Defining the Risk of Elective Cyclosporine Withdrawal in Stable Kidney Transplant Recipients

Abstract

Although it is known that elective cyclosporine (CsA) withdrawal increases the risk for acute rejection, few studies have been large enough to identify risk factors for acute rejection after CsA withdrawal. We examined risk factors for acute rejection in 464 kidney transplant recipients who underwent elective CsA withdrawal. The incidence of acute rejection within 6 months of CsA withdrawal was 20/141 (14.2%) in the period January 1986 to May 1989, but only 14/323 (4.5%) since May 1989 (p = 0.0002). Among those transplanted since May 1989, the incidence was 5/20 (25%) for those with both 2 HLA‐B and 2 HLA‐DR mismatches, compared with only 9/298 (3.0%) for those with fewer mismatches (p < 0.0001). In Cox proportional hazards analysis, risk factors for acute rejection within 6 months, or at any time after elective CsA withdrawal, were date of transplant January 1986 to May 1989 (compared with more recently May 1989 to March 1999), younger age, obesity, as well as B and DR mismatches. Recipient race (83% were white), acute rejection during the first year before withdrawal (31%), mycophenolate mofetil (17%), and other variables failed to predict postwithdrawal acute rejection. We concluded that avoiding CsA withdrawal in the relatively small number of recipients with both 2 HLA‐B and 2 HLA‐DR mismatches could further reduce our already low incidence of acute rejection following elective CsA withdrawal.

Clinical diagnosis of metabolic syndrome: predicting new-onset diabetes, coronary heart disease, and allograft failure late after kidney transplant

“…Future clinical trials are needed to study the impact of interventions that reduce the risk of CHD, NODAT, and also metabolic syndrome. Such trials could study the impact of steroid avoidance [35], CNI withdrawal [36], switching from CNIs to mTOR inhibitors [37], and higher doses of mycophenolate mofetil along with lower levels of CNIs, on modifying the risks of CHD, NODAT, and metabolic syndrome. Trials studying new agents that increase HDL cholesterol could test whether or not these agents modify the risks of CHD and metabolic syndrome [38].…”

Predictive Factors of Acute Rejection after Early Cyclosporine Withdrawal in Renal Transplant Recipients Who Receive Mycophenolate Mofetil

“…Anjum et al (17) reported an increased risk for patients with both two HLA-B and two HLA-DR mismatches. The measurement of the frequency of precursor cytotoxic T lymphocytes in the peripheral blood could allow identification of patients in whom minimization of immunosuppression can be achieved safely (9,18).…”

Toxicity-Sparing Protocols Using Mycophenolate Mofetil in Renal Transplantation

“…Although acute rejection occurred more frequently in patients electing CsA withdrawal, there was no difference in graft survival over nearly 6 years of follow-up compared with patients electing to remain on CsA. The risk of acute rejection was similar in patients treated with MMF, and those treated with AZA (4/67; 6% versus 26/314; 8%), although the small number of patients receiving MMF precludes drawing firm conclusions regarding the impact of these agents on acute rejection (41).…”

“…Anjum et al (41) evaluated risk factors for acute rejection in a large cohort of stable renal transplant patients (nϭ464) undergoing voluntary CsA withdrawal. CsA withdrawal was begun 1 year after transplant/last rejection episode.…”