PLA2R1 and HLA-DQA1 gene variations in idiopathic membranous nephropathy in South China.

INTRODUCTION: Associations of variations in PLA2R1 and HLA-DQA1 genes with susceptibility to idiopathic membranous nephropathy (IMN) have been well documented. Association with spontaneous remission, however, is poorly defined in the Chinese Han population. METHODS: A Chinese cohort of 117 IMN patients and 138 healthy controls were recruited between July 2009 and November 2019. Case-control studies for single-nucleotide polymorphisms (SNPs) within HLA-DQA1 (rs2187668) and PLA2R1 (rs35771982, rs4664308, rs3749117, rs3749119) genes were performed. The contributions of these polymorphisms to predict susceptibility, titre of autoantibodies against the M-type phospholipase A2 receptor (anti-PLA2R1), glomerular PLA2R1 expression, and spontaneous remission were analysed. RESULTS: We found that variations in PLA2R1 (SNPs rs35771982, rs4664308, rs3749117) were strongly associated with IMN susceptibility, while SNP (rs2187668) within HLA-DQA1 did not increase the risk of IMN. All SNPs in PLA2R1 and HLA-DQA1 were not statistically associated with anti-PLA2R1 titre, glomerular PLA2R1 expression and spontaneous remission after Bonferroni correction (P>0.0167). Clinical and pathological parameters such as lower levels of serum albumin, higher levels of anti-PLA2R1 and glomerular PLA2R1 expression were independent risk factors for non-spontaneous remission. CONCLUSION: This study confirms that variations in PLA2R1 (SNPs rs35771982, rs4664308, rs3749117) are risk factors for IMN. We found excellent association of serum albumin level, anti-PLA2R1 titre and glomerular PLA2R1 positivity with non-spontaneous remission in IMN.

Renal Outcomes of Pregnant Patients with Immunoglobulin A Nephropathy: A Systematic Review and Meta-Analysis.

BACKGROUND: Is the prognosis of immunoglobulin A nephropathy (IgAN) influenced by pregnancy and delivery? The answer to this question still remains to be a controversial topic. Here, we undertook a systematic review and meta-analysis to obtain the overall estimate of potential effect of IgAN and pregnancy on each other. METHODS: We systematically searched MEDLINE, EMBASE, Chinese Biological Medicine and Cochrane for cohort and case-control studies; a total of 1,378 articles were reviewed and 9 studies were included in the end. OR and mean difference (MD) were calculated with a random-effects model, kidney events and pregnancy outcomes were analyzed respectively. RESULTS: The key finding of the meta-analysis of 145 renal events in 1,198 participants was that there was no difference in renal outcomes (defined as doubling of serum creatinine (SCr), 50% decline in glomerular filtration rate [GFR] and end-stage kidney disease) of pregnant women compared with non-pregnant women who had IgAN (OR 0.90; 95% CI 0.59-1.37; p = 0.63). Subgroup analysis indicated that there was no significant difference between the 2 groups according to sample size, follow-up year, age, level of SCr and proteinuria at baseline. There was no difference in the change of the eGFR/creatinine clearance rate (mL/min/1.73 m2 per year) in IgAN patients with pregnancy compared with non-pregnancy (MD -0.11 mL/min; 95% CI -0.50-0.27; p = 0.57) as well. Women with IgAN had a higher likelihood of pregnancy outcomes compared with the Chinese general population, while they had a lower risk of preterm delivery, preeclampsia and low birth weight compared with those who had lupus nephritis or diabetic nephropathy. CONCLUSIONS: Pregnancy did not accelerate kidney disease deterioration in women with IgAN in stages of chronic kidney disease 1-3. Moreover, patients with IgAN had a relatively low risk of adverse pregnancy events compared with those with lupus nephritis or diabetic nephropathy.

Plasmadiafiltration ameliorating gut mucosal barrier dysfunction and improving survival in porcine sepsis models.

BACKGROUND: The object of this study is to explore whether the plasmadiafiltration (PDF) is more effective in improving the intestinal mucosal barrier function by removing more key large molecular inflammatory mediators and then prolonging the survival time. METHODS: Totally, 24 porcine sepsis models induced by cecal ligation and puncture (CLP) operation were randomly divided into three groups: PDF group, high-volume hemofiltration (HVHF) group, and control group, and received 8 h treatment, respectively. The expression of ZO-1 and occludin in intestinal mucosal epithelial cells were detected by immunohistochemistry, and apoptotic protein caspase-3-positive lymphocytes were signed in mesenteric lymph nodes by TUNEL staining. The hemodynamic parameters were measured by invasive cavity detection. The tumor necrosis factor alpha (TNFα) and high-mobility group protein 1 (HMGB1) were tested by ELISA method. And then, the survival curves with all-cause death were compared with three groups. RESULTS: PDF led to a superior reversal of sepsis-related hemodynamic impairment and serum biochemistry abnormalities and resulted in longer survival time compared with HVHF and control (p < 0.01). Definitive protection from excessive TNF-α and HMGB1 response were only achieved by PDF. A more regular distribution pattern of ZO-1 and occludin along the epithelium was found in PDF animals (p < 0.01). The presence of apoptotic lymphocytes was significantly reduced in the PDF animals (p < 0.01). CONCLUSIONS: PDF can effectively eliminate more pivotal inflammatory mediators of TNFα and HMGB1 and reduce the inflammation damage of the intestinal mucosal barrier and apoptosis of lymphocyte then improve the circulation function and prolong the survival time.