Multivisceral Transplantation / 대한이식학회지

Small bowel transplantation is the most rapidly evolving area of the solid organ transplantation. Pathophysiologic nature of the intestinal failure leads various surgical options performing intestinal transplantation, e.g. isolated intestine, liver and intestine, and multivisceral transplantation. Because of high dosing of immunogenic tissue from the allograft, prevention and treatment of the acute rejection is still one of the main hurdles to improve clinical outcome after transplantation. With the contribution of refining surgical skills, novel immunosuppressive therapy, and upgraded patient management before and after transplantation, clinical outcome has been improved significantly for last decade. The indication of the intestinal transplantation, however, still remained to use this novel treatment option as a life- saving procedure in intestinal failure patients and not to be justified for pre-emptive intestinal transplantation. Intestinal or multivisceral transplantation has so many unveiled areas, which warrants additional vigorous study.

Intestinal and Multivisceral Transplantation

Intestinal transplantation has been established as a treatment option for patients that suffer from intestinal failure with complications from total parenteral nutrition. It is still rapidly evolving and just reached a landmark of 1, 000 cases worldwide. Intestinal allografts can be transplanted as isolated, combined with the liver or as a part of a multivisceral allograft. Tacrolimus-based immunosuppression regimens have been used universally with improved outcomes. Clinical outcome in intestinal transplantation has improved significantly over time, impacted by refinement of surgical technique and novel immunosuppression. However rejection, infection, and technical complications still remain the most difficult barrier to improve patient and graft survival.

Effect of Mycophenolic Acid and Rapamycin on the Proliferation of Glomerular Mesangial Cell of Rat

PURPOSE: Excess proliferation of mesenchymal cells such as vascular smooth muscle cells and glomerular mesangial cells, cause transplant vascular sclerosis and glomerulosclerosis, which are typical pathological lesions of chronic allograft dysfunction. Mycophenoic acid (MPA) and rapamycin (RPM) were recently reported to have strong anti-proliferative potentials toward vascular smooth muscle cells. However, the potential effects of these drugs, either alone or in combination, on glomerular mesangial cells, remain to be reported. METHODS: Primary cultured mesangial cells, from Sprague-Dawley rats, were isolated, and stimulated with 10ng/ml of PDGF. The test drugs MPA and RPM were administered at various concentrations, either alone or in combination, 15 minutes before the addition of the PDGF. The cell proliferation was assessed by [3H]-thymidine incorporation. RESULTS: The PDGF effectively stimulated the proliferation of the mesangial cells. The MPA inhibited the proliferation in a dose-dependent manner. In comparison to the stimulated control, the MPA (above 500 nM) showed a significant inhibitory effect. The IC50 of the MPA, against PDGF-stimulated mesangial cell proliferation, was between 500 nM and 1microM. The RPM, at 10 nM, showed a significant inhibitory effect. In a linear regression analysis, the RPM was supposed to suppress the mesangial proliferation in a dose-dependent manner (P<0.05). The pattern of inhibition for the MPA and RPM combination was very similar to that of either the MPA or the RPM alone. Both the MPA and RPM were shown to independently suppress the mesangial proliferation from a multiple regression analysis (R2=0.415, P<0.001). CONCLUSION: We demonstrated that MPA and RPM significantly inhibited the proliferation of glomerular mesangial cells, and that these effects were well maintained when used in combination. Our data indicate that both MPA and RPM have unique potentials in preventing the development of transplant mesangial proliferation in renal transplant recipients.

Effect of Mycophenolic Acid and Rapamycin on the Proliferation and Collagen Synthesis of the Vascular Smooth Muscle Cell of Rat / 대한이식학회지

PURPOSE: Vascular smooth muscle cell (VSMC) proliferation and extracellular matrix protein accumulation play important roles in chronic allograft vasculopathy. Mycophenolic acid (MPA) or rapamycin (RPM) was reported to inhibit VSMC proliferation in vitro and in vivo. However, effects of MPA or RPM on collagen synthesis of VSMCs, and the combined effects of MPA and RPM treatment on VSMC proliferation are not yet reported. METHODS: VSMCs isolated from the aorta of Sprague-Dawley rats were cultured with EMEM supplemented with 10% fetal bovine serum and insulin/ transferrin. Growth arrested and synchronized cells were pretreated with test drugs (alone or combination of various concentrations of MPA and RPM) 1 hour before the addition of 10 ng/ml PDGF. Cell proliferation was assessed by [H3]- thymidine incorporation, and collagen synthesis by [H3]- proline incorporation. RESULTS: PDGF increased cell proliferation and collagen synthesis by 3.4- and 2.1-fold, respectively, compared to control. MPA at above 100 nM or RPM at above 1 nM effectively inhibited PDGF-induced cell proliferation and collagen synthesis. The IC50 of MPA or RPM against PDGF-stimulated cell proliferation was between 100 nM and 1 micrometer or between 1 nM and 10 nM, respectively. The combination of MPA and RPM showed additive effects on PDGF-induced VSMC proliferation in a multiple regression analysis (R2=0.508, P<0.05). CONCLUSION: The present study demonstrated that MPA or RPM significantly inhibited PDGF-induced VSMC proliferation. These independent phenomena were well maintained as suggested by additive effects after combination treatment. PDGF-induced collagen synthesis was also effectively suppressed by the treatment of MPA or RPM.

The Results of Renal Transplantation after Lymphocyte Cross-match Negative Conversion by Combination Therapy with Plasmapheresis, Intravenous Gamma Globulin and Potent Immunosuppresants in Patients with Positive LCM / 대한이식학회지

PURPOSE: It is well-known that kidney transplantation cannot be done if recipient has circulating antibodies showing positive lymphocyte cross-match (LCX) to organ donor. In the United States and European countries, the incidence of positive LCX to cadaveric donors in patients who are on the waiting list is up to 20~40%. Unfortunately, these patients also show high rate of positive LCX to live donors when they have donor candidates in their family members and have to be on dialysis until compatible donor comes up. Recently, Eugene J Schweitzer and his associates at the University of Maryland used the combination therapy with plasmapheresis, intravenous gamma globulin and potent immunosuppression to induce negative conversion of LCX in patients who were LCX positive to their living donors and reported the good results after the trial. We did the combination therapy in patients who had positive LCX to their living donors and reported the results. METHODS: Seven patients, four women and three men who showed positive LCX to their living donors, underwent the conversion trials between January 1 and July 31, 2002. The mean age of patients was 43.86 (35~60) and the duration of dialyses varies from 9 to 120 months. We used combination therapy with plasmapheresis, intravenous gamma globulin injection, tacrolimus, mycophenolate mofetil (MMF) and steroids. Plasmapheresis had been done on every other day up to 6 times to induce negative conversion of LCX. If patient continue to show positive LCX to donor after 6 times of plasmapheresis, we stopped the therapy. The numbers of plasmapheresis varies from two to six times. Kidney transplantations were preformed immediately after negative conversion of LCX as a semi-elective procedures. Five to ten day courses of ATG (or OKT3) were used as an induction immunosuppression after transplantation and tacrolimus, MMF, and steroids were used as a maintenance immunosuppression. RESULTS: We could achieve negative conversion of LCX in six out of seven patients, and kidney transplantations were performed in these 6 patients successfully. There was no hyperacute rejection during the operations, but three patients developed acute rejection episodes during their early postoperative periods. Steroid pulse therapies were used as a primary therapy to treat acute rejection and all three patients showed complete recovery of their graft function after the treatments. Baseline serum creatinine level varies from 1.0 mg/dl to 1.9 mg/dl with 3 to 6 months follow-up periods after transplantations. We could not induce negative conversion in one patient and he remained on hemodialysis. CONCLUSION: We did successful kidney transplantations in six patients who achieved negative conversion of LCX to their donors after the combination therapy with plasmapheresis and potent immunosuppression. All patients showed excellent graft function since their operations and did not have any significant complications except three reversible acute rejection episodes. According to the results, although it is preliminary, we recommend the use of the combination therapy in patient who has LCX positive living donor. Further long-term study with more numbers of patients is needed for the evaluation of the efficacy of this trial.

Granzyme B and TIA-1 Expression in Chronic and Acute on Chronic Renal Allograft Rejection

Although active inflammation may be deleterious and indicate immunologic activation in chronically rejected grafts, the underlying mechanism of tissue destruction has been little studied. Twenty-four cases of chronic rejection (CR) with or without acute rejection (AR) were stained with antibodies against CD3, CD8, CD68, granzyme B and TIA-1, and the number of positive cells were counted. Eleven cases of AR served as controls. The number of CD3 and CD8 positive cells increased in the acute on CR group compared to the CR group. About a half of CD3 positive T cells were CD8 positive in both groups, however, the proportion of TIA-1 or granzyme B positive cells was higher in the acute on CR group. The numbers of CD3, CD68, granzyme B and TIA-1 positive cells were higher in the AR group than the acute on CR group, however, no significant difference was found between the two groups. Serum creatinine level and proteinuria at the time of biopsy and the percentages of late onset AR and graft failure rate were higher in the acute on CR group than the CR group. Summarizing, these results suggest that infiltration of activated T cells containing cytotoxic granules plays a role in graft destruction in acute on CR.

Factors Affecting the First 3-year Quality of Graft Function after Live Donor Kidney Transplantation

PURPOSE: We designed this study to identify the risk factors affecting the quality of graft after live donor kidney transplantation. METHODS: The study cohort included 259 adult patients who had been followed up for an average of 37 months after transplantation. Cyclosporine (CsA) and steroids were used as main immunosuppressive agents. Seven variables [HLA match, numbers of acute rejection (AR) within post-transplant 1 year, blood type compatibility, use of anti-lymphocyte antibody, age of donor (DA), age of recipient, and the donor kidney weight to recipient body weight ratio (KW/BW)] were examined by multiple regression analysis during the first 3 years. Serum creatinine (Scr), creatinine clearance rate (Ccr) and the 24 hours urinary excretion of protein (24 UP) were used as parameters. RESULTS: AR, DA, or KW/BW independently affected the quality of graft function. Scr, Ccr, or 24 UP at post-transplant 1 year was strongly correlated with AR (p<0.0001, p=0.002, or p=0.002, respectively). However, Scr, Ccr, or 24 UP at post-transplant 3 years was strongly affected by KW/BW (p<0.0001, p<0.0001, or p=0.008, respectively) or DA (p<0.0001, p=0.001, or p=0.039, respectively). CONCLUSION: Non-immunologic factors independently affected the graft function through the study periods. The impact of non-immunologic factors on the function of the graft increased year by year. During renal allocation, KW/BW and DA should be included as reference indices to improve the long-term graft function.

Ratio of Kidney Weight to Recipient Weight Correlates with the 3-Year Graft Function / 대한이식학회지

Reduced renal mass, increased recipient body size, and their mismatching are the potential risk factor to explain the non-immunologic graft dysfunction. Present study was designed to assess the effect of mismatch between donor kidney weight (KW) and recipient body weight (BW) on the 3-year graft function in live donor renal transplantation (TX) patients (pts) who were operated before Nov. 1995 under cyclosporine. To remove immunologic injuries and effect of glomerulonephritis (GN), the pts experiencing episode of acute rejection or showing post-TX biopsy-proven GNs were excluded. A total of 82 pts cohort was identified and followed up till Nov. 1998. The donor KW after cold flushing, BW of recipient at TX, and renal parameters at 3-year post-TX such as serum creatinine (Scr), creatinine clearance ratio (CCR) and 24-hour urinary excretion of protein (24UP) were recorded. First, any correlation between the index value of the KW/BW ratio and each parameters was studied by the regression analysis, and secondly, the pts were stratified into 3 groups by the KW/BW ratio (3.5 4.0) and compared with each parameters by ANOVA test. Scr, CCR, and 24 UP was well correlated with the ratio KW/BW (p4.0) have significantly lower Scr, higher CCR and lower 24 UP compared with pts showing medium or low ratio. In conclusion, the mismatch between the donor KW and recipient BW has a substantial effect on the medium term graft function. Since estimating the kidney volume by CT scan or ex vivo after bench surgery is simple and easily applicable in clinical practice, KW/BW ratio is to be considered for the selection or allocation of potential donor in both cadaveric and living donor TX programs.

Long-term (>10 years) Result of Kidney Transplantation between HLA Identical Siblings / 대한이식학회지

Degree of HLA matching between donor and recipient is a well-known risk factor affecting the renal allograft function and survival. This study presents long-term clinical outcomes of kidney transplantation between HLA identical siblings from a single center. A total of 60 patients (pts), who has been followed up more than 10 years were identified and constituted the cohort of this study. The graft and patient survival were estimated with Kaplan-Meier's analysis method. Causes of graft loss and pts' death, episode of acute and chronic rejection, allograft function, and long-term complications were reviewed from medical records. Before 1984, azathioprine (AZA) and steroids were used for immunosuppression, but cyclosporine (regular oral solution, regular capsules or microemulsion preparation) and a low dose steroid has been the mainstay of immunosuppression since 1984. Earlier 37 pts were treated with AZA/steroids protocol (AZA group) and later 23 pts were immunosuppressed with cyclosporine (CsA)/steroids protocol (CsA group). Mean duration of follow-up months was 151 in AZA and 114 in CsA group respectively. Mean age of recipients at the time of transplantation was 34.1 years in AZA and 34.7 years in CsA group. Ten year graft survival in each group were 67.6% and 65.2% (p=0.672) and patient survival were 82.7% and 80.0% (p=0.833) respectively. Adoption of CsA/steroids protocol since 1984 did not significantly improve the graft and patient survival comparing AZA/steroids protocol. During the period, 12 patients died of various causes. The leading causes of patient death were cerebrovascular disease (3) and infection (3). Twenty-two grafts were lost: 13 in AZA and 9 in CsA group. The common causes of graft loss were pts' death with functioning graft (12), chronic rejection (5), and poor compliance (4). We could not find any differences in the causes of mortality and graft loss between the AZA and CsA groups. Mean serum creatinine in the chronic rejection-free pts at post-transplant 10 year were 1.4 and 1.3 mg/dl in or CsA group. CsA/steroids protocol did not improve the long-term outcome in HLA matched pairs. Long surviving transplant recipients continue to experience a variety of medical and surgical complications. For this reason, continued follow-up by experienced medical personnel is essential. Measures need to be taken to prevent and manage these late complications. Continued investigation into new and better immunosuppressive modalities is essential in an attempt to prevent the long-term consequences of maintenance immunosuppression.

Long-term (>10 years) Result of Kidney Transplantation between HLA Identical Siblings / 대한이식학회지

Degree of HLA matching between donor and recipient is a well-known risk factor affecting the renal allograft function and survival. This study presents long-term clinical outcomes of kidney transplantation between HLA identical siblings from a single center. A total of 60 patients (pts), who has been followed up more than 10 years were identified and constituted the cohort of this study. The graft and patient survival were estimated with Kaplan-Meier's analysis method. Causes of graft loss and pts' death, episode of acute and chronic rejection, allograft function, and long-term complications were reviewed from medical records. Before 1984, azathioprine (AZA) and steroids were used for immunosuppression, but cyclosporine (regular oral solution, regular capsules or microemulsion preparation) and a low dose steroid has been the mainstay of immunosuppression since 1984. Earlier 37 pts were treated with AZA/steroids protocol (AZA group) and later 23 pts were immunosuppressed with cyclosporine (CsA)/steroids protocol (CsA group). Mean duration of follow-up months was 151 in AZA and 114 in CsA group respectively. Mean age of recipients at the time of transplantation was 34.1 years in AZA and 34.7 years in CsA group. Ten year graft survival in each group were 67.6% and 65.2% (p=0.672) and patient survival were 82.7% and 80.0% (p=0.833) respectively. Adoption of CsA/steroids protocol since 1984 did not significantly improve the graft and patient survival comparing AZA/steroids protocol. During the period, 12 patients died of various causes. The leading causes of patient death were cerebrovascular disease (3) and infection (3). Twenty-two grafts were lost: 13 in AZA and 9 in CsA group. The common causes of graft loss were pts' death with functioning graft (12), chronic rejection (5), and poor compliance (4). We could not find any differences in the causes of mortality and graft loss between the AZA and CsA groups. Mean serum creatinine in the chronic rejection-free pts at post-transplant 10 year were 1.4 and 1.3 mg/dl in or CsA group. CsA/steroids protocol did not improve the long-term outcome in HLA matched pairs. Long surviving transplant recipients continue to experience a variety of medical and surgical complications. For this reason, continued follow-up by experienced medical personnel is essential. Measures need to be taken to prevent and manage these late complications. Continued investigation into new and better immunosuppressive modalities is essential in an attempt to prevent the long-term consequences of maintenance immunosuppression.

Effectiveness of Cipol-N(R) in Primary Living Donor Kidney Transplant Patients: Open-Label, Multi-Center Study / 대한이식학회지

Cyclosporine (CsA) has been one of the main immunosuppressants after kidney transplantation since its introduction in Korea. There was remarkable improvement of graft survival in kidney transplantation with CsA, compared with azathioprine. Cipol-N(R)(Chong Kun Dang, Korea), microemulsion gelatin capsule formulation of CsA, is a new generic drug. This pure domestic brand of CsA was tested for bioequivalence in healthy adults compared with the reference drug of the same formulation, Sandimmun-Neoral(R)(Novartis, Switzerland) in 1997. This open-label, multi-center study is designed to evaluate the efficacy of Cipol-N(R) in primary kidney transplant recipients for 6 months after transplantation. A total of 59 patients from 4 medical centers were enrolled in the study. Maintenance immunosuppressive protocol was based on CsA and steroid dual therapy, which was induced 2 days prior to the operation. Acute rejection was diagnosed with clinical or pathological clue. Clinical criteria for the diagnosis of acute rejection were oliguria, graft swelling and tenderness, rising serum creatinine, fever, and papillary swelling and increased vascular resistant index on Doppler ultrasonography. Steroid pulse therapy was used as primary treatment. Steroid resistant acute rejection was treated with anti-lymphocyte agents such as OKT3, ATG, or ALG. The primary efficacy endpoint was onset of acute rejection or treatment failure, defined as graft loss, death, or premature termination from the study for any reason. Incidence and severity of acute rejection, actual survival rate of patient and graft, function of the graft, pharmacokinetics of the Cipol-N(R), and the primary efficacy variables were evaluated 6 months after transplantation. All enrolled patients were included in the primary analyses of efficacy on the basis of intent to treat. Mean age of the patients was 37.1 10.4 years old. Male and female ratio was 42:17. There were 38 related pairs, which included 5 HLA identical and 33 HLA haplo-identical matches, and 21 unrelated pairs. A total of 10 patients were withdrawn from the study before post- transplant 6 months. The causes for premature withdrawal were patient's request without specific reason (6), partially rescued acute rejection (3), and patient's death (1). There were 27 episodes of acute rejection in 25 patients, which were diagnosed clinically (11) and pathologically (16). Steroid pulse therapy and anti-lymphocyte agent were used in 24 and 3 cases respectively. There were 4 patients, who showed partial rescue but no graft loss due to acute rejection. Patient and graft survival was 98.3% at post-transplant 6 months. Serum creatinine concentration showed 1.3-1.7 mg/dl all through the study period, which meant relatively stable graft function. Mean daily doses of Cipol-N(R) at post-transplant 1 and 6 months were 325 and 300 mg respectively. With this short term study, we can report that Cipol-N(R) showed relatively good efficacy in primary living donor kidney transplantation. Further study is needed for the evaluation of long term efficacy and safety.

Effectiveness of Cipol-N(R) in Primary Living Donor Kidney Transplant Patients: Open-Label, Multi-Center Study / 대한이식학회지

Cyclosporine (CsA) has been one of the main immunosuppressants after kidney transplantation since its introduction in Korea. There was remarkable improvement of graft survival in kidney transplantation with CsA, compared with azathioprine. Cipol-N(R)(Chong Kun Dang, Korea), microemulsion gelatin capsule formulation of CsA, is a new generic drug. This pure domestic brand of CsA was tested for bioequivalence in healthy adults compared with the reference drug of the same formulation, Sandimmun-Neoral(R)(Novartis, Switzerland) in 1997. This open-label, multi-center study is designed to evaluate the efficacy of Cipol-N(R) in primary kidney transplant recipients for 6 months after transplantation. A total of 59 patients from 4 medical centers were enrolled in the study. Maintenance immunosuppressive protocol was based on CsA and steroid dual therapy, which was induced 2 days prior to the operation. Acute rejection was diagnosed with clinical or pathological clue. Clinical criteria for the diagnosis of acute rejection were oliguria, graft swelling and tenderness, rising serum creatinine, fever, and papillary swelling and increased vascular resistant index on Doppler ultrasonography. Steroid pulse therapy was used as primary treatment. Steroid resistant acute rejection was treated with anti-lymphocyte agents such as OKT3, ATG, or ALG. The primary efficacy endpoint was onset of acute rejection or treatment failure, defined as graft loss, death, or premature termination from the study for any reason. Incidence and severity of acute rejection, actual survival rate of patient and graft, function of the graft, pharmacokinetics of the Cipol-N(R), and the primary efficacy variables were evaluated 6 months after transplantation. All enrolled patients were included in the primary analyses of efficacy on the basis of intent to treat. Mean age of the patients was 37.1 10.4 years old. Male and female ratio was 42:17. There were 38 related pairs, which included 5 HLA identical and 33 HLA haplo-identical matches, and 21 unrelated pairs. A total of 10 patients were withdrawn from the study before post- transplant 6 months. The causes for premature withdrawal were patient's request without specific reason (6), partially rescued acute rejection (3), and patient's death (1). There were 27 episodes of acute rejection in 25 patients, which were diagnosed clinically (11) and pathologically (16). Steroid pulse therapy and anti-lymphocyte agent were used in 24 and 3 cases respectively. There were 4 patients, who showed partial rescue but no graft loss due to acute rejection. Patient and graft survival was 98.3% at post-transplant 6 months. Serum creatinine concentration showed 1.3-1.7 mg/dl all through the study period, which meant relatively stable graft function. Mean daily doses of Cipol-N(R) at post-transplant 1 and 6 months were 325 and 300 mg respectively. With this short term study, we can report that Cipol-N(R) showed relatively good efficacy in primary living donor kidney transplantation. Further study is needed for the evaluation of long term efficacy and safety.

Postprandial Hepatic Volume Change: Spiral CT Evaluation in Case of Liver Cirrhosis

PURPOSE: To investigate the usefulness of evaluating liver cirrhosis through the measurement of liver volume. MATERIALS AND METHODS: In a control group(20 normal subjects) and 20 cirrhotic patients, variations in liver volume before and after a meal were obtained. A case-control study was conducted between the two groups. RESULTS: In the control group, the range of increased liver volume after the meal was 67-186ml. Mean increased liver volume was 119.3ml, the range of percentage increase was 6-12% and the mean percentage increase was 9.89%. In cirrhotic patients, the range of increased liver volume after the meal was 1-20ml. Mean increased liver volume was 6.9ml, the range of percentage increase was 0-1.9% and the mean percentage increase was 0.65%. Compared with the control group, cirrhotic patients showed a much smaller increase in liver volume (p<0.01). CONCLUSION: Difference in variation of liver volume between a control group and cirrhotic patients before and after a meal can be used for the evaluation of liver cirrhosis.

Efficacy of Tacrolimus in Primary Kidney Transplant Patients: Multi-center, Open-label, Prospective Study / 대한이식학회지

Introduction of tacrolimus has been accepted as one of the major advance in the management of rejection following solid organ transplantation. This open-label, multi-center study is designed to confirm the efficacy of tacrolimus in primary kidney transplantation. A total of 64 renal transplant recipients were recruited from 4 medical centers, and received dual drug therapy consists of tacrolimus and low-dose corticosteroids after kidney transplantation. Tacrolimus was started 2 days prior to the transplantation with the dosage of 0.2 mg/kg/day. Daily dose of tacrolimus was modulated to maintain the trough blood level between 15 ng/ml and 20 ng/ml for the first 3 months and between 10 ng/ml and 15 ng/ml for the next 3 months after the transplantation. Steroid pulse therapy with methylprednisolone was used as a first line modality of acute rejection treatment. Steroid resistant rejection was treated with anti- lymphocyte agents. Post-transplant diabetes mellitus was defined as the cases when patients who had no history of glucose intolerance need the use of oral hypoglycemics and/or insulin for 30 days or longer to control their hyperglycemia after transplantation. There were 51 live donor and 13 cadaveric donor transplantations. Live donor transplantation consisted with 33 related (10 HLA identical, 23 HLA haplo- identical) and 18 unrelated pairs. Mean age of the patients was 39.4 9.6 (range; 22-58). There were 36 male and 28 female patients. There were 21 acute rejection episodes in 17 patients (26.6%) during the first 6 months after transplantation. Six patients were treated with anti-lymphocyte agents, and 4 patients showed complete response but 2 episodes (9.5%) showed partial rescue. Six-month patient and graft survivals were 100% and 98.4%, respectively. A total of 18 patients (28.1%) experienced glucose intolerance during the study period. Tacrolimus showed satisfactory efficacy in primary kidney transplantation. Long-term follow up is needed for further evaluation of efficacy and safety.

Polyomavirus Induced Interstital Nephritis in Renal Allograft Recipient / 대한이식학회지

We report our experience of renal polyomavirus infection after renal allograft leading to graft dysfunction. A fourty seven-years-old male patient, has been on Tacrolimus based dual immunosuppression, showed graft dysfunction with rising serum creatinine at post-transplant day 140. His graft function had been good without any acute rejection episode. A tentative diagnosis of acute rejection was rendered and core needle biopsy was performed. Viral infection was initially suggested by the occurrence of markedly enlarged tubular epithelial cells containing large nuclei with smudgy chromatin pattern. Confirmatory diagnosis of human polyomavirus induced interstitial nephritis was obtained by electron microscopy, which showed viral particles in the nuclei of tubular epithelial cells. After Tacrolimus was converted to cyclosporine, renal function was stabilized. A review of the literature indicates that asymptomatic infection, ureteric stricture, and hemorrhagic cystitis are other possible manifestations of polyomavirus in the human urogenital tract. According to some prior reports, polyomavirus induced interstitial nephritis might be a cause of graft loss. But our patient has retained a stable graft function with a chnange of immunosuppression.

Relationship of Proteinuria and Graft Survival According to the Degree of Transplant Glomerulopathy / 대한이식학회지

Transplant glomerulopathy (TG) is a special form of glomerular injury in renal allografts. It affects varying proportions of glomeruli, which may have an influence on the amount of proteinuria or graft survival. We reviewed 32 cases of TG to evaluate histologic changes and graft outcome. The severity of TG as well as acute and chronic changes of the glomerular, tubulointerstitial and vascular compartment were scored according to Banff classification. There were 17 cases of cg1, 3 cases of cg2 and 12 cases of cg3. There was no significant difference in age, duration of transplant at time of biopsy and duration of follow-up between groups. Serum creatinine level and the degree of proteinuria were higher in cg3 and statistically significant. However, there was no difference in the degree of glomerulosclerosis, interstitial inflammation, fibrosis, tubular atrophy or vascular wall thickening between groups. Graft failure was present in 13 cases, mostly due to chronic rejection including sepsis and CMV infection in one case each. Five-year graft survival was 84.1% and was not significantly different from cases without TG. In conclusion, the severity of TG indicates profuse proteinuria, but does not affect graft outcome, which indicates tubulointerstitial and vascular pathology as being a more important prognosticator.

Mycophenolate Mofetil in Living Donor Renal Allograft Recipients: Prospective Study up to 1 Year Post-transplantation / 대한이식학회지

No abstract available.

Pregnancy in Female Patients with Renal Transplantation: Safety to mother, neonate and allograft / 대한이식학회지

We retrospectively reviewed 48 pregnancies in 36 female patients after renal transplantation until February, 1998 at Yonsei University College of Medicine. All patients were maintained on cyclosporine-based immunosuppressive regimen before, during and after pregnancy. Patients were divided into two groups; group 1 (Delivery Group) of 25 women with 26 pregnancies and group 2 (Abortion Group) of 19 women with 22 pregnancies. Mean interval between renal transplantation and conception is 31.8+/- 22.9 months. Serum creatinine was reported before, during and after pregnancy and there was no significant changes of its mean value in both groups. Mean daily dosage of cyclosporine were similar in patients. Average gestational age was 37.0+/- 2.0 weeks and the incidences of very low birth weight (VLBW), low birth weight (LBW) and small for gestational age (SGA) were 7.7%, 63.5% and 84.6%, respectively. Pregnancy-related complications during pregnancy in group 1 were urinary tract infection in 11 cases, preeclampsia in 7 cases, hypertension in 4 cases and proteinuria in 3 cases. There was no acute rejection or graft loss during pregnancy. The premature deliveries less than 37 weeks were 12 cases (46.2%). Low birth-weight of neonate was significantly related with maternal pre-pregnant hypertension (1793.3+/- 393.0 gm in patients with hypertension vs. 2471.2+/- 468.1 gm in patients without hypertension; p=0.001). Pregnancy in female renal transplant patients is relatively safe while they are monitored in a tertiary care center with close monitoring of cyclosporine A (CsA) dosing, serum creatinine levels and the other laboratory values by a transplant surgeon, nephrologist, obstetrician and pediatrician.

Long-term Follow-up of Living Kidney Donors / 대한이식학회지

Kidney transplantation using living donors has been performed in our hospital since the very start in 1979. In recent years, we have expanded living donor pool, including unrelated one, because the number of cadaveric donors is insufficient. A very important issue in living kidney donor transplantation is whether the donation is safe or not for the donor. The aim of this study was to examine the long-term impact of uninephrectomy on the renal function, blood pressure, and proteinuria in living kidney donors. We could followed 59 donors who had donated a kidney more than 10 years ago. Among these 59 donors, 19 donors visited hospital and were undertaken physical examination and laboratory evaluation. We checked blood pressure, BUN/creatinine, 24 hours urine protein, and creatinine clearance to these donors. The rest 40 donors were traced by telephone survey for medical history and survival. The mean duration of follow-up were 12.8 +/-2.6 and 13.2+/- 2.5 years, respectively in both group of the donors. The mean age at last follow-up were 44.3+/- 11.2 and 46.7+/- 11.1 years old, respectively. Actually 2 patients proved to have well controlled hypertension with anti-hypertensive medications. Mean values of systolic and diastolic blood pressure were 129+/- 19 and 82+/- 11 mmHg in 19 donors, which showed no difference from general population compared with nationwide survey of blood pressure. There were no difference of BUN/creatinine, 24 hours urine protein, and creatinine clearance between pre-nephrectomy and follow-up values. There was one patient death in the telephone surveyed group, who died of stomach cancer. No body had specific medical illness and took hypertensive medication in the telephone surveyed group. We could not demonstrate any deterioration of renal function and development of uninephrectomy induced hypertension in living kidney donor more than 10 years after kidney donation.

Effect of Cyclosporine, Mycophenolic Acid, and Rapamycin on the Proliferation of Rat Aortic Vascular Smooth Muscle Cells: in Vitro Study / 대한이식학회지

Proliferative and obliterative arteriopathy resulting ischemic end organ dysfunction is the main histologic feature of chronic rejection after organ transplantation. This vascular narrowing and intimal hyperplasia produced by chronic rejection is one of the major factor that limits long-term survival after solid organ transplantation. At present, effective prophylactic and therapeutic strategies for chronic rejection is still missing. The proliferation and migration of smooth muscle cells and finally deposition of extracellular matrix account for much of the arterial intimal thickening in organ allografts. In vivo animal models of hyperplastic vascular luminal narrowing induced by allogeneic or mechanical injury to the vasculature indicate that certain immunosuppressive drugs have inhibitory properties on smooth muscle cell proliferation. This study summarizes the inhibitory effects of different immunosuppressive drugs in vitro on the growth factor-induced proliferation of vascular smooth muscle cells isolated from rat aorta. Rapamycin and mycophenolic acid potently inhibited the proliferation of vascular smooth muscle cells at clinically attainable concentration, individually. Cyclosporine showed limited inhibition of smooth muscle cell proliferation, but the inhibitory concentration50 (IC50) values were just below cytotoxic levels. Therefore these direct antiproliferative action on vascular smooth muscle cells by rapamycin or mycophenolic acid, in vitro, may prevent the development of arterial intimal thickening associated with chronic rejection.