Significant risk factors for occurrence of cancer after renal transplantation: a single center cohort study of 1265 cases.

Occurrence of cancer after renal transplantation remains a major problem, and the second cause of death. We performed a retrospective analysis of first cancer, first skin cancer, and first organ cancer (including posttransplant lymphoproliferative disease [PTLD]) among 1265 cases from 1979 to 2006. The occurrence of cancer was clearly a time-dependent event justifiying the use of Kaplan-Meier survival and Cox regression methods. The 10-year cumulative incidences of first cancer, first skin cancer, and first organ cancer were 24.6%, 14.5%, and 14.5%, respectively. Recipient age was a major, independent risk factor for the 3 endpoints with a 6% increased relative risk for each year increment (P < .0001). Female gender was also a major, independent risk factor, but only for skin cancer (P = .0002). We could not demonstrate any difference between the immunosuppressive drugs used for induction or maintenance therapy, especially between antithymocyte globulin (ATG) vs anti-CD25, cyclosporine vs tacrolimus, and azathioprine vs mycophenolate mofetil. Large cohorts are needed with strict stratifications for recipient age and gender to detect any difference, if any, among the drugs.

Pharmacokinetics of a new extended-release nifedipine formulation following a single oral dose, in human volunteers.

This study aimed to define the pharmacokinetics of nifedipine following oral administration of a new extended-release formulation. Twelve healthy volunteers of both sexes, aged 39 +/- 4 years, were treated with a single oral tablet of a new extended-release formulation containing 40 mg of nifedipine. Samples of venous blood were taken before dosing, after 30 min and at 1, 2, 4, 8, 12, 16, 20 and 24 h after administration. Nifedipine concentration was measured by means of a high-performance liquid chromatography method. Noncompartmental pharmacokinetics parameters were then calculated. The plasma concentration of nifedipine increased slowly and in seven subjects biphasic peaks occurred. The mean values were as follows: t(max): 8.5 +/- 1.2 h; C(max): 36.55 +/- 6.76 ng/ml; AUC: 347.06 +/- 51.61 ng/h/ml; AUC 409.99 +/- 61.08 ng/h/ml; A(half-life): 2.26 +/- 0.36 h; D(half-life): 2.43 +/- 0.44 h; E(half-life): 4.62 +/- 0.79 h. Twenty-four hours after administration nifedipine was still detectable (3.17 +/- 0.67 ng/ml). Arterial blood pressure decreased and heart rate increased concurrently and proportionally to the increase in nifedipine concentration. Extended-release nifedipine formulations have better tolerability profiles than immediate-release formulations, which are at present not recommended in the treatment of hypertension, hypertensive crises or myocardial infarction. This new extended-release formulation has interesting pharmacokinetic parameters and may be effective in conditions in which dihydropyridine calcium channel blockers are indicated.

Kidney graft survival rates do not improve by era: the impact of the age factor.

We performed this study to evaluate whether older ages of donors and recipients negatively affected long-term graft survival. We compared 5-year graft survival rates of 89 recipients transplanted between 1991 and 1995 (period A) versus 221 recipients transplanted between 1996 and 2000 (period B). Acute rejection rates and the number of donors and recipients >50 years of age were compared in the two periods. The 5-year graft survival rate in period B was 76.3% versus 82% in period A. In period B, the acute rejection incidence was 18% versus 40% in period A (P < .001). The overall 5-year graft survival was 86.2% for donors aged 21-50 years and 65.7% for donor's aged >50 years (P < .0001) in period A versus 84.1% and 68%, respectively, in period B (P = .0023). In period A, 23.6% of donors and 35.9% of recipients were >50 years old, versus 50.2% and 42.9%, respectively, in period B. The graft survival rate in period B was worse than in period A, although the acute rejection rate was lower. The older age of both donors and recipients in period B seemed to be an important cause of worse outcomes.