Sex differences in response to cyclosporine immunosuppression in experimental kidney transplantation

V. Müller, Attila J. Szabo, Aaron Erdely, You Lin Tain, Chris Baylis

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

1. Female donors and recipients have increased risk of acute rejection and subsequent chronic allograft nephropathy (CAN), especially when cyclosporine A (CsA) is used. Decreased renal nitric oxide (NO) production is associated with chronic kidney disease. In the present study, we investigated the impact of gender, CsA dose and renal NO synthase (NOS) on CAN. 2. Kidneys from male and female F344 rats were transplanted into same-sex Lewis allograft or F344 isograft recipients and recipient rats were treated with 1.5 or 3 mg/kg per day CsA for 10 days. Grafts were removed at 22 weeks post-transplantation. Normal two-kidney F344 rats were investigated as age-matched controls. 3. Low-dose CsA was associated with accelerated CAN in female rats compared with male rats; however, with high-dose CsA, allograft females had similar pathology/function to allograft males. Isograft females (similar to isograft males) had no graft failure and only slightly, albeit significantly, greater injury than age-matched controls. Isograft females had higher renal cortical neuronal (n) NOS but lower medullary endothelial (e) NOS than isograft males. There was no difference in renal eNOS and nNOS between allograft groups. 4. In conclusion, 1.5 mg/kg per day CsA is not sufficient to prevent early graft loss in females. When the dose of CsA is doubled, allograft females and males have similar post-transplant survival. Renal NOS expression was unremarkable in any transplant group.

Original languageEnglish
Pages (from-to)574-579
Number of pages6
JournalClinical and Experimental Pharmacology and Physiology
Volume35
Issue number5-6
DOIs
Publication statusPublished - May 2008

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Sex Characteristics
Kidney Transplantation
Immunosuppression
Cyclosporine
Allografts
Isografts
Kidney
Nitric Oxide Synthase
Transplants
Inbred F344 Rats
Chronic Renal Insufficiency
Nitric Oxide
Transplantation
Pathology
Wounds and Injuries

Keywords

  • Cyclosporine
  • Immunosuppression
  • Kidney transplantation
  • Sex difference

ASJC Scopus subject areas

  • Physiology
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Sex differences in response to cyclosporine immunosuppression in experimental kidney transplantation. / Müller, V.; Szabo, Attila J.; Erdely, Aaron; Tain, You Lin; Baylis, Chris.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 35, No. 5-6, 05.2008, p. 574-579.

Research output: Contribution to journalArticle

Müller, V. ; Szabo, Attila J. ; Erdely, Aaron ; Tain, You Lin ; Baylis, Chris. / Sex differences in response to cyclosporine immunosuppression in experimental kidney transplantation. In: Clinical and Experimental Pharmacology and Physiology. 2008 ; Vol. 35, No. 5-6. pp. 574-579.
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