Association of histologic variants in FSGS clinical trial with presenting features and outcomes

Clin J Am Soc Nephrol. 2013 Mar;8(3):399-406. doi: 10.2215/CJN.06100612. Epub 2012 Dec 6.

Abstract

Background and objectives: 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.

Design, setting, participants, & measurements: 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Age Factors
  • Biomarkers / blood
  • Biopsy
  • Black or African American
  • Child
  • Child, Preschool
  • Creatinine / blood
  • Disease Progression
  • Drug Resistance
  • Female
  • Glomerulosclerosis, Focal Segmental / drug therapy
  • Glomerulosclerosis, Focal Segmental / ethnology
  • Glomerulosclerosis, Focal Segmental / pathology*
  • Humans
  • Hypoalbuminemia / ethnology
  • Hypoalbuminemia / pathology
  • Immunosuppressive Agents / therapeutic use
  • Kaplan-Meier Estimate
  • Kidney / drug effects
  • Kidney / pathology*
  • Kidney Failure, Chronic / ethnology
  • Kidney Failure, Chronic / pathology
  • Male
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Proteinuria / ethnology
  • Proteinuria / pathology
  • Remission Induction
  • Risk Assessment
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome
  • United States / epidemiology
  • White People
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Biomarkers
  • Immunosuppressive Agents
  • Creatinine