Obesity exacerbates ischemia-reperfusion injury and senescence in murine kidneys and perirenal adipose tissues.

Background: Obesity is a major worldwide health problem and can be related to cellular senescence. Along with the rise in obesity, the comorbidity of renal ischemia-reperfusion (IR) injury is increasing. Whether obesity accelerates the severity of IR injury and whether senescence contributes to these conditions remain unclear. We studied the degree of injury and cellular senescence in the IR kidneys and perirenal adipose tissues of high-fat-diet-induced obese mice. Methods: C57BL/6 mice fed standard chow or a high-fat diet for 16 weeks were randomized to renal IR or sham group (n = 6-10 each). Renal IR was performed by unilateral clamping of the right renal pedicle for 30 minutes. Six weeks after surgery, renal function, perirenal fat/renal senescence, and histology were evaluated ex vivo. Results: Obese mice showed more renal tubular damage and fibrosis in IR injury than control mice, even though the degree of ischemic insult was comparable. Renal expression of senescence and its secretory phenotype was upregulated in either IR injury or with a high-fat diet and was further increased in the IR kidneys of obese mice. Fat senescence and the expression of tumor necrosis factor alpha were also increased, especially in the perirenal depot of the IR kidneys, with a high-fat diet. Conclusion: A high-fat diet aggravates IR injury in murine kidneys, which is associated, at least in part, with perirenal fat senescence and inflammation. These observations support the exploration of therapeutic targets of the adipo-renal axis in injured obese kidneys.

Impact of nonspecific allograft biopsy findings in symptomatic kidney transplant recipients.

A for-cause biopsy is performed to diagnose the cause of allograft dysfunction in kidney transplantation. We occasionally encounter ambiguous biopsy results in symptomatic kidney transplant recipients. Yet, the allograft survival outcome in symptomatic recipients with nonspecific allograft biopsy findings remains unclear. The purpose of this study was to analyze the impact of nonspecific for-cause biopsy findings in symptomatic kidney transplant recipients. We retrospectively collected records from 773 kidney transplant recipients between January 2008 and October 2021. The characteristics of transplant recipients with nonspecific findings in the first for-cause biopsy were analyzed. Nonspecific allograft biopsy findings were defined as other biopsy findings excluding rejection, borderline rejection, calcineurin inhibitor toxicity, infection, glomerulonephritis, and diabetic nephropathy. The graft outcome was compared between recipients who had never undergone a for-cause biopsy and those who had a first for-cause biopsy with nonspecific findings. The graft survival in recipients with nonspecific for-cause biopsy findings was comparable to that in recipients who did not require the for-cause biopsy before and after propensity score matching. Even in symptomatic kidney transplant recipients, nonspecific allograft biopsy findings might not be a poor prognostic factor for allograft survival compared to recipients who did not require the for-cause biopsy.

Association between anti-endothelial antigen antibodies and allograft rejection in kidney transplantation.

BACKGROUND: Endothelial cells are vital in the transplant immune system as semiprofessional antigen-presenting cells. Few studies have investigated the importance of anti-endothelin subtype A receptor (ETAR) antibodies in kidney transplantation. Here, we aimed to analyze the association between anti-angiotensin II type I receptor (AT1R) and anti-ETAR antibodies and the association between the presence of anti-endothelial antibodies and the risk of allograft rejection in kidney transplantation. METHODS: In total, 252 patients who underwent kidney transplantation were enrolled in this study. Antibodies for human leukocyte antigens (HLAs) and non-HLAs were analyzed immediately before transplantation. Patients were categorized based on the occurrence of antibody-mediated rejection (AMR) or T-cell-mediated rejection (TCMR) by 2017 Banff classification. All p-values were two-tailed, and statistical significance was set at p < 0.05. RESULTS: Patients with anti-AT1R antibodies had a 3.49-fold higher risk of TCMR than those without anti-AT1R antibodies. Patients with anti-ETAR antibodies had a 5.84-fold higher risk of AMR than those without anti-ETAR antibodies. The hazard ratio of AMR in patients with both HLA DSAs and anti-ETAR antibodies, relative to patients without anti-ETAR antibodies and HLA DSAs, was 32.85 (95% CI = 1.82-592.91). CONCLUSION: Our findings indicated that anti-ETAR antibodies are associated with AMR, and patients with both anti-ETAR antibodies and de novo HLA DSAs were at a high risk of AMR.

Recombinant human KAI1/CD82 attenuates M1 macrophage polarization on LPS-stimulated RAW264.7 cells via blocking TLR4/JNK/NF-κB signal pathway.

KAI1/CD82, a membrane tetraspanin protein, can prevent various cancers and retinal disorders through its anti-angiogenic and anti-metastatic capacity. However, little is known about its anti-inflammatory effect and molecular mechanism. Therefore, the present study aimed to inLPSvestigate effect of a recombinant protein of the large extracellular domain of human KAI1 (Gly 111-Leu 228, rhKAI1) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophage-like cells and mouse bone marrow-derived macrophages (BMDM) and to identify its underlying mechanism. Our data showed that rhKAI1 suppressed expression levels of classically macrophages (M1) phenotyperelated surface markers F4/80+CD86+ in LPS-stimulated BMDM and RAW264.7 cells. In addition, LPS markedly increased mRNA expression and release levels of pro-inflammatory cytokines and mediators such as interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, cyclooxygenase-2, nitric oxide and prostaglandin E2, whereas these increases were substantially down-regulated by rhKAI1. Furthermore, LPS strongly increased expression of NF-κB p65 in the nuclei and phosphorylation of ERK, JNK, and p38 MAPK. However, nuclear translocation of NF-κB p65 and phosphorylation of JNK were greatly reversed in the presence of rhKAI1. Especially, rhKAI1 markedly suppressed expression of toll-like receptor (TLR4) and prevented binding of LPS with TLR4 through molecular docking predict analysis. Importantly, Glu 214 of rhKAI1 residue strongly interacted with Lys 360 of TLR4 residue, with a binding distance of 2.9 Å. Taken together, these findings suggest that rhKAI1 has an anti-inflammatory effect on LPS-polarized macrophages by interacting with TLR4 and down-regulating the JNK/NF-κB signaling pathway. [BMB Reports 2023; 56(6): 359-364].

CD82 attenuates TGF-ß1-mediated epithelial-mesenchymal transition by blocking smad-dependent signaling in ARPE-19 cells.

In retinal pigment epithelial (RPE) cells, transforming growth factor-beta (TGF-ß) plays a critical role in epithelial-mesenchymal transition (EMT), which contributes to various fibrotic retinal disorders. In the present study, we investigated the effect of recombinant human cluster of differentiation 82 (rhCD82), a tumor metastasis suppressor, on TGF-ß-induced EMT in the human RPE cell line APRE-19. The results show that TGF-ß1 significantly enhanced cell migration, invasion and the expression of EMT-mediate factors in ARPE-19 cells. However, rhCD82 markedly inhibited cell mobility and the expression of epithelial marker, zonula occludens-1, as well as increased the expression of mesenchymal markers, such as vimentin and α-smooth muscle actin in TGF-ß1-treated APRE-19 cells. In addition, TGF-ß1 upregulated the phosphorylation of Smad, extracellular signal regulated kinase (ERK) and glycogen synthase kinase-3ß (GSK-3ß), but only phosphorylation of Smad was suppressed by rhCD82. Noteworthy, rhCD82 greatly suppressed the expression of TGF-ß receptor I (TGFRI), TGFRII and integrins in TGF-ß1-treated APRE-19 cells. In particular, the result of molecular docking analysis and structural modeling show that rhCD82 partially interacts with the TGF-ß1 binding sites of TGFRI, TGFRII, integrin ß1 and integrin αv. Taken together, this finding suggested that rhCD82 suppressed TGF-ß1-induced EMT of RPE by blocking of Smad-dependent pathway, which is caused by rhCD82 interaction with TGFRs and integrins, suggesting new insight into CD82 as a potential therapeutic strategy in fibrotic retinal disorders.

Graft-Versus-Host Disease Developed After En Bloc Kidney Transplant From a Pediatric Donor: A Case Report.

Graft-versus-host disease is a rare but a potentially fatal complication that can occur after kidney transplant. Furthermore, graft-versus-host disease after kidney transplant has been reported in only a few studies. We present a rare case of graft-versus-host disease in a patient who underwent kidney transplant. A patient who underwent hemodialysis received an en bloc kidney transplantfrom a pediatric donor, and the graft function was excellent. Mild diarrhea started on postoperative day 25. Six days after the onset of diarrhea, pancytopenia worsened and fever persisted. However, there were no test findings indicating infection or adverse medical effects. Graft-versus-host disease was diagnosed after a short tandem repeat evaluation of lymphocytes from the recipient's peripheral blood, which revealed 4.7% donor cells.The findings in this study provide insight into cases where symptoms such as fever and pancytopenia of unknown cause appear after kidney transplant, and we suggest that it is necessary to differentiate these symptoms from graft-versus-host disease.

Endoscopic visualization of graft status in patients with pancreas transplantation.

BACKGROUND: Enteric drainage into the recipient duodenum in pancreas transplantation (PT) can identify the graft duodenum by endoscopy. This study aimed to identify the characteristic endoscopic findings associated with graft failure or acute rejection in patients with PT. METHODS: We reviewed the medical records of patients who underwent PT with duodenoduodenostomy (DD) between January 2015 and August 2019. During this period, there were 44 PTs with DD in 42 patients; 122 endoscopies were performed and analyzed. RESULTS: Overall, pancreatic graft survival was 82% at a mean follow-up of 27 months (range 6-55 months). There were 8 graft failures and 10 acute rejections. In all 8 graft failures, a deep ulcer covered with fibrinous exudates of the graft duodenum was confirmed on endoscopy. Diffuse erythema inside the graft duodenum was observed in 8 of 10 acute rejections. The factors associated with acute rejection were elevated serum lipase level (OR 8.5, p = 0.02) and diffuse erythema inside the graft duodenum on endoscopy (OR 20.5, p < 0.01) in multivariate analysis. CONCLUSIONS: In PT with DD patients, graft failure can be visualized by endoscopy, and diffuse erythema inside the graft duodenum may be a finding of acute rejection.

Reducing Supply Cost by Standardization of Surgical Equipment in Laparoscopic Appendectomy.

BACKGROUND AND OBJECTIVES: Compensation for increased medical services from reimbursement systems are sometimes insufficient. Generally, appendectomies are performed by individual surgeons with their preferred instrument. Surgical equipment standardization is known to reduce medical cost without compromising patient safety. Hence, we investigated the effectiveness of surgical equipment standardization to reduce the required operative cost for laparoscopic appendectomy at our tertiary hospital. METHODS: Nine surgeons at our tertiary hospital agreed to use standardized equipment for laparoscopic appendectomy. We compared outcomes among patients who underwent laparoscopic appendectomy between December 2012 and June 2013 before standardization (control group) and between August 2015 and February 2016 after standardization. Participating provider and staff convenience was also surveyed using a questionnaire. RESULTS: The implementation of standardized equipment for laparoscopic appendectomy decreased intraoperative supply cost from US $552.92 to $450.17. Operative times also decreased from 73.8 to 53.3 minutes. However, hospital days and complication rates remained unchanged. Participants responded that surgical equipment standardization improved efficiency in the operating room and reduced the cost. CONCLUSION: Surgical equipment standardization in laparoscopic appendectomy is effective in reducing intraoperative supply cost without compromising patient safety.

Technical factors that minimize the occurrence of early graft failure in pancreas transplantation.

Pancreatic transplantation is the only treatment for insulin-dependent diabetes resulting in long-term euglycemia without exogenous insulin. However, pancreatic transplantation has become debatable following the improvements in the results of islet transplantation and artificial pancreas. Therefore, surgeons who perform pancreas transplants require the best surgical technique that can minimize technical failure. We aimed to report our experiences with pancreatic transplantations. We transplanted 65 pancreatic grafts between 2015 and 2020. Except for one death due to hypoxic brain damage after surgery, no postoperative technical failure was observed. We usually perform duodeno-duodenal anastomosis using the transperitoneal approach, with retrocolic placement of the graft pancreas. There was no leakage from the duodenum even after immunologic graft failure. To prevent venous thrombosis, which is the most common cause of technical failure, we used the inferior vena cava for anastomosis and added graft venoplasty with a patch of donor vena cava or aortic interposition graft to the bench procedure; subsequently, there were no cases of technical failure due to thrombosis post-transplantation. Therefore, the 1-year graft survival (insulin-free) rate was more than 95%. The improving the surgical technique will maintain pancreatic transplantation as the best treatment for insulin-dependent diabetes.

ABO-Incompatible Living Donor Liver Transplantation With a Simplified Desensitization and Immunosuppression Protocol: A Single-Center Retrospective Study.

OBJECTIVES: New desensitization strategies have made ABO-incompatible living donor liver transplant an attractive option for patients with end-stage liver disease. We aimed to report our experience with 20 consecutive patients who underwent ABO-incompatible living donor liver transplant using a simplified desensitization and immunosuppression regimen. MATERIALS AND METHODS: We retrospectively analyzed 20 ABO-incompatible living donor liver transplant cases (August 2015 to July 2019). The ABO-incompatible living donor liver transplant protocol involved rituximab administration (375 mg/m2 body surface area) at 2 to 3 weeks before transplant, subsequent plasma exchanges (target isoagglutinin titer of ≤1:8), basiliximab administration (20 mg on day of surgery and on postoperative day 4), and intravenous immunoglobulin administration (2 g/day from day of surgery to postoperative day 7). No graft local infusion therapy or splenectomy was performed. RESULTS: The living donor liver transplant procedure involved a modified rightlobe graft(18 patients), a right posterior segment graft (1 patient), or a left lobe (1 patient). The most common reason for liver transplant was hepatitis B virus-associated liver cirrhosis (16 patients); 14 patients had hepatocellular carcinoma. The mean age was 55.4 ± 6.3 years, mean Model End-stage LiverDisease score was 14.7 ± 7.7, and mean graft-to-recipient weight ratio was 1.07 ± 0.2%. The median initial anti-ABO antibody titers were 1:16 forimmunoglobulin M (range, 1:2 to 1:256) and 1:48 for immunoglobulin G (range, 1:4 to 1:>2048). The median number of plasma exchanges was 2 (range, 0-12). No patients had biopsy-confirmed antibody-mediated rejection. No bacterial or fungal infections were observed. Biliary anastomotic stricture was observed in 9 patients. CONCLUSION: This ABO-incompatible living donor liver transplant protocol with rituximab, plasma exchange, low-dose intravenous immunoglobulin, and immunosuppression (equivalent to ABO-compatible living donor liver transplant) could be a safe and effective way to overcome antibody-mediated rejection and other complications.

Successful defibrotide treatment of a patient with veno-occlusive disease after living-donor liver transplantation: A case report.

RATIONALE: Veno-occlusive disease (VOD) is characterized by painful hepatomegaly, ascites, weight gain, and jaundice with nonthrombotic, fibrous obliteration of the centrilobular hepatic veins. VOD after liver transplantation is a rare complication, with an incidence of approximately 2%; however, it can be life-threatening in severe cases. The precise etiology and mechanism of VOD after liver transplantation remains unclear. Acute cellular rejection, antibody-mediated rejection, and treatment with tacrolimus or azathioprine may be associated with the development of VOD after liver transplantation. Additionally, the optimal treatment of VOD after liver transplantation has not yet been established and focuses on supportive care. Defibrotide is an anti-ischemic and antithrombotic drug with no systemic anticoagulant effects. Moreover, only a few reports have investigated the use of defibrotide for VOD after liver transplantation, which has shown promising results. PATIENT CONCERNS: A 39-year-old woman with primary biliary cholangitis underwent living-donor liver transplantation at our center. She experienced right upper quadrant pain with increased ascites, pleural effusion, and weight gain on postoperative day 14. DIAGNOSES: Imaging and pathological tests showed no evidence of rejection or vessel complications. VOD was diagnosed clinically based on the findings of weight gain, ascites, jaundice, and pathological biopsy. INTERVENTIONS: Defibrotid, 25 mg/kg/day, was administered intravenously for 21 days. OUTCOMES: She showed complete clinical resolution of the VOD. LESSONS: Herein, we report a case of successful defibrotide treatment of VOD after living-donor liver transplantation.

Usefulness of Preoperative Magnetic Resonance Spectroscopy to Improve the Safety of a Living Liver Donor.

OBJECTIVES: The steatosis of graft liver is an important factor in liver transplant that determines the graft function in the recipient and the recovery of the remnant liver in the living donor. We analyzed the data of living donors from our center to evaluate whether magnetic resonance imaging and magnetic resonance spectroscopy can replace liver biopsy. MATERIALS AND METHODS: From May 2010 to May 2019, data from a total of 239 living donors was collected. There were 84 patients who had no magnetic resonance imaging or magnetic resonance spectroscopy data, and they were excluded. The result of preoperative liver biopsy was compared with preoperative magnetic resonance imaging and magnetic resonance spectroscopy data. The steatosis was defined by the degree of macrosteatosis. RESULTS: The magnetic resonance imaging of the fat fraction was a good parameter to predict fatty changes between normal and fatty liver groups (3.09 ± 3.38% for normal 7.48 ± 4.07% for fatty liver; P < .001). The magnetic resonance spectroscopy was also a good parameter to predict fatty changes between normal and fatty liver groups (2.09 ± 1.43% for normal and 6.89 ± 2.68% for fatty liver; P < .001). Linear regression showed that pathology results were significantly correlated with magnetic resonance spectroscopy (P < .001, R2 = 0.604) but not with magnetic resonance imaging (P < .001, R2 = 0.227). CONCLUSIONS: Magnetic resonance spectroscopy has several benefits for quantifying hepatic steatosis during a living donor liver transplant evaluation, including no radiation exposure, and a noninvasive procedure. Moreover, preoperative magnetic resonance spectroscopy can determine an anatomic variation of the bile duct, which helps improve the safety of the living donor. However, more clinical data and further studies are needed to ensure that preoperative magnetic resonance spectroscopy is essential.

Epidermoid cyst in an intrapancreatic accessory spleen in the pancreas head: a case report.

BACKGROUND: An epidermoid cyst in an intrapancreatic accessory spleen (ECIPAS) in the pancreas head is an extremely rare condition. The natural course of this condition is not well known, and it is difficult to diagnose before surgery due to the lack of specific imaging findings. CASE PRESENTATION: A tumor was found in the head of the pancreas in a 68-year-old man with abdominal distension and discomfort. Magnetic resonance imaging (MRI) suggested a malignant tumor, such as a colloid cancer. The tumor was removed surgically, with pathologic examination showing that it was an ECIPAS. CONCLUSION: ECIPAS cannot be easily distinguished from other pancreatic cystic tumors, making it necessary to include ECIPAS in the differential diagnosis of these tumors. Unnecessary surgical resection may be avoided by more accurate preoperative diagnosis based on clinical and imaging characteristics.

Efficacy and Safety of Weight Reduction of the Donor in Hepatic Steatosis for Living Donor Liver Transplantation.

BACKGROUND Use of steatotic livers is a known risk factor for increased primary nonfunction after liver transplantation. This study investigated the efficacy and clinical outcome of simple weight reduction of steatosis for donors undergoing living-donor liver transplantation (LDLT). MATERIAL AND METHODS We defined two groups: the reduction group, which included donors with >30% macrovesicular steatosis and body mass index (BMI) >25 kg/m², and the conventional group, which included donors with.

Eosinophil-to-monocyte ratio is an excellent predictor of acute cellular rejection in pancreas transplant alone recipients.

Serum pancreatic enzymes (serum amylase and lipase) are sensitive markers for monitoring acute rejection in pancreatic transplant recipients. However, those enzymes are not specific, as their levels are elevated in other conditions. We evaluated the eosinophil-to-monocyte ratio (EMR) in peripheral blood as a biomarker of acute rejection in the clinical setting in recipients of pancreatic transplant alone. We performed 32 cases of pancreatic transplantation alone since 2015. Nine patients were diagnosed with rejection. Serum amylase and lipase levels and eosinophil and monocytes counts were analyzed and compared retrospectively between the non-rejection and rejection groups. The serum eosinophil count, eosinophil fraction of the complete blood count, and serum amylase and lipase levels were significant predictors of rejection according to the receiver operation characteristic (ROC) curve. However, the EMR was the best indicator of rejection based on the ROC curve (area under the curve 0.918, sensitivity 100%, specificity 76.2% at the cutoff value 0.80, P < .001). The combination of EMR and the lipase level had 100% sensitivity and 90.5% specificity. The EMR is a simple and excellent predictor of acute rejection in recipients of pancreatic transplant alone.

Elevation of Preoperative Ammonia Level Is Not Associated With the Incidence of Postoperative Delirium in Patients with Liver Transplantation: A Propensity Score Matching Analysis.

INTRODUCTION: The preoperative elevation of ammonia may be associated with postoperative neurologic complications. The aim of this study was to evaluate the effect of preoperative ammonia level on the incidence of delirium in patients after liver transplantation (LT). MATERIALS AND METHODS: Patients (n = 260) who received LT from January 2010 to July 2017 in a single university hospital were retrospectively reviewed. The patients' demographic data, perioperative managements, and postoperative complications were assessed. Patients were divided into the following 2 groups: those who had a preoperative elevation (Group A, n = 158) and those with a normal range (Group C, n = 102). The cut-off value for a normal serum ammonia level in our hospital was defined as 32 µg/dL. RESULTS: After propensity score matching, there was no difference in the incidence of delirium between the groups (P = .784). Delirium occurred in 8 of 68 (11.76%) patients in Group A and 7 of 68 (10.29%) patients in Group C after LT. In addition, there was no difference in the incidence of delirium between the groups, even patients were categorized based on serum ammonia levels into 3 groups as follows: < 32 µg/dL (28/158 [17.72%]), 32 to 65 µg/dL (28/158 [17.72%]), and >65 µg/dL (28/158 [17.72%]) (P = .134). CONCLUSIONS: The preoperative serum ammonia level was not related with the incidence of postoperative delirium. The high elevation group, especially those with greater than 65 µg/dL of preoperative ammonia, was also not related with the incidence of delirium. However, our study is limited by its retrospective design, so future prospective studies are needed.

Temporary Cessation of Immunosuppression for Infection May Contribute to the Development of Graft-vs-Host Disease After ABO-Incompatible Living Donor Liver Transplantation: A Case Report.

Graft-vs-host disease (GVHD) after liver transplantation is a rare complication with a high mortality rate. A complex interplay between donor and recipient immunity plays a role in the development of GVHD. Infection following liver transplantation is one of the most common complications in a recipient of an organ transplant who is immunosuppressed. On clinical signs of infection, the immune reaction of the recipient can be reconstituted by withdrawal of immunosuppression in order to help combat infection. However, the discontinuation of immunosuppression could restore the donor's immune activity rather than that of the recipient. There is little information available as to whether the discontinuation of immunosuppression for severe infection could contribute to the development of GVHD in a patient who underwent ABO-incompatible (ABO-I) living donor liver transplantation (LDLT). Herein, we present a unique case of GVHD following ABO-I LDLT, for which the cessation of immunosuppression could be responsible.

Progression of diabetic nephropathy after successful pancreas transplantation alone: a case report.

Pancreas transplantation is the only method that can nearly cure insulin-dependent diabetes mellitus. However, the effect of pancreas transplantation on patients with diabetic nephropathy has recently been considered controversial. In this report, we present a case of abrupt aggravation of proteinuria after successful pancreas transplantation alone without evidence of calcineurin inhibitor (CNI) toxicity. A 22-year-old female patient with type I diabetes mellitus underwent pancreas transplantation alone. The patient already had retinopathy and mild proteinuria, which in this case, may mean diabetic nephropathy. Her glucose levels were managed within the normal range after successful pancreas transplantation. However, the amount of proteinuria fluctuated. Kidney needle biopsy was performed owing to severe elevation of proteinuria, 2 years after the transplantation. Electron microscopy revealed diabetic glomerulosclerosis without evidence of CNI toxicity. This case indicates that diabetic nephropathy can be aggravated after pancreas transplantation, despite well-managed glucose levels and absence of CNI toxicity.