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Kidney Week

Abstract: SA-PO712

JAK1/2 Inhibitor and/or Losartan Preserved Long-Term Peritoneal Membrane Structure/Function during Intraperitoneal Instillation of Dialysate in Polycystic Rats

Session Information

  • Peritoneal Dialysis - II
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Dialysis

  • 608 Peritoneal Dialysis

Authors

  • Zhang, Pei, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States
  • Miyata, Kana N., Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States
  • Adler, Sharon G., Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States
  • La page, Janine A., Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States
  • Nast, Cynthia C., Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Dai, Tiane, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States
Background

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. We test whether a JAK1/2 inhibitor (JAK1/2i) and/or an ARB maintains PM structure/function in rats with polycystic kidneys (PCK) chronically infused with 4.25% Dianeal x 16 wks.

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) 0.9% Saline; (3) 4.25% Dianeal; (4) 4.25% Dianeal + JAK1/2i (5mg/kg BID); (5) 4.25% Dianeal + Losartan (5mg/kg BID); and (6) 4.25% Dianeal + Losartan +JAK1/2i (5mg/kg BID each). Peritoneal equilibration testing (PET) measured peritoneal function by calculating initial dialysate glucose at time 0 (D0) and measuring it 90 minutes after dialysate infusion (D). Parietal peritoneum submesothelial compact zone (SMCZ) width was morphometrically measured in > 60 sections/rat. Data were analyzed by one-way-ANOVA followed by Tukey test. Results are mean+SEM.

Results

Widened SMCZ in Gps 1-3 was due to fibrosis. Fibrosis was reduced in all 3 treatment groups, with the greatest effect in the JAK1/2i group. D/Do glucose measurements showed functional impairment in rats receiving Dianeal, with function maintained in all 3 treatment groups similarly (Table). *P<0.05, #P<0.01.

Conclusion

Summary. Treatment with JAK1/2i, losartan, and both preserved peritoneal structure/function during long-term 4.25% Dianeal exposure. Morphologic protection was superior in the JAK1/2i alone group. Conclusion.Long-term JAK1/2i and/or losartan intraperitoneal treatment preserves peritoneal integrity by limiting peritoneal fibrosis and functional decline. Angiotensin inhibition is advocated to maintain residual renal function. These data show that ARBs also protect peritoneal structure/function.

Funding

  • Other NIH Support