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Miguel Gonzalez Molina

Bio: Miguel Gonzalez Molina is an academic researcher from Yahoo!. The author has contributed to research in topics: Transplantation & Mycophenolic acid. The author has an hindex of 5, co-authored 5 publications receiving 249 citations.

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Journal ArticleDOI
TL;DR: Basiliximab immunoprophylaxis is safe, well tolerated, and shows a trend toward reduction in number of acute rejection episodes in renal transplant patients receiving cyclosporine, mycophenolate mofetil, and steroids.
Abstract: Background. Acute rejection remains a major problem in renal transplantation. Immunoprophylaxis with basiliximab (Simulect) has achieved significant reductions in acute rejection episodes in renal allograft recipients receiving dual immunosuppression. This study explored the tolerability and cumulative benefit of combining basiliximab with triple-drug therapy-cyclosporine (USP Modified, Neoral), mycophenolate mofetil, and steroids. Methods. In a randomized, double-blind, placebo-controlled, multicenter study, 123 kidney transplant recipients received either basiliximab at 20 mg before transplantation (day 0) and 20 mg on day 4 (n=59), or placebo (n=64). All received triple-drug immunosuppression and were followed for 6 months. Results. Tolerability of basiliximab was equivalent to placebo, with no increase in serious adverse events, infection, malignancy, or posttransplant lymphoproliferative disorder. At 6 months, there were trends in favor of basiliximab over placebo in the incidences of first biopsy-confirmed acute rejection (15.3% vs. 26.6%, P=NS) and of acute rejection treated with antibody (5.1% vs. 15.6%, P=NS). Kaplan-Meier estimates at 4 weeks and 6 months were significantly in favor of basiliximab treatment for first acute rejection, biopsy-confirmed rejection, rejection episodes treated with antibody therapy, and treatment failure. Renal function improved more rapidly in the basiliximab group, with mean creatinine clearance at week 2 being 54.7 mL/min versus 43.2 mL/min for placebo (P=0.034). At 12 months, patient survival was 100% in both groups; graft survival was 94.9% with basiliximab and 92.2% with placebo. Conclusions. Basiliximab immunoprophylaxis is safe, well tolerated, and shows a trend toward reduction in number of acute rejection episodes in renal transplant patients receiving cyclosporine, mycophenolate mofetil, and steroids.

132 citations

Journal ArticleDOI
TL;DR: Treatment with MMF reduced the progressive deterioration of renal function in patients with chronic allograft nephropathy, independently of the blood levels of CsA.
Abstract: BACKGROUND Although studies have shown that mycophenolate mofetil (MMF) with cyclosporine (CsA) and prednisone can reduce the incidence of acute rejection and increase the half-life of the graft, the effects of MMF on established chronic allograft nephropathy (CAN) are controversial. METHODS We studied 121 patients with biopsy-proven CAN, 59 treated with CsA and prednisone and 62 treated with triple-drug therapy with azathioprine. At inclusion, each group received 2 g per day of MMF and azathioprine was stopped. Renal function was measured by the glomerular filtration rate (GFR) obtained by creatinine clearance (Cockcroft-Gault) and monitored by the slope of the GFR, adjusted using linear regression. RESULTS The median follow-up, after incorporation of MMF, was 36 (13-36) months, with 103 (85.1%) having a full 3-year follow-up. Before the introduction of MMF, there was progressive deterioration in renal function (GFR: 54.8+/-20.9 vs. 39.7+/-14.0 mL/min, P<0.001). After introduction of MMF, renal function remained stable (GFR: 39.7+/-14.0 vs. 41.3+/-10.8 mL/min, P=NS), with a significant change in the slope of the GFR (-0.0144 vs. +0.00045, P<0.001). In 65 patients in whom CsA blood levels remained unchanged during follow-up (148.0+/-65.6 vs. 154.1+/-58.2, P=NS), the slope of the GFR showed a reduction in loss of renal function (-0.0147 vs. -0.0001, P<0.001). CONCLUSIONS Treatment with MMF reduced the progressive deterioration of renal function in patients with CAN, independently of the blood levels of CsA.

47 citations

Journal ArticleDOI
TL;DR: Sirolimus therapy may induce reflex sympathetic dystrophy syndrome in renal transplant recipients and the symptoms remitted 3-10 months after treatment with calcitriol, with or without nifedipine or calcitonin, and in one case with suppression of sirolimu.
Abstract: The reflex sympathetic dystrophy syndrome (RSDS) in organ transplant recipients has only previously been reported in patients treated with calcineurin inhibitors. We retrospectively analyzed 393 renal transplant patients treated with sirolimus, 9 of whom developed RSDS. All the patients reported varying degrees of pain in the legs, affecting the knees, ankles, and/or feet, plus cutaneous erythema. The onset of pain ranged from 1-6 months after transplantation. At the time of diagnosis of RSDS, the mean serum creatinine was 1.4 mg/dL (range 1.0-1.7) and bone scintigraphy with 99mTc pyrophosphate showed increased uptake in all cases. The symptoms remitted 3-10 months after treatment (mean, 4 months) with calcitriol, with or without nifedipine or calcitonin, and in one case with suppression of sirolimus. We conclude that sirolimus therapy may induce RSDS in renal transplant recipients.

23 citations

Journal ArticleDOI
TL;DR: Triple therapy with Az in 1990 and 1994 and with MMF in 1998 were the most frequently used immunosuppressive regimens in the Spanish kidney transplant population.
Abstract: Background. Although new immunosuppressive agents have improved the results of renal transplants (RTs), long-term graft loss remains high. We evaluated the impact of different immunosuppressive regimens on patient and graft survival. Methods. Data from 3365 patients receiving cadaver RTs in Spain during the years 1990, 1994 and 1998 were retrospectively analysed. All data were entered into a specially designed database. Graft and patient survival rates were estimated by the Cox regression method and results expressed as percentage survival. A maximum-likelihood estimate of the projected graft half-life (median value) was calculated by Weibull regression. Results. In 1990 graft and patient survival differed significantly from the other treatment years (P ¼ 0.0006 and P ¼ 0.0101, respectively). The risk of graft loss was significantly higher for cyclosporine (CsA), prednisone (P) and azathioprine (Az) than for CsA þ P, which in turn was higher than for CsA þ P plus polyclonal antibodies [antilymphocyte globulin (ALG)/antithymocyte globulin (ATG)]. Risk of patient death was also significantly higher for CsA þ P þ Az than for CsA þ P. No significant differences between treatment groups were found in graft and patient survival for 1994 and 1998. The projected median graft life for patients with the most used immunosuppressive regimen for each year was 12.9 years for CsA þ P þ Az and 15.6 years for CsA þ P plus mycophenolate mofetil (MMF). Conclusions. Triple therapy with Az in 1990 and 1994 and with MMF in 1998 were the most frequently used immunosuppressive regimens in the Spanish kidney transplant population. The best results were seen after induction therapy with polyclonal antibodies.

5 citations


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TL;DR: Belatacept, an investigational selective costimulation blocker, did not appear to be inferior to cyclosporine as a means of preventing acute rejection after renal transplantation and may preserve the glomerular filtration rate and reduce the rate of chronic allograft nephropathy.
Abstract: Background Renal transplantation is the standard of care for patients with end-stage renal disease. Although maintenance immunosuppression with calcineurin inhibitors yields excellent one-year survival, it is associated over the long term with high rates of death and graft loss, owing in part to the adverse renal, cardiovascular, and metabolic effects of these agents. The use of potentially less toxic agents, such as belatacept, a selective blocker of T-cell activation, may improve outcomes. Methods We randomly assigned renal-transplant recipients to receive an intensive or a less-intensive regimen of belatacept or cyclosporine. All patients received induction therapy with basiliximab, mycophenolate mofetil, and corticosteroids. The primary objective was to demonstrate the noninferiority of belatacept over cyclosporine in the incidence of acute rejection at six months (with an upper bound of the 95 percent confidence interval around the treatment difference of less than 20 percent). Results At six months,...

792 citations

Journal ArticleDOI
TL;DR: Given a 40% risk of rejection, seven patients would need treatment with IL-2Ra in addition to standard therapy, to prevent one patient from undergoing rejection, with no definite improvement in graft or patient survival.
Abstract: Background: Interleukin 2 receptor antagonists (IL-2Ra) are increasingly used to treat renal transplant recipients. This study aims to systematically identify and summarize the effects of using IL-2Ra as induction immunosuppression, as an addition to standard therapy, or as an alternative to other antibody therapy. Methods: Databases, reference lists, and abstracts of conference proceedings were searched extensively to identify relevant randomized controlled trials in all languages. Data were synthesized using the random effects model. Results are expressed as relative risk (RR), with 95% confidence intervals (CI). Results: A total of 117 reports from 38 trials involving 4,893 participants were included. When IL-2Ra were compared with placebo (17 trials; 2,786 patients), graft loss was not significantly different at 1 year (14 trials: RR 0.84; CI 0.64–1.10) or 3 years (4 trials: RR 1.08; CI 0.71–1.64). Acute rejection was significantly reduced at 6 months (12 trials: RR 0.66; CI 0.59–0.74) and at 1 year (10 trials: RR 0.67; CI 0.60–0.75). At 1 year, cytomegalovirus infection (7 trials: RR 0.82; CI 0.65–1.03) and malignancy (9 trials: RR 0.67; CI 0.33–1.36) were not significantly different. When IL-2Ra were compared with other antibody therapy, no significant differences in treatment effects were demonstrated, but IL-2Ra had significantly fewer side effects. Conclusions: Given a 40% risk of rejection, seven patients would need treatment with IL-2Ra in addition to standard therapy, to prevent one patient from undergoing rejection, with no definite improvement in graft or patient survival. There is no apparent difference between basiliximab and daclizumab.

207 citations

Journal ArticleDOI
TL;DR: There was no difference in graft loss at any time point, or for acute rejection diagnosed clinically, but the was benefit of ATG therapy over IL2Ra for biopsy-proven acute rejection at one year.
Abstract: Background Interleukin 2 receptor antagonists (IL2Ra) are used as induction therapy for prophylaxis against acute rejection in kidney transplant recipients. Use of IL2Ra has increased steadily since their introduction, but the proportion of new transplant recipients receiving IL2Ra differs around the globe, with 27% of new kidney transplant recipients in the United States, and 70% in Australasia receiving IL2Ra in 2007. Objectives To systematically identify and summarise the effects of using an IL2Ra, as an addition to standard therapy, or as an alternative to another immunosuppressive induction strategy. Search methods We searched the Cochrane Renal Group’s specialised register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE to identify new records, and authors of included reports were contacted for clarification where necessary. Selection criteria Randomised controlled trials (RCTs) in all languages comparing IL2Ra to placebo, no treatment, other IL2Ra or other antibody therapy. Data collection and analysis Data was extracted and assessed independently by two authors, with differences resolved by discussion. Dichotomous outcomes are reported as relative risk (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). Main results We included 71 studies (306 reports, 10,520 participants). Where IL2Ra were compared with placebo (32 studies; 5,854 patients) graft loss including death with a functioning graft was reduced by 25% at six months (16 studies: RR 0.75, 95% CI 0.58 to 0.98) and one year (24 studies: RR 0.75, 95% CI 0.62 to 0.90), but not beyond this. At one year biopsy-proven acute rejection was reduced by 28% (14 studies: RR 0.72, 95% CI 0.64 to 0.81), and there was a 19% reduction in CMV disease (13 studies: RR 0.81, 95% CI 0.68 to 0.97). There was a 64% reduction in early malignancy within six months (8 studies: RR 0.36, 95% CI 0.15 to 0.86), and creatinine was lower (7 studies: MD -8.18 µmol/L 95% CI -14.28 to -2.09) but these differences were not sustained. When IL2Ra were compared to ATG (18 studies, 1,844 participants), there was no difference in graft loss at any time point, or for acute rejection diagnosed clinically, but the was benefit of ATG therapy over IL2Ra for biopsy-proven acute rejection at one year (8 studies:, RR 1.30 95% CI 1.01 to 1.67), but at the cost of a 75% increase in malignancy (7 studies: RR 0.25 95% CI 0.07 to 0.87) and a 32% increase in CMV disease (13 studies: RR 0.68 95% CI 0.50 to 0.93). Serum creatinine was significantly lower for IL2Ra treated patients at six months (4 studies: MD -11.20 µmol/L 95% CI -19.94 to -2.09). ATG patients experienced significantly more fever, cytokine release syndrome and other adverse reactions to drug administration and more leucopenia but not thrombocytopenia. There were no significant differences in outcomes according to cyclosporine or tacrolimus use, azathioprine or mycophenolate, or to the study populations baseline risk for acute rejection. There was no evidence that effects were different according to whether equine or rabbit ATG was used. Authors' conclusions Given a 38% risk of rejection, per 100 recipients compared with no treatment, nine recipients would need treatment with IL2Ra to prevent one recipient having rejection, 42 to prevent one graft loss, and 38 to prevent one having CMV disease over the first year post-transplantation. Compared with ATG treatment, ATG may prevent some experiencing acute rejection, but 16 recipients would need IL2Ra to prevent one having CMV, but 58 would need IL2Ra to prevent one having malignancy. There are no apparent differences between basiliximab and daclizumab. IL2Ra are as effective as other antibody therapies and with significantly fewer side effects.

203 citations