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

Vivette D. D'Agati, Joan M. Alster, J. Charles Jennette, David B. Thomas, James Pullman, Daniel A. Savino, Arthur H. Cohen, Debbie S. Gipson, Jennifer J. Gassman, Milena K. Radeva, Marva M. Moxey-Mims, Aaron L. Friedman, Frederick J. Kaskel, Howard Trachtman, Charles E. Alpers, Agnes B. Fogo, Tom H. Greene, Cynthia C. Nast

Research output: Contribution to journalArticlepeer-review

117 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)399-406
Number of pages8
JournalClinical Journal of the American Society of Nephrology
Issue number3
StatePublished - Mar 7 2013
Externally publishedYes

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation


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