The recipient candidate was a 51-year-old male with end-stage renal disease owing to diabetes mellitus. The initial immunosuppressive regimen included basiliximab for induction and tacrolimus, mycophenolate mofetil, and steroids. Urine output was 413 mL/day on the operative day and 100 mL/day on the postoperative day (POD) 1. There was no definite stenosis of the ureter or vessels. He had anuria on POD 2~4 and he had undergone hemodialysis. His serum creatinine level did not decrease. Therefore, a graft biopsy was performed on POD 4. The pathologic finding was consistent with acute calcineurin inhibitor (CNI) toxicity. There was no evidence of rejection or acute tubular necrosis. Anuria continued on POD 6; therefore, we started sirolimus instead of a CNI based regimen. Graft function was gradually recovered 1 day after reduction of CNI dose and hemodialysis was stopped. The serum creatinine level was normalized on POD 10. He was discharged on POD 21.
Anuria ; Biopsy ; Calcineurin* ; Constriction, Pathologic ; Creatinine ; Delayed Graft Function* ; Diabetes Mellitus ; Humans ; Kidney Failure, Chronic ; Kidney Transplantation ; Male ; Middle Aged ; Necrosis ; Renal Dialysis ; Sirolimus ; Steroids ; Tacrolimus ; Transplants ; Ureter

BACKGROUND: In solid organ transplantation patients, complications of cholelithiasis may run a fulminant course, resulting in high morbidity and mortality under immunosuppression and may even result in rejection. Here, we reviewed medical records of 66 patients in order to determine the outcome of management approach for asymptomatic gallstones in renal transplantation patients. METHODS: We retrospectively reviewed clinical courses of 66 cases of renal transplantation performed between 2000 and 2012 at Kosin University Gospel Hospital. RESULTS: Among 66 cases, eight had gallstones before transplantation. Three of these cases had undergone previous cholecystectomy for symptomatic gallstones, one had a simultaneous laparoscopic cholecystectomy and renal transplantation, and four were observed by regular abdominal ultrasonography. One patient was found to have cholangitis, and endoscopic retrograde biliary drainage was performed, resulting in alleviation of symptoms. Among 58 cases without preoperative gallstones, three developed gallstones after transplantation. One patient had cholecystitis, and the symptoms subsided after conservative treatment. CONCLUSIONS: For patients with asymptomatic gallstones who are awaiting renal transplantation, expectant management should be considered.
Cholangitis ; Cholecystectomy ; Cholecystectomy, Laparoscopic ; Cholecystitis ; Cholelithiasis ; Drainage ; Gallstones* ; Humans ; Immunosuppression ; Kidney Transplantation* ; Medical Records ; Mortality ; Organ Transplantation ; Retrospective Studies ; Transplants ; Ultrasonography

BACKGROUND: Lung transplantation (LTx) is a life-saving treatment for patients with end-stage lung disease; however, the shortage of donor lungs has been a major limiting factor to increasing the number of LTx. Growing experience following LTx using donor lungs after cardiac death (DCD) has been promising, although concerns remain. The purpose of this study was to develop a DCD lung harvest model using an ex vivo lung perfusion (EVLP) system and to assess the function of presumably damaged lungs harvested from the DCD donor in pigs. METHODS: The 40 kg pigs were randomly divided into the control group with no ischemic lung injury (n=5) and the study group (n=5), which had 1 hour of warm ischemic lung injury after cardiac arrest. Harvested lungs were placed in the EVLP circuit and oxygen capacities (OC), pulmonary vascular resistance (PVR), and peak airway pressure (PAP) were evaluated every hour for 4 hours. At the end of EVLP, specimens were excised for pathologic review and wet/dry ratio. RESULTS: No statistically significant difference in OC (P=0.353), PVR (P=0.951), and PAP (P=0.651) was observed in both groups. Lung injury severity score (control group vs. study group: 0.700+/-0.303 vs. 0.870+/-0.130; P=0.230) and wet/dry ratio (control group vs. study group: 5.89+/-0.97 vs. 6.20+/-0.57; P=0.560) also showed no statistically significant difference between the groups. CONCLUSIONS: The function of DCD lungs assessed using EVLP showed no difference from that of control lungs without ischemic injury; therefore, utilization of DCD lungs can be a new option to decrease the number of deaths on the waiting list.
Death ; Heart Arrest ; Humans ; Lung Diseases ; Lung Injury ; Lung Transplantation ; Lung* ; Organ Preservation ; Oxygen ; Perfusion* ; Swine* ; Tissue Donors* ; Vascular Resistance ; Waiting Lists ; Warm Ischemia

BACKGROUND: Normal renal function and health have been recognized as important factors in living donors after kidney donation. The purpose of this study was to evaluate the health status and health-promoting lifestyle in living donors after kidney donation. METHODS: A total of 678 living-kidney donors were counted in our center from January 1990 to December 2011. Only 84 donors agreed to participate in the survey by telephone. We received consent for participation in our survey from 48 donors (57.1%). Data were collected from May to August 2013 using donor characteristics, health status, and Health Promoting Lifestyle Profile I (HPLP-I). RESULTS: The donors were predominantly female (62.5%) and the average age was 48.9+/-11.8 years, and the average period after nephrectomy was 9.7+/-5.7 years. The characteristics of donors included ideal body weight (37.5%), overweight (37.5%) in body mass index, and good health status (81.3%). Most donors underwent an annual medical check-up (56.2%), no health problem (81.3%), and no disease (64.6%). However, one patient was treated with dialysis for renal failure due to diabetes. The total average score for HPLP-I was 128.3+/-13.9. Higher than average scores (116.3+/-19.1) were observed for the general middle-aged woman. There were statistically significant differences in self-realization and nutrition in subsection of HPLP-I. Self-realization showed a higher score for Christian (F=2.743, P=0.041) and good health (F=3.389, P=0.017). Nutrition showed a higher score for overweight, obesity (F=6.783, P=0.000), and older than 60 (F=3.854, P=0.009). CONCLUSIONS: Most living kidney donors were healthy after their donation and had relatively high scores for health-promoting lifestyle. However, one patient had a serious health problem. In addition, younger, longer period after donation, and the rare health examination of donors showed a lower health-promoting lifestyle. Designed and continuous health-care management after transplantation is needed for kidney donors.
Body Mass Index ; Dialysis ; Female ; Humans ; Ideal Body Weight ; Kidney Transplantation ; Kidney* ; Life Style* ; Living Donors* ; Nephrectomy ; Obesity ; Overweight ; Renal Insufficiency ; Telephone ; Tissue Donors

BACKGROUND: Kidney injury molecule-1 (KIM-1) is known as a good ancillary marker of acute kidney injury (AKI) and its expression has also been observed in acute rejection and chronic graft dysfunction. We tested usefulness of KIM-1 as an indicator of acute and chronic renal graft injury by correlating KIM-1 expression with renal graft function and histology. METHODS: A total of 133 zero-time biopsies and 42 follow-up biopsies obtained within 1 year posttransplantation were selected. Renal tubular KIM-1 staining was graded semiquantitatively from 0 to 3 and the extent of staining was expressed as the ratio of KIM-1 positive/CD10 positive proximal tubules using Image J program. RESULTS: KIM-1 was positive in 39.8% of zero-time biopsies. KIM-1 positive cases were predominantly male and had received grafts from donors with older age, deceased donors, and poor renal function at the time of donation, compared with KIM-1 negative cases. KIM-1 expression showed correlation with delayed graft function and acute tubular necrosis. In comparison of KIM-1 expression between stable grafts (n=23) and grafts with dysfunction (n=19) at the time of repeated biopsy, the intensity/extent of KIM-1 staining and renal histology at zero-time did not differ significantly between the two groups. Histologically, KIM-1 expression was significantly increased with both acute and chronic changes of glomeruli, tubules and interstitium, peritubular capillaritis, and arteriolar hyalinosis. CONCLUSIONS: KIM-1 can be used as an ancillary marker of AKI and a nonspecific indicator of acute inflammation and tubulointerstitial fibrosis. However, KIM-1 expression at zero-time is not suitable for prediction of long-term graft dysfunction.
Acute Kidney Injury ; Allografts* ; Biopsy* ; Delayed Graft Function ; Fibrosis ; Follow-Up Studies ; Humans ; Inflammation ; Kidney* ; Male ; Necrosis ; Tissue Donors ; Transplants

Current immunosuppressants have nonspecific immuosuppressive effects, and are not helpful for tolerance induction. Consequently, transplant patients cannot discontinue using them, and their nonspecific immunosuppressive effects result in many side effects, including infection and malignancy. However, most of cellular immunotherapy can have donor antigen-specific immunsuppressive effects. Therefore, cell therapy could be an alternative or adjunctive to nonspecific immunosuppressants. Polyclonal or antigen-specific Foxp3+ regulatory T cells have been actively tried for prevention of acute rejection, treatment of chronic rejection, or tolerance induction in clinical trials. Regulatory macrophages are also under clinical trials for kidney transplant patients. IL-10-secreting type 1 regulatory T cells and donor- or recipient-derived tolerogenic dendritic cells will also be used for immunoregulation in clinical trials of kidney transplantation. These cells have antigen-specific immunoregulatory effects. Mesenchymal stromal cells (MSCs) have good proliferative capacity and immunosuppressive actions independently of major histocompatibility complex; therefore, even third-party MSCs can be stored and used for many patients. Cell therapy using various immunoregulatory cells is now promising for not only reducing side effects of nonspecific immunosuppressants but also induction of immune tolerance, and is expected to contribute to better outcomes in transplant patients.
Cell- and Tissue-Based Therapy* ; Dendritic Cells ; Humans ; Immune Tolerance ; Immunosuppressive Agents ; Immunotherapy ; Kidney ; Kidney Transplantation* ; Macrophages ; Major Histocompatibility Complex ; Mesenchymal Stromal Cells ; T-Lymphocytes, Regulatory ; Tissue Donors

Two-signal models are useful in explaining various types of immune responses. In particular, secondary, so-called costimulatory, signals are critically required for the process of T-cell activation, survival, differentiation, and memory formation. Early studies in rodent models showed that targeting T-cell costimulatory pathways elicits immunological tolerance, providing a basis for development of costimulatory therapeutics in allograft rejection. However, as the classic definition of T-cell costimulation continues to evolve, simple blockade of costimulatory pathways has limitations in prevention of allograft rejection. Furthermore, functions of costimulatory molecules are much more diverse than initially anticipated and beyond T cells. In this mini-review, we will discuss CD137-CD137L bidirectional signals as examples showing that two-signals can be applicable to multiple phases of immune responses.
Adaptive Immunity* ; Allografts* ; Memory ; Rodentia ; T-Lymphocytes

A 47-year-old man developed chronic alcoholic liver cirrhosis and end-stage renal disease. He underwent blood-type-compatible liver transplantation with a graft from his daughter. After 8 months, sequential ABO-incompatible (ABOi) kidney transplantation was performed, with his brother as the donor (A to O). The patient had anti-A antibody titers (1:256). We performed pretransplant desensitization, including administration of rituximab, mycophenolate mofetil, tacrolimus, and prednisolone 2 weeks before the scheduled transplantation, and plasmaphresis (PP) and administered an intravenous immunoglobulin injection. The patient underwent PP before kidney transplantation until the anti-A antibody titer was <1:8. The patient achieved normal renal function within 4 posttransplantation days. Postoperative bleeding (diffuse hemorrhage) requiring additional blood transfusions and radiological intervention (drainage procedure) occurred 9 days after transplantation. The patient was discharged on day 20 of hospitalization. Nine months after the kidney transplantation, the recipient's and donor's liver and kidney functions were normal. ABOi renal transplantation after liver transplantation can be successfully performed in patients with high baseline anti-ABO antibody titers after preconditioning with rituximab and PP, and quadruple immunosuppressive therapy. However, caution is required regarding an increased risk of bleeding complications.
Blood Transfusion ; Hemorrhage ; Hospitalization ; Humans ; Immunoglobulins ; Kidney ; Kidney Failure, Chronic* ; Kidney Transplantation* ; Liver ; Liver Cirrhosis, Alcoholic* ; Liver Transplantation* ; Middle Aged ; Nuclear Family ; Prednisolone ; Rituximab ; Siblings ; Tacrolimus ; Tissue Donors ; Transplants

BACKGROUND: Analyzing the medical expenses of the family members of brain dead organ donors would be helpful in ascertaining better ways of applying national assistance, which is important for promotion of brain dead organ donation. METHODS: We collected data regarding the medical expenses of 119 brain dead organ donors from January 2009 to December 2013 at a single institution that specializes in organ donation. Donation year, cause of brain death, age, and admission days were deemed factors affecting medical expenses, and these were analyzed. Medical expenses were compared with national assistance (maximum of 1.8 million Korean won [KRW]). RESULTS: Average age of donors was 42.7 years, and, in the older age group, there was a lower average for medical expenses (P=0.025). Brain dead organ donations that were consented to within 2 days after the brain death comprised 41.2%, and medical expenses increased as the consent days were delayed (P<0.001). Average medical expense for donor families was 2,161,297 KRW, and the average national assistance to the families was 577,056 KRW. The medical expenses of 73 donors (61.3%) were below the national assistance maximum; 19 (16.0%) had no charges of their own with other insurance coverage. CONCLUSIONS: National assistance for medical expenses to family members of brain dead organ donors is necessary in Korea, where the rate of brain dead organ donation is very low. As 61% of donors were covered below the maximum assistance amount, there could be additional ways to utilize the remaining budget.
Brain Death* ; Budgets ; Health Expenditures ; Humans ; Insurance Coverage ; Korea ; Tissue and Organ Procurement ; Tissue Donors*

BACKGROUND: Introduction of calcineurin inhibitor (CNI) has markedly improved the outcome of kidney transplantation. While therapeutic drug monitoring is used to adjust the dosage of CNI, some patients, particularly children, still suffer from rejection, infection, and CNI toxicity. This study was conducted in order to assess the adequacy of immunosuppression using pharmacodynamic monitoring. METHODS: Pharmacodynamic monitoring was performed for 64 pediatric kidney allograft recipients. Expression of nuclear factor of activated T lymphocytes (NFAT)-regulated genes in patients' mononuclear cells was measured by quantitative polymerase chain reaction of interleukin-2, interferon-gamma (IFN-gamma), and granulocyte-macrophage colony stimulating-factor before (trough) and 1.5 hour (peak) after ingestion of tacrolimus and the residual gene expression (RGE) was calculated. Global immune response was assessed by Cylex-ImmuKnow assay. Trough and peak levels of tacrolimus were measured and clinical findings of rejection episodes and infectious complications were reviewed retrospectively. RESULTS: Global immune response measured byImmuKnow did not show correlation with trough and peak levels of tacrolimus. Adenosine triphosphate level of ImmuKnow was higher in patients with Epstein-Barr virus (EBV) infection than in those without infectious complications (515.4+/-149.0 ng/mL vs. 342.7+/-155.3 ng/mL, P=0.006). Mean RGE of the three NFAT-regulated genes showed negative correlation with tacrolimus peak levels. RGE of IFN-gamma was lower in patients with other infections except EBV than in those without infectious complications (34.0%+/-7.5% vs. 56.0%+/-30.2%, P <0.001). CONCLUSIONS: RGE of NFAT-regulated genes and ImmuKnow did not show significant correlation with clinical manifestation of under- or over-suppression of immune function in pediatric kidney allograft recipients. Further studies are required for development of optimal pharmacodynamic monitoring for pediatric kidney transplantation recipients.
Adenosine Triphosphate ; Allografts ; Calcineurin* ; Child ; Drug Monitoring ; Eating ; Gene Expression ; Herpesvirus 4, Human ; Humans ; Immunosuppression ; Interferon-gamma ; Interleukin-2 ; Kidney ; Kidney Transplantation* ; Polymerase Chain Reaction ; Retrospective Studies ; T-Lymphocytes ; Tacrolimus