Association of Histologic Variants in FSGS Clinical Trial... : Clinical Journal of the American Society of Nephrology (original) (raw)

Original Articles

Association of Histologic Variants in FSGS Clinical Trial with Presenting Features and Outcomes

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

Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.

Correspondence: Dr. Vivette D. D’Agati, Columbia University Medical Center, Department of Pathology; Renal Pathology Laboratory VC14-224, 630 West 168th Street, New York, NY 10032. Email: [email protected]

Received June 16, 2012

Accepted October 27, 2012

Clinical Journal of the American Society of Nephrology 8(3):p 399-406, March 2013. | DOI: 10.2215/CJN.06100612

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.