Tacrolimus with Mycophenolate Mofetil (MMF) or Sirolimus vs. Cyclosporine with MMF in Cardiac Transplant Patients: 1-Year Report

The most advantageous combination of immunosuppressive agents for cardiac transplant recipients has not yet been established. Between November 2001 and June 2003, 343 de novo cardiac transplant recipients were randomized to receive steroids and either tacrolimus (TAC) + sirolimus (SRL), TAC + mycophenolate mofetil (MMF) or cyclosporine (CYA) + MMF. Antilymphocyte induction therapy was allowed for up to 5 days. The primary endpoint of >/=3A rejection or hemodynamic compromise rejection requiring treatment showed no significant difference at 6 months (TAC/MMF 22.4%, TAC/SRL 24.3%, CYA/MMF 31.6%, p = 0.271) and 1 year (p = 0.056), but it was significantly lower in the TAC/MMF group when compared only to the CYA/MMF group at 1 year (23.4% vs. 36.8%; p = 0.029). Differences in the incidence of any treated rejection were significant (TAC/SRL = 35%, TAC/MMF = 42%, CYA/MMF = 59%; p < 0.001), as were median levels of serum creatinine (TAC/SRL = 1.5 mg/dL, TAC/MMF = 1.3 mg/dL, CYA/MMF = 1.5 mg/dL; p = 0.032) and triglycerides (TAC/SRL = 162 mg/dL, TAC/MMF = 126 mg/dL, CYA/MMF = 154 mg/dL; p = 0.028). The TAC/SRL group encountered fewer viral infections but more fungal infections and impaired wound healing. These secondary endpoints suggest that the TAC/MMF combination appears to offer more advantages than TAC/SRL or CYA/MMF in cardiac transplant patients, including fewer >/=3A rejections or hemodynamic compromise rejections and an improved side-effect profile.     

Calcineurin inhibitor withdrawal and conversion to mycophenolate mofetil and steroids in cardiac transplant recipients with chronic renal failure: a word of caution

Abstract: Background: Chronic renal failure (CRF) is a common complication of calcineurin inhibitor (CNI)‐based immunosuppression following cardiac transplantation (HTx). The aim of this prospective study was to evaluate the impact of an immunosuppressive conversion from CNIs to mycophenolate mofetil (MMF) and steroids in cardiac transplant recipients with CRF on renal and cardiac graft function. Methods: Since 1999, 12 HTx recipients (10 men; 58 ± 3.6 yr of age; 8.7 ± 4.2 yr after HTx) with CNI‐based immunosuppression and a calculated creatinine clearance (CreaCl) <50 mL/min were included. Most patients (10/12) were on cyclosporine and two patients were on tacrolimus prior inclusion. MMF was started with 0.5 g/d and adjusted according to the target trough levels (2–4 ng/mL). Prednisone dosage was 0.4 mg/kg. Subsequently, CNIs were completely withdrawn. Acute rejection episodes were excluded one and three months after conversion by endomyocardial biopsy and by echocardiography every three months thereafter. Results: After a mean follow‐up of 20 ± 16 months, CreaCl improved significantly: pre‐conversion vs. post‐conversion: 32.8 ± 12.2 mg/dL vs. 42.8 ± 21.14 mg/dL, p = 0.03. However, four acute rejection episodes occurred and patients were reconverted to CNIs. Additionally, six patients had a new onset of graft vessel disease (GVD) one yr after conversion. As a result of these adverse events, the study was stopped after inclusion of only 12 of the scheduled 30 patients. Conclusions: Conversion to MMF and steroids after HTx improves renal function, but increases the risk for recurrent rejection and GVD. Therefore, MMF and steroids should only be considered in patients with a markedly low risk for rejection.     

Mycophenolate mofetil monotherapy in liver transplant recipients

Kriss M, Sotil EU, Abecassis M, Welti M, Levitsky J. Mycophenolate mofetil monotherapy in liver transplant recipients.
Clin Transplant 2011: 25: E639–E646. © 2011 John Wiley & Sons A/S. Abstract:  Introduction: Complete conversion of calcineurin inhibitor (CNI) immunosuppressant therapy to non‐nephrotoxic agents such as mycophenolate mofetil (MMF) is controversial, but may be safe in selected patients, although appropriate protocols and long‐term benefits of conversion are not well reported. Methods: We analyzed all liver transplant (LT) recipients at our institution who were converted from CNI‐based therapy to MMF monotherapy because of renal dysfunction (n = 23) and compared them with patients remaining on CNI‐based therapy (n = 23). Renal function, rejection episodes, and markers of CNI‐related comorbidities (lipid profile, blood pressure, and glycosylated hemoglobin) were noted. Results: Overall, serum creatinine (SCr) and calculated glomerular filtration rate improved on MMF monotherapy. This improvement was significant when compared with patients who remained on CNI‐based therapy. Improvement was most pronounced in patients with milder renal dysfunction (SCr <2.2 mg/dL prior to conversion) (n = 14) with decrease in SCr from 1.63 ± 0.29 to 1.34 ± 0.26 mg/dL (p = 0.02) at last follow‐up. Five patients on MMF monotherapy (21.7%) progressed to end‐stage renal disease (ESRD), while only two (8.7%) had rejection episodes following conversion. Clinical markers of CNI‐related comorbidities also improved. MMF monotherapy was well tolerated. Conclusion: In summary, our data support the safety and efficacy of CNI to MMF monotherapy conversion.     

Two yr mycophenolate mofetil plus low-dose calcineurin inhibitor for renal dysfunction after liver transplant

Abstract:  We assessed the efficacy and outcome of low through level of calcineurin inhibitors (CNI) and introducing mycophenolate mofetil (MMF) in liver transplant (LT) patients with CNI-related renal dysfunction. Thirty LT patients were converted to combined therapy and compared with 30 patients used as a contemporary control group receiving CNI only. The two groups were matched for sex, age, months after LT, immunosuppressive treatment, creatinine level, presence of diabetes and calculated glomerular filtration rate (GFR) via Cockroft-Gault method. After two years, in the MMF serum creatinine decreased from 1.65 mg/dL (range 1.33–3.5) to 1.4 mg/dL (range 0.9–4.7) (p = 0.002) and GFR increased from 51 mL/min (range 18.9–72.2) to 57.6 mL/min (range 16–92.2) (p < 0.001), whereas the controls not showed any improvement. The logistic regression models employing improvement of creatinine and GFR of at least 10% with respect to baseline as dependent variables showed the use of MMF (p = 0.004 and p = 0.019, respectively) as the only statistically significant parameter. Multiple linear regression analysis identified only MMF as independent predictor of Δcreatinine and ΔGFR (p = 0.002 and p < 0.001, respectively). No rejection episode was observed (three in controls). This study demonstrates the medium-term efficacy and safety of MMF plus low dose CNI in reducing nephrotoxicity in LT recipients.     

Improved renal function after conversion from tacrolimus/sirolimus to tacrolimus/mycophenolate mofetil in kidney transplant recipients

BACKGROUND: There is limited data on the potential nephrotoxicity of sirolimus (SRL) and tacrolimus (TAC) in combination. METHODS: We reviewed the course of 97 kidney transplant patients treated with SRL and reduced-dose TAC. Conversion from SRL to mycophenolate mofetil (MMF) was prescribed in a minority (n = 19) for various nonrenal side effects. We compared outcomes of converted patients to those remaining on TAC/SRL (n = 78). RESULTS: TAC levels were increased in converters (P = 0.009). Rejection rates were similar between groups over 18 months (21% vs. 16%, p = ns). Serum creatinine (Cr) and MDRD glomerular filtration rate (GFR) were similar between groups at nadir and six-months, but at 18 months the percent change from six-month Cr was +17% in non-converters vs. -10% in converters (P = 0.004 for the difference). The difference in GFR between groups at 18 months was also significant (P = 0.01). By multivariate analysis, only conversion to MMF was associated with a greater percent change in Cr from 6 to 18 months (P = 0.015). Conversion to MMF also correlated with higher GFR at 18 months independent of rejection, delayed graft function, and ethnicity. CONCLUSIONS: Conversion from TAC/SRL to TAC/MMF led to improved renal function despite increased TAC exposure after conversion.     

A calcineurin antagonist-free induction/maintenance strategy for immunosuppression in elderly recipients of renal allografts from elderly cadaver donors: long-term results from a prospective single centre trial

BACKGROUND: With the aim to improve the inferior outcomes in elderly recipients of kidneys from elderly cadaver donors, we applied and investigated a therapeutic regimen consisting of calcineurin inhibitor (CNI)-free, mycophenolate mofetil (MMF)-based immunosuppressive (i.s.) induction/maintenance protocol. In this article, we report the long-term results of this clinical trial. METHODS: A total of 89 recipients (mean age: 63.8 yr) of kidneys from cadaver donors (mean age: 66.8 yr) were consecutively recruited for this 5-yr, prospective, open, single centre, pilot trial. Induction therapy consisted of MMF and steroids in conjunction with a short course (4-10 d) of rabbit antithymocyte globulin (ATG). Maintenance treatment was performed with MMF/steroids or MMF alone under strict therapeutic drug monitoring by aiming target mycophenolic acid (MPA)-trough levels between 2 and 6 mg/mL. RESULTS: Cumulative 5-year patient and renal allograft survival was 87.69% and 69.81%, respectively. Acute rejection episodes occurred in 23.6% (21 patients). Long-term function of the old renal allografts proved to be satisfactory as reflected by serum creatinine-values of 1.53 mg/dL and urea-values of 57.9 mg/dL at 5 yr. CONCLUSION: Application of a nephrotoxicity- and atherogenicity-free, MMF-based i.s. induction/maintenance protocol in elderly recipient of kidneys from elderly cadaver donors leads to improved long-term outcomes which are comparable with data from young recipients who have received allografts from young cadaver donors.     

The use of an anti-CD25 monoclonal antibody and mycophenolate mofetil enables the use of a low-dose tacrolimus and early withdrawal of steroids in renal transplant recipients

BACKGROUND: Reducing calcineurin-inhibitor-induced nephrotoxicity and simultaneously avoiding long-term steroid related side-effects is a desirable goal in renal transplantation. We examined the hypothesis that using anti-CD25 monoclonal antibody induction and mycophenolate mofetil (MMF) would allow the lowering of target pre-dose blood concentrations of tacrolimus immediately after transplantation and subsequently stopping steroids at 5 months. METHODS: Eighty-two kidney recipients were enrolled in a single-center study comparing two tacrolimus-based protocols. Group I (n = 41) patients received a standard-dose tacrolimus (blood concentration 10-15 ng/mL) with MMF and a standard dose corticosteroid. Group II (n = 41) patients were treated with a low-dose tacrolimus (blood concentration 5-10 ng/mL) and MMF, a low-dose corticosteroid (stopped after 5 months) and induction with daclizumab. RESULTS: Patient (95.1 versus 100%) and graft survival (92.6 versus 97.5%) at 1 yr were not different between groups. Patients of group II experienced significantly less acute rejections than group I (17.1 versus 41.4% p = 0.03). Delayed graft function occurred less often in group II (5 versus 12% p = 0.43). Graft function at 1 yr was significantly better in group II (serum creatinine 1.49 versus 1.69 mg/dL and creatinine clearance 59.6 versus 49 mL/min; p < 0.05). Corticosteroids could be stopped after 5 months in 82.9% of group II patients. CONCLUSION: A regimen consisting of anti-CD25 monoclonal antibody induction and MMF allows the safe and efficient use of low-target pre-dose trough concentrations of tacrolimus and enables the early discontinuation of steroids. Preliminary results indicate a better 1-yr graft function compared to a normal-dose tacrolimus regimen.     

Posttransplant diabetes mellitus: incidence and risk factors

Posttransplant diabetes mellitus (PTDM) is common post transplantation and is associated with tacrolimus (TAC) and steroid therapy. The aim of the present study was to analyze the incidences of PTDM and associated risk factors. METHODS: We selected renal transplant recipients treated with TAC, mycophenolate mofetil (MM), and steroids. Exclusion criteria were recipients <18 years old, history of diabetes, recipients of kidney/pancreas, and/or those receiving cyclosporine or sirolimus. PTDM was defined as glucose >126 mg/dL, with or without drug therapy. RESULTS: Among 67 patients who fulfilled the inclusion criteria, 18 (26.8%) developed PTDM within 2 months of transplantation. Compared with normal glucose patients, the PTDM group was older, male, received a kidney from deceased donors, and showed higher pretransplant glucose levels. No differences were noticed in renal function or daily dose of TAC or steroids. However, TAC trough levels in the first month were higher among the PTDM group, despite the lower dose per kilogram. After 1 year of follow-up, weight gain as well as daily TAC per kilogram dose was less among PTDM patients. Analysis of potential risk factors showed a higher incidence of hepatitis C virus infection in the PTDM group, as well as a higher frequency of HLA DR13. CONCLUSION: The incidence of PTDM diagnosed in the early posttransplant period in the present series was 26.8%. Risk factors included older age, male gender, recipients of kidneys from deceased donors, hepatitis C virus infection, higher pretransplant glucose levels, and higher TAC trough levels during the first month posttransplant.     

Immunosuppression with Belatacept‐Based,Corticosteroid‐Avoiding Regimens in De Novo Kidney Transplant Recipients

Current immunosuppressive regimens in renal transplantation typically include calcineurin inhibitors (CNIs) and corticosteroids, both of which have toxicities that can impair recipient and allograft health. This 1‐year, randomized, controlled, open‐label, exploratory study assessed two belatacept‐based regimens compared to a tacrolimus (TAC)‐based, steroid‐avoiding regimen. Recipients of living and deceased donor renal allografts were randomized 1:1:1 to receive belatacept‐mycophenolate mofetil (MMF), belatacept‐sirolimus (SRL), or TAC‐MMF. All patients received induction with 4 doses of Thymoglobulin (6 mg/kg maximum) and an associated short course of corticosteroids. Eighty‐nine patients were randomized and transplanted. Acute rejection occurred in 4, 1 and 1 patient in the belatacept‐MMF, belatacept‐SRL and TAC‐MMF groups, respectively, by Month 6; most acute rejection occurred in the first 3 months. More than two‐thirds of patients in the belatacept groups remained on CNI‐ and steroid‐free regimens at 12 months and the calculated glomerular filtration rate was 8–10 mL/min higher with either belatacept regimen than with TAC‐MMF. Overall safety was comparable between groups. In conclusion, primary immunosuppression with belatacept may enable the simultaneous avoidance of both CNIs and corticosteroids in recipients of living and deceased standard criteria donor kidneys, with acceptable rates of acute rejection and improved renal function relative to a TAC‐based regimen.     

Withdrawal of steroids: a randomized prospective study of prednisone and tacrolimus versus mycophenolate mofetil and tacrolimus in liver transplant recipients with autoimmune hepatitis

The aim of this study was to evaluate the success of steroid (PRED) withdrawal due to replacement by mycophenolate mofetil (MMF) in orthotopic liver transplant (OLT) recipients with autoimmune hepatitis (AIH). Thirty patients with AIH > 12 months after OLT randomized to receive either PRED and tacrolimus (TAC) or MMF and TAC were followed for 24 months. Withdrawal of steroids showed no difference regarding graft and patient survival. Also we demonstrated significantly lower glucose levels with lower HbA1c and a reduced need for insulin as well as a significantly lower serum cholesterol in the MMF group. Patients without steroids showed a lower incidence of osteopenia. Maintenance therapy in OLT patients with AIH may be performed safely using MMF instead of prednisone.     

Use of enteric‐coated mycophenolate sodium in liver transplant patients with intestinal intolerance caused by mycophenolate mofetil

Abstract: Background: Post‐transplant gastrointestinal (GI) side effects can impair a patient’s quality of life (QoL). This study investigates the improvement in GI side effects and related QoL changes in recipients of liver transplantation (OLT) after converting patients from mycophenolate mofetil (MMF) to enteric‐coated mycophenolate sodium (EC‐MPS). Methods: Thirty‐four patients who underwent OLT and suffered from GI intolerability were included in this study. Infectious causes of GI intolerability were excluded. QoL assessed by the Gastrointestinal Quality of Life Index was evaluated before conversion and at months 3, 6 and 12 post‐conversion. All patients received baseline immunosuppression of one calcineurin inhibitor, MMF, with or without steroids. Patients were converted from MMF to EC‐MPS on an equimolar basis. Paired t‐test was used to assess differences in mean score changes over time. Results: Conversion from MMF to EC‐MPS for GI intolerability post‐OLT shows statistically significant improvement in GI‐related QoL at 3, 6, and 12 months when compared to baseline assessments (p < 0.05 for total mean score); nonetheless, one‐third of patients discontinued EC‐MPS. No rejection episodes, deaths or graft loss were seen during the study period. Conclusion: OLT recipients who develop GI side effects caused by MMF can be safely converted to EC‐MPS with improvement to their QoL.     

Hypogammaglobulinemia and bronchiectasis in mycophenolate mofetil‐treated renal transplant recipients: an emerging clinical phenomenon?

Boddana P, Webb LH, Unsworth J, Brealey M, Bingham C, Harper SJ. Hypogammaglobulinemia and bronchiectasis in mycophenolate mofetil‐treated renal transplant recipients: an emerging clinical phenomenon?
Clin Transplant 2011: 25: 417–419. © 2010 John Wiley & Sons A/S. Abstract: Background: Mycophenolate mofetil (MMF) inhibits T‐ and B‐cell proliferation and can cause acquired or secondary hypogammaglobulinemia. This finding and the subsequent development of opportunistic infection, including pneumonia, have been reported in patients receiving MMF. Chronic pulmonary infection and hypogammaglobulinemia predispose to bronchiectasis, and we aimed to establish the incidence and clinical pattern of this condition within our MMF‐treated renal transplant population. Methods: We performed a retrospective analysis of MMF‐treated transplant recipients. Two hundred and eighty‐nine patients were identified and for each, demographic, clinical, radiological and laboratory data from case notes and electronic records were collected. Results: Twenty‐three of 289 patients had recurrent severe chest infections (>2 episodes) between 12 and 95 months after the introduction of MMF. The mean age was 53 ± 17 yr. Pulmonary lesions fulfilled clinical, radiographic and computerized tomography criteria for bronchiectasis in 7/289 (2.4%). All seven patients with bronchiectasis had low serum IgG levels. Three patients had sufficient samples available for B‐cell phenotype analysis but no conclusive results emerged. No cases of post‐transplant bronchiectasis were identified in our transplant population not receiving MMF. Discussion: We report seven cases of bronchiectasis in renal transplant patients receiving MMF. We speculate that low immunoglobulin levels may contribute to the development of this significant pulmonary disease.     

Immunosuppression with generic tacrolimus and mycophenolate mofetil in renal transplant recipients: preliminary report in Chile

The association of tacrolimus (TAC) and mycophenolate mofetil (MMF) in renal transplant patients has diminished the incidence of acute rejection. We evaluated the use of generic TAC and MMF as primary immunosuppression in 6 living related (LR) and 11 cadaveric (C) donor renal transplant recipients (9 men, 8 women) of mean age 37 +/- 12 years (range, 17-56 years) between May 2006 and June 2007. From day 0 all patients received TAC, MMF, and prednisone without antibody induction. They were followed for the development of acute rejection, graft loss, side effects, and mortality. Mean follow-up was 7.6 months (range, 2-15 months). No biopsy-proven acute rejection episodes, graft loss, or recipient deaths were observed. Creatinine levels at the end of the study were 1.90 +/- 1.0 mg/dL (range, 0.62-4.25 mg/dL for C recipients and 1.19 +/- 0.15 mg/dL (range, 0.91-1.35 mg/dL) for LR recipients. Mean systolic and diastolic blood pressures were 130/73 mm Hg with 12 patients (70.5%) on antihypertensive therapy with calcium antagonists and beta-blockers. Mean (range) of total cholesterol, triglycerides, and glucose were 172 (110-244) mg/dL, 139 (69-277) mg/dL, and 89 (63-129) mg/dL, respectively. MMF was suspended in 1 patient due to diarrhea and 1 other because of leukopenia. We observed that generic TAC and MMF yielded effective and safe immunosuppression in terms of mortality, biopsy-proven acute rejection, and graft loss with a low incidence of adverse effects during the study period.     

A Randomized Trial to Assess the Impact of Early Steroid Withdrawal on Growth in Pediatric Renal Transplantation: The TWIST Study

Minimizing steroid exposure in pediatric renal transplant recipients can improve linear growth and reduce metabolic disorders. This randomized multicenter study investigated the impact of early steroid withdrawal on mean change in height standard deviation score (SDS) and the safety and efficacy of two immunosuppressive regimens during the first 6 months after transplantation. Children received tacrolimus, MMF, two doses of daclizumab and steroids until day 4 (TAC/MMF/DAC, n = 98) or tacrolimus, MMF and standard‐dose steroids (TAC/MMF/STR, n = 98). Mean change in height SDS was 0.16 ± 0.32 with TAC/MMF/DAC and 0.03 ± 0.32 with TAC/MMF/STR. The mean treatment group difference was 0.13 (p < 0.005 [95% CI 0.04–0.22]), 0.21 in prepubertal (p = 0.009 [95% CI 0.05–0.36]) and 0.05 in pubertal children (p = ns). Frequency of biopsy‐proven acute rejection was 10.2%, TAC/MMF/DAC, and 7.1%, TAC/MMF/STR. Patient and graft survival and renal function were similar. Significantly greater reductions in total cholesterol and triglycerides but significantly higher incidences of infection and anemia were found with TAC/MMF/DAC (p < 0.05 all comparisons). Early steroid withdrawal significantly aided growth at 6 months more so in prepubertal than pubertal children. This was accompanied by significantly better lipid and glucose metabolism profiles without increases in graft rejection or loss.     

The ORION Study: Comparison of Two Sirolimus‐Based Regimens versus Tacrolimus and Mycophenolate Mofetil in Renal Allograft Recipients

Safety and efficacy of two sirolimus (SRL)‐based regimens were compared with tacrolimus (TAC) and mycophenolate mofetil (MMF). Renal transplantation recipients were randomized to Group 1 (SRL+TAC; week 13 TAC elimination [n = 152]), Group 2 (SRL + MMF [n = 152]) or Group 3 (TAC + MMF [n = 139]). Group 2, with higher‐than‐expected biopsy‐confirmed acute rejections (BCARs), was sponsor‐terminated; therefore, Group 2 two‐year data were limited. At 1 and 2 years, respectively, graft (Group 1: 92.8%, 88.5%; Group 2: 90.6%, 89.9%; Group 3: 96.2%, 95.4%) and patient (Group 1: 97.3%, 94.4%; Group 2: 95.2%, 94.5%; Group 3: 97.0%, 97.0%) survival rates were similar. One‐ and 2‐year BCAR incidence was: Group 1, 15.2%, 17.4%; Group 2, 31.3%, 32.8%; Group 3, 8.2%, 12.3% (Group 2 vs. 3, p < 0.001). Mean 1‐ and 2‐year modified intent‐to‐treat glomerular filtration rates (mL/min) were similar. Primary reason for discontinuation was adverse events (Group 1, 34.2%; Group 2, 33.6%; Group 3, 22.3%; p < 0.05). In Groups 1 and 2, delayed wound healing and hyperlipidemia were more frequent. One‐year post hoc analysis of new‐onset diabetes posttransplantation was greater in TAC recipients (Groups 1 and 3 vs. 2, 17% vs. 6%; p = 0.004). Between‐group malignancy rates were similar. The SRL‐based regimens were not associated with improved outcomes for kidney transplantation patients.     

Impact of combined mycophenolate mofetil and low-dose calcineurin inhibitor therapy on renal function, cardiovascular risk factors, and graft function in liver transplant patients: preliminary results of an open prospective study

As liver transplantation (LT) is now being performed with excellent 1-year graft survival rates of 85% to 90%, attention has been shifted to reducing long-term complications of calcineurin inhibitors (CNI). We randomized LT patients (2:1) who displayed renal dysfunction under CNI treatment to either mycophenolate mofetil (MMF) (1000 mg twice a day) followed by stepwise reduction of CNI (n = 21; Tac trough levels <4 ng/mL, CsA trough levels <50 ng/mL); or continue their current CNI dose (n = 11; control group). Three months after study entry, we observed significantly decreased mean values in the CNI reduction group of serum creatinine (1.88 +/- 0.36 versus 1.58 +/- 0.33 mg/dL, P < .001) and BUN (39.2 +/- 11.8 versus 29.9 +/- 9.59 mg/dL, P < .001) with a significantly increased GFR (51.4 +/- 10.8 versus 61.6 +/- 14.1 mL/min, P < .001). Improved renal function in these long-term LT recipients (5.6 +/- 3.6 years posttransplant; range, 2 to 13 years) suggests at least a partial reversibility of CNI-induced renal damage. Furthermore, we found an improved lipid profile as well as a significantly decreased mean systolic (140 +/- 19 versus 130 +/- 14 mm Hg, P < .01) and diastolic (82 +/- 9 to 74 +/- 8 mm Hg, P < .001) blood pressure 3 months after introduction of MMF therapy. Additionally, transaminases significantly improved in the CNI reduction group within this time period (ALT 37.9 +/- 25.9 versus 25.2 +/- 13.2, P < .05). MMF and CNI-reduced immunosuppressive regimens may improve long-term patient survival, suggesting a broad application within the liver transplant setting.     

A critical analysis of racial difference with mycophenolate mofetil (MMF) dosing,clinical outcomes and adverse effects in pediatric kidney transplant patients

Jensen CJ, Shrivastava S, Taber DJ, Weimert NA, Shatat IF, Orak J, Chavin KD, Baliga PK. A critical analysis of racial difference with mycophenolate mofetil (MMF) dosing, clinical outcomes and adverse effects in pediatric kidney transplant patients.
Clin Transplant 2011: 25: 534–540. © 2010 John Wiley & Sons A/S. Abstract: There is paucity in the data examining the differences in mycophenolate mofetil (MMF) dosing and outcomes among pediatric kidney transplant recipients (PKTX) between races. The aims of this study were as follows (i) to assess whether higher doses of MMF are being utilized in African American (AA) PKTX (ii) to determine whether there is a correlation between MMF dose and outcomes between races, and (iii) to assess the adverse effects of MMF between races. This study analyzed 109 PKTX who received MMF between 7/99 and 5/08. Demographics were similar between groups. Fewer AAs received kidneys from living donors (18% vs. 44%), spent more time on dialysis (1.0 vs. 0.5 yr), and had more human leukocyte antigen mismatches (4 vs. 3). MMF doses among AA patients were higher throughout the study, with statistical differences at week 4, month 3, and month 18. AA patients had significantly higher acute rejection rates and trended toward poorer graft survival; infections, adverse events from MMF and post‐transplant lymphoproliferative disease tended to be lower in the AA patients. AA PKTX received higher MMF doses within the first three yr post‐transplant compared to their non‐AA counterparts, yet demonstrate significantly more acute rejection episodes. Importantly, MMF caused fewer adverse events in AA patients, despite these patients receiving higher doses.     

A single‐staggered dose of calcineurin inhibitor may be associated with neurotoxicity and nephrotoxicity immediately after liver transplantation

Abstract: The aim of the present work was to assess the incidence of neuro‐nephrotoxicity after a single‐staggered dose of calcineurin inhibitors (CI) with different immunosuppressive approaches. From January to December 2006, all liver transplantation (LT) recipients at risk of renal or neurological complications treated with extracorporeal photopheresis (ECP) + mycophenolate mofetil + steroids and staggered introduction of CI (ECP group) were compared with a historical control group on standard CI‐based immunosuppression. The ECP group included 24 patients with a mean model for end‐stage liver disease (MELD) score of 19.9 ± 11.1. The control group consisted of 18 patients with a mean MELD score of 12.5 ± 5.2 (p = 0.012). In the ECP group CI were introduced at a mean of 9.2 ± 6.2 d (4–31 d) after LT. Five patients in the ECP group presented acute neuro‐nephrotoxicity after the first CI administration on post‐transplant d 4, 5, 6, 6, and 14. Overall patient survival at one, six, and 12 months was 100%, 95.8%, and 95.8% in the ECP group vs. 94.4%, 77.7%, and 72.2% in the control group (p < 0.001). In conclusion, we showed that CI toxicity may occur after a single‐staggered dose administration, ECP seems to be a valuable tool for managing CI‐related morbidity regardless of the concomitant immunosuppressive regimen, being associated with a lower mortality rate in the early post‐transplant course.     

Renal function in patients with cadaveric kidney transplants treated with tacrolimus or cyclosporine

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.     

Immunosuppression without calcineurin inhibition: optimization of renal function in expanded criteria donor renal transplantation

Abstract: Introduction: To assess the efficacy of calcineurin inhibitor (CNI)‐free immunosuppression vs. calcineurin‐based immunosuppression in patients receiving expanded criteria donor (ECD) kidneys. Patient and methods: Thirteen recipients of ECD kidneys were enrolled in this pilot study and treated with induction therapy and maintained on sirolimus, mycophenolate mofetil (MMF) and prednisone. A contemporaneous control group was randomly selected comprised of 13 recipients of ECD kidneys who had been maintained on CNI plus MMF and prednisone. Results: For the study group vs. the control group, two‐yr graft survival was 92.3% vs. 84.6% (p = NS), two‐yr patient survival was 100% vs. 92.3% (p = NS) and the acute rejection rates were 23% vs. 31% (p = NS), respectively. Renal function was significantly better in the study group compared with control up to the six‐month mark, after which, it remained numerically but not statistically significant. Complications were more common in the study group, but serious adverse events requiring discontinuation were rare. Conclusion: This pilot study demonstrates that CNI‐free regimens can be safely implemented in patients receiving ECD kidneys with excellent two‐yr patient and graft survival and good renal allograft function. Longer follow‐up in larger randomized controlled trials are necessary to establish these findings.