Objective To examine risk of malignancy and death in patients with kidney transplant who receive the immunosuppressive drug sirolimus.Design Systematic review and meta-analysis of individual patient data.Data sources Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2013.Eligibility Randomized controlled trials comparing immunosuppressive regimens with and without sirolimus in recipients of kidney or combined pancreatic and renal transplant for which the author was willing to provide individual patient level data. Two reviewers independently screened titles/abstracts and full text reports of potentially eligible trials to identify studies for inclusion. All eligible trials reported data on malignancy or survival. Results The search yielded 2365 unique citations. Patient level data were available from 5876 patients from 21 randomized trials. Sirolimus was associated with a 40% reduction in the risk of malignancy (adjusted hazard ratio 0.60, 95% confidence interval 0.39 to 0.93) and a 56% reduction in the risk of non-melanoma skin cancer (0.44, 0.30 to 0.63) compared with controls. The most pronounced effect was seen in patients who converted to sirolimus from an established immunosuppressive regimen, resulting in a reduction in risk of malignancy (0.34, 0.28 to 0.41), non-melanoma skin cancer (0.32, 0.24 to 0.42), and other cancers (0.52, 0.38 to 0.69). Sirolimus was associated with an increased risk of death (1.43, 1.21 to 1.71) compared with controls.Conclusions Sirolimus was associated with a reduction in the risk of malignancy and non-melanoma skin cancer in transplant recipients. The benefit was most pronounced in patients who converted from an established immunosuppressive regimen to sirolimus. Given the risk of mortality, however, the use of this drug does not seem warranted for most patients with kidney transplant. Further research is needed to determine if different populations, such as those at high risk of cancer, might benefit from sirolimus.

Renal transplant recipients (RTR) have a 50-200-fold higher risk for nonmelanoma-skin cancer (NMSC) causing high rates of morbidity and sometimes mortality. Cohort-studies gave evidence that a sirolimusbased immunosuppression may inhibit skin tumor growth. This single-center, prospective, assessorblinded, randomized trial investigated if switching to sirolimus treatment inhibits the progression of premalignancies and moreover how many new NMSC occur compared to continuation of the original immunosuppressive therapy. Forty-four RTR (mean age 59.9 years, mean duration of immunosuppression 229.5 months) with skin lesions were randomized to sirolimus or continuation of their original immunosuppression. Blinded dermatological assessment at month 6 and 12 by the same dermatologist evaluated the clinical change compared to baseline. Biopsy was performed in suspected malignancy. Already the 6-month-assessment showed significant superiority of sirolimus-therapy: a stop of progression, even regression of preexisting premalignancies (p < 0.0005). This effect was increased at month 12 (p < 0.0001). Nine patients developed histologically confirmed NMSC: one in the sirolimus group, eight in the control group, p = 0.0176. Sirolimus-based immunosuppression in RTR, even when established many years after transplantation, can delay the development of premalignancies, induce regression of preexisting lesions and decelerate the incidence of new NMSC.

Live kidney donation is increasing rapidly. Increases of blood pressure and proteinuria but no accelerated loss of renal function in kidney donors have been described. The credibility of this research is hampered by retrieval rates of only 50-70% of donors.We studied renal function, blood pressure, proteinuria, parathyroid hormone, 1,25(OH) 2 cholecalciferol and calcium and phosphate excretion in a live kidney donor cohort with a 93% retrieval rate. A comprehensive physical and laboratory examination including 24-h urine collection was conducted. None of the 152 donors had renal failure. Mean time after uninephrectomy was 11 ± 7 (range: 1-28) years. GFR had declined by 25%. Blood pressure had increased from 125 ± 15/79 ± 11 to 134 ± 19/81 ± 9 mmHg (p < 0.01) but remained significantly below normal. Fifty six percent of donors developed proteinuria (>150 mg/day), but only 10% had albuminuria. Nineteen percent had increased PTH, 30% had a decreased tubular reabsorption rate of phosphate. Regarding risk factors for a higher loss of GFR, greater increases in blood pressure or proteinuria no consistent picture emerged. Because of the high incidence of proteinuria and possible changes in bone metabolism inclusion of kidney donors in registries appears worthwhile.