TESTING Corticosteroids in IgA Nephropathy: A Continuing Challenge.
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ABSTRACT:
SUBMITTER: Tam FWK
PROVIDER: S-EPMC5753322 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
Publications
TESTING Corticosteroids in IgA Nephropathy: A Continuing Challenge.
Tam Frederick W K FWK Pusey Charles D CD
Clinical journal of the American Society of Nephrology : CJASN 20171213 1
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Project description: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.
| S-EPMC10890070 | biostudies-literature
Project description:The optimal treatment for IgA nephropathy (IgAN) remains unknown. Some patients respond to corticosteroids, suggesting that more aggressive treatment may provide additional benefit. We performed a randomized, multicenter, controlled trial to determine whether adding azathioprine to steroids improves renal outcome. We randomly assigned 207 IgAN patients with creatinine ≤2.0 mg/dl and proteinuria ≥1.0 g/d to either (1) a 3-day pulse of methylprednisolone in months 1, 3, and 5 in addition to both oral prednisone 0.5 mg/kg every other day and azathioprine 1.5 mg/kg per day for 6 months (n = 101, group 1) or (2) steroids alone on the same schedule (n = 106, group 2). The primary outcome was renal survival (time to 50% increase in plasma creatinine from baseline); secondary outcomes were changes in proteinuria over time and safety. After a median follow-up of 4.9 years, the primary endpoint occurred in 13 patients in group 1 (12.9%, 95% CI 7.5 to 20.9%) and 12 patients in group 2 (11.3%, CI 6.5 to 18.9%) (P = 0.83). Five-year cumulative renal survival was similar between groups (88 versus 89%; P = 0.83). Multivariate Cox regression analysis revealed that female gender, systolic BP, number of antihypertensive drugs, ACE inhibitor use, and proteinuria during follow-up predicted the risk of reaching the primary endpoint. Treatment significantly decreased proteinuria from 2.00 to 1.07 g/d during follow-up (P < 0.001) on average, with no difference between groups. Treatment-related adverse events were more frequent among those receiving azathioprine. In summary, adding low-dose azathioprine to corticosteroids for 6 months does not provide additional benefit to patients with IgAN and may increase the risk for adverse events.
| S-EPMC3013548 | biostudies-literature
Project description:The Oxford classification for IgA nephropathy (IgAN) was updated in 2017. We have validated the revised Oxford classification considering treatment with corticosteroids/immunosuppressors. In this retrospective analysis, 871 IgAN patients were enrolled. Patients were divided into two groups, those treated with or without corticosteroids/immunosuppressors. The 20-year renal prognosis up to end-stage renal disease was assessed using the Oxford classification. In all patients, the renal survival rate was 87.5% at 10 years and 72.6% at 20 years. The T score alone was significantly related to renal prognosis in the Kaplan-Meier analysis and multivariate Cox regression analysis. In the non-treatment group (n = 445), E, S, T, and C scores were significantly related to renal survival rates, however, in the treatment group (n = 426), T score alone was significantly related to renal prognosis on Kaplan-Meier analysis, indicating that corticosteroids/immunosuppressors improved renal prognosis in E1, S1, and C1. In patients with E1, S1, or C1, the treatment group showed significantly better renal prognosis than the non-treatment group in univariate and multivariate analysis. The Oxford classification and T score were used to determine renal prognosis in IgAN patients. Corticosteroids/immunosuppressors improved renal prognosis, especially E1, S1, and C1 scores.
| S-EPMC7341848 | biostudies-literature
Project description:Background: The efficacy and safety of corticosteroids and immunosuppressive therapy remain controversial for the treatment of immunoglobulin A nephropathy (IgAN). This study aimed to evaluate the effects of corticosteroid and immunosuppressant therapy in Chinese patients with early-stage IgAN whose estimated glomerular filtration rate (eGFR) was ≥45 ml/min/1.73 m2 and proteinuria was ≥1 g/24 h at biopsy. Methods: Patients with biopsy-proven IgAN were retrospectively enrolled from four study centers between 2007 and 2016. Patients were regularly followed up for at least 1 year or until the study end point. Patients were categorized into three treatment groups: supportive care (SC), steroids alone (CS), and steroids plus immunosuppressants (IT). The observed responses to therapy included complete remission (CR), partial remission (PR), no response (NR), and end-stage renal disease (ESRD). The primary end point of the current study was defined as a 50% decline in eGFR and/or ESRD. Results: A total of 715 patients (male 47% and female 53%) were recruited and followed up for 44.69 ± 24.13 months. The observed CR rate was 81.8% with corticosteroids alone (CS), 62.7% with corticosteroids + immunosuppresants (IT), and 37% with supportive care alone (SC). Renal outcomes were remarkably better in the CS group compared with the SC and IT groups (the percentage of patients reaching the end point in each group was 4.6 vs. 14.4 vs. 11.5%, respectively; p = 0.001). Moreover, 36 and 80-month renal survival were significantly better for the CS group (98.3 and 86.4%) than for the IT (94.2 and 82.4%) and SC (94.0 and 51.6%) groups. Early CKD stage also presented with better kidney survival (p < 0.001). Renal survival of CKD stage 1 patients was relatively good regardless of the specific treatment regimen. CS and IT treatment significantly improved renal survival for CKD stage 2 patients when compared with the SC group (p < 0.001 and 0.007, respectively). However, renal survival of CKD stage 3a patients was not impacted by any of the three treatment regimens. Subgroup analysis also showed that renal survival of patients with proteinuria >3.5 g, M1, E0, S1, T0, and C0 was significantly better in the CS group than in the SC and IT groups. A multivariate model showed that hypertension, serum creatinine, E1 lesion, and T1/T2 lesion remained independent predictors of poor renal survival. Conclusions: Immunosuppressive therapy does not have further benefit beyond that provided by steroids. Corticosteroids plus optimal supportive care may further be beneficial in treating early-stage IgAN patients in that it could significantly improve the short-term renal outcome.
| S-EPMC7643022 | 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: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
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: Not available
| S-EPMC10690074 | biostudies-literature
Project description:IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is considered that the pathogenesis of IgAN involves the 'multiple hit theory' and the immune-inflammatory mechanism; however, these theories have certain limitations. The gold standard for diagnosing IgAN is still renal biopsy. Although renal biopsy is accurate, it is traumatic and is associated with some risks and limitations, so there is a need for non-invasive diagnostic methods. According to recent studies, microRNAs (miRNAs) play important roles in the occurrence and development of IgAN; thus, they provide the possibility of the noninvasive diagnosis of IgAN and also have some value in predicting prognosis. This review summarizes the current research status of miRNAs in the occurrence, development, diagnosis, and prognosis of IgAN. We also highlight some interesting and challenging points that require further study.
| S-EPMC8462925 | biostudies-literature
Project description:Background and objectiveThe 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.MethodsEligible 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.ResultsOur 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).ConclusionsLow-dose corticosteroids combined with leflunomide are a safe and effective treatment for progressive IgA nephropathy.Trial registrationThe PROSPERO registration number is CRD42022361883.
| S-EPMC10926645 | biostudies-literature