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S Gil-Vernet

Publications and source records attributed to S Gil-Vernet.

At least 37 records · Page 2Linked to original sources
PubMed1999

Fluvastatin and low-density lipoprotein oxidation in hypercholesterolemic renal transplant patients.

BACKGROUND: Hyperlipidemia contributes to the development and progression of vascular disease in organ transplant patients. Oxidative modification of low-density lipoproteins (LDLs) has been suggested as a key event in early atherogenesis. METHODS: We conducted a pilot study in renal transplanted patients with persistent hypercholesterolemia above 6.5 mmol/liter. We studied the LDL oxidation before and after one year of fluvastatin treatment. Twenty patients (12 males and 8 females, 46 +/- 10 years old) who received a kidney transplant 24 +/- 18 months before the study were treated with fluvastatin (20 mg/day for 12 weeks). Patients with a total cholesterol under 6.3 mmol/liter continued to receive 20 mg/day for another 40 weeks (group I, N = 10). Nine patients with a total cholesterol above 6.3 mmol/liter received 40 mg/day for a further 40 weeks (group II). RESULTS: Cyclosporine levels did not experience a significant variation. Total and LDL cholesterol decreased significantly in both groups (21.7 and 27.9% in group I, 18.3 and 27.2% in group II, respectively). The lag-phase time, which was significantly enlarged before fluvastatin treatment in the patients with respect to the controls (N = 18, 82 +/- 45 vs. 50 +/- 8 min) was shortened after one year of fluvastatin treatment (64 +/- 24 vs. 50 +/- 8 min, P = 0.04). Fluvastatin was stopped in only one patient because of nausea and vomiting. Transaminases and creatin-phospho-kinase were not altered. All of the patients maintained a functioning graft during the study period. CONCLUSIONS: Fluvastatin significantly reduced total and LDL cholesterol, without interferences with cyclosporine A through levels. Fluvastatin has not demonstrated an antioxidant effect in our renal hypercholesterolemic transplant patients.

Adult↗
PubMed1999

Donor age and delayed graft function as predictors of renal allograft survival in rejection-free patients.

BACKGROUND: Transplant recipients of kidneys harvested from old donors have a high incidence of delayed graft function (DGF) and a poor graft outcome. This result is partly explained by the increased incidence of acute rejection in patients suffering from DGF. However, the long-term impact of donor age and DGF in rejection free renal transplants is not well established. The aim of the present work is to evaluate the impact of donor age and DGF on long-term outcome in renal transplants with or without acute rejection. PATIENTS: We review all cadaveric kidney transplants performed in our centre between April 1984 and December 1995 treated with a cyclosporin-based immunosuppression. RESULTS: Five hundred and ninety-five patients were included. The overall incidence of DGF was 29.1%, and this event was associated with an increased donor age and cold ischaemia time. Univariate and multivariate analysis showed that graft loss was associated with acute rejection (relative risk (RR) 2.24, 95% confidence interval (CI) 1.62-3.01); DGF (RR 1.83, 95% CI 1.32-2.54); donors >50 years (RR 1.65, 95% CI 1.13-2.38); and retransplantation (RR 1.52, 95% CI 1.01-2.31). In rejection-free patients there were two independent predictors of graft failure: donor >50 years (RR 2.40, 95% CI 1.45-4.01); and DGF (RR 2.42, 95% CI 1.53-3.84). CONCLUSIONS: Regardless of the presence of acute rejection, delayed graft function amplifies the detrimental effect of advanced donor age on long-term graft outcome.

Adult↗
PubMed1998

Low-dose cyclosporine and mycophenolate mofetil in renal allograft recipients with suboptimal renal function.

BACKGROUND: Cyclosporine (CsA) nephrotoxicity can be identified by functional changes and chronic renal damage. CsA-associated renal fibrosis has been related to the overproduction of transforming growth factor (TGF)-beta1, a fibrogenic cytokine. Mycophenolate mofetil (MMF) may allow CsA dose reduction without increasing the risk of rejection. METHODS: We studied the impact of CsA dose reduction in association with MMF on renal function and TGF-beta1, production in 16 long-term renal allograft recipients with suspected CsA nephrotoxicity. Two grams/day of MMF were introduced, and CsA dose was reduced to reach whole-blood levels between 40 and 60 ng/ml within 1 month. CsA dose and levels, renal function parameters, and platelet-poor plasma TGF-beta1 levels were evaluated before and 6 months thereafter. RESULTS: MMF allowed a decrease in both the mean dose of CsA (3.8+/-1.35 vs. 2.2+/-0.73 mg/kg/day; P<0.01) and CsA levels (148+/-36 vs. 53+/-19 ng/ml; P<0.001). The reduction of CsA was associated with a decrement of serum creatinine levels (210+/-46 vs. 172+/-41 micromol/L; P<0.001) and an increase in both the glomerular filtration rate (32.9+/-12 vs. 39.1+/-14 ml/min/1.73 m2; P<0.02) and renal plasma flow (195+/-79 to 218.6+/-74.02 ml/min/1.73 m2; P<0.02). There was a reduction in plasma TGF-beta1 levels (4.6+/-4.2 vs. 2.0+/-1.4 ng/ml; P=0.003) and CsA levels correlated with TGF-beta1 (r=0.536, P=0.002). No rejection episodes occurred, and an improvement in both systolic (149+/-13 vs. 137+/-12 mmHg; P<0.01) and diastolic blood pressure (89+/-14 vs. 83+/-10 mmHg; P<0.04) were observed. CONCLUSIONS: These short-term results show that MMF introduction allows a CsA dose reduction, which improves renal function, reduces TGF-beta1 production, and improves the control of hypertension, without increasing the incidence of acute rejection.

Adult↗
PubMed1998

Recipient body surface area as a predictor of posttransplant renal allograft evolution.

BACKGROUND: The aim of the present study was to analyze whether minor differences in recipient body surface area have any predictive value on renal allograft evolution. METHODS: For this study, we considered 236 pairs of recipients who received a kidney from the same donor at our center between March 1985 and December 1995. Pairs in whom at least one patient presented any of the following events were excluded: graft loss during the first year of follow-up, diabetes mellitus, noncompliance with treatment, chronic pyelonephritis, and recurrent or de novo glomerulonephritis. Recipients of each pair were classified as large or small according to their body surface area (BSA). The percentage difference of BSA in each pair was calculated, and two cohorts of pairs were defined: BSA difference < or = 10% (n=76 pairs) and BSA difference >10% (n=70 pairs). RESULTS: The large recipients of the cohort with a BSA difference >10% showed a higher incidence of posttransplant delayed graft function (22/70 vs. 12/70, P=0.075), hypertension at 1 year of follow-up (51/70 vs. 35/70, P=0.006), and a higher serum creatinine level at 1-year follow-up (173 vs. 142 micromol/L, P=0.003), whereas in the cohort with a BSA difference < or = 10%, posttransplant evolution in large and small recipients was not different. Multivariate analysis showed that recipient BSA was an independent predictor of delayed graft function, posttransplant hypertension, and serum creatinine at 1-year follow-up. CONCLUSIONS: Relatively small differences in recipient BSA influence renal allograft evolution. Consequently, our data support that recipient size should be taken into consideration for renal allograft allocation.

Adult↗
PubMed1998

Primary immunosuppression with mycophenolate mofetil and antithymocyte globulin for kidney transplant recipients of a suboptimal graft.

BACKGROUND: In renal transplantation the beneficial immunosuppressive effects of cyclosporin (CsA) may be curtailed by its nephrotoxicity, specially in patients receiving a cadaveric allograft from suboptimal donors or at risk of delayed graft function. Mycophenolate mofetil (MMF) and antithymocyte globulin (ATG) have each demonstrated to be potent immunosuppressants in renal transplantation. In a prospective analysis we have studied the results at 6 months of the combination of MMF, ATG and low-dose steroids in patients with low immunological risk receiving a first cadaveric renal allograft from a suboptimal donor or at risk of delayed graft function. METHODS: Patients with preformed reactive antibodies < 500% receiving a first graft from a suboptimal donor (age > or = 40 years, non-heart-beating, acute renal failure, arterial hypertension) or at risk of delayed graft function (cold ischaemia time > or = 24 h) were eligible for this open single-arm pilot trial. From September 1996 to March 1997 we recruited 17 patients. They were treated with MMF 2 g p.o. preoperatively, and after transplantation at 3 g/day; rabbit ATG i.v. at 2 mg/kg preoperatively, and 1.5 mg/kg/day the first day after transplantation, followed by four doses of 1 mg/kg on alternate days; prednisone was given at 0.25 mg/kg/day and reduced progressively to 0.1 mg/kg/day at 3 months. Primary outcomes were incidence of biopsy-proven acute rejection, delayed graft function, opportunistic infections, graft and patient survival, and the need for introduction of CsA treatment. RESULTS: delayed graft function occurred in two cases (12%). Four of 17 patients (24%) had a biopsy-proven acute rejection (2 grade I and 2 grade II) within the first 3 months after transplantation. CsA was added in two cases with grade II biopsy-proven acute rejection, and in one with grade I biopsy-proven acute rejection. In one patient MMF was replaced by CsA because of gastrointestinal intolerance. Mean serum creatinine 6 months after transplantation was 159+/-59 micromol/1. Cytomegalovirus tissue invasive disease occurred in one patient (6%). At 6 months follow-up all patients are alive with functioning allografts. CONCLUSIONS: These preliminary results suggest that in low-immunological-risk patients who receive a suboptimal renal allograft or at risk of delayed graft function, the combination of MMF, ATG, and steroids is an efficient immunosuppressive regime that may avoid the use of CsA in 70% of the recipients.

Adult↗
PubMed1998

Incidence of leukopenia and cytomegalovirus disease in kidney transplants treated with mycophenolate mofetil combined with low cyclosporine and steroid doses.

Mycophenolate mofetil (MMF) combined with conventional cyclosporine and steroids doses efficiently prevents acute rejection in kidney transplants. However, this regimen has been associated with an increased incidence of cytomegalovirus (CMV) disease and leukopenia, specially in patients receiving MMF at 3 g/d, suggesting that the combination of two powerful immunosuppressants carries the risk of overimmunosuppression. For this reason, we treated a group of patients with MMF 3 g/d combined with low cyclosporine and steroids doses. Eighty-two kidney transplants performed at two centers and enrolled in the European Mycophenolate Mofetil Cooperative Study were randomized to receive: A) placebo (n = 27); B) MMF 2 g/d (n = 27); and C) MMF 3 g/d (n = 28). In this double blind study all patients received cyclosporine and steroids at conventional doses. Fifteen kidney transplants enrolled in an MMF open pharmacokinetic study were treated with MMF 3 g/day combined with low cyclosporine and steroid doses (group D). Efficacy was evaluated as the incidence of biopsy proven acute rejection, and safety focused on CMV disease and leukopenia. Patients receiving MMF showed a low incidence of biopsy proven rejection (B) 18.5%; C) 10.7%; and D) 13.3%). Patients of group C had a high incidence of CMV disease (35.7%) when compared with the other groups (lower than 8%). Incidence of leukopenia was higher in patients treated with MMF (B) 25.9%; C) 39.3%; and D) 40%) than in placebo treated patients (7.4%). Patients in group (C) displayed leukopenia mainly in the context of CMV disease, while patients of group (D) had leukopenia not related to CMV infection. All patients of group (D) who presented leukopenia recovered after MMF reduction dose, while in group (C) there were 5 out of 28 patients who required MMF withdrawal. We propose that a reasonable approach to take advantage of a powerful non-nephrotoxic immunosuppressant such as MMF, could be the administration of this drug at 3 g/d from the time of transplantation combined with low CsA and steroid doses.

Adult↗
PubMed1997

Steroid withdrawal in mycophenolate mofetil-treated renal allograft recipients.

BACKGROUND: Acute rejection is an inherent risk of the withdrawal of steroids in renal allograft recipients. Mycophenolate mofetil is a potent immunosuppressant that, when given with cyclosporine (CsA), reduces the incidence of acute rejection and may facilitate discontinuation of steroids without increasing the risk of rejection. METHODS: In an open pilot study, steroids were withdrawn from 26 adult cadaveric kidney transplant recipients. Corticosteroids were discontinued between 4 and 30 (mean 17) months after transplantation, and steroid-free follow-up ranged from 7 to 18 (mean 10) months. RESULTS: Mean CsA doses, CsA blood levels, and serum creatinine at the time of steroid withdrawal and at last patient visit after cessation of steroids were 4.2+/-1.2 mg/kg/day and 3+/-0.8 mg/kg/day (P<0.001), 170+/-53 ng/ml and 113+/-34 ng/ml (P<0.001), and 133+/-36 microM/L and 130+/-37 microM/L (NS), respectively. No rejection episodes occurred after steroid withdrawal. CONCLUSIONS: This open study shows that corticosteroids can be safely and successfully withdrawn from renal allograft recipients receiving CsA and mycophenolate mofetil.

Acute Disease↗
PubMed1997

Early protocol renal allograft biopsies and graft outcome.

To evaluate whether biopsies performed early after transplantation in stable grafts can predict graft failure due to chronic transplant nephropathy, a protocol biopsy was performed at three months in 98 patients treated with antilymphocytic antibodies, cyclosporine and prednisone. Patients were followed for 58 +/- 16 months. Histological diagnosis according to the Banff schema were: normal (N = 41), borderline changes (N = 12), chronic transplant nephropathy (CTN; N = 30), CTN associated to borderline changes (N = 11) and acute rejection (N = 4). Biopsies displaying acute rejection were not considered for statistical analysis. Since clinical characteristics of patients displaying CTN either with or without tubulitis were not different, biopsies were grouped as presence or absence of CTN. Patients displaying CTN had an increased incidence of acute rejection before performing biopsy (24.3 vs. 3.9%, P = 0.003), a higher mean cyclosporine level until biopsy (242 +/- 74 vs. 214 +/- 59 ng/ml, P = 0.049) and a lower actuarial graft survival (80.5% vs. 94.4%, P = 0.024). We conclude that early protocol biopsies are useful to detect patients at risk of losing their graft due to chronic transplant nephropathy.

Adult↗
PubMed1996

Association of quantitative cytomegalovirus antigenemia with symptomatic infection in solid organ transplant patients.

A prospective virologic follow-up of solid organ transplant patients was designed to determine the usefulness of antigenemia and viremia as virologic markers for the diagnosis of cytomegalovirus (CMV) infections, and also for monitoring CMV disease and therapy control. A total of 629 blood samples from 127 patients (60 liver, 47 kidney, and 20 heart transplant recipients) were studied by tube and shell vial cultures, and by antigenemia assay. This later was carried out by an indirect immunofluorescent assay method for formalin-fixed cytospin slides containing 2 x 10(5) leukocytes, using a monoclonal antibody directed against the CMV pp65 antigen. CMV was detected by at least one of the three methods in 238 specimens (37.8%) from a total of 63 patients. The antigenemia assay was positive in 215 (90.3% of positive samples). A total of 94 samples were detected only by this marker, which occurred either in samples with low positive counts (70.2% with antigenemia counts < 10 positive cells/10(5) leukocytes) or in specimens from treated patients. There were 30 episodes of CMV disease in 23 patients. Antigenemia was positive in all these episodes, 27 of them with counts > 20 positive cells/10(5) leukocytes. With this cut-off, positive and negative predictive values for symptomatic CMV infection were 100% and 97.2%, respectively. The antigenemia assay is a rapid, sensitive, specific, and early marker of CMV infection in transplantees. Cultures became negative with antiviral therapy while remaining antigenemia detectable. There was an association between highest quantitative antigenemia test results and clinical symptoms in our patients. In its quantitative version, the assay is useful to detect symptomatic infection and appears to be a helpful tool in managing patients at risk and in guiding antiviral therapy.

Antigens, Viral↗
PubMed1996

Hepatitis C virus-associated membranoproliferative glomerulonephritis in renal allografts.

In renal transplantation, chronic allograft nephropathy is the leading cause of long-term graft losses, transplant glomerulopathy being its glomerular form. Differential diagnosis from recurrent or de novo membranoproliferative glomerulonephritis should be established. Whether hepatitis C virus is associated with cryoglobulinemia and glomerular damage in renal allograft recipients, as in native kidneys, is not known. We identified six hepatitis C virus-infected renal allograft recipients with proteinuria higher than 1.5 g/day, microhematuria, and membranoproliferative glomerulonephritis. Virologic and immunologic studies were conducted. Low serum levels of circulating immune complexes and cryoglobulins were observed, which were type II immunoglobulin G polyclonal-immunoglobulin Mk monoclonal in all six patients. Classical serum complement pathway activation and at least one type of autoantibodies were present in all of them. Hepatitis C virus RNA was found in higher concentrations in cryoprecipitate than in serum (percentage of enrichment ranged from 341 to 18,200%). Hepatitis C virus genotype was 1b in 4 of 6 patients, 1a in 1 of 6 patients, and 2a in 1 of 6 patients. In renal histology prominent parietal diffuse deposition of immunoglobulin M was the rule. Glomerular subendothelial electron-dense deposits with fibrillar appearance were observed in the two patients in which electron microscopy provided information about glomeruli. In renal allograft recipients hepatitis C virus infection may be associated with type II cryoglobulinemia which may lead to membranoproliferative glomerulonephritis. Immunologic and virologic studies may help to differentiate hepatitis C virus-associated membranoproliferative glomerulonephritis from transplant glomerulopathy.

Adult↗
PubMed1995

[Therapeutic immunoadsorption in Goodpasture disease].

The extraction of circulating antiglomerular basement membrane (GBM) antibodies by plasmapheresis (PP) has allowed the prognosis of Goodpasture's disease to markedly improve. Immunoabsorption (IA) may improve the results of PP upon allowing more effective immunoglobulin extraction. Two patients with Goodpasture disease were treated with IA. A rapid decrease was observed in the serum levels of anti GBM antibodies and improvement in respiratory failure. In one of the patients this regimen was administered following the observation of a lack of clinical response of pulmonary hemorrhage in three PP sessions (9 liters of treated plasma). In this patient, the IA processed 39 liters of plasma and the method was found to be equally effective on reinstatement (29 liters) on the occasion of a relapse in the pulmonary symptoms presented at three weeks after the first treatment. Both cases showed renal involvement. In one case this was incipient and the treatment was associated with non progression of the kidney disease, normalization of the urine sediment and preservation of renal function. In the second case treatment was initiated at an advanced disease state with no changes in dialysis needs. Immunoadsorption has shown to be effective in the treatment of pulmonary hemorrhage in Goodpasture's disease. Onset of treatment at an early stage of the kidney disease may avoid progression to renal failure.

Adult↗
PubMed1995

Evaluation of a preservation solution containing fructose-1,6-diphosphate and mannitol using the isolated perfused rat kidney. Comparison with Euro-Collins and University of Wisconsin solutions.

The renal preservation ability of a flushing solution (F-M) with fructose-1,6-diphosphate (1 g/dl) and mannitol (2 g/dl) during cold ischaemia was studied with the isolated perfused rat kidney model and compared with the Euro-Collins (EC) and University of Wisconsin (UW) solutions. Kidneys were stored in hypothermia for 4 and 18 h after initial flushing with the solution being tested, and then reperfused at 37 degrees C in an isolated perfusion circuit for 90 min with a Krebs-Henseleit solution containing 4.5% albumin. Forty-four kidneys were studied and divided in a control group and six study groups according to the cold ischaemia time and flushing solution used. Renal functional parameters of plasma flow rate (PFR), renal vascular resistance (RVR), urine flow rate (UFR) glomerular filtration rate (GFR), fractional (FRNa) and net (TNa) sodium reabsortion were assessed during reperfusion. Conventional histology and malondialdehyde tissue levels (MDA) were also evaluated. Our results show that PFR, RVR, and UFR were similar in all study groups. After 4 and 18 h of cold ischaemia, GFR, FRNa and TNa were better, and conventional histology worse in F-M than in EC flushed kidneys. After 4 and 18 h of cold ischaemia, GFR, FRNa and TNa, in fact, were not different between F-M and UW flushed kidneys. After 4 h of cold ischaemia, conventional histology was similar in F-M and UW flushed kidneys. Nevertheless, after 18 h of cold ischaemia, UW flushed kidneys showed worse histological parameters than F-M flushed kidneys. After 4 h of cold ischaemia, MDA was similar in kidneys flushed with three solutions. After 18 h of cold ischaemia MDA was higher in EC than in F-M or UW flushed kidneys. In summary, our newly developed cold storage solution shows promising results in renal preservation and its ability to preserve is at least as good as UW solution assessed in the isolated perfused rat kidney.

Adenosine↗