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S Gil-Vernet

Publications and source records attributed to S Gil-Vernet.

At least 19 recordsLinked to original sources

Immunosuppression for dual kidney transplantation with marginal organs: the old is better yet.

Immunosuppressive protocols in dual kidney transplantation (DKT) are based on calcineurin inhibitors (CNI). We wonder whether a CNI-free immunosuppression can improve outcome in older patients receiving a DKT with marginal donor organs. Thirty-six were treated with CsA, MMF and prednisone (CsA group) and 42 with rATG, SRL, MMF and prednisone (SRL group). Incidence of delayed graft function and acute rejection was 44% and 11% in the CsA group, and 40% and 8% in the SRL group. CMV infection incidence was low in both protocols. Three-year patient survival was 89% in the CsA and 76% in the SRL group. One- and 3-year graft survival after censoring for dead with a functioning allograft was 94.2% and 94% in CsA and 95% and 90% in SRL, respectively. Renal function was similar in both groups whereas proteinuria was higher in the SRL group. Uninephrectomy due to graft thrombosis or urinary-related complications was numerically higher in the SRL (21%) than in the CsA group (8%) (p = 0.13) and it was associated with renal failure and proteinuria. In DKT, a new induction immunosuppressive protocol based on rATG, SRL, MMF and prednisone does not offer any advantage in comparison to the old CsA, MMF and prednisone.

Calcineurin Inhibitors↗

Posttransplant diabetes mellitus in renal allograft recipients: A prospective multicenter study at 2 years.

The purpose of this study was to investigate the incidence and risk factors for the development of diabetes mellitus after kidney transplantation (PTDM). A total of 1783 nondiabetic renal allograft recipients transplanted from January 2000 to December 2002 were included. Diabetes was diagnosed following American Diabetes Association criteria. While 1276 patients were treated with tacrolimus (Tac), mycophenolate mofetil (MMF), and steroids, 507 patients received cyclosporine-ME (CsA), MMF, and steroids. PTDM incidence at 6, 12, and 24 months was 14.2%, 12.8%, and 13.3%, respectively. Cumulative incidence during the follow-up was 21.6%. Only 121 of the diabetic patients (47.6%) at 6 months remained diabetic at 24 months. Furthermore, 60 patients of 116 patients on insulin at 6 months (51.7%) remained on treatment at 24 months. The cumulative incidence of PTDM was similar in the two immunosuppressive treatments (19.7% on CsA-MMF vs 22.3% on Tac-MMF; P = NS). However, at 24 months, 14 of 50 diabetic patients on CsA-MMF (28%) and 74 of 161 patients on Tac-MMF (45.9%) were on insulin treatment (P < .05). By Cox regression analysis, age older than 60 years (RR 1.61; 95%CI 1.28-2.04; P < .001), body mass index (BMI) > 30 kg/m2 at transplantation (RR 1.66; 95%CI 1.27-2.16; P < .001), and immunosuppression with Tac (RR 1.30; 95%CI 1.02-1-66; P = .033) were associated with PTDM. In conclusions, the incidence of PTDM at 24 months in immunosuppressive protocols including MMF is about 22%, and it is associated with older age, increased BMI, and immnunosuppression with Tac.

Adrenal Cortex Hormones↗

Subclinical rejection associated with chronic allograft nephropathy in protocol biopsies as a risk factor for late graft loss.

Chronic allograft nephropathy (CAN) in protocol biopsies is associated with graft loss while the association between subclinical rejection (SCR) and outcome has yielded contradictory results. We analyze the predictive value of SCR and/or CAN in protocol biopsies on death-censored graft survival. Since 1988, a protocol biopsy was done during the first 6 months in stable grafts with serum creatinine <300 micromol/L and proteinuria <1 g/day. Biopsies were evaluated according to Banff criteria. Borderline changes and acute rejection were grouped as SCR. CAN was defined as presence of interstitial fibrosis and tubular atrophy. Mean follow-up was 91 +/- 46 months. Sufficient tissue was obtained in 435 transplants. Biopsies were classified as normal (n = 186), SCR (n = 74), CAN (n = 110) and SCR with CAN (n = 65). Presence of SCR with CAN was associated with old donors, percentage of panel reactive antibodies and presence of acute rejection before protocol biopsy. Cox regression analysis showed that SCR with CAN (relative risk [RR]: 1.86, 95% confidence interval [CI]: 1.11-3.12; p = 0.02) and hepatitis C virus (RR: 2.27, 95% CI: 1.38-3.75; p = 0.01) were independent predictors of graft survival. In protocol biopsies, the detrimental effect of interstitial fibrosis/tubular atrophy on long-term graft survival is modulated by SCR.

Adolescent↗

Clinical and virological effects during two years of ongoing adefovir dipivoxil in the treatment of lamivudine-resistant chronic hepatitis B infection.

OBJECTIVE: Our aim was to evaluate the efficacy and safety of adding adefovir to lamivudine therapy for hepatitis B virus (HBV)-infected patients resistant to Ramivudine. PATIENTS AND METHODS: Among 17 studied patients, 7 had chronic active HBV infection and 10 were posttransplant with HBV infection (9 with de novo HBV). They received lamivudine plus adefovir therapy for 2 years. We assessed reductions in serum HBV-DNA and alanine aminotransferase (ALT) levels, loss of HBeAg (in HBeAg+ cases), and HBsAg clearance. RESULTS: A virological response, as defined by HBV-DNA below the cut off by hybridization, was observed in 12 (70.6%) patients and loss of HBeAg in 4 (44.4%) of the 9 initially HBeAg-positive cases. A biochemical response, defined as a decreased serum ALT to the normal range, occurred in 4 (26.7%) patients. Median serum creatinine increased in 3 of 15 (20%) patients, excluding those on hemodialysis. There were two noteworthy cases of sustained HBsAg seroconversion with adefovir (11.8%): one patient with de novo HBV infection posttransplantation and positive hepatitis C virus-RNA serology, and one patient with decompensated HBV cirrhosis in whom viral replication ceased, making him eligible for transplantation. CONCLUSIONS: Currently, adefovir is an effective rescue therapy that broadens the existing range of options for patients with lamivudine-resistant chronic hepatitis B infection, particularly those with decompensated cirrhosis awaiting a liver graft, and those with recurrent posttransplantation HBV. The relatively small biochemical response seen in these patients may be attributable to the high prevalence of concomitant hepatitis C virus infection (41%).

Adenine↗

Therapy with plasmapheresis and intravenous immunoglobulin for acute humoral rejection in kidney transplantation.

BACKGROUND: Acute humoral rejection (AHR) is characterized by acute graft dysfunction associated with de novo production of donor-specific alloantibodies (DSA) and C4d deposition in peritubular capillaries of the renal allograft. It has been reported the combination of plasmapheresis (PP) and intravenous gamma globulin (IVIG) as effective rescue therapy for established AHR. METHODS: Between 1999 and 2004, seven kidney allografts recipients suffered from AHR diagnosed by severe rejection and C4d staining in peritubular capillaries. All patients had a negative cross-match before renal transplantation. RESULTS: All patients were treated with daily sessions of PP and in four cases IVIG was added after the last PP session. Tacrolimus and mycophenolate mofetil were employed as maintenance immunosuppressive regimen. In one case, rituximab was added to PP and IVIG owing to refractory humoral rejection. At 1 year, patient survival was 100%, allograft survival was 70%, and the mean serum creatinine was 201 micromol/L. CONCLUSIONS: AHR is a severe form of rejection associated with a poor prognosis, but its early diagnosis and treatment with PP and IVIG allows reversal of AHR reaching a 70% graft survival at 1 year.

Acute Disease↗

Long-term effect of hepatitis C virus chronic infection on patient and renal graft survival.

BACKGROUND: Hepatitis C virus (HCV) infection increases morbimortality in renal transplantation. The immune response against the HVC is not predictable in a great proportion of patients developing into chronic liver disease, glomerulonephritis, or both. PATIENTS: We analyzed the impact of posttransplant chronic hepatitis development on patient and graft survival in 200 HCV-positive/HBsAg-negative renal allograft recipients transplanted between 1981 and 2003. RESULTS: Ninety-eight patients developed chronic ALT elevation (ALT+), while 102 did not (ALT-). There was no difference in acute rejection episodes (ARE), acute tubular necrosis, donor and recipient age, gender, HLA mismatches, and number of previous renal transplants. Development of ALT+ was associated with a worse patient survival (90% vs 65% at 15 years of follow-up, P = .007; RR = 3.8, CI = 1.4-10.1), an effect that was independent of other variables as time on dialysis and age. The main causes of death among ALT+ were chronic liver disease (52%), cardiovascular (26%), and infection (13%), whereas in ALT- they were cardiovascular (33%), cancer (33%), and chronic liver disease (16%). Conversely, graft survival (censoring for patient death with a functioning graft) was higher among ALT+ (50% vs 35% at 15 years of follow-up, P = .04; RR = 1.5, CI = 1.19-2.22). Causes of graft loss in ALT- patients were chronic allograft nephropathy (CAN, 53%), glomerulonephritis (GN, 18%), acute rejection episode (AR, 22%), and death (5%), whereas among ALT+ they were CAN (36%), GN (31%), ARE (10%), and death (21%; P = .01). By multivariate analysis, ALT- (RR = 1.6, CI = 1.07-2.55, P = .02) and de novo GN (RR = 2, CI = 1.29-3.09, P = .002) were associated with worse renal allograft survival. CONCLUSION: Our results suggested that a better immune response against the HCV lead to greater patient survival but poorer graft survival.

Adult↗

Arterial elasticity measurement in renal transplant patients under anticalcineurin immunosuppression.

INTRODUCTION: Calcineurin inhibitors may be associated with decreased arterial elasticity and increased vascular risk. We measured pulse wave velocity (PWV) in large or small arteries as an index of elasticity. The aim of our study was to determine aortic and radial arterial elasticity in 30 stable kidney transplant patients treated with calcineurin inhibitor immunosuppression. PATIENTS AND METHODS: In stable kidney transplant patients we determined the usual biochemical parameters as well as lipid profiles, 24-hour blood pressure (BP) monitoring (CBPM) using a chronobiological program (Garapa), and PWV with a HDI-PWV CR-2000 monitor. RESULTS: Sixteen patients received cyclosporine (CsA, G-1) and 14 tacrolimus (G-2) immunosuppression. There were no baseline differences regarding age (G-1: 56 +/- 12 years, G-2: 56 +/- 14 years), renal transplant follow-up (G-1: 7 +/- 3 years, G-2: 7.5 +/- 3 years), Systolic BP, pulse pressure or plasma creatinine (G-1: 163 +/- 35 umol/L, G-2: 173 +/- 26 umol/L). Patients in the G-1 showed higher diastolic BP (79 +/- 11 vs 74 +/- 8 mm Hg), greater proteinuria (1.26 +/- 0.4 vs 0.6 +/- 0.2 g/d, P < .05), total cholesterol (5.51 +/- 1.2 mmol/L) and low-density lipoprotein (3.08 +/- 0.3 vs 2.99 +/- 0.3 mmol/L, P = NS). Aortic arterial elasticity was decreased in G-1 patients (10.4 +/- 6 vs 14.3 +/- 2 mL/mm Hg x10, P < .05) as well as that in the radial artery (G-1: 5.52 +/- 1 vs 5.57 +/- 1.2 mL/mm Hg x100, P = NS). Almost 100% of the patients presented normal diurnal BP with high nocturnal BP in a nondipper pattern in both groups. CONCLUSION: Calcineurin immunosuppression may contribute to arterial stiffness in kidney transplant patients. No differences between CsA or tacrolimus were observed in our study. CBPM and PWV are useful tools to evaluate subclinical atherosclerosis in renal transplant patients.

Adult↗

Beneficial effect of concomitant induction with antilymphoblast globulin, cyclosporine, and steroids on long-term renal allograft outcome.

BACKGROUND: The addition of induction therapy with antilymphocytic antibodies to cyclosporine (CsA) based immunosuppression, has reduced acute rejection incidence and improved short-term survivals, but has not had well-established effects on long-term renal transplant survival. PATIENTS: We analyzed the long-term allograft outcome of patients included in a prospective randomized clinical study conducted in our center 15 years ago by comparing two strategies: (A) horse antilymphoblast globulin (ALG) given at 10 mg/kg on alternate days to a maximum of 6 doses with low-dose CsA started at 8 mg/kg per day and prednisone at 0.25 mg/kg per day, versus (B) CsA started at 15 mg/kg per day and prednisone at 0.5 mg/kg per day. Diabetic and highly sensitized patients (PRA > 70%) were excluded from the study. RESULTS: The characteristics of the 50 patients enrolled in each group were not different. Although patient survival was not different (88% in group A vs 77% in group B), recipients treated with ALG showed a lower incidence of acute rejection episodes (20% vs 44%, P = .01) and better death-censored renal allograft survival (57% vs 41%, P = .03). Among rejection-free patients, graft survival was 15% higher in group A (60% vs 45%, P = .12). Multivariate Cox regression analysis showed that an acute rejection episode (relative risk [RR]: 2.44, 95% confidence interval [CI] 1.36-4.39; P = .0029) rather than ALG immunosuppression (RR 0.74, 95% CI 0.41-1.33; P = NS) was an independent predictor of death-censored graft survival. CONCLUSIONS: In summary, we confirmed that concomitant induction therapy with ALG, CsA, and steroids improves long-term renal allograft survival.

Adrenal Cortex Hormones↗

Histologic findings in protocol biopsies performed in stable renal allografts under different immunosuppressive schedules.

Protocol biopsies performed in stable renal allografts show different degrees of acute and chronic lesions. Histologic findings in protocol biopsies have been related to graft outcome. We evaluated histologic lesions observed in protocol biopsies performed in patients under different immunosuppression therapies. From June 1988 a protocol biopsy was performed at approximately 4 months in patients who fulfilled the following criteria: serum creatinine <300 micromol/L; stable renal function; and proteinuria <1 g/d. Histologic lesions were graded according to 1997 Banff criteria. For the present study we considered the following groups according to immunosuppressive schedule: (i) induction therapy with polyclonal or monoclonal antilymphocytic antibodies associated with cyclosporine and prednisone (n=201); (ii) cyclosporine, mycophenolate mofetil, and prednisone (n=127); and (iii) tacrolimus, mycophenolate mofetil, and prednisone (n=51). On protocol biopsy patients treated with tacrolimus displayed a lower acute score (0.61+/-1.01 vs 1.24+/-1.23 in group I, 1.28+/-1.41 in group II; P<.0001) and a higher proportion of normal biopsies (57.1% vs 41.9% in group I, 45.1% in group II; P=.016). A similar proportion of chronic lesions (chronic score of group I: 1.30+/-1.56; group II: 1.34+/-1.80; group III: 1.51+/-0.95; P=NS) was observed in the three groups. Protocol biopsies displayed fewer acute lesions in patients treated with tacrolimus. This result suggests that the efficacy of new immunosuppression schedules can be evaluated using the protocol biopsy as a surrogate marker of graft outcome.

Adult↗

[Effect of cyclosporin and tacrolimus on lipoprotein oxidation after renal transplantation].

BACKGROUND: Cyclosporin A is a lipogenic immunosuppressor that can induce posttransplant hyperlipidaemia. Oxidation of low-density lipoprotein (LDL) has been recognized as a major atherogenic factor. Tacrolimus seems to be less lipogenic with an apparently better cardiovascular profile than CsA. METHODS: We have studied the lipidic profile and the oxidation of HDL and LDL in 20 renal transplant patients, 12 male and 8 female, mean age 45 +/- 10 year, who where switched from CsA to tacrolimus due to CsA adverse effects. LDL were determined by ultracentrifugation. Oxidation study before and 6 months after conversion to tacrolimus was performed by adding CuSO4. RESULTS: After conversion, systolic blood pressure (BP) decreased from 154 +/- 21 to 133 +/- 21 mm Hg (p = 0.008), diastolic BP from 97 +/- 13 to 77 +/- 15 mm Hg (p = 0.016), total cholesterol from 6.08 +/- 0.9 to 5.68 +/- 1.1 mmol/l (p = 0.02), LDL-chol from 3.29 +/- 1.01 to 2.96 +/- 0.3 mmol/l (p = 0.04) and apo-B lipoprotein from 1.42 +/- 0.28 to 1.15 +/- 0.34 mg/dl (p = 0.003). The oxidation of LDL improved after conversion: the initial dienic compounds decreased from 95 +/- 20 to 63 +/- 12 umol/g and the final DC from 207 +/- 56 to 107 +/- 35 umol/g. Lag-phase increased from 33 +/- 21 to 45 +/- 17 min (p < 0.05). CONCLUSION: Tacrolimus has improved hyperlipidaemia in our cyclosporin previously treated patients and increased the resistance to oxidation of high and low-density lipoproteins.

Adult↗

Efficacy of interferon for chronic hepatitis C virus-related hepatitis in kidney transplant candidates on hemodialysis: results after transplantation.

OBJECTIVES: Interferon-alpha (IFN) may have undesirable effects on a functioning graft. The aim of this study was to evaluate IFN treatment in kidney transplant candidates during the hemodialysis period as well as the results after transplantation. METHODS: A total of 29 noncirrhotic hemodialysis patients with chronic hepatitis C virus (HCV) infection (based on long-term rise in ALT, HCV serology, HCV RNA by polymerase chain reaction methods, and histological evidence) were included. Tolerability to IFN treatment, pre- and posttransplantation therapeutic results, and long-term outcome were recorded. IFN regimen consisted of 3 million units (MU) times per week after hemodialysis sessions for 6 months, followed by 1.5 MU after each hemodialysis session for an additional 6 months. All patients gave informed consent for participation. RESULTS: IFN therapy was fairly well tolerated. Adverse effects due to IFN toxicity, renal disease, or causes related to the immunological properties of IFN were observed in 24% of patients. At the end of treatment, ALT had normalized in 23/28 patients (82.1%), and HCV RNA had cleared in 23/28 patients (82.1%). During follow-up, HCV RNA was persistently negative in 18 patients (64%, including transplant recipients). A total of 14 patients (nine HCV RNA-negative) received a kidney transplant. Mean follow-up after the procedure was 41 +/- 28 months. In all, 12 patients had a functioning graft, one had acute vascular rejection, and one died of carcinoma. All transplanted patients maintained normal ALT levels, and eight remained HCV RNA-negative. CONCLUSIONS: Treatment results in our study population were better than those observed in the general population. The long-term response achieved, which was maintained after transplantation, supports the use of IFN for HCV hepatitis in kidney transplant candidates under hemodialysis.

Adult↗

Post-transplant lymphomas: a 20-year epidemiologic, clinical and pathologic study in a single center.

BACKGROUND AND OBJECTIVES: To study the incidence, clinical presentation, pathologic features and outcome of post-transplant lymphomas (PTL) during the past 20 years. DESIGN AND METHODS: We undertook a descriptive study of all biopsy-proven cases of PTL diagnosed in our hospital from 1979 through 1999. The average annual incidence rate of PTL was analyzed at 5-year intervals from 1979 to 1999. Risk ratios were estimated by comparing the incidence of PTL among transplanted patients with that of lymphoma observed in the general population of the region. Survival analysis was performed at the univariate level using the Kaplan Meier technique and at the multivariate level by Cox hazard models. RESULTS: Seventeen of 1,860 transplanted patients developed a PTL (0.9%). The risk of PTL was calculated to be almost 8-fold higher than the risk of lymphoma in the general population. The risk was highest among those who had received a heart transplant (RR=35.6). The mean time between transplant and the diagnosis of PTL was 31 +/- 29 months. Of all PTL, 88% were of B-cell origin and 53% of the cases tested were Epstein-Barr virus (EBV)-positive. The median survival was 24 months. The majority of patients with allograft involvement died within the 2 months following diagnosis (hazard ratio 5.3; 95% CI 1.4-20.7). INTERPRETATION AND CONCLUSIONS: Organ transplantation is a major risk factor for the development of lymphoma, a disease with a particularly bad prognosis when it develops at the site of the allograft. Early diagnosis and more specific treatment may improve PTL survival.

Adult↗

[Analysis of 500 liver transplantations at Bellvitge Hospital, Spain].

BACKGROUND: We present the experience of the liver transplantation program at the Hospital of Bellvitge with 500 transplantations performed during 15 years, to describe changes in liver transplantation observed throughout the time and to analyze the long term results. PATIENTS AND METHOD: Five groups each one including 100 consecutive transplantations are studied. RESULTS: The main indications were hepatocellular carcinoma (23%), alcoholic cirrhosis (22.8%), and post-hepatitis C cirrhosis (18.8%). Sixty-five retransplantations were performed in 59 patients (13%), being the more frequent indications arterial thrombosis (13 patients) and primary nonfunction of graft (10 patients). In 10 patients a hepatorenal transplantation was performed. In group I, the most frequent donor cause of death was cranial traumatism (80%), while in group V it was the vascular pathology (52%). There were other significative differences between these groups of patients (I vs V): patients with stage 2 or 3 from UNOS status (45 vs 19%), blood use (29.6 [26] vs 4.6 [5.3] PRBC), ICU stay (13 [13] vs 7.4 [11] days), hospital stay (40 [52] vs 23.7 [17] days), rejection rate (46 vs 20%) and primary graft nonfunction (9 vs 3%). However, the infection rates (48 vs 54.5%) and biliary tract complications (26 vs 20%) have not shown statistically significant differences. Actuarial one and 5-year survival are 83 and 70% respectively. CONCLUSIONS: An important and progressive improvement of liver transplantation results has been observed. However, de novo tumours, hepatitis C virus recurrence and chronic rejection can limit long term results.

Age Factors↗

Protocol renal allograft biopsies and the design of clinical trials aimed to prevent or treat chronic allograft nephropathy.

BACKGROUND: The minimum sample size to perform a clinical trial aimed to modify the natural history of chronic allograft nephropathy (CAN) is very large. Since the presence of chronic tubulointerstitial damage in renal protocol biopsy specimens is an independent predictor of late outcome, we evaluated whether protocol biopsies could facilitate the design of trials aimed to prevent or treat CAN. METHODS: Two hundred eighty-two protocol biopsy specimens were obtained 3 months after transplantation in 280 patients with serum creatinine levels <300 micromol/L, proteinuria <1000 mg/day, and stable function. The specimens were evaluated according to the Banff criteria. RESULTS: Graft survival depended on the presence of CAN and renal transplant vasculopathy (RTV). Thus, biopsy specimens were classified as: (a) no CAN (n=174); (b) CAN without RTV (n=87); and (c) CAN with RTV (n=21). Graft survival at 10 years was 95%, 82%, and 41%, respectively (P=0.001). Total serum cholesterol before transplantation was 4.5+/-1.1, 4.6+/-1.1, and 5.3+/-1.6 mmol/L, respectively (P=0.009) and it was the only predictor of RTV. Power analysis (beta=20%, alpha=5%) was done to evaluate whether protocol biopsies can facilitate the design of clinical trials aimed either to prevent or treat CAN. We showed that the most feasible approach would be to use the presence of CAN as the primary efficacy end point in a prevention trial. To demonstrate a 50% reduction in the incidence of CAN at 3 months, 570 patients would be required. CONCLUSIONS: Protocol biopsies may allow a reduction of sample size and especially the time of follow-up in a trial aimed to prevent CAN.

Biopsy↗