Sex differences in response to cyclosporine immunosuppression in experimental kidney transplantation.

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.