[Show abstract][Hide abstract] ABSTRACT: The optimal immunosuppressive strategy for renal transplant recipients at high immunologic risk remains a topic of investigation. This prospective single arm pilot study was undertaken to evaluate the safety and efficacy of a combined tacrolimus and sirolimus regimen in recipients at immunological high risk and to compare outcomes with a contemporaneous control group received tacrolimus and mycophenolate mofetil. Patients that received a renal allograft between 2010 and 2011 at high risk (defined as panel reactive antibodies > 50%, 4 or more human leukocyte antigen mismatches, or retransplantation) were enrolled. All patients received basiliximab induction and corticosteroids. A total of 28 recipients treated with tacrolimus and sirolimus were enrolled in this study and 69 recipients were retrospectively reviewed as a control group. The sirolimus group showed a higher, but not statistically significant, incidence of biopsy proven acute rejection and a lower glomerular filtration rate than the control group. Furthermore, sirolimus group was associated with significant increases in BKV infection (P = 0.031), dyslipidemia (P = 0.004), and lymphocele (P = 0.020). The study was terminated prematurely due to a high incidence of adverse events. A de novo tacrolimus/sirolimus combination regimen may not be an ideal choice for recipients at high immunological risk.
Journal of Korean medical science 06/2015; 30(6):682-7. DOI:10.3346/jkms.2015.30.6.682 · 1.25 Impact Factor
[Show abstract][Hide abstract] 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).
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.
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.
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.
[Show abstract][Hide abstract] 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.
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).
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
[Show abstract][Hide abstract] 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.
Journal of Korean Medical Science 08/2014; 29(8):1069-76. DOI:10.3346/jkms.2014.29.8.1069 · 1.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: 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. Methods: A comparative, parallel, randomized, open-label 1-year study has been performed in 148 patients from five transplant centers to compare the efficacy and tolerability of everolimus and reduced exposure CsA (the investigational group) or enteric-coated mycophenolate sodium and standard-exposure CsA (the control group) in combination with basiliximab and steroids. The eligible subjects were randomly assigned at 1 month after transplantation. Efficacy failure (biopsy-proven acute rejection, death, graft loss, or loss to follow-up), safety, and renal function were evaluated. Results: One graft loss has been reported in the control group and no patient death were reported in either group. The incidence of biopsy-proven acute rejection until 12 months after transplantation of the investigational group was 7.5%, compared to 11.1% of the control group (P=0.565). The mean estimated glomerular filtration rates of the investigational group at 12 months after transplantation was significantly higher (68.1±16.8 ml/min/1.73 m2) than that of the control group (60.6±15.8 ml/min/1.73 m2; P=0.016). There was no significant difference (P>0.05) in the incidence of discontinuations and serious adverse events between the groups. Conclusion: The results of this study provide the evidences that (1) the calcineurin inhibitor (CNI) minimization by the introduction of everolimus after 1-month posttransplantation keeps the incidences of acute rejection and addtional risks as low as the conventional immunosuppression; (2) it allows minimizing CNI exposure, consequently reducing CNI nephrotoxicity and preserving renal function.
[Show abstract][Hide abstract] ABSTRACT: Background
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.
KNOW-KT is a multicenter, observational cohort study encompassing 8 transplant centers in the Republic of Korea. KNOW-KT will enroll 1,000 KT recipients between 2012 and 2015 and follow them up to 9 years. At the time of KT and at pre-specified intervals, clinical information, laboratory test results, and functional and imaging studies on cardiovascular disease and metabolic complications will be recorded. Comorbid status will be assessed by the age-adjusted Charlson co-morbidity index. Medication adherence and information on quality of life (QoL) will be monitored periodically. The QoL will be assessed by the Kidney Disease Quality of Life Short Form. Donors will include both living donors and deceased donors whose status will be assessed by the Kidney Donor Risk Index. Primary endpoints include graft loss and patient mortality. Secondary endpoints include renal functional deterioration (a decrease in eGFR to <30 mL/min/1.73 m2), acute rejection, cardiovascular event, albuminuria, new-onset diabetes after transplant, and QoL. Data on other adverse outcomes including episodes of infection, malignancy, recurrence of original renal disease, fracture, and hospitalization will also be collected. A bio-bank has been established for the acquisition of DNA, RNA, and protein from serum and urine samples of recipients at regular intervals. Bio-samples from donors will also be collected at the time of KT. KNOW-KT was registered in an international clinical trial registry (NCT02042963 at http://www.clinicaltrials.gov) on January 20th, 2014.
The KNOW-KT, the first large-scale cohort study in Asian KT patients, is expected to represent the Asian KT population and provide information on their natural course, complications, and risk factors for complications.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.