Insulin Secretion and Insulin Resistance Trajectories over 1 Year after Kidney Transplantation: A Multicenter Prospective Cohort Study

Background@#We investigated the changing patterns of insulin secretion and resistance and risk factors contributing to the development of post-transplant diabetes mellitus (PTDM) in kidney recipients under tacrolimus-based immunosuppression regimen during 1 year after transplantation. @*Methods@#This was a multicenter prospective cohort study. Of the 168 subjects enrolled in this study, we analyzed a total 87 kidney transplant recipients without diabetes which was assessed by oral glucose tolerance test before transplantation. We evaluated the incidence of PTDM and followed up the index of insulin secretion (insulinogenic index [IGI]) and resistance (homeostatic model assessment for insulin resistance [HOMA-IR]) at 3, 6, 9 months, and 1 year after transplantation by oral glucose tolerance test and diabetes treatment. We also assessed the risk factors for incident PTDM. @*Results@#PTDM developed in 23 of 87 subjects (26.4%) during 1 year after transplantation. More than half of total PTDM (56.5%) occurred in the first 3 months after transplantation. During 1 year after transplantation, insulin resistance (HOMA-IR) was increased in both PTDM and no PTDM group. In no PTDM group, the increase in insulin secretory function to overcome insulin resistance was also observed. However, PTDM group showed no increase in insulin secretion function (IGI). Old age, status of prediabetes and episode of acute rejection were significantly associated with the development of PTDM. @*Conclusion@#In tacrolimus-based immunosuppressive drugs regimen, impaired insulin secretory function for reduced insulin sensitivity contributed to the development of PTDM than insulin resistance during 1 year after transplantation.

Insulin Secretion and Insulin Resistance Trajectories over 1 Year after Kidney Transplantation: A Multicenter Prospective Cohort Study

Background@#We investigated the changing patterns of insulin secretion and resistance and risk factors contributing to the development of post-transplant diabetes mellitus (PTDM) in kidney recipients under tacrolimus-based immunosuppression regimen during 1 year after transplantation. @*Methods@#This was a multicenter prospective cohort study. Of the 168 subjects enrolled in this study, we analyzed a total 87 kidney transplant recipients without diabetes which was assessed by oral glucose tolerance test before transplantation. We evaluated the incidence of PTDM and followed up the index of insulin secretion (insulinogenic index [IGI]) and resistance (homeostatic model assessment for insulin resistance [HOMA-IR]) at 3, 6, 9 months, and 1 year after transplantation by oral glucose tolerance test and diabetes treatment. We also assessed the risk factors for incident PTDM. @*Results@#PTDM developed in 23 of 87 subjects (26.4%) during 1 year after transplantation. More than half of total PTDM (56.5%) occurred in the first 3 months after transplantation. During 1 year after transplantation, insulin resistance (HOMA-IR) was increased in both PTDM and no PTDM group. In no PTDM group, the increase in insulin secretory function to overcome insulin resistance was also observed. However, PTDM group showed no increase in insulin secretion function (IGI). Old age, status of prediabetes and episode of acute rejection were significantly associated with the development of PTDM. @*Conclusion@#In tacrolimus-based immunosuppressive drugs regimen, impaired insulin secretory function for reduced insulin sensitivity contributed to the development of PTDM than insulin resistance during 1 year after transplantation.

Whole Body Bone Scan for Detecting Missed Bone Injuries in Multiple Trauma Patients

PURPOSE: Patients with multiple traumas often experience multiple fractures that are missed or overlooked, despite the use of imaging, careful history taking, and physical examinations. This study aimed to evaluate the usefulness of whole body bone scan (WBBS) for detecting missed bone injuries in patients with multiple traumas. METHODS: We evaluated 30 patients with multiple traumas who underwent WBBS at single tertiary referral center between March 2008 and February 2016. We assessed the association of patient demographics with WBBS uptake as a binomial outcome variable. RESULTS: There were no significant differences in patient demographics by WBBS. The mean injury severity score did not differ by WBBS (18.1 in the WBBS-negative group vs. 18.4 in the WBBS-positive group), and duration from admission to the evaluation of the WBBS was similar (5.4 days in both groups). The most common uptake site in the WBBS was the ribs (n=7), followed by the tibia (n=3), skull (n=2), ankle (n=1), and sternum (n=1). None of the missed injuries required further treatment, such as manual reduction or surgery. CONCLUSION: WBBS was useful for detecting missed bone injuries in patients with multiple trauma.

Which patients with intestinal obstruction need surgery? The delta neutrophil index as an early predictive marker

PURPOSE: Predicting the need for surgical intervention among patients with intestinal obstruction is challenging. The delta neutrophil index (DNI) has been suggested as a useful marker of immature granulocytes, which indicate an infection or sepsis. In this study, we evaluated the impact of the DNI as an early predictor of operation among patients with intestinal obstruction. METHODS: A total of 171 patients who were diagnosed with postoperative intestinal obstruction were enrolled in this study. Medical records, including data for the initial CRP level, WBC count, and DNI were reviewed. Receiver operating characteristic (ROC) curves were generated to clarify the optimal DNI cutoff values for predicting an operation. RESULTS: Among the 171 patients, 38 (22.2%) needed surgical intervention. The areas under the initial CRP, WBC, and DNI ROC curves were 0.460, 0.449, and 0.543, respectively. The optimal cutoff value for predicting further surgical intervention according to the initial DNI level was 4.3%. The accuracy of the cutoff value was 74.9%, the sensitivity was 23.7%, and the specificity was 89.5% (positive predictive value, 23.7%; negative predictive value, 89.5%). In the multivariate analysis, initial DNI levels ≥ 4.3% were significantly associated with surgical intervention (odd ratio, 3.092; 95% confidence interval, 1.072–8.918; P = 0.037). CONCLUSION: The initial DNI level in patients with intestinal obstruction may be a useful predictor for determining the need for surgical intervention.

Management of Opportunistic Infections after Organ Transplantation / 대한이식학회지

Solid organ transplantation is a therapeutic option for end-stage organ diseases. However, complications including infection and graft rejection, which are related to immunosuppressive therapy, remain the major causes of morbidity and mortality following solid organ transplantation. The optimal approach to infection in solid organ transplant recipients is prevention; failing this, prompt and aggressive diagnosis and therapy are essential. In addition, the epidemiology of infections after solid organ transplantation has shifted as a result of changes in immunosuppressive strategies and improved survival. Immunosuppression must be linked with appropriate vaccinations, donor and recipient screening, patient education regarding infectious risks and lifestyle, monitoring, and antimicrobial prophylaxis.

Effect of donor-specific antibodies and panel reactive antibodies in living donor liver transplant recipients

PURPOSE: Preformed circulating donor-specific antibodies (DSAs) immunologically challenge vascular endothelium and the bile duct. However, the liver is an immune-tolerant organ and can avoid immunological challenges. This study was undertaken to analyze the effects of DSAs after adult living donor liver transplantation (LDLT). METHODS: We retrospectively reviewed 219 LDLT patients' records treated at our center. RESULTS: Of the 219 patients, 32 (14.6%) were DSA (+) and 187 (85.4%) were DSA (-). Class I DSAs were present in 18 patients, class II in seven patients, and both in seven patients. Seven patients (3.2%) showed DSA to HLA-A, four (1.8%) to HLA-B, seven (3.2%) to HLA-DR, and 14 (6.4%) to two or more HLAs. More DSAs were observed in female recipients than male recipients in the DSA (+) group. The DSA (+) group showed significantly higher levels of class I and II panel reactive antibody (PRA) than did the DSA (-) group. No significant intergroup differences were found between incidences of primary nonfunction, acute rejection, vascular complication, or biliary complication. There were no significant differences in graft survival rates between the two groups. However, the recipients with multiple DSAs tended to have more acute rejection episodes and events of biliary stricture and lower graft survival rates than did patients in the DSA (-) group. CONCLUSION: In LDLT, the presence of multiple DSAs and high PRA seemed to be associated with poor graft outcomes, although our results did not reach statistical significance. Large cohort studies are necessary to clarify the impact of DSA and PRA in LDLT.

Evaluation of Independent Risk Factors Affecting Renal Allograft Survival by Transplant Era / 대한이식학회지

BACKGROUND: Using long-term (more than 30 years) data from a single center, this retrospective study evaluated changes of independent risk factors affecting renal allograft survival by transplant era. METHODS: Of 3,000 cases of kidney transplantation, 2,708 (90.3%), including their follow-up observations, were reviewed. Transplant era was classified according to immunosuppressive regimens as either early group (transplant serial No. 1~1,500) or recent group (transplant serial No. 1,501~3,000). RESULTS: There was a significant difference observed in pre-transplant clinical manifestations between the early and recent groups. The number of elderly recipients and donors, number of deceased donors, and cases related to pre-transplant diabetes, pre-emptive transplantation, and retransplantation were differed relative to transplant era. The short- and long-term graft survival rate of the recent group improved significantly, and the effect of human leukocyte antigen mismatching and living donor type disappeared in the recent group. Moreover, pre-emptive transplantation and retransplantation were effective only in the recent group. However, non-immunological factors such as elderly recipients and donors, and immunologic factors such as episodes of acute rejection and types of immunosuppressive regimen were persistent independent risk factors affecting graft survival rate. CONCLUSIONS: According to the retrospective survival analysis of a large number of recipients in a single center, risk factors for kidney transplant patients differed by transplant era. However, the independent risk factors associated with elderly recipients and donors (non-immunologic), and episodes of acute rejection, and types of immunosuppressive regimen (immunologic) persisted regardless of transplant era.

Clinical Characteristics and Treatment Outcomes of Colorectal Cancer in Renal Transplant Recipients in Korea

PURPOSE: Transplant recipients in Asia appear to be at a higher risk for developing colorectal cancer (CRC). This study was performed to identify the clinicopathological features and oncologic outcomes of CRC in post-renal transplants in Korea. MATERIALS AND METHODS: We retrospectively reviewed the records of 17 patients with CRC out of 2,630 recipients who underwent renal transplantation between 1994 and 2007. These patients (transplant group) were compared with general CRC patients (n=170, control group) matched, based on the closest date of surgery to the transplant group. RESULTS: During 29.7 months of the median follow-up period, the recurrent and survival rates from recurrence were worse in the transplant group than in the control group (35.2% versus 15.2%; p=0.048 and p=0.025). The 2-year patient survival rate of the transplant group was significantly worse than the control group in advanced cancer (stages III-IV; 45.7% versus 71.6%; p=0.023). In early cancer (stages 0-I), there was no significant difference in 5-year patient survival rate between the two groups (100% versus 92.6%, respectively; p=0.406). CONCLUSION: In spite of a poor prognosis of advanced CRC in the transplant group, the early stage CRC of the transplant group showed a comparable oncologic outcome compared with the control group. Regular screening and early detection of CRC are essential in the post-transplant setting.

Sirolimus/steroids Maintenance Therapy after Early Cyclosporine Withdrawal: 12-month Efficacy and Safety Results of Multicenter Single Arm Pilot Study in Primary Renal Allograft Recipients in Korea

PURPOSE: Sirolimus has potent anti-rejection activity as well as the ability to prolong allograft survival and reduce nephrotoxicity. This study was designed to evaluate the efficacy and safety of sirolimus in Korean de novo renal transplantation. METHODS: We included 79 patients who received sirolimus at nine Korean transplantation centers in the intention-to-treat and valid-for-safety analyses. The study was an open, single treatment arm multicenter trial with 12 months of patient follow-up. Initially, patients received 2 mg of sirolimus (after 6 mg of loading does) with cyclosporine and steroids. Sirolimus was administered for up to 12 months. Antibody induction was not used. At 3 months after transplantation, cyclosporine was progressively withdrawn over 4 to 8 weeks while sirolimus was adjusted to obtain trough concentrations within 15~30 ng/ml up to 6 months and concentrations within 12~24 ng/ml between 7 and 12 months. RESULTS: The proportion of patients who completed the 12-month sirolimus medication per protocol was 74.7% (59/79). Cyclosporine withdrawal was possible in 64 recipients (81.0%). Fifteen patients discontinued sirolimus before cyclosporine withdrawal, and 5 recipients did so after successful cyclosporine withdrawal. Most common causes of sirolimus discontinuation were graft rejection (n=8). Incidence of biopsy-proven acute rejection within 6 months after transplantation was 15.2%. Patient and graft survival rates at 12 months post transplantation were 97.5% and 96.2%, respectively. During the study period, three graft losses occurred by patient death. CONCLUSION: Based on this study, cyclosporine and sirolimus induction followed by cyclosporine withdrawal at 3 months post-transplant is considered to be efficient and safe after primary renal transplantation.

Clinical Characteristics of Acute Appendicitis in Kidney Transplant Recipients / 대한이식학회지

BACKGROUND: Appendicitis is a common surgical disease. There are many problems for the early diagnosis of acute appendicitis in kidney transplant patients; differential diagnosis for acute rejection, limitation in imaging study, problems of immunosuppressant and non-characteristic symptoms. METHODS: We reviewed medical records and transplant database of 2,947 renal transplant patients between April, 1979 and September, 2009 retrospectively. Patient's characteristics, diagnostic methods for appendicitis and operative/postoperative progresses were analyzed. RESULTS: Of the 2,947 renal transplant patients, there were 15 (0.51%, 13 males and 2 females) acute appendicitis patients. Mean age at the diagnosis of appendicitis was 37.2+/-10.1 years. Fourteen (93.3%) patients suffered from prodromal symptom, such as abdominal pain, direct or rebound tenderness, nausea and vomiting. There were 12 (80%) patients with leukocytosis (WBC count >10,000/microliter). Computed tomography scans were performed in 5 (33.4%) patients for diagnosis. Laparoscopic appendectomies were applied for 8 (53.4%) patients. In pathologic diagnosis, 2 cases were reported as 'non pathologic diagnosis' complications occurred in 2 patients as remnant appendicitis and pancreatitis. However, there was no patient with mortality and renal failure during the hospitalization. CONCLUSIONS: There were no significant differences between the transplant patients and the general population in the incidence, clinical features, diagnosis and postoperative progresses of acute appendicitis.

Hepatic Splenosis Preoperatively Diagnosed as Hepatocellular Carcinoma in a Patient with Chronic Hepatitis B: A Case Report

We report on a case of hepatic splenosis. A 32-yr-old man underwent a splenectomy due to trauma at the age of 6. He had been diagnosed as being a chronic hepatitis B-virus carrier 16 yr prior to the surgery. The dynamic computer tomography (CT) performed due to elevated serum alpha-fetoprotein (128 ng/mL) demonstrated two hepatic nodules, which were located near the liver capsule. A nodule in Segment IVa had a slight enhancement during both the arterial and portal phases, and another nodule in Segment VI showed a slight enhancement only in the portal phases. Dynamic magnetic resonance imaging (MRI) of the mass in Segment VI showed enhanced development in the arterial phases and slight hyperintensivity to the liver parenchyma in the portal phases. These imaging findings suggested a hypervascular tumor in the liver, which could be either focal nodular hyperplasia, adenoma, or hepatocellular carcinoma (HCC). Even though these lesions were diagnosed as HCC, some of the findings were not compatible with typical HCC. On dynamic CT and MRI, all lesions showed a slight arterial enhancement and did not show early venous washout. All lesions were located near the liver capsule. These findings, along with a history of splenectomy, suggested a diagnosis of hepatic splenosis.

Posttransplant Lymphoproliferative Disorders in Kidney Transplant Patients: Report from a Single-center over 25 Years / 대한이식학회지

BACKGROUND: Posttranplant lymphoproliferative disorder (PTLD) is a fatal complication of organ transplantation and standard treatment is either ineffective or too toxic to tolerate. This study aims to evaluate the characteristics of PTLD patients retrospectively. METHODS: We enrolled 2,630 kidney recipients who underwent transplantation from April 1979 to June 2007. And we retrospectively reviewed clinical manifestations of PTLD. RESULTS: Among one hundred ninety post-transplant malignancies from 2,630 renal recipients, 11 PTLD were diagnosed during 195.3+/-11.5 months (0~388 months) of mean follow up duration. PTLD predominantly occurred in male (Male : Female=10 : 1) and mean age of PTLD patients at the time of PTLD diagnosis was 51+/-15 year (18~71 year). Mean time interval to PTLD diagnosis were 126.6+/-74.8 months (6~240 months). In aspect of WHO classification, there were no early lesion, 1 polymorphic PTLD (9.1%), 10 monomorphic PTLD (90.9%) and no other types. In aspect of involved organ, GI tract was involved in 1 case, lung in 2 cases, bone in 2 cases, spleen in 2 cases, neck node in 2 cases, liver in 1 case, and multiple organs in 1 case. CONCLUSIONS: Our findings showed that the prevalence of PTLD was 0.46%, which was less than reports from Western countries. We also found that the late onset PTLD was more than early onset one, which was another difference from previous reports.

Clinical Outcomes of Spousal Donor Kidney Transplantation: Single Center Experience / 대한이식학회지

BACKGROUND: The supply of deceased donors is limited in Korea and most of kidney transplantations are performed using living related or unrelated donors. In this study, we investigated the clinical characteristics and outcomes of spousal donor kidney transplantation at our center. METHODS: From January 2000 to August 2008, we performed 909 cases of kidney transplantations. In this study, 475 one-haplomatch living-related donor (LRD) and 50 spousal donor kidney transplantations were retrospectively analyzed. We compared the outcomes of spousal donor group with those of one-haplomatch LRD group. We also compared the outcomes of husband-to wife with those of wife-to-husband subgroup. RESULTS: The number of Human leukocyte antigen (HLA) mismatch was significantly larger in spousal group (3.3+/-1.2) than in LRD group (2.7+/-0.7). The proportion of tacrolimus use was higher in spousal group (72.0%) than in LRD group (26.6%). The incidence rate of delayed graft function was higher in spousal group (4.0%) than in LRD group (0.4%). There was no significant difference in the incidence of acute rejection between the two groups. Graft survival rates in spousal group (98.0% at 1 year and 91.5% at 5 year) were comparable to those in LRD group (99.6% at 1year and 98.7% at 5 year) (P=0.321). There were no significant differences in the incidence of acute rejection and graft survival rates between the subgroups (husband-to-wife vs. wife-to- husband). CONCLUSIONS: We achieved excellent outcomes by using spousal donor as an option to reduce the donor organ shortage.

Ethyl Pyruvate Ameliorates Renal Ischemia- reperfusion Injury

PURPOSE: Reactive oxygen species (ROS) significantly contribute to ischemia-reperfusion injury, and are also associated with the gradual loss of renal function and renal failure following renal transplantation. Pyruvate is an endogenous antioxidant, but its use as a therapeutic agent for treating conditions mediated by oxidative stress is limited due to its poor stability in solution. However, ethyl pyruvate (EP), a soluble pyruvate derivative, has far greater stability than pyruvate; thus, may serve as a practical pyruvate precursor. Therefore, the ability of EP in the prevention of renal ischemia-reperfusion injury was assessed. METHODS: Sprague-Dawley rats (n=54) were subjected to 40 minutes of renal warm ischemia. The animals were divided into three groups: the sham group without warm ischemia (n=18), the EP group (n=18, EP given before ischemia), and the ischemic control (n=18). The serum levels of creatinine and TNF-alpha were measured 1, 3 and 5 days after induction of ischemia. The expression of high mobility group box-1 (HMGB-1), a delayed inflammatory mediator, was also assessed by Western blot of renal specimens. RESULTS: In the EP group, late improvements in the serum levels of creatinine and TNF-alpha were observed in comparison with the ischemic control. Based on this delayed effect, the expression of HMGB-1 was assessed in renal tissue. The HMGB-1 expression increased over time during the ischemia process, but EP suppressed this expression 3 and 5 days after renal ischemia-reperfusion injury. CONCLUSION: These results have demonstrated, for the first time, that EP ameliorates renal ischemia-reperfusion injury. EP attenuates the renal ischemia-reperfusion injury, at least in part, by suppressing the expression of HMGB-1, a late mediator of delayed inflammation.

Pre-transplant Serum Soluble CD30 Level; Correlation with Panel Reactive Antibodies and Lymphocyte Cross Matching / 대한이식학회지

PURPOSE: Serum level of soluble form CD30 (sCD30), a marker for T helper 2-type cytokine-producing T cells, is used as a marker of immunologic status of pre-transplant recipient that can predict graft rejection and graft survival. This study compared pre-transplant serum sCD30 levels with conventional pre-transplant immunologic parameter, such as panel- reactive antibodies (PRA) and lymphocyte cross matching (LCM). METHODS: Adult seventy two patients were enrolled this study. The blood for tests was sampled simultaneously. Measurement of serum sCD30 level was performed using enzyme-linked immunosorbent assay kit (Bender MedSystems, Co. CA, USA). We tested PRA using a commercial ELISA kit (Lambda Cell Tray Lymphocytotoxicity assay)(One Lambda Inc. CA, USA). We established LCM tests for T cells by Modified NIH (National institute center of health)/Johnson's Method/AHG (Anti human globulin), and for B cells by warm test. RESULTS: Mean score of sCD30 was 90.3+/-6.4 U/mL, ranged from 12.2 to 244.4 U/mL. There was no significant correlation between patient's age or sex and sCD30 level. The correlation between sCD30 and mode or duration of dialysis was not statistically significant clinical situation. The result of LCM didn't show significant correlation with sCD30 level (87.3+/-55.7 U/mL in LCM positive group versus 91.9+/-1.3 U/mL in LCM negative group, P=0.696). And sCD30 level equal to or more than 86 U/mL could not predict the positive result of LCM. The positive and negative predictive value of sCD30 to LCM was merely 27.8% and 58.3% (P=0.322). Also the correlation between sCD30 level and PRA was not significant (P=1.0). CONCLUCION: There was no significant correlation between serum sCD30 level and conventional immunologic parameter such as PRA or LCM. That means the pre-transplant monitoring of the sCD30 level can be used as an independent immunologic parameter.

Long-term Change of Renal Function after Donor Nephrectomy for Kidney Transplantation / 대한이식학회지

PURPOSE: Occurrence of renal failure and its related complications such as hypertension are long-term problems after donor nephrectomy for living donor kidney transplantation. We retrospectively reviewed renal function of unilateral kidney donor. METHODS: From 669 living donors for kidney transplantation from December 1998 to October 2006, laboratory data related to renal function are collected from hospital medical record retrospectively in 251 (37.5%) donors who were followed-up after discharge. The selection criteria of donors were: 1) pre-nephrectomy serum creatinine level below 1.5 mg/dL, 2) no radiologic abnormality in bilateral kidney. The donor nephrectomy was performed by conventional open nephrectomy or video assisted minilaparotomy surgery. The estimated glomerular filtration rate (e-GFR) by Modification of Diet in Renal Disease (MDRD) study was used as renal function monitoring parameter. RESULTS: In immediate post-nephrectomy period, e-GFR was decreased to 67.8+/-4.6% of pre-nephrectomy level (93.8+/-9.9 mL/min/1.73 m2). The urinary protein excretion for 24 hours was increased to 255% of pre-nephrectomy level (76.4+/-4.6 mg/day), but cases with proteinuria more than 300 mg per day were only 4 cases (1.7%, 4/251). After 14.0+/-5.2 months follow-up (range: 1~80 months), two cases (0.8%, 2/251) of renal failure (chronic kidney disease stage 5) were found. Relative renal function (post-nephrectomy e-GFR ratio versus pre-nephrectomy e-GFR, %) was increased by post-nephrectomy duration. The mean scores of e-GFR ratio within post-nephrectomy 2 months, 3~11 months, 12~23 months and after 24 months were 64.8+/-10.4%, 66.4+/-9.7%, 69.5+/-10.9% and 75.8+/-17.6% respectively. The relative e-GFR ratio after 24 months was significantly different from those of within 24 months (P<0.0001 by ANOVA). In linear regression analysis, mean increment of e-GFR ratio per post-nephrectomy year was 2.88%. CONCLUSION: In spite of possibility of renal failure, our study shows the long-term compensation of residual renal function after nephrectomy.

Risk Factors of Post-transplantation Diabetes Mellitus in Renal Transplant Recipients / 대한이식학회지

PURPOSE: The aim of this study was to assess the incidence of post-transplantation diabetes mellitus (PTDM) in renal allograft recipients and investigate the risk factors contributing to the development and progression of PTDM and its underlying pathogenic mechanism(s). METHODS: We analyzed the incidence and risk factors of PTDM after renal transplantation, retrospectively. A total of 913 renal transplant recipients with normal glucose tolerance (NGT) were enrolled. The recipient who needs medical treatment of hyperglycemia more than one month was considered as PTDM patient. We classified PTDM as early PTDM (within post-Tx 1 year) and late PTDM. RESULTS: Two hundred seven cases of PTDM were developed (22.7%) out of 913 patients. The cumulative incidence of PTDM was 9.4%, 20.5% and 29.0% at post-transplantation 1-, 5- and 10 year respectively. In uni-variate and multivariate analysis of PTDM onset, elderly recipients, tacrolimus-based immunosuppressive group and hepatitis B virus carrier group showed significantly higher incidence of PTDM. Among 207 cases of PTDM, early and late PTDM were 85 cases and 122 cases respectively. The late PTDM developed persistently after post-transplant 5 years. In risk factor analysis of early and late PTDM, late PTDM showed different results compared to early PTDM. The clinical conditions that cause larger dose or high level of calcineurin inhibitor (CNI), such as double immunosuppressive regimen group, induction immunosuppressive therapy-free group and unrelated donor transplant group, were a significant independent risk factor of late PTDM. CONCLUSION: Our data showed clinical clues that persistent cumulative CNI exposure was correlated with onset of late PTDM. Careful selection of immunosuppressive regimen in high-risk recipients such as elderly patients and hepatitis B virus carrier may decrease the development of PTDM.

Surgical Complications are Major Problems Concerning Overseas Kidney Transplantation in Comparison Study with Domestic Deceased Donor Kidney Transplantation / 대한이식학회지

PURPOSE: As increasing overseas kidney transplant recipients, the post-transplantation management of these recipients is not unusual. Shortage of donor information and operative findings is an obstacle to post-transplant evaluation and management of overseas transplant recipients. We retrospectively reviewed the post-transplant clinical manifestation of overseas transplant recipient, and compared with those of domestic deceased donor transplant recipient. METHODS: Sixty overseas transplant recipients and 39 deceased donor transplant recipient in our center from January 2002 to August 2006 were enrolled in this study. Among the post-transplant outcomes, we focused the episodes of post-transplant complication, acute rejection and graft functional status. RESULTS: In comparison of pre-transplant clinical manifestation, overseas transplant recipients were more elderly, male predominant and less retransplantation than domestic deceased transplant cases. Remarkable surgical complications (35%, 21/60) were observed in overseas transplant recipients which was significantly higher than those of domestic transplant recipients (5.1%, 2/39 cases)(P=0.03). The urologic complication was major (14 cases) complication, and intraoperative hematoma (5 cases) and vascular complication (2 cases) succeed. Interventional procedure or surgical correction was performed in six recipients with urinary leakage obstruction. Excluding post-transplant acute tubular necrosis, the post-transplant outcomes, such as incidence of acute rejection, graft survival rate and graft function within post-transplant 3 year, of overseas transplant recipient were statistically similar with these of domestic deceased donor recipients. CONCLUSION: Considering that overseas transplant recipient had high incidence of surgical or urologic complication, the initial evaluation of post-transplant recipient was focused on completion of surgical procedure by using radiologic imaging study.

Effects of Mycophenolic Acid on Oleic Acid- induced Rat Vascular Smooth Muscle Cell Proliferation

PURPOSE: Vascular smooth muscle cell (VSMC) proliferation plays an important role in the development and progression of chronic allograft vasculopathy. Mycophenolic acid (MPA) inhibits various mesenchymal cell proliferation, and reactive oxygen species (ROS) are involved in the anti-pro-liferative effect of MPA. In this study, we investigated the effects of MPA on oleic acid (OA)-induced VSMC proliferation and also the role of ROS in these processes. METHODS: Primary cultured rat VSMCs from Sprague-Dawley were stimulated with OA 100micrometer. MPA 0.1~10micrometer and N-acetylcystein (NAC) 5 mM were administered 1 hour before adding the OA. Cell proliferation was measured by Methylthiazoletetrazolium (MTT) assay, proliferating cell nuclear antigen (PCNA) expression by Western blot analysis, and dichlorofluorescein (DCF)-sensitive cellular ROS by flow cytometry. RESULTS: OA at 100micrometer significantly increased MTT level by 1.6-fold as well as PCNA expression at 48 hours in rat VSMCs. OA also induced DCF-sensitive cellular ROS by 1.6-fold at 5 minutes and the increment of cellular ROS remained for up to 1 hour. MPA at above 1micrometer inhibited OA- induced VSMC proliferation and cellular ROS in a dose-ependent manner. NAC 5 mM also inhibited OA-induced rat VSMC activation. CONCLUSION: These results suggest that MPA inhibits OA-induced VSMC proliferation partially through the inhibition of cellular ROS.

Effects of Inosine Monophosphate Dehydrogenase Inhibition on Platelet-derived Growth Factor- Induced Fibronectin Secretion and Cellular Reactive Oxygen Species in Mouse Mesangial Cells / 대한이식학회지

PURPOSE: Mesangial cell extracellular matrix (ECM) synthesis plays an important role in various renal diseases. Mycophenolic acid (MPA), which is an inhibitor of inosine monophosphate dehydrogenase (IMPDH), inhibits mesangial cell proliferation and ECM synthesis. However, the exact mechanism of MPA has not been clearly elucidated in mesangial cells. To examine the relative importance of IMPDH on the inhibitory action of MPA, we compared the effects of MPA or IMPDH2 siRNA on platelet-derived growth factor (PDGF)-induced fibronectin secretion and cellular reactive oxygen species (ROS) in mouse mesangial cells (MMC). METHODS: MMC were stimulated with PDGF 10 ng/ml with or without MPA 0.1~10micrometer, IMPDH2 siRNA 10~50 nM, or N-acetylcystein (NAC). IMPDH2 siRNA was transiently transfected by lipofectamine for 24 hours. MPA 0.1~10micrometer, ribavirin 10~100micrometer, and NAC 5 mM were administered 1 hour before the stimulation. Cell viability was measured by methylthiazoletetrazolium (MTT) assay, fibronectin secretion by Western blot analysis, and dichlorofluorescein (DCF)-sensitive cellular ROS by flow cytometry. RESULTS: PDGF 10 ng/ml effectively increased fibronectin secretion and cellular ROS in MMC. MPA and NAC at concentration without affecting basal level of fibronectin and cellular ROS ameliorated PDGF-induced fibronectin secretion and cellular ROS. However, IMPDH2 siRNA only partially reduced PDGF- induced fibronectin secretion and cellular ROS in MMC. CONCLUSION: These results suggest that MPA may inhibit PDGF-induced fibronectin secretion partly through IMPDH2 or cellular ROS in MMC, and there may be other mechanisms on the inhibitory action of MPA in mesenchymal cells.