Disease causing mutations in inverted formin 2 regulate its binding to G-actin, F-actin capping protein (CapZ α-1) and profilin 2

Mutations in inverted formin 2 (INF2) cause focal segmental glomerulosclerosis (FSGS) a major cause of end-stage kidney disease. In the present study, we show that disease associated mutations reduce INF2 auto-inhibition and cause increased binding to monomeric G-actin, profilin 2 and the F-actin capping protein, CapZ α-1.

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Focal Segmental Glomerulosclerosis, Risk Factors for End Stage Kidney Disease, and Response to Immunosuppression

Kidney360 ◽

10.34067/kid.0006172020 ◽

2020 ◽

pp. 10.34067/KID.0006172020

Author(s):

Benjamin M. Forster ◽

Robert Nee ◽

Dustin J. Little ◽

Peter J. Greasley ◽

James B. Hughes ◽

...

Keyword(s):

Risk Factors ◽

Kidney Disease ◽

Focal Segmental Glomerulosclerosis ◽

Renal Survival ◽

End Stage Kidney Disease ◽

Interstitial Inflammation ◽

Segmental Glomerulosclerosis ◽

End Stage

Background: Focal segmental glomerulosclerosis (FSGS) is a heterogeneic glomerular disease. Risk factors for end- stage kidney disease (ESKD) and impact of immunosuppression treatment (IST) has varied in previously published cohorts. These cohorts were limited by relatively small case numbers, short follow up, lack of racial/ethnic diversity, a mix of adult and pediatric patients, lack of RAAS inhibition, or lack of subgroup analysis of IST. Methods: We compared demographics, clinical characteristics, histopathology and IST to long term renal survival in a large, ethnically diverse, adult cohort of 338 biopsy-proven FSGS cases with long term follow up in the era of RAAS inhibition using data from the United States Department of Defense health care network. Results: Multivariate analysis showed that nephrotic range proteinuria (NRP), estimated glomerular filtration rate <60 ml/min/1.73m2, hypoalbuminemia, interstitial fibrosis and tubular atrophy, and interstitial inflammation at diagnosis as well as the absence of remission were all associated with worse long term renal survival. IgM, C3, and a combination of IgM/C3 immunofluorescence staining were not associated with reduced renal survival. IST was not associated with improved renal survival in the whole cohort, or in a subgroup with NRP. However, IST was associated with better renal survival in a subgroup of FSGS cases with both NRP and hypoalbuminemia and hypoalbuminemia alone. Conclusion: Our study suggests that IST should be reserved for FSGS patients with nephrotic syndrome. It also introduces interstitial inflammation as a potential risk factor for ESKD and does not support the proposed pathogenicity of IgM and complement activation.

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Kidney Outcome in Primary Focal Segmental Glomerulosclerosis (FSGS) by Using a Predictive Model

10.21203/rs.2.11407/v1 ◽

2019 ◽

Author(s):

Shahrzad Ossareh ◽

Mansoureh Yahyaei ◽

Mojgan Asgari ◽

Hanri Afghahi

Keyword(s):

Kidney Disease ◽

Predictive Model ◽

Focal Segmental Glomerulosclerosis ◽

Interstitial Fibrosis ◽

Cox Model ◽

End Stage Kidney Disease ◽

Model Interaction ◽

Segmental Glomerulosclerosis ◽

End Stage ◽

Adjusted Model

Abstract Background: Focal segmental glomerulosclerosis (FSGS) is one of the important causes of end stage kidney disease (ESKD). We evaluated the risk factors of progression of primary FSGS to chronic kidney disease (CKD) or ESKD with a predictive model including clinical and histological predictors. Methods: 201 patients with primary FSGS (59% male, mean age: 38±15 years), were studied. Time-dependent Cox model and C statistics were used for the predictive model. Interaction and correlation between independent variables were estimated. Results: During 55±27 months of follow-up, 82 patients (41%) developed CKD (46) or ESKD (36) patients. In adjusted model, 1 unit of higher serum creatinine (SCr) at baseline (HR:1.39, 95%CI: 1.15-1.70) and 1% increase in glomeruli with segmental glomerulosclerosis (SGS) (HR: 1.03, 95% CI: 1.02-1.04) or interstitial fibrosis/tubular atrophy (IF/TA) (HR: 1.03, 95% CI: 1.01-1.05) increased the risk of CKD/ESKD. In adjusted model, higher baseline proteinuria and collapsing variant were not associated with risk of CKD/ESKD. By adding SGS and IF/TA scores to baseline SCr in the model, discrimination by C statistics was 0.83 (95%CI: 0.77-0.90). Median renal survival was 3.1 years (95% CI: 2.2-4.1 years) in patients with highest risks score (baseline eGFR<25 ml/min/1.73 m2+ IF/TA/SGS> 50%), and 8.1 years (95% CI: 7.7-8.6 years).in those with lowest score (baseline eGFR>75 ml/min/1.73 m2+ IF/TA/SGS <5%). Conclusion: In primary FSGS, higher baseline SCr, increased SGS and IF/TA, but not baseline proteinuria and collapsing pathology, were the predictors for CKD/ESKD. These findings indicated the importance of timely detection and referral in prognosis of primary FSGS. Keywords: Focal segmental glomerulosclerosis, End stage kidney disease, Pathology

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A novel truncating PAX2 mutation in a boy with renal coloboma syndrome with focal segmental glomerulosclerosis causing rapid progression to end-stage kidney disease

CEN Case Reports ◽

10.1007/s13730-019-00419-y ◽

2019 ◽

Vol 9 (1) ◽

pp. 19-23 ◽

Cited By ~ 1

Author(s):

Ken Saida ◽

Koichi Kamei ◽

Naoya Morisada ◽

Masao Ogura ◽

Kentaro Ogata ◽

...

Keyword(s):

Kidney Disease ◽

Focal Segmental Glomerulosclerosis ◽

Rapid Progression ◽

End Stage Kidney Disease ◽

Segmental Glomerulosclerosis ◽

Renal Coloboma Syndrome ◽

End Stage

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Clinical and laboratory features that differentiate familial from sporadic focal segmental glomerulosclerosis in adolescents and adults

Journal of Rare Diseases Research & Treatment ◽

10.29245/2572-9411/2021/1.1199 ◽

2021 ◽

Vol 6 (1) ◽

pp. 1-5

Author(s):

Maria Goretti Polito ◽

Michelle Tiveron Passos ◽

Danilo Euclides Fernandes ◽

Gianna Mastroianni-Kirsztajn

Keyword(s):

Serum Albumin ◽

Focal Segmental Glomerulosclerosis ◽

Steroid Resistance ◽

End Stage Kidney Disease ◽

Steroid Resistant ◽

Best Management ◽

Segmental Glomerulosclerosis ◽

Laboratory Features ◽

Adolescents And Adults ◽

End Stage

Background: Focal segmental glomerulosclerosis (FSGS) is an important cause of end-stage kidney disease in children and adults. Although most cases are sporadic (s), familial (f) presentation is also described. The purpose of the present study was to establish clinical and laboratory profiles of fFSGS vs. primary sFSGS, contributing to the distinguishing diagnosis in clinical practice and best management, in particular when mutation analysis is not available. Methods: Demographic, clinical and laboratorial parameters were studied in 124 patients 12 years and older with FSGS, subdivided in sFSGS (n=89) and fFSGS (n=35). Results: General and clinical features were similar, as well as serum creatinine at disease presentation. Proteinuria levels were more frequently ≥ 3g/day in sFSGS (63.8%) than in fFSGS (44%, p=0.080), and serum albumin levels were < 3.0 g/dL in 45.8% and 20%, respectively (p=0.046). The groups were statistically different regarding steroid resistance, corresponding to 60% in sFSGS and 100% in fFSGS (p=0.001). Conclusions: The studied groups were clinically similar, except that proteinuria tended to be higher (nephrotic range) and serum albumin was lower in sFSGS vs. fFSGS. In addition, all treated fFSGS patients were steroid resistant. At presentation it is important to characterize if the patient has fFSGS, that will contribute to further disease management, and disease history will be the first clue for such differential diagnosis.

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Chronic kidney disease: a review of proteomic and metabolomic approaches to membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy biomarkers

Proteome Science ◽

10.1186/s12953-019-0155-y ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 4

Author(s):

Amir Taherkhani ◽

Reyhaneh Farrokhi Yekta ◽

Maede Mohseni ◽

Massoud Saidijam ◽

Afsaneh Arefi Oskouie

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Iga Nephropathy ◽

Focal Segmental Glomerulosclerosis ◽

Membranous Glomerulonephritis ◽

Renal Diseases ◽

Segmental Glomerulosclerosis ◽

Therapeutic Procedures ◽

Definition Of ◽

End Stage

AbstractChronic Kidney Disease (CKD) is a global health problem annually affecting millions of people around the world. It is a comprehensive syndrome, and various factors may contribute to its occurrence. In this study, it was attempted to provide an accurate definition of chronic kidney disease; followed by focusing and discussing on molecular pathogenesis, novel diagnosis approaches based on biomarkers, recent effective antigens and new therapeutic procedures related to high-risk chronic kidney disease such as membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy, which may lead to end-stage renal diseases. Additionally, a considerable number of metabolites and proteins that have previously been discovered and recommended as potential biomarkers of various CKDs using ‘-omics-’ technologies, proteomics, and metabolomics were reviewed.

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Kidney Outcome in Primary Focal Segmental Glomerulosclerosis (FSGS) by Using a Predictive Model

10.21203/rs.2.11407/v3 ◽

2020 ◽

Author(s):

Shahrzad Ossareh ◽

Mansoureh Yahyaei ◽

Mojgan Asgari ◽

Hanri Afghahi

Keyword(s):

Kidney Disease ◽

Predictive Model ◽

Focal Segmental Glomerulosclerosis ◽

Interstitial Fibrosis ◽

Cox Model ◽

Tubular Atrophy ◽

Model Interaction ◽

Segmental Glomerulosclerosis ◽

End Stage ◽

Adjusted Model

Abstract Background: Focal segmental glomerulosclerosis (FSGS) is one of the important causes of end stage kidney disease (ESKD). We evaluated the risk factors of progression of primary FSGS to chronic kidney disease (CKD) or ESKD with a predictive model including clinical and histological predictors.Methods: 201 patients with primary FSGS (59% male, mean age: 38±15 years), were studied. Time-dependent Cox model and C statistics were used for the predictive model. Interaction and correlation between independent variables were estimated.Results: During 55±27 months of follow-up, 82 patients (41%) developed CKD (46) or ESKD (36) patients. In adjusted model, 1 unit of higher serum creatinine (SCr) at baseline (HR:1.39, 95%CI: 1.15-1.70) and 1% increase in glomeruli with segmental glomerulosclerosis (SGS) (HR: 1.03, 95% CI: 1.02-1.04) or interstitial fibrosis/tubular atrophy (IF/TA) (HR: 1.03, 95% CI: 1.01-1.05) increased the risk of CKD/ESKD. In adjusted model, higher baseline proteinuria and collapsing variant were not associated with risk of CKD/ESKD. By adding SGS and IF/TA scores to baseline SCr in the model, discrimination by C statistics was 0.83 (95%CI: 0.77-0.90). Median renal survival was 3.1 years (95% CI: 2.2-4.1 years) in patients with highest risks score (baseline eGFR<25 ml/min/1.73 m2+ IF/TA/SGS> 50%), and 8.1 years (95% CI: 7.7-8.6 years).in those with lowest score (baseline eGFR>75 ml/min/1.73 m2+ IF/TA/SGS <5%).Conclusion: In primary FSGS, higher baseline SCr, increased SGS and IF/TA, but not baseline proteinuria and collapsing pathology, were the predictors for CKD/ESKD. These findings indicated the importance of timely detection and referral in prognosis of primary FSGS.

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