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Biomedical subjects

Yu Seun Kim

Publications and source records attributed to Yu Seun Kim.

At least 19 recordsLinked to original sources
PubMed2006

Pretransplant soluble CD30 level has limited effect on acute rejection, but affects graft function in living donor kidney transplantation.

BACKGROUND: Serum soluble CD30 (sCD30) levels might be a useful marker of immunologic status in pre transplant (Tx) recipients. We retrospectively correlated preTx sCD30 levels (high versus low) on postTx graft survival, incidence of acute rejection, and graft function using stored preTx serum. METHODS: Of 254 recipients who underwent kidney Tx, 120 recipients were enrolled under the uniform criteria (living donor, age >25 years, viral hepatitis free, diabetes free). RESULTS: The preTx sCD30 was not significantly associated with differences in graft survival rate during 47.5+/-11.4 months of follow-up (P = 0.5901). High sCD30 (> or =115 U/ml) was associated with a higher incidence of clinically or pathologically defined acute rejection than low sCD30, but the difference was not statistically significant (33.9% vs. 22.4%, P = 0.164). The response rate to antirejection therapy in patients with high sCD30 was inferior to those with low sCD30, but also was not statistically significant (33.3% vs. 7.7%, P = 0.087). However, mean serum creatinine levels in high sCD30 patients at one month, one year, and three years postTx were significantly different from those with low sCD30 (P < 0.05). In multiple regression analysis, acute rejection episodes, donor age, kidney weight/recipient body weight ratio, and preTx sCD30 levels were independent variables affecting the serum creatinine level three years postTx. CONCLUSION: PreTx sCD30 level has a limited effect on the incidence of acute rejection and response to antirejection treatment, but inversely and independently affects serum creatinine level after living donor kidney transplantation.

Adult↗
PubMed2006

Urinary HLA-DR and CD54 expression--indicators for inflammatory activity in decoy cell shedding patients.

BACKGROUND: Polyomavirus (PV) nephropathy may coexist with or follow acute renal transplant rejection. The aim of this study was to evaluate whether HLA-DR and CD54 are useful cellular markers for surveillance of acute rejection in PV-infected patients. METHODS: A prospective study was conducted using 205 renal transplant patients. Urine samples were collected at a regular interval post-transplantation for routine cytology and immunocytochemistry. Urinary levels of tumour necrosis factor alpha, soluble interleukin-2 receptor and interleukin-6 were used as adjunctive markers for acute rejection. RESULTS: Of the 699 total samples, decoy cells were identified in 100 samples of 50 patients. Patients with decoy cell-positive (DCP) samples had higher serum creatinine levels than decoy cell-negative (DCN) samples (1.55 vs 1.41 mg/dl, respectively; P = 0.006). DCP samples were also more likely to be HLA-DR positive (50.0 vs 32.4%; P = 0.029), as well as CD54 positive (17.4 vs 6.9%; P = 0.038). However, serum creatinine levels did not correlate with HLA-DR or CD54 positivity among DCP samples. Instead, CD54 positivity correlated with decoy cell grades. Immunosuppression decreased in 11 DCP patients, and HLA-DR was negatively converted in three of them. None of the patients developed acute clinical rejection. Urinary cytokine levels did not correlate with serum creatinine levels, nor did they correlate with HLA-DR or CD54 status among DCP patients. CONCLUSIONS: Urinary tubular HLA-DR and CD54 expression increased in decoy cell shedding patients but did not indicate a concomitant acute rejection. These markers may instead indicate renal inflammatory activity associated with viral reactivation, which has the potential to progress to PV interstitial nephritis.

Acute Disease↗
PubMed2006

Technical refinement for third kidney transplantation.

To overcome the technical difficulties of a third renal transplantation, we developed a refined technique. After native ureteral stenting, the subhepatic retroperitoneum was approached by way of a midline incision. The renal vein was sewn to the vena cava, the artery to the common iliac artery, and the ureter to the native stented ureter.

Adult↗
PubMed2006

Mycophenolic acid inhibits mesangial cell activation through p38 MAPK inhibition.

Mesangial cell (MC) proliferation and extracellular matrix (ECM) accumulation are major pathologic features of chronic renal disease including chronic allograft nephropathy (CAN). Mycophenolic acid (MPA), a potent immunosuppressant, has emerged as a treatment to prevent CAN because it inhibits MC proliferation and ECM synthesis, but the mechanism involved has not been clarified. The present study examined relative role of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK) activation in inhibitory effect of MPA on MC activation. Growth arrested and synchronized primary rat MC (passages 7-11) were stimulated by PDGF 10 ng/ml in the presence and absence of clinically attainable dose of MPA (0-10 microM). Cell proliferation was assessed by [(3)H]thymidine incorporation, fibronectin and the activation of ERK and p38 MAPK by Western blot analysis, and total collagen by [(3)H]proline incorporation. PDGF increased cell proliferation by 4.6-fold, fibronectin secretion by 3.2-fold, total collagen synthesis by 1.8-fold, and the activation of ERK and 38 MAPK by 5.6-fold and 3.1-fold, respectively, compared to control. MPA, at doses inhibiting PDGF-induced MC proliferation and ECM synthesis, effectively blocked p38 MAPK activation but reduced ERK activation by 23% at maximal concentration tested (10 microM). Exogenous guanosine partially reversed the inhibition of MPA on p38 MAPK activation. Inhibitor of ERK or p38 MAPK suppressed PDGF-induced MC proliferation and ECM synthesis. In conclusion, MPA inhibits p38 MAPK activation leading to inhibiting proliferation and ECM synthesis in MC. Guanosine reduction is partially responsible for inhibitory effect of MPA on p38 MAPK activation in MC.

Animals↗
PubMed2006

Carvedilol inhibits platelet-derived growth factor-induced extracellular matrix synthesis by inhibiting cellular reactive oxygen species and mitogen-activated protein kinase activation.

BACKGROUND: Vascular smooth muscle cell (VSMC) proliferation, migration, and extracellular matrix (ECM) synthesis are major pathologic features of chronic allograft vasculopathy. Carvedilol, an anti-hypertensive agent, might be an effective agent for preventing the development and progression of chronic allograft vasculopathy, since it can inhibit VSMC proliferation and migration. The present study was designed to examine the effect of carvedilol on platelet-derived growth factor (PDGF)-induced ECM synthesis in rat VSMCs. Furthermore, we evaluated whether carvedilol inhibits PDGF-induced cellular reactive oxygen species (ROS) and the activation of mitogen-activated protein kinase (MAPK). METHODS: Primary cultured rat VSMCs were stimulated with PDGF-BB (10 ng/ml) in the presence or absence of carvedilol, and the effects of carvedilol were compared with those of ROS or MAPK inhibitors. Fibronectin secretion, proliferating cell nuclear antigen (PCNA) expression, and each MAPK activation were determined by Western blot analysis, total collagen synthesis by [3H]-proline incorporation, and cellular ROS by flow cytometry. RESULTS: PDGF significantly increased PCNA expression, fibronectin secretion, total collagen synthesis, cellular ROS, and MAPK activation in rat VSMCs. Carvedilol at doses that inhibited PDGF-induced cell proliferation, inhibited ECM synthesis, cellular ROS, or subsequent MAPK activation. Structurally different anti-oxidants and extracellular signal-regulated protein kinase or p38 MAPK inhibitor effectively inhibited PDGF-induced fibronectin secretion and total collagen synthesis. CONCLUSIONS: These results suggest that carvedilol inhibits PDGF-induced VSMC proliferation and matrix protein synthesis by inhibiting cellular ROS and the subsequent activation of MAPK. Thus the targeted inhibition of cellular ROS and MAPK might provide an effective therapeutic strategy to treat chronic allograft vasculopathy.

Animals↗
PubMed2006

Association of genetic variations in CCR5 and its ligand, RANTES with clearance of hepatitis B virus in Korea.

Immunogenetic factors may play a role in determining the susceptibility of an individual to viral infection. The aim of current study was to investigate the association of clearance of hepatitis B virus (HBV) with promoter polymorphisms within the CC chemokine receptor 5 (CCR5) and its major ligand, regulated upon activation, normal T cells expressed and secreted (RANTES) genes. Five chemokine system polymorphisms (CCR5 Delta32, CCR5 promoter 59029G/A, 59353C/T, RANTES -403G/A, and -28C/G) were studied in a total of 698 subjects. The carriage of each genetic variant was compared among "spontaneously recovered" group (n = 243), "chronic carrier" group (n = 349), and "unexposed" group (n = 106). CCR5 59029G promoter variant was associated with clearance of HBV infection in an acute phase (OR = 1.71, P = 0.006, dominant model; OR = 2.17, P < 0.001, recessive model) and amelioration of hepatic inflammation (P = 0.003) with the control of HBV replication (P = 0.04) in chronic carriers. Interestingly, CCR5 59029 was linked completely to CCR5 59353, and CCR5 Delta32 homozygosity or heterozygosity was not found in any Korean patient. No association was seen with RANTES polymorphisms at position -403 and -28. The CCR5 59029G/CCR5 59353T polymorphism may play a role in the clearance of HBV infection.

Adult↗
PubMed2005

Combined effects of losartan and pravastatin on interstitial inflammation and fibrosis in chronic cyclosporine-induced nephropathy.

BACKGROUND: Statins and angiotensin II type I receptor blockers have synergistic effects on vascular smooth-muscle-cell proliferation and the progression of renal diseases. We evaluated whether combined treatment with losartan (LSRT) and pravastatin (PRVT) affords superior protection compared with their respective monotherapies in treating chronic cyclosporine (CsA)-induced nephropathy in rats. METHODS: Rats maintained on a low salt diet were given vehicle, CsA (15 mg/kg), CsA and LSRT (10 mg/kg), CsA and PRVT (5 mg/kg), or a combination of CsA, LSRT, and PRVT for 28 days. Basic parameters (renal function, systolic blood pressure, serum high-sensitivity C-reactive protein [hs-CRP], and lipid profiles), histopathology (arteriolopathy, tubulointerstitial fibrosis, and inflammatory cell infiltration), and inflammatory and fibrotic factors (intrarenal CRP, angiotensin II, osteopontin, and transforming growth factor [TGF]-beta1) were studied. RESULTS: LSRT or PRVT treatment significantly attenuated the histopathologic changes induced by CsA, and combined treatment with LSRT and PRVT further decreased these parameters compared with giving each drug alone. Increased levels of angiotensin II, intrarenal CRP, osteopontin, and TGF-beta1 in CsA-treated rat kidney were reduced by treatment with either LSRT or PRVT and were further decreased by the combination of the two drugs. There were no significant differences in systolic blood pressure or serum lipid parameters between groups. CONCLUSIONS: Combined treatment with LSRT and PRVT provided synergistic effects in attenuating inflammatory and fibrotic processes in a rat model of chronic CsA-induced nephropathy, and this effect was independent of their hypolipidemic and hypotensive actions.

Animals↗
PubMed2005

Chronologically different impacts of immunologic and non-immunologic risk factors on renal allograft function.

INTRODUCTION: Upon analysis of the risk factors affecting renal graft survival and function, the time-dependent effects of each risk factor should be differentiated from their net effects. To evaluate the chronologically different impacts of risk factors on graft renal function, we reviewed 390 recipients who received a kidney from 1-haplotype-matched living-related donors. MATERIALS AND METHODS: Until 5-yr post-transplantation (TX), yearly serum creatinine (Scr), 24-h urinary excretion of protein, and their yearly changes were compared by the episodes of acute rejection within 1 yr, the kidney weight to recipient body weight (KW/BW) ratio, the donor/recipient (D/R) age ratio, and the D/R gender pairing. The Kaplan-Meier method, Cox proportional hazard model, ANOVA, and repeated measures ANOVA were each applied for different purposes. RESULTS: Only the episodes of acute rejection were a significant risk factor affecting graft survival. The episodes of acute rejection, KW/BW ratio, D/R age ratio, and D/R gender pairing consistently and independently had significant influences on Scr. Recipients having the lowest KW/BW ratio (first quartile) or the highest D/R age ratio (fourth quartile) had rapid increments of Scr after 4-yr post-TX. After 3-yr post-TX, there were significant correlations between the number of non-immunologic risk factors present and the yearly changes in Scr. CONCLUSIONS: Non-immunologic factors had a detrimental effect on renal graft function, especially after 3-yr post-TX. If immunologic risks seem to be similar, size matching, age, and gender pairing should be considered for better long-term graft function in renal TX recipients.

Age Factors↗
PubMed2005

Metabolic demand and renal mass supply affecting the early graft function after living donor kidney transplantation.

BACKGROUND: Graft mass has been demonstrated to be a determinant of outcome after kidney transplantation. An insufficient nephron might fail to meet the metabolic demands of the recipient and lead to hyperfiltration. METHODS: The study population was restricted to live donor transplants demonstrating immediate function that had neither ischemic injury, episodes of rejection, nor any complications that resulted in a functional decrease of the graft. The donated kidney was weighed just after cold flush, and the recipient's serum creatinine (Scr) was measured on a daily basis postoperatively. When the recipient's Scr reached the baseline, the recipient's 24-hour urine was collected for the amount of proteinuria (Upr), creatinine excretion (Ucr), and creatinine clearance (Ccr) calculation. As the parameters of the metabolic demands of donor and recipient, body weight, height, body surface area, lean body weight, and body mass index were noted. Pearson correlation and linear regression were carried out. RESULTS: The graft function, as measured by Scr, Ucr, and Upr, was not directly correlated with the graft weight but rather correlated with the ratios of graft weight to the parameters of recipient's metabolic demands. As recipient size increased, the metabolic demand has increased. The parameters of recipient's metabolic demands were directly correlated with Scr and Ucr, rather than with Upr. CONCLUSION: During living donor and recipient matching, both the potential sizes of the donated kidney and the recipient should be considered in terms of the early graft function after transplantation.

Adult↗
PubMed2004

IgA nephropathy in renal allografts-recurrence and graft dysfunction.

With time after transplantation, the recurrence of IgA nephropathy (IgAN) becomes a relevant cause of graft dysfunction and failure. However, only limited information has been published regarding the related clinical and histological features. In this article, we review studies on recurrent IgAN in the English literature and describe our own clinical experience. The clinical and histological features related to recurrence are still indeterminate, but features associated with graft dysfunction include proteinuria, glomerulosclerosis, mesangial proliferation, glomerular crescents and interstitial fibrosis.

Glomerulonephritis, IGA↗
PubMed2004

Oxidative stress and chronic allograft nephropathy.

Oxidative stress defined as outbalanced generation of reactive oxygen species (ROS) than the existing antioxidative defense mechanisms plays an important role in tissue injury. Ischemia/reperfusion accompanied during organ transplantation is well- established oxidative stress-induced tissue injury. We hypothesized that oxidative stress may also play a role in the development and progression of chronic allograft nephropathy (CAN), since that ROS are major signaling molecules of growth factors and cytokines [platelet-derived growth factors, transforming growth factor-beta1(TGF-beta1)] upregulated in the kidney of CAN, that ROS in turn upregulate TGF-beta1, and that mycophenolic acid may inhibit features of CAN [proliferation and extracellular matrix (ECM) accumulation in vascular smooth muscle cells and glomerular mesangial cells] through inhibiting cellular ROS. Cellular ROS activate signal transduction cascade (protein kinase C, mitogen-activated protein kinases, and janus kinases) and transcription factors (nuclear factor-kappaB, activated protein-1, specificity protein 1, and signal transducers and activators of transcription) leading to regulation of genes and proteins involved in cellular proliferation, ECM remodeling, and apoptosis accompanied in CAN. This review is intended to provide an overview of oxidative stress in renal allograft nephropathy.

Chronic Disease↗
PubMed2004

Transplant graft vasculopathy: an emerging target for prevention and treatment of renal allograft dysfunction.

Maintenance of healthy endothelium is essential to vascular homeostasis, and preservation of endothelial cell function is critical for transplant allograft function. Damage of microvascular endothelial cells is now regarded as a characteristic feature of acute vascular rejection and chronic allograft nephropathy, which is an important predictor of graft loss and is often associated with transplant vasculopathy. In this review, we will discuss the role of microvascular endothelium, in renal allograft dysfunction, particularly as it relates to markers of endothelial dysfunction and endothelial repair mechanisms. We also discuss the potential for therapies targeting endothelial dysfunction and transplant graft vasculopathy.

Humans↗
PubMed2004

Rapamycin inhibits platelet-derived growth factor-induced collagen, but not fibronectin, synthesis in rat mesangial cells.

Rapamycin, a macrocyclic lactone, is effective in reducing the incidence of acute rejection after renal transplantation. The inhibitory effects of rapamycin on lymphocyte proliferation and the molecular mechanisms that were involved have been described. However, its effects on glomerular mesangial cells have not been clearly understood, and here, we examined the effect of rapamycin on platelet-derived growth factor (PDGF)-induced extracellular matrix synthesis as well as cell proliferation in mesangial cells. Rat mesangial cells were isolated from the glomeruli of Sprague-Dawley rats and cultured with Dulbecco's modified Eagles medium containing 20% fetal bovine serum. Different concentrations of rapamycin were administered 1 hour before the addition of 10 ng/ml of PDGF into growth arrested and synchronized cells. Cell proliferation was assessed by [3H]thymidine incorporation, total collagen synthesis by [3H]proline incorporation, and fibronectin secretion into the medium by Western blot analysis. In the mesangial cells, PDGF increased cell proliferation by 4.6-fold, total collagen synthesis by 1.8-fold, and fibronectin secretion by 3.2-fold. Rapamycin above 10 nM significantly inhibited PDGF-induced proliferation and collagen synthesis, but the treatment of rapamycin up to 1 microM did not show any significant effects on PDGF-induced fibronectin secretion. These inhibitory effects of rapamycin on PDGF-induced mesangial cell proliferation and collagen synthesis reflect the potential value of rapamycin in the prevention and treatment of glomerulosclerosis in patients with chronic allograft nephropathy.

Animals↗
PubMed2004

Video assisted minilaparotomy surgery (VAMS)--live donor nephrectomy: 239 cases.

We have devised a new surgical method of video-assisted minilaparotomy surgery-live donor nephrectomy (VAMS-LDN), which is a hybridized form of laparoscopic and open surgeries that combines the advantages of both. We present the findings of our series of 239 consecutive patients. Since 1993 we have performed 239 successful VAMS-LND. All 239 healthy kidney donors' characteristics and their postoperative courses were retrospectively reviewed and the data were compared to 95 open donor nephrectomies performed during the same period. The mean age and weight of the patients were 37.9 +/- 11.0 years and 62.4 +/- 7.9 kg, respectively. The mean operating time was 154 +/- 41 minutes, which was similar to open donor nephrectomy but shorter than laparoscopic donor nephrectomy. There were no major intraoperative complications except two tears to lumbar veins which required transfusion. The mean warm ischemic time was 2.1 +/- 0.7 minutes, which was equal to open donor nephrectomy. The patients experienced less postoperative pain and recovered quicker than the open donor nephrectomy patients. VAMS-LDN is a safe and minimally invasive technique for live donor nephrectomy, incorporating advantages of both conventional open and laparoscopic methods. We suggest that VAMS-LDN is a viable option for living donor kidney transplantation.

Adult↗
PubMed2004

Peritubular capillary C4d deposition in chronic allograft dysfunction.

Peritubular capillary (PTC) C4d staining represents a marker for acute humoral rejection, however, the impact of positive staining on chronic allograft dysfunction has received little attention. Ninety-three renal allograft biopsies from 93 patients were selected from a total of 174 renal allograft biopsies, which were obtained 6 months or more after transplantation (median: 89 months). Fresh frozen renal tissue was stained with monoclonal antibody against C4d. Sixteen of 93 biopsies showed C4d staining in PTC. C4d staining was positive in 40% of acute rejection cases (n=15) and 21% of chronic rejection cases (n=24). When the samples were divided according to C4d positivity, the C4d (+) group had a higher proportion of acute rejection than the C4d (-) group. However, no significant difference was observed between the two groups in terms of the prevalence of chronic rejection. Degrees of histological injury including tubulitis, interstitial inflammation and interstitial fibrosis were not significantly different between C4d (+) and C4d (-) groups. However, the 2-year graft survival rate after biopsy was lower in the C4d (+) group than in the C4d (-) group (24.8% versus 59.0%, p=0.1255). C4d staining in PTC is associated with late acute rejection, but not with chronic rejection based on conventional morphologic criteria in patients with chronic allograft dysfunction.

Adult↗
PubMed2004

Clinical outcomes of tuberculosis in renal transplant recipients.

Tuberculosis (TB) is an important cause of morbidity and mortality in renal transplant recipients. Rifampin has a potent sterilizing activity, but it reduces the serum concentrations of the immunosuppressive agents. Moreover, the possible contribution made by mycobacterial infection to the incidence of graft rejection or renal dysfunction remains unclear. In this study, we investigated the recurrence of TB and graft survival duration according to rifampin usage, and we evaluated the factors that could influence the duration time until the recurrence of TB. Seventy-eight TB patients diagnosed after kidney transplantation were studied. Pulmonary TB was diagnosed in 26 of the 78 patients (33.3%), pleural TB in 23 (29.5%), combined pulmonary and pleural TB in 5 (6.4%), miliary TB in 19 (24.4%), and intestinal TB in 2 patients. In the pulmonary (pulmonary TB and pleural TB) TB group, no differences in graft survival and the TB free duration period were observed between the rifampin usage subgroup and the non- rifampin usage subgroup. In the extrapulmonary TB group, no difference was found in mean graft survival time between the rifampin usage subgroup and the non-rifampin usage subgroup, but the rifampin usage subgroup showed that the TB had a tendency to recur later than for the non-rifampin usage subgroup (87 +/- 8 vs. 44 +/- 7 months, respectively, p=0.30). The factor affecting the duration period until the recurrence of TB was the treatment duration (RR=0.761, p=0.030). This study suggests that rifampin does not affect graft survival in renal transplant recipients in whom immunosuppression is carefully monitored. Also, the study results indicate that rifampin may prevent a recurrence of extrapulmonary tuberculosis. Prolonged treatment appears to be appropriate for renal transplant recipients with TB.

Adult↗
PubMed2004

The diagnostic value of the adenosine deaminase activity in the pleural fluid of renal transplant patients with tuberculous pleural effusion.

The assessment of the adenosine deaminase activity (ADA) in the pleural effusion is used for the diagnosis of tuberculous pleural effusion (TPE). To examine whether the procedure can be applied to immunocompromised patients, we analyzed the ADA activity in the pleural fluid of renal transplant recipients. We studied 23 renal transplant patients with TPE (21 men and 2 women; the mean age, 33 years). They were treated at the Yonsei University Hospital between January 1985 and December 2001. Patients with granuloma in the pleural biopsy specimen or positive for Mycobacterium tuberculosis in the pleural fluid culture were recruited. The ADA activity in the pleural effusion of 23 renal transplant patients with TPE was compared with 23 immunocompetent patients with TPE. The mean ADA activity was 69.5 +/- 4.6 in renal transplant patients and 65.0 +/- 4.9 U/L in immunocompetent patients. Applying the 40 U/L cut-off point, the positivity of ADA was 91.3% in renal transplant patients, and 86.9% in immunocompetent patients. We thus concluded that the measurement of ADA in the pleural fluid is a useful means in the diagnosis of TPE in renal transplant patients.

Adenosine Deaminase↗