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F Citterio

Publications and source records attributed to F Citterio.

At least 19 recordsLinked to original sources
PubMed2006

Lymphocele after renal transplantation: the influence of the immunosuppressive therapy.

Lymphocele is a complication of renal transplantation, representing a lymphatic collection around the grafted kidney. The use of the immunosuppressive agent sirolimus (SRL) has been associated with a significant increase in lymphocele formation. This complication has been related to the antiproliferative activity of SRL, which delays surgical wound repair and closure of injured lymphatic vessels. The aim of this study was to relate the incidence of lymphocele with immunosuppression among 158 renal transplant patients operated with routine closure of all the visible lymphatic vessels around the iliac vessels and at the renal hilum. The incidence of lymphocele was not significantly different among the various immunosuppressive regimens.

Drainage↗
PubMed2006

Incidence of posttransplant diabetes mellitus in kidney transplant recipients immunosuppressed with sirolimus in combination with cyclosporine.

Sirolimus (SRL) in combination with Cyclosporine A (CsA) and steroids has been shown to lower the incidence of acute renal allograft rejection episodes, allowing CsA sparing. We retrospectively compared the incidence of posttransplant diabetes mellitus (PTDM) among kidney transplant recipients (KTx) immunosuppressed with SRL + CsA versus CsA alone. Patients were divided into two groups: SRL + CsA (n = 38) versus CsA (n = 48). Mean follow-up was 53.9 +/- 17.1 months. Seventeen/86 subjects (19.8%) developed diabetes after transplantation (7 IFG, 8.1%; 10 PTDM, 11.6%). The incidence was significantly higher in SRL + CsA (12/38 patients, 31.6%) compared with CsA (5/43 patients, 10.4%) (P = .0144, odds ratio 3.97). More patients required treatment in the SRL + CsA compared to CsA alone cohort (13.2% vs 2.1%, P = .051): 4 pts (10.5%) became insulin- dependent among SRL+CsA, vs none in the CsA group. Use of OHD was similar in both groups (2.6% SRL + CsA vs 2.1% CsA). There were no significant differences between the two groups in terms of age, sex distribution, BMI, or serum creatinine at 1 to 3 and 5 years from transplantation. All PTDM patients are alive at follow-up, while two grafts were lost due to chronic renal allograft dysfunction. Within the limits of a small retrospective study, we observed that SRL in combination with CsA increased the diabetogenic potential of CsA. A possible explanation of our findings is that higher CsA doses were used in the early experience with SRL + CsA; therefore the higher incidence of PTDM that we observed in the SRL + CsA combination may be a sign of toxicity. Careful monitoring of blood levels is mandatory in the SRL + CsA combination to avoid pleiotropic toxicity.

Adult↗
PubMed2006

Immunosuppression and cancer: A comparison of risks in recipients of organ transplants and in HIV-positive individuals.

The comparison of cancers occurring excessively among HIV-infected and transplanted individuals may help to elucidate the relationship between immune surveillance, viral infections, and cancer. A longitudinal study was conducted on 2002 HIV-infected Italian subjects, 6072 HIV-infected French individuals, and 2878 Italian recipients of solid organ transplants. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were computed to quantify the risk for cancer, compared with the French and Italian general populations. The SIRs for all cancers were 9.8 (95% CI: 9.0-10.6) for HIV-infected individuals versus 2.2 (95% CI: 1.9-2.5) for transplant recipients. In both groups, most of the excess risk was attributable to virus-related cancers, such as Kaposi's sarcoma (KS; SIR = 451 in HIV-positive individuals, 125 in transplant recipients), non-Hodgkin's lymphoma (NHL; SIR = 62.1 and 11.1, respectively), and liver cancer (SIR = 9.4 and 4.1, respectively). Significantly increased SIRs for anal cancer and Hodgkin's lymphoma were found only among HIV-positive individuals. Among women younger than 40 years of age, a more than 10-fold increase in cervical cancer risk was found in both groups. Among HIV-infected individuals treatment with highly active antiretroviral therapies drastically reduced SIRs for KS and NHL only. These results show that HIV-infected individuals and transplant recipients share a similar pattern of cancer risk, largely due to virus-related cancers.

Cohort Studies↗
PubMed2005

Addition of sirolimus to cyclosporine in long-term kidney transplant recipients to withdraw steroid.

The aim of this study was to evaluate the feasibility of a steroid-free maintenance immunosuppression regimen in long-term renal transplant (KTx) recipients after addition of sirolimus (SRL) to cyclosporine (CsA)-based immunosuppression. A multicenter, prospective pilot study of steroid withdrawal (SW) was initiated for KTx patients. SW was divided into three phases: (A) conversion to a SRL + CsA + steroid regimen; (B) steroid tapering and withdrawal; and (C) maintenance with SRL + CsA. Primary endpoints of the study were incidence of acute biopsy-proven rejection (AR) and safety. In the A and B phases of the study 42 KTx patients (132 +/- 75 months post-Tx) were entered into the study, 18 of 42 (43%) with severe, acute side effects due to the CsA + SRL combination. These side effects were reversible with reduction of CsA or with suspension of the SRL/CsA combination. An amendment was introduced in the protocol to drastically reduce the CsA exposure to <50 ng/mL (trough) at the time of SRL addition. After this amendment, 39 other KTx patients entered the study and only 3 of 39 (8%) were discontinued because of toxic side effects. In the overall cohort of 81 KTx patients, the incidence of AR after SW was low (n = 5, 6.1%), all occurring within the first 3 months after SW. These findings indicate: (1) addition of SRL to very low-maintenance CyA exposure allows safe SW in KTx; (2) with the SRL + CsA combination, the incidence of AR after SW is low in long-term KTx patients; and (3) in the first 3 months after SW strict monitoring for early diagnosis and treatment of AR is mandatory.

Adrenal Cortex Hormones↗
PubMed2005

Severe limb lymphedema in sirolimus-treated patients.

We report two kidney transplant recipients who developed severe limb lymphedema under sirolimus (SRL) immunosuppression. The patients received SRL 10 and 2 mg/d to achieve target levels of 10 to 20 ng/mL with tapering doses of prednisone. Renal function and drug levels were monitored monthly. Patient 1 developed lymphedema of the left upper limb 3 years posttransplantation, after having been exposed to high SRL doses in the preceding 2 years (mean SRL dose-9.5 mg/d, mean trough level-26.3 ng/mL, mean serum creatinine-1.63 mg/dL). In patient 2 lymphedema of both upper and lower right limbs occurred 18 months posttransplantation (mean SRL dose-3.2 mg/d, mean trough level-8.8 ng/mL, mean serum creatinine-2.9 mg/dL). Hypercholesterolemia and hypertriglyceridemia were also observed in both patients before SRL reduction/conversion. No signs of hematopoietic toxicity were observed. In both patients magnetic resonance (MR) angiography of the limb was negative for vascular obstruction, and lymphoscintigraphy revealed lymphatic obstruction. In patient 1 lymphedema improved significantly following SRL reduction and lymphatic drainage massage therapy. Patient 2 was converted to cyclosporine (CsA) improving markedly after conversion. Hypercholesterolemia and hypertriglyceridemia also improved significantly in both patients after reduction/conversion. We conclude that SRL may facilitate the occurrence of lymphatic obstruction by mechanisms that are presently unexplained. Lymphedema of the limbs in renal transplant recipients under SRL treatment, especially if on the same side as the hemodialysis access, should warn the transplant physician to rapidly reduce or withdraw SRL before the occurrence of complete obstruction.

Adult↗
PubMed2005

Gonadal function and immunosuppressive therapy after renal transplantation.

UNLABELLED: End-stage renal disease is associated with disorders in hypothalamic-pituitary-gonadal function. Immunosuppressive therapies may influence the restoration of normal levels of gonadal hormones after renal transplantation. The aim of the present study was to evaluate the hormonal status of successful renal transplant recipients who were treated with different immunosuppressive agents. METHODS: Testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured in 59 male renal transplant recipients with stable graft function with serum creatinine <2.5 mg/dL. Patients were treated with three different immunosuppressive regimens: group I, calcineurin inhibitors (CI; n = 15), group II, sirolimus without calcineurin inhibitors (SRL; n = 15), group III, sirolimus in combination with calcineurin inhibitors (SRL * CI; n = 29). RESULTS: Testosterone was significantly lower in group II versus group I (3.12 +/- 1.23 versus 4.39 +/- 1.53 ng/mL; P < .0197). Group III had higher testosterone values than group II, but lower than group I. FSH and LH were also higher in the SRL group, but the differences were not statistically significant, perhaps because of the small number of patients. No relationship was found between testosterone blood levels and age, posttransplant follow-up, renal function, time on dialysis, body mass index, steroid use, or posttransplant diabetes. CONCLUSION: Sirolimus seems to impair the improvement of gonadal function after renal transplantation. Further prospective studies are needed to confirm these data before patients are advised of this potential side effect.

Creatinine↗
PubMed2004

Evolution of the therapeutic drug monitoring of cyclosporine.

The argument for the therapeutic monitoring of cyclosporin A (TDM-CyA), to optimize efficacy and safety, has been discussed in the last 25 years and it is still debated. Although CyA has been for more than 20 years the mainstay of immunosuppression in organ transplantation, no consensus has yet been achieved on TDM-CyA. The first proposed use of CyA was at fixed doses, but this was soon abandoned, and the predose, trough C0 blood level concept was introduced as a tool for TDM-CyA; however, no correlation could ever be shown between the various proposed trough therapeutic windows and major clinical events. On the contrary, the TDM-CyA of full area-under-the-curve (AUC) 0-12 exposure, significantly correlated with acute rejection and renal toxicity. The use of Neoral demonstrated that the region of most variability in CyA pharmacokinetics and the greatest calcineurin inhibition were confined within the AUC0-4, introducing the concept of absorption profiling. A further simplification come from the demonstration that C2, the single blood concentration measurement 2 hours after Neoral administration, was a significant accurate predictor of AUC0-4. The TDM-CyA with C2 has now been clinically validated in kidney, liver, and heart transplant recipients. In the last 25 years of TDM-CyA, some concepts have become clear: inadequate CyA exposure is a key risk factor for acute rejection and may contribute to the development of chronic rejection; C0 predose monitoring does not accurately measure CyA exposure. Thus, C2 single sampling offers today an innovative, simple, and accurate alternative for the pharmacokinetic clinical monitoring of CyA.

Area Under Curve↗
PubMed2004

Posttransplant diabetes mellitus after kidney transplantation with different immunosuppressive agents.

Posttransplant diabetes mellitus (PTDM) is a disturbing side effect of immunosuppression. The aim of this study was to evaluate the effect of different immunosuppressive agents on the development of PTDM in renal transplant recipients (KTx). The incidence of PTDM was evaluated in 538 consecutive KTx. Baseline immunosuppression was azathioprine (AZA), cyclosporine (CSA), or tacrolimus (TAC), or sirolimus in combination with calcineurin inhibitors (SIR). All patients received steroids for both induction and maintenance therapy during the first 6 months posttransplantation. Mean follow-up after KTx was 73 +/- 53.5 months (range 6 months to 16 years). PTDM was defined as two consecutive blood glucose determinations above 126 mg/dL. Thirty-six of 538 (6.7%) recipients experienced PTDM, 31 of whom required insulin treatment and five oral antidiabetic medications. PTDM occurred at 25.3 +/- 38 months posttransplantation in 4.8% of KTx treated with AZA, 4.8% of CSA, 6.5% of KTx treated with TAC and 12.5% of KTx treated with SIR. The time of onset of PTDM was significantly shorter (P =.003) among TAC (2.1 +/- 1.7 months posttransplantation) versus CSA (27.8 +/- 34 months). PTDM disappeared in 6 of 36 patients. We conclude that with current levels of immunosuppression, there is no difference in the incidence of PTDM between TAC- and CSA-treated KTx.

Administration, Oral↗
PubMed2004

Plasma levels of transforming growth factor-beta1 in renal transplant recipients receiving different immunosuppressive regimens.

Experimental and clinical evidence support the role of transforming growth factor beta-1 (TGF-beta(1)), a cytokine with complex immune and nonimmune effects, on the development of chronic renal allograft nephropathy (CAN). We investigated the effects of different immunosuppressive regimens on circulating TGF-beta(1) plasma levels in stable kidney transplant (KTx) recipients. Two hundred ninety-nine TGF-beta(1) plasma levels were measured in 125 kidney transplant (KTX) recipients exhibiting stable renal function, immunosuppressed with cyclosporine (CsA), tacrolimus (TAC), or sirolimus (SIR), and in 18 normal healthy volunteers (C). Activated immunoreactive TGF-beta(1) was detected in platelet-depleted plasma by an enzyme-linked immunoadsorbent assay. Multivariate analyses correlated immunosuppressive regimens with TGF-beta(1) levels. KTX recipients displayed significantly higher TGF-beta(1) levels compared to C (P =.0005). Patients receiving CsA had significantly higher TGF-beta(1) plasma levels compared to those receiving TAC or SIR (P =.0384). Multivariate analyses showed no correlation between TGF-beta(1) levels and immunosuppressive drug trough blood levels or doses, but only correlations with the main immunosuppressive drug. These data show that: (1) TGF-beta(1) production is activated in kidney transplant recipients; (2) CsA patients display significantly higher plasma TGF-beta(1) levels. Follow-up studies seek to assess the possible relationship with clinical events.

Graft Survival↗
PubMed2004

C2 is an age-independent parameter for optimal cyclosporine exposure in long-term kidney transplant recipients.

The argument for therapeutic drug monitoring (TDM) of cyclosporine (Cya) has been discussed for the last two decades. So far, a generalized consensus has been reached for TDM of Cya microemulsion in adult transplant recipients, being Cya blood levels obtained 2 hours after the administration (C2), the most reliable in reflecting the overall Cya exposure. However, clear guidelines are not available for the pediatric population because of the distinct metabolism of the drug in this patient population. Therefore, adult data do not necessarily apply to children. In this retrospective analysis, the authors sought to define a universal parameter for pharmacokinetic clinical monitoring of Cya in long-term kidney transplant recipients, regardless of their age. Lower C2 levels were observed in all patients, adult and pediatric, who eventually developed chronic allograft dysfunction (CRAD) compared with patients who maintained stable kidney function throughout the entire follow-up (pediatric CRAD, 933 +/- 455 ng/mL; vs Stable, 1236 +/- 347 ng/mL, P = .0001; and adult CRAD, 781 +/- 518 ng/mL; vs Stable, 1088 +/- 452 ng/mL, P = .009). On the other hand, the risk of Cya underexposure was not highlighted by trough level monitoring (C0) because all patients have been maintained steadily on therapeutical C0 levels for the entire follow-up. In conclusion, for Cya maintenance therapy, C2 appears to be a superior strategy to C0 monitoring in both adult and pediatric kidney transplant recipients.

Adolescent↗
PubMed2003

Long-term predictive value of cyclosporine microemulsion C2 level for chronic renal allograft dysfunction.

This observational study was undertaken in maintenance renal transplant recipients to assess the relationship between cyclosporine C(2) and the long-term risk of chronic renal allograft dysfunction (CRAD). Pharmacokinetic profiling was undertaken twice yearly in 79 patients with stable graft function receiving cyclosporine microemulsion (Neoral) and steroids. Mean time since transplantation at study entry was 56 +/- 49 months posttransplant. At the end of the observational period (mean 43 +/- 14 months) 24 patients (30%) had developed CRAD, defined as proteinuria > 500 mg/24 hours associated with a rising serum creatinine and confirmed by graft biopsy. There were no significant differences at baseline between patients who did vs did not develop CRAD, except for reduced incidence of acute rejection in CRAD-free patients. The cyclosporine AUC was significantly higher among patients without CRAD (5707 ng. h/mL vs 3994 ng. h/mL, P =.0007). Mean C(2) was also significantly higher: 1001 ng/mL in the CRAD-free group versus 640 ng/mL in the CRAD group (P =.002). There was no significant difference in C(0). Regression analysis showed that the best predictors for the occurrence of CRAD were a low AUC (relative risk [RR] 1.54, P <.0001), a low C(2) (RR 1.30, P <.0001) and proteinuria (RR 4.95, P <.0001). Probability of freedom from CRAD was 90% for C(2) > 900 ng/mL. C(2) appears to be a superior strategy to C(0) monitoring of cyclosporine in stable renal transplant patients with regard to the risk of CRAD. C(2) values above 900 ng/mL are appropriate to minimize the risk of CRAD among patients receiving cyclosporine microemulsion and steroids.

Adult↗
PubMed2003

Design of a trial comparing sirolimus plus mycophenolate mofetil versus sirolimus plus cyclosporine.

We present the study design of a prospective, multicenter, randomized trial aimed at comparing the effects of two different combinations of sirolimus. Renal transplant recipients will be allocated to receive either sirolimus and mycophenolate mofetil (group A) or sirolimus and cyclosporine (group B). The primary endpoint will be the graft function at 3, 6, 12, 24, 36, 48, and 60 months. A number of secondary endpoints will also be considered. To obtain a significant difference in the primary endpoint 180 patients will be enrolled.

Adult↗