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Abstract A 73‐year‐old woman with a history of rheumatoid arthritis treated with methotrexate (MTX) for the last 10 years was referred to our hospital for a pancreatic tumor examination. Contrast‐enhanced abdominal computed tomography revealed a 20‐mm‐diameter hypovascular tumor in the pancreatic tail. A hypoechoic mass with heterogeneous internal echo was found on an endoscopic ultrasound (EUS). An EUS‐guided fine‐needle biopsy (EUS‐FNB) was performed with a 22‐gauge Franseen‐tip needle. Histologic examination of EUS‐FNB specimens from the pancreatic tumor revealed the proliferation of atypical spindle cells. Immunohistochemical staining for CD20 and Ki‐67 was positive in the atypical cells. Immunohistochemical staining for CD3 was partially positive in the atypical cells. Epstein–Barr virus‐encoded RNA in situ hybridization showed positive staining. MTX‐related lymphoproliferative disorder (MTX‐LPD) with Epstein‐Barr virus infection was diagnosed. MTX treatment was immediately discontinued, and treatment was initiated by a hematologist. However, her condition rapidly deteriorated, and she died of multiple organ failure 4 weeks after diagnosis. MTX‐LPD can complicate gastrointestinal lesions. However, most lesions are localized in the stomach and rarely complicate pancreatic lesions. MTX‐LPD is classified as an “iatrogenic” LPD. Therefore, immediate action, such as MTX discontinuation, is necessary. In conclusion, endoscopists should be aware that MTX‐LPD lesions can occur in the pancreas and gastrointestinal tract. Moreover, EUS‐FNB can be useful in the diagnosis of this rare pancreatic tumor.

Tumor blood vessels have leaky and low blood flow properties, which lead to hypoxia and low nutrient levels in the tumor tissue area known as the tumor microenvironment (TME). We reported that the prolyl-hydroxylase (PHD) inhibitor Roxadustat normalized tumor blood vessels, improved tumor tissue perfusion, and re-oxygenated the tumor tissue. Recently, several PHD inhibitors including Roxadustat, Daprodustat, Molidustat, and Vadadustat, were evaluated in clinical trials and approved for treating renal anemia. In this study, we showed that PHD inhibitors reconstituted tumor blood vessels and improved the TME, and some agents exhibited differential effects on tumors in a mouse model.

Orally active hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors that stabilize HIF protein and stimulate the production of erythropoietin have been approved to treat renal anemia. Our previous report suggested that HIF-1α dependent fibrogenic mechanisms are operating at the early onset of renal fibrosis and its contribution declines with the progression in mouse unilateral ureteral obstruction (UUO) model. The aim of the study is to evaluate the renal fibrogenic potential of FG4592, a recently approved orally active HIF prolyl hydroxylase inhibitor in mouse UUO model. Male C57BL/6J mice orally given FG-4592 (12.5 mg/kg/day and 50 mg/kg/day) were subjected to UUO. Neither dose of FG-4592 affected renal fibrosis or macrophage infiltration. FG-4592 had no effects on increased mRNA of collagen I, collagen III or transforming growth factor-β1. At 3 days after UUO, higher dose of FG-4592 potentiated the increased mRNA expression of profibrogenic molecules, plasminogen activator inhibitor 1 (Pai-1) and connective tissue growth factor (Ctgf) but such potentiation disappeared at 7 days after UUO. It is suggested that FG-4592 used in the present study had little effects on renal fibrosis even though high dose of FG-4592 used in the present study transiently potentiated gene expression of Pai-1 and Ctgf in the UUO kidney. Keywords: Hypoxia-inducible factor, Prolyl hydroxylase domain-containing protein, Renal fibrosis, FG-4592

Summary: The tumor microenvironment (TME) polarizes tumor-infiltrating macrophages toward tumor support. Macrophage-abundant tumors are highly malignant and are the cause of poor prognosis and therapeutic resistance. In this study, we show that the prolyl hydroxylase (PHD) inhibitor FG-4592 (FG) inhibits tumor growth of macrophage-abundant tumors and prolongs mouse survival. FG not only normalizes tumor vessels and improves tumor oxygenation but also directly affects macrophages and activates phagocytosis through the PHD-hypoxia-inducible factor (HIF) axis. Remarkably, FG can promote phagocytic ability of the Ly6Clo subset of tumor-infiltrating macrophages, leading to tumor growth inhibition. Moreover, Ly6Cneg macrophages contributed to blood vessel normalization. Using a malignant tumor mouse model, we characterized macrophage function and subsets. Altogether, our findings suggest that the PHD inhibitor can promote the anti-tumor potential of macrophages to improve cancer therapy. : Microenvironment; Immune Response; Cancer Subject Areas: Microenvironment, Immune Response, Cancer

Background/Aims: Vascular calcification is common and progressive in chronic kidney disease, including kidney transplant recipients (KTRs). However, the risk factors associated with the progression of aortic calcification (AoC) in KTRs have not been fully elucidated. In the present study, we evaluated AoC and examined the factors associated with its advancement in KTRs. Materials: This was a prospective longitudinal study that included 98 KTRs. We quantitatively investigated infrarenal abdominal AoC using the Agatston score, as measured by multi-slice computed tomography. After the baseline investigation, a follow-up scan was performed after 3 years, and the Agatston scores were obtained again. The changes in laboratory data affecting the 2nd Agatston scores were examined by multivariable analysis using non-linear regression after adjustment for several confounders. Results: The 2nd Agatston scores were significantly greater than the baseline Agatston scores (p < 0.001). After adjustment for the confounders, the change in corrected serum calcium exhibited a significant non-linear correlation with the 2nd Agatston scores (p = 0.022 for non-linearity/p = 0.031 for the effect of corrected serum calcium). Moreover, an interaction was present from the baseline AoC in the effect of corrected serum calcium on the progression of AoC, and the effect of hypercalcemia was greater in patients with higher baseline Agatston scores (p = 0.049). Conclusion: The present study revealed that hypercalcemia is a risk factor for the development of infrarenal abdominal AoC in KTRs. Furthermore, the effect of hypercalcemia was greater in patients with more severe vascular calcification.

Abstract Background Successful pregnancy outcomes after in vitro fertilization in kidney transplant recipients have been reported, but few cases of successful pregnancy after ABO-incompatible kidney transplantation have been described. Herein, we report on a successful pregnancy after in vitro fertilization in an ABO-incompatible kidney transplant recipient with rituximab, focusing on the changes in immunity. Case presentation A 35-year-old woman with end-stage kidney disease caused by IgA nephropathy was referred for kidney transplantation and successfully underwent an ABO-incompatible living-donor kidney transplant using rituximab from her 66-year-old father at the age of 36. Because she and her husband desired childbearing, they received fertility treatments, and embryo cryopreservation was performed before transplantation. Two years after the transplant, she desired pregnancy. Although immunoglobulin levels such as IgG, IgA and IgM had recovered to almost normal range, the peripheral CD19+ cells and CD20+ cells remained depleted. At 6 months after conversion from mycophenolate mofetil to azathioprine, frozen embryo transfer was performed during the hormone replacement cycle. At 37 weeks and 4 days gestation, a healthy baby girl weighing 2220 g was delivered by cesarean section for arrest of labor. There were no complications in both the recipient and her baby during the perinatal period. At 5 years after the transplant, the recipient has had no major complications including rejection or infection. Conclusions It is possible for women receiving ABO-incompatible kidney transplantation with rituximab to successfully become pregnant and deliver a heathy baby after in vitro fertilization, if IgG levels recover to normal range despite depleted peripheral blood B cells.

Abstract Background Enzalutamide is an oral androgen receptor targeted agent that has been shown to improve survival in PREVAIL trials and has been approved for patients with chemo-naïve metastatic castration-resistant prostate cancer (CRPC). Meanwhile, flutamide is a non-steroidal oral anti-androgen that was commonly used before the approval of bicalutamide. The objective of the OCUU-CRPC study is to compare the efficacy and safety between second-line hormonal therapy of enzalutamide and flutamide as alternative anti-androgen therapy (AAT) after combined androgen blockade (CAB) therapy that included bicalutamide in patients with CRPC. Methods A total of 100 patients with CRPC with or without distant metastases after disease progression who received CAB therapy with bicalutamide were randomly assigned at a 1:1 ratio according to distant metastases to the enzalutamide (160 mg/day, 4 × 40 mg capsules once daily) and flutamide (375 mg/day; 3 × 125 mg tablets thrice daily) groups. The primary endpoint for the drug efficacy is the response rate of prostate-specific antigen (PSA) (i.e., the ratio of patients whose PSA declined by ≥50% from baseline) at 3 months. Meanwhile, the secondary endpoints are PSA progression rate at 3 and 6 months, PSA response rate at 6 months, change in quality of life, PSA progression-free survival, and safety. The patient registration started in January 2015 and will end in March 2018, and the follow-up period is 6 months after the last patient registration. The main result will be reported in March 2019. Discussion In the OCUU-CRPC study, we compare the efficacy and safety of enzalutamide or alternative AAT with flutamide in participants with CRPC who were previously treated with a CAB therapy with bicalutamide. The expected results of this study will be that enzalutamide is superior to flutamide in terms of PSA response. A longer time to disease progression with enzalutamide over flutamide may translate to better overall survival. However, flutamide may be more accessible for patients owing to its lower cost than enzalutamide. Trial registration The OCUU-CRPC study was prospectively registered at clinicaltrials.gov (NCT02346578, January 2015) and University Hospital Medical Information Network (UMIN000016301, January 2015).

Abstract Background Selective plasma exchange (SePE) is a new simple plasma exchange (PE) modality that enables removal of small and medium-sized molecules without removing larger substances such as coagulation factors. In this study, we examined the efficacy of SePE for removal of isoagglutinins in pre-transplant desensitization for ABO-incompatible (ABOi) kidney transplantation. Materials and methods A case series study was performed in 15 ABOi kidney transplant recipients (KTRs) who underwent SePE alone (7 cases) and SePE in combination with double-filtration plasmapheresis or simple plasma exchange (8 cases). The target processed plasma volume (PV) was set at 2 PV, and 5% albumin solution was used as the substitution fluid in all SePE sessions. Changes in isoagglutinin titers (IgG and IgM) and serum IgG, IgM, and fibrinogen levels were examined. We also compared the decrease in isoagglutinin titers between SePE and conventional methods (PE and double-filtration plasmapheresis). Results A total of 29 sessions of SePE were performed in the 15 KTRs. Isoagglutinin titers were controlled to ≤ 1:16 in all patients except for 2 with high isoagglutinin titers, and there were no cases of antibody-mediated rejection. SePE led to a median twofold decrease in isoagglutinin titers (IgG and IgM), with median IgG, IgM, and fibrinogen removal rates of 64.2, 11.7, and 25.5%, respectively. Side effects occurred in only 4 of the 29 sessions. Neither titer decreased after SePE in 30% of the sessions. However, the reductions in isoagglutinin titers in patients undergoing SePE were significantly less than those in patients treated with conventional methods. Conclusion Because SePE is less efficient in removing isoagglutinins compared to conventional methods, the use of SePE alone should be limited to patients with low isoagglutinin titers, and SePE in combination with conventional methods should be used for patients with high isoagglutinin titers. SePE may be a useful treatment option, if applied in appropriate cases, due to its lower cost (about half the price of PE using fresh frozen plasma in Japan) and fewer side effects. However, care is required because about 25% of fibrinogen is removed during SePE.

We have investigated the finite element modeling for the elevator wire rope 8×S(19) to reproduce the stiffnesses in both axial and radial directions. In order to validate the finite element calculation, compression test to measure the radial-direction stiffnesses of strand, fiver core and wire rope have been newly proposed. From the experimental result of strand, it is found that the radial-direction stiffness is greatly lower than axial-direction one and is affected by the contact situation between wires. It is also found that our finite element model well reproduce the stiffnesses of strand in the both directions. From the experimental result of fiber core, it is found that load-displacement curve in the radial direction involves a hysteresis, reflecting the mechanical property of fiber. The fiber core is modeled as an elastic body with the Young modulus of 300 MPa. From the experimental result of wire rope, load-displacement curve in the radial direction involves a hysteresis as well as the fiber core and the stiffness is similar with that of the fiber core. The stiffness increases as the tension of wire rope is increased. That is due to the strong contacts between wires and between strand and fiber core. Assembled finite element model of wire rope well reproduces the stiffnesses of wire rope in the both directions.

Abstract Background Peritoneal dialysis (PD) access is important for patients undergoing PD. However, one of the potential complications of peritoneal dialysis access is damage to the dialysis tubing. Although most dialysis tubing damage is due to human error, there have been reports of damages attributed to pets owned by the patients. Much of the damage caused by pets has been attributable to cat biting or scratching, whereas the present case is an extremely rare case of dialysis tubing damage caused by a pet cockatoo. Case presentation A 65-year-old male with end-stage renal disease due to diabetic nephropathy who had been undergoing continuous ambulatory peritoneal dialysis (CAPD) for 6 years was admitted to our hospital with the chief complaint of dialysis tubing damage. While the patient was playing with his pet cockatoo on his belly after taking it out of its cage, the bird bit into his dialysis tubing of his transfer set without him realizing it, thus damaging the tube. The patient noticed that his dialysis tubing was leaking and realized that it had been damaged. He folded the end of the damaged tube, secured it with a rubber band to prevent further leakage, and made an emergency visit to our hospital. Upon inspection, we found that the dialysis tubing was completely disconnected, 28 cm from the metal connector of the connection tube. After consultation, the damaged tube was replaced. As a preventive measure for peritonitis, antibiotics were administered orally for 1 week (oral levofloxacin, 250 mg every 48 h). The patient was instructed to be careful when handling his cockatoo, and his CAPD treatment has been continued without incident to date. Conclusion This is a rare case report of PD tubing damage caused by a cockatoo kept at home. It may be necessary to pay sufficient attention to PD equipment damage by birds in PD patients keeping large birds, such as cockatoos.

Introduction: The diagnosis of BK virus nephropathy is based on renal biopsy findings, and the diagnosis of presumptive BK virus nephropathy is made by sustained plasma BK virus DNA loads of > 4 log10 copies/ml. However, the BK virus plasma viral load cutoff of 4 log10 copies/ml may underestimate the diagnosis of BK virus nephropathy. In this study, we evaluated the clinical significance of BK viremia in kidney transplant recipients. Patients and Methods: From January 2010 to November 2015, we experienced 8 kidney transplant recipients who developed BK viremia. We retrospectively analyzed these recipients, focusing on the plasma BK viral load at onset of BK viremia, time to BK viremia after transplantation, frequency of BK virus nephropathy, and our treatment for BK viremia. Results: The median plasma BK virus polymerase chain reaction at the diagnosis of BK viremia was 1600 copies/ml (370–9400 copies/ml). The median time to BK viremia after transplantation was 10.9 months (1.4–67.9 months). Three patients were associated with BK virus nephropathy on biopsy. Clearance of BK viremia was observed in all of these cases after intervention. Conclusions: Our study demonstrated that intervention in BK viremia with a viral load of < 4 log10 copies/ml may be needed to prevent the development of graft dysfunction and BK virus nephropathy in kidney transplant recipients. Keywords: BK virus, BK viremia, Kideny transplantation, Mizoribine, Cyclosporine

Résumé Contexte L’objectif de notre étude rétrospective était d’évaluer la survie à 5 ans et le délai de transition du cancer de la prostate hormono-sensible au cancer de la prostate résistant à la castration chez des patients porteurs d’un cancer de la prostate hormono-sensible qui étaient traités par un antagoniste de la gonadolibérine, le dégarélix. Un autre objectif était d’évaluer les effets sur les résultats cliniques et oncologiques du remplacement du dégarélix par un agoniste de la gonadolibérine après obtention d’un état stable et contrôlé. Résultats Notre analyse repose sur les données de 108 patients atteints d’un cancer de la prostate traités par dégarélix. Parmi ceux-ci, le traitement par dégarélix a été remplacé par un agoniste de la gonadolibérine chez 57 (groupe modifié), et le traitement par dégarélix a été poursuivi chez les autres patients (groupe inchangé). La survie globale à 5 ans était statistiquement plus élevée pour le groupe modifié (96.6%) que pour le groupe inchangé (74,1%; p = 0.006). Les chances de survie cancer-spécifiques à 5 ans était également plus élevées pour le groupe modifié (100%) que pour le groupe inchangé (84,6%; p = 0.027). Le délai moyen de transition du cancer de la prostate hormono-sensible au cancer de la prostate résistant à la castration était comparable dans le groupe modifié (43,3 mois) et dans le groupe inchangé (35,2 mois). Des taux sériques plus bas d’antigène spécifique de la prostate et de phosphatase alcaline ont été maintenus après le remplacement du dégarélix par un agoniste de la gonadolibérine. Conclusions Le dégarélix est. efficace dans le traitement du cancer de la prostate. Le traitement par dégarélix peut aussi être remplacé en toute sécurité par un agoniste de la gonadolibérine sans aucun effet clinique ou oncologique indésirable. Mots-clés Antagonistes et inhibiteurs de la gonadolibérine, Agoniste de la gonadolibérine, Cancer de la prostate, Dégarélix, Résistant à la castration

Background: Cancer-related fatigue is one of the most prevalent symptoms that patients with cancer experience, but the mechanisms underlying it are unknown. We aimed to quantify and mechanistically evaluate the improvement in fatigue related to administration of the Kampo medicine, Kamikihito. Materials and methods: Initially, we recruited outpatients with urological diseases and compared fatigue levels of 37 patients with cancer with a control group of 23 volunteers who had recovered completely from cancer or who were being treated for dysuria. Fatigue level was estimated using an autonomic function analyzer. Then, Kamikihito was administered to another 35 patients treated with hormone or antitumor therapy for prostate cancer and metastatic renal cell cancer. Subjective fatigue and other problems of the patients were assessed using the Chalder fatigue scale, the Center for Epidemiologic Studies Depression scale, and the Epworth sleepiness scale. Serum levels of derivatives of reactive oxygen species and biological antioxidant potential were also measured. Results: Patients in the cancer treatment group experienced more fatigue compared with the control patients when evaluated using an autonomic function analyzer. The group of 35 patients who were administered Kamikihito showed improved scores for fatigue, depression, and sleepiness. Autonomic nervous system balance was also improved with Kamikihito administration. The Kamikihito group also had significantly lower reactive oxygen species metabolite levels and significantly higher antioxidant potential. Conclusions: Fatigue was more serious in patients with cancer than in control patients. Kamikihito rescued this fatigue and improved anxiety and sleepiness. It restored autonomic nervous system balance and antioxidant function. Keywords: Autonomic nerve system, Cancer-related fatigue, Fatigue score, Japanese traditional herbal medicine, Oxidative stress

The aim of the study is to clarify the role of hypoxia-inducible factor-1 (HIF-1) in the development of renal fibrosis in mouse obstructive nephropathy. We used mice with floxed HIF-1α alleles and tamoxifen-inducible Cre/ERT2 recombinase under ubiquitin C promoter to induce global HIF-1α deletion. Following tamoxifen administration, mice were subjected to unilateral ureteral obstruction (UUO). At 3, 7 and 14 days after UUO, renal gene expression profiles and interstitial fibrosis were assessed. HIF-1 dependent up-regulation of prolyl hydroxylase 3 and glucose transporter-1 was observed in the obstructed kidney at 3 and 7 days but not at 14 days after UUO. Various factors promoting fibrosis were up-regulated during the development of fibrosis. HIF-1 dependent gene expression of profibrotic molecules, plasminogen activator inhibitor 1, connective tissue growth factor, lysyl oxidase like 2 and transglutaminase 2 was observed in the obstructed kidney but such HIF-1 dependency was limited to the early onset of renal fibrosis. Global HIF-1 deletion tended to attenuate interstitial collagen I deposition at 3 days but had no effects thereafter. It is suggested that HIF-1 dependent profibrogenic mechanisms are operating at the early onset of renal fibrosis but its contribution declines with the progression in mouse UUO model.

A 73-year-old woman with chief complaint of macroscopic hematuria was diagnosed as having left renal tumor with pancreatic invasion. Nephrectomy was performed. Pathological diagnosis was clear cell carcinoma, pT3a. Three months after the operation, liver metastasis appeared and sunitinib was started. Most of the liver metastases disappeared; however, a new lesion appeared, and sunitinib was switched to axitinib, which was effective on the residual lesion, but the new lesion had poor response. Transarterial chemoembolization was performed to treat the liver metastases, and all metastatic lesions disappeared. There was no recurrence at 2 years, and axitinib was discontinued.

Objectives Serious adverse effects, including arrhythmia and cardiac arrest, result from rapid intravenous high concentration of potassium chloride (KCl). We aimed to eliminate prescription of undiluted KCl and encourage dilution of KCl to 400 mEq/L and 40 mEq/L in the intensive care units (ICUs) and general and outpatient departments, respectively.Methods Before the first intervention, we collected data regarding high-concentration KCl and interviewed representatives of physicians prescribing high-concentration KCl. Based on the guidelines in other countries on safely used concentrations of KCl (400 mEq/L), we negotiated with physicians to dilute KCl below 400 mEq/L. In the first intervention, we made rules based on surveys above. In the second intervention, we revised the rules based on opinions from physicians and pharmacists and investigated the change in the number of prescriptions of KCl concentration in each department. Continuing efforts with the safety manager ensured compliance of the rules by physicians and nurses in all departments.Results After the first and second interventions, prescriptions for undiluted KCl in ICUs and general wards were eliminated (median=0). Prescriptions for

Background/Aims: We have reported that the eGFR overestimates renal function when glycemic control is poor. It has been reported that eGFR calculated by serum creatinine underestimates GFR in living kidney donors. We compared the utility of the eGFR in diabetic patients, non-diabetic patients and living kidney donors. Forty diabetic patients, 40 non-diabetic patients, and 40 living kidney donors were enrolled. Methods: GFR was measured by inulin clearance (Cin). eGFR was calculated based on serum creatinine (eGFRcr) or serum cystatin C (eGFRcys). We compared the agreements between each of the eGFR and Cin in each group. Results: There were significant and positive correlations between each eGFR and Cin in diabetic patients and non-diabetic patients. However, the intraclass correlation coefficients (ICC) between each eGFR and Cin in diabetic patients (ICC: eGFRcr 0.699, eGFRcys 0.604) were weaker than those in non-diabetic patients (ICC: eGFRcr 0.865, eGFRcys 0.803). The correlation coefficients between each eGFR and Cin (eGFRcr; r = 0.422, p = 0.0067 and eGFRcys; r = 0.358, p = 0.0522) in living kidney donors were significantly weaker than those in non-diabetic patients. The ICCs between each eGFR and Cin (ICC: eGFRcr 0.340, eGFRcys 0.345) in living kidney donors were significantly weaker than those in non-diabetic patients. Conclusions: Based on Cin, eGFR was accurate in non-diabetic patients. However, eGFR was inaccurate in living kidney donors and relatively inaccurate in diabetic patients.

Background/Aims: Hyperuricemia has been reported to affect renal hemodynamics in rat models. We evaluate the relationship between serum uric acid and intrarenal hemodynamic parameters in humans, utilizing the plasma clearance of para-aminohippurate (CPAH ) and inulin (Cin). Methods: Renal and glomerular hemodynamics were assessed by simultaneous measurement of CPAH and Cin in 58 subjects. Of these, 19 subjects were planned to provide a kidney for transplantation; 26 had diabetes without proteinuria; and 13 had mild proteinuria. Renal and glomerular hemodynamics were calculated using Gomez`s formulae. Results: Cin was more than 60 ml/min/1.73m2 in all subjects. Serum uric acid levels correlated significantly with vascular resistance at the afferent arteriole (Ra) (r = 0.354, p = 0.006) but not with that of the efferent arteriole (Re). Serum uric acid levels (β = 0.581, p = a after adjustment for several confounders (R2 = 0.518, p = Conclusions: These findings suggest, for the first time in humans, that higher serum uric acid levels are associated significantly with Ra in subjects with Cin > 60 ml/min/1.73m2. The increase in Ra in subjects with higher uric acid levels may be related to dysfunction of glomerular perfusion.

IntroductionLiving donor kidney transplantation is preferable to deceased donor transplantation due to its superior long-term patient and graft survivals. However, ABO blood group incompatibility is a major barrier to living donor kidney transplantation. ABO-incompatible kidney transplantation has been performed in Japan since the late 1980's, but it is still globally uncommon. The objective of this study is to compare the clinical outcomes of ABO-incompatible kidney transplantation (ABO-IKT) with that of ABO-compatible kidney transplantation (ABO-CKT) at an institution where only about two kidney transplants are performed a month on average.DesignA single center propensity score-matched cohort study.Patients and methodsWe retrospectively collected and analyzed the data of 240 patients with end-stage kidney disease (ESKD) who underwent living donor kidney transplantation at Osaka City University Hospital from January 1999 to December 2016, of which 66 patients were ABO-IKT. The remaining 174 patients who underwent ABO-CKT were studied as the control group, and the clinical outcomes of ABO-IKT and ABO-CKT recipients were compared based on propensity score matching.ResultsAfter propensity score matching, there were no significant differences in both patient survival and death-censored graft survival rates between the ABO-IKT and ABO-CKT groups. Moreover, there were no significant differences in estimated glomerular filtration rate as well as frequency of acute cellular rejection, antibody-mediated rejection, infectious adverse events, malignancies, and post-operative bleeding between the two groups.ConclusionCurrently, ABO-IKT may be an acceptable treatment for patients with ESKD even at a low-volume transplant center.

Background/Aim: The aim of the present study was to quantitatively examine factors associated with aortic calcification in non-dialysis CKD patients. Methods: We quantitatively investigated aortic calcification from the renal artery to the bifurcation in 149 non-dialysis CKD patients (58±16 years; 96 males and 53 females, 48 diabetics; eGFR 40.3±29.3 ml/min), and measured Agatston scores using multi-slice computed tomography. Result: Of 149 patients, aortic calcification was present in 117. In patients with aortic calcification, age (pConclusions: Hyperphospatemia, chronic inflammation, diabetes, and decreased GFR are associated significantly with the presence of aortic calcification in non-dialysis CKD patients. Decreased eGFR was associated significantly and independently with the quantitative degree of aortic calcification.

A 68-year-old man was introduced to our hospital for the treatment of lung and mediastinum lymph node metastases that originated from an urachal carcinoma 4 years after a partial cystectomy. First-line chemotherapy with an S-1 and cisplatin combination was ineffective. The patient received FOLFIRI plus bevacizumab chemotherapy as salvage chemotherapy. Stability was achieved after eight cycles of FOLFIRI plus bevacizumab therapy. We conducted a biopsy of the metastatic tumor, and the pathology of the biopsy tissue was partially necrotic. To our knowledge, this case represents the first report of a metastatic urachal carcinoma treated with FOLFIRI plus bevacizumab.

Abstract.: The role of renal dendritic cells (DCs) in renal fibrosis is unknown. The present study was conducted to examine the relative role of renal DCs and macrophages in the development of renal fibrosis in murine obstructive nephropathy. CD11c-diphtheria toxin receptor (DTR) transgenic mice and CD11b-DTR transgenic mice were subjected to unilateral ureteral obstruction. To conditionally and selectively deplete DCs or macrophages, DT was given to these mice and kidneys were harvested on day 5. Ureteral obstruction elicited renal fibrosis characterized by tubulointerstitial collagen III deposition and accumulation of α-smooth muscle actin–positive cells. Flow cytometric analysis revealed a marked increase in cell counts of F4/80+ macrophages, F4/80+ DCs, as well as neutrophils and T cells in the obstructed kidney. DT administration to CD11c-DTR mice led to selective depletion of renal CD11c+ DCs, but did not affect renal fibrosis. In contrast, administration of DT to CD11b-DTR mice resulted in ablation of all monocyte lineages including macrophages and DCs and attenuated renal fibrosis. Our results do not support the role of renal DCs, but confirm the importance of monocyte lineage cells other than DCs in the development of the early phase of renal fibrosis following ureteral obstruction in mice. Keywords:: renal fibrosis, inflammation, monocyte, macrophage, dendritic cell

Although liposome-encapsulated clodronate has been used as a means to deplete macrophages from certain tissues, target leukocyte subtypes within the kidney are not clearly known under normal and pathologic conditions. The present study was therefore conducted to examine the effects of liposome clodronate on renal infiltrating cell type following unilateral ureteral obstruction (UUO) and tried to correlate these changes to the mechanisms of early development of renal fibrosis. Renal infiltrating leukocyte subtypes and counts were determined by using multicolor flow cytometric analysis of cell suspensions from obstructed kidneys. UUO for 5 days elicited renal tubular apoptosis and renal fibrosis and showed 4-fold increase in renal leukocytes including monocytes/macrophages, dendritic cells, and T-cells. Repeated administration of liposome clodronate selectively depleted F4/80+ monocytes/macrophages and F4/80+ dendritic cells but not F4/80− dendritic cells or other cell types in both obstructed and non-obstructed kidneys. Tubular apoptosis and renal fibrosis were also significantly attenuated by liposome clodronate. Increased gene expression of TNF-α and TGF-β observed in obstructed kidneys were markedly attenuated by depletion of renal mononuclear phagocytes. These findings suggest that F4/80+ monocytes/macrophages and/or F4/80+ dendritic cells play a pivotal role in the development of obstruction-induced tubular apoptosis and renal fibrosis, possibly through TNF-α and TGF-β dependent mechanisms. Keywords:: obstructive nephropathy, ureteral obstruction, macrophage, dendritic cell, liposome clodronate

Abstract.: Tubulointerstitial fibrosis is a common feature of many progressive renal diseases and is a main determinant that leads to an irreversible loss of renal function. In chronic cyclosporin A nephrotoxicity, we previously reported that inflammatory responses such as macrophage infiltration preceded interstitial fibrosis. This inflammation was accompanied by an elevation in renal nuclear factor κB (NF-κB) activity. Similar findings were obtained in chronic tacrolimus nephrotoxicity and obstructive nephropathy. Inhibition of NF-κB markedly attenuated renal inflammation and interstitial fibrosis in these models. Furthermore, administration of oral adsorbent (Kremezin®) significantly attenuated the increase in renal NF-κB activity and concomitantly reduced interstitial inflammation and renal fibrosis in chronic renal failure rats. Elimination of indoxyl sulfate by this adsorbent is likely involved in this mechanism since it is known that indoxyl sulfate activates NF-κB in renal tubular cells. It is suggested that strategy aiming at NF-κB inhibition is important to prevent the progression of renal fibrosis. Keywords:: nuclear factor κB, renal fibrosis, nephrotoxicity, unilateral ureteral obstruction, oral adsorbent

To investigate whether manganese superoxide dismutase (MnSOD) genetic polymorphism is associated with the clinical significance of prostate cancer.Prostates were obtained from 194 deceased men 45 years or older who did not have a history of prostate cancer. Serial sections and histological examinations of the prostate were performed. The MnSOD genotypes of the specimens were determined by polymerase chain reaction restriction fragment length polymorphism analysis.Of the 194 men, 31 and 26 had clinically insignificant and significant prostate cancer. Clinically significant cancer comprised 29% and 58% of the cancers in men 70 years old, respectively. The age-specific proportion of significant cancer significantly increased with the advance of age (p

Heterogeneous nuclear ribonucleoprotein (hnRNP) K is a part of the ribonucleoprotein complex which regulates diverse biological events. While overexpression of hnRNP K has been shown to be related to tumorigenesis in several cancers, both the expression patterns and biological mechanisms of hnRNP K in renal cell carcinoma (RCC) cells remain unclear. In this study, we showed that hnRNP K protein was strongly expressed in selected RCC cell lines (ACHN, A498, Caki-1, 786-0), and knock-down of hnRNP K expression by siRNA induced cell growth inhibition and apoptosis. Based on immunohistochemical (IHC) analysis of hnRNP K expression in human clear cell RCC specimens, we demonstrated that there was a significant positive correlation between hnRNP K staining score and tumor aggressiveness (e.g., Fuhrman grade, metastasis). Particularly, the rate of cytoplasmic localization of hnRNP K in primary RCC with distant metastasis was significantly higher than that in RCC without metastasis. Additionally, our results indicated that the cytoplasmic distribution of hnRNP K induced by TGF-β stimulus mainly contributed to TGF-β-triggered tumor cell invasion in RCC cells. Dominant cytoplasmic expression of ectopic hnRNP K markedly suppressed the inhibition of invasion by knock-down of endogenous hnRNP K. The expression level of matrix metalloproteinase protein-2 was decreased by endogenous hnRNP K knock-down, and restored by ectopic hnRNP K. Therefore, hnRNP K may be a key molecule involved in cell motility in RCC cells, and molecular mechanism associated with the subcellular localization of hnRNP K may be a novel target in the treatment of metastatic RCC.

A 62-year-old man was referred to our hospital for an axillary mass. Computed tomography (CT) revealed a right axillary tumor and a left renal tumor. Needle biopsies of lung tumor and renal tumor were performed, but a definite diagnosis was impossible. Because his performance status worsened and the lung tumor grew day by day, chemotherapy with gemcitabine and cisplatin was started without definite diagnosis. However, the chemotherapy could not be continued because of interstitial pneumonia and the patient died because of the progression of disease. The final histopathologic diagnosis was pulmonary pleomorphic carcinoma based on immunohistochemical staining.