Membranous Nephropathy in Pregnancy

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.

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Infection-Related Acute Care Events among Patients with Glomerular Disease

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.05900420 ◽

2020 ◽

Vol 15 (12) ◽

pp. 1749-1761

Author(s):

Dorey A. Glenn ◽

Candace D. Henderson ◽

Michelle O’Shaughnessy ◽

Yichun Hu ◽

Andrew Bomback ◽

...

Keyword(s):

Risk Factors ◽

Serum Albumin ◽

Acute Care ◽

Incidence Rates ◽

Hazard Ratio ◽

Glomerular Disease ◽

Urinary Protein ◽

Adjusted Hazard Ratio ◽

Creatinine Ratio

Background and objectivesInfections contribute to patient morbidity and mortality in glomerular disease. We sought to describe the incidence of, and identify risk factors for, infection-related acute care events among Cure Glomerulonephropathy Network (CureGN) study participants.Design, setting, participants, & measurementsCureGN is a prospective, multicenter, cohort study of children and adults with biopsy sample–proven minimal change disease, FSGS, membranous nephropathy, or IgA nephropathy/vasculitis. Risk factors for time to first infection-related acute care events (hospitalization or emergency department visit) were identified using multivariable Cox proportional hazards regression.ResultsOf 1741 participants (43% female, 41% <18 years, 68% White), 163 (9%) experienced infection-related acute care events over a median follow-up of 17 months (interquartile range, 9–26 months). Unadjusted incidence rates of infection-related acute care events were 13.2 and 6.2 events per 100 person-years among pediatric and adult participants, respectively. Among participants with versus without corticosteroid exposure at enrollment, unadjusted incidence rates were 50.6 and 28.6 per 100 person-years, respectively, during the first year of follow-up (adjusted hazard ratio for time to first infection, 1.31; 95% CI, 0.89 to 1.93), and 4.1 and 1.1 per 100 person-years, respectively, after 1 year of follow-up (hazard ratio, 2.99; 95% CI, 1.54 to 5.79). Hypoalbuminemia combined with nephrotic-range proteinuria (serum albumin ≤2.5 g/dl and urinary protein-creatinine ratio >3.5 mg/mg), compared with serum albumin >2.5 g/dl and urinary protein-creatinine ratio ≤3.5 mg/mg, was associated with higher risk of time to first infection (adjusted hazard ratio, 2.49; 95% CI, 1.51 to 4.12).ConclusionsAmong CureGN participants, infection-related acute care events were common and associated with younger age, corticosteroid exposure, and hypoalbuminemia with proteinuria.

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

Annals of the Academy of Medicine, Singapore ◽

10.47102/annals-acadmedsg.2020138 ◽

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

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Risk Factors for Reduced Salivary Flow Rate in a Japanese Population: The Hisayama Study

BioMed Research International ◽

10.1155/2015/381821 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 9

Author(s):

Kenji Takeuchi ◽

Michiko Furuta ◽

Toru Takeshita ◽

Yukie Shibata ◽

Yoshihiro Shimazaki ◽

...

Keyword(s):

Risk Factors ◽

Serum Albumin ◽

Regression Model ◽

Flow Rate ◽

Salivary Flow ◽

Community Dwelling ◽

Salivary Flow Rate ◽

Multivariate Logistic Regression Model ◽

Plaque Score

The purpose of this study was to determine distinct risk factors causing reduced salivary flow rate in a community-dwelling population using a prospective cohort study design. This was a 5-year follow-up survey of 1,377 community-dwelling Japanese individuals aged ≥40 years. The salivary flow rate was evaluated at baseline and follow-up by collecting stimulated saliva. Data on demographic characteristics, use of medication, and general and oral health status were obtained at baseline. The relationship between reduced salivary flow rate during the follow-up period and its predictors was evaluated after adjustment for confounding factors. In a multivariate logistic regression model, higher age and plaque score and lower serum albumin levels were significantly associated with greater odds of an obvious reduction in salivary flow rate (age per decade, odds ratio [OR] = 1.25, 95% confidence interval [CI] = 1.03–1.51; serum albumin levels <4 g/dL, OR = 1.60, 95% CI = 1.04–2.46; plaque score ≥1, OR = 1.53, 95% CI = 1.04–2.24). In a multivariate linear regression model, age and plaque score remained independently associated with the increased rate of reduced salivary flow. These results suggest that aging and plaque score are important predictors of reduced salivary flow rate in Japanese adults.

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

BMC Nephrology ◽

10.1186/s12882-020-02042-x ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 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.

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Relationship between renal tissues phospholipase A2 receptor and its serum antibody and clinical condition and prognosis of idiopathic membranous nephropathy: a meta-analysis

BMC Nephrology ◽

10.1186/s12882-019-1638-x ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Dan Dong ◽

Ting-ting Fan ◽

Ying-ying Wang ◽

Lu Zhang ◽

Li Song ◽

...

Keyword(s):

Serum Creatinine ◽

Serum Albumin ◽

Membranous Nephropathy ◽

Remission Rate ◽

Meta Analysis ◽

Negative Group ◽

Urine Protein ◽

Positive Group ◽

Phospholipase A2 Receptor ◽

Significant Difference

Abstract Objective To investigate the correlation of M-type phospholipase A2 receptor (PLA2R) expression and serum anti-PLA2R antibody with the clinical parameters and prognosis of patients with idiopathic membranous nephropathy (IMN). Methods A literature search for relevant original articles published between January 2009 and October 2019 was conducted on domestic and foreign databases. RevMan 5.3 software was used for meta-analysis. Results Eighteen studies were included in this meta-analysis. There were 1235 anti-PLA2R antibody-positive and PLA2R-positive patients, and 407 serum anti-PLA2R antibody-negative and PLA2R-negative patients. Compared with negative group, patients in the serum PLA2R antibody -positive group had lower serum albumin [SMD = -1.11, 95% CI (− 1.82, − 0.40), P < 0.00001], higher age [MD = 2.71, 95% CI (1.94, 3.48), P < 0.00001], and lower estimated glomerular filtration rate (eGFR) [MD = -10.34, 95% CI (− 12.09, − 8.60), P < 0.00001]; no significant between-group difference was observed with respect to 24-h urine protein and serum creatinine. However, no significant difference was observed between renal tissues PLA2R -positive and -negative groups with respect to serum albumin, eGFR, serum creatinine, and 24-h urine protein. Remission rate in the serum anti-PLA2R antibody -positive group was lower than that in the -negative group [OR = 0.41, 95% CI (0.28, 0.61),P < 0.00001]; however, no significant between-group difference in this respect was observed between the renal tissue PLA2R-positive and -negative groups. In the serum anti-PLA2R antibody -positive group, the higher titer subgroup had lower remission rate [OR = 0.19, 95% CI (0.07, 0.55),P = 0.002]. No significant difference was observed between anti-PLA2R antibody -positive and -negative groups with respect to adverse events. Serum anti-PLA2R antibody titer did not affect the adverse event rate. Conclusion As compared to PLA2R, serum anti-PLA2R antibody is more closely related with IMN disease progression.

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Maternal and Fetal Outcomes of Pregnancy in Nephrotic Syndrome Due to Primary Glomerulonephritis

Frontiers in Medicine ◽

10.3389/fmed.2020.563094 ◽

2020 ◽

Vol 7 ◽

Author(s):

Rossella Siligato ◽

Guido Gembillo ◽

Valeria Cernaro ◽

Francesco Torre ◽

Antonino Salvo ◽

...

Keyword(s):

Risk Factors ◽

Nephrotic Syndrome ◽

Kidney Disease ◽

Survival Data ◽

Neonatal Intensive Care ◽

Fetal Outcomes ◽

Primary Glomerulonephritis ◽

Ckd Stage ◽

Kidney Disease Progression

Chronic kidney disease (CKD) affects 3% of pregnancies, impacting on maternal and fetal outcomes, and at the same time, a recurrent question in nephrology regards gestation impact on kidney function. Observational studies stated that CKD stage, pre-existent hypertension, and proteinuria are the main predictors of possible complications, such as maternal CKD progression, maternal or fetal death, prematurity, small for gestational age (SGA) newborn, or admission to the neonatal intensive care unit. In this regard, given the prominence of proteinuria among other risk factors, we focused on primary nephrotic syndrome in pregnancy, which accounts for 0.028% of cases, and its impact on materno-fetal outcomes and kidney survival. Data extracted from literature are scattered because of the small cohorts investigated in each trial. However, they showed different outcomes for each glomerular disease, with membranous nephropathy (MN) having a better maternal and fetal prognosis than focal and segmental glomerulosclerosis (FSGS), membranoproliferative glomerulonephritis (MPGN), or minimal change disease (MCD). Nephrotic syndrome does not have to discourage women to undertake a pregnancy, but the correct management may include a specific evaluation of risk factors and follow-up for adverse materno-fetal events and/or maternal kidney disease progression.

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Serum Antibody and Glomerular Antigen of Antiphospholipase A2 Receptor in Chinese Patients with Idiopathic Membranous Nephropathy

BioMed Research International ◽

10.1155/2020/1693710 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Qiu-hua Zhang ◽

Mian Wu ◽

Zhi-gang Hu ◽

Xiao-bin Liu ◽

Biao Huang ◽

...

Keyword(s):

Renal Function ◽

Serum Creatinine ◽

Serum Albumin ◽

Membranous Nephropathy ◽

Serum Antibody ◽

Chinese Patients ◽

Idiopathic Membranous Nephropathy ◽

Phospholipase A2 Receptor ◽

Secondary Membranous Nephropathy ◽

Clinical Correlations

Background. M-type phospholipase A2 receptor (PLA2R) is the first autoantigen responsible for idiopathic membranous nephropathy (IMN). However, serum PLA2R antibody (PLA2R-Ab) can be inaccurate in distinguishing between IMN and secondary membranous nephropathy, while renal PLA2R antigen (PLA2R-Ag) emerges as an ancillary diagnostic. The present study is aimed at examining the associations between PLA2R-Ab in sera and PLA2R-Ag in kidneys in IMN patients. Methods. A total of 93 patients with IMN were retrospectively identified. Their serum PLA2R-Ab and renal PLA2R-Ag expression levels were determined, and the clinical correlations between these parameters and clinical features were examined. Results. The sensitivities of serum PLA2R-Ab and renal PLA2R-Ag for diagnosing IMN were 74.2% and 88.2%, respectively (P<0.001), with poor consistency. Higher serum PLA2R-Ab levels were correlated to stronger renal PLA2R-Ag expression (P=0.048). Patients with positive PLA2R-Ab significantly differed from those with negative levels, in terms of proteinuric levels over 24 hours (4.54 vs. 3.46 g/day, P=0.015) and serum albumin (23.28 vs. 27.95 g/L, P=0.038). Among patients with positive renal PLA2R-Ag, patients with positive PLA2R-Ab had significantly higher 24-hour proteinuria, when compared to patients with negative PLA2R-Ab (4.57 vs. 3.08 g/day, P=0.005). Among those with positive PLA2R-Ab in sera, their PLA2R-Ab levels were correlated with the estimated glomerular filtration and serum creatinine. Conclusion. Serum PLA2R-Ab exhibits a closer correlation with proteinuric severity and renal function, when compared to renal PLA2R-Ag.

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P0341RITUXIMAB IN THE TREATMENT OF PRIMARY MEMBRANOUS NEPHROPATHY - A COMPARATIVE STUDY OF THREE REGIMEN

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa144.p0341 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Harbir Singh Kohli ◽

Raja Ramachandran ◽

Manish Rathi ◽

Ranjana Minz ◽

Ritambhra Nada Duseja

Keyword(s):

Targeted Therapy ◽

Adverse Events ◽

Serum Albumin ◽

Cumulative Dose ◽

Membranous Nephropathy ◽

Response Rate ◽

Secondary Outcome ◽

Therapy Initiation ◽

Significant Difference

Abstract Background and Aims Different rituximab dosing schedules have been used to manage primary membranous nephropathy (PMN). Better response rate and toxicity needs to be balanced to arrive at correct dose. The dosing schedules in PMN as of now are an on the lines of the management of lymphoma or rheumatoid arthritis. In the current study, we report the 1-year outcome of patients treated with three dosing schedules of rituximab in PMN. Method The current report is a study of patient of PMN treated with three different dosing schedules of rituximab treatment. The study included PMN patients with nephrotic syndrome (proteinuria>3.5 g/day and serum albumin of < 3.5 g/dL). Patients with secondary membranous nephropathy and a history of prior exposure of immunosuppressive therapy in the last three months were excluded from the study. The three dosing schedules of rituximab were 1 g (on day 0,15) (regimen 1), 375 mg/m2 (weekly for four weeks) (regimen 2) or CD19 targeted rituximab therapy (375 mg/m2 as the initial dose and additional dose 100 mg, when the CD19 cell count was> 5/ul or >1%, done every month for 12 months) (regimen 3). Serum PLA2R autoantibodies were done before rituximab therapy and at six months of therapy initiation. Primary outcomes: Remission at the end of 12 months of therapy initiation. Secondary outcome: Complete remission (CR) and partial remission (PR), remission with different treatment schedules and adverse events. Definition: CR: reduction of proteinuria to <0.5 g/d and with creatinine clearance of >60 ml/min/1.73m2 and serum albumin > 3.5 g/dl. PR: reduction of proteinuria to 0.5–3.5 g/day and stable serum creatinine. A p-value of <0.05 was considered significant. Results The study included 87 patients of PMN. The mean age of the patients was 33.36±15.38 (range 15-61) years. Thirty-two (36.4%) and 56 (63.6%) patients received rituximab as the first-line therapy and for relapsing/resistant disease, respectively. Forty, 15 and 33 patients received regimen 1, 2 and 3, respectively. The median proteinuria, serum albumin and creatinine at the baseline before rituximab therapy was 5.90 (IQR 4.20,9.75) gm, 2.50 (IQR 2.15,3.25) g/dl and 0.88 (IQR 0.77,1.09) mg/dl, respectively. At the end of 12 months of follow-up, 55 (56.8%) patients received remission. Nineteen (21.6%) and 32 (36.3%) patients achieved CR and PR, respectively. In regimen 1, 12 (30%) and 13 (32.5%) patients achieved CR and PR, respectively. In regimen 2, 2 (13.3%) and 5 (33.3%) patients achieved CR and PR, respectively. In regimen 3, 5 (15.6%) and 14 (43.7%) patients achieved CR and PR, respectively. One patient in the CD19 targeted therapy (regimen 3) was lost to follow-up after the 1st dose; all but one patient in the received regimen three as a second-line treatment. There was a significant association of anti-PLA2R to clinical response (p<0.05). There was no difference in the response rate among the three groups (p>0.05). A total of 7 (7.9%) patients had severe adverse events, there was no difference in the 3 regimens. (p>0.05) The cumulative dose in regimen 3 was significantly less as compared to regimen 1 & 2 (p<0.01) Conclusion Rituximab induces remission in two-thirds of the patients with PMN. There is no significant difference in the remission rates between different rituximab regimens. CD19 targeted therapy is equally effective with lower cumulative dose.

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Serum Albumin Still of Interest to Predict Outcomes in Membranous Nephropathy in the Era of Phospholipase A2 Receptor

Kidney International Reports ◽

10.1016/j.ekir.2020.06.040 ◽

2020 ◽

Vol 5 (9) ◽

pp. 1611-1612

Author(s):

Marion Delafosse ◽

Eléonore Ponlot ◽

Nicolas Hanset ◽

Emmanuel Estève ◽

Jean-Jaques Boffa ◽

...

Keyword(s):

Serum Albumin ◽

Phospholipase A2 ◽

Membranous Nephropathy ◽

Phospholipase A2 Receptor

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

American Journal of Nephrology ◽

10.1159/000437236 ◽

2015 ◽

Vol 42 (1) ◽

pp. 70-77 ◽

Cited By ~ 26

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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