Abstract: SA-PO349

Impact of Intrarenal and Circulating APOL1 Expression Levels on Phenotypes in Nephrotic Syndrome

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Yasutake, K, University of Michigan, Ann Arbor, Michigan, United States
  • Berg, Anders H., None, Boston, Massachusetts, United States
  • Shukha, Khuloud, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Pollak, Martin R., Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, United States
  • Sampson, Matt G., University of Michigan, Ann Arbor, Michigan, United States

Group or Team Name

  • NEPTUNE
Background

Although high-risk (HR) APOL1 genotypes are associated with FSGS development & worse outcomes in patients with nephrotic syndrome (NS), less is known about the relationship between APOL1 expression & clinical parameters. While in population & CKD cohorts, circulating APOL1 levels are not CKD-associated, this relationship has not been studied in NS. Intrarenal APOL1 expression level is not associated with HR genotype in NS patients. But higher APOL1 expression, even the wildtype form, is associated with cytotoxicity & FSGS in model systems. Does increased APOL1 expression contribute to poor outcomes in NS across races? To assess this, we characterized associations of intrarenal & circulating APOL1 expression levels with clinical & histological phenotypes in black & non-black patients in the Nephrotic Syndrome Study Network (NEPTUNE).

Methods

NEPTUNE is a prospective study of NS patients of all ages receiving a clinically indicated biopsy. We identified APOL1 genotyped patients with baseline & longitudinal clinical data and intrarenal mRNA expression profiling of microdissected glomeruli (GLOM) (n=160) or tubulointerstitium (TI) (n=193). 95 also had circulating APOL1 protein levels measured with ELISA. Non-blacks made up 29% of patients with intrarenal & 68% with circulating expression. As a function of baseline GLOM, TI, or circulating APOL1 expression, we modeled baseline eGFR, interstitial fibrosis (IF) on biopsy, complete remission (CR), & a composite endpoint. We also did analyses stratified by race & risk genotype.

Results

In multivariable analyses of black patients, higher TI expression of APOL1 was significantly associated with lower eGFR (-9.8ml/min per doubling of APOL1 expression; p=0.02) and increased IF(p=0.01), independent of APOL1 risk genotype. These associations were not observed with TI APOL1 expression in non-black or GLOM in black & non-black patients. There were no significant association of circulating APOL1 levels with clinical or histologic parameters, across races & risk genotypes.

Conclusion

In black patients with NS, elevated TI APOL1 expression, independent of risk genotype, was associated with lower eGFR & more fibrosis. It may be worth investigating whether decreasing intrarenal APOL1 level is beneficial in any black NS patient. Further inquiry in larger cohorts of non-blacks with NS is also warranted.

Funding

  • NIDDK Support