Early Steroid Withdrawal After Kidney Transplantation in Patients at Risk for New-Onset Diabetes After Transplantation

BackgroundNew-onset diabetes after transplantation (NODAT) is a serious complication after kidney transplantation because of worse graft survival and increased risk of cardiovascular events. It is partly induced by immunosuppressive therapies such as corticosteroids. This study aimed to assess whether early corticosteroid withdrawal on day 4 (early steroid withdrawal [ESW] group) could prevent the development of NODAT within 2 years posttransplantation while maintaining good graft and patient survival rates.MethodsThis was an observational, single-center, retrospective study. All patients received an induction therapy of antithymocyte globulin or basiliximab and maintenance therapy of tacrolimus/mycophenolate mofetil/corticosteroids. Patients were either weaned off corticosteroids on day 4 (ESW group) or were maintained on corticosteroids for at least 3 months (standard group). NODAT was defined as the initiation of any oral hypoglycemic agent or insulin at 3 months and up to 2 years posttransplantation in previously nondiabetic recipients.ResultsBetween January, 1, 2010, and December 14, 2014, 492 recipients were included in this study; 88 received the ESW strategy, and 404 received the standard strategy. Age and body mass index (BMI) were significantly higher in the ESW group. The incidence of NODAT was 36.8% in the ESW group and 8.8% in the standard group (odds ratio [OR], 47.5; P < .001). Compared with a matched sample from the standard group that had the same probability to benefit from ESW at baseline, ESW was still associated with a significantly increased risk of NODAT (OR, 4.41; P = .018). Among recipients with a BMI >25 kg/m², the ESW strategy significantly decreased the risk of NODAT compared with the standard strategy (OR, 0.07; P = .013). Safety endpoints (eg, acute rejection, de novo–specific antibodies, graft function/survival) did not differ between groups.ConclusionDespite a reassuring safety profile, ESW on day 4 after kidney transplantation only had a marginal effect on the incidence of NODAT.     

Diabetes Mellitus After Living Donor Liver Transplantation: Data From Mainland China

Most reported data on posttransplantation diabetes mellitus (PTDM) are from Western countries with patients who underwent deceased donor liver transplantation. A retrospective study was performed to assess the prevalence and predictive factors of PTDM in the context of living donor liver transplantation (LDLT) in the Chinese population using the definition of PTDM proposed in 2003 by the World Health Organization and the American Diabetes Association. The prevalence of DM after LDLT in our study was 25% (21/84), and the incidence of PTDM was 14.9% (11/74) with 64% of cases diagnosed within 3 months after LDLT; 9.5% were observed to show impaired fasting glucose postoperatively. Multivariate analysis identified body mass index ≥ 25 kg/m² before LDLT as the only independent risk factor for developing PTDM. Only one patient was operated for hepatitis C virus (HCV) infection. Hepatitis B virus (HBV)-related diseases were common in our study population, accounting for 78.6% of all patients. Both HCV and HBV infection status were not independent risk factors for developing PTDM. In addition, a greater tacrolimus trough blood level in the PTDM group versus no-DM group was observed at 3 months post-LDLT (11.03 ng/mL vs 4.87 ng/mL). The mean tacrolimus dose was not significantly different between the two groups. In conclusion, PTDM was prevalent among Chinese LDLT recipients.     

Long-term Changes in Spleen Volume After Living Donor Liver Transplantation in Pediatric Recipients

Background

Living donor liver transplantation (LDLT) is a definitive procedure for splenomegaly caused by liver cirrhosis and portal hypertension, but splenomegaly persists in some patients. The aim of this study was to clarify the long-term changes in the spleen volume after LDLT.

Repaglinide in the Management of New-Onset Diabetes Mellitus After Renal Transplantation

The purpose of this study was to investigate the use of the short-acting insulin secretion drug repaglinide in new-onset diabetes mellitus (NODM) after renal transplantation. Twenty-three Caucasian patients with NODM after renal transplantation were selected to receive repaglinide therapy and were followed for at least 6 months. A control group treated with rosiglitazone was chosen for comparison. Successful repaglinide treatment was defined as a significant improvement of blood glucose concentrations and HbA1c <7% in the absence of glucosuria and without the need for the addition of further anti-diabetic agents. After 6 months of treatment with repaglinide, 14 of the 23 patients were successfully treated. Mean HbA1c decreased from 7.6 +/- 0.6% to 5.8 +/- 0.6% in 14 patients treated successfully. In nine patients, hyperglycemia persisted, and they were switched to insulin treatment (HbA1c 8.5 +/- 2.9% at the beginning to 7.4 +/- 2.2%). Mean serum creatinine levels, cyclosporine A and tacrolimus blood levels did not change significantly following institution of repaglinide therapy. The rate of successful treatment and the degree of HbA1c decrease were similar compared to rosiglitazone-treated control patients. The data from our observational study indicate that repaglinide can be an effective treatment option in Caucasian patients with NODM after renal transplantation.     

Donor Outcomes After Liver Donation in Adult to Adult Living Donor Liver Transplantation

Objectives

This study aims to investigate postdonation outcomes of adult living donor liver transplantation donors and remnant liver regeneration in different graft types.

Steroid Withdrawal Using Everolimus in ABO-Incompatible Kidney Transplant Recipients With Post-Transplant Diabetes Mellitus

Background

The effectiveness of everolimus (EVR) for ABO-incompatible (ABOi) kidney transplantation is unknown. We evaluated outcomes of conversion from steroid to EVR in ABOi kidney transplant recipients.

Long-Term Outcome of Early Steroid Withdrawal After Kidney Transplantation in African American Recipients Monitored by Surveillance Biopsy

Generally chronic steroid therapy is standard care for African American (AA) kidney recipients because of their higher incidence of rejections and lower long-term graft survival. This prospective study evaluated the long-term safety and efficacy of early steroid withdrawal (ESW) in AA recipients. A total of 206 recipients were studied; 103 AA and 103 non-AA recipients monitored by serial surveillance biopsies from 1 to 60 months posttransplantation to evaluate subclinical acute rejections (SCAR) and chronic allograft injury (CAI). Biopsy-proven clinical acute rejections (BPAR) and SCAR were treated. Primary end point was BPAR and secondary end points were 5-year SCAR, CAI and survival. Incidences of BPAR was 16% versus 14% (p = 1.0), prevalence of CAI due to hypertension was 48% versus 30% (p = 0.05) and interstitial fibrosis/tubular atrophy was 47% versus 32% (p = 0.05) and the mean serum creatinine levels were 2.1 versus 1.8 mg/dL (p = 0.05) at 5-years in AA versus non-AA recipients. The incidence of SCAR was 23% versus 11% at 1 month (p = 0.04), 12% versus 3% at 3 years (p = 0.04) and 10% versus 1% at 5 years (p = 0.04) in AA and non-AA recipients, respectively. Five-year patient survivals were 81% and 88% (p = 0.09) and graft survivals were 71% and 73%(p = 0.19) in AA and non-AA groups, respectively. After early steroid withdrawal AA kidney recipients have significantly lower renal function and higher SCAR and CAI but 5-year graft survival are comparable to non-AA recipients.     

Clinical Significance of Plasma Tenascin-C Levels in Recipients With Prolonged Jaundice After Living Donor Liver Transplantation

BackgroundFocusing on tenascin-C (TNC), whose expression is enhanced during the tissue remodeling process, the present study aimed to clarify whether plasma TNC levels after living donor liver transplantation (LDLT) could be a predictor of irreversible liver damage in the recipients with prolonged jaundice (PJ).MethodsAmong 123 adult recipients who underwent LDLT between March 2002 and December 2016, the subjects were 79 recipients in whom we could measure plasma TNC levels preoperatively (pre-) and on postoperative days 1 to 14 (POD1 to POD14). Prolonged jaundice was defined as serum total bilirubin level >10 mg/dL on POD14, and 79 recipients were divided into 2 groups: 56 in the non-PJ (NJ) group and 23 in the PJ group.ResultsThe PJ group had significantly increased pre-TNC; smaller grafts; decreased platelet counts POD14; increased TB-POD1, -POD7, and -POD14; increased prothrombin time–international normalized ratio on POD7 and POD14; and higher 90-day mortality than the NJ group. As for the risk factors for 90-day mortality, multivariate analysis identified TNC-POD14 as a single significant independent prognostic factor (P = .015). The best cut-off value of TNC-POD14 for 90-day survival was determined to be 193.7 ng/mL. In the PJ group, the patients with low TNC-POD14 (<193.7 ng/mL) had satisfactory survival, with 100.0 % at 90 days, while the patients with high TNC-POD14 (≥193.7 ng/mL) had significantly poor survival, with 38.5 % at 90 days (P = .004).ConclusionsIn PJ after LDLT, plasma TNC-POD14 is very useful for diagnosing postoperative irreversible liver damage early.     

Prevalence and Treatment of New-Onset Diabetes Mellitus After Liver Transplantation in Korean Children: A Single-Center Study

The aim of this study was to investigate the prevalence, clinical characteristics, and management of new-onset diabetes mellitus (NODM) in Korean children with liver transplantation (LT). We retrospectively analyzed the medical records of 200 pediatric patients (5 months to 17 years old) who underwent LT at Asan Medical Center between January 1994 and December 2010; 26 pediatric patients who died at the maximal follow-up after LT or who were lost to follow-up were excluded from the study. Among these 174 children, NODM after LT developed in 18. The median interval time at the presentation of NODM after LT was 15 days (range, 1 day to 16.0 years), whereas the median patient age of NODM diagnosis was 10 years (range, 1.1 to 17.0 years). Insulin treatment with reduction in tacrolimus dosage, steroid tapering, and conversion from tacrolimus to cyclosporine with or without mycophenolate mofetil is highly effective in NODM after LT. In conclusion, careful diabetes mellitus monitoring and modification of immunosuppressive regimen should be required in pediatric patients after LT.     

Quality of Life and Problems Affecting Recipients More Than 10 Years After Living Donor Liver Transplantation

Background

We initiated living donor liver transplantation (LDLT) in 1991, allowing us to examine issues related to long-term survival. The aim of this study was to review the long-term outcomes of LDLT in children.

Patients and Methods

We performed 116 LDLT from 1991 to present, including 17 recipients who survived >10 years. They were evaluated for growth, immunosuppressive therapy, complications, and quality of life (QOL).

Results

The average age at LDLT was 5.4 years (range, 6 months to 17 years), with a present average age of 17.2 years (range, 11-28 years). At the time of LDLT, 6 recipients had growth retardation with body weights low for age by 2 standard deviations (SD). However, 4 of 6 recipients who underwent LDLT before age of 2 years caught up, reaching average heights and body weights for their ages. Among 6 recipients who were diagnosed with acute rejections by biopsy >5 years after LDLT, 5 improved after steroid pulse therapy. One recipient with a steroid-resistant acute rejection was administered deoxyspergualin after steroids. Chronic rejection was not observed in this series. One recipient has not required immunosuppressive therapy for >4 years with a good present condition.

Conclusion

The majority of LDLT recipients achieved a good QOL during long-term survival; they are pursuing normal studies.     

Incisional Hernia in Recipients of Adult to Adult Living Donor Liver Transplantation

Background

After receiving a living donor liver transplant (LDLT), an incisional hernia is a potentially serious complication that can affect the patient’s quality of life. In the present study we evaluated surgical hernia repair after LDLT.

Materials and methods

Medical records of patients who underwent surgery to repair an incisional hernia after LDLT in Turgut Ozal Medical Center between October 2006 and January 2010 were evaluated in this retrospective study. A reverse-T incision was made for liver transplantation. The hernias were repaired with onlay polypropylene mesh. Age, gender, post-transplant relaparatomy, the type, the result of surgery for the incisional hernia, and risk factors for developing incisional hernia were evaluated.

Results

An incisional hernia developed in 44 of 173 (25.4 %) patients after LDLT. Incisional hernia repair was performed in 14 of 173 patients (8.1 %) who underwent LDLT from October 2006 to January 2010. Relaparatomy was associated with incisional hernia (p = 0.0002). The mean age at the time of the incisional hernia repair was 51 years, and 79 % of the patients were men. The median follow-up period was 19.2 (13–36) months after the hernia repair. Three patients with intestinal incarceration underwent emergency surgery to repair the hernia. Partial small bowel resection was required in one patient. Postoperative complications included seroma formation in one patient and wound infection in another. There was no recurrence of hernia during the follow-up period.

Conclusions

The incidence of incisional hernia after LDLT was 25.4 % in this study. Relaparatomy increases the probability of developing incisional hernia in recipients of LDLT. According to the results of the study, repair of an incisional hernia with onlay mesh is a suitable option.     

Outcome After Steroid Withdrawal in Heart Transplantation

Background

There is a lack of consensus and insufficient data to assess the impact of late steroid withdrawal after heart transplantation (HTx). The aim of the study was to investigate the security and feasibility of corticosteroid withdrawal at 1 year after transplantation.

Methods and Results

Steroid withdrawal was attempted after at least 12 months of treatment in 86 HTx patients who fulfilled the criteria. At 1 and 3 months after drug discontinuation, patients underwent 2 endomyocardial biopsies (EMB). After a mean follow-up of 25 ± 13 months, 63% of the patients remained steroid free. In 30 patients (35%) corticosteroids were reinitiated, in 15 cases because of acute rejection (7%), 5 (6%) because of worsening renal function, 5 (6%) because of malignancy, 3 (4%) because of adverse effects of immunosuppressive drugs, and 2 because of severe allograft coronary artery disease. Four patients (5%) died after drug discontinuation. There was a significant decrease in total cholesterol (198 ± 35 to 181 ± 38 mg/dL; P < .001) and low-density lipoprotain (LDL) cholesterol levels (113 ± 30 to 105 ± 30 mg/dL; P < .001). There were no differences in mortality between patients with and without corticosteroids.

Conclusion

Steroid withdrawal is feasible and safe in HTx patients. In our study, it was successfully maintained in 63% of the patients. EMB is helpful to identify patients with acute rejection at 1 and 3 months after withdrawal. Short- to mid-term metabolic benefits are significant reductions in serum total and LDL cholesterol.     

New-Onset Diabetes After Transplantation: Comparison Between a Cyclosporine-Based and a Tacrolimus-Based Immunosuppressive Regimen

Introduction

New-onset diabetes after transplantation (NODAT) is a complication of renal transplantation (RT) with an adverse effect on graft survival.

Risk Factors for Development of New-Onset Diabetes Mellitus and Progressive Impairment of Glucose Metabolism After Living-Donor Liver Transplantation

Background

New-onset diabetes mellitus (NODM) has a negative impact on graft and patient survivals. Hepatitis C virus (HCV) infection, high body mass index, increased donor and recipient ages, and calcineurin inhibitor (CNI) type have been identified as risk factors for the development of NODM. We aimed to elucidate the risk factors for the development of NODM and those for progressive glucose intolerance in adult living-donor liver transplant (LDLT) recipients.

Methods

We collected data from 188 primary liver transplant recipients (age > 16 years) who underwent LDLT from June 1991 to December 2011 at Hiroshima University Hospital. Risk factors for NODM and progressive impairment of glucose metabolism in pre-transplantation diabetes mellitus (DM) recipients were examined.

Results

Pre-transplantation DM was diagnosed in 32 recipients (19.3%). The overall incidence of NODM was 6.0% (8/134 recipients). Multivariate analysis revealed that old recipient age (≥55 years) is a unique predictive risk factor for developing NODM. The incident of pre-transplantation DM was significantly higher in recipients with HCV infection than in those without HCV. A high pre-transplantation triglyceride level was an independent risk factor for progressive impairment of glucose tolerance among 32 LDLT recipients with pre-transplantation DM. All of the NODM patients were being treated with tacrolimus at the time of diagnosis. Switching the CNI from tacrolimus to cyclosporine allowed one-half of the patients (4/8) to withdraw from insulin-dependent therapy. NODM and post-transplantation glucose intolerance had no negative impact on patient and graft outcomes.

Conclusions

Older age of the recipient (≥55 years) was a significant risk factor for NODM. Hypertriglyceridemia in the recipients with DM is an independent risk factor for post-transplantation progressive impairment of glucose metabolism. NODM had no negative impact on outcomes in the LDLT recipients.     

Adult Living Donor Liver Transplantation

Adult living donor liver transplantation (LDLT) begun in response to deceased donor organ shortage and waiting list mortality, grew rapidly after its first general application in the United States in 1998. There are significant risks to the living donor, including the risk of death and substantial morbidity, and two highly publicized donor deaths have led to decreased LDLT since 2001. Significant improvements in outcomes have been seen over recent years that have not been reported in single center studies; however, LDLT still comprises less than 5% of adult liver transplants, significantly less than in kidney transplantation where living donors now comprise the majority. The ethics, optimal utility and application of LDLT remain to be defined. In addition, studies to date have focused on post-transplant outcomes and not included the potential impact of LDLT on waiting time mortality. Future analyses should include appropriate control or comparison groups that capture the effect of LDLT on overall mortality from the time of listing. Further growth of LDLT will depend on defining the optimal recipient and donor characteristics for this procedure as well as broader acceptance and experience in the public and in transplant centers.     

Dysfunction in Patients With Small-for-Size Grafts After Living Donor Liver Transplantation

The relationship between postoperative percentage fall of platelet (PLT) counts and graft dysfunction after living donor liver transplantation (LDLT) in recipients with small-for-size (SFS) graft has not been fully evaluated. We retrospectively studied 50 adult-to-adult LDLT recipients with a graft-to-recipient weight ratio of <0.8% between 1999 and 2011. Graft dysfunction was defined as the presence of hyperbilirubinemia, coagulopathy, or ascites on 3 consecutive days during the first postoperative week. Each clinical sign of dysfunction was assigned 1 point. Postoperative percentage fall in PLT counts, graft dysfunction score, and postoperative complications according to the Clavien-Dindo classification were investigated. Overall, 31 patients (62%) exhibited a PLT count fall of more than 50%, and 19 (38%) patients exhibited a PLT count fall of less than 50% at postoperative day (POD) 3. Receiver operating characteristic curve analysis indicated that at POD 3, the cutoff value of PLT count fall was 56% for a graft dysfunction score of 2 or 3 (sensitivity, 70%; specificity, 63.3%). Fourteen of 20 patients (70%) with a dysfunction score of 2 or 3 and 11 of 30 patients (37%) with a dysfunction score of 0 or 1 showed a fall in PLT count >56% at POD 3 (P = 0.021). Grade 2 to 5 complications were more observed in patients with a dysfunction score of 2 or 3 than in patients with a dysfunction score of 0 or 1 (P < 0.001). The fall of PLT count at POD 3 >56% is an ominous sign that can predict the graft dysfunction after LDLT in recipients with SFS graft.Key words: Thrombocytopenia, Small-for-size graft, Portal hypertension, Small-for-size syndrome, Graft dysfunctionSince living donor liver transplantation (LDLT) has become widely accepted as a treatment of choice for end-stage liver disease (ESLD),¹ we often encounter a situation involving graft-size mismatching. A graft-to-recipient weight ratio (GRWR) of <0.8% has been demonstrated as a predictor of poor morbidity and mortality.² Patients with ESLD frequently suffer from thrombocytopenia and refractory ascites caused by portal hypertension before surgery. In LDLT, portal hypertension is not immediately relieved after surgery, especially when using a small graft; moreover, it leads to graft dysfunction and so-called small-for-size (SFS) syndrome.^2,3 Use of the smaller graft may contribute to slow recovery of platelet (PLT) counts or protracted thrombocytopenia.In the clinical setting, the lowest PLT counts are usually observed during the first week after LDLT and recover with restoration of graft function. The delayed recovery of PLT counts may lead to increased morbidity and mortality resulting from bleeding-related complications and infections during the postoperative period.^4,5 Previous studies have not clearly demonstrated the relationship between postoperative thrombocytopenia and graft dysfunction following LDLT, especially in SFS graft recipients.The aim of this study was to investigate whether the observed early postoperative percentage fall of PLT counts predicts the graft dysfunction of patients with an SFS graft (GRWR <0.8%) after LDLT.     

Steroid Avoidance Versus Steroid Withdrawal After Simultaneous Pancreas-Kidney Transplantation

Two steroid-sparing immunosuppressive regimens were prospectively compared in recipients of simultaneous pancreas-kidney transplants, one did not include steroids at all and the other included steroids for the first 3 months following transplantation. All patients received rabbit anti-thymocyte globulin, mycophenolate mofetil (MMF) and cyclosporine. Fifty patients were randomised in an open-label, single center and prospective study. The incidence of biopsy-proven acute rejection during the first 12 months after transplantation was the primary endpoint of the study. The incidence of biopsy-proven acute rejection was 4% in both groups. No statistically significant difference in patient (96 and 100%), kidney (96 and 100%) or pancreas (84 and 92%) survival was observed 1 year after transplantation in the steroid avoidance and steroid withdrawal groups, respectively. The total number of adverse events (including severe ones), length of hospitalization and infectious episodes did not differ between groups. Blood glucose and insulin levels, lipid profile and hemoglobin A1C levels did not differ statistically between the two groups. However, the 1-year serum creatinine level was significantly higher in the steroid avoidance group (132 vs. 114 micromol/L; p = 0.02). Steroid avoidance and steroid withdrawal 3 months after transplantation are safe and effective regimens for diabetic patients with pancreas-kidney transplants.     

Risk Factors for New-Onset Diabetes Mellitus After Heart Transplantation: A Nomogram Approach

BackgroundNew-onset diabetes mellitus after transplantation (NODAT) is a leading cause of morbidity and mortality after heart transplantation (HT), which still remains a clinical challenge.MethodsIn this study, 522,708 follow-up records of HT were reviewed. After screening, 14,452 patients were analyzed when combined with immunosuppression records. We divided all patients into no-NODAT group, NODAT group, and preexisting diabetes group based on whether the patient had diabetes and the time when it occurred. Cox regression models were used to examine independent risk factors. A nomogram was established to predict the incidence of NODAT after HT. The machine learning method were used to confirm the prediction accuracy and reliability of the nomogram.ResultsPatients who experienced NODAT after HT had poor survival compared with those without NODAT. Tacrolimus, cyclosporine A (CsA), rapamycin, donor age, and recipient age at the time of transplant were significant predictors of NODAT. Tacrolimus had a more significant association with NODAT, followed by rapamycin and CsA. The nomogram method we adopted in this study had an accuracy of 63% in predicting the incidence of NODAT.ConclusionThe survival probability of HT recipients with NODAT showed a significant decreasing tendency. However, there was no difference in survival probability between patients with preexisting diabetes and patients with NODAT. Tacrolimus had a more significant association with NODAT than CsA and rapamycin.