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Biomedical subjects

M A Gentil

Publications and source records attributed to M A Gentil.

At least 19 recordsLinked to original sources
PubMed2006

Epidemiology of urinary infections in renal transplant recipients.

Urinary tract infection (UTI) remains a significant cause of infectious complications in renal transplant recipients. We evaluated prospectively all the UTIs in 161 kidney recipients transplanted between July 2003 and July 2005. All patients received prophylaxis with sulfadoxine-pyrimethamine. We excluded asymptomatic bacteriuria. Forty-one patients (25%) suffered at least one UTI episode. Ninety-two episodes of infection were confirmed with an incidence rate of 97 UTI episodes per 100 patient-years. The most common clinical features were uncomplicated acute bacterial cystitis, 71 episodes (77%), and acute pyelonephritis, 21 episodes (23%). Microbiological isolation was confirmed in 58 episodes (63%). Bacterial infections were the most frequent etiologies: gram-negative bacilli in 52 (90%), gram-positive cocci in 4 (7%), fungal in 2 (3%), and one viral BK virus (2%) infection. The causative microorganisms were E. coli as the principal isolated agent in 41 cases (71%), including 10 (24%) that were extended-spectrum betalactamases (ESBLEC). All episodes showed a favorable course. The survival rate of the graft at the end of the study period was 90.7%, and the survival rate of the transplant recipients was 97.5%. The incidence of UTI in transplant patients who received antibiotic prophylaxis was high. E. coli (ESBLEC) was the main agent isolated. Uncomplicated UTI, the most frequent post transplantation infection, showed a good prognosis.

Adolescent↗
PubMed2005

Cost of renal transplant maintenance immunosuppression: effect of control of vascular risk factors.

In 3 renal transplant cohorts treated in Spain in 1990, 1994, and 1998 (total number, 3279), we studied the frequency of certain cardiovascular risk factors. Their effect on the cost of drugs was assessed from the data from 1 center; the mean cost of antihypertensive agents per patient-year was 349 euros, and of lipid-lowering drugs was 294 euros. Between 1990 and 1998 the frequency of use of antihypertensive agents at 2 years increased from 70% to 80%, and that of lipid-lowering agents from 12% to 46% (P < .001). Patients received various regimens of immunosuppression at the second year, as follows: (1) steroid-free: cyclosporine, 2.3%; tacrolimus, 9.9%; cyclosporine plus mycophenolate, 16.2%; and tacrolimus plus mycophenolate, 11.8% (P < .001); (2) antihypertensive agents: 74.9% of patients receiving tacrolimus, with or without mycophenolate, versus 80.7% of those receiving cyclosporine (P = .022); (3) lipid-lowering drugs: 28.4% of patients receiving tacrolimus, with or without mycophenolate, versus 51.1% of those receiving cyclosporine (P < .001). The increase in associated drug costs must be added to the recent large increase in the cost for immunosuppressive agents, which rose from 3854 euros per year, in 1990 to 5374 euros per year in 1998. A lower cost of associated drugs tends to lessen the overall cost of therapies with tacrolimus. Because cardiovascular disease is the main cause of death, these findings should be taken into account in the assessment of the long-term cost-benefit ratio.

Antihypertensive Agents↗
PubMed2005

Effect of new immunosuppressive regimens on cost of renal transplant maintenance immunosuppression.

Although newer immunosuppressive drugs control acute rejection better and have short-term economic advantages, their long-term cost-effectiveness is unknown. We studied the frequency with which different maintenance immunosuppression regimens were used in 3 renal transplantation cohorts treated in 1990, 1994, and 1998 (total number, 3279). We calculated the mean annual immunosuppressive costs based on the true costs in a medium-sized hospital. Cyclosporine, with or without azathioprine, was used almost exclusively as the initial maintenance immunosuppressive therapy in 1990-1994. In 1998, 65% of patients received mycophenolate mofetil (MMF), and 20% received tacrolimus (Tac). A growing number of patients from 1990-1994 were converted to MMF (12%-17%) and Tac (4%-8%), while treatment of those from the 1998 cohort remained stable. According to year 2000 costs, the mean immunosuppressive cost at 1 year in 1998 (5380 euros) was almost twice that of 1994 (2902 euros) or 1990 (2855 euros). In these 2 groups the mean cost was stable until 1996, then increased faster in the 1994 cohort (24.8%) than in the 1990 cohort (17.3%), although it remained significantly lower than that in 1998. Correction of the evolution of drug prices and the purchasing value of the peseta greatly absorbed these changes. The MMF and Tac regimens showed greater mean graft life, but without reaching statistical significance in a multivariate study. The introduction of new immunosuppressive drugs has had an important economic effect since 1996; its cost-effectiveness is still pending confirmation in Spain.

Azathioprine↗
PubMed2005

Minimal model analysis in nondiabetic renal transplant recipients with hepatitis C.

INTRODUCTION: Epidemiological data suggest that hepatitis C virus (HCV) infection may contribute to the development of posttransplantation diabetes mellitus (PTDM). METHODS: We investigated the glucose metabolism in 19 renal transplant recipients with antiHCV antibodies and without DM according to World Health Organization criteria before or after transplantation. We measured insulin sensitivity (SI), glucose effectiveness (SG), and pancreatic insulin response using the frequently sampled intravenous glucose tolerance test (FSIGTT). SI and SG were estimated using the Bergman minimal model method and pancreatic insulin response was expressed as the area under insulin curve (AUIC) between 0 and 19 minutes. RESULTS: Impaired glucose tolerance was shown in 42% of patients, some (31.5%) in the range of glucose intolerance (KG: 1-1.5) and others (10.5%) in the diabetes range (KG < 1). SI and SG were decreased in 39% and 63% of patients, respectively. Pancreatic insulin response revealed high variation among patients although showing a tendency to be enhanced. CONCLUSIONS: A high number of HCV-positive renal transplant recipients without clinically manifest PTDM have impaired glucose tolerance, which suggests the future development of diabetes in these patients.

Adult↗
PubMed2005

Two doses of daclizumab with delayed introduction of low-dose tacrolimus in elderly recipients of cadaveric renal transplants from donors >55 years of age.

BACKGROUND: Renal transplants from elderly donors have a high incidence of delayed graft function, which can be increased by the initial use of calcineurin inhibitors. Our purpose was to assess the safety and efficacy of an immunosuppressive regimen using anti-IL-2R antibodies and MMF that allows delayed introduction of low-dose tacrolimus using elderly donors to elderly recipients. METHODS: This observational study involved 13 transplant centers. In total there were 119 patients (age 60.5 +/- 6.6 years, range 50 to 77) who received a kidney from a donor of mean age 64 +/- 5 years (range 55 to 76), 94% of whom died from a CVA. Immunosuppression consisted of daclizumab (1 mg/kg in two doses; preoperatively and on day 14) combined with steroids, mycophenolate mofetil (initial dose of 2 g/d), and tacrolimus (0.1 mg/kg per day). Tacrolimus was introduced before day 7 (mean 5.5 days) and adjusted to a target level of 5 to 8 ng/mL. The mean follow-up was 8 months. RESULTS: Two grafts were lost due to primary nonfunction and acute rejection and 48 patients (40%) required dialysis due to delayed graft function, although it was generally of short duration (median 4 days; only 2 cases >2 weeks). Acute rejection occurred in 16 patients (13.4%), of whom 13 were biopsy-confirmed (10.9%; Banff 1997 grades I and II). Three patients withdrew from the study, and three died (sepsis, accident, and cardiovascular event). The remaining 111 patients continued follow-up, with a median creatinine value of 1.5 mg/dL at 12-months. Eighty-six percent of patients had at least one episode of infection, half of which were urinary tract infections. There were 16 cases of CMV infection. CONCLUSIONS: Based on the initial results, our immunosuppressive regimen seems to offer good short-term renal function while maintaining an acceptable rejection rate and a low incidence of serious infections.

Aged↗
PubMed2005

Antibodies against the donor antigen glutathione S-transferase T1 after renal transplantation.

The aim of the present study was to determine whether a kidney graft expressing the glutathione S-transferase T1 enzyme (GSTT1) could cause an alloimmune response in a recipient with the null GSTT1 genotype that was similar to that observed in liver transplant. We have found anti-GSTT1 antibodies in the sera of a number of patients and confirmed that only one of the four possible genetic combinations--positive donor/null receptor--could lead to the production of these antibodies. Nevertheless, the main finding of this study is that in kidney transplantation, this mismatch was not sufficient to trigger an immune reaction. Longer follow-up of the posttransplant evolution of the patients is required in order to clarify the contribution of the factors involved in this process.

Adult↗
PubMed2005

Treatment of hepatitis C virus with interferon in hemodialysis patients awaiting kidney transplant.

INTRODUCTION: Hepatitis C virus (HCV) infection is associated with worsening disease progression after renal transplant, and to date there is no available treatment for use at this stage. It has therefore been recommended to treat HCV infection with interferon (IFN) during the dialysis period while the patient is on the waiting list for transplantation. METHODS: We analyzed data from 27 patients on hemodialysis awaiting transplant, who were under IFN treatment for chronic HCV infection (dominant genotype, 1b). The starting regime was IFN alpha-2b, 3 MU x 3/week (n = 20) or pegylated IFN alpha-2a, 135 mg/week (n = 7). If there was clearance of HCV RNA in the first 3 to 6 months, we attempted to prolong IFN treatment for 1 year, although in many patients the dose had to be reduced. A sustained response was defined as viral clearance for at least 12 months after the end of treatment. RESULTS: Viremia was negative in 13 patients (48.1%) at the end of treatment, but two of these patients relapsed, to give an overall long-term response rate of 11 patients (40.7%) and incomplete follow-up in three patients. Viral clearance was not achieved in 11 patients. In three patients (12%), IFN had to be suspended before finishing the third month of therapy due to side effects (mainly pancytopenia and intolerance of a previous kidney graft). Seven patients showing a sustained response underwent transplant, maintaining a negative viremia result. CONCLUSIONS: IFN treatment was effective in a high proportion of dialysis patients with HCV infection, with response rates possibly even higher than for the general population. However, its use is restricted by a high incidence of side effects.

Antiviral Agents↗
PubMed2005

Alendronate in kidney transplant patients: a single-center experience.

INTRODUCTION: Osteoporosis following a renal transplant is an important cause of morbidity. Several studies have demonstrated the efficiency of diphosphonates for the prevention and treatment of osteoporosis. METHODS: We evaluated the effect of alendronate treatment on bone mineral density (BMD) in patients with osteoporosis (lumbar spine and/or hip t-scores < or = -2.5). Two study groups were established: group A (n = 13), patients treated orally with vitamin D, calcium, and alendronate (70 mg/week) and group B (n = 12) patients receiving only vitamin D and calcium. The immunosuppression regimen mostly used was steroids and cyclosporine. BMD was determined at the lumbar spine and hip using a Hologic 4500 QDR densitometer at the start of treatment and after 1 year. RESULTS: The study groups showed no significant differences in age, sex, menopause, or transplant time. Group A received a mean of 1.80 +/- 1.3 microg vitamin D/week and 1.3 +/- 2.1 g calcium/d, compared to 1.1 +/- 1 microg and 1.25 +/- 2.3 g, respectively for group B (NS). After a mean of 411.15 +/- 107.75 days of treatment, a significant increase in BMD at the femoral neck was recorded in group A, but not at the level of the spine (+5.57% +/- 3.5%, P < .05 and -0.42% +/- 12%, NS, respectively). No significant changes were observed in group B (-1.45% +/- 8% femoral neck and +1.69% +/- 3.5% hip, NS). Dyspepsia was reported by 7% of patients. CONCLUSIONS: In this preliminary analysis, alendronate produced, improvements are so far limited to an increased BMD in the hip.

Alendronate↗
PubMed2005

Plasmapheresis for the prophylaxis and treatment of recurrent focal segmental glomerulosclerosis following renal transplant.

We evaluated 10 patients with primary focal segmental glomerulosclerosis (FSGS) treated with plasmapheresis (PS) following renal transplantation. Three patients lost their first graft due to FSGS recurrence. In seven patients, PS was indicated as treatment for probable recurrence defined as the onset of proteinuria above 1 g/24 hours. In the remaining three patients, treatment was started in the first week posttransplant as prophylaxis against recurrence. The PS protocol was 17 sessions with the exchange of 2.5 L of plasma for 5% albumin over 10 to 12 weeks. Losartan (25 to 100 mg/d) was given to most patients at the end of PS treatment. The mean follow-up time after PS was 10 months. All patients currently have a functioning graft. A full response to treatment, defined as persistently reduced proteinuria to less than 500 mg/24 hours or the lack of recurrence in prophylactic treatment, was achieved in six patients. Three patients showed a partial decrease in proteinuria (to less than 1 g/24 hours). One patient failed to respond and still has nephrotic range proteinuria. No adverse effects of PS were recorded. A prompt start of PS combined with the use of losartan yields good results in the prophylaxis and treatment of recurrent FSGS following renal transplant in terms of quickly reduced proteinuria. Given the natural course of FSGS, a longer follow-up is needed to estimate the impact of PS on graft survival.

Adult↗
PubMed2005

Influence of the current management of renal transplant recipients on the prevalence of anemia and related costs.

The use of mycophenolate mofetil (MMF) and renin-angiotensin system blockers (RAB) to prevent and treat chronic graft nephropathy may affect the incidence of anemia in renal transplant recipients. We compared 2 sets of cadaver-donor recipients, namely those followed at the end of 1995 (group 1; n = 252) versus 2003 (group 2; n = 530) in terms of general characteristics, incidence of anemia (hemoglobin [Hb] < or =13 g/L males, 12 g/L females) or severe anemia (Hb < or =11 g/L males, 10 g/L females) and use cost of treatment with erythropoietin (EPO). Group 2 was significantly older, heavier and longer since grafting. Fifty-seven percent received MMF, 21% received azathioprine, and 5% received rapamycin. In group 1, 83% were given azathioprine. RAB were administered to 35.1% in group 2 versus 14.7% in group 1 (P < .001). Mean blood pressure was identical in the 2 groups, but graft function was worse in group 2 (Cockroft, 62 vs 74 mL/min; P < .001). Mean Hb levels (13.66 + - 3.1 vs 13.82 + - 1.7 g/L) and prevalence of anemia (36.9% vs 34.5%) for groups 1 and 2, respectively, were similar. The rate of severe anemia, however, was lower in group 2 (2.3% vs 8.7%; P < .001). The use of EPO increased from 2.8% (group 1) to 8.7% (group 2; P < .01). In 2003, the cost of EPO was calculated at 1982 Euros/patient-year and 91,150 Euros per year for the whole patient group. Despite accumulation of predisposing factors, the control of anemia in our patients has improved due to the expanded use of EPO. Along with its high cost, EPO therapy has potential positive repercussions on the quality of life and patient prognosis. Therefore, we need to precisely define the optimal use of EPO in renal transplant recipients.

Adult↗
PubMed2005

Pharmacokinetics of mycophenolate mofetil in kidney transplant patients with renal insufficiency.

Mycophenolate mofetil (MMF) is an immunosuppressant that is widely used for prophylaxis of rejection in solid organ transplantation. In this study, we examined the effect of renal insufficiency on the pharmacokinetics of MMF, particularly on the free fraction of drug in renal transplant patients. Our study was performed on 10 patients with severe renal insufficiency (creatinine clearance [CrCl] <30 mL/min), and 10 control patients with preserved renal function (CrCl >90 mL/min). All the patients had received a cadaveric donor graft at least 1 year prior and were clinically stable under treatment with MMF and cyclosporine. For each patient, we determined 12-hour areas under the curve (AUC(0-12 h)) for the metabolites: mycophenolic acid (MPA), 7-O-mycophenolic acid glucuronide (MPAG), and the free non-protein-bound fraction of MPA (f-MPA). The two groups were matched for age, sex, and MMF dose. Mean AUC(0-12 h) values for MPA were similar in both groups. The renal insufficiency group showed a significantly increased AUC(0-12 h) for MPAG (1550 +/- 392 vs 3527 +/- 1130 microg.h/mL, P < .001) and increased trough and AUC(0-12 h) values for f-MPA (0.023 +/- 0.02 vs 0.094 +/- 0.07 microg/mL, P = .003, and 0.87 +/- 0.3 vs 1.52 +/- 0.8 microg . h/mL, P = .016, respectively). We proposed that these differences should be taken into account when deciding upon the dose of this drug for the subset of patients with impaired transplant function.

Area Under Curve↗
PubMed2004

Quantitative pp65 antigenemia in the diagnosis of cytomegalovirus disease: prospective assessment in a cohort of solid organ transplant recipients.

OBJECTIVES: To assess the accuracy of quantitative pp65 antigenemia (pp65Ag) in the diagnosis of CMV disease, in a cohort of solid-organ transplant recipients. METHODS: Prospective observational study during the first 6 months following transplantation, with determination of pp65Ag at weeks 2, 4, 6, 8, 10, 11, 12, 14 and 16. Sensitivity (S), specificity (E), positive and negative predictive values (PPV, NPV), and the optimal cut-off point for diagnosing CMV disease, were determined. RESULTS: The cohort consisted of 35 liver, 26 renal and 12 heart graft recipients. Thirteen (17.2%) were seronegative and received a seropositive graft. Of 583 blood samples, pp65Ag was positive in 109 (18.7%) from 37 patients (51%). Twenty-two patients developed CMV disease (0.3 episodes/patient); gastrointestinal disease was the most frequent (15 episodes), followed by viral syndrome (3 episodes). Patients with positive pp65Ag had a relative risk for CMV disease of 6.19 [IC95%=1.99-19.04], (P=.0001). Diagnostic values of pp65Ag were: S=86%, E=65%, PPV=51%, NPV=92%. The cut-off of > or =10 infected cells/10(5), at weeks 2, 4, 6 and 8 obtained the best PPV (0, 67, 91 and 54%), and NPV (47, 52, 67 and 50%). CONCLUSIONS: In the studied population, the presence of positive pp65Ag was associated with a high risk of developing CMV disease, and the most useful cut-off point for the diagnosis was > or =10 infected cells/10(5).

Adult↗
PubMed2004

[Interstitial pneumonitis associated with sirolimus administration in a renal transplantation patient: a clinical case].

Sirolimus is an immunosuppressive drug which has proved its effectivity to reduce the incidence of acute rejection in renal transplantation receptors. As this drug lacks nephrotoxic effects, its simultaneous use with other anticalcineurinic drugs allows the use of reduced doses. Thrombocytopenia and hyperlipidemia are the best known side-effects of sirolimus administration. Alterations in hepatic biochemistry results are also common. Some instances of interstitial pneumonitis associated to its use have been recently reported. In this paper we present a clinical case related to this rare but already confirmed adverse side-effect, which apart from the other more common nosologies occurring in immunosuppressed patients, should be taken into account in the differential diagnosis of interstitial pneumonitis in patients who are being administered this drug.

Aged↗
PubMed2004

[Association between diabetes mellitus and hepatitis C in kidney transplant patients].

BACKGROUND: Diabetes mellitus appearing after transplant (PTDM) has generally been attributed to immunosuppressive treatment. However, the findings of several studies suggest a possible relationship between hepatitis C virus (HCV) infection and diabetes mellitus, both in the general population and in liver or kidney transplant patients. METHODS: We reviewed data corresponding to 325 kidney transplant patients who did not have diabetes before transplant and were treated with ciclosporin A posttransplant. We explored whether factors such as age, gender, weight, renal disease, immunosuppression, rejection episodes or HCV could be independent risk factors for PTDM. RESULTS: Ninety four of the 325 patients were HCV positive and 231 were HCV negative. PTDM was observed in 22.3% of the HCV positive patients versus 6.5% of the HCV negative patients (p < 0.001). The independent factors found by multivariate analysis to be predictive of PTDM were: HCV positivity (OR: 5.65, IC 95%: 2.6-12), body mass index (OR: 1,10, IC 95%: 1.02-1.2) and age (OR: 1.07, IC 95%: 1.03-1.12). CONCLUSIONS: Our findings support a link between HCV and PTDM.

Adult↗
PubMed2003

Immunoprophylaxis with Simulect (basiliximab) in kidney transplantation: results from routine clinical practice at 18 kidney transplant units.

OBJECTIVE: The objective of this study is to assess a Simulect (basiliximab) regimen in routine clinical practice in the Spanish kidney transplantation units to evaluate efficacy and safety. METHODS: In this prospective, observational study, data on demographics, parameters of efficacy, and safety in patients who under with kidney transplantation treated with Simulect (basiliximab) were collected through an on-line collection system. RESULTS: One hundred sixty three patients at 18 kidney transplant units included 12 months follow-up. The patient mean age was 52 years (DS 13,67) including 96 (58.90%) men and 67 (41.10%) women. Cold ischemia time was 19 hours (DS 6,79). Only 2 patients presented with PRA >50%. For prophylactic immunosuppression, 67.13% of patients received triple therapy with CNI (cyclosporine 49.65% or tacrolimus 17.48%), MMF (66.43%) or AZA (10.49%), and steroids. Incidence of acute rejection (AR) at 12 months was 12.27% (1.84% steroid-resistant). In subgroup analysis, AR was 13.5% in nondiabetics and 4.5% in diabetics, including 3 steroid-resistant episodes (1.84%) in nondiabetics and none in diabetics. In relation to donor age, AR was incidence 10.3% in patients with kidneys from donors aged 50 years or younger and 10.6% when donors were older than 50 years, including 1 (1.73%) and 2 (1.93%) steroid-resistant episodes, respectively. The graft and patient survival rates at 12 months were 90% and 98%, respectively. CONCLUSIONS: Simulect (basiliximab) used in routine clinical practice provided good prophylaxis against acute rejection in several kidney transplant patient populations, similar to that observed in randomized clinical studies with excellent tolerability and safety.

Adrenal Cortex Hormones↗