IgA nephropathy: a review of existing and emerging therapies.
Ontology highlight
ABSTRACT:
SUBMITTER: Noor SM
PROVIDER: S-EPMC10479631 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Publications
IgA nephropathy: a review of existing and emerging therapies.
Noor Sahibzadi Mahrukh SM Abuazzam Farah F Mathew Roy R Zhang Zhiwei Z Abdipour Amir A Norouzi Sayna S
Frontiers in nephrology 20230523
IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. Recently, there have been multiple advances in the understanding of IgAN pathophysiology and therapeutic options. Despite the advent of new treatment options, individual risk stratification of the disease course and choosing the best treatment strategy for the patient remains challenging. A multitude of clinical trials is ongoing, opening multiple opportunities for enrollment. In this brief review we discuss ...[more]
Similar Datasets
Project description:IgA nephropathy is the most common primary glomerulonephritis with potentially serious outcome leading to end stage renal disease in 30 to 50% of patients within 20 to 30 years. Renal biopsy, which might be associated with risks of complications (bleeding and others), still remains the only reliable diagnostic tool for IgA nephropathy. Therefore, the search for non-invasive diagnostic and prognostic markers for detection of subclinical types of IgA nephropathy, evaluation of disease activity, and assessment of treatment effectiveness, is of utmost importance. In this review, we summarize treatment options for patients with IgA nephropathy including the drugs currently under evaluation in randomized control trials. An early initiation of immunosupressive regimens in patients with IgA nephropathy at risk of progression should result in the slowing down of the progression of renal function to end stage renal disease.
| S-EPMC7730306 | biostudies-literature
Project description:Purpose of the reviewImmunoglobulin A (IgA) nephropathy (IgAN) is the most common primary glomerular kidney disease. Children and adults are presumed to have the same disease and are treated similarly. However, there are differences between childhood IgAN and adult IgAN that may require unique treatment considerations, even after transition to adult nephrology services. A narrative review was conducted to compare childhood and adult IgAN and to describe the distinct characteristics of childhood IgAN. Reframing childhood IgAN can inform guideline recommendations unique to childhood IgAN, the development of targeted therapies, and clinical trial design.Sources of informationMedline and Embase were searched for reports on children and adults with IgAN published between January 2013 and December 2023 (updated May 2024). The search was not restricted by age group, outcomes reported, language, or study design. Randomized controlled trials (RCTs), observational studies, review articles, and nephrology conference abstracts were included. A total of 3104 reports were retrieved. Forty-seven reports (37 primary studies and 10 reviews) were included in the review. Two RCTs and 35 observational studies included a total of 45 085 participants (9223 children and 35 862 adults).MethodData were extracted for primary IgAN and not for IgA vasculitis-associated nephritis. Findings were described with no statistical comparisons due to variations in interventions and outcome definitions.Key findingsGross hematuria was the obvious clinical difference between childhood IgAN and adult (60-88% vs 15-20%). Nephrotic syndrome was more common in children, approaching up to 44%, while <18% of adults had nephrotic syndrome. Children were biopsied sooner (6 vs 15 months) and had more inflammatory kidney lesions (mesangial hypercellularity: 41-82% vs 38-64%; endocapillary hypercellularity: 39-58% vs 17-34%). Chronic kidney lesions were more prevalent in adults (segmental sclerosis: 62-77% vs 8-51%; interstitial fibrosis/tubular atrophy: 34-37% vs 1-18%). The use of immunosuppressive therapy was higher in children (46-84% vs 35-56%). Children were started on immunosuppressive therapy sooner than adults. Adults were more likely to be optimized with renin-angiotensin system inhibitors (87-94% vs 49-75%). Children had better kidney function than adults at diagnosis (estimated glomerular filtration rate of 90-128 vs 50-88 ml/min/1.73 m2), and children also had better kidney survival, with kidney failure of 3.1% vs 13.4% at 5 years. Children had more risk alleles for IgAN and higher levels of mannose-binding lectin than adults.LimitationsMost studies were retrospective and observational, with limited data on children and disease mechanisms. Data were not pooled for analysis because of important differences in definitions and measurements of baseline characteristics and outcomes. Data from countries with established urine screening programs were different compared to countries without urine screening programs. Some observed differences may be due to practice variation and delayed diagnosis in adults (lead-time bias). Well-designed prospective studies and standardized measures for kidney function assessment and outcomes can reduce heterogeneity and improve results from reviews.ConclusionInherent differences between childhood IgAN and adult IgAN may be due to distinct disease mechanisms. Approaching childhood IgAN as a separate condition could lead to the discovery of targeted therapies and improve management during childhood and after the transition to adult care.
| S-EPMC11898040 | biostudies-literature
Project description:Rosacea is a chronic inflammatory skin disease characterized by centrofacial erythema, papules, pustules, and telangiectasias. The onset of rosacea typically occurs after 30 years of age. It is estimated that approximately 2-5% of adults worldwide are affected. While the exact etiology of rosacea remains unknown, its pathogenesis is thought to be multifactorial with both environmental and genetic factors implicated. Ultraviolet radiation, heat, steam, ingested agents, including spicy foods and alcohol, host vasculature, dermal matrix degeneration, genetic susceptibility, and microbial organisms, including Demodex mites and Heliobacter pylori, have been implicated in the development of rosacea. Recently, mast cells (MCs) have emerged as key players in the pathogenesis of rosacea through the release of pro-inflammatory cytokines, chemokines, proteases, and antimicrobial peptides leading to cutaneous vasodilation, angiogenesis, and tissue fibrosis. Several existing and emerging topical, oral, and injectable therapeutics have been associated with improvement of rosacea symptoms based on their ability to stabilize and downregulate activated MCs. Herein, we review the data implicating MCs in the pathogenesis of rosacea and discuss interventions that may stabilize this pathway.
| S-EPMC8484408 | biostudies-literature
Project description:Familial hypercholesterolemia (FH), an autosomal dominant disorder of LDL metabolism that is characterized by elevated LDL-cholesterol, is commonly encountered in patients with atherosclerotic coronary heart disease. Combinations of cholesterol-lowering therapies are often used to lower LDL-cholesterol in patients with FH; however, current treatment goals for LDL-cholesterol are rarely achieved in patients with homozygous FH (HoFH) and are difficult to achieve in patients with heterozygous FH (HeFH). Therapies that lower LDL-cholesterol through LDL receptor-mediated mechanisms have thus far been largely ineffective in patients with HoFH, particularly in those with negligible (<2%) LDL receptor activity. Among patients with HeFH who were at very high risk for atherosclerotic cardiovascular disease events, combined therapy consisting of a high dose of high-intensity statin, ezetimibe, and proprotein convertase subtilisin Kexin type 9 inhibitor failed to lower LDL-cholesterol to minimal acceptable goals in more than 50%. This article provides a framework for the use of available and emerging treatments that lower LDL-cholesterol in adult patients with HoFH and HeFH. A framework is provided for the use of angiopoietin-like protein 3 inhibitors in the treatment of HoFH and HeFH.
| S-EPMC8065289 | biostudies-literature
Project description:IgA nephropathy (IgAN) is a leading cause of CKD and renal failure. Recent international collaborative efforts have led to important discoveries that have improved our understanding of some of the key steps involved in the immunopathogenesis of IgAN. Furthermore, establishment of multicenter networks has contributed to rigorous design and execution of clinical trials that have provided important insights regarding immunotherapy in IgAN. In this article, we review emerging developments in clinical and translational IgAN research and describe how these novel findings will influence future strategies to improve the outcome of patients with IgAN.
| S-EPMC5383386 | biostudies-literature
Project description:ObjectiveGalactose-deficient IgA1 was evaluated in patients with IgA nephropathy(IgAN) and controls in order to determine the predictive value of galactose-deficient IgA1 in cases of IgA nephropathy.MethodsPubMed, EMBASE, Cochrane central register of controlled trials, CNKI, CBM disc, and VIP database were searched to identify eligible studies that evaluated a difference in aberrant IgA1 glycosylation in IgAN patients compared with controls. A meta-analysis was conducted to evaluate the impact of galactose-deficient IgA1(Gd-IgA1) levels in different groups.ResultsA total of 22 studies (n = 1657) met inclusion criteria. The mean Newcastle-Ottawa Scale (NOS) score was 7.2 and ranged from 6 to 8. The standard mean difference(SMD) in the meta-analysis of 20 studies of the level of Gd-IgA1 in the serum and/or supernatant of cultured cells was higher in the IgAN group compared with healthy controls as well as in those with other renal diseases (SMD = 1.76, 95% CI = 1.18-2.34, P<0.00001; SMD = 1.05, 95% CI = 0.05-2.04, P = 0.04). The data synthesis suggested that IgAN patients had similar levels of serum Gd-IgA1, with no significant differences, compared with first-degree relatives and Henoch-Schonlein purpura nephritis (HSPN) patients (MD = 0.04, 95% CI = 0.00-0.08, P = 0.05; MD = -46.03, 95% CI = -217.70-125.64, P = 0.60). In addition, the combined MD of 5 studies indicated that there were no significant differences in Gd-IgA1 levels among patients with varying severities of IgAN (MD = 0.02, 95% CI = -0.02-0.05, P = 0.28).ConclusionsThe pooled evidence suggests that the level of Gd-IgA1 in the serum or supernatant of cultured cells from peripheral blood or tonsils may be a useful biomarker for predicting IgA nephropathy, though the level of Gd-IgA1 was not significantly associated with disease severity.
| S-EPMC5117702 | biostudies-literature
Project description:Immunoglobulin A nephropathy (IgAN), characterized by mesangial deposition of galactose-deficient-IgA1 (Gd-IgA1), is the most common biopsy-proven primary glomerulonephritis worldwide. Recently, an improved understanding of its underlying pathogenesis and the substantial risk of progression to kidney failure has emerged. The "four-hit hypothesis" of IgAN pathogenesis outlines a process that begins with elevated circulating levels of Gd-IgA1 that trigger autoantibody production. This results in the formation and deposition of immune complexes in the mesangium, leading to inflammation and kidney injury. Key mediators of the production of Gd-IgA1 and its corresponding autoantibodies are B-cell activating factor (BAFF), and A proliferation-inducing ligand (APRIL), each playing essential roles in the survival and maintenance of B cells and humoral immunity. Elevated serum levels of both BAFF and APRIL are observed in patients with IgAN and correlate with disease severity. This review explores the complex pathogenesis of IgAN, highlighting the pivotal roles of BAFF and APRIL in the interplay between mucosal hyper-responsiveness, B-cell activation, and the consequent overproduction of Gd-IgA1 and its autoantibodies that are key features in this disease. Finally, the potential therapeutic benefits of inhibiting BAFF and APRIL in IgAN, and a summary of recent clinical trial data, will be discussed.
| S-EPMC10867227 | biostudies-literature
Project description:ObjectiveIgA nephropathy (IgAN) and IgA vasculitis (IgAV) are part of a similar clinical spectrum. Both clinical conditions occur with the coronavirus disease 2019 (COVID-19). This review aims to recognize the novel association of IgAN and IgAV with COVID-19 and describe its underlying pathogenesis.MethodsWe conducted a systematic literature search and data extraction from PubMed, Cochrane, ScienceDirect, and Google Scholar following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsOur search identified 13 cases reporting IgAV and IgAN associated with COVID-19 infection and 4 cases of IgAN following COVID-19 vaccination. The mean, mode, and median ages of patients were 23.8, 4, and 8 years, respectively. Most cases associated with COVID-19 infection were reported in males (77%). Rash and purpura (85%) were the most common clinical features, followed by gastrointestinal symptoms (62%). In symptomatic cases, skin or renal biopsy and immunofluorescence confirmed the diagnosis of IgAN or IgAV. Most patients were treated with steroids and reported recovery or improvement; however, death was reported in two patients.ConclusionThere is a paucity of scientific evidence on the pathogenesis of the association of IgAN and IgAV with COVID-19, which thus needs further study. Current research suggests the role of IgA-mediated immune response, evidenced by early seroconversion to IgA in COVID-19 patients and the role of IgA in immune hyperactivation as the predominant mediator of the disease process. Clinicians, especially nephrologists and paediatricians, need to recognize this association, as this disease is usually self-limited and can lead to complete recovery if prompt diagnosis and treatment are provided.
| S-EPMC8479423 | biostudies-literature
Project description:IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and a common cause of end-stage renal disease. Evaluation of a kidney biopsy is necessary for diagnosis, with routine immunofluorescence microscopy revealing dominant or co-dominant IgA immunodeposits usually with complement C3 and sometimes IgG and/or IgM. IgA nephropathy reduces life expectancy by more than 10 years and leads to kidney failure in 20-40% of patients within 20 years of diagnosis. There is accumulating clinical, genetic, and biochemical evidence that complement plays an important role in the pathogenesis of IgA nephropathy. The presence of C3 differentiates the diagnosis of IgA nephropathy from the subclinical deposition of glomerular IgA. Markers for the activation of the alternative and mannan-binding lectin (MBL) pathways in renal-biopsy specimens are associated with disease activity and portend a worse renal outcome. Complement proteins in the circulation have also been evaluated in IgA nephropathy and found to be of prognostic value. Recently, genetic studies have identified IgA nephropathy-associated loci. Within these loci are genes encoding products involved in complement regulation and interaction with immune complexes. Put together, these data identify the complement cascade as a rational treatment target for this chronic kidney disease. Recent case reports on the successful use of humanized anti-C5 monoclonal antibody eculizumab are consistent with this hypothesis, but a better understanding of the role of complement in IgA nephropathy is needed to guide future therapeutic interventions.
| S-EPMC6433978 | biostudies-literature
Project description:IntroductionGalactose-deficient IgA1 (Gd-IgA1) and related IgA/IgG immune complexes have been identified as the key drivers in the pathogenesis of IgA nephropathy (IgAN). However, their roles in the development of secondary IgAN are still unknown.MethodsIn this study, we measured the plasma Gd-IgA1 level, IgA/IgG complex, and Gd-IgA1 glomerular deposits in 100 patients with various kinds of secondary IgAN. Plasma Gd-IgA1 was measured using a lectin-based enzyme-linked immunosorbent assay, and Gd-IgA1 in glomerular deposits was examined by double immunofluorescent staining using its specific monoclonal antibody KM55.ResultsPatients with secondary IgAN presented with higher plasma Gd-IgA1 levels compared to healthy controls (median, 354.61 U/ml; interquartile range [IQR], 323.93, 395.57 U/ml vs. median, 303.17 U/ml; IQR, 282.24, 337.92 U/ml, P < 0.001) or patients with other kidney diseases (median, 314.61 U/ml; IQR, 278.97, 343.55 U/ml, P < 0.001). A similar trend was observed in plasma IgA/IgG immune complexes or IgA1. There were no differences between secondary and primary IgAN in plasma Gd-IgA1 levels (median, 378.54 U/ml; IQR, 315.96, 398.33 U/ml, P = 0.700) and IgA1-IgG complex levels (median, 18.76 U/ml; IQR, 14.51, 22.83 U/ml vs. median, 19.11 U/ml; IQR, 13.21, 22.37 U/ml, P = 0.888). Co-localized IgA1 and Gd-IgA1 of both secondary and primary IgAN indicated that they both share the feature of Gd-IgA1 deposits on the glomerular mesangium.ConclusionOur study strongly suggests that secondary IgAN shares a similar galactose-deficient IgA1-oriented pathogenesis with primary IgAN.
| S-EPMC7000803 | biostudies-literature