Quantitative Assessment of the Portal Pressure for the Liver Surgery Using Serological Tests.

OBJECTIVE: To establish a reliable equation to predict hepatic venous pressure gradient (HVPG) using serological tests for surgical patients with hepatocellular carcinoma (HCC). BACKGROUND: Accurate assessment of portal pressure for surgical patients with HCC is important for safe hepatic resection (HR). The HVPG is regarded as the most reliable method to detect portal hypertension. However, HVPG is not utilized in many medical centers due to invasiveness of procedure. METHODS: Between 2006 and 2008, 171 patients (Correlation cohort), who underwent liver surgery in a tertiary hospital, were enrolled. Preoperative measurements of the HVPG and serological tests were performed simultaneously. Correlation between the HVPG and serological tests were analyzed to establish an equation for calculated HVPG (cHVPG). Between 2008 and 2013, 510 surgical patients (Application cohort) were evaluated, and HR recommended when cHVPG < 10 mm Hg. The outcomes of HR were analyzed to evaluate reliability of the cHVPG for HR. RESULTS: In the correlation cohort, the equation for cHVPG was established using multivariate linear regression analysis; cHVPG (mm Hg) = 0.209 × [ICG-R15 (%)] - 1.646 × [albumin (g/dL)] - 0.01×[platelet count (10)] + 1.669 × [PT-INR] + 8.911. In the application cohort, 425 patients with cHVPG < 10 mm Hg underwent HR. Among them, 357 had favorable value of ICG-R15 < 20% (group A), and 68 had unfavorable value of ICG-R15 ≥ 20% (group B). There was no significant difference in patient demographics, tumor characteristics, operative outcome, and survival rates between group A and B. CONCLUSIONS: The equation for cHVPG of this study was established on statistical reliability. The cHVPG could be useful to predict portal pressure quantitatively for surgical patients with HCC using serological tests.

Bare-Metal Stent in Dysfunctional Hemodialysis Access: An Assessment of Circuit Patency according to Access Type and Stent Location.

Purpose: To evaluate the circuit patency after nitinol bare-metal stent (BMS) placement according to the type of access and location of the stent in dysfunctional hemodialysis access. Materials and Methods: Between January 2017 and December 2019, 159 patients (mean age, 64.1 ± 13.2 years) underwent nitinol BMS placement for dysfunctional access. The location of stents was as follows: 18 brachiocephalic vein, 51 cephalic arch, 40 upper arm vein, 10 juxta-anastomotic vein, 7 arteriovenous (AV) anastomosis, and 33 graft-vein (GV) anastomosis. Circuit patency was evaluated by the Kaplan-Meier method, and cox regression model. Results: A total of 159 stents were successfully deployed in 103 AV fistula (AVF) and 56 AV graft (AVG). AVG showed lower primary and secondary patency at 12-months compared with AVF (primary patency; 25.0% vs. 44.7%; p = 0.005, secondary patency; 76.8% vs. 92.2%; p = 0.014). Cox regression model demonstrated poorer primary patency at 12 months after stenting in the cephalic arch and GV anastomosis compared with the other sites. Conclusion: AVF showed better primary and secondary circuit patency at 12 months following the placement of BMS compared with AVG. Stents in the cephalic arch and GV anastomosis were associated with poorer primary patency at 12 months compared to those in other locations.

Changes in glucose metabolism among recipients with diabetes 1 year after kidney transplant: a multicenter 1-year prospective study.

Background: Diabetes mellitus is a common and crucial metabolic complication in kidney transplantation. It is necessary to analyze the course of glucose metabolism in patients who already have diabetes after receiving a transplant. In this study, we investigated the changes in glucose metabolism after transplantation, and a detailed analysis was performed on some patients whose glycemic status improved. Methods: The multicenter prospective cohort study was conducted between 1 April 2016 and 31 September 2018. Adult patients (aged 20 to 65 years) who received kidney allografts from living or deceased donors were included. Seventy-four subjects with pre-transplant diabetes were followed up for 1 year after kidney transplantation. Diabetes remission was defined as the results of the oral glucose tolerance test performed one year after transplantation and the presence or absence of diabetes medications. After 1-year post-transplant, 74 recipients were divided into the persistent diabetes group (n = 58) and the remission group (n = 16). Multivariable logistic regression was performed to identify clinical factors associated with diabetes remission. Results: Of 74 recipients, 16 (21.6%) showed diabetes remission after 1-year post-transplant. The homeostatic model assessment for insulin resistance numerically increased in both groups throughout the first year after transplantation and significantly increased in the persistent diabetes group. The insulinogenic index (IGI30) value significantly increased only in the remission group, and the IGI30 value remained low in the persistent diabetes group. In univariate analysis, younger age, newly diagnosed diabetes before transplantation, low baseline hemoglobin A1c, and high baseline IGI30 were significantly associated with remission of diabetes. After multivariate analysis, only newly diagnosed diabetes before transplantation and IGI30 at baseline were associated with remission of diabetes (34.00 [1.192-969.84], P = 0.039, and 17.625 [1.412-220.001], P = 0.026, respectively). Conclusion: In conclusion, some kidney recipients with pre-transplant diabetes have diabetes remission 1 year after transplantation. Our prospective study revealed that preserved insulin secretory function and newly diagnosed diabetes at the time of kidney transplantation were favorable factors for which glucose metabolism did not worsen or improve 1 year after kidney transplantation.

Cytomegalovirus-Associated Hemophagocytic Syndrome Diagnosed by Liver Biopsy in a Kidney Transplant Recipient.

Hemophagocytic syndrome (HPS) is a rare but potentially life-threatening disease in kidney transplant recipients, and is caused by systemic proliferation of macrophages actively phagocytizing other blood cells in the bone marrow, lymph nodes, and the spleen. Here, we report a 40-year-old male kidney transplant recipient who presented with fever, bicytopenia, and elevated liver enzymes 2 months after transplantation. Given that cytomegalovirus antigenemia and real-time polymerase chain reaction tests were positive, liver biopsy was performed under an assumption of cytomegalovirus-induced hepatitis. Hepatic histology revealed multifocal microabscess with cytomegalovirus inclusion bodies, marked Kupffer cell hyperplasia, and erythrophagocytosis by activated macrophages. As laboratory findings such as hyperferritinemia, elevated serum lactate dehydrogenase, low natural killer cell activity, and high soluble interleukin-2 receptor were also compatible with HPS, the recipient was diagnosed as having cytomegalovirus-induced hepatitis combined with reactive HPS. Following intravenous ganciclovir therapy with continuous administration of tacrolimus and corticosteroid, the symptoms resolved and laboratory findings were normalized. As far as we know, this is the first report of cytomegalovirus-induced hepatitis combined with reactive HPS in a kidney transplant recipient that is diagnosed by liver biopsy.

Development and Evaluation of Tannic Acid-Coated Nanosuspension for Enhancing Oral Bioavailability of Curcumin.

Curcumin (CUR) has been used in the treatment of various diseases such as cough, fever, skin disease, and infection because of various biological benefits such as anti-inflammatory, antiviral, antibacterial, and antitumor activity. However, CUR is a BCS class 4 group and has a limitation of low bioavailability due to low solubility and permeability. Therefore, the purpose of this study is to prepare a nanosuspension (NSP) loaded with CUR (CUR-NSP) using a statistical design approach to improve the oral bioavailability of CUR, and then to develop CUR-NSP coated with tannic acid to increase the mucoadhesion in the GI tract. Firstly, the optimized CUR-NSP, composed of sodium dodecyl sulfate (SDS) and polyvinylpyrrolidone/vinyl acetate (PVP/VA), was modified with tannic acid (TA). The particle size and polydispersity index of the formulation measured by laser scattering analyzer were 127.7 ± 1.3 nm and 0.227 ± 0.010, respectively. In addition, the precipitation in distilled water (DW) was 1.52 ± 0.58%. Using a differential scanning calorimeter and X-ray diffraction analysis, the stable amorphous form of CUR was confirmed in the formulation, and it was confirmed that CUR-NSP formulation was coated with TA through a Fourier transform-infrared spectroscopy. In the mucoadhesion assay using the turbidity, it was confirmed that TA-CUR-NSP had higher affinity for mucus than CUR-NSP under all pH conditions. This means that the absorption of CUR can be improved by increasing the retention time in the GI tract of the formulation. In addition, the drug release profile showed more than 80% release, and in the cellular uptake study, the absorption of the formulation (TA-CUR-NSP) containing TA acting as an inhibitor of P-gp was increased by 1.6-fold. In the evaluation of antioxidant activity, the SOD activity of TA-CUR-NSP was remarkably high due to TA, which improves cellular uptake and has antioxidant activity. In the pharmacokinetic evaluation, the maximum drug plasma concentration of the TA-coated NSP formulation was 7.2-fold higher than that of the pure drug. In all experiments, it was confirmed that the TA-CUR-NSP is a promising approach to overcome the low oral bioavailability of CUR.

Mathematical model for early functional recovery pattern of kidney transplant recipients using serum creatinine.

Background: Commonly used equations for calculating estimated glomerular filtration rate (eGFR) are not applicable when serum creatinine (Scr) is rapidly changing like the post-transplant period. A new mathematical model applicable to the post-transplant period is required. Methods: All 623 patients who underwent kidney transplantation from January 2008 to June 2018 at a single institute were included to validate the Scr mathematical equations, and 14,360 Scr laboratory results from the time of re-perfusion to 30 days post-transplantation were analyzed. Results: In the validation of model equations, linear regression analysis yielded adjusted R2 values of 0.972 and 0.925 for equation 5 (applicable when renal function is changing) and equation 1 (applicable when renal function is unchanged), respectively. In selected cases, the population comprised individuals who presented an adjusted R2 value >0.95 with equation 5. Linear regression analysis showed that adjusted R2 values and Pearson's correlation coefficients for equation 5 and equation 1 were 0.994 and 0.997 (P<0.001) and 0.956 and 0.978 (P<0.001), respectively. Most of the eGFR formulas are mathematically applicable only if the creatinine input rate equals the creatinine output rate when comparing between commonly used eGFRs and creatinine clearance using the modeled equation. Conclusions: The proposed equations can provide a new perspective for calculating renal function during the early phase of kidney transplantation. A study of a correlation between the equations and long-term graft outcomes is required.

Clinical Study of Standard- vs Reduced-Dose Tacrolimus Combined With Generic Mycophenolate Mofetil in De Novo Kidney Transplantation: A Prospective Randomized Trial.

BACKGROUND: The lowering of calcineurin inhibitor exposure is possibly considered as the proper strategy to prevent calcineurin inhibitor-induced nephrotoxicity in kidney transplant. This clinical study was designed to compare the efficacy and tolerability of reduced-dose tacrolimus with standard-dose mycophenolate mofetil (MMF) vs standard-dose tacrolimus with reduced-dose MMF. METHODS: A prospective, multicenter, open-label, randomized, and parallel-group clinical trial was conducted at 4 transplant centers in Korea. A total sample size was 108, and eligible patients were randomly assigned in a 1:1 ratio to either reduced-dose tacrolimus with standard-dose MMF (the study group) or standard-dose tacrolimus with reduced-dose MMF (the control group) for 6 months in de novo kidney transplant recipients. Graft function, the incidence of efficacy failure, and adverse events were compared. RESULTS: The mean estimated glomerular filtration rate at 6 months post-transplantation was 69.83 ± 16.68 mL/min/1.73 m2 in the study group and 69.92 ± 17.55 mL/min/1.73 m2 in the control group (P > .05). The overall incidence of biopsy-proven acute rejection was 3.64% (n = 2) in the study group, compared to 3.77% (n = 2) in the control group (P > .05). There was no graft loss, death, or loss of follow-up in either group. CONCLUSION: In conclusion, the results suggest that tacrolimus minimization with standard-dose MMF provides adequate immunosuppression with proper renal function and similar rate of incidence of acute rejection compared with the regimen including standard-dose tacrolimus with reduced-dose MMF.

Improvement of medication adherence with simplified once-daily immunosuppressive regimen in stable kidney transplant recipients: A prospective cohort study.

BACKGROUND: Many immunosuppressive drugs are prescribed as twice-daily dosing. A simplified once-daily dosing of immunosuppressive drug regimen may improve medication adherence. We investigated medication adherence of simplified once-daily immunosuppressive regimen consisting of extended-release tacrolimus, sirolimus, and corticosteroids along with the efficacy and safety of this regimen. METHODS: This study was a prospective, multicenter, controlled and cohort trial. Stable kidney transplant recipients who had received transplantation at least 3 months before the study enrollment were eligible for the study. Participants were required to fill-out the self-reported immunosuppressant therapy barrier scale (ITBS) questionnaire before and after the conversion. Other clinical laboratory parameters and adverse events were evaluated until 6 months post-conversion. RESULTS: A total of 160 kidney recipients comprised the intention-to-treat population. The mean total ITBS score was 19.5 ± 4.0 at pre-conversion and 6 months after converting, the mean total ITBS score was 16.6 ± 3.6 (p < 0.001). Particularly, the ITBS scores of 4 questions related to the frequency of medication dosing were significantly different between pre-conversion and post-conversion. Only 1 patient (0.62%) was diagnosed as biopsy-confirmed acute rejection in the study period. There was no significant change in the mean estimated glomerular filtration rate after the conversion. Overall 95 patients (59.4%) had an adverse event and 28 patients (17.5%) had a serious adverse event. No graft loss and 1 death were reported. CONCLUSION: Medication adherence after the conversion to the once-daily immunosuppressive regimen was significantly improved with no additional risks of efficacy failure or adverse events.

Insulin Secretion and Insulin Resistance Trajectories over 1 Year after Kidney Transplantation: A Multicenter Prospective Cohort Study.

BACKGROUND: We investigated the changing patterns of insulin secretion and resistance and risk factors contributing to the development of post-transplant diabetes mellitus (PTDM) in kidney recipients under tacrolimus-based immunosuppression regimen during 1 year after transplantation. METHODS: This was a multicenter prospective cohort study. Of the 168 subjects enrolled in this study, we analyzed a total 87 kidney transplant recipients without diabetes which was assessed by oral glucose tolerance test before transplantation. We evaluated the incidence of PTDM and followed up the index of insulin secretion (insulinogenic index [IGI]) and resistance (homeostatic model assessment for insulin resistance [HOMA-IR]) at 3, 6, 9 months, and 1 year after transplantation by oral glucose tolerance test and diabetes treatment. We also assessed the risk factors for incident PTDM. RESULTS: PTDM developed in 23 of 87 subjects (26.4%) during 1 year after transplantation. More than half of total PTDM (56.5%) occurred in the first 3 months after transplantation. During 1 year after transplantation, insulin resistance (HOMA-IR) was increased in both PTDM and no PTDM group. In no PTDM group, the increase in insulin secretory function to overcome insulin resistance was also observed. However, PTDM group showed no increase in insulin secretion function (IGI). Old age, status of prediabetes and episode of acute rejection were significantly associated with the development of PTDM. CONCLUSION: In tacrolimus-based immunosuppressive drugs regimen, impaired insulin secretory function for reduced insulin sensitivity contributed to the development of PTDM than insulin resistance during 1 year after transplantation.

En bloc transplantation of horseshoe kidney in Korea.

Transplantation of the horseshoe kidney can be performed en bloc or split into 2 grafts according to the vascular anomaly and the existence of the urinary collecting system in isthmus. From 2011 to 2014, there were 3 horseshoe kidney transplantations in Korea and transplantations were performed at 2 different centers. The transplantations were carried out successfully for all recipients without complications. All recipients have shown good graft kidney function after transplantation. No severe complication was revealed during follow-up period. We described the surgical technique used in the en bloc method to overcome various vascular anomalies and difficulties in choosing cannulation site and postoperative complications. En bloc transplantation of a horseshoe kidney is a useful strategy for patients with end-stage renal disease, and can provide favorable outcomes compared to the transplantation of a normal kidney.

Risk factor for ischemic-type biliary lesion after ABO-incompatible living donor liver transplantation.

AIM: To evaluate the risk factors for ischemic-type biliary lesion (ITBL) after ABO-incompatible (ABO-I) adult living donor liver transplantation (ALDLT). METHODS: Among 141 ALDLTs performed in our hospital between 2008 and 2014, 27 (19%) were ABO-I ALDLT and 114 were ABO-identical/compatible ALDLT. In this study, we extensively analyzed the clinico-pathological data of the 27 ABO-I recipients to determine the risk factors for ITBL after ABO-I ALDLT. All ABO-I ALDLT recipients underwent an identical B-cell depletion protocol with preoperative rituximab, plasma exchange (PE), and operative splenectomy. The median follow-up period after transplantation was 26 mo. The clinical outcomes of the 27 ABO-I ALDLT recipients were compared with those of 114 ABO-identical/compatible ALDLT recipients. RESULTS: ITBL occurred in four recipients (14.8%) between 45 and 112 d after ABO-I ALDLT. The overall survival rates were not different between ABO-I ALDLT and ABO-identical/compatible ALDLT (P = 0.303). Among the ABO-I ALDLT recipients, there was no difference between patients with ITBL and those without ITBL in terms of B-cell and T-cell count, serum isoagglutinin titers, number of PEs, operative time and transfusion, use of graft infusion therapy, or number of remnant B-cell follicles and plasma cells in the spleen. However, the perioperative NK cell counts in the blood of patients with ITBL were significantly higher than those in the patients without ITBL (P < 0.05). Preoperative NK cell count > 150/µL and postoperative NK cell count > 120/µL were associated with greater relative risks (RR) for development of ITBL (RR = 20 and 14.3, respectively, P < 0.05). CONCLUSION: High NK cell counts in a transplant recipient's blood are associated with ITBL after ABO-I ALDLT. Further research is needed to elucidate the molecular mechanism of NK cell involvement in the development of ITBL.