Experience with cyclosporine A and azathioprine double therapy in low‐risk recipients of first cadaveric renal allografts
Authors: Russ Graeme R. , May Steven , Jacob Chakko K. , Mathew Timothy H. , Disney Alex P. S. , Pugsley David J. , Barratt Lindsay J. , Fraenkel Margaret B. , Clarkson Anthony R. , Woodroffe Andrew 
Published: September 2024

Eighty‐one low‐risk first cadaveric renal allograft (CD1) recipients have been studied to evaluate an immunosuppressive regime consisting of azathioprine (AZA) [2 mg/kg initially] and cyclosporine A (CSA) [8 mg/kg initially] but without prednisolone in the first instance. All patients were transfused and had less than 50% panel‐reactive antibodies in both peak and current sera. The dose of CSA was tapered to 4 mg/kg at 10 weeks and the AZA to 1 mg/kg at 17 wk. Rejection episodes were treated with 3 × 1 g i.v. boluses of methylprednisolone. After the second episode, or if the first episode was severe, patients were commenced on oral prednisolone at a dose of 30 mg/day reducing to a baseline of 10 mg 12 wk later. Steroid‐unresponsive or histologically severe rejection was treated with OKT3 or ATG. Median follow‐up to the end of March 1989 was 15.5 months (range 3‐33). The 12‐month actuarial patient and graft survivals were 97% and 87% respectively. Four patients died with functioning grafts at 2, 7, and 17 months of infection (3) and at 13 months of myocardial infarction (1). Three grafts were lost to rejection at 4, 7 and 9 months. Four grafts experienced extensive intragraft thromboses in the 1st wk, leading to graft failure in 2, and 1 graft developed major vessel thrombosis at 5 months. Thirty‐eight patients required post‐operative dialysis. Of these, 2 never functioned, 3 diuresed without CSA reduction, 17 functioned after a 50% reduction and 16 functioned after cessation of CSA. Excluding 2 grafts which failed in the first 2 d because of vascular complications, 20 patients (25%) never experienced rejection, 31 (39%) developed their first rejection in the 1st wk, 18 (23%) in wk 2‐4 and 10 (13%) after the 1st month. Fifteen patients required OKT3 or ATG for severe rejection. Fifty‐one patients (65%) received courses of oral steroids of longer than 4 wk, 35 for rejection, 10 after cessation of CSA for toxicity, and 3 after cessation or reduction of AZA for toxicity. Thirteen (37%) of the patients on prednisolone for rejection have had it stopped at between 7 and 25 months without further rejection. Of the 65 patients with functioning grafts who have been followed for more than 6 months, 38 (59%) are taking CSA and AZA alone and 26 (40%) are taking prednisolone either with AZA and CSA (15), with AZA alone (8) or with CSA alone (3). One patient is taking only CSA. There were 30 infections in 28 patients. The most significant of these were 14 CMV (5 associated with OKT3), 1 Torula, 2 wound infection, 3 bacterial septicemia, 1 fungal septicemia, 2 bacterial pneumonia and several episodes of ascending cholangitis in 1 patient. This experience shows that 35% of low‐risk CD1 recipients can be successfully treated with CSA and AZA without prednisolone and that, after 6 months, maintenance immunosuppression can be achieved without long‐term steroids in more than half of the group.