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In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n = 359) or remain on standard calcineurin inhibitor (CNI) therapy (n = 356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and steroids. The primary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, was similar for everolimus versus CNI: mean (standard error) 0.3(1.5) mL/min/1.73 2 versus -1.5(1.5) mL/min/1.73 2 (p = 0.116). Biopsy-proven acute rejection (BPAR) at month 12 was more frequent under everolimus versus CNI overall (9.7% vs. 4.8%, p = 0.014) and versus tacrolimus-treated patients (2.6%, p < 0.001) but similar to cyclosporine-treated patients (8.8%, p = 0.755). Reporting on de novo donor-specific antibodies (DSA) was limited but suggested more frequent anti-HLA Class I DSA under everolimus. Change in left ventricular mass index was similar. Discontinuation due to adverse events was more frequent with everolimus (23.6%) versus CNI (8.4%). In conclusion, conversion to everolimus at 10-14 weeks posttransplant was associated with renal function similar to that with standard therapy overall. Rates of BPAR were low in all groups, but lower with tacrolimus than everolimus., (© 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Left ventricular hypertrophy (LVH) regression after kidney transplantation may be influenced by immunosuppression. In a 24-month open-label, multicenter, phase-IV study, 71 kidney allograft recipients without previous acute rejection, showing eGFR >40 ml/min and proteinuria <500 mg/day and between 6 months and 3 years post-transplantation, were randomized to receive everolimus (EVR) + mycophenolic acid (MPA) or were maintained on tacrolimus (TAC) + MPA. The aim was to assess whether the conversion to EVR could reduce left ventricular mass index (LVMi) at month-24. LVMi at month-24 decreased without differences between groups (TAC: 54.0 vs. 48.2 g/m 2.7 ; EVR: 53.4 vs. 49.4 g/m 2.7 ). The LVH prevalence at baseline and month-24 was 59.4% and 40.6% in TAC group and 57.1% and 50.0% in EVR group. EVR conversion was associated with nearly disappearance of concentric LVH and concentric remodeling pattern. The procollagen type I N-terminal propeptide at month-24 showed greater reduction in EVR group (51.6 vs. 58.2 mg/l; P = 0.004). Conversion from TAC to EVR was associated with a significant improvement of eGFR (P = 0.0315, ancova). Adverse events were similar between groups without rejection episode or graft loss. Conversion from TAC to EVR did not further reduce LVMi after 24 months, although its effect on concentric LVH deserves further investigation (NCT01169701)., (© 2016 Steunstichting ESOT.)

Introduction: The relationship between anticalcineurin (CNI) drugs and the development new-onset diabetes mellitus after kidney transplantation (NODAT) is well established. Among these agents cyclosporine shows lesser diabetogenicity than tacrolimus. It has been described that conversion from tacrolimus to cyclosporine improves glycemic control; however, there are no studies showing whether this reduced risk is maintained upon long-term follow-up., Objective: To evaluate whether CNI drugs conversion from tacrolimus to cyclosporine helps to maintain better glycemic control., Materials and Methods: We retrospectively evaluated the evolution of glucose metabolism at 5 years after conversion from tacrolimus to cyclosporine in eight patients (six men) with NODAT. Mean age was 42.8 ± 15 years, and time after transplantation to conversion 128 ± 40 months. We analyzed fasting serum glucose, lipid metabolism, renal function, and cyclosporine levels at 0, 6, 12, 24, 36, 48, and 60 months after conversion., Results: At 6 months after conversion, improved glucose metabolism was observed (268 ± 161 versus 121 ± 31 mg/dL; P < .01) although it was minimal in one case with persistent high blood glycemic levels. Only two patients maintained a normal glucose at the end of follow-up. Five subjects showed increased glycemia at 12 to 24 months after conversion requiring antidiabetic therapy: three patients, insulin and two oral antidiabetic agents. Two patients lost their allografts due to chronic rejection at 32 and 50 months respectively. Among the other six patients, renal function remained stable (1.9 ± 0.6 versus 2.11 ± 0.97 mg/dL; P = NS). There was no significant differences among the other variables. Cyclosporine levels remained stable during the follow-up., Conclusion: Conversion of renal transplant patients with NODAT from tacrolimus to cyclosporine improves glucose metabolism in the short term but glycemia increases thereafter., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Tacrolimus is a well-established immunosuppressive agent for the treatment and prevention of solid organ graft rejection. It is available as an immediate-release, twice-daily formulation (Tacrolimus BID) and a prolonged-release, once-daily formulation (Tacrolimus QD). In a previous study of the pharmacokinetics (PK) of these formulations, mean systemic exposure [area under the curve from 0 to 24 hours (AUC0-24)] of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than for Tacrolimus BID; by day 14, systemic exposure was similar; however, the mean dose of Tacrolimus QD was higher to achieve similar systemic exposure as Tacrolimus BID., Methods: To further compare the PK of the tacrolimus formulations during the first 2 weeks posttransplant, a substudy was performed in a subset of patients enrolled into a phase III trial in de novo kidney transplant recipients comparing Tacrolimus QD and Tacrolimus BID. To minimize the difference in exposure observed in the earlier study, tacrolimus therapy was initiated before transplant. The PK analysis set comprised 34 patients (17 patients per treatment group) who had 4 complete PK profiles and no major PK-related protocol violations., Results: Mean AUC0-24 of tacrolimus on day 1 was approximately 16% lower for Tacrolimus QD than for Tacrolimus BID, although by day 3 onward, the exposure was similar between treatment groups. Analysis of dose-normalized AUC0-24 (dose normalized to 0.1 mg/kg) showed a similar pattern. There was a good correlation between AUC0-24 and concentration of tacrolimus at 24 hours postdose for both formulations (Tacrolimus QD, r = 0.87; Tacrolimus BID, r = 0.92), and the slope of the line of best fit was similar., Conclusions: These results suggest that initiating tacrolimus therapy before transplant reduces the difference in exposure between Tacrolimus QD and Tacrolimus BID.

Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC(0-24) of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC(0-24) and C(min) for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID.

Background: Exposure to mycophenolic acid (MPA), the primary active metabolite of mycophenolate mofetil (MMF), is correlated with therapeutic efficacy of MMF but varies depending on the concomitantly administered immunosuppressive drugs., Methods: A 3-month pharmacokinetic substudy of the prospective, randomized, multicentre, open-label Symphony study was performed. Eighty-three adult renal transplant patients received standard-dose cyclosporine, MMF 2 g/day and corticosteroids, or daclizumab induction, MMF 2 g/day and corticosteroids plus low-dose cyclosporine, low-dose tacrolimus or low-dose sirolimus. The area under the concentration-time curve (AUC(0-12)) of MPA and its metabolites between treatment groups was compared. Pharmacokinetic sampling was performed before MMF administration and at 20, 40, 75 min; 2, 3, 6, 8, 10 and 12 h post-dose on Day 7 and Months 1 and 3., Results: Compared with standard-dose cyclosporine, patients receiving low-dose tacrolimus or low-dose sirolimus had significantly higher AUC(0-12) values for MPA at Day 7 and Month 1 and for free MPA at Day 7, and significantly lower AUC(0-12) values for 7-O-MPA-glucuronide (MPAG) at Month 1 and for acyl-glucuronide at Months 1 and 3 (P < 0.05). AUC(0-12) of MPA and free MPA was significantly greater with low-dose tacrolimus and low-dose sirolimus than with low-dose cyclosporine in the first month (P < 0.05). The ratio of MPA to MPAG exposure was significantly higher in the three low-dose groups than in the standard-dose cyclosporine group (P < 0.05)., Conclusions: Standard- and low-dose cyclosporine reduces the exposure of MPA and free MPA compared to low-dose tacrolimus or low-dose sirolimus in patients given the same dose of MMF.

Introduction: Renal function predicts graft survival in kidney transplant patients. This study compared the 2-year evolution of renal function in patients treated with cyclosporine or tacrolimus in combination with mycophenolate mofetil (MMF) and prednisone., Methods: We studied 1558 cadaveric renal transplant recipients from 14 Spanish hospitals between January 2000 and December 2002. Of these, 1168 were treated with tacrolimus and 390 with cyclosporine. The primary efficacy endpoint was long-term renal function. Renal function was measured by serum creatinine and glomerular filtration rate (GFR) by creatinine clearance calculated from the Cockcroft-Gault formula. This report summarizes the 2-year results., Results: At 24 months the tacrolimus group showed significantly better serum creatinine (1.5 +/- 0.7 vs 1.8 +/- 0.8 mg/dL, P < .001) and GFR (60.5 +/- 20.9 mL/min vs 47.9 +/- 10.0, P < .001) than the cyclosporine group. Additionally, recipients with ideal graft donors (23.5 +/- 2.8 vs 24.0 +/- 2.9 years) had a better serum creatinine at 2 years (1.23 +/- 0.2 vs 1.5 +/- 0.4 mg/dL, P < .05). Multivariate analysis showed that tacrolimus was an independent factor associated with better renal function: odds ratio 1.6, 95% confidence interval (1.2 to 2.2), P < .001., Conclusions: Patients with a renal transplant treated with tacrolimus in combination with MMF and prednisone displayed better renal function at 2 years than those who received cyclosporine.

Posttransplant diabetes mellitus (PTDM) occurs in approximately 15% to 20% of renal transplant patients. It has important clinical implications for graft function and survival. Anticalcineurin drugs are associated with an increased risk of developing PTDM. There is a little evidence that conversion from tacrolimus to cyclosporine (CsA)-based immunosuppression improves glucose metabolism and reverses diabetes. This prospective study included nine renal transplant patients (mean age of 34 +/- 20) with PTDM under immunosuppression with tacrolimus. Five were switched directly to CsA and the other four (glycemia > 250 mg/dL) required insulin and were simultaneously switched to CsA. Basal blood levels of tacrolimus were 7.9 +/- 1.9 ng/dL. Conversion was associated with an early, significant improvement of glycemia and HbA1c blood levels (P < .01). At the end of the follow-up, the glycemia (105 +/- 20 mg/dL) and Hb1Ac (5.1 +/- 0.4 mg/dL) were normal. Insulin was discontinued between 3 and 6 months in all patients who required it at the beginning. Cholesterol did not change significantly and triglycerides decreased significantly (basal 210 +/- 85 mg/dL, at 12 months 125 +/- 29, P < .01). Graft function was stable with a mean serum creatinine of 1.7 +/- 0.2 mg/dL. CsA blood levels remained stable during all follow-up periods (P = NS). There were neither episodes of acute rejection nor secondary effects related to the medication. In summary, renal transplant patients receiving tacrolimus who develop PTDM may display better control of hyperglycemia by a switch to CsA.

Introduction: Low-density lipoprotein (LDL) oxidation is considered a key factor in the biological processes that trigger and accelerate atherosclerosis. Reported data suggest that tacrolimus improves the lipid profile in renal transplant recipients., Objective: The objective of this study was to analyze the effect of converting from cyclosporine to tacrolimus on lipoprotein oxidation in renal transplant recipients., Methods: We studied a group of 12 recipients (6 men and 6 women of mean age 55 +/- 11 years) treated with a cyclosporine-mycophenolate mofetil (MMF)-prednisone combination that was converted to tacrolimus-MMF-prednisone because of gingival hyperplasia. The LDL fraction was isolated by density-gradient ultracentrifugation. Oxidative stress was studied before converting (baseline) and at 6 and 12 weeks, thereafter by in vivo oxidation analysis of LDL, a direct assay of oxidized LDL (oxLDL) and oxLDL autoantibodies (Ab-oxLDL) using enzyme-immunoassay techniques. We measured total cholesterol (TC), triglyceride, LDL-cholesterol, high-density lipoprotein (HDL)-cholesterol, ApoA1, ApoB, and Lp(a) levels., Results: The change to tacrolimus resulted in significant decreases in TC levels, 213 +/- 30 (B) versus 185 +/- 27 (12s) (P < .01); LDL, 129 +/- 24 (B) versus 104 +/- 14 (12s) (P = .002); and ApoB 98 +/- 15 (B) versus 85 +/- 10 (12s) (P < .01). HDL levels significantly increased (45 +/- 10 vs 48 +/- 10 [12s]; P = .018), whereas oxLDL concentrations decreased significantly after conversion (B) (55.42 +/- 10.61 vs 12s 45.76 +/- 10.21; P < .01). Converting to tacrolimus produced a nonsignificant decrease in Ab-oxLDL (baseline 204.88 +/- 134.49 vs 12s 179.51 +/- 143.54). A correlation was observed between LDL and oxLDL (r = 65, P = .02 [B] and r = 0.7, P = .01 [12s]) but not between oxLDL levels and Ab-oxLDL concentration (r = -0.05, P = .87 [3] and r = -0.1, P = .77 [12s])., Conclusions: In renal transplantation, tacrolimus therapy was associated with a better lipid profile and lower in vivo LDL oxidation when compared with cyclosporine treatment.

Background: Corticosteroid-free maintenance immunosuppression after organ transplantation eliminates the well-known corticosteroid-related side effects and may help to improve long-term outcome. We investigated whether a corticosteroid-free tacrolimus (Tac)/mycophenolate mofetil (MMF) regimen, in combination with daclizumab (Dac) induction therapy, provides adequate immunosuppression after renal transplantation., Methods: This 6-month, open-label, multicenter, parallel-group study involved 538 renal patients randomized (1:1) to a Dac/Tac/MMF regimen (n = 260) or a Tac/MMF/corticosteroids regimen (n = 278) as a control group., Results: Of the patients who completed the study, 88.8% in the Dac/Tac/MMF group were free from corticosteroid therapy at month 6. The incidence of biopsy-proven acute rejection was 16.5% in both treatment groups; the incidence of biopsy-proven corticosteroid-resistant acute rejection was 4.3% and 5.0% with Tac/MMF/corticosteroids and Dac/Tac/MMF, respectively (P = NS for both comparisons). Renal function was also similar in both groups: median serum creatinine at month 6 was 125.0 micromol/L (Tac/MMF/corticosteroids) and 131.0 microml/L (Dac/Tac/MMF), P = 0.277. The overall safety profile was similar with both regimens. However, compared with the Tac/MMF/steroid regimen, a significantly reduced incidence of new-onset insulin-dependent diabetes mellitus (5.4% vs. 0.4%, P = 0.003) was found with steroid-free immunosuppression. Moreover, mean total cholesterol concentrations increased from baseline in the Tac/MMF/corticosteroids group by 0.19 mmol/L, whereas in the Dac/Tac/MMF group, levels decreased by 0.19 mmol/L, P = 0.005., Conclusions: Corticosteroid-free immunosuppression with a Dac/Tac/MMF regimen is as effective at preventing acute rejection after renal transplantation as a standard triple regimen of Tac/MMF/corticosteroids. Furthermore, the safety benefits reported with Dac/Tac/MMF treatment may help improve the long-term outcome for renal-transplant patients.

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.

Calcineurin inhibitors (CIs) contribute to cardiovascular risk (CR) in renal transplant (RT) patients. However, the CR profile in RT patients without preexistent diabetes is not well known. We compared CR factors in 191 nondiabetic RT recipients with functioning grafts beyond 1 year, receivingly either CsA (Neoral; n=100) or tacrolimus (Tac; n= 91). Clinical data and pretransplant CR profiles were similar in both groups. There were no differences in acute rejection episodes and graft survival rates during follow-up. The overall proportions of posttransplant diabetes (9% versus 6%), and of hypertension (73% vs 63%) were similar in both groups. Hyperlipidemia was more frequent in the CsA group (58% vs 31%; P=.0001). The cholesterol levels in the CsA group showed at 3 months (232+/-47 vs 202+/-42 m/dL; P=.0001), 6 months (232+/-49 vs 205+/-41 mg/dL; P=.0001), and 12 months (217+/-50 vs 202+/-40 mg/dL; P=.028), despite receiving a greater proportion of lipid-lowering drugs (49% vs 15%; P=.0001). Logistic regression analysis showed that CsA was an independent predictor of posttransplant hyperlipidemia (OR: 5.8, CI 95%; 3.3-10.7; P=.0001) as were age, female gender, pretransplant dyslipidemia, and body mass index (BMI). Interestingly, an interaction was observed between pretransplant BMI and CIs: Among pretransplant normal weight patients (BMI <25 kg/m2), CsA produced a greater incidence of hyperlipidemia than tacrolimus (58% vs 23%; P=.0001) while not among patients who were overweight (BMI >25 kg/m2: pretransplant 58% vs 42%; P=.341). In conclusion, CsA confers a higher risk of hyperlipidemia after RT in nondiabetic patients, particularly those with normal pretransplant weight.

Aim: Hepatic metabolism of sildenafil uses the same metabolic pathway as the calcineurin inhibitors (cyclosporine/tacrolimus), through the CYP3A4 isoenzyme. The aim of this pilot study was to evaluate the potential interaction between sildenafil therapy and circulating levels of cyclosporine and tacrolimus in a group of steady-state renal transplant recipients with erectile dysfunction., Material and Methods: A prospective pilot study of sildenafil interactions was carried out in 9 stable male renal transplant recipients with severe erectile dysfunction (mean age 50 +/- 8 years, range 38-64). All patients were receiving therapy with calcineurin inhibitors (5 with cyclosporine and 4 with tacrolimus). Erectile dysfunction was evaluated by clinical history, physical examination, International Index of Erectile Function (IIEF) questionnaire and the nocturnal penile tumescence test (RigiScan). Each patient received a first dose of 50 mg of sildenafil, one hour before sexual activity and a second dose at 72 hours of 50 or 100 mg according to the clinical response to the first dose. We evaluated the efficacy and safety of sildenafil and the evolution of cyclosporine-tacrolimus levels. Cyclosporine and tacrolimus trough whole blood concentrations were determined in basal conditions (before starting sildenafil) and on days 1, 4 and 7 after sildenafil therapy., Results: Eighty-nine percent of patients (n = 8) required a complete 100 mg dose of sildenafil. There was a positive clinical response in two-thirds of cases (6 patients). In 5 patients (55%) sildenafil administration produced a complete response, in one patient the response was incomplete, and in the remaining 3 cases (33%) no clinical response was observed. Associated side effects included self-limited tachycardia in one patient and mild visual disturbances in another. Cyclosporine and tacrolimus levels remained stable in all patients. There were no significant differences in circulating levels of cyclosporine (basal 120 +/- 47; day 1: 116 +/- 55; day 4: 123 +/- 56 and day 7: 121 +/- 56 ng/ml p = NS) or tacrolimus (basal 11.6 +/- 1.3; day 1: 11.9 +/- 1.3; day 4: 11.1 +/- 1.0 and day 7: 11.8 +/- 0.9 ng/ml p = NS) over the study period., Conclusions: Sildenafil therapy is safe and effective for the treatment of erectile dysfunction in renal transplant recipients. Recommended therapeutic doses of sildenafil did not modify cyclosporine and tacrolimus trough blood levels.

Abstract: Since calcineurin inhibitors (CNI) have been introduced, they have become the cornerstone of immunosuppression for renal transplant patients, but their cardiovascular and neurological toxicities, and primarily their renal toxicity, have brought about an increased effort to find combinations of immunosuppressants that are either CNI-free or that use minimum doses of these drugs. The weight of immunosuppression therefore lies with drugs that have a better toxicity profile. The POP observational transverse study including 213 renal transplant patients was designed to study CNI minimization strategies. The mean time of transplant evolution to the time of reduction was 9.9 ± 11.8 months. The acute rejection rate to the start of reduction was 9.4%. Almost all the patients were undergoing treatment with CNI + mycophenolate mofetil (MMF) + steroids in the immediate posttransplantation period. When reduction was chosen, all patients were undergoing treatment with MMF (mean dose at the start of reduction = 1490.7 ± 478.0 mg/d). Among the cohort, 66.7% of patients were being treated with tacrolimus (mean C0 levels 13.3 ± 6.6 ng/mL) and 33.3% with cyclosporine (mean C0 levels 192.2 ± 94.0 ng/mL; mean C2 levels 1097.5 ± 457.6). The main reasons for withdrawal were nephrotoxicity (55.9% of the cases), as well as prevention of adverse effects (21.6%). The mean target CNI dose reduction was 41.4% ± 21.45% in the tacrolimus group and 28.6 ± 10.0% in the cyclosporine group. In conclusion, CNI toxicity, primarily renal toxicity, makes reduction of these drugs based on the use of full MMF doses an alternative to manage renal transplant patients. [Copyright &y& Elsevier]

Background Renal transplantation in highly sensitized patients represents a major clinical challenge leading to long periods on the waiting list. When a living donor is available, the use of different strategies to desensitize recipients with preformed human leukocyte antigen antibodies can allow a successful transplantation. Methods We performed a retrospective observational study including all living donor kidney transplantation (LDKT) with desensitization (DS) from 2008 to 2014 in our transplant unit. The rates of rejection and graft survival were evaluated. DS consisted of plasma exchange (PE), rituximab (RTX), and intravenous immunoglobulin (IVIG) induction with thymoglobulin and maintenance immunosuppression with tacrolimus, corticosteroids, and mycophenolate mofetil. Results From 2008 to 2014, we performed 368 LDKT, with 31 receiving desensitization. Seven cases from a clinical trial were excluded. Demographic data and outcomes were recorded. All of the patients received RTX + PE + IVIG. DS was performed for positive complement-dependent cytotoxicity cross-match (4.2%), T-cell– and/or B-cell–positive flow cytometry cross-match (87.5%) and presence of donor-specific antibodies alone (8.3%). We identified 23 episodes of rejection in 12 patients (50%); 79% were antibody-mediated rejections (AMR). Graft failure was 12.5%, with a mean time to graft loss of 229 ± 203 days. Mean follow-up was 37 ± 27 months, and graft survival was 91% and 86% at 1 and 5 years, respectively. Conclusions Desensitization in LDKT appears to offer an acceptable option for highly sensitized patients. In our series, 41% presented an AMR and 12.5% showed transplant glomerulopathy in protocol and/or indication biopsies. However, short-term outcomes and graft survival were satisfactory. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]