Immunosuppression for membranous nephropathy

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Patient Survival After the Diagnosis of Cancer in Renal Transplant Recipients: A Nested Case-Control Study

Introduction. Malignancy is a well-known complication after renal transplantation. We studied the influence of cancer on patient survival in the Dutch renal transplant population in a nested case-controlled analysis. Methods. Between March 1966 and May 2008, 15,227 renal transplantations in 12,805 recipients were registered in the Netherlands Organ Transplant Registry database. Total follow-up was 89,651 person years. We performed an analysis of patient and graft survival both from the day of transplantation and the diagnosis of cancer in recipients with invasive cancer. Recipients without invasive cancer, matched for gender, age, and year of transplantation, served as a control group. For the survival analysis after the diagnosis of cancer, the matched control group consisted of patients with a functioning graft at the moment the index patient was diagnosed with cancer. Results. Cancer had been registered in 908 (7.1%) patients, 630 (69%) of them died with functioning kidney, 510 (81%) because of their malignancy (at 8.2 years after transplantation, median). The median patient survival after transplantation was 11.9 vs. 16.8 years in the study and control group, respectively (P<0.001). The median patient and graft survival after the diagnosis of cancer was 2.1 vs. 8.3 (P<0.001) and 25 vs. 22.4 (P<0.001) years in the study and control group, respectively. Conclusion. Mortality because of cancer is observed at a significantly later time after transplantation compared with mortality because of the other main lethal complications. It significantly affects life expectancy and carries a poor prognosis with a limited survival after diagnosis

Addition of isradipine (Lomir) results in a better renal function after kidney transplantation:A double-blind, randomized, placebo-controlled, multicenter study

Background. After successful kidney transplantation patients may suffer from the adverse effects due to the use of calcineurin inhibitors. Calcium channel blockers are effective in the treatment of hypertension and may ameliorate cyclosporine- (CsA) induced impairment of renal function after kidney transplantation. Calcium channel blockers may also modulate the immune-system which may result in reduction of acute rejection episodes. Patients and methods. From June 1995 till 1997 the effect of isradipine (Lomir) on renal function, incidence and severity of delayed graft function (DGF), and acute rejection after kidney transplantation, was studied in 210 renal transplant recipients, who were randomized to receive isradipine (n=98) or placebo (n=112) after renal transplantation in a double-blind fashion. Results. In the isradipine group renal function was significantly better at 3 and 12 months (P=0.002 and P=0.021) compared with the placebo group. DGF was present, in both groups: isradipine: (28+6)/98 (35%); placebo: (35+9)/112 (40%), P=0.57. Severity of DGF was comparable in both groups (isradipine: 9.1+/-8.7 vs. placebo: 9.3+/-8.1 days). No statistical difference was found in incidence or severity of biopsy-proven acute rejection [isradipine: (42+6)/98 (49%) versus placebo: (46+9)/112 (49%), P=1.00]. Renal vein thrombosis was observed in eight patients, This proved to be associated with the route of administration of the study medication [6/45 (13%) on i.v. medication versus 2/165 (1%) on oral medication, P Conclusions. Addition of isradipine results in a better renal function after kidney transplantation, without effect on incidence or severity of DGF or acute rejection

The pharmacokinetic-pharmacodynamic relationship for mycophenolate mofetil in renal transplantation

Background: Mycophenolate mofetil, a pro-drug for mycophenolic acid, reduces the likelihood of allograft rejection after renal transplantation. We studied the relationship between mycophenolic acid pharmacokinetics and the likelihood of rejection in a randomized concentration-controlled trial. Methods: Under double-blind conditions, recipients of kidney transplants were followed for evidence of allograft rejection for 6 months. In addition to mycophenolate mofetil, patients received usual doses of cyclosporine (INN, ciclosporin) and corticosteroids, The dose of mycophenolate mofetil (given twice daily) was controlled by feedback, with mycophenolic acid area under the concentration-time curve (AUC) as the controlled variable. Patients were randomly assigned to 1 of 3 target AUC groups. Results: Logistic regression analysis showed a significant (P < .0001) relationship between mycophenolic acid AUC and the likelihood of rejection. High mycophenolic acid values were associated with a very low probability of rejection. An AUC of 15 mu g.h/mL yielded 50% of maximal achievable efficacy with a 4% change of efficacy for a 1 mu g.h/mL change in AUC at the midpoint of the logistic curve. Exploratory analyses showed other variables (eg, the maximum observed plasma concentration, predose plasma concentration, and drug dose) had poorer predictive power for the rejection outcome. Bivariate regression confirmed the importance of AUC as a highly predictive variable and showed low predictive value of other variables, once the contribution of AUC had been considered. The characteristic side effects of mycophenolate mofetil therapy appeared related to drug dose but not to mycophenolic acid concentration. Conclusions The AUC of mycophenolic acid is predictive of the likelihood of allograft rejection after renal transplantation in patients receiving mycophenolate mofetil