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Kidney Week

Abstract: PO2054

Prevention of Triglyceridemia by (Non-)Anticoagulant Heparin(oids) Does Not Preclude Transplant Vasculopathy and Glomerulosclerosis

Session Information

Category: Transplantation

  • 1901 Transplantation: Basic

Authors

  • Shrestha, Pragyi, University Medical Center Groningen, Groningen, Groningen, Netherlands
  • Katta, Kirankumar, Oslo University Hospital Ullevål, Oslo, Oslo, Norway
  • Talsma, Ditmer, University Medical Center Groningen, Groningen, Groningen, Netherlands
  • Naggi, Annamaria, Ronzoni Institute, Milano, Milano, Italy
  • Hillebrands, Jan-luuk, University Medical Center Groningen, Groningen, Groningen, Netherlands
  • Van de sluis, Bart, University Medical Center Groningen, Groningen, Groningen, Netherlands
  • van den Born, Jacob, University Medical Center Groningen, Groningen, Groningen, Netherlands
Background

Chronic Transplant Dysfunction (CTD) is associated with increased PCSK9 and dyslipidemia. We recently showed defective lipoprotein clearance by increased PCSK9–hepatic syndecan-1 interaction in renal condition. Targeting PCSK9 by heparin(oids) might be a therapeutic option to improve dyslipidemia and CTD. We investigated the effects of (non-)anticoagulant heparin(oids) on serum lipids, syndecan-1 and PCSK9 levels and CTD development.

Methods

Kidney allotransplantation was performed from female Dark Agouti to male Wistar Furth recipients. Transplanted rats received daily subcutaneous injections of saline, unfractionated heparin, RO-heparin or NAc-heparin (2mg heparin(oid)/kg BW) until sacrifice after 9 weeks of treatment.

Results

Saline-treated recipients developed hypertension, proteinuria, and loss of creatinine clearance, (all p<0.05 compared to baseline), along with glomerulosclerosis and arterial neointima formation. Saline-treated recipients showed significant increase in plasma TGs (p<0.05), borderline increase in non-HDLc to HDLc ratio (p=0.051), approximately 10-fold increase in serum syndecan-1 (p<0.05), without significant increase in serum PCSK9 level at 8 weeks compared to baseline. Heparin and non-anticoagulant RO-heparin administration in transplanted rats completely prevented increase in TGs compared to saline treated recipients at 8 weeks (both p<0.05). Heparin(oids) treatment did not influence serum TC, plasma syndecan-1 and PCSK9 levels, creatinine clearance, proteinuria, glomerulosclerosis and arterial neointima formation, 8 weeks after transplantation. Combining all groups, increased syndecan-1 shedding was associated with TC (r=0.5; p=0.03) and with glomerulosclerosis (r=0.53; p=0.021), whereas non-HDLc/HDLc ratio associated with neointima score in the transplanted kidneys (r=0.65; p<0.001).

Conclusion

Prevention of triglyceridemia by (non)anticoagulant heparin(oid) did neither influence PCSK9/syndecan-1, nor precluded CTD, which did however associated with shedding of lipoprotein clearance receptor syndecan-1 and unfavorable cholesterol profile.