ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2023 and some content may be unavailable. To unlock all content for 2023, please visit the archives.

Abstract: SA-PO989

HIV-Associated Nephropathy (HIVAN) Phenotype Is a Consequence of Compromised Parietal Epithelial Trans-Differentiation in the APOL1 Renal Risk Milieu

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology


  • Kumar, Vinod, Post Graduate Institute of Medical Education and Research, Chandigarh, Chandigarh, India
  • Malhotra, Ashwani, Northwell Health Feinstein Institutes for Medical Research, Manhasset, New York, United States
  • Skorecki, Karl, Bar-Ilan University, Ramat Gan, Tel Aviv, Israel
  • Singhal, Pravin C., Northwell Health Feinstein Institutes for Medical Research, Manhasset, New York, United States

HIV-infected patients with African ancestry carrying APOL1 variants (ARRVs G1 and G2) have a several-fold higher risk of developing HIVAN than patients with APOL1 wild-type (G0). HIV enhances APOL1 expression in parietal epithelial cells (PECs). We hypothesized that HIV-mediated PECs’ proliferation and transition are compromised in the ARRV milieu & result in PECs’ accumulation in Bowman's space, manifesting HIVAN phenotype (a collapsing variant).


The cultured human parietal epithelial cells (PECs) were transduced with vector, G0, G1 & G2 & analyzed for their proliferative, fibrotic, & podocyte (PD)-specific differentiation phenotype (transition markers) using western blotting (WB). For phenotype-specific proliferative, profibrotic, and transition markers under the HIV milieu, V/G0/G1/G2-PECs were transduced with HIV(NL4-3) for 48hr(n=4) & analyzed by WB. The expression of mTOR signaling and PECs’ transition markers was measured using Western blotting and miR193a expression by RT-PCR to evaluate the involved mechanisms. Renal tissues from control & Tg26 (a HIVAN model) mice were analyzed for miR193a & mTOR expression by FISH & IHC in PECs.


In vitro studies, G1/G2-PECs displayed an increased expression of profibrotic (CD44, PERK, α-SMA, Fibronectin, Vimentin, MMP9, SNAIL) but an attenuated expression of transition markers in control and HIV milieus when compared to G0-PECs; in contrast, G0-PECs showed attenuated expression of profibrotic but an enhanced expression of transition markers in HIV milieu. These findings indicate that PEC to PD transition is compromised in G1/G2-PECs in the control and HIV milieu. G1/G2-PECs also displayed increased expression of p-mTOR,p-70S6K,p-4EBP, & p-eEF, indicating the activation of mTOR signaling. Renal cortical sections of Tg26 mice showed an increased accumulation of PECs in their Bowman's space and increased miR193a & mTOR expression by PECs compared to control mice.


HIVAN phenotype (collapsing variant) results from the compromised transition in profibrotic PECs to podocytes in APOL1 renal risk (G/G2) milieu in HIV-infected patients.


  • NIDDK Support