The Clinical Significance of Uric Acid and Complement Activation in the Progression of IgA Nephropathy

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.

“…Laboratory parameters were measured as described [23]. For 24-hour urine collection, individual mice were placed in metabolic cages with access to diets.…”

Section: Methodsmentioning

confidence: 99%

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

Wang¹,

Gai

et al. 2017

“…Elevated serum creatinine concentration, minimal proteinuria, hyperuricemia and undesirable histological characteristics have been identified as baseline predictors of progression of IgAN [9-12]. Of them, histopathological examination of renal biopsy tissues is regarded as the gold standard for diagnosing IgAN, which manifests as an increase in mesangial matrix, endocapillary proliferation, along with focal necrosis and interstitial fibrosis [12].…”

Section: Introductionmentioning

confidence: 99%

Serum Matrix Metalloproteinase-7 Level is Associated with Fibrosis and Renal Survival in Patients with IgA Nephropathy

Zhang

Ren

Wang

et al. 2017

Background/Aims: In view of the latest findings that matrix metalloproteinase-7 (MMP-7) acted as a vital marker and pathogenic mediator of renal fibrosis in a murine model, we hypothesized that serum MMP-7 level might serve as a noninvasive prognostic biomarker in IgA nephropathy (IgAN) patients. Methods: We conducted a retrospective follow-up study of 244 IgAN patients for a median of 81.9 months. Serum MMP-7 was detected at the time of diagnosis, and renal progression was assessed by Cox proportional hazards method. Results: Compared with healthy populations, the serum levels of MMP-7 were significantly elevated in IgAN patients. Besides, serum MMP-7 levels were well correlated with renal scarring lesions characterized by glomerular sclerosis and interstitial fibrosis. Follow-up analyses revealed that increased serum MMP-7 levels were linked with a greater risk of poor renal outcome with a hazard ratio of 1.898 per doubling MMP-7 concentration. By contrast with the first quartile, the risk of deterioration in renal function elevated such that the hazard ratio for the second quartile was 1.805, 3.383 for the third, and 5.173 for the fourth quartile of the MMP-7 level. Conclusions: This study showed that the higher serum MMP-7 levels were independently associated with renal fibrosis and poor prognosis in IgAN.

“…In Asia, 40% of native-kidney biopsies were diagnosed as IgAN, compared with 20% in Europe, 5-10% in the United States, and less than 5% in Central Africa [5]. 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].…”

Section: Introductionmentioning

confidence: 99%

Association Between <b><i>IFN-γ</i></b> 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.