Tacrolimus more tolerable than cyclosporine in renal transplant patients

Short-term renal transplant outcomes on patient survival, graft survival and function, and rejection rates are comparable between tacrolimus and cyclosporine, a Singapore study has found. Tacrolimus also appears more tolerable but is associated with opportunistic and more severe infections.

Results, however, are uncertain due to confounding by different baseline characteristics, according to the researchers.

The researchers conducted a single-centre retrospective chart review on ABO- and human leucocyte antigen (HLA)-compatible kidney transplantations between 1 January 2011 and 15 August 2018. Included were patients who received basiliximab induction, prednisolone, mycophenolate, and either tacrolimus or cyclosporine. Participants were followed for at least 1 year. Recipients of transplantations at other institutions or other immunosuppressive regimens were excluded.

The researchers then collected patient and graft outcomes, as well as adverse effects. Forty-nine patients received cyclosporine and 120 tacrolimus. The latter were older, had more deceased donor transplants, a higher proportion with donor-specific antibodies (DSAs) present and more HLA mismatches. [Proc Singapore Healthc 2020;29:217-222]

At 1 year, no differences were seen in patient and graft survival, graft function, and acute rejections between cyclosporine and tacrolimus despite adjustments for age, transplant type, presence of DSAs, and total HLA mismatches.

Notably, patients in the tacrolimus group had more infection-related admissions (odds ratio, 0.27, 95 percent confidence interval, 0.098–0.73; p=0.01) after adjusting for age, transplant type, acute rejections, HLA mismatches, and presence of DSAs. They also had increased severity and more opportunistic infections.

On the other hand, more patients in the cyclosporine group required a change to alternative immunosuppressants (p=0.003).

“Our study demonstrated more infection-related admissions, more severe infections and susceptibility to opportunistic infections on tacrolimus versus cyclosporine, in contrast to previous studies,” the researchers said. “One reason may be genetic variations in CYP3A5 involved in tacrolimus metabolism.” [Saudi J Kidney Dis Transplant 2018;29:1376-1385; Transplantation 1997;64:436-443; Expert Opin Drug Metab Toxicol 2016;12:555-565; Drug Des Devel Ther 2015;9:473-485]

Tacrolimus was also found to be a more robust immunosuppressant than cyclosporine. This potentially contributed to more admissions for opportunistic infections and more severe infections in the current study. [Ann Transplant 2012;17:86-99; Curr Opin Infect Dis 2005;18:342-345]

Moreover, BK virus (BKV) infections requiring admission were greater in the tacrolimus group. This finding was consistent with earlier studies showing increased severity and persistence of BKV infections on tacrolimus. [Transplantation 2012;94:396-402; Am J Transplant 2005;5:582-594]

“More patients on cyclosporine required crossover to tacrolimus in our study, mainly due to graft rejection and unpredictable drug levels, similar to findings by Vincenti [and colleagues],” the researchers said. [Transplantation 2002;73:775-782]

“Tacrolimus may also be more tolerable with fewer cosmetic side effects, and some adverse effects (eg, tremors) may be reversible with a dose reduction,” they added. [Eur J Clin Pharmacol 2010;66:1177-1187; Turk J Urol 2013;39:16-21; Transplantation 1997;64:436-443]