Function In Liver Transplant Recipients Research Articles

FRI-462 - Biochemical and Serological Markers of Liver Function in Liver Transplant Recipients with Primary Biliary Cholangitis

FRI-462 - Biochemical and Serological Markers of Liver Function in Liver Transplant Recipients with Primary Biliary Cholangitis

Long-Term Renal Function in Liver Transplant Recipients After Conversion From Calcineurin Inhibitors to mTOR Inhibitors

Renal dysfunction often occurs in liver transplant (LT) recipients receiving calcineurin inhibitor (CNI)-based immunosuppressive regimens, increasing morbidity and mortality rates. Replacement of CNIs by mTOR inhibitor-based immunosuppressive protocols may prevent renal impairment in LT recipients. Outcomes in patients who underwent LT between 1996 and 2010 at our center and who were switched from CNI-based to mTOR inhibitor-based immunosuppression were retrospectively analyzed. Renal course, hyperlipidemia, and graft rejection were assessed in patients maintained on this CNI-free regimen for at least 24 months. Of the 85 patients switched from CNI-based to mTOR inhibitor-based, CNI-free immunosuppression, 78 met the inclusion criteria. Within the first 6 weeks after switching, the covariable adjusted estimated glomerular filtration rate (eGFR) increased 5.6 mL/min [95% confidence interval 2.6-8.7 mL/min, p<0.001], but there were no further statistically noticeable changes in eGFR. Concentrations of cholesterol and triglycerides increased statistically, noticeable within the first 12 months after drug conversion. Histologically proven graft rejection was observed in 4 patients (5.1%) after conversion. Conversion from CNI-based to CNI-free, mTOR inhibitor-based immunosuppression after LT is safe and can result in significant renal recovery. CNI-free, mTOR inhibitor-based immunosuppression is a potential option for patients with contraindications for CNIs and for LT recipients with rapid reduction in kidney function due to CNIs.

The Impact of Antiviral (HCV) Therapy on Kidney Function in Liver Transplant Recipients

The Impact of Antiviral (HCV) Therapy on Kidney Function in Liver Transplant Recipients

Maturation state and function of monocyte derived dendritic cells in liver transplant recipients.

Dendritic cells (DCs) are potent antigen presenting cells for triggering of the immune reaction post transplantation. These cells are centrally involved in the initiation of T cell-dependent immune responses. To compare the level of DC maturation and function in liver transplant recipients with healthy controls. In this study, twelve peripheral blood samples were selected from six liver transplant patients and six healthy controls. After the generation of DCs from monocytes, expression levels and mean fluorescent intensity (MFI) of several DC maturation markers were evaluated using flow cytometry. Secretion of IL-6, IL-12 and IL-23 proinflammatory cytokines was determined using ELISA. Gene expressions of TLR-2, TLR-4 and IL-23 were analyzed using real-time PCR. DC expression markers including CD83 (p=0.007) and CD86 (p=0.02), as well as secretion of IL-6 (p=0.02) and IL-12 (p=0.007) by DCs were significantly increased in liver transplant patients compared with healthy controls. The MFI of CD86 (p=0.009) and HLA-DR (p= 0.005) expression on DCs was also higher in patients. The expression of TLR-2 transcripts in DCs of patients was higher than that of the controls (p=0.03). Based on these findings, increased frequency of DCs expressing CD83 and CD86, higher expression of CD86, HLA-DR, and TLR-2 as well as elevated secretion of proinflammatory cytokines in DCs of liver transplant recipient's point to the more mature phenotype and active function of DCs in patients compared with controls.

Everolimus With Reduced Tacrolimus Preserves Long-Term Renal Function in Liver Transplant Recipients: 36 and 48 Months Results From The H2304E1 Study.

Everolimus With Reduced Tacrolimus Preserves Long-Term Renal Function in Liver Transplant Recipients: 36 and 48 Months Results From The H2304E1 Study.

Everolimus-based immunosuppression in liver transplant recipients: a single-centre experience.

Everolimus, a mammalian target of rapamycin inhibitor, has been shown to reduce growth factor-mediated cell proliferation, but data regarding its effectiveness and impact on renal function and recurrence of hepatocellular carcinoma (HCC) in liver transplant (LT) recipients are limited. We evaluated LT recipients with a calcineurin inhibitor (CNI)-based immunosuppression regimen in whom everolimus treatment was initiated. The changes in laboratory data, including glomerular filtration rate (GFR), compared to the baseline (i.e. the day of everolimus conversion), were assessed. Totally, 44 consecutive patients (32 men, age 55±7years) were commenced on everolimus [indications: renal dysfunction post-LT (16 patients, group 1); prevention of HCC recurrence (21 patients) or others (7 patients), group 2] at 6months (range 1-206) post-LT. After 48 (range 12-76) months, all patients were alive without any rejection episodes. Compared to group 2 patients, group 1 patients had significantly greater improvement in renal function (DGFR: 12±5 vs. -0.4±0.2ml/min, p=0.02). GFR at baseline (OR 0.08, p=0.002) and the combination of everolimus + MMF (OR 0.14, p=0.024) were the factors independently associated with improvement in renal function. Finally, HCC recurrence was observed less frequently in the everolimus group of patients (n=21) compared to the CNI-historical control group (n=22) with HCC before LT [0/21 (0%) vs. 4/22 (18.5%), log rank p=0.055), although the two groups of recipients had similar baseline characteristics and follow-up. Everolimus is effective and is associated with low rates of HCC recurrence and improvement of renal function in LT recipients.

Improved renal function in liver transplant recipients treated for hepatitis C virus with a sustained virological response and mild chronic kidney disease

Hepatitis C virus (HCV) is associated with renal complications. We aimed to determine whether a sustained virological response (SVR) was associated with improvements in renal function (RF) in liver transplant (LT) recipients treated for HCV. Changes in RF were compared 1, 3, and 5 years after therapy as a function of the stage of chronic kidney disease (CKD) before treatment (BT). Variables associated with renal dysfunction [RD; 4-variable Modification of Diet in Renal Disease (MDRD-4) value 60 mL/minute] at the last follow-up (LFU) were evaluated for all treated LT patients with a minimum follow-up of at least 1 year since the end of treatment (EOT; n = 175). There were 99 patients with stage 2 CKD BT (MDRD-4 value 60-89 mL/minute/1.73 m(2) ), and an improvement in RF was observed more frequently among SVR patients versus nonresponders (NRs). The median changes in the MDRD-4 values BT to 1, 3, and 5 years after treatment were -0.5, 4.5, and 9.4 mL/minute for the SVR patients and -1, -0.3, and -1.5 mL/minute for the NRs (P = 0.61, P = 0.06, and P = 0.004, respectively). RD was present in 31% of the patients at the LFU at a median of 3.8 years after EOT (range 1-9 years). The follow-up did not differ between SVR patients and NRs. RD was present at the LFU in 19% of SVR patients versus 40% of NRs (P = 0.002). In the multivariate analysis, RD at the LFU was associated with NRs [relative risk (RR) 3.8, 95% confidence interval (CI) = 1.3-11.23, P = 0.01], EOT MDRD-4 values (RR = 1.022, 95% CI = 1.001-1.04, P = 0.04), and female sex (RR = 5.6, 95% CI = 1.84-17.5, P = 0.002). In conclusion, SVR leads to improved RF in HCV-infected LT recipients with stage 2 CKD BT.

Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation

Michael R. Lucey, Norah Terrault, Lolu Ojo, J. Eileen Hay, James Neuberger, Emily Blumberg, and Lewis W. Teperman Division of Gastroenterology and Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI; Gastroenterology Division, Department of Medicine, University of California San Francisco, San Francisco, CA; Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor, MI; Mayo Clinic, Rochester, MN; Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom; Division of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, PA; and Department of Surgery, NYU Transplant Associates, New York, NY

Renal dysfunction in liver transplant recipients: Evaluation of the critical issues

Major progress has been made in the field of liver transplantation since the first procedure was performed nearly 50 years ago. Despite these improvements, renal dysfunction before and after liver transplantation remains a major complicating factor associated with increased health care costs, morbidity, and mortality. Creatinine-based estimates of renal function are inaccurate in the setting of end-stage liver disease and often lead to underdiagnosis and late intervention. This issue is critical in that it is important to understand both the etiology and chronicity of renal dysfunction before liver transplantation because the treatment clearly varies, especially with respect to simultaneous liver-kidney (SLK) transplantation. Because of the scarcity of available grafts, identifying appropriate candidates for SLK transplantation is crucial. Hepatorenal syndrome is common in liver transplant candidates; however, other etiologies of renal dysfunction need to be considered. Renal dysfunction after liver transplantation is common and may have an acute or chronic presentation. Although calcineurin inhibitors (CNIs) have been associated with post-liver transplant nephrotoxicity, their role may be overestimated, and other contributing etiologies should remain in a clinician's differential diagnosis. Alternatives to CNIs have been evaluated; however, a safe immunosuppressive regimen that achieves the preservation of renal function in liver transplant recipients remains to be established. In this review of the literature, renal dysfunction in the setting of liver transplantation is evaluated, and the critical issues that are barriers to improved outcomes are highlighted.

ImmuKnow as a diagnostic tool for predicting infection and acute rejection in adult liver transplant recipients: A systematic review and meta-analysis

Immune status monitoring of transplant recipients could identify patients at risk of acute rejection, infection, and cancer, which are important sources of morbidity and mortality in these patients. The ImmuKnow assay provides an objective assessment of the cellular immune function of immunosuppressed patients. Inconclusive results concerning the ability of the ImmuKnow test to predict acute rejection and infection have raised concerns about the predictive value of ImmuKnow in liver transplant recipients. We conducted a systematic literature review to identify studies published up to March 2012 that documented the use of ImmuKnow for monitoring immune function in liver transplant recipients. The study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 score. We identified 5 studies analyzing ImmuKnow performance for infection and 5 studies analyzing ImmuKnow performance for acute rejection. The pooled sensitivity, specificity, positive likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 83.8% [95% confidence interval (CI) = 78.5%-88.3%], 75.3% (95% CI = 70.9%-79.4%), 3.3 (95% CI = 2.8-4.0), 14.6 (95% CI = 9.6-22.3), and 0.824 ± 0.034, respectively, for infection and 65.6% (95% CI = 55.0%-75.1%), 80.4% (95% CI = 76.4%-83.9%), 3.4 (95% CI = 2.4-4.7), 8.8 (95% CI = 3.1-24.8), and 0.835 ± 0.060, respectively, for acute rejection. Heterogeneity was low for infection studies and high for acute rejection studies. In conclusion, the ImmuKnow test is a valid tool for determining the risk of further infection in adult liver transplant recipients. Significant heterogeneity across studies precludes the conclusion that ImmuKnow identifies liver transplant patients at risk for rejection.

Proteinuria Following Sirolimus Conversion is Associated With Deterioration of Kidney Function in Liver Transplant Recipients

The role of sirolimus (SRL) conversion in the preservation of kidney function in liver transplant (LT) recipients with calcineurin inhibitor (CNI) nephrotoxicity is unclear. Data on 102 LT recipients with deteriorating kidney function after CNI exposure who were later converted to SRL were retrospectively reviewed. Kidney function was assessed using serum creatinine and estimated glomerular filtration rate (eGFR) at time of conversion and serially thereafter. The primary endpoint was stabilization or improvement of kidney function as assessed by eGFR at last recorded follow-up compared with eGFR at the time of conversion. After a median (interquartile range) of 3.1 (1.6-4.5) years of follow-up, serum creatinine decreased from 1.9 ± 0.8 to 1.8 ± 0.7 mg/dL (P=0.25) and eGFR increased from 40.8 ± 16.7 to 44.3 ± 20.0 mL/min (P=0.03). During the same time period, 24-hr urinary protein excretion increased from median (interquartile range) of 72 (0-155) to 382 (169-999) mg/day (P=0.0001). Sixty-five (64%) patients achieved the primary endpoint and 37 (36%) experienced deterioration in kidney function. Independent predictors of deterioration of kidney function after SRL conversion were development of proteinuria ≥ 1000 mg/day (odds ratio [OR]: 3.3, confidence interval [CI]: 1.1-9.5 P=0.03), post-LT diabetes (OR: 4.2, CI: 1.6-11.1, P=0.004), and higher eGFR at time of conversion (OR: 1.6, CI: 1.2-2.2, P=0.003). Improvement or stabilization of kidney function occurred in the majority of LT recipients converted to SRL for CNI nephrotoxicity. Proteinuria ≥ 1000 mg/day, post-LT diabetes, and higher baseline eGFR were independent predictors of kidney function loss after SRL conversion.

The assessment of GFR after orthotopic liver transplantation using cystatin C and creatinine-based equations

The measurement of kidney function after orthotopic liver transplantation (OLT) is still a clinical challenge. Cystatin C (CysC) has been proposed as a more accurate marker of renal function than serum creatinine (sCr). The aim of this study was to evaluate sCr- and CysC-based equations including the Chronic kidney disease (CKD)-EPI to determine renal function in liver transplant recipients. CysC and sCr were measured in 49 patients 24 months after OLT. The glomerular filtration rate (GFR) was calculated using the MDRD 4, the Cockroft-Gault, Hoek, Larsson, and the CKD-EPI equations based on sCr and/or CysC. As reference method, inulin clearance (IC) was estimated. Bias, precision, and accuracy of each equation were assessed and compared with respect to IC. Forty-five percent had a GFR < 60 ml/min/1.73 m(2) according to the IC. The Larsson, the Hoek and the CKD-EPI-CysC formula identified the highest percentage of patients with CKD correctly (88%, 88%, and 84%, respectively). The sCr-based equations showed less bias than CysC-based formulas with a similar precision. All CysC-based equations were superior as compared with sCr-based equations in the assessment of renal function in patients with an IC < 60 ml/min/1.73 m(2).

Ursodeoxycholic acid treatment to resolve abnormal function in liver transplant recipients

熊去氧胆酸(UDCA)在肝移植后主要拮抗疏水性胆汁酸的细胞毒性,但其对肝移植患者的保护作用尚存争议[1].本研究观察了华西医院127例肝移植术后患者使用UDCA的临床资料,现报道如下.一、资料与方法1.研究对象:收集我院2002年1月-2009年3月712例肝移植患者.术后平均随访35个月,随访方案采用移植术后3月内每半月随访1次,术后3～6个月患者每月随访1次,术后6～ 12个月患者每2个月随访1次,术后1年以上患者每3个月随访1次.符合本实验入组条件者127例(1例患者因不良反应退出研究). 关键词：熊脱氧胆酸;缺血再灌注损伤;肝移植

Hot-topic debate on kidney function: Renal-sparing approaches are beneficial

1. Renal function is frequently compromised in candidates for transplantation with advanced cirrhosis. These patients frequently have chronic and irreversible kidney changes at the time of transplantation. 2. The accumulated incidence of chronic renal failure is high in liver transplant recipients. Chronic renal failure has a deleterious impact on the outcome. 3. Calcineurin inhibitor (CNI)-based immunosuppression is highly effective at preventing rejection. However, CNI nephrotoxicity has a central role in the occurrence of chronic renal failure. 4. Renal function impairment frequently occurs within the first year after transplantation. Once renal function is significantly impaired [glomerular filtration rate (GFR) < 60 mL/minute/1.73 m(2) ], any intervention is unlikely to result in a return to normal renal function. Early interventions are needed to prevent chronic and irreversible kidney injury. 5. De novo CNI minimization has been proven to be effective at reducing the rate of impaired renal function after transplantation. The reduction in the CNI doses should be offset by the addition of mycophenolate mofetil or enteric-coated mycophenolate sodium. 6. Delayed CNI minimization in patients with established renal insufficiency may result in a significant improvement in the GFR, even though the increase in the GFR after minimization is generally modest. 7. Mammalian target of rapamycin (mTOR) inhibitors are considered nonnephrotoxic immunosuppressive agents. They may be an option for improving renal function in liver transplant recipients. However, not all patients with renal dysfunction benefit from a switch to mTOR inhibitors. In addition, the benefits in terms of renal function should be balanced against specific side effects. 8. New immunosuppressive agents without intrinsic nephrotoxicity are currently under development for solid organ transplantation. These agents could help to reduce the burden of impaired renal function in transplantation in the near future.

Is beta‐trace protein an alternative marker of glomerular filtration rate in liver transplant recipients?

Renal insufficiency is common after liver transplantation (LT). The use of creatinine (Crea) as a marker of the glomerular filtration rate (GFR) is limited in patients after LT. Beta-trace protein (BTP), an alternative marker of GFR, is independent of muscle mass and has not been evaluated in LT recipients. To evaluate BTP as an alternative tool to monitor renal function in LT recipients. We determined the diagnostic performance of BTP in comparison to Crea and cystatin C (CysC) in 52 patients, who concomitantly underwent (99m)Tc-DTPA-clearance measurements. Furthermore, we evaluated bias, precision and accuracy of five recently developed BTP-based equations to estimate GFR. The average measured GFR was 51 (46.1; 56.0) ml/min/1.73 m(2). Using a cut-off of 30 ml/min/1.73 m(2) the area under the curve (AUC) was nearly identical for all markers. At a decision point of 60 ml/min/1.73 m(2) BTP showed only a trend towards a higher AUC compared with Crea and CysC (0.806 vs. 0.754 and 0.760, respectively; P>0.2). In comparison to the modification of diet in renal disease-formula (MDRD) only one of five BTP-based equations displayed a significantly higher accuracy within 30% of the measured GFR (84.6 vs. 59.6%; P=0.006). None of these equations showed a significant improvement compared with MDRD with respect to bias and precision. Beta-trace protein can be used as an alternative diagnostic tool to detect moderate or severe GFR reduction in patients after LT. Furthermore BTP-based equations are able to estimate GFR in LT recipients. However, these equations fail to perform constantly better than the MDRD formula.

Conversion From Calcineurin Inhibitor to Either Mycophenolate Mofetil or Sirolimus Improves Renal Function in Liver Transplant Recipients With Chronic Kidney Disease: Results of a Prospective Randomized Trial

Background Chronic kidney disease (CKD) has emerged as a significant cause of morbidity and a risk factor for mortality after orthotopic liver transplantation (OLT). The use of calcineurin inhibitor (CNI)-based immunosuppression is an important etiologic factor for developing CKD. CNI discontinuation or minimization protocols with replacement of the CNI with non-nephrotoxic drugs, such as mycophenolate mofetil (MMF) or sirolimus (SRL), may have the potential to preserve or recover renal function. Patients and Methods In this prospective, randomized, single-center study with CNI discontinuation, OLT recipients with CKD (measured glomerular filtration rate [GFRm] 15–45 mL/min/1.73 m 2) were randomized to either SRL or MMF-based immunosuppression. The main objective was to study the effect of CNI discontinuation on renal function. Secondary aims were to assess the frequency of biopsy-proven acute rejection episodes (BPAR) and adverse events (AE). Renal function was followed with GFRm using 51-Chromium EDTA clearance at baseline, 3 months, and 1 year. Patients were stratified according to baseline GFRm > versus <30 mL/min/1.73 m 2. The 25 patients were enrolled for MMF (n = 13) or SRL (n = 12). The median age at inclusion was 59 years (range, 25–66) and the median number of years after OLT was 4.4 (range, 1–13). Twenty-two patients were followed up for a year; MMF (n = 12) and SRL (n = 10). Results Mean GFRm for the whole cohort (n = 25) was 31+/−8 mL/min/1.73 m 2 at baseline. After 3 months the GFRm (n = 23) increased to 40+/−10 mL/min/1.73 m 2 ( P = .0001) and at 1 year 42 +/− 11 mL/min/1.73 m 2 (n = 22). There was not significant difference between the MMF and the SRL study arms. The cohort (n = 8) with baseline GFRm <30 mL showed a 63% ( P = .003) increased filtration after 1 year. There was no significant difference in the frequency or severity of AE between the study arms with the exception of oral ulcerations and persistent hypertriglyceridemia in the SRL group. Two deaths occurred, 1 in each study arm, both probably unrelated to the change in immunosuppression. There were no BPAR episodes. Conclusion CNI discontinuation and replacement with either MMF or SRL resulted in a significant improvement in renal function even in those patients with severe CKD. The protocol was effective with no acute rejection episodes. The SRL arm showed a higher frequency of oral apthous ulcerations and hypertriglyceridemia. Future studies addressing long-term renal function after CNI discontinuation are needed.

Use of Sirolimus in Liver Transplant Recipients with Renal Insufficiency: A Systematic Review and Meta-Analysis

Sirolimus is used in patients with renal insufficiency after liver transplantation (LT) and especially in those with calcineurin inhibitor (CNI)-associated nephrotoxicity. We conducted a systematic review of all randomized controlled trials and observational studies to test the hypothesis that the use of sirolimus is associated with an improvement in renal function at 1 year in LT recipients with renal insufficiency [glomerular filtration rate (GFR) < 60 mL/minute or creatinine level ≥ 1.5 mg/dL]. We performed a search of all major databases, conference proceedings, and relevant journals through December 2009 and contacted content experts, corresponding authors, and the pharmaceutical manufacturer. A random effects model was used to determine the pooled estimate of the change in renal function and pooled risk estimates of adverse events that may be associated with sirolimus-based therapy at 1 year. Eleven studies (three randomized controlled trials and eight observational studies) met the final inclusion criteria. A nonsignificant improvement of 3.38 mL/minute [95% confidence interval (CI) = -2.93 to 9.69] was observed in methodologically sound observational studies and controlled trials reporting the primary outcome. In controlled trials, baseline GFR >50 mL/min sirolimus use was associated with an improvement of 10.35 mL/minute (95% CI = 3.98-16.77) in GFR or creatinine clearance. Sirolimus was not significantly associated with death [relative risk (RR) = 1.12, 95% CI = 0.66-1.88] or graft failure (RR = 0.80, 95% CI = 0.45-1.41), although reporting was incomplete. It was associated with a statistically significant risk of infection (RR = 2.47, 95% CI = 1.14-5.36), rash (RR = 7.57, 95% CI = 1.75-32.70), ulcers (RR = 7.44, 95% CI = 2.03-27.28), and discontinuation of therapy (RR = 3.61, 95% CI = 1.32-9.89). Conversion to sirolimus from CNIs is associated with a nonsignificant improvement in renal function in LT recipients with renal insufficiency, although the results are limited by heterogeneity, a risk of bias, and a lack of standardized reporting.

P96 Longitudinal changes in renal function in liver transplant recipients: impact of acute kidney injury and the assessment of the decline in estimated glomerular filtration rate over 5 years post liver transplantation

IntroductionOrthotopic liver transplantation (OLT) can valuably increase long term survival in patients with cirrhosis. After the immediate transplant period cardiovascular morbidity and mortality become increasingly important and chronic kidney disease...

Assessing Renal Function With Daclizumab Induction and Delayed Tacrolimus Introduction in Liver Transplant Recipients

Calcineurin inhibitor-induced renal dysfunction is a major problem in liver transplantation. Interleukin-2 receptor antagonist induction followed by delayed tacrolimus (Tac) administration may minimize the renal insult without compromising immunoprotection. This open, randomized, multicenter trial evaluated the benefit of daclizumab induction with delayed Tac on renal function at 6 months; an observational study was continued for 18 months. Liver transplant patients with a 12-hr serum creatinine (SrC) level less than 180 micromol/L received either delayed Tac with daclizumab induction (n=98) or standard Tac (n=101) both combined with mycophenolate mofetil and steroids. The primary endpoint was the incidence of SrC level more than 130 micrommol/L at 6 months. The incidence was 22.4% with delayed Tac and 29.7% with standard Tac (P=ns), which remained unchanged at 12 months (21.6% and 23.9%) but increasing slightly at 24 months (29.0% and 32.9%), respectively. A post hoc analysis of renal function was done based on patients stratification by SrC at 12 hr (<or=100micromol/L or >100 micromol/L) showing no difference in SrC values at 6 months regardless of the 12-hr values despite a trend toward better estimated glomerular filtration rate for patients with 12-hr value less than 100 micromol/L in the delayed Tac group. Biopsy-proven acute rejection was similar at 6 months (17.5% and 18.75%), 12 months (23.5% and 23.8%), and 24 months (24.5% and 25.7%), respectively. Patient and graft survival in both groups were comparable and good. Similar types and incidences of adverse events were reported in both groups at all time. Delay of Tac does not benefit renal function in liver transplant recipients with a good renal function at baseline.

Improvement of Renal Function After Conversion to Mycophenolate Mofetil Combined With Low-Level Calcineurin Inhibitor in Liver Transplant Recipients With Chronic Renal Dysfunction

Introduction Calcineurin inhibitors (CNI) are the main pathogenic factors for renal dysfunction in solid organ transplant recipients. Introduction of non-nephrotoxic immunosuppressive drugs, such as mycophenolate mofetil (MMF), may allow discontinuation or reduction of CNI treatment, thereby improving renal function. The aim of this study was to assess the feasibility, efficacy and safety of MMF introduction and CNI dosage reduction in the maintenance immunosuppressive protocol to improve renal function in liver transplant recipients with chronic renal dysfunction. Patients and Methods We prospectively included 88 liver transplant recipients including 74 men and an overall mean age of 58.8 ± 10.3 years who all displayed chronic renal dysfunction (creatinine >1.4 mg/dL) and proteinuria <1 g/d. They were subdivided into 3 groups according to the basal creatinine value 1.4–1.7 mg/dL (group I; n = 41); 1.8–2.0 mg/dL (group II; n = 28); and >2 mg/dL (group III; n = 19). MMF was initiated at 1.5–2.0 g/d. Reduction of tacrolimus or cyclosporine dosage was performed to achieve respective target trough levels of <5 ng/mL or <50 ng/mL. We performed periodic determinations of arterial pressure, liver function tests, serum creatinine, blood cells count, CNI levels, and proteinuria. Results Creatinine values after conversion were 1.4 ± 0.5 mg/dL in the overall group. Improvement of renal function was more frequent among groups I (80.4%) and II (92.8%) versus III (73.6%). Normalization of creatinine values was more frequent in group I (68.2%) with respect to cohorts II (21.4%) and III (10.5%). Rejection was not detected. Conclusion Application of an immunosuppressive protocol with MMF and low-level CNI in liver transplant recipients with chronic renal dysfunction was associated with improvement or normalization of creatinine, without an increased risk of rejection. Early conversion is needed to achieve the best results.