Focal segmental glomerulosclerosis in idiopathic membranous glomerulonephritis: a clinico-pathological and stereological study

Gupta, Ruchika; Sharma, Alok; Mahanta, Pranab Jyoti; Jacob, Tony George; Agarwal, Sanjay Kumar; Roy, Tara Sankar; Dinda, Amit Kumar

doi:10.1093/ndt/gfp521

Cited by 26 publications

(32 citation statements)

References 10 publications

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“…The evaluation of FSGS as a predictor factor of renal function outcome has gained much interest but results remain conflicting, with some investigators supporting a pathogenic role of FSGS in declining renal function, providing FSGS and the severity of tubulointerstitial fibrosis as the only independent factors of disease outcome, while others doubt that there is any correlation of FSGS with renal function outcome …”

Section: Discussionmentioning

confidence: 99%

Histological grading in primary membranous nephropathy is essential for clinical management and predicts outcome of patients

et al. 2019

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AimsDiagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment.Methods and resultsHistological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re‐evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15–85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow‐up period was 122.3 (112–376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P < 0.0001, P = 0.001 and P = 0.02, respectively) and at the end of follow‐up (P = 0.004, P < 0.0001, P < 0.0001 and P = 0.04, respectively). In multiple regression and binary logistic analysis, the presence of FSGS and degree of TA were the most significant parameters predicting renal function outcome, defined either by eGFR (end), FSGS (r = 0.6, P < 0.0001) and TA (r = 0.6, P < 0.0001), or by the endpoint of >50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation.ConclusionsThe presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long‐term follow‐up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings.

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Section: Discussionmentioning

confidence: 99%

Histological grading in primary membranous nephropathy is essential for clinical management and predicts outcome of patients

et al. 2019

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“…Several studies have suggested various histopathologic features on renal biopsy at diagnosis to be associated with a worse renal outcome [4,5,6,7,8,9,10,11,12]. Histopathologic findings that have been reported as meaningful predictors of outcome in i-MN include glomerular scarring and severity of tubulointerstitial disease.…”

Section: Discussionmentioning

confidence: 99%

“…For example, although smaller studies have suggested that several histopathologic features are associated with worse outcomes in i-MN [4,5,6,7,8,9,10,11,12], a large, collaborative study from Toronto found that pathology did not influence outcomes [13]. The literature contains similar discrepancies regarding the prognostic importance of clinical and laboratory parameters.…”

Section: Introductionmentioning

confidence: 99%

Idiopathic Membranous Nephropathy: Clinical and Histologic Prognostic Features and Treatment Patterns over Time at a Tertiary Referral Center

Sprangers¹,

Bomback²,

Cohen³

et al. 2012

Am J Nephrol

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Background: Idiopathic membranous nephropathy (i-MN) is a leading cause of nephrotic syndrome in adults and results in end-stage renal disease in approximately one third of patients. There are few large, long-term US studies evaluating clinical and histologic prognostic factors in i-MN. Methods: We describe 132 patients with biopsy-proven i-MN who were followed for a mean period of 68 months at our tertiary referral center from 1977 to 2009, and we analyzed clinical and histologic features that predicted renal outcomes. Results: The presence of hypertension and treating physician’s decision to institute immunosuppression were negative predictors of attaining complete or partial remission. Among clinical variables, impaired renal function (eGFR <60 ml/min/1.73 m²) at time of presentation was the only variable at presentation associated with an increased risk of reaching end-stage renal disease. The use of statins and RAAS blockers were protective. The choice of corticosteroids as the initial immunosuppressive agent by referring physicians decreased over time but even in the most recent era (2000–2008) was significant (33%). Conclusion: Renal function at presentation and non-white race were the main predictors of a worse renal outcome. Corticosteroid therapy is still being adopted as first-line therapy in a significant number of patients in this era. The development of guidelines may help clarify the treatment strategies of i-MN.

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“…Segmental glomerulosclerosis can be seen in other glomerular diseases, including IgA nephropathy, with primarily mesangial pathology 20 and in membranous nephropathy, although this may reflect post-adaptive FSGS. 21 Barisoni et al have proposed a broad definition that makes room under the FSGS tent for segmental glomerulosclerosis with GLA mutations (Fabry disease) and COL4 mutations (Alport syndrome). 22 ADM9 spectrum mutations would then fit within the subcategory of genetic FSGS, the common feature of these diseases being podocyte injury that stems from the mutation.…”

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confidence: 99%

Glomerular pathology in autosomal dominant MYH9 spectrum disorders: what are the clues telling us about disease mechanism?

Kopp

2010

Kidney International

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Genetic variation in MYH9, encoding non-muscle heavy chain IIA, has been recognized for over a decade as the cause of an autosomal dominant syndrome characterized by macrothrombocytopenia, neutrophil inclusions, and glomerular pathology. More recently, genetic variation in the MYH9 region on chromosome 22 has been associated with chronic kidney disease in African-descent individuals. A better understanding of the disease mechanisms responsible for glomerular injury in autosomal dominant MYH9 syndromes will lead to fuller appreciation of the role of this gene in glomerular biology.

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Focal segmental glomerulosclerosis in idiopathic membranous glomerulonephritis: a clinico-pathological and stereological study

Cited by 26 publications

References 10 publications

Histological grading in primary membranous nephropathy is essential for clinical management and predicts outcome of patients

Histological grading in primary membranous nephropathy is essential for clinical management and predicts outcome of patients

Idiopathic Membranous Nephropathy: Clinical and Histologic Prognostic Features and Treatment Patterns over Time at a Tertiary Referral Center

Glomerular pathology in autosomal dominant MYH9 spectrum disorders: what are the clues telling us about disease mechanism?

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