scholarly journals The Association Between Variants in PLA2R and HLA-DQA1 and Renal Outcomes in Patients With Primary Membranous Nephropathy in Western China

2020 ◽  
Author(s):  
Shulei Fan ◽  
Qiuxia Wang ◽  
Amanda Y Wang ◽  
Ping Zhang ◽  
Xiang Zhong ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Clinical Manifestations ◽  
Human Leukocyte ◽  
Western China ◽  
Renal Outcome ◽  
Nucleotide Polymorphisms ◽  
Renal Outcomes ◽  
Phospholipase A2 Receptor ◽  
Hla Dqa1

Abstract Background：Both Genome-wide associations and our previous study have shown that single nucleotide polymorphisms (SNPs) of M-type phospholipase A2 receptor (PLA2R) and human leukocyte antigen complex class II HLA-DQα-chain 1 (HLA-DQA1) gene were identified to be associated with primary membranous nephropathy (PMN). However, whether these SNPs affect clinical manifestation and renal outcome for PMN patients is poorly defined. Here, we evaluated whether there is an association between these SNPs and clinical manifestations and renal outcomes of PMN in a western Chinese cohort.Methods: Seven SNPs within PLA2R and one SNP in HLA-DQA1 were selected in our study. Clinical data from 314 patients with PMN were collected and the relationship between the genotype and phenotype was evaluated. A total of 186 patients had follow-up data. We assessed the treatment responses and renal outcomes between patients with these gene polymorphisms after a median follow-up of 18.6 months. Results: Eight SNPs were not associated clinical manifestations of PMN patients (Pc<0.05). rs3828323 T allele was marginally significantly associated with hypertension (P=0.008, Pc=0.064, OR=1.821). After treatment for PMN, urea (OR=1.184, 95%CI:1.030-1.361, P=0.017) was a risk factor for non-remission of the disease, eGFR (OR=0.984, 95%CI:0.970-0.998, P=0.028) and albumin (OR=0.922, 95%CI:0.880-0.966, P=0.001) were protective factors for non-remission of the disease. We also identified that PMN patients with CT/TT genotype for rs3828323 achieved higher cumulative survival rate than patients with CC genotype.Conclusions：Rs3828323 may influence hypertension and renal outcome in patients with PMN. Further research is needed to explore the mechanism for this genotype-disease phenotype association.

scholarly journals The association between variants in PLA2R and HLA-DQA1 and renal outcomes in patients with primary membranous nephropathy in Western China

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shulei Fan ◽  
Qiuxia Wang ◽  
Amanda Y. Wang ◽  
Ping Zhang ◽  
Xiang Zhong ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Clinical Manifestations ◽  
Human Leukocyte ◽  
Western China ◽  
Renal Outcome ◽  
Nucleotide Polymorphisms ◽  
Renal Outcomes ◽  
Phospholipase A2 Receptor ◽  
Hla Dqa1

Abstract Background Both Genome-wide associations and our previous study have shown that single nucleotide polymorphisms (SNPs) of M-type phospholipase A2 receptor (PLA2R) and human leukocyte antigen complex class II HLA-DQα-chain 1 (HLA-DQA1) gene were identified to be associated with primary membranous nephropathy (PMN). However, whether these SNPs affect clinical manifestation and renal outcome for PMN patients is poorly defined. Here, we evaluated whether there is an association between these SNPs and clinical manifestations and renal outcomes of PMN in a western Chinese cohort. Methods Seven SNPs within PLA2R and one SNP in HLA-DQA1 were selected in our study. Clinical data from 314 patients with PMN were collected and the relationship between the genotype and phenotype was evaluated. A total of 186 patients had follow-up data. We assessed the treatment responses and renal outcomes between patients with these gene polymorphisms after a median follow-up of 18.6 months. Results Eight SNPs were not associated with clinical manifestations of PMN patients (Pc < 0.05). rs3828323 T allele was marginally significantly associated with hypertension (P = 0.008, Pc = 0.064, OR = 1.821). After treatment for PMN, the SR group (including CR and PR) had lower serum creatinine level (68.4 ± 18.8 μmol/L vs. 122.8 ± 126.6 μmol/L, P < 0.001), urea (5.5 ± 1.9 mmol/L vs. 8.0 ± 4.0 mmol/L, P < 0.001), uric acid (358.5 ± 95.1 μmol/L vs. 392.8 ± 118.1 μmol/L, P = 0.037) and urinary protein (0.23 (0.76,1.05) g/d vs. 3.01 (2.06,7.95) g/d, P < 0.001), higher eGFR (100.0 ± 20.1 ml/min/1.73m2 vs. 77.1 ± 35.3 ml/min/1.73m2, P < 0.001) and albumin (41.1 ± 5.1 g/L vs.30.4 ± 8.2 g/L, P < 0.001). We also identified that PMN patients with CT/TT genotype for rs3828323 achieved higher cumulative survival rate than patients with CC genotype. Conclusions Rs3828323 may influence hypertension and renal outcome in patients with PMN. Further research is needed to explore the mechanism for this genotype-disease phenotype association.

scholarly journals Predictive values of serum phospholipase A2 receptor antibody and urinary IgG, α1- macroglobulin in patients with idiopathic membranous nephropathy and nephrotic syndrome

2020 ◽  
Author(s):  
Lili Liu ◽  
Haitao Wang ◽  
Ban Zhao ◽  
Xin Liu ◽  
Ying Sun ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Multivariate Regression ◽  
Idiopathic Membranous Nephropathy ◽  
Renal Outcome ◽  
Predictive Values ◽  
Receptor Antibody ◽  
Phospholipase A2 Receptor

Abstract BackgroundThe biomarkers predicting long-term outcome of idiopathic membranous nephropathy (IMN) with nephrotic syndrome (NS) remains indeterminacy. We conducted this study to evaluate the different features between phospholipase A2 receptor (PLA2R)-associated and non-PLA2R-associated IMN, and to explore the association between serum PLA2R antibody (PLA2R-Ab), urinary immunoglobulin G (UIgG), urinary α1-macroglobulin (Uα1m) and renal outcomes in patients with idiopathic membranous nephropathy (IMN) and nephrotic syndrome (NS). MethodsIMN patients who were biopsy-proven and presenting NS were retrospectively recruited for the present study. Serum PLA2R-Ab levels were detected by enzyme-linked immunosorbent assay (ELISA) kits, and values over 20 RU/mL was considered positive. UIgG) and Uα1m were measured by immunonephelometry and corrected by urinary creatinine. The clinicopathologic features, remission and renal outcome were compared between the PLA2R-associated and non-PLA2R-associated IMN patients. Furthermore, the predictive values of biomarkers (PLA2R-Ab, UIgG/Cr and Uα1m/Cr) for remission and renal outcome were assessed by multivariate regression. The renal endpoint was defined as progression to end stage kidney disease (ESRD) or estimated glomerular filtration rate (eGFR) decline ≥50% of baseline. ResultsA total of 111 IMN patients were enrolled this study, and 81 (73.0%) of them were PLA2R-associated. The mean age, 24-hour proteinuria and eGFR showed no difference between PLA2R-associated and non-PLA2R-associated groups (p>0.05). However, PLA2R-associated IMN patients had significantly higher UIgG/Cr (17.78 vs. 9.82 mg/g; median, p=0.001) and Uα1m (0.339 vs 0.202 mg/g; median, p<0.001) when compared to non-PLA2R-associated patients. Histologically, the PLA2R-associated group represented more proportion of patients with acute tubular necrosis (ATN) (27.16% vs. 3.33%, P=0.006) and glomerular C3 deposits (88.89% vs. 70.00%, P=0.016) than the non-PLA2R-associated group. During a median follow-up of 40 months (range 9 to 92), non-PLA2R-associated patients had significantly higher remission rate at the 6th and 12th month and end of follow-up, even after adjusting for the use of immunosuppressor. Furthermore, 11 (13.6%) patients reaching renal endpoint were all PLA2R-associated IMN. Multivariate regression analysis represented that baseline serum PLA2R-Ab titer was an independent predictor of remission (OR, 1.002; 95% confidence interval [CI] 1.001 to 1.004; p=0.002) and renal outcome (HR, 1.002; 95% CI 1.001-1.003, p= 0.004). Receiver operating characteristic (ROC) showed that serum PLA2R-Ab titer >216.93 RU/ml (AUC=0.778, p=0.003), UIgG/Cr >15.76mg/g (AUC=0.758, p=0.005) and Uα1m/Cr >0.3042mg/g (AUC=0.738, p=0.010) predicted renal failure in patients with IMN and NS. Kaplan-Meier curves indicated that subjects with combination of all three high biomarkers had significantly shorter renal survival (log rank p=0.007) than subjects with ≤2 high biomarkers. ConclusionHigh PLA2R-Ab levels is poor prognosis predictor of IMN in addition to proteinuria. In addition, combination of multiple factors (PLA2R-Ab, UIgG and Uα1m) represents a stronger predictive power. These findings suggested the potential different pathogenesis and progression in IMN with NS. Keywords: idiopathic membranous nephropathy, phospholipase A2 receptor antibody, urinary IgG, urinary α1- macroglobulin, nephrotic syndrome.

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

2021 ◽  
Vol 50 (1) ◽  
pp. 33-41
Author(s):  
Fan Wang ◽  
Ting-Ting Wang ◽  
Xiao-Wan Liang ◽  
Jian-Da Lu ◽  
Qiong-Hong Xie ◽  
...  
Keyword(s):  
Risk Factors ◽  
Serum Albumin ◽  
Membranous Nephropathy ◽  
Spontaneous Remission ◽  
Idiopathic Membranous Nephropathy ◽  
Nucleotide Polymorphisms ◽  
Case Control Studies ◽  
Chinese Han ◽  
Phospholipase A2 Receptor ◽  
Hla Dqa1

ABSTRACT 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. Keywords: HLA-DQA1, idiopathic membranous nephropathy, PLA2R1, susceptibility, spontaneous remission

scholarly journals Correction to: The association between variants in PLA2R and HLA-DQA1 and renal outcomes in patients with primary membranous nephropathy in Western China

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shulei Fan ◽  
Qiuxia Wang ◽  
Amanda Y. Wang ◽  
Ping Zhang ◽  
Xiang Zhong ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Western China ◽  
Renal Outcomes ◽  
Hla Dqa1

An amendment to this paper has been published and can be accessed via the original article.

scholarly journals A multicenter, prospective, observational study to determine association of mesangial C1q deposition with renal outcomes in IgA nephropathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Li Tan ◽  
Yi Tang ◽  
Gaiqin Pei ◽  
Zhengxia Zhong ◽  
Jiaxing Tan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Iga Nephropathy ◽  
Cox Regression ◽  
Renal Outcome ◽  
Matched Cohort ◽  
Negative Group ◽  
Renal Survival ◽  
Cox Regression Analysis ◽  
Renal Outcomes

AbstractIt was reported that histopathologic lesions are risk factors for the progression of IgA Nephropathy (IgAN). The aim of this study was to investigate the relationships between mesangial deposition of C1q and renal outcomes in IgAN. 1071 patients with primary IgAN diagnosed by renal biopsy were enrolled in multiple study centers form January 2013 to January 2017. Patients were divided into two groups: C1q-positive and C1q-negative. Using a 1: 4 propensity score matching (PSM) method identifying age, gender, and treatment modality to minimize confounding factors, 580 matched (out of 926) C1q-negative patients were compared with 145 C1q-positive patients to evaluate severity of baseline clinicopathological features and renal outcome. Kaplan–Meier and Cox proportional hazards analyses were performed to determine whether mesangial C1q deposition is associated with renal outcomes in IgAN. During the follow-up period (41.89 ± 22.85 months), 54 (9.31%) patients in the C1q negative group and 23 (15.86%) patients in C1q positive group reached the endpoint (50% decline of eGFR and/or ESRD or death) respectively (p = 0.01) in the matched cohort. Significantly more patients in C1q negative group achieved complete or partial remission during the follow up period (P = 0.003) both before and after PSM. Three, 5 and 7-year renal survival rates in C1q-positive patients were significantly lower than C1q-negative patients in either unmatched cohort or matched cohort (all p < 0.05). Furthermore, multivariate Cox regression analysis showed that independent risk factors influencing renal survival included Scr, urinary protein, T1-T2 lesion and C1q deposition. Mesangial C1q deposition is a predictor of poor renal survival in IgA nephropathy.Trial registration TCTR, TCTR20140515001. Registered May 15, 2014, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1074.

scholarly journals Membranous nephropathy in patients with HIV: a report of 11 cases

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Vivek Charu ◽  
Nicole Andeen ◽  
Vighnesh Walavalkar ◽  
Jessica Lapasia ◽  
Jin-Yon Kim ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Viral Loads ◽  
Phospholipase A2 Receptor ◽  
Immunodeficiency Virus ◽  
Antibody Titers ◽  
Stage Renal Disease ◽  
End Stage ◽  
Nephrotic Range Proteinuria ◽  
Tissue Reactivity

Abstract Background Membranous nephropathy (MN) has been recognized to occur in patients with human immunodeficiency virus (HIV) infection since the beginning of the HIV epidemic. The prevalence of phospholipase A2 receptor (PLA2R)-associated MN in this group has not been well studied. Methods We conducted a retrospective review of electronic pathology databases at three institutions to identify patients with MN and known HIV at the time of renal biopsy. Patients with comorbidities and coinfections known to be independently associated with MN were excluded. Results We identified 11 HIV-positive patients with biopsy-confirmed MN meeting inclusion and exclusion criteria. Patient ages ranged from 39 to 66 years old, and 10 of 11 patients (91%) were male. The majority of patients presented with nephrotic-range proteinuria, were on anti-retroviral therapy at the time of biopsy and had low or undetectable HIV viral loads. Biopsies from 5 of 10 (50%) patients demonstrated capillary wall staining for PLA2R. Measurement of serum anti-PLA2R antibodies was performed in three patients, one of whom had positive anti-PLA2R antibody titers. Follow-up data was available on 10 of 11 patients (median length of follow-up: 44 months; range: 4–145 months). All patients were maintained on anti-retroviral therapy (ARV) and 5 patients (52%) received concomitant immunosuppressive regimens. Three patients developed end-stage renal disease (ESRD) during the follow-up period. Conclusions MN in the setting of HIV is often identified in the setting of an undetectable viral loads, and similar to other chronic viral infection-associated MNs, ~ 50% of cases demonstrate tissue reactivity with PLA2R antigen, which may be seen without corresponding anti-PLA2R serum antibodies.

Membranous Nephropathy in Pregnancy

2020 ◽  
Vol 51 (4) ◽  
pp. 304-317 ◽  
Author(s):  
Zi-ning Liu ◽  
Zhao Cui ◽  
Ying-dong He ◽  
Yi-miao Zhang ◽  
Fang Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Serum Albumin ◽  
Membranous Nephropathy ◽  
Fetal Loss ◽  
Urinary Protein ◽  
Fetal Outcomes ◽  
Child Bearing ◽  
Phospholipase A2 Receptor ◽  
Birth Weight Percentile

Background: Primary membranous nephropathy (pMN) is less common in women of child-bearing age. The kidney risk factors to adverse maternal-fetal outcomes and the effects of pregnancy on pMN process need to be investigated. Methods: We retrospectively screened all the patients with biopsy-proven pMN from 2008 to 2018. Any cases of pregnancy that occurred at the time of pMN diagnosis or during follow-up were included in the study. Clinical and pathological data were collected from all patients at the time of kidney biopsy and their gestational results were recorded. Results: Of the 27 pregnancies with gestational time of 35.9 ± 4.5 weeks, 10 adverse maternal-fetal events occurred, including fetal loss (11%), preterm delivery (26%), and severe preeclampsia (15%). The kidney parameters were relatively stable with all preserved kidney function. Time-averaged urinary protein (p < 0.001) and serum albumin (p < 0.001), maximum urinary protein (p = 0.001) and minimum serum albumin (p = 0.01) before week 20, anti-phospholipase A2 receptor (PLA2R) positivity (p = 0.03), and no remission during pregnancy (p = 0.004) were risk factors to adverse maternal-fetal outcomes. Time-averaged urinary protein and serum albumin correlated with the birth weight percentile of neonates. Conclusions: Pregnancy in pMN patients showed risks to adverse maternal-fetal events. Heavy proteinuria, especially before week 20 of gestation, severe hypoalbuminemia, positive anti-PLA2R, and no remission were risk factors to worse outcomes.

scholarly journals Anti-PLA2R Antibodies as a Prognostic Factor in PLA2R-Related Membranous Nephropathy

2015 ◽  
Vol 42 (1) ◽  
pp. 70-77 ◽  
Author(s):  
Sjoerd A.M.E.G. Timmermans ◽  
Myrurgia A. Abdul Hamid ◽  
Jan Willem Cohen Tervaert ◽  
Jan G.M.C. Damoiseaux ◽  
Pieter van Paassen ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Immunosuppressive Agents ◽  
Immunosuppressive Treatment ◽  
Survival Rates ◽  
Spontaneous Remission ◽  
Correct Selection ◽  
Persistent Proteinuria ◽  
Phospholipase A2 Receptor ◽  
Elisa Testing

Background: The natural course of idiopathic membranous nephropathy (MN) varies, as it is known through favorable outcomes in most patients. However, one third of patients with idiopathic MN will slowly progress to end-stage renal disease (ESRD). To prevent disease progression, patients at high risk to develop ESRD are treated with immunosuppressive agents. Therefore, a correct selection of patients who need immunosuppressive treatment is important. Methods: Here, we evaluated the prognostic value of anti-phospholipase A2 receptor 1 antibody (anti-PLA2R) levels regarding clinical outcome in a well-defined cohort of 73 PLA2R-related MN patients with long-term follow-up. At baseline, patients were subdivided into patients with either low or high antibody levels based on ELISA testing. Results: Spontaneous remission rates were highest among patients with low anti-PLA2R levels (79%; hazard ratio 2.72 (95% CI 1.22-6.08), p = 0.02) after a median follow-up of 2.9 (95% CI 0.8-5.0, p < 0.001) years, whereas high anti-PLA2R levels were associated with persistent proteinuria (p = 0.04) and/or the need for immunosuppressive therapy (p < 0.001). Renal survival rates were 97% at 5 years, 93% at 10 years, and 89% at 15 years; however, this was not different between the anti-PLA2R groups. ESRD occurred significantly faster in patients with severe proteinuria as compared to patients with either mild (p = 0.02) or moderate proteinuria (p = 0.05). Conclusions: Low anti-PLA2R levels may predict spontaneous remissions in patients with PLA2R-related MN. Therefore, we suggest that quantification of anti-PLA2R is of value to monitor these patients.

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