Improved renal survival in Japanese children with IgA nephropathy.
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ABSTRACT:
SUBMITTER: Yata N
PROVIDER: S-EPMC2335295 | biostudies-other | 2008 Jun
REPOSITORIES: biostudies-other
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Project description:The clinical course of IgA nephropathy (IgAN) and its outcome are extremely variable. Proteinuria at baseline has been considered one of the most important risk factors. More recently, mean proteinuria of follow-up (time-average proteinuria: TAp) was described as a stronger marker of renal survival, suggesting to consider it as a marker of disease activity and response to treatment. We evaluated predictors of renal survival in IgAN patients with different degrees of renal dysfunction and histological lesions, focusing on the role of the therapy in influencing TAp. We performed a retrospective analysis of three prospective, randomized, clinical trials enrolling 325 IgAN patients from 1989 to 2005. Patients were divided into 5 categories according to TAp. The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16.6%) and renal survival was much better in groups having lower TAp. The median follow up was 66.6 months (range 12 to 144). The primary endpoint of the 100% increase of serum creatinine occurred in 54 patients (16,6%) and renal survival was much better in groups having lower TA proteinuria. At univariate analysis plasma creatinine and 24h proteinuria, systolic (SBP) and diastolic (DBP) blood pressure during follow-up and treatment with either steroid (CS) or steroid plus azathioprine (CS+A) were the main factors associated with lower TAp and renal survival. At multivariate analysis, female gender, treatment with S or S+A, lower baseline proteinuria and SBP during follow-up remained as the only variables independently influencing TAp. In conclusion, TA-proteinuria is confirmed as one of the best outcome indicators, also in patients with a severe renal insufficiency. A 6-month course of corticosteroids seems the most effective therapy to reduce TAp.
| S-EPMC4945016 | biostudies-literature
Project description:The management strategy for IgA nephropathy (IgAN), has undergone constant improvements since the disease entity was first described 50 years ago. However, it is still unknown how these changes affected the long-term renal survival of IgAN patients. We systematically evaluate changes in IgAN renal survival by searching PubMed, Embase, and the Cochrane Library Database of Systematic Reviews from inception to 19 May 2024. We included a large sample of 103076 IgAN cases from 158 studies. Renal survival rates were 94.16% (95% CI: 94.02% to 94.31%), 88.68% (95% CI: 88.48% to 88.87%), and 78.13% (95% CI: 77.82% to 78.43%) at three, five, and ten-year, respectively. Over the past few decades, there haven't been any sound changes in the 3-year and 5-year renal survival rates. The kidney survival rate in developed countries is higher than in developing countries. Researchers consistently show that while proteinuria < 1.0 g/24 h, renal survival rates increase dramatically. In IgAN, long-term renal survival fluctuated rather than continuously improving over time. Our system review's findings indicate that supportive care-the most important recommendation for managing IgAN has shown promising results. The long-term outcomes of IgAN could be significantly improved by the latest developed treatment options.
| S-EPMC11360644 | biostudies-literature
Project description:IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis, whose prognosis is highly variable. Interstitial fibrosis is a strong independent prognosis factor. Among microRNA involved in renal fibrogenesis, only few have been investigated in IgAN. In the context of IgAN, we aimed to analyze the role of miR-21-5p, miR-214-3p and miR-199a-5p, three established "fibromiRs" involved in renal fibrosis. Fifty-six IgAN biopsy specimens were retrospectively scored according to Oxford classification. Renal expression of miR-21-5p, miR-214-3p and miR-199a-5p were significantly associated with T score (miR-21-5p T0 RQ median = 1.23, T1 RQ = 3.01, T2 RQ = 3.90; miR-214-5p T0 RQ = 1.39, T1 RQ = 2.20, T2 RQ = 2.48; miR-199a-5p T0 RQ = 0.76, T1 RQ = 1.41, T2 RQ = 1.87). miR-21-5p expression was associated with S score (S0 RQ median = 1.31, S1 RQ = 2.65), but not miR-214-3p nor miR-199a-5p. In our cohort, poor renal survival was associated with high blood pressure, proteinuria and elevated creatininemia, as well as T and S scores. Moreover, renal expression of miR-21-5p, miR-214-3p were associated with renal survival. In conclusion, miR-21-5p, miR-214-3p and miR-199a-5p are three "fibromiRs" involved in renal fibrosis in the course of IgAN and miR-21-5p and miR-214-3p are associated with renal survival.
| S-EPMC4893709 | biostudies-other
Project description: Not available
| S-EPMC10783253 | 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:BackgroundWe aimed to validate the Japanese histological grading classification (JHGC) in our population of IgA immunoglobulin (IgAN) cases.MethodsWe conducted a retrospective cohort study at Taichung Veterans General Hospital in Taiwan from January 2011 to December 2023. The process involved assessing JHGC's clinical, histological, and merged grading system. Composite renal outcomes based on glomerular filtrate rate (eGFR) were considered.ResultsThe study included 359 IgAN by renal biopsies. Kidney function at the time of biopsy was suboptimal, with average SCr of 1.3 mg/dL, eGFR of 54.0 mL/min/1.732 m2, and urine protein-creatinine ratio (UPCR) of 1.2 mg/mg. JHGC effectively identified different severity levels of histological and clinical aspects in Taiwanese IgAN. Initial 4-histological classification showed significantly higher MEST-C scores (p < 0.001). Merging grade III and IV was reasonable in Japanese and Taiwanese populations. The clinical grading system (3C) was associated with histological status and proteinuria, but there was no significant trend with SCr, eGFR, and blood urea nitrogen. Significant differences were found among the three groups (log-rank p < 0.01), but C-grade I and II lacked significant difference in long-term renal outcomes. We separated UPCR < 0.5 mg/mg into two groups: eGFR≥ and <60 mL/min/1.732 m2. The new grading system effectively differentiated risk factors for renal outcomes (log-rank p < 0.01), suggesting the need for separation in Taiwanese IgAN.ConclusionsOur study externally validated JHGC in non-Japanese IgAN. Despite applicability to our population, we recommend a new classification specifically for Taiwanese IgAN patients with increased case numbers in eGFR ≥ 60 mL/min/1.732 m2 and UPCR < 0.5 g/day group.
| S-EPMC10707328 | biostudies-literature
Project description:IgA nephropathy (IgAN) and IgA vasculitis-associated nephritis (IgAVN) are among the most frequent childhood glomerular diseases and are characterized by significant variability in clinical manifestations, pathological presentation and long-term outcomes. IgAVN, alternatively called purpura nephritis, is pathologically indistinguishable from kidney-limited IgAN. In Chinese children, the clinical presentations and pathological manifestations of IgAN and IgAVN are variable. The severity of proteinuria and abnormalities in kidney function and blood pressure of children in China are comparable to those of children in Europe, the USA, and Japan. Compared to Caucasian children and Japanese children, crescents were more common in Chinese children with IgAN or IgAVN. Approximately 10-20% of childhood IgAN or IgAVN progresses to impaired kidney function in China. Since 2007, a series of guidelines on the diagnosis and treatment of pediatric kidney diseases has been published following the principles of evidence-based medicine. However, a large difference exists between the Chinese evidence-based guidelines and the guidelines developed by Kidney Disease: Improving Global Outcomes (KDIGO) in 2021. Chinese children with IgAN or IgAVN were more likely to be treated with steroids or immunosuppressive agents. Further studies exploring the optimal treatment regimen for childhood IgAN or IgAVN are needed in the future.
| S-EPMC10154255 | biostudies-literature
Project description:BackgroundThe objective of this study is to investigate the clinical and pathological differences between patients with IgA nephropathy (IgAN) and IgA vasculitis associated nephritis (IgAVN).MethodsA total of 253 patients with IgAN and 71 patients with IgAVN were retrospectively included in the study, and clinical and laboratory data were collected and analysed.ResultsCompared with IgAVN group, months from onset to kidney biopsy were significantly prolonged in IgAN patients because of the lack of obvious symptoms such as rash, abdominal symptoms, and joint pain (13.5 ± 26.6 vs. 10.2 ± 31.6 months, P = 0.007), and the levels of serum creatinine (92.3 ± 94.7 vs. 68.9 ± 69.2 µmol/L, P = 0.015) was higher and eGFR (99.1 ± 35.2 vs. 123.4 ± 41.8 mL/min/1.73m2, P < 0.001) was lower in IgAN group. The pathological results revealed that patients with IgAN have a greater degree of chronic kidney injury compared to patients with IgAVN. In addition, the levels of plasma D-Dimers (1415.92 ± 1774.69 vs. 496.78 ± 711.91 ng/mL, P < 0.001) and fibrinogen degradation products (FDP) (3.92 ± 4.73 vs. 1.63 ± 2.46 µg/mL, P = 0.001) were significantly higher in IgAVN patients than in IgAN patients. The deposition of fibrinogen in the renal tissues was more severe and the cumulative partial remission rate was higher in patients with IgAVN as compared to those with IgAN (P = 0.001).ConclusionsIn comparison, IgAN patients had poorer renal function, whereas IgAVN patients had more severe coagulation abnormalities. These findings provide a basis for the differentiation of the two diseases at an early stage.
| S-EPMC10811929 | biostudies-literature
Project description:IgA nephropathy (IgAN) is the most common type of glomerulonephritis worldwide, which follows a chronic but nonetheless highly variable course of progression. IgA immune complexes are the primary source of renal deposits in IgAN. Apart from the presence of granular IgA1 deposits in the glomerular mesangium and mesangial hypercellularity as common features, the detailed process of IgA1 deposition and clearance in the kidney remains unclear. We sought to examine the dynamics of IgA deposition and tissue plasticity in response to deposits including their intrarenal clearance. We followed a synthetic approach to produce a recombinant fusion between IgA Fc (rIgA) and a biotin tag, which was subsequently induced with streptavidin (SA) to form an oligomeric poly-IgA mimic. Both uninduced rIgA (mono-rIgA) and polymeric SA-rIgA (poly-rIgA) were injected intravenously into Wistar rats. Plasma IgA levels and renal and liver histology were examined in a time series. In contrast to mono-rIgA, this synthetic poly-rIgA analog formed renal deposits exclusively in the glomerulus and were mostly cleared in 3 h. However, repeated daily injections for 12 days caused long-lasting and stronger glomerular IgA deposition together with IgG and complement C3, in association with mesangial cell proliferation, matrix expansion, and variable degrees of albuminuria and hematuria that phenocopied IgAN. Ex vivo, poly-rIgA bound cultured mesangial cells and elicited cytokine production, in addition to activating plasma C3 that was consistent with the actions of IgA immune complexes in IgAN pathogenesis. Remarkably, the kidneys were able to reverse all pathologic manifestations and restore normal glomerular histology 2 weeks after injections were halted. The synthetic model showed the kinetics between the intricate balance of renal deposition and clearance, as well as glomerular plasticity towards healing. Together, the results revealed a priming effect of existing deposits in promoting stronger and longer-lasting IgA deposition to cause renal damage. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
| S-EPMC8324010 | biostudies-literature
Project description:IntroductionChildhood IgA nephropathy (cIgAN) is a primary glomerulonephritis clinically characterized by microscopic hematuria and proteinuria, the presence of which may potentially overlap with Alport syndrome. Interestingly, earlier studies suggested that familial IgAN could be linked to the chromosome 2q36 region, also the coding region for collagen type 4 alpha 3/4 (COL4A3/A4).MethodsTo investigate a possible relationship or phenocopy between Alport syndrome and cIgAN, COL4A3, COL4A4, and COL4A5 exons were sequenced in 36 cIgAN patients. Clinical data and treatment were collected retrospectively. COL4A3/A4/A5 variants were classified according to American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) guidelines.ResultsFour of 36 cIgAN patients were affected by ACMG class 4/5 COL4A3 heterozygous variants (COL4A3-cIgAN). We found no COL4A4 or COL4A5 variant. Despite having rare and deleterious COL4A3 variants, 3 of 4 COL4A3-cIgAN children developed clinical and biologic features of active IgAN rather than Alport syndrome. Response to intensive immunosuppressive treatment was favorable, leading to a reduction of endocapillary and extracapillary proliferation lesions. High levels of immune immunoglobulin G and A (IgG/IgA) complexes, reduction of proteinuria, and gradual stabilization of estimated glomerular filtration rate (eGFR) argued against Alport syndrome. Nevertheless, COL4A3-cIgAN patients seemed predisposed to a more serious IgAN presentation compared with the non‒COL4A3-cIgAN group, with more glomerulosclerosis and a lower eGFR over time. One of the 4 patients underwent kidney transplant with subsequent IgAN recurrence.ConclusionsPredisposition factors for developing serious cIgAN flare-up should be considered for cIgAN with COL4A3 pathologic heterozygous variants. COL4A3 variants, usually responsible for Alport syndrome in adults, should not automatically exclude an immunosuppressive regimen in cIgAN. Moreover, evidence of an ACMG class 4/5 COL4A3 variant in early-stage cIgAN could be a helpful tool for stratifying severity of cIgAN beyond the Oxford classification.
| S-EPMC8116726 | biostudies-literature