groups (MD: -0.38, 95% CI: -0.50 to -0.25, p < 0.001 and relative risk (RR) = 3.31, 95% CI: 1.73 to 6.36, p < 0.001). No appreciable variations were observed in eGFR between HCQ groups and control groups in treating patients with IgAN (MD: -2.00, 95% CI: -4.36 to 0.36, p = 0.10). Moreover, no serious adverse events were observed during HCQ treatment. CONCLUSIONS: Our results indicate HCQ is an efficient, secure treatment for IgAN.

Composition analysis of Compound Shenhua Tablet, a seven-herb Chinese medicine for IgA nephropathy: evaluation of analyte-capacity of the assays.

Compound Shenhua Tablet, a medicine comprising seven herbs, is employed in treating IgA nephropathy. This study aimed to meticulously analyze its chemical composition. Based on a list of candidate compounds, identified through extensive literature review pertinent to the tablet's herbal components, the composition analysis entailed the systematic identification, characterization, and quantification of the constituents. The analyte-capacity of LC/ESI-MS-based and GC/EI-MS-based assays was evaluated. The identified and characterized constituents were quantified to determine their content levels and were ranked based on the constituents' daily doses. A total of 283 constituents, classified into 12 distinct categories, were identified and characterized in the Compound Shenhua Tablet. These constituents exhibited content levels of 1-10 982 µg·g-1, with daily doses of 0.01-395 µmol·d-1. The predominant constituents, with daily doses of ≥ 10 µmol·d-1, include nine organic acids (citric acid, quinic acid, chlorogenic acid, cryptochlorogenic acid, gallic acid, neochlorogenic acid, isochlorogenic acid C, isochlorogenic acid B, and linoleic acid), five iridoids (specnuezhenide, nuezhenoside G13, nuezhenidic acid, secoxyloganin, and secologanoside), two monoterpene glycosides (paeoniflorin and albiflorin), a sesquiterpenoid (curzerenone), a triterpenoid (oleanolic acid), and a phenylethanoid (salidroside). Additionally, there were 83, 126, and 55 constituents detected in the medicine with daily doses of 1-10, 0.1-1, and 0.01-0.1 µmol·d-1, respectively. The combination of the LC/ESI-MS-based and GC/EI-MS-based assays demonstrated a complementary relationship in their analyte-capacity for detecting the constituents present in the medicine. This comprehensive composition analysis establishes a solid foundation for further pharmacological research on Compound Shenhua Tablet and facilitates the quality evaluation of this complex herbal medicine.

[IgA nephropathy: the beginning of a new therapeutic era]. / Néphropathie à IgA: le début d'une nouvelle ère thérapeutique.

Primary IgA nephropathy is a common glomerular disease, heterogeneous in its clinical presentation. Historically considered to assume a benign course, we actually know that up to 40% of the cases progress to end stage renal disease at 20-30 years. Clinical and basic research has now allowed to understand the pathophysiology of this disease, to predict its course and to treat progressive forms more aggressively. This article summarizes classical treatments and recent therapeutic additions (sparsentan and targeted-release budenoside), which demonstrated remarkable efficacy. Complement inhibitors and B cells or plasma cells inhibitors to target aberrant IgA production have already emerged as new potential treatments. Collectively these advances may open a new therapeutic era in the management of this disease.

La néphropathie à IgA primaire est une maladie glomérulaire fréquente, hétérogène dans sa présentation clinique. Longtemps considérée comme bénigne, nous savons aujourd'hui que jusqu'à 40 % des cas progressent vers l'insuffisance rénale terminale après 20 à 30 ans de progression. La recherche a maintenant permis de mieux comprendre la physiopathologie de cette maladie, d'en prédire le devenir et de traiter plus agressivement les formes évolutives. Cet article fait le point sur les traitements classiques et les additions récentes (sparsentan et budénoside à libération entérique) qui ont démontré une efficacité remarquable. Les inhibiteurs du complément, des lymphocytes B ou des plasmocytes, ciblant la production d'IgA pathogéniques, montrent des résultats prometteurs. Ces avancées ouvrent une ère thérapeutique nouvelle dans la prise en charge de cette maladie.

Refractory IgA Nephropathy: A Challenge for Future Nephrologists.

IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage kidney disease (ESKD). Presently, the primary strategy for managing IgAN revolves around optimizing blood pressure and mitigating proteinuria. This is achieved through the utilization of renin-angiotensin system (RAS) inhibitors, namely, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As outlined by the KDIGO guidelines, individuals who continue to show a persistent high risk of progressive ESKD, even with comprehensive supportive care, are candidates for glucocorticoid therapy. Despite these therapies, some patients have a disease refractory to treatment, defined as individuals that present a 24 h urinary protein persistently >1 g after at least two rounds of regular steroids (methylprednisolone or prednisone) and/or immunosuppressant therapy (e.g., mycophenolate mofetil), or who do not tolerate regular steroids and/or immunosuppressant therapy. The aim of this Systematic Review is to revise the current literature, using the biomedical database PubMed, to investigate possible therapeutic strategies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, fecal microbiota transplantation, as well as blockade of complement components.