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The Impact of Donor and Recipient Age in the Outcome of Kindney Transplatation.

Geun Seok YANG ; Oh Jung KWON ; Jong Myoung KANG ; Hae Young PARK

The Journal of the Korean Society for Transplantation.2005;19(1):22-26.

PURPOSE: As general population survival has improved in the last few decades, the age of patients participating in renal transplantation also has increased. This study aimed to investigate the impact of donor and recipient age as predictor of long-term graft survival in renal transplantation. METHODS: We analyzed the transplantation outcome in 598 patients, who received renal transplantation from 1978 to 2003 at Hanyang Universitiy. Patients were divided into four groups according to the age at renal transplantation. Group A (donor age> or =50, recipient age> or =50, n=19/3.2%), group B (donor age> or =50, recipient age<50, n=153/25.5%), group C (donor age<50, recipient age> or =50, n=69/11.6%), group D (donor age<50, recipient age<50, n=357/59.8%). Univariate analysis was used to assess the effect of donor and recipient age as predictor factors of graft outcome. We used Kaplan Meier log-rank method for graft survival and P values less than 0.05 were considered significant. RESULTS: In elderly donor group, graft survival was 89.8% at 1 year, 76.4% at 3 years and younger donor group was 92.8 at 1year, 84.0% at 3 years and the differences showed statistic significance (P=0.009). Univariate analysis of age factor showed a significant reduction of graft survival in recipients transplanted with kidneys coming from donors older than 50 years, however recipient age greater than 50 years was not found as an independent risk factor. The incidence of rejection was 24.6% in elderly donor group and 23.5% in younger donor group (P=NS). Among the four groups, the most valuable result was group D and the 1 year and 3 years graft survival were 93.1%, 84.5% respectively but it was not significant statistically (P=0.50). CONCLUSION: This result is important for the design of allocation and transplantation strategies for kidneys procured in elderly donors and recipients.
Age Factors ; Aged ; Graft Survival ; Humans ; Incidence ; Kidney ; Kidney Transplantation ; Risk Factors ; Tissue Donors* ; Transplants

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Effect of Unilateral Nephrectomy on Rat Kidney in Early Stages of Aging.

Kye Won KWON ; So Young JIN ; Yu Seun KIM ; Kyu Hun CHOI ; Hyeon Joo JEONG

The Journal of the Korean Society for Transplantation.2005;19(1):14-21.

PURPOSE: Despite an increasing usage of old or marginal donor kidneys in renal transplantation, little attention has been directed to the structural and functional changes occurring in the remnant kidney of old donor. In this study, the functional and structural changes were assessed in the remnant rat kidneys of early stages of aging after uninephrectomy (UNx) and compared with that of young rats. METHODS: Twelve month-old and 7~9 week-old Sprague- Dawley (SD) male rats underwent UNx and were sacrificed following 1, 3, and 5 weeks after UNx. Extract and Sham- operated kidneys were used as control. Serum creatinine, 24hr urinary protein excretion, and urinary nitric oxide (NO) were measured. The extract kidneys were examined for routine histology and also for immunohistochemical stains for ED-1, inducible NO synthase (iNOS), and PCNA and TUNEL assay. RESULTS: In control rats, there was no difference in 24hr urine protein excretion and urinary NO level between old and young rats. However, the mean serum creatinine level was higher in old rats than that of young rats. After UNx, urinary NO level was significantly increased in old but not in young rats, without accompanying a significant increase of proteinuria or serum creatinine level. Histological injuries of remnant kidneys were not significantly increased after 5 weeks in old rats. However, TUNEL indices were persistently increased at 5 weeks with a return of PCNA indices to a basal level, The number of ED-1 positive cells and interstitial iNOS expression were also increased in remnant kidney of old rats, however, they were not statistically significant. CONCLUSION: UNx does not seem to affect the short-term renal function or histology in 12-month-old rats. However, persistent increase of TUNEL indices at 5 weeks may suggest parenchymal atrophy and a functional decrease in the long-run. A longer observation may be necessary to predict long-term sequelae of UNx in old rats.
Aging* ; Animals ; Apoptosis ; Atrophy ; Coloring Agents ; Creatinine ; Humans ; In Situ Nick-End Labeling ; Infant ; Kidney Transplantation ; Kidney* ; Male ; Nephrectomy* ; Nitric Oxide ; Nitric Oxide Synthase ; Proliferating Cell Nuclear Antigen ; Proteinuria ; Rats* ; Tissue Donors

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Effects of Tautomycetin on the Proliferation and Fibronectin Secretion in Vascular Smooth Muscle Cells and Glomerular Mesangial Cells.

Ji Hye KIM ; Tae Young LEE ; Jehyun PARK ; Hunjoo HA ; Shin Wook KANG ; Yu Seun KIM

The Journal of the Korean Society for Transplantation.2005;19(1):8-13.

PURPOSE: Proliferation and extracellular matrix (ECM) accumulation in the vascular smooth muscle cell (VSMC) and glomerular mesangial cell (MC) play key roles in the development and the progression of transplant glomerulosclerosis and chronic allograft nephropathy. Tautomycetin (TMC), a newly developed immunosuppressive agent, induces T-lymphocyte apoptosis through the inhibition of tyrosine kinase and protein phosphatase 1. We examined the effects of TMC on platelet-derived growth factor (PDGF)-induced proliferation and ECM synthesis in cultured VSMCs and MCs of Sprague- Dawley rats, and investigated the molecular mechanisms that are involved. METHODS: Different concentrations of TMC were administered 1 hour before the addition of PDGF 10 ng/mL into the growth-arrested and synchronized cells. Cell proliferation was assessed by methylthiazoletetrazolium (MTT) assay. Caspase-3 cleavage, fibronectin secretion, and the activation of Akt, ERK, and p38 MAPK were assessed by Western blot analysis, respectively. RESULTS: PDGF 10 ng/ mL increased cell proliferation, fibronectin secretion, and the activation of Akt, ERK, and p38 MAPK in both VSMCs and MCs. In both cultured cells, TMC at above 1 microgram/mL significantly reduced basal MTT and increased cleavage caspase-3 in a dose-dependent manner. TMC at 100 ng/mL decreased the PDGF-induced VSMC and MC proliferation without cytotoxicity. However, fibronectin secretion and the activation of Akt, ERK, and p38 MAPK were not affected at this low concentration of TMC, respectively. CONCLUSION: The present data demonstrated that low-dose TMC reduced PDGF-induced VSMC and MC proliferation without affecting the fibronectin secretion and cellular kinase activation.
Allografts ; Animals ; Apoptosis ; Blotting, Western ; Caspase 3 ; Cell Proliferation ; Cells, Cultured ; Extracellular Matrix ; Fibronectins* ; Mesangial Cells* ; Muscle, Smooth, Vascular* ; p38 Mitogen-Activated Protein Kinases ; Phosphotransferases ; Platelet-Derived Growth Factor ; Protein Phosphatase 1 ; Protein-Tyrosine Kinases ; Rats ; T-Lymphocytes

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Pancreas Transplantation-Present and Future.

Duck Jong HAN

The Journal of the Korean Society for Transplantation.2005;19(1):1-7.

For patients with insulin dependent diabetes mellitus (IDDM) and renal failure from diabetic nephropathy, simultaneous pancreas-kidney transplantation(SPK) has become an accepted therapy. The benefits of pancreas transplantation are that it normalizes glucose control without the need for insulin administration, improves QOL (quality of life) of diabetic patients and prevents sequelae of hyperglycemia such as diabetic neuropathy, retinopathy and nephropathy. At present, over 1,000 cases/year of pancreas transplantation are performed worldwide, the majority in the US. Currently, there are three types of pancreas transplantation: SPK (simultaneous pancreas and kidney), PAK (pancreas after kidney), and PTA (pancreas transplantation alone). SPK transplantation is the most prevalent, representing 80~90% of the cases, but sometimes PTA is considered in the early stage of diabetic complications to prevent the progression of diabetic retinopathy. Management of surgical complications and rejection has been the key to success of pancreas transplantation. Surgical technique can be categorized according to different pancreas exocrine secretion drainage, including enteric drainage, duct injection and bladder drainage. Medications for postoperative management include antibiotics to prevent infectious disease, anticoagulants and immunosuppressants. Usually, the immunosuppressive protocol for pancreas transplantation is more aggressive than that for kidney transplantation. It is very important to closely monitor graft function for the successful outcome. Currently graft survival has been improved as around 85% of 1 yr graft survival and fairly good longterm survival. In near future islet cell transplantation will be an alternative treatment modality in DM in the condition of improved long term graft survival.
Anti-Bacterial Agents ; Anticoagulants ; Communicable Diseases ; Diabetes Complications ; Diabetes Mellitus ; Diabetic Nephropathies ; Diabetic Neuropathies ; Diabetic Retinopathy ; Drainage ; Glucose ; Graft Survival ; Humans ; Hyperglycemia ; Immunosuppressive Agents ; Insulin ; Islets of Langerhans ; Kidney Transplantation ; Pancreas Transplantation ; Pancreas* ; Renal Insufficiency ; Transplants ; Urinary Bladder

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Effect of Donor's and Recipient's Body Traits on the Early Graft Function after Living Donor Kidney Transplantation.

Su Yun CHOI ; Chang Kwon OH ; Ji Hye KIM ; Gyu Tae SHIN ; Heungsoo KIM ; Se Joong KIM

The Journal of the Korean Society for Transplantation.2004;18(1):50-54.

PURPOSE: Renal graft mass has been known as a determinant of the outcome after kidney transplantation. We evaluated the correlation between the donated kidney weight and the recipient's creatinine clearance (Ccr), the donated kidney weight and serum creatinine (Scr) as well as the correlation between the donor traits and graft function after living-donor transplantation in adults. METHODS: The weight of a donated kidney was measured just after flushing during the operative procedures, and the recipient's Scr was measured on a daily basis postoperatively. When the Scr of the recipient reached the baseline level, we collected the recipient's 24-hour urine for the Ccr calculation. Based on the measured body weight and height, body surface area (BSA) and lean body weight (LBW) were calculated. Pearson correlation analysis was carried out using the SPSS. RESULTS: The weight of donated kidney was significantly correlated with the post-transplant recipient's Ccr (P=0.022). Scr was significantly correlated with the variable of graft weight/ recipient body weight ratio (P=0.047, Pearson correlation=-0.539), graft weight/recipient BSA ratio (P=0.028, Pearson correlation=-0.438), graft weight./recipient LBW ratio (P=0.001, Pearson correlation=-0.603), donor body weight/recipient body weight ratio (P<0.001, Pearson correlation= 0.667), donorBSA/recipient BSA ratio (P<0.001, Pearson correlation=0.743), donor LBW/recipient LBW ratio (p<0.001 Pearson correlation=0.759). CONCLUSIONS: It may be appropriate to select potential living donors based on the predicted size of the kidney, especially for the recipient who will likely to have higher metabolic demands.
Adult ; Body Height ; Body Weight ; Creatinine ; Flushing ; Humans ; Kidney Transplantation* ; Kidney* ; Living Donors* ; Surgical Procedures, Operative ; Tissue Donors ; Transplants*

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Time-dependent Effect of Non-immunologic Factors on the Graft Survival and Graft Function in Haplotype Matched Living Donor Renal Transplant Recipients.

Myoung Soo KIM ; Sung Min MYOUNG ; Dong Kee KIM ; Kyu Ha HUH ; Soon Il KIM ; Yu Seun KIM ; Kyung Ock JEON ; Hyun Jung KIM ; Jong Hoon LEE ; Kiil PARK

The Journal of the Korean Society for Transplantation.2004;18(1):37-49.

PURPOSE: In the analysis of risk factors affecting the renal graft survival and graft function, time-dependent effect of each risk factor should be differentiated from net effect of risk factor. We attempted to analyze the impact of immunologic and/or non-immunologic risk factors on the graft function and survival after renal transplantation among the recipients having same immunologic risks at the time of transplantation. METHODS: Three hundred ninety recipients who underwent haplotype matched living related donor kidney transplantation and have been regularly followed-up were retrospectively evaluated in a single center. All recipients were treated with cyclosporine-based double or triple regimens. The graft function was evaluated by serum creatinine (Scr) level and 24 hours urinary excretion of protein every year until 5 years after transplantation. The donor kidney weight/ recipient body weight ratio (KW/BW), donor age/ recipient age ratio (DA/RA), donor-recipient sex (D-R sex) relationship, and episodes of acute rejection (AR) within 1 year were regarded as the potential risk factors affecting the graft survival and function in this study. Kaplan-Meier method and Cox proportional-hazard model were used for survival analysis. ANOVA to evaluate time-point difference of graft function, and repeated measures ANOVA to evaluate the yearly difference of graft function were used. RESULTS: Only the episode of AR was a significant risk factor affecting the graft survival. However, each non-immunologic risk factors (KW/BW, DA/RA, D-R sex) and AR episode persistently showed statistically significant impact on Scr level until 5 years after transplantation. Recipients having lowest KW/BW (1st Q KW/BW) and highest DA/RA (4th Q DA/RA) had experienced accelerated increment of Scr level from 4th year after transplantation. From 3rd year after transplantation, there is a significant correlation between the numbers of non-immunologic risk factor the recipients having had and yearly increment of Scr level. However, episode of AR didn't influence the annual slope of Scr level even 4th year after transplantation. CONCLUSIONS: Non-immunologic risk factors had an detrimental effect on renal graft function, especially from 3rd year after transplantation. To have a better long-term graft function, non-immunologic risk factors should be considered from the time of live donor evaluation for transplantation. From the early period of transplantation, the recipients should be aware of the negative impact of overweight in terms of graft function and other metabolic derangement.
Body Weight ; Creatinine ; Graft Survival* ; Haplotypes* ; Humans ; Kidney ; Kidney Transplantation ; Living Donors* ; Overweight ; Retrospective Studies ; Risk Factors ; Tissue Donors ; Transplantation* ; Transplants*

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3 Year Results of Tacrolimus in Kidney Transplantation: Single Center Experience.

Hyun Chul KIM ; Sung Bae PARK ; Seung Yeup HAN ; Eun Ah HWANG ; Dong Suk JEON ; Hyung Tae KIM ; Won Hyun CHO ; Chaol Hee PARK

The Journal of the Korean Society for Transplantation.2004;18(1):31-36.

PURPOSE: Results of the US randomized, comparative, multicenter study demonstrated that tacrolimus (Tac) was equivalent to cyclosporine (CyA) in 1-year patient and graft survival in recipients of cadaveric renal transplants. However, the incidence and severity of acute rejection was significantly lower in Tac-treated patients compared with CyA-treated patients. This retrospective, non-randomized single center study represents results of follow-up to 3 years posttransplant. METHODS: A total of 97 kidney transplant recipients were included; 41 received Tac-based immunosuppression, and 56 received CyA-based immunosuppression and followed for 3 years posttransplant. Serious adverse events were also monitored over 3 years. RESULTS: The three-year patient survival rates were 95.0% and 96.5% for Tac and CyA, respectively (P=NS). Corresponding graft survival rates were 90.2% and 91.0%, respectively (P=NS). However, the incidence of acute rejection was significantly less in the Tac-group compared with the CyA-group (17.1% vs. 35.7%, P=0.043). The rate of crossover was significantly higher in the CyA-group (4.9% vs. 21.4%, P=0.013). Renal function at 3 years was similar in both treatment groups. The incidence of posttransplant diabetes mellitus (PTDM), head-ache and alopecia was significantly less in the CyA-group, and that of hypertension, hypercholesterolemia after transplantation was significantly less in Tac-group. The incidence of hirsutism and gingival hyperplasia was negligible in Tac-group. Incidence of hand tremor, hyperkalemia, bacterial and viral infection, and malignancy was comparable in both groups. The incidence of PTDM was significantly less in CyA-group (26.8% vs. 7.1%, P=0.008). Nine (81.8%) of the 11 Tac patients with PTDM were off of insulin at 3 years. CONCLUSIONS: Tacrolimus is a very effective primary immunosuppressive agent in renal transplant recipient. The reduced incidence of acute rejection along with decreased incidence of hypertension and hyperlipidemia after transplantation suggests potential long-term advantage with the use of this drug.
Alopecia ; Cadaver ; Cyclosporine ; Diabetes Mellitus ; Follow-Up Studies ; Gingival Hyperplasia ; Graft Survival ; Hand ; Hirsutism ; Humans ; Hypercholesterolemia ; Hyperkalemia ; Hyperlipidemias ; Hypertension ; Immunosuppression ; Incidence ; Insulin ; Kidney Transplantation* ; Kidney* ; Retrospective Studies ; Survival Rate ; Tacrolimus* ; Transplantation ; Tremor

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Retrospective Study Comparing Cyclosporine Microemulsion and Tacrolimus in Living Donor Renal Transplant Recipient.

Won Hyun CHO ; Hyong Tae KIM ; Ja Hyun KOO ; Hyuk Soo JANG ; Choal Hee PARK ; Sung Bae PARK ; Hyun Chul KIM

The Journal of the Korean Society for Transplantation.2004;18(1):23-30.

PURPOSE: In order to achieve an adequate immunosuppression and avoid side effects of immunosuppressant, various combination of immunosuppressant have been tried. METHODS: To review the result of living donor renal transplantation according to the type of calcineurin inhibitor (group 1: microemulsion cyclosporine with mycophenolate mofetil and steroid (n=53) / group 2: tacrolimus with mycophenolate mofetil and steroid (n=44)), we retrospectively reviewed renal transplant recipients between January 1997 through December 2001 in Dongsan medical center. RESULTS: The biopsy proven acute rejection rate were 30.2% in cyclosporine group, while 20.5% in tacrolimus group. Among the 9 cases of acute rejection in tacrolimus group, four cases were associated with BK virus infection. The response rate of acute rejection to steroid pulse therapy was 75.0% and 66.7% in group 1 and 2 respectively. There were no statistical difference in serial changes of serum creatinine after transplantation, number of recipients whose serum creatinine more than 2.0 mg% and proteinuria more than 100 mg/dL, checked at one year. To treat the side effect and intractable acute rejection, calcineurin inhibitors were exchanged each other in 5 recipients. Average steroid daily dosage at one year was 7.10+/-2.82 mg in cyclosporine group while 5.27+/-1.45 mg in tacrolimus group. Overall graft survival were no significant difference between groups up to 24 months but in recipients who developed acute rejection showed better graft survival in cyclosporine group while recipients without acute rejection had better survival in tacrolimus group. CONCLUSIONS: Tacrolimus based immunosuppression showed lower incidence of acute rejection and better steroid sparing effect but developed more polyoma virus infection which eventually deteriorate graft function and survival up to two years.
Biopsy ; BK Virus ; Calcineurin ; Creatinine ; Cyclosporine* ; Graft Survival ; Humans ; Immunosuppression ; Incidence ; Kidney ; Kidney Transplantation ; Living Donors* ; Polyomavirus ; Proteinuria ; Retrospective Studies* ; Tacrolimus* ; Transplantation* ; Transplants

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Effects of Mycophenolic Acid and Rapamycin on PDGF-induced Mesangial Cell Proliferation and Extracellular Matrix Production.

Myoung Soo KIM ; Jehyun PARK ; Hunjoo HA ; Kyu Ha HUH ; Jiyeon SEO ; Yu Seun KIM ; Hae Jin KIM ; Kiil PARK

The Journal of the Korean Society for Transplantation.2004;18(1):13-22.

BACKGROUND: Excess proliferation and extracellular matrix (ECM) accumulation of mesenchymal cells such as vascular smooth muscle cells (VSMC) and glomerular mesangial cells cause chronic allograft nephropathy showing transplant vascular sclerosis and glomerulosclerosis. Mycophenolic acid (MPA) and rapamycin (RPM) are well known as strong inhibitors of VSMC proliferation, but their effects on the glomerular mesangial cells are not yet clearly understood. This study examined the effects of MPA or RPM on PDGF-induced proliferation and ECM accumulation in rat glomerular mesangial cells. METHODS: Mesangial cells isolated from the glomeruli of Sprague-Dawley rats were cultured with DMEM containing 20% fetal bovine serum. Growth arrested and synchronized cells were administered with test drugs (MPA10 nM~10micrometer, RPM 0.1 nM~1micrometer) before the addition of PDGF 10 ng/mL. Cell proliferation was assessed by [3H]thymidine incorporation, collagen by [3H]proline incorporation, and fibronectin, ERK, and p38 MAPK by Western blot analysis. RESULTS: PDGF increased mesangial cell proliferation by 4.64-fold. Compared to stimulated control, MPA above 500 nM and RPM above 10 nM showed a significant inhibitory effect in a dose- dependent manner. The IC50 of MPA and RPM against PDGF-induced mesangial cell proliferation were around 500 nM and 100 nM, respectively. The collagen synthesis was also inhibited by MPA and RPM, but the fibronectin secretion was inhibited by MPA alone. The proliferation of mesangial cell correlated with activation of ERK and p38 MAPK. MPA, but not RPM, inhibited ERK and p38 MAPK activation. CONCLUSIONS: This study demonstrated that MPA and RPM significantly inhibited PDGF-induced proliferation and ECM production in rat glomerular mesangial cells. The inhibitory effects of MPA, but not RPM, are correlated with ERK and p38 MAPK.
Allografts ; Animals ; Blotting, Western ; Cell Proliferation ; Collagen ; Extracellular Matrix* ; Fibronectins ; Inhibitory Concentration 50 ; Mesangial Cells* ; Muscle, Smooth, Vascular ; Mycophenolic Acid* ; p38 Mitogen-Activated Protein Kinases ; Rats ; Rats, Sprague-Dawley ; Sclerosis ; Sirolimus*

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Post-Renal Transplantation Dyslipidemia.

Jaeseok YANG ; Curie AHN

The Journal of the Korean Society for Transplantation.2004;18(1):1-12.

Long-term survivors in renal transplantation have been increasing, as medical care has improved in addition to development of new immunosuppressants. Therefore, cardiovascular disease, especially ischemic heart disease and chronic allograft dysfunction have become main obstacles to longer survival and better quality of life. Dyslipidemia, which is a well-known risk factor of ischemic heart disease in general population, is more common in renal transplantation patients. Moreover, dyslipidemia is suggested as a nonimmunological risk factor of chronic allograft dysfunction. Therefore, it is important to manage dyslipidemia properly to improve patient and graft survival in renal transplantation. But, specific approach, tailored to renal transplant patients is necessary in the treatment of dyslipidemia, because there are significant differences between renal transplantation patients and general population. We present here, epidemiology, mechanism, and impact of dyslipidemia on ischemic heart disease and chronic allograft dysfunction, and overall approach to dyslipidemia in renal transplantation patients, including treatment guideline.
Allografts ; Cardiovascular Diseases ; Dyslipidemias* ; Epidemiology ; Graft Survival ; Humans ; Immunosuppressive Agents ; Kidney Transplantation ; Myocardial Ischemia ; Quality of Life ; Risk Factors ; Survivors

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