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Background Renal transplant recipients have an increased cancer risk. The mammalian target of rapamycin inhibitor sirolimus (SRL) has immunosuppressive and antitumour activities but knowledge about its use in recipients with cancer is limited. Methods We retrospectively analysed 726 renal allograft recipients converted to SRL from 10 German transplant centres. Patient and graft survival were analysed depending on malignancy status prior to conversion and tumour entity. Results Malignancy before conversion to SRL was reported in 230 patients, with 137 patients having skin cancers and 101 having solid cancers. Cancer occurred 4.6 ± 9.4 (median 3.0) years after transplantation. Basal cell carcinoma, squamous cell carcinoma and Bowen's disease were the most prevalent skin cancers, while carcinomas of the kidney, colon and breast were the most prevalent solid cancers before conversion. Patients with prior malignancy were older and had better renal function at conversion compared with patients without a history of cancer. After conversion to SRL, cancer incidence rates (IRs) of all tumours were lower compared with rates before conversion. Cancer IRs after conversion were higher in patients with malignancy before conversion compared with those without. Patient survival was worse in patients with solid cancers compared with patients with skin cancers or without malignancies. Biopsy-proven acute rejections in the first year after conversion were less frequent in patients with malignancy compared with those without. Graft survival and renal function in all cancer types were better than in patients converted to SRL without cancers. Conclusions Conversion to SRL in patients with a history of cancer is safe regarding renal function and graft survival, while patient survival is largely dependent on tumour entity. [ABSTRACT FROM AUTHOR]

Sirolimus is an established immunosuppressant in renal transplantation with antineoplastic and antiviral features, but side effects like proteinuria limit its use. The aim of this retrospective multicenter observational study is to define predictors for determining which patients most likely benefit from a sirolimus-based therapy. All patients from 10 German centers that were switched to a sirolimus-containing maintenance immunosuppression in 2000 to 2008 after 3 months or later post-transplantation were enrolled (n = 726). Observation times after switching to sirolimus ranged from 4 days to 9 years (median: 24.3 months). With multinomial logistic regression, risk factors for the endpoints terminal graft failure and withdrawal of sirolimus therapy compared to successful therapy were identified. Successful sirolimus therapy was observed in 304 patients. Forty patients died with functioning graft. Therapy failures included graft loss (n = 106) and sirolimus-discontinuation for various reasons (n = 276). Successful sirolimus-use was predicted in 83% and graft failure in 65%, whereas prediction of deliberate sirolimus-discontinuation was poor (48%). Most favorable results for sirolimus-use were observed in patients switched in 2006 to 2008. Using ROC analysis, an estimated glomerular filtration rate (eGFR) below 32 mL/min was shown to be the cut-off in patients withdrawing from therapy as a result of renal reasons, as well as in patients with graft loss. Proteinuria above 151 mg/L was shown to be predictive for patients with graft failure. eGFR and proteinuria are the major determinants for successful sirolimus-therapy. Our findings help stratifying patients who will benefit most from this therapy and avoid toxicities in patients without potential benefits for this therapy. [ABSTRACT FROM AUTHOR]

The kallikrein–kinin system (KKS) was investigated in autosomal dominant polycystic kidney disease (ADPKD)-affected rats (PKD) and compared to unaffected controls (SD) and 5/6 nephrectomized rats (5/6 Nx). In addition, patients with ADPKD compared to patients with nonpolycystic kidney disease and healthy controls have been investigated.Plasma and urine samples for determination of creatinine, protein, kallikrein (KAL) and bradykinin (BK) were taken in male 3- and 9-month-old PKD, SD and 9-month-old 5/6 Nx. The same parameters were determined in young (age: 20–40 years) and old (41–65 years) male patients with ADPKD and compared to age-matched patients with nonpolycystic kidney disease and age-matched healthy controls. Plasma and urine KAL were measured by chromogenic peptide substrate, and kinins were determined by radioimmunoassay.Urine KAL and BK levels were increased in PKD compared to age-matched SD. No differences with respect to serum KAL were found between PKD and SD. In 5/6 Nx, urinary BK levels showed a trend towards higher compared to old SD (p=0.06). KAL and BK were not increased in serum and urine of patients with ADPKD, in contrast to rats. Urinary KAL excretion was reduced in patients with ADPKD and advanced renal failure.Our results demonstrate an age-dependent activation of the renal KKS in rats with ADPKD, whereas the KKS is not activated in patients with ADPKD and advanced renal failure. These data indicate that there are fundamental differences in the factors influencing the course of the disease in human and rat ADPKD. [Copyright &y& Elsevier]