Diagnosis and monitoring of IgA nephropathy: the role of biomarkers as an alternative to renal biopsy

Moresco, Rafael Noal; Speeckaert, Marijn M.; Delanghe, Joris

doi:10.1016/j.autrev.2015.05.009

Cited by 42 publications

(27 citation statements)

References 95 publications

(180 reference statements)

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“…Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and is the leading cause of end-stage renal disease (ESRD) [1, 2]. According to Kidney Disease Improving Global outcomes (KDIGO) guideline, renin-angiotensin system inhibitor for IgAN patients with persistent proteinuria ≥0.5 g/d, and renin-angiotensin system inhibitor plus corticosteroid for IgAN patients with persistent proteinuria ≥1 g/d are recommended [3].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of mycophenolate mofetil in patients with IgA nephropathy: an update meta-analysis

Jia

Zhou

et al. 2017

BMC Nephrol

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BackgroundThe application of mycophenolate mofetil (MMF) in treating patients with immunoglobulin A nephropathy (IgAN) remains uncertain. This update meta-analysis was performed to re-evaluate the therapeutic potential of MMF in IgAN.MethodsArticles were obtained by searching the electronic databases without language restriction. Randomized controlled trials studying the role of MMF in treating IgAN were collected. The quality of included studies was critically evaluated. Data analyses were performed by using RevMan 5.3 software.ResultsA total of 297 articles were screened and eight articles were finally included. Among the eight randomized controlled trials, five and three were high quality and low quality, respectively. Both fixed-effect and random-effect model were used. Pooled results by combining all the eight studies suggested that IgAN patients in MMF group had a higher remission rate than that in control group. Compared to placebo or corticosteroid monotherapy, MMF monotherapy exerted a higher remission rate and side effect rate in both main analysis and subgroup analysis by human race. Compared to corticosteroid plus other immunosuppressive agent therapy, corticosteroid plus MMF therapy had a higher remission rate, lower serum creatinine doubling rate, progression to end-stage renal disease rate and side effects rate. Subgroup analysis by therapeutic regimen further confirmed these results between corticosteroid plus MMF therapy and corticosteroid plus cyclophosphamide therapy. Funnel-plot displayed a symmetrical figure, indicating no publication bias existed.ConclusionsMMF has the potential in treatment of IgAN, especially for Asians. The evidence currently available shows that MMF monotherapy has a more efficacy but higher side effects when compared to placebo or corticosteroid monotherapy in treatment of Asians with IgAN. While MMF combined with corticosteroid regimen has a more efficacy and lower side effects when compared with corticosteroid plus cyclophosphamide regimen.

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Section: Introductionmentioning

confidence: 99%

Efficacy and safety of mycophenolate mofetil in patients with IgA nephropathy: an update meta-analysis

Jia

Zhou

et al. 2017

BMC Nephrol

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“…3 The diagnosis relies on histopathologic evaluation with findings of deposits of galactose-deficient IgA (gd-IgA) in the glomerular mesangial region in addition to mesangial cell proliferation and mesangial matrix expansion. 4 Moreover, the amount of gd-IgA deposited is not correlated with mesangial cell damage or kidney injury. 5 However, mesangial cell proliferation and inflammation induced by gd-IgA deposits are important for disease development.…”

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confidence: 98%

Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy

Liu

Lassén

Nair

et al. 2017

JASN

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IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (=19) and controls (=22). Using curated glomerular cell type-specific genes from the published literature, we found differential expression of a much higher percentage of mesangial cell-positive standard genes than podocyte-positive standard genes in IgAN. Principal coordinate analysis of expression data revealed clear separation of patient and control samples on the basis of mesangial but not podocyte cell-positive standard genes. Additionally, patient clinical parameters (serum creatinine values and eGFRs) significantly correlated with scores derived from the expression profile of mesangial cell-positive standard genes. Among patients grouped according to Oxford MEST score, patients with segmental glomerulosclerosis had a significantly higher mesangial cell-positive standard gene score than patients without segmental glomerulosclerosis. By investigating mesangial cell proteomics and glomerular transcriptomics, we identified 22 common pathways induced in mesangial cells by gd-IgA, most of which mediate inflammation. The genes, proteins, and corresponding pathways identified provide novel insights into the pathophysiologic mechanisms leading to IgAN.

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“…Immunoglobulin A nephropathy (IgAN) is the most common cause of primary glomerulonephritis (GN) worldwide 1 . The diagnosis of IgAN is based on dominant or co-dominant mesangial deposits of IgA alone or with IgG and/or IgM in the glomerular mesangium 1,2 . Recent studies revealed that mesangial deposition of abnormally glycosylated IgA1 molecule could activate local complement system and induce in ammation via the classical, alternative and lectin pathway 3,4 .…”

Section: Introductionmentioning

confidence: 99%

Mesangial IgM Deposition predicts renal outcome in patients with IgA nephropathy: A multicenter, prospective, observational study

TAN

Tang

Pei

et al. 2020

Preprint

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BackgroundMesangial IgM deposition is commonly found in patients with immunoglobulin A nephropathy (IgAN). This study aims to investigate the relationships between mesangial IgM deposition and disease progression in IgAN patients.MethodsA total of 1239 patients with biopsy-proven primary IgAN were enrolled in this multicenter, prospective, observational study between January 2013 and August 2017. According to the degree of IgM deposition, 1239 patients were divided into three groups: Grade 0 (no or trace; n = 713, 57.55%), Grade 1 (mild; n = 414, 33.41%), Grades 2 + 3 (moderate and marked; n = 112, 9.04%). Using a 1: 1 propensity score matching (PSM) method identifying age, gender, and treatment modality to minimize confounding factors, 1042 matched patients (out of 1239) with different degrees of IgM deposition were enrolled to evaluate the severity of baseline clinicopathological features and renal outcome: Grade 0 (n = 521, 50.00%), Grade 1 (n = 409, 39.25%), Grades 2 + 3 (n = 112, 10.75%). Kaplan–Meier and Cox proportional hazards analyses were performed to determine whether different degrees of mesangial IgM deposition are associated with varying renal outcomes in IgAN.ResultsDuring a mean follow-up of 48.90 ± 23.86 and 49.01 ± 23.73 months, before and after adjusting for propensity scores respectively, the rate of complete remission (CR) was progressively lower with increased IgM deposition in both unmatched (63.39%, 46.14%, 45.54%) and matched cohort (61.80%, 46.45%, 45.54%), whereas the proportion of patients progressing to end stage renal disease (ESRD) showed reverse correlation (P < 0.001). Kaplan–Meier analysis indicated negative correlation between the intensity of mesangial IgM deposits and cumulative renal survival (all P < 0.05). Moreover, Cox regression analysis revealed that the degree of mesangial IgM deposition predicted renal outcome independent of MESTC score and clinical variables in the unmatched (Grade 1, HR, 1.59; 95% CI, 1.11–2.29; P = 0.01; Grades 2 + 3, HR, 1.69; 95% CI, 1.02–2.08; P = 0.04) and matched cohort (Grade 1, HR, 1.84; 95% CI, 1.19–2.85; P = 0.01; Grades 2 + 3, HR, 1.91; 95% CI, 1.01–3.24; P = 0.04).ConclusionsMesangial IgM deposition plays an important role in renal prognosis and is independently associated with worse renal outcomes in patients with IgAN.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

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Diagnosis and monitoring of IgA nephropathy: the role of biomarkers as an alternative to renal biopsy

Cited by 42 publications

References 95 publications

Efficacy and safety of mycophenolate mofetil in patients with IgA nephropathy: an update meta-analysis

Efficacy and safety of mycophenolate mofetil in patients with IgA nephropathy: an update meta-analysis

Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy

Mesangial IgM Deposition predicts renal outcome in patients with IgA nephropathy: A multicenter, prospective, observational study

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