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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.
Epstein-Barr Virus Infections ; Gastrointestinal Tract ; Herpesvirus 4, Human ; Kidney Transplantation ; Lymph Nodes ; Lymphoproliferative Disorders ; Risk Factors ; Transplants

Cryptococcosis commonly affects patients with immune dysfunction, as in the case of immunosuppression in organ transplant patients or as acquired immunodeficiency syndrome in patients afflicted with human immunodeficiency virus. The varied appearance of cryptococcal skin lesion makes clinical diagnosis of cutaneous cryptococcosis difficult. Cryptococcosis proves to be a fatal fungal infection in the immunocompromised patient. Therefore, diagnosis and early treatment of cryptococcosis become vital. A 56-year-old renal transplant recipient, with an ongoing immunosuppression regimen of cyclosporine, prednisolone, and mycophenolate mofetil, was admitted with a 2-week history of pain and edema of right arm without respiratory symptoms. Despite empiric antibiotic therapy, the patient continued to complain of severe tenderness of the involved arm and fever persisted as well. On the third day of hospital stay, a biopsy of the erythematous skin lesion was acquired. On the eighth day of hospital stay, results of both skin biopsy and blood cultures showed the presence of Cryptococcus neoformans. The treatment was begun with intravenous fluconazole (400 mg/day). After 4 days of antifungal treatment, the patient developed fever along with cough with purulent sputum. As the new developing symptoms were suggestive of pneumonia, especially of pulmonary cryptococcosis, the antifungal agent was changed from fluconazole to amphotericin B treatment (0.8 mg/kg, 50 mg/day). Chest computer tomography showed improvement in the pneumonic infiltration and consolidation after 4 weeks of amphotericin B treatment. In conclusion, cellulitis in immunocompromised patients should be suspected in case of highly atypical infectious etiology, and skin biopsy should not be delayed if empiric antibiotic therapy does not control the inflammatory response. Additionally, the patient should be treated with intravenous amphotericin B treatment in case of severe cryptococcosis.
Acquired Immunodeficiency Syndrome ; Amphotericin B ; Arm ; Biopsy ; Cellulitis ; Cough ; Cryptococcosis ; Cryptococcus neoformans ; Cyclosporine ; Edema ; Fever ; Fluconazole ; HIV ; Humans ; Immunocompromised Host ; Immunosuppression ; Kidney Transplantation ; Length of Stay ; Middle Aged ; Mycophenolic Acid ; Pneumonia ; Prednisolone ; Skin ; Sputum ; Thorax ; Transplants

Antiphospholipid syndrome nephropathy (APSN) is well documented in the literature as the renal involvement of the antiphospholipid syndrome (APS). A review of literature also shows that among antiphospholipid antibodies, lupus anticoagulant (LA) positivity is recognized as the strongest risk factor for APSN. In addition, APSN is also known to be associated with a poor functional outcome in the first posttransplant year. Therefore, it is a general belief that renal transplantation may be life threatening in APS patients. Furthermore, the presence of LA at the time of transplantation is particularly associated with a high rate of allograft APSN and the consequent poor transplantation outcomes. Here, we report the case that thrombotic acute kidney injury due to APSN after kidney transplantation can be successfully treated if anticoagulation therapy is timely applied with a prompt diagnosis.
Acute Kidney Injury ; Antibodies, Antiphospholipid ; Antiphospholipid Syndrome ; Humans ; Kidney ; Kidney Transplantation ; Lupus Coagulation Inhibitor ; Risk Factors ; Transplantation, Homologous ; Transplants

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.
Carcinoma, Renal Cell ; Follow-Up Studies ; Graft Survival ; Humans ; Immunosuppression ; Incidence ; Kidney ; Kidney Transplantation ; Mass Screening ; Nephrectomy ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Rate ; Transplants

BACKGROUND: Tissue microarray analysis (TMA) is a high-throughput method for histologic evaluation, immunohistochemistry, and in situ hybridization using paraffin embedded tissue. Despite its high efficiency as an experimental tool, TMA is limited because it only contains a very small tissue fragment from each case. Therefore, the purpose of this study was to evaluate the validity of TMA in a study of nephrotoxicity caused by immunosuppressants. METHODS: Male Sprague-Dawley rats were treated with vehicle (n=16), cyclosporine (n=23), and cyclosporine plus losartan (n=13) for a maximum of 7 weeks. After animal sacrifice, renal tissues were embedded in paraffin and processed into slides for microscopic examination using conventional methods and the TMA technique. Acute tubular injury, vascular hyaline change, and interstitial fibrosis were scored in both conventional and TMA slides. The number of interstitial macrophages was counted after ED-1 immunohistochemistry and the results also compared between conventional and TMA slides. RESULTS: The degree of acute tubular injury and interstitial fibrosis showed a significant agreement between conventional and TMA methods (kappa value, 0.79 and 1.00, respectively). The number of interstitial macrophages counted in conventional and TMA slides showed a significant correlation as well (r=0.934, P<0.001). However, the degree of vascular hyaline changes showed less agreement between conventional and TMA methods (kappa value, 0.40). CONCLUSIONS: TMA is a useful and reliable method for the study of nephrotoxicity induced by immunosuppressive agents. TMA also reflects the findings of conventional methods, especially for acute and chronic tubular and interstitial changes.
Acute Kidney Injury ; Animals ; Cyclosporine ; Fibrosis ; Humans ; Hyalin ; Immunohistochemistry ; Immunosuppressive Agents ; In Situ Hybridization ; Losartan ; Macrophages ; Male ; Paraffin ; Rats, Sprague-Dawley ; Tissue Array Analysis ; Vascular System Injuries

BACKGROUND: Steroid pulse therapy has been used for patients with acute rejection after kidney transplantation. The ABCB1 gene codes for P-glycoprotein, a transporter that is involved in the metabolism of steroids. However, the role of ABCB1 polymorphisms has not been investigated in patients with acute rejection after kidney transplantation. METHODS: Among 763 patients that received kidney or simultaneous pancreas-kidney transplantation at Seoul National University Hospital between May 1996 and July 2009, 684 patients agreed to genetic sampling for polymorphisms. Acute rejection was defined as biopsy-proven, acute cellular rejection with increased serum creatinine, or in the context of delayed or slow graft function. Steroid-resistance was defined as no improvement in serum creatinine, need for additional OKT3 or ATG treatment, or repeated acute rejection within 30 days. Three polymorphisms of ABCB1 gene (C1236T, C3435T, G2677T/A) were assessed. RESULTS: C allele frequency of C3435T was 59.3% and of C1236T 40.1%. Patients who were steroid-resistant (n=37) had higher serum creatinine at kidney biopsy compared to those who were steroid-sensitive (n=49, P<0.001). The frequency of ABCB1 gene polymorphisms (C1236T and C3435T) did not differ significantly between patients who were steroid-sensitive and those who were resistant. An association with G2677T/A could not be analyzed due to a high failure rate of genotyping. CONCLUSIONS: ABCB1 gene polymorphisms (C1236T and C3435T) were not associated with steroid resistance in patients with acute cellular rejection after kidney transplantation.
Biopsy ; Creatinine ; Gene Frequency ; Humans ; Kidney ; Kidney Transplantation ; Muromonab-CD3 ; P-Glycoprotein ; Rejection (Psychology) ; Steroids ; Transplants

BACKGROUND: Lung transplantation (LTx) is an effective treatment for end stage lung disease. However, the shortage of donor lungs has been a major limiting factor to increase the number of LTx. Ex vivo lung perfusion (EVLP) is a currently approved method to evaluate lung function and to repair donor lung with poor function. The purpose of this study was to develop EVLP system in pig model and to maintain lung function during 4 hours of EVLP. METHODS: Bilateral lung blocks were harvested from five 40 kg pigs. These blocks were applied in EVLP perfused with 37degrees C Steen solution. We performed arterial blood gas (ABG) analyses before death and also every 1 hour for 4 hours after application of EVLP and calculated oxygen capacities (OC) using the results of ABG. We also calculated pulmonary vascular resistance (PVR) and peak airway pressure (PAP) every 1 hour for 4 hours. After EVLP procedure, we excised specimens for pathologic review. RESULTS: We found that OC gradually decreased during the 4 hour period of EVLP; however, no statistically significant difference was obtained. PVR declined sharply after 1 hour of EVLP (P=0.031) and then remained constant for 3 hours. PAP significantly increased after 3 hours (P<0.0001). Pathologic investigations revealed various findings from normal lung to severe pulmonary edema. CONCLUSIONS: On the results of this study, we could preserve the lung function for 4 hours using EVLP. We conclude that application of EVLP in clinical setting can make more donor lungs available for LTx. However, we also understand that more studies and training are needed in clinical practice.
Humans ; Lung ; Lung Diseases ; Lung Transplantation ; Organ Preservation ; Oxygen ; Perfusion ; Swine ; Tissue Donors ; Unrelated Donors ; Vascular Resistance

BACKGROUND: The purpose of this study was to identify the attitude of physicians stemming from their experiences of caring for potential brain death donors during the organ donation process. METHODS: Grounded theory methodology was used for this study. In depth interviews were conducted with six physicians who had experience of management of potential brain death donors. Data collection was done from January to October 2011. Theoretical sampling was used until the data reached saturation. RESULTS: As a result of the analysis, dilemma of organ donation solicitation was identified as the core category. Twelve subcategories were identified and they were integrated to the core category. Obtaining organ donation counseling skills was identified as the consequence. CONCLUSIONS: The results of the study will provide a frame for understanding the attitudes stemming from their experience of caring for potential brain death donor and helping the development of effective intervention strategies for increasing organ donation.
Brain ; Brain Death ; Counseling ; Data Collection ; Humans ; Tissue and Organ Procurement ; Tissue Donors

C4d is produced from the direct interaction between antibodies and tissue injury at an antibody binding site in a graft. C4d deposition along peritubular capillaries (PTCs) in a renal allograft is a characteristic finding of antibody-mediated rejection (AMR), and is a useful diagnostic tool of AMR. The C4d along PTCs is associated with poor graft survival. Therefore C4d is regarded as a biomarker of AMR and was included in the diagnosis criteria of AMR at 2007 Banff conference. However, although C4d assay is widely used, it has several limitations. ABO-incompatible transplantations develop C4d along the PTCs in the majority of grafts but this seems to be graft accommodation rather than AMR. Recent studies reported that more than half of renal allograft biopsies with chronic AMR were C4d-negative. Without treatment, the C4d-negative AMR can cause scarring within the graft, transplant glomerulopathy (TG) or even graft loss. C4d is not a certain indicator of antibody-mediated rejection and C4d staining is not always highly sensitive for detecting AMR. Measuring endothelial gene expression in kidney graft biopsies with alloantibody can be another sensitive and specific method to diagnose AMR and predict graft outcomes. Because of these complexities, at the 2011 Banff meeting, criteria for diagnosis of chronic AMR in the kidney were refined, and the need for inclusion of C4d-negative AMR in the Banff classification was investigated.
Antibodies ; Binding Sites, Antibody ; Biopsy ; Capillaries ; Cicatrix ; Factor IX ; Gene Expression ; Graft Survival ; Kidney ; Rejection (Psychology) ; Transplantation, Homologous ; Transplants