Post-transplant lymphoproliferative disorder (PTLD) is a serious complication resulting in mortality and renal graft failure. PTLD is a heterogeneous disorder, which causes different clinical forms of disease from non-specific viral syndrome to malignant lymphoma and has various etiologies, clinical features, and treatment strategies. Here, we report on a patient who had a PTLD in the hilum of a transplanted kidney at 5 months after renal transplantation. The PTLD resulted in hydronephrosis of the transplanted kidney and graft dysfunction by local urinary tract obstruction. Despite treatment including immunosuppression reduction and rituximab administration, we removed the transplanted kidney from the recipient because the PTLD did not respond to the therapy.
Humans ; Hydronephrosis ; Immunosuppression ; Kidney Transplantation ; Kidney* ; Lymphoma ; Lymphoproliferative Disorders* ; Mortality ; Rituximab ; Transplants ; Urinary Tract*

Thrombotic microangiopathy (TMA) is a serious complication of solid organ transplantation. Drug-induced TMA is typically caused by immunosuppressants, particularly calcineurin inhibitors. Withdrawing the causative drug can be one of the treatments for TMA. However, the more immunosuppressants are reduced, the more risk of rejection increases. Even if TMA is successfully resolved, the outcomes of patient and graft survival would be worse than expected. Therefore, it is necessary to maintain efficient and safe immunosuppression therapy. We report on a case of de novo TMA after kidney transplantation triggered by tacrolimus and reactivated by sirolimus. Belatacept, a novel CTLA4 Ig fusion protein, was administered for maintenance immunosuppressant with mycophenolate mofetil and prednisolon. The patient had excellent early graft outcome, and there have been no adverse events so far.
Abatacept ; Calcineurin ; Graft Survival ; Humans ; Immunosuppression* ; Immunosuppressive Agents ; Kidney Transplantation* ; Kidney* ; Organ Transplantation ; Sirolimus ; Tacrolimus ; Thrombotic Microangiopathies* ; Transplants

A 44-year-old man was admitted for evaluation of asymptomatic graft dysfunction. An allograft biopsy revealed diffuse interstitial infiltration of lymphocytes (i3) with moderate tubulitis (t3) and SV40-positive renal tubular epithelial cells. The patient was diagnosed with BK virus nephropathy, and immunosuppression was modified with discontinuing mycophenolate and reducing tacrolimus. Leflunomide treatment was also started simultaneously. However, serum creatinine increased to 3.0 mg/dL; therefore, the patient underwent a second allograft biopsy, in which the crescent was no longer evident but tubulitis (t2) and fibrosis (i2) persisted. On day 20, leflunomide was switched to ciprofloxacin due to leukopenia. The serum creatinine increased to 3.3 mg/dL, and the third biopsy showed slightly improved tubulitis and interstitial inflammation. We then administered an intravenous infusion of immunoglobulin. On day 70, the renal function was stable and the BK serum viral load was low, and the patient was discharged. This is a case of severe crescentic BK nephropathy with successful outcome treated with aggressive treatment and this method will be useful in renal transplant patients.
Adult ; Allografts ; Biopsy ; BK Virus ; Ciprofloxacin ; Creatinine ; Epithelial Cells ; Fibrosis ; Humans ; Immunoglobulins ; Immunosuppression ; Inflammation ; Infusions, Intravenous ; Kidney Transplantation ; Leukopenia ; Lymphocytes ; Polyomavirus ; Tacrolimus ; Transplants ; Viral Load

Microvascular thrombosis is an uncommon pathological finding in deceased donor kidneys. It is associated with disseminated intravascular coagulation (DIC) after brain injury in the donor. Although DIC in deceased kidney donors is known to have no association with graft outcome, microvascular thrombosis with DIC in a donor can cause renal graft impairment. For this reason, some transplantation centers do not accept these kidneys. A 39-year-old female donor had a subarachnoid hemorrhage. After a short period of cardiopulmonary resuscitation, we applied extracorporeal membrane oxygenation to maintain hemodynamic stability. The laboratory data were consistent with DIC. The recipient was a 38-year-old male patient who had been undergoing hemodialysis for 7 years because of end-stage renal disease of unknown cause. Zero-time graft biopsy revealed multiple intraluminal fibrin thrombi without peritubular capillaritis. Delayed graft function occurred after transplantation, and hemodialysis was started. Graft renal biopsy was performed on the third day after transplantation. The percentage of intraglomerular fibrin thrombi had decreased, and no significant peritubular capillaritis or C4d staining was observed. The function of the transplanted kidney started to recover, and hemodialysis was discontinued on the 10th day after surgery without specific treatment. Follow-up biopsy performed 20 days after the transplantation revealed normal kidney with completely resolved fibrin thrombi. We report herein a case of microvascular thrombosis in renal allograft from a DIC donor.
Adult ; Allografts ; Biopsy ; Brain Injuries ; Cardiopulmonary Resuscitation ; Dacarbazine ; Delayed Graft Function* ; Disseminated Intravascular Coagulation* ; Extracorporeal Membrane Oxygenation ; Female ; Fibrin ; Follow-Up Studies ; Hemodynamics ; Humans ; Kidney ; Kidney Failure, Chronic ; Male ; Renal Dialysis ; Subarachnoid Hemorrhage ; Thrombosis* ; Tissue Donors* ; Transplants

PURPOSE: The major limitation of adult-to-adult living donor liver transplantation (A-A LDLT) is the adequacy of the graft size. As an alternative, dual grafts from two living donors can solve the problem of graft-size insufficiency and guarantee the donor safety in many occasions. The present study aims to introduce the usefulness of dual-grafts A-A LDLT by review of our single center experience. METHODS: After the first successful pediatric LDLT in December 1994 and A-A LDLT in February 1997, 392 LDLTs including 73 pediatric and 319 adult cases were performed at Asan Medical Center until December 2001. Among 319 A-A LDLTs, 20 recipients implanted dual grafts were retrospectively analysed from March 2000 to December 2001. RESULTS: The ratio of graft volume to standard liver volume of the recipients ranged from 46.6% to 78.9%. More than 50% of the standard liver volume of the recipients was implanted in 16 patients. There was acute rejection episode in two patients, which were responded by pulsed steroid therapy. There were 3 in- hospital mortality (<3 month posttransplantation). CONCLUSION: In LDLT, the donor safety is the major concern. Although the donor has a large right lobe of liver that is adequate as a graft for large-size recipient, the remaining left lobe of liver is sometimes too small to endanger the donor safety. In this circumstance, the donor cannot be accepted to donate his or her right or left lobe of liver. Dual grafts from two living donors can help to alleviate the problem of small-for-size graft and secure the donor safety.
Adult ; Chungcheongnam-do ; Hospital Mortality ; Humans ; Liver Transplantation* ; Liver* ; Living Donors* ; Retrospective Studies ; Tissue Donors ; Transplants*

PURPOSE: It is difficult to differentiate BKV nephritis (BKVN) from acute rejection. We diagnosed 8 cases of BKVN in renal transplantation recipients. Herein, we report the clinical nature of BKVN in terms of diagnosis, treatment and prognosis. METHODS: Between June 1998 and September 2002, 8 cases of BKVN were confirmed by H and E stain, immunohistochemical study against SV40, and electron microscopy in renal allograft biopsy samples. Additionally, between April and September 2002, we obtained urine sample for urine cytology from 49 potential donors, 40 end-stage renal failure patients awaiting renal transplantation, and 140 renal transplant recipients who were hospitalized with variable causes and 32 renal transplants as a routine follow-up. RESULTS: In 7 male and 1 female patients, BKVN was diagnosed mean of 20.4 months after transplantation. The kind of immunosuppression they had been on were mycophenolate mofetil (6/8), azathioprine (1/8), cyclosporin (4/8), tacrolimus (4/8). Range of whole blood levels of cyclosporine and tacrolimus at the time of diagnosis of BKVN were 187.5~252.5 ng/ml and 11~16.5 ng/ml, respectively. Four patients had treated acute rejection episode, and in 6 patients, pathologically proven acute rejection was found concomitantly with BKVN. After reduction of net immunosuppression (discontinuation of MMF and AZA, dose reduction of cyclosporine or tacrolimus, and switch from tacrolimus to cyclosporine), renal function of 3 patients was fully recovered. However, 4 patients with delayed diagnosis lost grafts. In urine cytologic examination, 15 patients (one in end-stage renal failure patient, 10 in renal transplant recipients with elevated serum creatinine, 2 in patients with other infection, and 2 in other situation) were found to secrete decoy cell through urine. CONCLUSION: BKVN should be considered in the differential diagnosis of renal allograft dysfunction. Early diagnosis of BKVN and reduction of net immunosuppression can rescue the grafts. Monitoring of decoy cell in the urine cytology is a simple diagnostic tool both for screening of graft with dysfunction and follow-up of grafts after diagnosis and treatment of BKVN.
Allografts ; Azathioprine ; Biopsy ; BK Virus* ; Creatinine ; Cyclosporine ; Delayed Diagnosis ; Diagnosis* ; Diagnosis, Differential ; Early Diagnosis ; Female ; Follow-Up Studies ; Humans ; Immunosuppression ; Kidney Failure, Chronic ; Kidney Transplantation ; Male ; Mass Screening ; Microscopy, Electron ; Nephritis ; Nephritis, Interstitial* ; Prognosis* ; Tacrolimus ; Tissue Donors ; Transplantation ; Transplants

PURPOSE: Survival rate after renal transplantation has increased in according to the prolonged graft survival due to a development of new immunosuppressive agents and operative techniques. Therefore, the develpment of malignancy in renal transplant recipients has become the major cause of morbidity and mortality. METHODS: The retrospective analysis was performed in 4 patients with malignancy among the 315 patients who underwent kidney transplantation in our hospital from August 1990 to March 2001 and 1 patient with malignancy who underwent kidney transplantation in other hospital and was followed up in our hospital. RESULTS: In five malignancy, 3 were adenocarcinoma in stomach, 1 lobular carcinoma in breast and 1 squamous cell carcinoma in uterine cervix. The mean age of these patients at diagnosis of malignancy was 48.4 (35~60) and the average interval between renal transplantation and diagnosis of malignancy was 69.8 months. Surgical resection was done in all five patients. Chemotherapy was performed in 1 patients with advanced gastric cancer and 1 patient with breast cancer. Four patients are now alive and one patient was lost during follow-up period. CONCLUSION: We reviewed the incidences and types of malignancy after renal transplantation in our hospital. Regular screening and careful surveillance are highly recommended in patients after renal transplantation.
Adenocarcinoma ; Breast ; Breast Neoplasms ; Carcinoma, Lobular ; Carcinoma, Squamous Cell ; Cervix Uteri ; Diagnosis ; Drug Therapy ; Female ; Follow-Up Studies ; Graft Survival ; Humans ; Immunosuppressive Agents ; Incidence ; Kidney Transplantation ; Mass Screening ; Mortality ; Retrospective Studies ; Stomach ; Stomach Neoplasms ; Survival Rate ; Transplantation*

PURPOSE: Mycophenolate mofetil (MMF) given orally as 1000 mg twice daily has shown to be effective in the suppression of acute allograft rejection following renal transplantation. However, Korean transplant patients are usually administered with a lower dose of MMF (1~1.5 gm/day) than the recommended dose due to high incidence of gastrointestinal intolerance. The purpose of this study was to characterize the pharmacokinetic parameters of the mycophenolic acid (MPA), the active form of MMF, in Korean kidney transplant recipients. METHODS: The plasma MPA concentrations of 10 Korean kidney transplant recipients (7 men and 3 women) administered with a suboptimal dose of MMF (750 mg twice a day) were measured at 2 weeks of the MMF therapy by HPLC method. RESULTS: Plasma MPA concentration-time curve pattern of patients taking lower doses of MPA was consistent with previously reported profiles of patients taking the fully recommended doses. The plasma MPA concentration-time curve was characterized by an early sharp peak within 1 hour and a small second peak in some patients at 4~12 hours postdose. The mean ( SD) Cmax was 8.73 4.65micro gram/ml, and the mean MPA AUC was calculated as 18.45 4.25micro gram hr/ml. The mean fraction of free MPA, which is pharmacologically active, was 1.60 0.23% and this value seemed similar to previously reported data. The patient's age, weight, body surface area, and renal function did not influence the MPA AUC. However, a difference in AUC according to sex was statistically significant (P=0.0227). Free fraction of MPA appeared not to be affected by serum albumin and renal function when creatinine clearance was above 40 ml/min. Correlation analysis between each plasma concentration and AUC for the limited strategy of MMF therapeutic drug monitoring (TDM) resulted that the concentrations of predose, 1 hr post-dose, and 8 hr post-dose were positively related with AUC value, and their coefficients of correlation were 0.74545 (P=0.0133), 0.68485 (P=0.0289), and 0.63636 (P=0.0479), respectively. CONCLUSION: This study have shown that the pattern of the time-concentration profile of MPA was similar to the results of other studies performed with Caucasians, although there was interindividual variability of MPA AUC, Cmax, and Tmax.
Allografts ; Area Under Curve ; Body Weight ; Chromatography, High Pressure Liquid ; Creatinine ; Drug Monitoring ; Humans ; Incidence ; Kidney Transplantation ; Kidney* ; Male ; Mycophenolic Acid* ; Plasma ; Serum Albumin ; Transplantation

PURPOSE: Four-hour area under the concentration-time curve (AUC0-4) was considered to be superior rather than C0 in predicting the development of acute rejection, and was reported most well correlated with C2 in post-transplant period. The purpose of this study was to demonstrate the correlation between AUC0-4 and each C0,1,2,3,4, and to compare C2 with C0 in predicting acute rejection in de-novo kidney recipients. METHODS: Fifty- six adult living donor kidney transplants were followed up 3 months after transplantation. Cyclosporine A (CsA) dose was adjusted with C0. AUC0-4 was measured on 5th and 19th post-operative day, and C2 as well as C0 was measured on post-operative 5, 12, 19, 30, 60, 90 days. RESULTS: Fifteen patients (26.8%) experienced acute rejection 12.0+/-10.9 (5~48) days after transplantation. CsA absorption pharmacokinetics was different with data based on Caucasian recipients. In more than 60% of patients, peak concentration (Cmax) was reached 2 hours after oral intake of CsA regardless the occurrence of acute rejection and postoperative days. AUC0-4 was most critically correlated with C2 on 5th and 19th post-operative days (R2>0.800, respectively). Recipients having acute rejection between 5th and 7th post-operative day, had statistically lowered AUC0-4, C2, C3 (P<0.05) compared with patients without acute rejection. CONCLUSION: In early post-transplant days, AUC0-4 was powerfully correlated with C2. Monitoring of C2 rather than C0 could predict the occurrence of acute rejection in this period. Value of C2 monitoring in Koreans beyond 7th day awaits further study by adjusting CsA dose with C2 rather than C0.
Absorption ; Adult ; Cyclosporine* ; Humans ; Kidney ; Kidney Transplantation ; Living Donors ; Pharmacokinetics

PURPOSE: Cyclosporine dosing is traditionally based on cyclosporine trough level (C0). Recently, however, it was reported that 2-hour post dose sampling point (C2) represents more precisely area under the curve (AUC) which measures drug exposure and that it has better correlations with acute rejection and cyclosporine nephrotoxicity than CO. we evaluated the clinical usefulness of C2 monitoring in living-donor renal transplant recipients during early post- transplant period. METHODS: Thirty-four renal transplant recipients with living related donor were included. Patients are divided into two groups (C0 and C2 group), in an alternating order. They received cyclosporine-based triple immunosuppression (Cyclosporine, Prednisolone, Mycophenolate mofetil). In both groups, cyclosporine dosing was based on C0 and C2, respectively, and adjusted to target level (C2: 1,600~2,000 ng/mL) Cyclosporine whole blood level was measured by radioimmunoassay. C0, C2 and AUC0-4 were measured regularly during early post-transplant period. RESULTS: For total 34 recipients (C0 group: 16 patients, C2 group: 18 patients), AUC0-4 was measured 95 times. Only 21% of the measurements, 20 of 95, were in the target level, 4,400~5,500 ng/mL, while 69% of them, 66 of 95, were less than 4,400 ng/mL. In C2 group, 69% of the total measurements for C2, 111 of 162, were less than 1,600 ng/mL. C2 correlated much more closely with AUC0-4 (R=0.936) than CO (R=0.450). No patient have acute rejection. 41.2% of the total patients, 14 of 34, haved cyclosporine hepatotoxicity and 14.7% of them, 5 of 34, haved cyclosporine nephrotoxicity. 31.3% of the patients in CO group, 5 of 16, haved cyclosporine hepatotoxicity and 18.8% of them, 3 of 16, have cyclosporine nephrotoxicity. C2 group haved cyclosporine hepatotoxicity in a half cases (9 of 18, 50%) and 18.8% of them, 2 of 18, have cyclosporine nephrotoxicity. Between two groups, there was no statistical difference in the correlations with cyclosporine hepatotoxicity and cyclosporine hepatotoxicity. CONCLUSION: C2 is more accurate single-sample marker for AUC0-4 than C0. Considering high frequency of cyclosporine hepatotoxicity and cyclosporine nephrotixicity, the target levels of AUC0 and C2 in living- donor transplantation would be lowered.
Cyclosporine ; Humans ; Immunosuppression ; Kidney Transplantation* ; Prednisolone ; Radioimmunoassay ; Tissue Donors ; Transplantation