Kyu Ha Huh

Wonju Severance Christian Hospital, Genshū, Gangwon-do, South Korea

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Publications (111)211.69 Total impact

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    ABSTRACT: Thalidomide was originally used to alleviate morning sickness in pregnant women, but was banned due to severe adverse effects. Since the discovery of its anticancer and anti-inflammatory properties, it has regained research interest. However, its mechanism of action is still unknown. Therefore, we examined the effects of thalidomide on effector T (Teff) and regulatory T (Treg) cells in splenocytes of mice. Splenic CD4(+), CD44(low), and CD62L(high) T lymphocytes (Tnaives) isolated from C57BL/6 mice were cultured for T-cell proliferation and Treg conversion. For T-cell proliferation, naive T cells (Tnaives) were cultured for 72 hours with anti-CD3 and anti-CD28 antibodies, and carboxyfluorescein succinimidyl ester (CFSE) labeling method was used. For Treg conversion, Tnaives were cultured for 72 hours with transforming growth factor-β1 (TGF-β1) and interleukin-2 (IL-2). Naïve T cells were plated at 1.5 × 10(5) cells on 96-well plates with 0, 1, 10, 50, or 100 μmol/L thalidomide. All samples were analyzed by flow cytometry after staining with CFSE, APC-conjugated anti-mouse CD4, and FITC-conjugated anti-mouse FoxP3. Thalidomide significantly decreased the proliferation of CD4(+) Teffs in a dose-dependent manner (P < .01). In contrast, conversion to CD4(+)FoxP3(+) Tregs tended to increase by thalidomide treatment, although the increase was not statistically significant. These findings suggest that thalidomide may have an immune modulatory effect by selectively suppressing CD4(+) Teff proliferation. Further studies will be needed to elucidate the underlying signaling pathway. Copyright © 2015 Elsevier Inc. All rights reserved.
    Transplantation Proceedings 04/2015; 47(3):787-90. DOI:10.1016/j.transproceed.2014.12.038 · 0.95 Impact Factor
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    ABSTRACT: Solid-phase immunoassays have improved detection sensitivity for donor-specific HLA antibody (DSHA) and permitted the accurate diagnosis of antibody-mediated rejection (AMR). However, DSHA is not always sufficient to explain the cause of AMR. Consequently, a means of assessing non-HLA antibodies is required to determine the cause of AMR. The aim of the present study was to evaluate the clinical implications of antibodies (Abs) targeting angiotensin II type I receptor (AT1R) in recipients with AMR but without serum DSHA. Non-HLA AMR cases diagnosed between January 2011 and June 2014 were included. Levels of anti-AT1R Abs (U/mL) were quantified by using AT1R assay kits (One Lambda, Calif, United States) with collected sera pretransplantation and at biopsy (cut-off value: 15 U/mL). Seventy-two patients were diagnosed with AMR during the above-mentioned period. Of them, 12 recipients (16.7%) had no DSHA. The sera of these 12 patients were tested (2 patients were only checked at time of biopsy). Nine patients (9/10) were presensitized for anti-AT1R Abs (median, 25.0 U/mL; range, 12.9 to 50.0 U/mL). Ten patients (10/12) were anti-AT1R- positive at time of biopsy (median, 23.2 U/mL; range, 11.4 to 50.0 U/mL). The mean time from transplantation to biopsy was 73 months. Eight patients experienced acute AMR, and 4 developed chronic AMR. Four patients showed negative C4d staining in peritubular capillaries (4/12). Patients were treated with plasmapheresis, low-dose intravenous immunoglobulin, and/or rituximab. AT1R Abs may play a significant role in AMR without detectable DSHA. Pretransplantation detection of AT1R Abs may be helpful for assessing the risk for non-HLA AMR. Copyright © 2015 Elsevier Inc. All rights reserved.
    Transplantation Proceedings 04/2015; 47(3):649-52. DOI:10.1016/j.transproceed.2014.11.055 · 0.95 Impact Factor
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    ABSTRACT: Coronary artery disease (CAD) is one of the leading causes of mortality in kidney transplantation (KT) recipients. Noninvasive coronary angiography with the use of multidetector computerized tomography (MDCT) is feasible with high sensitivity and negative predictive value to evaluate CAD. However, few studies have been conducted to elucidate the applicability of MDCT in KT. This study was designed to evaluate the prevalence and severity of CAD with the use of MDCT angiography in asymptomatic KT recipients. From September 2011 to November 2013, MDCT angiography was performed on 90 renal transplant recipients who had no pre-transplantation CAD history and stabilized post-transplantation renal function for 6-18 months. According to the MDCT results, we divided our study population into 2 groups: The no-CAD group (n = 36; 40.0%) and the CAD group (n = 54; 60.0%). Severity of CAD was categorized as follows: mild CAD, 1 vessel obstructive, 2 vessels obstructive (or in the proximal left anterior descending), and 3 vessels obstructive (or left main). Among the risk factors, pre-transplantation diabetes mellitus and lower levels of high-density lipoprotein, higher parathyroid hormone levels, higher coronary artery calcification scores, and rejection episodes were independent factors for CAD. Thirty-two (59.3%) of the CAD group had mild obstructive lesions and 22 (40.7%) had obstructive lesions in >1 vessel according to MDCT angiography. MDCT angiography is a useful and noninvasive method for detecting CAD even in asymptomatic KT recipients. Copyright © 2015 Elsevier Inc. All rights reserved.
    Transplantation Proceedings 04/2015; 47(3):675-8. DOI:10.1016/j.transproceed.2014.12.032 · 0.95 Impact Factor
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    ABSTRACT: Objective To examine the effect of the side of the allograft (left vs right) on early graft failure and long-term graft survival rates after conventional open living-donor nephrectomy (OLDN) or video-assisted minilaparotomy living-donor nephrectomy (VLDN). Methods We evaluated 2704 living-donor transplantations using OLDN or VLDN between 1991 and 2011 at a single institution. For analysis, the entire period was divided into “era 1” (1991-1997), when OLDN was prevalent; “era 2” (1998-2004), when both OLDN and VLDN were conducted; and “era 3” (2005-2011), when VLDN became prevalent. Results There were 822, 650, and 685 transplantations analyzed in eras 1, 2, and 3, respectively. There were no differences in causes of early graft failure between left and right allografts in any era. The right allograft survival rate in eras 1 and 2 was slightly lower than the left allograft survival rate. In era 2, during which both OLDN and VLDN were conducted, Kaplan-Meier analysis showed lower right allograft survival rate for OLDN. However, the long-term survival rates of the left and right VLDN grafts did not differ. Conclusion Right OLDN allografts demonstrated worse long-term survival rate than left OLDN allografts, but the right and left VLDN allografts had similar long-term survival rate. VLDN appears to be an appropriate treatment option when right donor nephrectomy is desired.
    Urology 10/2014; 84(4). DOI:10.1016/j.urology.2014.06.028 · 2.13 Impact Factor
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    ABSTRACT: Purpose The purpose of this study was to compare once-daily tacrolimus with twice-daily tacrolimus in terms of safety, efficacy, and patient satisfaction. Materials and Methods This prospective, randomized, open-label, multicenter study was conducted at three institutes. Patients in the investigational group were converted from tacrolimus twice daily to the same dose of extended-release tacrolimus once daily at 1 month post-transplantation, while patients in the control group were maintained on tacrolimus twice daily. The efficacies, safeties, and patient satisfaction for the two drugs at 6 months post-transplantation were compared. Results Sixty patients were enrolled and randomized to the investigational group (28 of 29 patients completed the study) or the control group (26 of 31 patients completed the study). At 6 months post-transplantation, composite efficacy failure rates including the incidences of biopsy-confirmed acute rejection in the investigational and control groups were 0% and 10.7%, respectively; patient survival was 100% in each group. No difference in estimated glomerular filtration rate values were observed at 6 months post-transplantation (p=0.97). The safety and satisfaction profile (immunosuppressant therapy barrier scale) of once-daily tacrolimus was comparable with that of twice-daily tacrolimus (p=0.35). Conclusion Conversion from twice-daily tacrolimus to once-daily tacrolimus one month after transplantation is safe and effective.
    Yonsei Medical Journal 09/2014; 55(5):1341-7. DOI:10.3349/ymj.2014.55.5.1341 · 1.26 Impact Factor
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    ABSTRACT: This study was designed to evaluate whether sirolimus (SRL) conversion effectively improves renal function and histopathology in calcineurin inhibitor (CNI)-treated renal recipients with mild to moderate renal insufficiency. SRL conversion from CNI was performed in patients who underwent kidney transplantation from 6 months to 5 yr prior to screening. Forty-five patients were enrolled. The effect of SRL conversion on graft function was evaluated, and protocol biopsies were performed preconversion and 1 yr after conversion. Overall graft function after SRL conversion gradually improved, and the improvement in renal function was closely associated with the shorter duration of CNI exposure. When we divided the patients by the duration of CNI exposure, the patients with less than 1 yr of CNI exposure demonstrated significant improvement, but patients with a greater than 1 yr CNI exposure did not exhibit significant improvement. In contrast, protocol biopsies demonstrated no significant improvements in the modified "ah" score or other Banff scores after SRL conversion. Furthermore, the duration of CNI treatment prior to SRL conversion was not associated with histological findings 1 yr after SRL conversion. SRL conversion improved graft function in renal recipients with mild to moderate renal insufficiency, but this effect is not accompanied by histological improvement. Graphical Abstract
    Journal of Korean Medical Science 08/2014; 29(8):1069-76. DOI:10.3346/jkms.2014.29.8.1069 · 1.25 Impact Factor
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    ABSTRACT: Everolimus and cyclosporine A (CsA) exhibit synergistic immunosuppressive activity when used in combination. We examined the safety and efficacy of the use of everolimus with a cyclosporine-sparing strategy in de novo renal transplant recipients.
    Transplantation 06/2014; 99(1). DOI:10.1097/TP.0000000000000225 · 3.78 Impact Factor
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    ABSTRACT: Asian patients undergoing kidney transplantation (KT) generally have better renal allograft survival and a lower burden of cardiovascular disease than those of other racial groups. The KNOW-KT aims to explore allograft survival rate, cardiovascular events, and metabolic profiles and to elucidate the risk factors in Korean KT patients.
    BMC Nephrology 05/2014; 15(1):77. DOI:10.1186/1471-2369-15-77 · 1.52 Impact Factor
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    ABSTRACT: Mycophenolic acid (MPA)-induced beta cell toxicity limits islet graft survival. However, the signal transduction mechanisms underlying MPA-induced β-cell toxicity have not been fully elucidated. Previously, we showed that MPA-induced pancreatic β-cell apoptosis proceeds via RhoGDI-α down-regulation linked to Rac1 activation. In the present study, we investigated factors affecting RhoGDI-α during MPA-induced β-cell apoptosis. The presence of RhoGDI-α-related protein was determined with the use of yeast 2-hybrid (Y2H) analysis. Y2H screening of RhoGDI-α was performed in yeast PBN204 strain containing 3 reporters (URA3, lacZ, and ADE2) under the control of different GAL promoters. INS-1E cells (an insulin-secreting pancreatic β-cell line) were treated with MPA for 12, 24, and 36 hours. Eighty-three real positives were obtained by Y2H analysis, and of these, arginine N-methyltransferase 3 (PRMT3) protein interacted with RhoGDI-α in INS-1E cells. PRMT3 gene expressions and its protein levels were significantly decreased during MPA-induced apoptosis. In summary, PRMT3 and RhoGDI-α were found to interact in INS-1E cells. Furthermore, MPA was found to regulate this interaction in INS-1E cells by down-regulating the gene expression of PRMT3. These findings suggest that control of the interaction between PRMT3 and RhoGDI-α could be used to prevent MPA-induced β-cell death.
    Transplantation Proceedings 05/2014; 46(4):1229-32. DOI:10.1016/j.transproceed.2013.12.016 · 0.95 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e823. DOI:10.1016/j.juro.2014.02.2241 · 3.75 Impact Factor
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    ABSTRACT: Kidney injury molecule-1 (KIM-1) is known as a good ancillary marker of acute kidney injury (AKI) and its expression has also been observed in acute rejection and chronic graft dysfunction. We tested usefulness of KIM-1 as an indicator of acute and chronic renal graft injury by correlating KIM-1 expression with renal graft function and histology.
    01/2014; 28(3):135. DOI:10.4285/jkstn.2014.28.3.135
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    ABSTRACT: Immunologic responses of infants and younger children differ from those of adults. Therefore, application of different pretransplant strategies for antibody depletion in younger ABO-incompatible transplant recipients is appropriate. A 12-month-old male infant with end stage renal disease after acute tubular necrosis was scheduled to undergo kidney transplantation from an ABO-incompatible living donor. He did not undergo pretransplant plasmapheresis, as the titer of the anti-ABO antibody was less than 1:4. After kidney transplantation, posttransplant renal function and anti-ABO titers were stable until posttransplant 2 years.
    01/2014; 28(1):39. DOI:10.4285/jkstn.2014.28.1.39
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    ABSTRACT: We propose an equation that predicts graft function after kidney transplantation by using donated kidney volume and recipient body surface area (BSA). Included were 261 cases of living kidney transplantation between 2007 and 2009. Preoperative computed tomography scans were performed and the donated kidney volume was measured by use of a three-dimensional reconstruction program (Ripidia). The estimated glomerular filtration rate (eGFR) was calculated by using the modification of diet in renal disease formula. Donated kidney volume, preoperative renal function, and demographic factors of both donors and recipients were evaluated as predictors. The mean ages of the donors and recipients were 40.8 and 41.6 years, respectively. The mean donated kidney volume and donated kidney volume/recipient BSA ratio were 153.4 mL and 96.9 mL/m(2), respectively. Mean preoperative and postoperative 12-month eGFR of recipients were 7.1 and 59.7 mL/min, respectively, and the mean preoperative eGFR of donors was 92.2 mL/min. Donated kidney volume/recipient BSA ratio, donor age, and recipient gender were the significant predictors of eGFR level (p<0.001) and eGFR<45 mL/min at postoperative 12 months (p=0.005, p<0.001, and p=0.006). From the multiple linear regression equation and predicted probability from logistic regression, we could calculate the equation for the ratio of living donor kidney volume to recipient BSA on graft function. Graft kidney volume/recipient BSA ratio, donor age, and recipient gender were predictors of graft function 12 months after kidney transplantation. Although we are concerned only with the preoperative, this equation model could help physicians to counsel patients concerning their postoperative prognosis and to avoid insufficient volume donations.
    Korean journal of urology 12/2013; 54(12):870-5. DOI:10.4111/kju.2013.54.12.870
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    ABSTRACT: Dysglycemia and dyslipidemia are important metabolic complications of organ transplantation. Statins are widely used to control dyslipidemia; however, long-term use of statins is related to diabetes mellitus (DM) and impaired fasting glucose (IFG). The aim of this study was to evaluate the influence of statins on the development of dysglycemia (IFG and/or DM) in renal allograft recipients. A total of 394 patients without previously known DM or IFG who underwent kidney transplantation were enrolled. Patients were grouped into the two groups according to the use of statin (control, n=149; statin, n=245). The major statins used were fluvastatin (80 mg/d, n=134) and atorvastatin (20 mg/d, n=111). We compared the incidence of IFG or DM during the follow-up period. The incidence of IFG was higher in the statin group than that in the control group (28.6% vs. 8.7%, P<0.001). The incidence of dysglycemia was significantly higher in the statin group (40.0% vs. 15.4%, P=0.001). Time to development of dysglycemia after transplantation was shorter in the statin group than in the control group (38.8±29.7 vs. 47.2±23.3 months, P=0.002). Statin use was associated with an increased risk for dysglycemia after adjustment for age, sex, body mass index, hypertension, cholesterol levels, hepatitis C infection, and type of immunosuppressant (hazard ratio=3.08, 95% confidence interval=1.91-4.98). The dysglycemic effect was more profound in the patients who used atorvastatin than in those who used fluvastatin (hazard ratio=2.21, 95% confidence interval=1.02-4.76). Statin treatment is associated with an elevation in fasting plasma glucose and in the development of dysglycemia in renal allograft recipients.
    Transplantation 11/2013; 97(4). DOI:10.1097/01.TP.0000437427.04733.ad · 3.78 Impact Factor
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    ABSTRACT: The organ shortage is as serious in Korea as in other parts of the world. As about one-third of the potential living donors are ABO incompatible (ABOi), transplantation across the blood group barrier can help overcome this shortage. One hundred and twenty-five ABOi kidney transplantations (KTs) were performed between 2007 and 2010 in Korea. We collected the perioperative and follow-up data for 118 of these patients until September 2011. The preconditioning and immunosuppressive protocols were almost identical across the different transplant centers, with rituximab but no splenectomy; pre-transplant plasmapheresis (PP) with target anti-A/B titer 8 or 16 on transplant day, on-demand, rather than routine, post-transplant PP, and tacrolimus-based immunosuppressants. The number of patients and participating centers showed a rapid increase over time, and in 2010, ABOi KT (n = 79) comprised 10% of all the living donor KTs in Korea. The mean follow-up period was 21 months (range, 1-56 months). Sixteen (14%) patients developed acute rejection, and three of these had antibody-mediated rejection (AMR). Two-yr patient and graft survival were 99.2% and 97.5%, respectively. No graft was lost due to AMR. ABOi KT is rapidly expanding in Korea with excellent medium-term outcome and will help mitigate the organ shortage.
    Clinical Transplantation 10/2013; 27(6). DOI:10.1111/ctr.12249 · 1.49 Impact Factor
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    ABSTRACT: In contrast with deceased donor transplantation, the clinical significance of pathologic findings in time-zero biopsies after living donor kidney transplantation are rarely reported, due to the expectation that histologic findings and renal function are normal. The aim of this study was to identify subclinical pathologic findings in living donors and examine the effect on early graft renal function. Between December 2006 and July 2011, 146 living-donor kidney transplant recipients were enrolled in this study. We retrospectively analyzed donor and recipient-related clinical parameters, and post-transplant 6 months and 1 year estimated glomerular filtration rate (eGFR) as early graft renal function. Time-zero biopsies were evaluated using the 2007 Banff criteria. Most abnormal histologic findings were of mild degree as determined by Banff scores. Global glomerulosclerosis (GS, 35.6%), tubular atrophy (CT, 36.3%), interstitial fibrosis (CI, 20.5%), vascular fibrous intimal thickening (CV, 4.1%), arteriolar hyaline thickening (AH, 14.4%), interstitial inflammation (I, 3.4%) were pathologic findings in time-zero biopsies. The univariate analysis revealed that donor age and gender were significantly associated with eGFR at post-transplant 6 months and at 1 year (P < .05). Furthermore, GS and CT were significantly associated with early graft renal function (P < .05). However, multivariate linear regression analysis showed only donor age was significantly associated with early graft renal function (P = .001). A mild degree of subclinical, pathologic findings on time-zero biopsy did not affect early graft renal function in living-donor kidney transplantation.
    Transplantation Proceedings 10/2013; 45(8):2937-40. DOI:10.1016/j.transproceed.2013.08.081 · 0.95 Impact Factor
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    ABSTRACT: Ischemia-reperfusion injury is an inevitable consequence of kidney transplantation, leading to metabolic acidosis. This study compared the effects of normal saline (NS) and Plasmalyte on acid-base balance and electrolytes during living donor kidney transplantation using the Stewart and base excess (BE) methods. Patients were randomized to an NS group (n = 30) or a Plasmalyte group (n = 30). Arterial blood samples were collected for acid-base analysis after induction of anesthesia (T0), prior to clamping the iliac vein (T1), 10 minutes after reperfusion of the donated kidney (T2), and at the end of surgery (T3). In addition serum creatinine and 24-hour urine output were recorded on postoperative days 1,2, and 7. Over the first postoperative 7 days we recorded episodes of graft failure requiring dialysis. Compared with the Plasmalyte group, the NS group showed significantly lower values of pH, BE, and effective strong ion differences during the postreperfusion period (T2 and T3). Chloride-related values (chloride [Cl(-)], free-water corrected Cl(-), BEcl) were significantly higher at T1, T2, and T3, indicating hyperchloremic rather than dilutional metabolic acidosis. Early postoperative graft functions in terms of serum creatinine, urine output, and graft failure requiring dialysis were not significantly different between the groups. Both NS and Plamalyte can be used safely during uncomplicated living donor kidney transplantation. However, Plasmalyte more stably maintains acid-base and electrolyte balance compared with NS especially during the postreperfusion period.
    Transplantation Proceedings 07/2013; 45(6):2191-6. DOI:10.1016/j.transproceed.2013.02.124 · 0.95 Impact Factor
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    ABSTRACT: Mycophenolic acid (MPA) is one of many effective immunosuppressive drugs. However, MPA can induce cellular toxicity and impair cellular function in β-cells. To explore the effects of MPA and the relation between MPA and Trx-1, we used various methods, including an Illumina microarray, to identify the genes regulated during pancreatic β-cell death following MPA treatment. INS-1E cells (a pancreatic β-cell line) and isolated rat islets were treated with MPA for 12, 24, or 36 h, and subsequent microarray analysis showed that (Trx1) gene expression was significantly reduced by MPA. Further, Trx1 overexpression increased the cell viability, decreased the activations of c-jun N-terminal kinase (JNK) and caspase-3 by MPA, and attenuated ROS upregulation by MPA. Furthermore, siRNA knockdown of Trx1 increased MPA-induced cell death and the activations of p-JNK and caspase-3, and MPA significantly provoked the apoptosis of insulin-secreting cells via Trx1 downregulation. Our findings suggest that the prevention of Trx1 downregulation in response to MPA is critical for successful islet transplantation.
    Cell Death & Disease 07/2013; 4(7):e721. DOI:10.1038/cddis.2013.247 · 5.18 Impact Factor
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    ABSTRACT: BACKGROUND: We explored the efficacy of the Oxford classification for assessing native immunoglobulin A nephropathy (IgAN) in posttransplantation patients compared with the glomerular injury score and Haas classification. METHODS: A total of 125 renal allograft biopsies obtained from 114 patients diagnosed with IgAN regardless of original disease were assessed. RESULTS: The average time to biopsy was 70.5±45.3 months after transplantation. Glomeruli showed normal histology in 18.4%. Mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), and tubulointerstitial fibrosis (T1-2) were present in 12.8%, 6.4%, 45.6%, and 20.8% of the samples, respectively. There was a significant correlation between Oxford-MEST scores and glomerular injury score or Haas subclass. S1 and T1-2 were correlated with elevated serum creatinine level, proteinuria, and decreased estimated glomerular filtration rate, and E1 was correlated with decreased estimated glomerular filtration rate at the time of biopsy. The 10- and 15-year graft survival rates were 62.9% and 34.3%, respectively. The graft survival rate was significantly lower in the presence of S1 and T1-2. Endocapillary hypercellularity, segmental sclerosis, and tubulointerstitial fibrosis predicted graft survival and endocapillary hypercellularity and tubulointerstitial fibrosis also predicted serum creatinine doubling. CONCLUSIONS: The Oxford classification scheme is useful for evaluating chronic graft dysfunction in patients with posttransplantation IgAN. In addition to tubulointerstitial fibrosis, the presence of endocapillary hypercellularity and segmental sclerosis should be included in the pathology report.
    Transplantation 05/2013; DOI:10.1097/TP.0b013e318291de65 · 3.78 Impact Factor

Publication Stats

320 Citations
211.69 Total Impact Points

Institutions

  • 2014
    • Wonju Severance Christian Hospital
      Genshū, Gangwon-do, South Korea
  • 2004–2014
    • Yonsei University
      • Department of Surgery
      Sŏul, Seoul, South Korea
  • 2003–2014
    • Yonsei University Hospital
      • • Department of Internal Medicine
      • • Surgery
      Sŏul, Seoul, South Korea
  • 2008
    • The Seoul Institute
      Sŏul, Seoul, South Korea