The impact of sex in primary glomerulonephritis

Cattran, Daniel C.; Reich, Heather N.; Beanlands, Heather; Miller, Judith; Scholey, James W.; Troyanov, Stéphan

doi:10.1093/ndt/gfm919

Cited by 112 publications

(116 citation statements)

References 41 publications

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“…Although this is consistent with the literature, suggesting males have a worse renal survival (5,7), it is important to note that despite a lower percentage of males within this group, their rate of progression was not significantly different from the females. This is consistent with a recent analysis from our group, wherein we demonstrated that progression (slope of CrCl) is not dependent on sex in MGN except when urine protein persistently exceeds 8 g/d (22).…”

Section: Discussionsupporting

confidence: 93%

The Natural History of the Non-Nephrotic Membranous Nephropathy Patient

Hladunewich

Troyanov

Calafati

et al. 2009

Clinical Journal of the American Society of Nephrology

111

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Background and objectives: Although early studies suggest that patients with idiopathic membranous nephropathy (MGN) and subnephrotic range proteinuria overall do well, these studies were small and follow-up was short or difficult to discern.Design Conclusions: Patients with MGN and sustained subnephrotic range proteinuria have an excellent prognosis. Conservative management with close monitoring is recommended given the difficulty predicting which patients will develop nephrotic range proteinuria and then progress more rapidly.

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Section: Discussionsupporting

confidence: 93%

The Natural History of the Non-Nephrotic Membranous Nephropathy Patient

Hladunewich

Troyanov

Calafati

et al. 2009

Clinical Journal of the American Society of Nephrology

111

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“…Furthermore, the multivariate Cox regression analysis shows that PLA 2 R-Ab levels together with men and older age are predictors for the increase in serum creatinine. Being a man has been discussed to be a predictor for an unfavorable outcome in patients with MN (16), and in our cohort, older patients had a 15% higher risk to reach the study end point per 5 years of age.…”

Section: Discussionmentioning

confidence: 57%

M-type Phospholipase A2 Receptor Autoantibodies and Renal Function in Patients with Primary Membranous Nephropathy

Hoxha¹,

Harendza²,

Pinnschmidt

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Loss of renal function in patients with primary membranous nephropathy cannot be reliably predicted by laboratory or clinical markers at the time of diagnosis. M-type phospholipase A 2 receptor autoantibodies have been shown to be associated with changes in proteinuria. Their eventual effect on renal function, however, is unclear.Design, setting, participants, & measurements In this prospective, open, multicenter study, the potential role of M-type phospholipase A 2 receptor autoantibodies levels on the increase of serum creatinine in 118 consecutive patients with membranous nephropathy and positivity for serum M-type phospholipase A 2 receptor autoantibodies was analyzed. Patients were included in the study between April of 2010 and December of 2012 and observed until December of 2013. The clinical end point was defined as an increase of serum creatinine by $25% and serum creatinine reaching $1.3 mg/dl.Results Patients were divided into tertiles according to their M-type phospholipase A 2 receptor autoantibody levels at the time of inclusion in the study: tertile 1 levels=20-86 units/ml (low), tertile 2 levels=87-201 units/ml (medium), and tertile 3 levels $202 units/ml (high). The median follow-up time of all patients in the study was 27 months (interquartile range=18-33 months). The clinical end point was reached in 69% of patients with high M-type phospholipase A 2 receptor autoantibodies levels (tertile 3) but only 25% of patients with low M-type phospholipase A 2 receptor autoantibodies levels. The average time to reach the study end point was 17.7 months in patients with high M-type phospholipase A 2 receptor autoantibodies levels and 30.9 months in patients with low M-type phospholipase A 2 receptor autoantibodies levels. A multivariate Cox regression analysis showed that high M-type phospholipase A 2 receptor autoantibodies levels-in addition to men and older age-are an independent predictor for progressive loss of renal function.Conclusions High M-type phospholipase A 2 receptor autoantibodies levels were associated with more rapid loss of renal function in this cohort of patients with primary membranous nephropathy and therefore, could be helpful for treatment decisions.

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“…Age at onset,50 years, women, baseline proteinuria,8 g/d, and preserved renal function at presentation are predictors of SR (37,38). The genetic variants analyzed in this study showed no significant association with SR, although 18% of NSR patients exhibited either high (more than two) or low (less than two) FCGR3B CN compared with 4% of SR patients; this finding suggests that alterations in FCGR3B CN could hinder SR. FCGR3B CN was correlated with protein expression and immune complex clearance (39); therefore, changes in FCGR3B CN could alter the balance between Fc receptors, disrupting the tightly regulated immune system (20) and impeding achievement of SR.…”

Section: Discussionmentioning

confidence: 58%

HLA-DQA1 and PLA2R1 Polymorphisms and Risk of Idiopathic Membranous Nephropathy

Bullich

Ballarín

Oliver³

et al. 2014

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Single nucleotide polymorphisms (SNPs) within HLA complex class II HLA-DQ a-chain 1 (HLA-DQA1) and M-type phospholipase A2 receptor (PLA2R1) genes were identified as strong risk factors for idiopathic membranous nephropathy (IMN) development in a recent genome-wide association study. Copy number variants (CNVs) within the Fc gamma receptor III (FCGR3) locus have been associated with several autoimmune diseases, but their role in IMN has not been studied. This study aimed to validate the association of HLA-DQA1 and PLA2R1 risk alleles with IMN in a Spanish cohort, test the putative association of FCGR3A and FCGR3B CNVs with IMN, and assess the use of these genetic factors to predict the clinical outcome of the disease.Design, settings, participants, & measurements A Spanish cohort of 89 IMN patients and 286 matched controls without nephropathy was recruited between October of 2009 and July of 2012. Case-control studies for SNPs within HLA-DQA1 (rs2187668) and PLA2R1 (rs4664308) genes and CNVs for FCGR3A and FCGR3B genes were performed. The contribution of these polymorphisms to predict clinical outcome and renal function decline was analyzed.Results This study validated the association of these HLA-DQA1 and PLA2R1 SNPs with IMN in a Spanish cohort and its increased risk when combining both risk genotypes. No significant association was found between FCGR3 CNVs and IMN. These results revealed that HLA-DQA1 and PLA2R1 genotype combination adjusted for baseline proteinuria strongly predicted response to immunosuppressive therapy. HLA-DQA1 genotype adjusted for proteinuria was also linked with renal function decline. ConclusionThis study confirms that HLA-DQA1 and PLA2R1 genotypes are risk factors for IMN, whereas no association was identified for FCGR3 CNVs. This study provides, for the first time, evidence of the contribution of these HLA-DQA1 and PLA2R1 polymorphisms in predicting IMN response to immunosuppressors and disease progression. Future studies are needed to validate and identify prognostic markers.

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The impact of sex in primary glomerulonephritis

Cited by 112 publications

References 41 publications

The Natural History of the Non-Nephrotic Membranous Nephropathy Patient

The Natural History of the Non-Nephrotic Membranous Nephropathy Patient

M-type Phospholipase A2 Receptor Autoantibodies and Renal Function in Patients with Primary Membranous Nephropathy

HLA-DQA1 and PLA2R1 Polymorphisms and Risk of Idiopathic Membranous Nephropathy

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