title: Association of histologic variants in FSGS clinical trial with presenting features and outcomes.
abstract: OBJECTIVE
  FSGS histologic variants have correlated with outcomes in retrospective studies. The FSGS Clinical Trial provided a unique opportunity to study the clinical impact of histologic variants in a well defined prospective cohort with steroid-resistant primary FSGS.
  
  
  METHODS
  Renal biopsies of 138 FSGS Clinical Trial participants aged 2-38 years enrolled from 2004 to 2008 were analyzed using the Columbia classification by core pathologists. This study assessed the distribution of histologic variants and examined their clinical and biopsy characteristics and relationships to patient outcomes.
  
  
  RESULTS
  The distribution of histologic variants was 68% (n=94) FSGS not otherwise specified, 12% (n=16) collapsing, 10% (n=14) tip, 7% (n=10) perihilar, and 3% (n=4) cellular. Individuals with not otherwise specified FSGS were more likely to have subnephrotic proteinuria (P=0.01); 33% of teenagers and adults had tip or collapsing variants compared with 10% of children, and subjects with these variants had greater proteinuria and hypoalbuminemia than not otherwise specified patients. Tip variant had the strongest association with white race (86%) and the lowest pathologic injury scores, baseline creatinine, and rate of progression. Collapsing variant had the strongest association with black race (63%, P=0.03) and the highest pathologic injury scores (P=0.003), baseline serum creatinine (P=0.003), and rate of progression. At 3 years, 47% of collapsing, 20% of not otherwise specified, and 7% of tip variant patients reached ESRD (P=0.005).
  
  
  CONCLUSIONS
  This is the first prospective study with protocol-defined immunomodulating therapies confirming poor renal survival in collapsing variant and showing better renal survival in tip variant among steroid-resistant patients.
authors.affiliation: Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, New York, USA. vdd1@columbia.edu
authors.forename: Vivette D
authors.initials: VD
authors.lastname: D'Agati
authors.forename: Joan M
authors.initials: JM
authors.lastname: Alster
authors.forename: J Charles
authors.initials: JC
authors.lastname: Jennette
authors.forename: David B
authors.initials: DB
authors.lastname: Thomas
authors.forename: James
authors.initials: J
authors.lastname: Pullman
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Savino
authors.forename: Arthur H
authors.initials: AH
authors.lastname: Cohen
authors.forename: Debbie S
authors.initials: DS
authors.lastname: Gipson
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Gassman
authors.forename: Milena K
authors.initials: MK
authors.lastname: Radeva
authors.forename: Marva M
authors.initials: MM
authors.lastname: Moxey-Mims
authors.forename: Aaron L
authors.initials: AL
authors.lastname: Friedman
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Kaskel
authors.forename: Howard
authors.initials: H
authors.lastname: Trachtman
authors.forename: Charles E
authors.initials: CE
authors.lastname: Alpers
authors.forename: Agnes B
authors.initials: AB
authors.lastname: Fogo
authors.forename: Tom H
authors.initials: TH
authors.lastname: Greene
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Nast
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D001741:Black or African American; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D004351:Drug Resistance; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000208:ethnology / Q000473:pathology*; D006801:Humans; D034141:Hypoalbuminemia / Q000208:ethnology / Q000473:pathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D007676:Kidney Failure, Chronic / Q000208:ethnology / Q000473:pathology; D008297:Male; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011507:Proteinuria / Q000208:ethnology / Q000473:pathology; D012074:Remission Induction; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D044465:White People; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D007166:Immunosuppressive Agents; D003404:Creatinine