Anti-Phospholipase A2 Receptor Antibody Expression at Different Stages of Idiopathic Membranous Nephropathy.

The significance of blood anti-phospholipase A2 receptor (PLA2R) antibodies in the diagnosis of different stages of idiopathic membranous nephropathy (IMN) was investigated. The expression and distribution of anti-PLA2R antibodies in renal biopsy tissue of patients with different stages of IMN were examined by immunohistochemistry. In addition, blood anti-PLA2R antibodies were determined by indirect immunofluorescence for the same patients, and the results were compared with the anti-PLA2R antibody expression in renal biopsy tissue. The positive fluorescence intensities of IMN stages I, IV, and V were mostly ± or + (40/80). There was no significant difference in fluorescence titer between these stages (p > 0.05). These results were consistent with the immunohistochemistry results, and the kappa statistic was 0.95. The positive fluorescence intensities of IMN stages II and III were mostly ++ to ++++ (33/60). There was no significant difference in fluorescence intensities between these two stages (p > 0.05), but there was a significant difference in fluorescence intensities between stages II and III and stages I, IV, and V (p < 0.001). These results were consistent with the immunohistochemistry results, and the kappa statistic was 0.97 (p < 0.001). Therefore, blood anti-PLA2R levels were positively correlated with anti-PLA2R expression in renal biopsy tissue in patients with different stages of IMN. In addition, the fluorescence intensities of IMN stages II and III were significantly different from those of stages I, IV, and V. Therefore, blood anti-PLA2R levels can be used for in vitro differential diagnosis and the monitoring of treatment, as it can distinguish stage II; and III; from stage I, IV, and V IMN.

Determination of IL-1B (rs16944) and IL-6 (rs1800796) genetic polymorphisms in IgA nephropathy in a northwest Chinese Han population.

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide, but etiology and pathogenesis continue to be poorly understood. Polymorphisms in the cytokine genes may play a role in the etiology and pathogenesis of IgAN. The incidence of different between diverse ethnic groups suggested important genetic influences on its pathogenesis. We genotype 10 single nucleotide polymorphisms (SNPs) in IL-1B and IL-6 gene using Sequenom Mass-ARRAY technology from 417 IgAN patients and 463 healthy controls of the Chinese Han population. We evaluated these SNPs associated with IgAN utilising the chi-square tests and genetic model analysis. We identified that the minor alleles of rs16944 ("A"), rs1800796 ("G") in IL-1B, IL-6 were involved in an increasingly risk of IgAN in allelic model analysis, respectively. The rs16944 in IL-1B and rs1800796 in IL-6 were associated with 1.23-fold (95% CI, 1.02-1.48, P = 0.031) and 1.33-fold (95% CI, 1.11-1.66, P = 0.003) increases in the risk of developing IgAN, respectively. There was only rs1800796 still correlated with IgAN in the allelic model after adjustment by age and gender and the Bonferroni correction. In addition, Haplotype Grs1800796A rs2069837G rs2069840 (P = 0.037) and G rs1800796A rs2069837C rs2069840 (P = 0.042) in IL-6were considered to be associated with increased IgAN risk. This study verified the IL-6, IL-1B genetic variants polymorphisms contributed to IgAN susceptibility in a Chinese Han population. Although we identified SNPs susceptibility, however, replication studies and functional research are required to confirm the genetic contribution in IgAN.

Association of genetic polymorphisms in IL-1R1 and IL-1R2 genes with IgA nephropathy in the Han Chinese population.

AIM: IgA nephropathy (IgAN) is the major cause of end-stage renal disease(ESRD) in Asia and its pathogenesis is influenced by both genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in IL1R1 and IL-1R2 may be associated with susceptibility to IgAN. In this study, we study the association between genetic variants of IL-1R1 and IL-1R2 and IgA nephropathy risk in the Chinese Han population. RESULT: In the allelic model analysis, the rs10490571 and rs3917225 were associated with a 1.40-fold, and 1.31-fold increased risk of IgA nephropathy, respectively. In the genetic model analysis, the rs10490571 in IL1R1 was associated with a 1.46-fold increased risk of IgAN in the dominant model and 1.36-fold increased risk in the Log-additive model, respectively. However, the rs3218977 in IL1R2 was associated with a 0.71-fold decrease risk of IgAN in the dominant model and a 0.71-fold decrease risk in the over-dominant model, respectively. We found four SNPs (rs11674595, rs4851521, rs719250, and rs3218896) constructed four haplotypes in the IL1R2 gene and none of the haplotype was significantly associated with risk of IgAN. MATERIALS AND METHODS: A case-control study was conducted including 426 nephropathy patients and 463 healthy controls. Chi-squared tests and genetic model were used to evaluate associations. >CONCLUSIONS: These findings suggested that IL-1R1 and IL-1R2 polymorphisms may contribute to the development of IgAN.

Fasudil inhibits tissue factor and plasminogen activator Inhibitor-1 secretion by peripheral blood mononuclear cells in CAPD patients.

Disturbances in hemostasis are common complications of kidney diseases and correlate well with cardiovascular mortality. Little is known about the effects of fasudil on tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) expression in peripheral blood mononuclear cells (PBMCs) in CAPD patients. PBMCs were isolated from 13 individuals with CAPD and 13 healthy subjects. After 4 h of incubation with or without LPS (10 ng/mL), TF and PAI-1 mRNA of PBMCs were detected by RT-PCR. The levels of TF and PAI-1 in culture supernatants of PBMCs were determined by ELISA. Compared with healthy controls, CAPD patients had increased TF, PAI-1 protein and mRNA expression by PBMCs at baseline and after stimulated by LPS (10 ng/mL) [p < 0.001]. The fasudil treatment resulted in a significant effect in decreasing TF and PAI-1 [p < 0.05] synthesis in PBMCs. TF and PAI-1 mRNA expression and activities in PBMCs were increased in CAPD patients. Fasudil reduced LPS-mediated TF and PAI-1 expression and activity in PBMCs. These effects may partially be relevant to the clinical benefits of fasudil in the treatment of CAPD patients.

Urinary hypoxia-inducible factor-1alpha levels are associated with histologic chronicity changes and renal function in patients with lupus nephritis.

PURPOSE: Tubulointerstitial hypoxia in the kidney is considered a hallmark of injury and a mediator of the progression of tubulointerstitial fibrosis. Hypoxia-inducible factor-1alpha (HIF-1alpha), a master transcription factor in cellular adaptation to hypoxia, regulates a wide variety of genes, some of which are closely associated with tissue fibrosis. The present study set out to characterize urinary HIF-1alpha expressions in patients with lupus nephritis (LN) and to explore whether urinary HIF-1alpha expressions are associated with histologic chronicity changes and renal function. MATERIALS AND METHODS: Urinary HIF-1alpha levels were measured by enzyme-linked immunosorbent assays in 42 patients with LN and in 30 healthy controls. Activity and chronicity indexes as well as tubular HIF-1alpha expressions were analyzed for each specimen. RESULTS: Urinary HIF-1alpha levels were higher in LN patients than in healthy controls (3.977±1.696 vs. 2.153±0.554 ng/mL, p<0.001) and were associated with histologic chronicity indexes (r=0.463, p<0.01) and eGFR (r=-0.324, p<0.05). However, urinary HIF-1alpha levels showed no correlation with histologic activity indexes, anti-dsDNA, ANA, complement 3 and 4 levels, proteinuria, systemic lupus erythematosis disease activity index, and WHO pathological classification (p>0.05). CONCLUSION: Urinary HIF-1alpha levels were elevated in LN patients and were associated with histologic chronicity changes and renal function, indicating that HIF-1alpha might contribute to histologic chronicity in LN.

[Clinical and pathological analysis of 217 patients with IgA nephropathy from Hainan Province].

OBJECTIVE: To study the clinical manifestation, pathological features and their correlation in patients with IgA nephropathy from Hainan Province. METHODS: The clinical and pathological data of 217 patients with IgA nephropathy diagnosed by renal biopsy were retrospectively analyzed. RESULTS: The incidence of IgA nephropathy was the highest in patients at the age of 30-39 years (50.38%). Clinically, IgA nephropathy of hematuria + albuminuria type was the most common among the patients (56.68%, 123/217) and associated with severe pathological changes, with 38.21% of the cases having pathological changes above grade III. The pathological types of IgA nephropathy included almost all the pathological types of primary glomerular disease, and type I was the most common (31.34%, 68/217) followed by type II. The progression of the pathological changes was associated with increased rate of hypertension. Immunopathological classification identified 48 (22.12%) simple IgA cases and 106 cases with complement deposition (48.85%). CONCLUSION: IgA nephropathy has diverse clinical manifestations, and the presence of concurrent hypertension often indicates severe pathological changes of the kidneys. For asymptomatic patients with hematuria in the presence or absence of albuminuria, early renal biopsy should be performed and appropriate therapy administered according to the pathological types.