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Abstract: TH-PO990

Clinical Outcome and Molecular Profile of Perihilar FSGS Are Similar to Other FSGS Subtypes

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Doshi, Neal, University of Michigan, Ann Arbor, Michigan, United States
  • Larkina, Maria, University of Michigan, Ann Arbor, Michigan, United States
  • Nast, Cynthia C., Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Hou, Jean, Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Laurin, Louis-Philippe, Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada
  • Eddy, Sean, University of Michigan, Ann Arbor, Michigan, United States
  • Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States
  • Nachman, Patrick H., University of Minnesota, Minneapolis, Minnesota, United States
  • Mariani, Laura H., University of Michigan, Ann Arbor, Michigan, United States
Background

Perihilar (PH) FSGS is hypothesized to be a result of podocyte loss from secondary causes including obesity, hypertension and low nephron mass. It is assumed to have a more favorable outcome than the immune mediated subtypes of FSGS, including FSGS NOS, but prior studies have included a referral population more likely to have a severe phenotype.

Methods

NEPTUNE is a multi-site observational cohort study of children and adults with nephrotic syndrome, enrolled at the time of clinically indicated renal biopsy. Cox models for time to either remission [defined as urine protein to creatinine ratio (UPCR <0.3mg/mg)] or ESRD/40% eGFR decline were adjusted for age, GFR, uPCR, race, and sex. Genomewide mRNA expression data from kidney biopsy tissue was generated using Affymetrx 2.1 ST platform. Differentially expressed genes (FDR <1%) for perihilar FSGS compared to all other subtypes was determined using Significance Analysis of Microarrays (SAM).

Results

Among 111 patients with FSGS, 28 were PH, 19 Collapsing, 13 Tip, and 51 NOS. Gene expression was available from the glomerulus compartment for 39 patients and from tubulointerstitial compartment for 56. Comparing PH to NOS subtype, there were no differences in obesity (71% vs 78%), edema (32% vs. 36%), or hypertension (25% vs. 38%). 52% of patiehts with a PH lesion had >50% foot process effacement. Adjusted survival models showed no difference in time to complete remission or loss of eGFR between PH and NOS subtypes (p-value 0.88 and 0.22, respectively) [Fig 1]. Only 3 glomerular (of 25,583) and 6 tubular genes (of 23,397) were differentially expressed between PH vs other subtypes.

Conclusion

Patients with PH lesions as defined by the Columbia classification criteria had similar clinical presentations, rate of remission and loss of GFR as compared to the NOS subtype. The tissue molecular profile was also similar for PH patients as compared to other subtypes, raising the possibility that the mechanism of underlying tissue damage may be shared across the subtypes despite heterogeneous initial insults and varied pathologic categories.

Funding

  • NIDDK Support