Cytomegalovirus-Associated Hemophagocytic Syndrome Diagnosed by Liver Biopsy in a Kidney Transplant Recipient

Hemophagocytic syndrome (HPS) is a rare but potentially life-threatening disease in kidney transplant recipients, and is caused by systemic proliferation of macrophages actively phagocytizing other blood cells in the bone marrow, lymph nodes, and the spleen.Here, we report a 40-year-old male kidney transplant recipient who presented with fever, bicytopenia, and elevated liver enzymes 2 months after transplantation. Given that cytomegalovirus antigenemia and real-time polymerase chain reaction tests were positive, liver biopsy was performed under an assumption of cytomegalovirus-induced hepatitis. Hepatic histology revealed multifocal microabscess with cytomegalovirus inclusion bodies, marked Kupffer cell hyperplasia, and erythrophagocytosis by activated macrophages. As laboratory findings such as hyperferritinemia, elevated serum lactate dehydrogenase, low natural killer cell activity, and high soluble interleukin-2 receptor were also compatible with HPS, the recipient was diagnosed as having cytomegalovirus-induced hepatitis combined with reactive HPS. Following intravenous ganciclovir therapy with continuous administration of tacrolimus and corticosteroid, the symptoms resolved and laboratory findings were normalized. As far as we know, this is the first report of cytomegalovirus-induced hepatitis combined with reactive HPS in a kidney transplant recipient that is diagnosed by liver biopsy.

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.

Different Bone Healing Effects of Undifferentiated and Osteogenic Differentiated Mesenchymal Stromal Cell Sheets in Canine Radial Fracture Model

Cell sheets technology is being available for fracture healing. This study was performed to clarify bone healing mechanism of undifferentiated (UCS) and osteogenic (OCS) differentiated mesenchymal stromal cell (MSC) sheets in the fracture model of dogs. UCS and OCS were harvested at 10 days of culture. Transverse fractures at the radius of six beagle dogs were assigned into three groups (n = 4 in each group) i.e. UCS, OCS and control. The fractures were fixed with a 2.7 mm locking plate and six screws. Cell sheets were wrapped around the fracture site. Bones were harvested 8 weeks after operation, then scanned by micro-computed tomography (micro-CT) and analyzed histopathologically. The micro-CT revealed different aspects of bone regeneration among the groups. The percentages of external callus volume out of total bone volume in control, UCS, and OCS groups were 42.1, 13.0 and 4.9% (p < 0.05) respectively. However, the percentages of limbs having connectivity of gaps were 25, 12.5 and 75% respectively. In histopathological assessments, OCS group showed well organized and mature woven bone with peripheral cartilage at the fracture site, whereas control group showed cartilage formation without bone maturation or ossification at the fracture site. Meanwhile, fracture site was only filled with fibrous connective tissue without endochondral ossification and bone formation in UCS group. It was suggested that the MSC sheets reduced the quantity of external callus, and OCS induced the primary bone healing.

Assessment of Venographic Abnormalities during Replacement of Dysfunctional Tunneled Hemodialysis Catheters and Outcome of Endovascular Salvage Techniques

PURPOSE@#To assess the venographic findings of central venous abnormalities before exchanging dysfunctional tunneled hemodialysis catheters and the outcome of endovascular salvage techniques.@*MATERIALS AND METHODS@#A total of 110 episodes of tunneled hemodialysis catheter dysfunction in 78 patients undergoing catheter-directed hemodialysis treatment from January 2011 to December 2015 were retrospectively evaluated. Venography was performed before catheter exchange, and the following procedures were conducted according to the venographic findings: balloon disruption of a fibrin sheath, angioplasty for central vein stenosis, or stent insertion. Technical success was defined as at least one successful session of hemodialysis with the exchanged catheter. Patients were followed until the study endpoints or the last hospital visit.@*RESULTS@#Venography showed abnormalities in patients with 67 of the 110 exchanged catheters, including central vein stenosis (n = 27), fibrin sheath formation (n = 17), and thrombus formation (n = 12). Technical success was confirmed in all cases. The estimated 30-day catheter patency for all assessable catheters was 61.7%. Nine catheters were removed during the follow-up period because of suspected catheter-related infections.@*CONCLUSION@#In approximately 60% of cases of dysfunctional tunneled hemodialysis catheter, abnormal venographic findings were observed in the patients. Following appropriate endovascular techniques could be helpful in improving catheter patency with a low risk of procedure-related complications.

En bloc transplantation of horseshoe kidney in Korea

Transplantation of the horseshoe kidney can be performed en bloc or split into 2 grafts according to the vascular anomaly and the existence of the urinary collecting system in isthmus. From 2011 to 2014, there were 3 horseshoe kidney transplantations in Korea and transplantations were performed at 2 different centers. The transplantations were carried out successfully for all recipients without complications. All recipients have shown good graft kidney function after transplantation. No severe complication was revealed during follow-up period. We described the surgical technique used in the en bloc method to overcome various vascular anomalies and difficulties in choosing cannulation site and postoperative complications. En bloc transplantation of a horseshoe kidney is a useful strategy for patients with end-stage renal disease, and can provide favorable outcomes compared to the transplantation of a normal kidney.

Clinical analysis of single filtration plasmapheresis using continuous renal replacement therapy machines in kidney transplantation

BACKGROUND: Plasmapheresis has become an essential element of kidney transplantation (KT). In the present study, we report clinical outcomes of filtration plasmapheresis using continuous renal replacement therapy machines with a single filter for the first time in Korea. METHODS: We retrospectively analyzed six patients who underwent filtration plasmapheresis for KT in our center; plasmapheresis was performed using the Plasmaflex (Baxter®) with a TPE 2000 filter set (Baxter®) in our hemodialysis unit. Five percent albumin was used as the replacement fluid, and intravenous immunoglobulin G was administered after each plasmapheresis session. The target preoperative ABO isoagglutinin titer was less than 1:8. RESULTS: Filtration plasmapheresis was performed in four patients for ABO-incompatible KT, one for antibody-mediated rejection after KT, and the last one for positive T cell crossmatch. Altogether, 46 sessions of plasmapheresis were performed. ABO isoagglutinin titers successfully declined to or below the target level in all patients, and all patients successfully received KT with no significant antibody titer rebound. Acute antibody-mediated rejection and positive T cell crossmatch were well treated with filtration plasmapheresis, and no patient required fresh frozen plasma infusion for coagulopathy. There were one episode of hypotension and three of hypocalcemia. No patients experienced bleeding, infection, or allergic reaction. CONCLUSION: Filtration plasmapheresis was effective and safe. Although our result is from a single center, our protocol appears to be promising.

Potential biomarkers as an indicator of vertical transmission of Johne's disease in a Korean native cattle farm

Paratuberculosis (PTB) is caused by Mycobacterium avium subsp. paratuberculosis (MAP) and is one of the most widespread and economically important diseases in cattle. After birth, calves are raised with natural breast feeding without separation from their mothers in most Korean native cattle (Hanwoo breed) farms. Vertical transmission of PTB has been reported, but the exact PTB infection route has not been revealed in Hanwoo farms. Calves of MAP seropositive dams were tested for MAP presence and MAP antibodies in feces and tissues. MAP was detected in calf tissues by using polymerase chain reaction. Expressions of genes reported to be prognostic biomarkers of MAP infection changed in both calves and cows (p < 0.05). Expression of two genes (HGF and SERPINE1) were significantly decreased in MAP-infected cattle and their offspring (p < 0.01). The results suggest that biomarker gene expression profiles can be useful in detecting early stage MAP infection. Based on the results, complete eradication of MAP may be possible if accurate diagnostic methods to detect infected calves are added to the current PTB eradication strategy, which, because infected individuals are likely to develop into fecal MAP shedders at any time, includes isolation of new born calves and feeding sterilized colostrum.

Cyclosporine Sparing Effect of Enteric-Coated Mycophenolate Sodium in De Novo Kidney Transplantation

PURPOSE: The increased tolerability of enteric-coated mycophenolate sodium (EC-MPS), compared to mycophenolate mofetil, among kidney transplant recipients has the potential to facilitate cyclosporine (CsA) minimization. Therefore, a prospective trial to determine the optimum EC-MPS dose in CsA-based immunosuppression regimens is necessary. MATERIALS AND METHODS: A comparative, parallel, randomized, open-label study was performed for 140 patients from four centers to compare the efficacy and tolerability of low dose CsA with standard dose EC-MPS (the investigational group) versus standard dose CsA with low dose EC-MPS (the control group) for six months in de novo kidney transplant recipients. Graft function, the incidence of efficacy failure [biopsy-confirmed acute rejection (BCAR), death, graft loss, loss to follow-up], and adverse events were compared. RESULTS: The mean estimated glomerular filtration rate (eGFR) of the investigational group at six months post-transplantation was non-inferior to that of the control group (confidence interval between 57.3 mL/min/1.73m² and 67.4 mL/min/1.73 m², p0.05) in the incidence of discontinuations and serious adverse events (SAE) between the groups. CONCLUSION: CsA minimization using a standard dose of EC-MPS kept the incidence of acute rejection and additional risks as low as conventional immunosuppression and provided therapeutic equivalence in terms of renal graft function and safety issues.

Fulminant multicentric osteosarcoma with systemic metastasis in a dog

A 15-year-old castrated mixed breed dog presented due to a 5-month history of cough and difficulty in ambulation. Necropsy showed multiple periosteal and intramedullary infiltrative masses in the appendicular skeleton. In addition, single and multiple neoplastic nodules were observed in several organs, including the lungs, liver, kidney, and heart. Microscopically, several skeletal neoplastic masses and nodules in the parenchymal organs revealed similar changes. The neoplastic cells were spindle- to polygonal-shaped with prominent osteoid production and occasional cartilaginous and bone formation. Based on the gross findings and histopathology results, the case was diagnosed as multicentric osteosarcoma with systemic metastases.

Current System for Allocation of Deceased Donor Kidney Transplantation / 대한이식학회지

BACKGROUND: This study was conducted to analyze the current system for allocation of deceased donor kidney transplantation in Korea, which includes an incentive regulation for candidates registered at the Hospital-based Organ Procurement Organization (HOPO). METHODS: Between January 2011 and November 2016, there were 2,655 deceased donors in Korea. During the same period, there were 21,247 current candidates and recipients of kidney, pancreas and simultaneous pancreas-kidney transplants. We analyzed data from all of these donors, candidates, and recipients. RESULTS: Mean waiting times for organ allocation of each priority differed significantly (2nd priority group, 1,701±974 days; 3rd priority group, 1,316±927 days; 4th priority group, 2,077±1,207 days). Additionally, HOPO candidates/deceased donor ratios were very different from each other (maximum, 49; minimum, 0.6). The number of deceased donors in region 1, 2, and 3 were 1,623, 429, and 603, respectively, while the number of transplantations in each region was 3,095, 597, and 1,165, respectively. The candidates registered at region 1 HOPO moved the longest distances on average for transplantation, and this value differed significantly different from that of other regions (56.18±91.9 km vs. 24.66±28.0 km vs. 26.20±37.3 km, P<0.05). CONCLUSIONS: The incentive system of current allocation system for deceased donor kidney in Korea does not coincide with the purpose of the ‘Declaration of Istanbul’ and unnecessary social costs have occurred. Therefore, we should make an effort to change our current allocation system to the geographic sequence of organ allocation system.

Ferret coronavirus infection in a domestic ferret (Mustela putorius furo)

A female domestic ferret (Mustela putorius furo) presented to a veterinary clinic with a clinical history of anorexia and poor body condition. Due to gradual deterioration of the body condition, explorative laparotomy was performed. Diffusely, the mesentery was severely thickened and adhered with prominent mesenteric lymph nodes. A portion of the mesentery and mesenteric lymph nodes were biopsied and fixed. Microscopic analysis revealed severe pyogranulomatous peritonitis and lymphadenitis, but staining revealed no bacterial organisms. However, immunohistochemistry for feline coronavirus exhibited strong immunoreactivity, primarily in the macrophages. Based on these results, the case was diagnosed as ferret coronavirus infection.

Pericardial mesothelioma in a dog with lymph node metastasis and chylothorax

Pericardial mesothelioma is a rare neoplasm in dogs. This report describes a case of pericardial mesothelioma in a 13-year-old Shih Tzu that presented with a clinical history of dyspnea. Hemorrhagic pericardial effusion and chylous pleural effusion with reactive mesothelial cells were identified by radiograph and cytology. Necropsy revealed multiple round nodules throughout the pericardium and regional lymph nodes in addition to chylothorax. Histopathology revealed invasive neoplasm on the pericardial surface with metastasis to the lymph nodes. The neoplastic cells were immunopositive to both cytokeratin and vimentin. Diagnosis of pericardial mesothelioma with regional lymph node metastasis was made.

Impact of Graft Kidney Volume and Weight on Graft Function in Living Donor Kidney Transplantation / 대한이식학회지

BACKGROUND: Low functional nephron mass and graft kidney-recipient body size mismatch can lead to poor graft function. To examine the impact of the ratios of the surrogates to recipient body surface area (BSA) and body weight on graft function within 5 years post-transplantation, we measured the graft kidney volume, using computed tomography with 3-dimensional reconstruction before transplantation, and measured the graft kidney weight during surgery in living donor kidney transplantation (LDKT). METHODS: Between February 2004 and November 2013, 142 LDKT recipients without delayed graft function, acute rejection, or infection within 5 years of transplantation were included. The graft function and its relations with graft kidney volume and its weight were analyzed. RESULTS: The graft kidney volume/recipient BSA ratio showed correlation with the estimated glomerular filtration rate (eGFR) of recipients after 3 years post-transplantation. We found a difference in the graft function between recipients with a graft kidney volume/recipient BSA ratio of > or =80.4 mL/m2 and those with a ratio of <80.4 mL/m2 (P<0.05). Multivariate analysis showed that the graft kidney volume/recipient BSA ratio, the graft kidney weight/recipient body weight ratio, donor age, donor eGFR, and donor/recipient BSA ratio are independent predictors of graft function at each period of transplantation (P<0.05). CONCLUSIONS: The graft kidney volume of living donors may predict graft function and during living donor and recipient matching, both the potential volume of the donated kidney and the body size of the recipient should be considered.

Metastatic lipid-rich mammary carcinoma in a dog / 대한수의학회지

An adult female dog was presented for evaluation of mammary gland masses. Complete blood count and serum chemistry data were within normal limits. Fine-needle aspiration cytology of the mammary masses revealed clusters of malignant epithelial cells with clear cytoplasmic vacuoles. Based on histopathological findings, a diagnosis of lipid-rich mammary carcinoma was made. Approximately 5 weeks after surgical removal, the tumor recurred at the surgery site and metastasis to the tibia was detected. Due to the poor prognosis and deterioration of the condition, the dog was euthanized.

Clinical Characteristics and Risk Factors for Renal Cell Carcinoma after Kidney Transplantation / 대한이식학회지

BACKGROUND: The occurrence of malignancy following kidney transplantation has been estimated three to five times the incidence compared to that of the general population. It is estimated that particularly in renal cell carcinoma (RCC), the relative risk increases. The aim of this study was to analyze the characteristics, risk factors, and prognosis of RCC following kidney transplantation. METHODS: Total number of 3,272 kidney recipients who underwent transplantation from April 1979 to December 2012 and patients who had RCC following kidney transplantation were retrospectively reviewed and analyzed. RESULTS: We found that among 232 cases of posttransplant malignancies, 25 recipients were diagnosed with RCC. We have observed in our study that it took an average of 175.2+/-71.0 months to develop RCC after their first kidney transplantation. However, with longer follow up period, interval incidence of RCC increased. Fourteen patients (56%) were diagnosed with RCC 15 years after transplantation. We also found that with reference to the risk factor analysis for posttransplant RCC, the long-term follow-up period was the only independent risk factor. In our study, 21 patients with RCC were treated with radical nephrectomy. Of them, 16 patients survived, and four RCC-related deaths occurred. Furthermore, the patient survival rate of RCC recipients was lower than that of the nonmalignancy group despite the graft survival rate were not different. CONCLUSIONS: We conclude that the incidence of RCC increased in a time-dependent manner following kidney transplantation. Therefore, we strongly recommend the procedure of regular-interval screening for the patients who are on compulsive long-term immunosuppression.

Posttransplant Lymphoproliferative Disorder without Epstein-Barr Virus Presented as Small Bowel Perforation in Renal Transplant Recipient: A Case Report / 대한이식학회지

Posttransplant lymphoproliferative disorder (PTLD) is documented as one of the serious complications leading to mortality particularly in organ transplant recipients receiving immunosuppressive therapy. Extant literature confirms beyond doubt that the most common site of involvement of PTLD is lymph nodes, and rarely involved is the gastrointestinal tract. It is a well-known fact that Epstein-Barr virus (EBV) is a risk factor for PTLD development. In this study, we report a case of PTLD presented as small bowel perforation without EBV infection after long-term immunosuppressive therapy in a renal transplant recipient.

Waiting Time for Deceased Donor Kidney Allocation in Korea: A Single Center Experience / 대한이식학회지

BACKGROUND: The kidney recovery rate associated with deceased donors has increased after the establishment of the Korean Network for Organ Sharing (KONOS). And the KONOS organ allocation system gives priority to candidates affiliated with a Hospital based Organ Procurement Organization (HOPO) and/or donor recovery hospital. Regardless of whether or not this organ allocation system is fair, it can make an important impact on the waiting time for an organ transplant. METHODS: A total of 157 deceased donor kidney transplantations were performed at Severance Hospital between January 2006 and April 2011. The recipients of these transplantations were retrospectively divided into five groups according to their allocation types; general allocation group (GA, n=54), HOPO priority group (HP, n=65), zero antigen mismatching group (ZM, n=23), marginal donor allocation group (MD, n=7), and the combined organ transplant allocation group (CT, n=8). The five groups were assessed in terms of their waiting time for organ allocation, cold ischemia time, and post-transplant graft outcome. RESULTS: Mean waiting time for organ allocation of the HP group (69.5+/-27.4 months) was significantly shorter than for the GA group (90.0+/-34.0 months)(P<0.05). However, the degree of HLA mismatching was not different between each group. The cold ischemia time for the HP group (301.5+/-133.9 min) was significantly shorter than all other groups, except for the ZM group. There were no differences between groups in terms of acute rejection episodes, delayed graft function events or graft survival rates. CONCLUSIONS: Our retrospective analysis of the kidney allocation pattern showed that there were disparities in distribution by priority of allocation. We should make a consensus within the Korean transplant society in order to further develop the allocation system to decease donor kidney transplantation time.

Clinico-pathological Features of Chlamydophila psittaci Infection in Parrots and Genetic Characterization of the Isolates / 대한수의학회지

Avian chlamydiosis is caused by Chlamydophila psittaci and considered as one of an important zoonotic disease throughout the world. Among more than 400 avian species including poultry and pet birds susceptible to the disease, psittacine birds were known to be mostly susceptible hosts. In Korea, no outbreak of the disease and genetic analysis of the agent in poultry and pet birds have been reported. With histopathological findings and genetic identification of a causative agent, avian chlamydiosis was identified in parrots submitted from the same pet bird farm in 2006 and 2009 for the diagnosis. Based on genetic sequences and phylogenetic analysis of ompA gene, the two isolates of Chlamydophila psittaci showed 100% of genetic similarity and belonged to genotype A, suggesting that the same agent might be continuously circulated in the farm. This result indicates that serological survey of the disease in pet bird farms and impact of the disease on significance in public health may be further studied.

Diagnostic imaging of malignant insulinoma in a dog / 대한수의학회지

Endocrine test data from a 13-year old intact female Maltese was indicative of the presence of an insulinoma, however ultrasonography identified a pancreatic mass only after 10 months after the first admission. Following identification of both pancreatic tumor and hepatic metastasis on computed tomography (CT), surgical excision of the mass was attempted. However, total excision failed because of tumor adhesion to adjacent large vessels. The pancreatic mass was monitored over the next 25 months via ultrasonography, CT, and positron emission tomography-computed tomography (PET-CT). Histopathological and immunohistochemical data confirmed the diagnosis of insulinoma with hepatic metastasis.