Clinicopathological Features and Outcomes of IgA Nephropathy with Hematuria and/or Minimal Proteinuria

Background/Aims: Obese patients and experimental animals exhibit high levels of inflammatory cytokines, such as tumor necrosis factor (TNF)-α. However, the role of TNF-α in the pathophysiologic process in obesity induced kidney damage is still unknown. Methods: We used TNF-α deficient mice and wild-type (WT) C57/BJ6 mice controls to study the effect of TNF-α on inflammation and oxidative stress in kidney by the model of high-fat diet (HFD) and primary isolated mouse renal proximal tubule cells treated with a mixture of free fatty acids (FFA). Results: Compared with the chow diet group, HFD-fed WT mice had higher urinary albumin and increased levels of renal fibrosis, glomerulosclerosis, inflammation, oxidative stress and apoptosis in the kidney. These changes were co-related with increased expression of TNF-α in the kidney and were attenuated by TNF-α deficiency. In vitro, accumulation of intracellular lipids induced TNF-α expression and oxidative stress in FFA treated primary proximal tubule cells. However, TNF-α inhibition with siRNA or TNF-α deficiency decreased the lipid induced oxidative stress in these cells. Conclusion: These findings suggest that TNF-α plays an important role in the HFD induced kidney damage, and targeting TNF-α and/or its receptors could be a promising therapeutic regimen for progressive nephropathy.

Section: Methodsmentioning

confidence: 99%

TNF-α Deficiency Prevents Renal Inflammation and Oxidative Stress in Obese Mice

Wang¹,

Gai

et al. 2017

“…Besides, proteinuria is an independent indicator for those with severe renal pathological injuries but show mild clinical characteristics, and indicate that these IgAN patients should undergo renal biopsies [6]. As for renal survival, study also reveals that hyperuricemia and the activation of complement (mainly the deposition of C3 in mesangium) are independent risk factors for renal survival in patients with IgAN [7]. Although the pathogenesis is not clear, recent studies have suggested that immune response, immune mediators, and heredity are associated with the susceptibility to IgAN [8, 9].…”

Section: Introductionmentioning

confidence: 99%

Association Between IFN-γ Gene Polymorphisms and IgA Nephropathy in a Chinese Han Population

Gao¹,

Wei²,

Liu³

et al. 2017

Background/Aims: IFN-γ was reported to be involved in the development and progression of Immunoglobulin A nephropathy (IgAN), however, few studies have investigated the association between IFN-γ polymorphisms and IgAN. Therefore, we performed a case-control study to assess the association between IFN-γ polymorphisms and the risk of IgAN. Methods: Sequenom MassARRAY was used to genotype two SNPs (rs1861494 and rs2430561) in 351 patients with IgAN and 310 healthy controls. Associations were evaluated as odd ratios (OR) with 95% confidence intervals (CI). Results: No association was found between IFN-γ rs1861494 and IgAN risk or clinical parameters. For rs2430561, the AA genotype was more common in patients with IgAN, compared with controls (AT vs. AA: OR = 0.57, P = 0.035). IFN-γ-rs2430561 T allele may be a protective factor for IgAN susceptibility (T vs. A: OR = 0.59, P = 0.04). Subgroup analysis based on clinical features revealed no significant association between rs2430561 polymorphism and clinical data such as gender, 24-h urine protein, blood pressure, Oxford classifcation and estimated glomerular fltration rate. IgAN patients had a higher IFN-γ serum level than healthy controls and patients with rs1861494 AA genotype had a higher IFN-γ serum level compared with those with AG/GG genotypes. Conclusions: IFN-γ polymorphisms may be involved in the development and progression of IgAN.

“…The prognosis is also highly variable and the outcome is difficult to predict in affected individuals [3]. Another study by Tan et al reveals that proteinuria is an independent risk factor in IgAN patients with severe renal pathological injuries but benign clinical features [4]. Although IgAN is benign during early stages of primary glomerular disease, about 50% of patients will progress to end-stage renal disease (ESRD) [5, 6].…”

Section: Introductionmentioning

confidence: 99%

Association of Interleukin-10 Polymorphisms (rs1800872, rs1800871, and rs1800896) with Predisposition to IgA Nephropathy in a Chinese Han Population: A Case-Control Study

Gao

Wei

et al. 2017

Background/Aims: IgA nephropathy (IgAN) is a common form of primary glomerulonephritis worldwide. Previous studies indicated that IL-10 single nucleotide polymorphisms (SNP) play an important role in IgAN pathogenesis, but the results were controversy. This study aimed to investigate the association between IL-10 SNPs (rs1800872, rs1800871, and rs1800896) with IgAN in a Chinese Han population. Methods: We conducted a case–control study that included 351 patients with IgAN and 310 age-, gender- and ethnicity-matched healthy controls. Three promoter SNPs (rs1800872, rs1800871, and rs1800896) of IL-10 were genotyped by Sequenom MassARRAY. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the relationship with IgAN. Results: We found that the rs1800896 did not correlate with IgAN risk, whereas rs1800872 and rs1800871 were significantly associated with increased IgAN risk in all genetic models. The haplotype analysis indicated that the CCA haplotype was associated with increased IgAN risk (OR = 1.36; 95% CI = 1.05–1.75). Moreover, there were no associations between these SNPs and blood pressure or gender, whereas the rs1800896 variant was correlated with higher 24-hour urine protein in patients with IgAN. Conclusion: Taken together, these results suggest that IL-10 is a susceptibility gene in patients with IgAN.