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J M Campistol

Publications and source records attributed to J M Campistol.

At least 19 recordsLinked to original sources
PubMed2006

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↗
PubMed2006

[Usefulness of 111In-oxine labelled platelets in the management of febrile syndrome in dialysis patients with non-functional renal allografts].

AIM: To evaluate the usefulness of 111In-oxine-labelled platelet scan in the therapeutic management of prolonged febrile syndrome in dialysis patients with a non-functional renal allograft. MATERIAL AND METHODS: One hundred and fifty-eight patients (94 men, 64 women; mean age 44 +/- 9 years) were studied. Duration of fever was 42 days (range 7-112). A total of 68 % of the patients (107/158) were on low doses of corticosteroids (<10 mg/day). Platelet scans were performed 48 hours after reinjection of 111In-ixone-labelled platelets. A platelet uptake index (PUI) was calculated by dividing the cpm/pixel in the allograft by the cpm/pixel in a mirror background. A PUI > or = 1.5 was considered as threshold for immunological fever. The final diagnosis of immunological fever was established when it disappeared after transplantectomy, embolization or high doses of corticosteroid therapy. Fever of non-immunological origin was established when it disappeared after antibiotic therapy. RESULTS: In 102/158 patients the fever was considered of immunological origin. In 56/158 patients the fever was considered of non immunological origin. Sensitivity and the specificity of the platelet scan was 80 % and 100 %, respectively. All those patients considered as having fever of immunological origin who had PUI <1.5 had been using corticosteroids during platelet scan. CONCLUSION: 111In-labelled platelet scintigraphy is a useful technique in the therapeutic management of prolonged febrile syndrome in dialysis patients with non-functional renal allograft. The use of corticosteroids can reduce the sensitivity of 111In- labelled platelet scan.

Adrenal Cortex Hormones↗
PubMed2005

Sirolimus-based therapy with or without cyclosporine: long-term follow-up in renal transplant patients.

This open-label, phase 3b, extension trial in renal transplant recipients (Sirolimus Study 311) assessed the long-term safety of sirolimus (SRL) administered with cyclosporine (CsA) (SRL + CsA group, n = 98) or without CsA (SRL group, n = 69). Renal transplant recipients who had either completed one of seven previous SRL studies sponsored by Wyeth Research or had participated for > or =3 months and reached a protocol-designated endpoint were eligible for enrollment. Data were available for 167 patients, all of whom initially received steroids. Mean total SRL exposure was 1526 days, including previous study participation. After enrollment in the extension study, there were significantly more acute rejections in the SRL + CsA group (6.1% vs 0%, P < .05). Differences in rates of graft loss (3.1% vs 1.4%) and death (6.1% vs 1.4%) were not significantly different between SRL + CsA and SRL groups, respectively. At 48 months after transplantation, calculated GFR (53.4 vs 70.9 mL/min) and hemoglobin (124.9 vs 136.6 g/L) were significantly better in the SRL group. Lipid values were not significantly different between groups at 48 months. The incidence of treatment-emergent increased creatinine, anemia, hypertension, headache, epistaxis, abnormal kidney function, and upper respiratory infection were significantly higher in the SRL + CsA group, whereas no adverse events were significantly higher in the SRL group. Malignancies were reported more frequently (11.2% vs 0%) with SRL + CsA. Results from this extension study indicate that SRL-based therapy without CsA is a safe alternative to combination therapy with CsA, offering long-term improvement in renal function with no increased risk of late acute rejection.

Adult↗
PubMed2005

Effect of apolipoprotein B polymorphism in kidney transplantation.

INTRODUCTION: In kidney transplant recipients, dyslipidemia is a cardiovascular risk factor that also contributes to the development and progression of chronic allograft nephropathy. Apolipoprotein B (ApoB), present in low-density lipoproteins (LDL), is an important protein component of chylomicrons and very-low-density lipoproteins (VLDL). The del allele of the ApoB signal peptide polymorphism has been associated with elevated levels of total and LDL cholesterol and greater risk of coronary disease. OBJECTIVE: The objective of this study was to assess the influence of ApoB polymorphism on allograft and patient survival among kidney transplant recipients. METHODS: In this study, we analyzed 516 renal transplant recipients (38% were women, 62% were men), aged 46 +/- 15 years, with a minimum follow-up of 12 months (mean, 1854 +/- 806 days). The ApoB signal peptide was analyzed (insertion/deletion) using polymerase chain reaction (PCR) using genomic DNA. Clinical donor-recipient variables were assessed using a Cox multivariate model. RESULTS: Polymorphism distribution was as follows: insertion/insertion (ins/ins) 51%, insertion/deletion (ins/del) 39%, and deletion/deletion (del/del) 9%, with no differences between the genders. Cholesterol levels at 12 months showed no differences between the ins/ins (217 +/- 46), ins/del (228 +/- 50), and del/del (227 +/- 54) groups. Presence of the ApoB signal peptide del/del or ins/del genotype was independently associated with lower patient survival in the group of men younger than 60 years (P < .05). Among the total deaths, cardiovascular causes predominated in the ins/del and del/del groups (50%) as compared with the ins/ins group (33%) (P < .01). CONCLUSIONS: ApoB genetic polymorphism (del allele) seems to have an adverse effect on the long-term survival of kidney transplant recipients.

Adult↗
PubMed2005

Evolution of proteinuria after conversion from calcineurin inhibitors (CNI) to sirolimus (SRL) in renal transplant patients: a multicenter study.

Conversion from calcineurin inhibitors (CNI) to sirolimus (SRL) has become an option in patients with chronic allograft nephropathy or other conditions. However, in some cases an increase of proteinuria has been reported after such therapeutic intervention. The aim of this study was to characterize the clinical course of this so far unexplained proteinuria after conversion. We performed a retrospective analysis evaluating 94 renal transplant patients from various Spanish centers. Proteinuria (629 determinations) and clinical developments were analyzed between 6 months before and 6 months after conversion. Patients were divided into three groups according to mean proteinuria before conversion (group A: <300 mg/d; group B: 300 to 2000 mg/d; and group C: >2 g/d). The mean proteinuria level was 1.69 g/24 h (n = 312 determinations) before and 2.36 g/24 h after conversion (n = 317 determinations; P = .006), which corresponds to an overall increase of 25% (1.55 to 1.69 g/24 h considering only determinations of 1 month before and 1 month after conversion; P = NS). We could not detect any clear correlation between proteinuria and serum creatinine nor between changes of proteinuria and changes of serum creatinine. A variance analysis for repeated measures showed an increase in proteinuria compared to the preconversion values (P = .003), and when the three groups of preconversion proteinuria were evaluated separately it could be observed that this change in the evolution of proteinuria was almost completely dependent of an increase in the group C (preconversion proteinuria greater than 2 g/d; P = .03), whereas in the other two groups changes were almost irrelevant. Finally, the switch to SRL in renal transplant recipients is followed by an increase in the level of proteinuria predominantly dependent of an increase in patients with high levels of preconversion proteinuria, whereas it seems to be irrelevant in patients without or with light or moderate proteinuria. These results suggest that this might not be a direct effect of SRL.

Calcineurin Inhibitors↗
PubMed2005

Efficacy of conversion to sirolimus in posttransplantation Kaposi's sarcoma.

UNLABELLED: The increased incidence of Kaposi's sarcoma (KS) in organ transplantation has been related to the KS herpes virus and the permissive effect of immunosuppressive therapy. We postulated that conversion to SRL in renal recipients with KS favored regression of KS lesions without increasing the risk of graft rejection. METHODS: In this study we performed a retrospective chart review of 7 caucasian renal transplant recipients affected by KS to determine demographic data, etiology of ESRD, immunologic risk factors, immunosuppressive treatment, KS disease follow-up, and renal function before and after SRL conversion. RESULTS: All seven patients were under calcineurin inhibitor treatment at the onset of KS which was limited to the skin, without regression despite attempts to minimize immunosuppression. After conversion to SRL, six patients showed progressive regression of KS lesions, with only hyperpigmented atrophic cutaneous lesions remaining after a mean time of 8.1 months (2-18 months). The seventh patient has completed 9 months follow-up with a near complete regression of KS lesions. One patient returned to hemodialysis after 13 months following irreversible acute renal failure not directly related to SRL conversion; in the other six, renal function was stable. The mean serum creatinine was 1.87 +/- 0.64 versus 1.74 +/- 0.68 mg/dL, pre-conversion versus the end of follow up, respectively. Mean SRL blood level was 9.2 +/- 2.0 ng/mL. CONCLUSION: After SRL conversion, patients with KS showed progressive regression without an increased risk of acute rejection. SRL offers a promising approach to the management of posttransplantation KS and probably other malignancies in organ transplant recipients.

Animals↗
PubMed2005

Kidney-specific proteins in patients receiving aprotinin at high- and low-dose regimens during coronary artery bypass graft with cardiopulmonary bypass.

BACKGROUND AND OBJECTIVE: The aim was to determine whether the administration of aprotinin can cause deleterious effects on renal function in cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Sixty consecutive patients with normal preoperative renal function undergoing elective coronary artery bypass surgery with CPB using the same anaesthetic; CPB and surgical protocols were randomized into three groups. Patients received placebo (Group 1), low-dose aprotinin (Group 2) or high-dose aprotinin (Group 3). Renal parameters measured were plasma creatinine, alpha1-microglobulin and beta-glucosaminidase (beta-NAG) excretion. Measurements were performed before surgery, during CPB and 24 and 72 h, and 7 and 40 days postoperatively. RESULTS: In the three groups, alpha1-microglobulin and beta-NAG excretions significantly increased during CPB, at 24 and 72 h, and 7 days postoperatively (P < 0.05) and had returned to preoperative levels at postoperative day 40. Plasma creatinine levels were within normal values at times recorded. In Groups 2 and 3, alpha1-microglobulin excretion during CPB was significantly higher than in Group 1 (P < 0.001), and 24h after surgery it still remained significantly higher in Group 3 compared to Groups 1 and 2 (P < 0.05). CONCLUSIONS: Aprotinin caused a significant increase in alpha1-microglobulin excretion but not in beta-NAG excretion during CPB, which may be interpreted as a greater renal tubular overload without tubular damage. This effect persisted for 24 h after surgery when high-dose aprotinin doses had been administered. Creatinine plasma levels were not sensitive to detect these prolonged renal effects in our study.

Acetylglucosaminidase↗
PubMed2005

[Pharmacogenetics of angiotensin system in non diabetic nephropathy].

BACKGROUND: Genetic variability could contribute to the response to pharmacological treatment in patients with nephropathy. In albuminuric diabetic patients the renoprotective effect of angiotensin I-converting enzyme (ACE) inhibition should be lower among homozygotes for the deletion allele (DD) compared to II-homozygotes. METHODS: A total of 71 non-diabetic chronic nephropathy patients were treated with losartan (n = 37) or amlodipine (n = 34). Blood pressure and proteinuria were determined before and after the treatment, and changes in the mean values were statistically compared. Patients were genotyped for the ACE-I/D, angiotensin I receptor type 1 (AGTR1)-1166 A/C, and angiotensinogen (AGT)-M235T polymorphims, and the reduction of blood pressure and proteinuria between the different genotypes were compared. RESULTS: The reduction in systolic or diastolic blood pressure was not found to be different between the ACE-I/D or AGT-M/T genotypes in patients treated with losartan or amlodipine. In patients treated with losartan, we found a significantly higher reduction of diastolic blood pressure in AGTR1-AA patients compared to AC patients (p = 0,0024). We did not find differences in proteinuria-reduction between the different genotypes in patients treated with losartan or amlodipine. CONCLUSIONS: Our data show that the effects of losartan and amlodipine on the absolute mean reduction of blood pressure and proteinuria in non-diabetic nephropathy patients are similar between the different ACE or AGT genotypes. Although based on a small number of patients, the AGTR1-AA genotype was associated with a significantly higher reduction in diastolic blood pressure among losartan-treated patients. Additional studies are necessary to refute or confirm this association.

Adult↗
PubMed2004

Cigarette smoke concentrate increases 8-epi-PGF2alpha and TGFbeta1 secretion in rat mesangial cells.

Epidemiological studies have shown that cigarette smoke, an oxidant agent, is a risk factor for the development of diabetic nephropathy (DN), in which pathogenesis transforming growth factor beta(1) (TGFbeta(1)) plays a key role. In our experimental model we exposed mesangial cell cultures to cigarette smoke concentrate (CSC) to study the effect of smoking on the pathogenesis of DN. Thus, we analyzed the effect of CSC on TGFbeta(1) and lipid peroxidation (8-epi-PGF(2alpha)) in rat mesangial cells. Furthermore, since the protein kinase C (PKC) pathway appears to be a key factor for the enhanced production of TGFbeta(1), we also analyzed the effect of the selective PKCbeta inhibitor LY379196 on TGFbeta(1) response to CSC. CSC induced an increase of both TGFbeta(1) and 8-epi-PGF(2) compared to basal conditions (5 mM glucose). The CSC-induced increase in TGFbeta(1) secretion was significantly suppressed by LY379196. These data suggest that smoking could increase TGFbeta(1) production, probably due to oxidative stress and PKCbeta activation. This finding supports the concept that smoking is a risk factor for DN development.

Animals↗
PubMed2004

New concepts in cyclosporine pharmacokinetic and dynamic monitoring: the impact of concomitant immunosuppression on target C2 concentrations.

BACKGROUND: There is a correlation between cyclosporine (CsA) pharmacokinetics (PK) and pharmacodynamics (PD), especially 2 hours after drug administration. AIM: To evaluate the relationship between CsA PK and PD profiles in two groups of stable renal transplant patients treated with CsA alone or CsA plus mycophenolate mofetil (CsA+MMF), so as to define the best target for C2 and clarify the impact of concomitant immunosuppression. METHODS: Thirty-eight stable renal transplant recipients were treated with CsA (n=20) or CsA+MMF (n=18). Twelve nontreated normal healthy controls (NHC) were also included. Calcineurin activity (CNa), IL-2 production, and CsA levels were measured at 0 and 2 hours postdose. RESULTS: There were no significant differences in median CsA C2 values and CNa between the CsA alone and the CsA+MMF groups (388 microg/L and 497.5 microg/L and CNa 2h; 3.92% alkaline phosphatase [AP]; 3.94% AP, respectively). In vitro production of IL-2 was significantly lower in the CsA+MMF group than in the CsA group (median IL-2 2h: 280.52 ng/L, 169.48 ng/L, P<.001). The correlations (r) between C2 and CNa 2h were: CsA r=0.74; CsA+MMF r=0.84 (P<.001 in both cases). CONCLUSIONS: In stable renal transplant patients, median CsA C2 values below 500 microg/L were associated with inhibition of CNa and IL-2 synthesis. CNa and IL-2 production may be good biological markers of CsA immunosuppression. The measurement of CNa depends mainly on CsA concentration, whereas in vitro IL-2 production reflects the effect of both CsA and MMF. Further studies are necessary to define the optimal C2 target concentration and the possible impact of concomitant immunosuppression.

Calcineurin Inhibitors↗
PubMed2004

Lessons from cyclosporine monotherapy in renal transplantation: the impact of acute rejection on long-term allograft outcome.

UNLABELLED: The introduction of cyclosporine in kidney transplantation rapidly improved short and medium term graft and patient survival rates. Initially many trials used cyclosporine monotherapy to avoid steroid toxicity, but high acute rejection rates lead to a change in the immunosuppressant scheme. The use of prophylactic steroids significantly decreased acute rejection rates, but the long-term benefit of such a reduction has not been assessed. METHODS: Retrospective analysis of the impact of early acute rejection on long-term outcome (10 years) in 264 consecutive renal transplants performed in a single institution between 1986 and 1993 using cyclosporine monotherapy (CM) (n=139) versus cyclosporine and prednisone (CS) (n=125). Different protocols were used for elderly or immunological high-risk patients and for transplants with delayed graft function and therefore these patients are not included. The incidence and severity of acute rejection episodes and long-term patient and graft survivals were analyzed. RESULTS: At 1 year, acute rejection episodes showed significantly higher frequency in the CM group than in the CS group (72.66% vs 46.40%). Nevertheless, graft and patient survival rates were similar at 1, 5, and 10 years (Graft: 96.38%, 78.77%, and 59.84% vs 92.59%, 75.62%, and 53.44%; PATIENT: 99.27%, 95.06%, and 84.76% and 95.9%, 93.09%, and 88.28%). CONCLUSION: The addition of prophylactic steroids decreases the incidence of acute rejection but does not improve the long-term graft survival. These findings suggest that in an era of new immunosuppressants, fewer acute rejection episodes will be evident requiring more effort to detect and treat subclinical rejections.

Adult↗
PubMed2003

Reflex sympathetic dystrophy syndrome in renal transplanted patients under immunosuppression with tacrolimus.

Reflex sympathetic dystrophy syndrome (RSDS), which probably has a multifactorial etiology, may appear after kidney transplantation. Its clinical manifestations include severe periarticular pain with inflammatory signs, especially in knees and ankles, causing functional disability. Symptoms develop during the first 3 months after transplantation and usually disappear 3 to 6 months later without sequelae. In renal transplant recipients it has previously been related to immunosuppressive treatment with cyclosporine. Therefore we had suggested that introducing tacrolimus could be a therapeutic option. We now present four cases of RSDS in kidney transplant recipients treated with tacrolimus. All but one patient were receiving tacrolimus monotherapy, excluding other drugs that might have been involved to cause the syndrome. It is also interesting that one of our cases develop RSDS long after transplantation when immunosuppressive treatment was changed. Symptoms correlated with an increase in alkaline phosphatase and with bone scintigraphy findings. All patients recovered without sequels 3 to 6 months afterward. In conclusion, RSDS is a relevant osteoarticular complication in patients receiving either anticalcineurinic drug (CyA or tacrolimus), even under monotherapy or with a low steroid dose.

Adult↗
PubMed2003

Bicêtre hospital experience with sirolimus-based therapy in human renal transplantation: the Sirolimus European Renal Transplant Study.

In 11 European centers, first cadaveric renal allograft recipients were randomized to CsA (n = 42) or sirolimus (n = 41). Dosing of these agents was concentration-controlled and open-labeled. All patients received corticosteroids and azathioprine. At 12 months, graft survival (98% sirolimus vs 93% CsA), patient survival (100% vs 98%), and incidence of biopsy-confirmed acute rejection (41% vs 38%) were similar. Serum creatinine was lower with sirolimus, significantly (P </=.05) so at 3 and 4 months, and serum uric acid and magnesium were normal. Laboratory abnormalities were reported significantly more often with sirolimus, which included hypertriglyceridemia (51% vs 12%), hypercholesterolemia (44% vs 14%), thrombocytopenia (37% vs 0%), leukopenia (39% vs 14%), and, of lesser importance, increased liver enzymes and hypokalemia. These abnormalities improved 2 months after transplantation when the sirolimus target trough level was lowered from 30 to 15 ng/mL. Occurrence of cytomegalovirus was comparable (14% vs 12%), but incidence of herpes simplex (24% vs 10%, P =.08) and pneumonia (17% vs 2%, P =.03) were higher with sirolimus. No gingival hyperplasia was seen with sirolimus, tremor was rare, and hypertension was less frequent (17% vs 33%). Two malignancies were observed with CsA, none with sirolimus. Results at 12 months suggest that sirolimus can be used as base therapy in the prophylaxis of acute renal transplant rejection, and has a safety profile that differs from that of CsA.

Adrenal Cortex Hormones↗
PubMed2003

Cardiovascular risk factors of sirolimus compared with cyclosporine: early experience from two randomized trials in renal transplantation.

INTRODUCTION: Renal transplant recipients are at a higher risk of cardiovascular events, including death. This paper examines cardiovascular risk factors in two phase II studies comparing cyclosporine (CsA) with sirolimus-based therapy. METHODS: In two phase II studies, patients (n = 161) were randomized at the time of transplantation to receive either sirolimus or CsA in triple-therapy regimens with either azathioprine (Study A) or mycophenolate mofetil (Study B), and corticosteroids. Sirolimus whole blood trough levels were targeted to 30 ng/mL for 2 months and 15 ng/mL thereafter. Pooled results of the two studies are reported. RESULTS: When patients receiving sirolimus were compared with those receiving CsA, peak cholesterol and trigylcerides at 2 months were markedly and significant higher with sirolimus therapy. The difference between groups decreased thereafter and was not significant from 12 through 24 months. Control of lipid parameters in sirolimus-treated patients was achieved by decreasing the target trough levels after 2 months and by using lipid-lowering agents. Sirolimus-based therapy was associated with a lower incidence of treatment-emergent hypertension (47.5% vs 29.6%, P <.024). At 24 months, the calculated glomerular filtration rate was significantly better with sirolimus (51.3 vs 65.1 mL/min, P <.001). There were no significant differences in the incidences of diabetes or death due to cardiovascular events. CONCLUSION: Patients receiving sirolimus experience an initial increase in lipid levels, but these effects are manageable with the use of lipid-lowering agents. Hypertension was less frequent and renal function was improved with CsA-free, sirolimus-based therapy. Based on this early experience, overall cardiovascular risk does not appear to be increased with sirolimus-based compared with CsA-based therapy.

Cardiovascular Diseases↗
PubMed2003

Early elimination of cyclosporine in kidney transplant recipients receiving sirolimus prevents progression of chronic pathologic allograft lesions.

Cyclosporine elimination in a regimen including sirolimus has been shown to be a safe and effective approach to improve graft function. Nevertheless, it is still unknown whether the functional benefit of CyA withdrawal coincides with a subsequent reduction in histologic lesions of chronic damage or development of chronic allograft nephropathy. This consideration would forecast a reduction in the rate of long-term graft loss. We analyzed 114 graft biopsies from a subgroup of 57 patients that had been included in a randomized study to eliminate CyA at 3 months posttransplant from a regimen including sirolimus either in group A CyA + SRL vs group B of SRL with CyA elimination at 3 months. Every patient had two biopsies, one at transplantation and another at 1 year. The biopsy reading was performed in a blinded manner by a central pathologist using the Banff 1997 and the CADI classifications. A significantly lower rate of progression of tubular and interstitial chronic lesions between basal and 1-year biopsies was observed for group B patients. In addition, the incidence of new cases of chronic allograft nephropathy during the first year was significantly lower in the group in which CyA had been eliminated at 3 months posttransplant. We conclude that early elimination of CyA in the first months posttransplant, when SRL is used as the main immunosuppressant, reduces the appearance or worsening of chronic histologic lesions, probably as a consequence of long-term CyA toxicity prevention.

Biopsy↗