Develop and Validate a Risk Score in Predicting Renal Failure in Focal Segmental Glomerulosclerosis

Introduction: The aim of this study was to develop and validate a risk score (RS) for end-stage kidney disease (ESKD) in patients with focal segmental glomerulosclerosis (FSGS). Methods: Patient with biopsy-proven FSGS was enrolled. All the patients were allocated 1:1 to the two groups according to their baseline gender, age, and baseline creatinine level by using a stratified randomization method. ESKD was the primary endpoint. Results: We recruited 359 FSGS patients, and 177 subjects were assigned to group 1 and 182 to group 2. The clinicopathological variables were similar between two groups. There were 23 (13%) subjects reached to ESKD in group 1 and 22 (12.1%) in group 2. By multivariate Cox regression analyses, we established RS 1 and RS 2 in groups 1 and 2, respectively. RS 1 consists of five parameters including lower eGFR, higher urine protein, MAP, IgG level, and tubulointerstitial lesion (TIL) score; RS 2 also consists of five predictors including lower C3, higher MAP, IgG level, hemoglobin, and TIL score. RS 1 and RS 2 were cross-validated between these two groups, showing RS 1 had better performance in predicting 5-year ESKD in group 1 (c statics, 0.86 [0.74–0.98] vs. 0.82 [0.69–0.95]) and group 2 (c statics, 0.91 [0.83–0.99] vs. 0.89 [0.79–0.99]) compared to RS 2. We then stratified the risk factors into four groups, and Kaplan-Meier survival curve revealed that patients progressed to ESKD increased as risk levels increased. Conclusions: A predictive model incorporated clinicopathological feature was developed and validated for the prediction of ESKD in FSGS patients.

[1]  B. Rovin,et al.  Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases. , 2021, Kidney international.

[2]  R. Katafuchi,et al.  Focal segmental glomerulosclerosis histologic variants and renal outcomes based on nephrotic syndrome, immunosuppression, and proteinuria remission. , 2021, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[3]  J. Wetzels,et al.  Therapeutic trials in adult FSGS: lessons learned and the road forward , 2021, Nature Reviews Nephrology.

[4]  D. Goldstein,et al.  Rare genetic causes of complex kidney and urological diseases , 2020, Nature Reviews Nephrology.

[5]  D. Gipson,et al.  Proteinuria Reduction and Kidney Survival in Focal Segmental Glomerulosclerosis. , 2020, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[6]  Shigeru Tanaka,et al.  Utility of Columbia classification in focal segmental glomerulosclerosis: renal prognosis and treatment response among the pathological variants. , 2020, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[7]  S. Ossareh,et al.  Kidney Outcome in Primary Focal Segmental Glomerulosclerosis (FSGS) by Using a Predictive Model. , 2019, Iranian journal of kidney diseases.

[8]  Keiichi Matsuzaki,et al.  Evaluating a New International Risk-Prediction Tool in IgA Nephropathy. , 2019, JAMA internal medicine.

[9]  K. Kiryluk,et al.  Kidney Failure Risk Prediction Equations in IgA Nephropathy: A Multicenter Risk Assessment Study in Chinese Patients. , 2018, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[10]  K. Nath,et al.  Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach. , 2018, Journal of the American Society of Nephrology : JASN.

[11]  Matthias Kretzler,et al.  Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies , 2018, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[12]  Feng Xu,et al.  Changes in the Spectrum of Kidney Diseases: An Analysis of 40,759 Biopsy-Proven Cases from 2003 to 2014 in China , 2017, Kidney Diseases.

[13]  M. Kretzler,et al.  An Outcomes-Based Definition of Proteinuria Remission in Focal Segmental Glomerulosclerosis. , 2017, Clinical journal of the American Society of Nephrology : CJASN.

[14]  N. Chen,et al.  Serum C3 and Renal Outcome in Patients with Primary Focal Segmental Glomerulosclerosis , 2017, Scientific Reports.

[15]  I. Buchan,et al.  An external validation of models to predict the onset of chronic kidney disease using population-based electronic health records from Salford, UK , 2016, BMC Medicine.

[16]  S. Hewitt,et al.  Reproducibility of the NEPTUNE descriptor-based scoring system on whole-slide images and histologic and ultrastructural digital images , 2016, Modern Pathology.

[17]  F. Kronenberg,et al.  Multinational Assessment of Accuracy of Equations for Predicting Risk of Kidney Failure: A Meta-analysis. , 2016, JAMA.

[18]  A. Gharavi,et al.  Novel mutations in the inverted formin 2 gene of Chinese families contribute to focal segmental glomerulosclerosis. , 2015, Kidney international.

[19]  A. Fogo Causes and pathogenesis of focal segmental glomerulosclerosis , 2015, Nature Reviews Nephrology.

[20]  Barry I. Freedman,et al.  APOL1 risk variants, race, and progression of chronic kidney disease. , 2013, The New England journal of medicine.

[21]  C. Zeng,et al.  The clinical course and long-term outcome of primary focal segmental glomerulosclerosis in Chinese adults. , 2013, Clinical nephrology.

[22]  V. D’Agati,et al.  Association of histologic variants in FSGS clinical trial with presenting features and outcomes. , 2013, Clinical journal of the American Society of Nephrology : CJASN.

[23]  P. Royston,et al.  External validation of a Cox prognostic model: principles and methods , 2013, BMC Medical Research Methodology.

[24]  R. D'Agostino,et al.  A risk score for chronic kidney disease in the general population. , 2012, The American journal of medicine.

[25]  V. D’Agati,et al.  Clinical trial of focal segmental glomerulosclerosis in children and young adults. , 2011, Kidney international.

[26]  N. Tangri,et al.  A predictive model for progression of chronic kidney disease to kidney failure. , 2011, JAMA.

[27]  A. McGrogan,et al.  The incidence of primary glomerulonephritis worldwide: a systematic review of the literature. , 2011, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[28]  Hsiu-Ching Hsu,et al.  A prediction model for the risk of incident chronic kidney disease. , 2010, The American journal of medicine.

[29]  C. Winkler,et al.  Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans , 2010, Science.

[30]  Heejung Bang,et al.  A simple algorithm to predict incident kidney disease. , 2008, Archives of internal medicine.

[31]  D. Vlahov,et al.  MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis , 2008, Nature Genetics.

[32]  V. D’Agati,et al.  Cellular focal segmental glomerulosclerosis: Clinical and pathologic features. , 2006, Kidney international.

[33]  R J Falk,et al.  Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. , 2006, Kidney international.

[34]  D. Gipson,et al.  Differential risk of remission and ESRD in childhood FSGS , 2006, Pediatric Nephrology.

[35]  J. Scholey,et al.  Focal and segmental glomerulosclerosis: definition and relevance of a partial remission. , 2005, Journal of the American Society of Nephrology : JASN.

[36]  E. Lewis,et al.  Focal segmental glomerulosclerosis in nephrotic adults: presentation, prognosis, and response to therapy of the histologic variants. , 2004, Journal of the American Society of Nephrology : JASN.

[37]  Agnes B Fogo,et al.  Pathologic classification of focal segmental glomerulosclerosis: a working proposal. , 2004, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[38]  P. Eggers,et al.  Trends in the epidemiology of focal segmental glomerulosclerosis. , 2003, Seminars in nephrology.

[39]  V. D’Agati,et al.  Pathologic classification of focal segmental glomerulosclerosis. , 2003, Seminars in nephrology.

[40]  G. D'Amico,et al.  A modern approach to selectivity of proteinuria and tubulointerstitial damage in nephrotic syndrome. , 2000, Kidney international.

[41]  T. Nishino,et al.  Clinical and morphological predictors of renal outcome in adult patients with focal and segmental glomerulosclerosis (FSGS). , 1996, Clinical nephrology.

[42]  M. Schwartz,et al.  Focal segmental glomerular sclerosis in adults: presentation, course, and response to treatment. , 1995, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[43]  E. Lewis,et al.  Primary focal segmental glomerulosclerosis: clinical course and response to therapy. , 1994, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[44]  M. Kretzler,et al.  An Outcomes-Based Definition of Proteinuria Remission in Focal Segmental Glomerulosclerosis , 2018 .

[45]  J. Kopp,et al.  Focal Segmental Glomerulosclerosis. , 2017, Clinical journal of the American Society of Nephrology : CJASN.

[46]  Huiliang Xie,et al.  Mineral metabolites and CKD progression in African Americans. , 2013, Journal of the American Society of Nephrology : JASN.

[47]  N. Chen,et al.  Increased risk of treatment failure and end-stage renal disease in familial focal segmental glomerular sclerosis. , 2013, Contributions to nephrology.

[48]  M. Uppin,et al.  Morphologic evaluation of renal function using semi-quantitative method in primary nonproliferative glomerular diseases. , 2011, Indian journal of pathology & microbiology.

[49]  S. Korbet Clinical picture and outcome of primary focal segmental glomerulosclerosis. , 1999, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.