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Kidney Week

Abstract: PO0985

Dual Therapy with JAK1/2 Inhibitor and Losartan Attenuates Dialysate-Induced Angiogenesis in Polycystic Rats

Session Information

  • Peritoneal Dialysis
    November 04, 2021 | Location: On-Demand, Virtual Only
    Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

  • 702 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

  • Zhang, Pei, Department of Nephrology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
  • Miyata, Kana N., The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, United States
  • Mahoney, Madisyn, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, United States
  • La page, Janine A., The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, United States
  • Nast, Cynthia C., Cedars Sinai Medical Center, Los Angeles, California, United States
  • Adler, Sharon G., The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, United States
  • Dai, Tiane, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, California, United States
Background

Long term peritoneal dialysis (PD) is limited by reduced efficacy over time. Early peritoneal membrane (PM) injury is characterized by inflammation which progresses to hypervascularity and fibrosis. JAK/STAT signaling mediates inflammatory pathways, including angiotensin signaling. Our previous study showed dual therapy with JAK1/2 inhibitor (JAK1/2i) and an ARB maintains PM structure and function in rats with polycystic kidneys (PCK) chronically infused with 4.25% Dianeal x 16 wks. By using VEGFR2 as an endothelial marker, we further investigated if this dual therapy can attenuate chronic dialysate infusion induced hypervascularity in this rat model.

Methods

PCK rats were used. Dialysate infusions were performed BID via an implanted subcutaneous port in the neck tunneled to the intraperitoneal cavity. The following treatments were administered: (1) No surgery/infusions; (2) 4.25% Dianeal; (3) 4.25% Dianeal + JAK1/2i (5mg/kg BID); (4) 4.25% Dianeal + Losartan (5mg/kg BID); and (5) 4.25% Dianeal + Losartan +JAK1/2i (5mg/kg BID each). Parietal peritoneum was used for immunohistochemical staining of VGEFR2, which was digitally quantified by using Qu Path program. Data were analyzed by one-way-ANOVA followed by Tukey test. Results are mean + SEM.

Results

VEGFR2 staining was significantly elevated after 16 weeks IP infusion of 4.25% Dianeal alone. JAK1/2i significantly reduced VEGFR2 expression; losartan tended to reduce VEGFR2, but this did not reach significance. Dual therapy with JAK1/2i and losartan resulted in the greatest reduction of VEGFR2

Conclusion

Long-term JAK1/2i, or JAK1/2i plus losartan intraperitoneal treatment reduces angiogenesis. Angiotensin inhibition is advocated to maintain residual renal function, by adding JAK1/2i, the combination also protects peritoneal structure/function by reducing angiogenesis.