Johnston O et al. (2008) Sirolimus is associated with new-onset diabetes in kidney transplant recipients. J Am Soc Nephrol 19: 1411–1418

Zuber J et al. (2008) Sirolimus may reduce fertility in male renal transplant recipients. Am J Transplant 8: 1471–1479

Results from two retrospective studies have now added to the mounting evidence that sirolimus is associated with serious adverse events.

Johnston et al. analyzed data from the United States Renal Data System on 20,124 nondiabetic adult recipients of a first, kidney-only transplant. During follow-up (median 2.63 years), patients treated with sirolimus plus ciclosporin, sirolimus plus tacrolimus, or sirolimus plus mycophenolate mofetil or azathioprine were at increased risk of new-onset diabetes (hazard ratios 1.61, P <0.0001, 1.66, P <0.0001 and 1.36, P <0.01, respectively) compared with patients who received ciclosporin plus mycophenolate mofetil or azathioprine.

Zuber et al. analyzed questionnaire responses, telephone conversations or face-to-face consultations with 95 men (aged 20–40 years) who underwent renal transplantation during the period 1995–2005. Spontaneous conception and pregnancies were recorded for the partners of 1 of the 17 patients who received continuous sirolimus, 22 of the 52 patients who did not receive sirolimus, and 12 of the 26 patients who received intermittent sirolimus; mean follow-up in the three groups was 5.6 ± 2.5 years, 5.0 ± 3.4 years and 6.9 ± 3.3 years, respectively. Partners of patients who received sirolimus had a lower spontaneous conception rate than those who were not given sirolimus (5.9 per 1,000 patient-years vs 92.9 per 1,000 patient-years; P = 0.007). Analysis of sperm from 19 patients showed that continuous sirolimus use was associated with a significantly lower sperm count than nonuse of sirolimus (28.6 ± 31.2 × 106 vs 292.2 ± 271.2 × 106; P = 0.006).