scholarly journals Identifying Therapeutic Strategies in IgA Nephropathy through Comprehensive Transcriptomic Characterization

2021 ◽  
Author(s):  
Kenneth Ofori ◽  
Amin Yakubu ◽  
Alex J. Rai
Keyword(s):  
Iga Nephropathy ◽  
Inflammatory Diseases ◽  
Coagulation Cascade ◽  
Tubulointerstitial Damage ◽  
Ppar Signaling ◽  
Gene Correlation ◽  
Differential Gene ◽  
Bioinformatic Approaches ◽  
Stage Renal Disease ◽  
End Stage

AbstractIgA nephropathy (IgAN) is an autoimmune disease and the most common primary glomerulonephritis. The four-hit hypothesis describes mechanism of the disease, from synthesis of galactose deficient IgA (GD-IgA), to recognition of GD-IgA by anti-glycan antibodies and deposition of the formed immune complex in the mesangium. Complement and coagulation cascade activation ensues, resulting in mesangial activation and cytokine release, podocyte injury, mesangial sclerosis and tubulointerstitial damage. Currently, there is no disease cure, and 30-40% of patients progress to end stage renal disease.Using complementary bioinformatic approaches, we demonstrate different levels of deviation of the transcriptome of the glomerulus in IgAN from normal, with the aim of identifying therapeutic targets. Approaches used herein include, deconvolution of the transcriptome to estimate immune constitution, co-regulation-based functional analysis of differentially expressed genes, modular co-expression analysis, network analysis of metabolic pathways and differential gene correlation analysis.We describe the immune composition in IgAN and the relatively low fold changes of the abundance of different immune cells and strength of immune signatures compared with control. Additionally, we identify enrichment of the intestinal network for IgA synthesis, repression of expression and dysregulation of networks of amino acid metabolism and PPAR signaling pathways in IgAN glomeruli. We also find loss of correlation between expression of matrix synthesizing and matrix degrading genes in IgAN.We conclude by discussing how therapies based on some nodes in these altered pathways described have been shown to be efficacious in IgAN and/or other inflammatory diseases and the potential of others in effective treatment.

scholarly journals Low Birth Weight and Risk of Progression to End Stage Renal Disease in IgA Nephropathy—A Retrospective Registry-Based Cohort Study

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153819 ◽  
Author(s):  
Paschal Ruggajo ◽  
Einar Svarstad ◽  
Sabine Leh ◽  
Hans-Peter Marti ◽  
Anna Varberg Reisæther ◽  
...  
Keyword(s):  
Cohort Study ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Renal Disease ◽  
Iga Nephropathy ◽  
End Stage Renal Disease ◽  
Risk Of Progression ◽  
Stage Renal Disease ◽  
End Stage

scholarly journals Increased Risk of End-Stage Renal Disease in Familial IgA Nephropathy

2002 ◽  
Vol 13 (2) ◽  
pp. 453-460
Author(s):  
Francesco Paolo Schena ◽  
Giuseppina Cerullo ◽  
Michele Rossini ◽  
Salvatore Giovanni Lanzilotta ◽  
Christian D’Altri ◽  
...  
Keyword(s):  
Renal Disease ◽  
Iga Nephropathy ◽  
End Stage Renal Disease ◽  
Upper Respiratory Tract ◽  
Renal Survival ◽  
First Degree Relatives ◽  
Increased Risk ◽  
Stage Renal Disease ◽  
Tract Infections ◽  
End Stage

ABSTRACT. Primary IgA nephropathy (IgAN) is characterized by recurrent episodes of macroscopic hematuria accompanied by upper respiratory tract infections or persistent asymptomatic microscopic hematuria with or without proteinuria. IgAN may involve one or more members of a family. Three generations of a cohort of 110 patients with biopsy-proven IgAN, living in Southern Italy, were checked for urinalysis, and the relative risk (RR) of developing the disease was evaluated. A total of 19 unrelated familial, 37 suspected, and 54 sporadic cases of IgAN were identified. Renal survival was estimated by the Kaplan-Meier method for censored data and compared by use of the log-rank test. More than 50% of the patients with IgAN clustered in kindred with more than two probably affected relatives. In 19 unrelated IgAN families, 8 had single-generation (SG) and 11 multigenerational (MG) involvement showing a prevalent vertical transmission of the trait. The RR was 16 times higher in first-degree relatives (odds ratio [OR], 16.4; 95% confidence interval [CI], 5.7 to 47.8; P < 0.0001) and >2 times higher, even if NS, in second-degree relatives (OR, 2.4; 95 % CI, 0.7 to 7.9; P = 0.145). The clinical and histologic picture of familial and sporadic IgAN appeared to be similar. The 20-yr renal survival rate from the apparent onset of the disease was significantly poorer in patients with familial (41%) than in patients with sporadic (94%) IgAN (P = 0.003). Furthermore, 15-yr renal survival from the time of renal biopsy was significantly worse in familial IgAN (P = 0.02); end-stage renal disease was present in 64% of familial and only in 8% of patients with sporadic IgAN. Finally, renal survival was significantly worse in patients belonging to families with SG rather than with MG involvement (P = 0.03). These data show, for the first time, that familial IgAN may be considered a nonbenign disease that occurs frequently in first-degree relatives. Familial IgAN has a poorer outcome than sporadic IgAN. Therefore, an accurate family history and urinalysis in all family members is urgently recommended in clinical practice. This procedure might avoid late referral of subjects with persistent and underestimated urinary abnormalities and late diagnosis of the disease.

scholarly journals Treatment effects of Chinese medicine (Yi-Qi-Qing-Jie herbal compound) combined with immunosuppression therapies in IgA nephropathy patients with high-risk of end-stage renal disease (TCM-WINE): study protocol for a randomized controlled trial

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Shen Li ◽  
Jin-pu Li
Keyword(s):  
High Risk ◽  
Renal Disease ◽  
Iga Nephropathy ◽  
End Stage Renal Disease ◽  
Controlled Trial ◽  
Eligible Patient ◽  
Study Phase ◽  
Double Blind ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background IgA nephropathy (IgAN) is the most common glomerular disease worldwide. It has a high incidence in Asians and is more likely to progress to end-stage renal disease (ESRD). For high-risk IgAN, which is clinically characterized by massive proteinuria and renal dysfunction, however, there has been no international consensus on treatment options. Compared with other developed countries, IgAN patients in China are often found to have severe kidney function loss at initial diagnosis. Yi-Qi-Qing-Jie formula (YQF; a compound recipe of Chinese medicinal herbs) has shown potential renal protection in our previous clinical studies. To further confirm the efficacy and safety of YQF in the treatment of high-risk IgAN, we have designed a prospective double-blind randomized placebo-controlled trial. Methods/design The TCM-WINE study is a single-center, prospective, double-blind randomized placebo-controlled trial. We plan to randomize 60 participants with biopsy-proven IgAN to a YQF combined group (YQF compound combined with prednisolone, and cyclophosphamide if necessary) or an immunosuppression group (placebo-YQF combined with prednisolone, and cyclophosphamide if necessary). The two groups will enter a 48-week in-trial treatment phase and receive post-trial follow-up until study completion (3 years). All patients will receive optimal supportive care. The primary composite outcome is defined as the first occurrence of a 40% decrease in estimated glomerular filtration rate (eGFR) from the baseline lasting for 3 months, initiating continuous renal replacement treatment, or death due to chronic kidney disease (CKD) during the 3-year study phase. The secondary endpoint events are defined as the mean annual eGFR decline rate (eGFR slope, ml/min per 1.73 m2 per year), which is calculated by the eGFR regression curve for each eligible patient, and proteinuria remission (prescribed as proteinuria < 0.5 g/day) at weeks 24, 36, and 48 during the in-trial phase. The remission rate of symptoms and inflammation status will be evaluated at week 48. Safety monitoring and assessment will be undertaken during the study. Discussion The TCM-WINE study will evaluate the effects and safety of YQF combined therapy compared with immunosuppression monotherapy on the basis of the optimal supportive treatment in high-risk IgAN. The evidence from this study will provide a novel, effective, and safe Chinese characteristic therapy for high-risk IgAN patients. Trial registration ClinicalTrials.gov, NCT03418779. Registered on 18 June 2018.

Role of Thrombotic Risk Factors in End-Stage Renal Disease

2009 ◽  
Vol 16 (2) ◽  
pp. 132-140 ◽  
Author(s):  
Gaurav Tripathi ◽  
Satya Narayan Sankhwar ◽  
Raj Kumar Sharma ◽  
Vinod Pandirikkal Baburaj ◽  
Suraksha Agrawal
Keyword(s):  
Risk Factors ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Serum Folate ◽  
Coagulation Cascade ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
Total Homocysteine ◽  
Stage Renal Disease ◽  
End Stage

Introduction: Genetic polymorphisms that are found among factors of the coagulation cascade are factor V leiden mutation (FVL), prothrombin (PT), and methylenetetrahydrofolate reductase (MTHFR), reported for thrombotic complications. We have investigated the associations of these gene polymorphisms in patients with end-stage renal disease (ESRD). Methods: We genotyped 258 patients for FV G1691A, PT G20210A, and MTHFR (C677T, A1298C) gene by using polymerase chain reaction—restriction fragment length polymorphism (PCR-RFLP) analysis and were compared with 569 healthy controls. Serum folate, total homocysteine (tHcys), and vitamin B12 were measured in both patients with ESRD and controls. Results: No homozygous individuals for the mutant AA genotype of FVL G1691A were observed in this study. The frequency of the heterozygous genotypes was (11.2%), which was nearly 3 times higher than that observed in controls (3.2%), with a odds ratio of 3.87 (P = .0001, 95% CI = 2.11-7.11). PT G20210A mutation was missing in both patients and the controls. At MTHFR locus, TT genotype of C677T was present in 9.6% among ESRD, while CC genotype of A1298C was present in 11.7% of the ESRD. In control group, it was significantly low that is, 4.2% and 3.2%, respectively (P = .0034; OR = 2.44, 95% CI = 1.36-4.36 and P < .0001; OR = 4.03; 95% CI = 2.2-7.37). The combined analysis of the 2 genotypes showed further increased risk in ESRD ~15 folds. Further, the carrier of TT and CC genotypes of C677T and A1298C had significantly higher total homocysteine (tHcys) level than those with CC and AA genotypes (P < .001). Conclusion: The carrier of FVL, TT genotype of C677T, and CC genotype of A1298C polymorphisms may act as risk factors for ESRD.

scholarly journals Impact of Selectin Gene Polymorphisms on Rapid Progression to End-Stage Renal Disease in Patients with IgA Nephropathy

2006 ◽  
Vol 45 (16) ◽  
pp. 947-951 ◽  
Author(s):  
Yusuke Watanabe ◽  
Tsutomu Inoue ◽  
Hirokazu Okada ◽  
Shuhei Kotaki ◽  
Yoshihiko Kanno ◽  
...  
Keyword(s):  
Renal Disease ◽  
Iga Nephropathy ◽  
End Stage Renal Disease ◽  
Gene Polymorphisms ◽  
Rapid Progression ◽  
Stage Renal Disease ◽  
End Stage

scholarly journals P0488IG A NEPHROPATHY: ANALYSIS OF 501 BIOPSY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Marwa Omrane ◽  
Raja Aoudia ◽  
Mondher Ounissi ◽  
Soumaya Chargui ◽  
Mouna Jerbi ◽  
...  
Keyword(s):  
Renal Biopsy ◽  
Iga Nephropathy ◽  
Vascular Lesions ◽  
Macroscopic Hematuria ◽  
Systematic Screening ◽  
Female Ratio ◽  
Male Predominance ◽  
Glomerular Lesions ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background and Aims Mesangial deposits Ig A was described the first time in 1968 by Berger and Hinglais. It remains the most common primary glomerulonephritis worldwide. It is often idiopathic but can also be secondary. The aim of our study is to describe the epidemiologic characteristics, the incidence and the anatomopathological features of 501 IgA nephropathy (IgA N) patients. Method It is a retrospective mono-centric study including patients having IgA N in the renal biopsy done in our department among a period of 17 years. Results We analyzed data of 8427 patients who underwent renal biopsy. 81% had glomerular nephropathy with 7.3% (501) IgA N. A male-to-female ratio of 2.27. The average age was 28.7 years. IgA N was primary in 80.2% cases and secondary in 17.8% cases. The most frequent secondary IgA N was rheumatoid purpura (74.8%). There was a male predominance in Berger‘s disease as well as in rheumatoid purpura. Berger’s disease was more common in adults, whereas rheumatoid purpura was more common in children. The main indication of renal biopsy was proteinuria with hematuria in 23.2% of cases and nephrotic syndrome in 23.8%. The association of non-nephrotic proteinuria, hematuria, arterial hypertension and renal injury was found in 9.3% whereas isolated macroscopic hematuria only in 6.4% of cases. According to HAAS classification, HAAS 3 was the most frequent. OXFORD classification used only from 2010, and M1, S1, E0, T0 and M1, S1, E0, T2 were the most frequent. Glomerular lesions were associated to tubulo interstitial and vascular lesions in 48.2% of cases. Conclusion IgA nephropathy is the most common glomerular disease and a frequent cause of end stage renal disease. Because of a clear increase of it’s incidence in our country and the delay in the diagnosis, a systematic screening of urines is needed in our country as it’s done in Singapore and Japan.

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