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Bladder cancer is the 9th leading cause of cancer death worldwide. The major problem in bladder cancer is primarily the high recurrence rate after drug treatment and resection. Although conventional screening methods, such as cystoscopy, urinary cytology and ultrasound sonography, have become widely used in clinical settings, the diagnostic performance of these modalities is unsatisfactory due to low accuracy or high invasiveness. Because circulating micro RNA (miRNA) profiles have recently been reported as an attractive tool for liquid biopsy in cancer screening, here, we performed global miRNA profiling of 392 serum samples of bladder cancer patients with 100 non-cancer samples and 480 samples of other types of cancer as controls. We randomly classified the bladder cancer and control samples into 2 cohorts, a training set (N = 486) and a validation set (N = 486). By comparing both controls, we identified specific miRNA, such as miR-6087, for diagnosing bladder cancer in the training and validation sets. Furthermore, we found that a combination of 7 miRNA (7-miRNA panel: miR-6087, miR-6724-5p, miR-3960, miR-1343-5p, miR-1185-1-3p, miR-6831-5p and miR-4695-5p) could discriminate bladder cancer from non-cancer and other types of tumors with the highest accuracy (AUC: .97; sensitivity: 95%; specificity: 87%). The diagnostic accuracy was high, regardless of the stage and grade of bladder cancer. Our data demonstrated that the 7-miRNA panel could be a biomarker for the specific and early detection of bladder cancer.

Arteriovenous fistula (AVF) after allograft biopsy occurs in 1.6-8.3% of kidney transplant patients and most cases remain asymptomatic. Here, we report a case of hemorrhagic shock in a kidney transplant recipient following bleeding from an AVF after graft biopsy. Immediate intensive care including angiographic embolization saved the patient and the allograft. A 62-year-old woman with end-stage renal disease caused by diabetic nephropathy underwent ABO-incompatible kidney transplantation. No complications occurred in the early postoperative period. However, serum creatinine levels did not decrease sufficiently and decreased graft diastolic blood flow was noted on ultrasound. Therefore, at 14 days after kidney transplantation, allograft biopsy was performed to elucidate the cause of allograft dysfunction. At 5 days after allograft biopsy, the patient developed hemorrhagic shock caused by bleeding from an AVF in the allograft. We immediately performed angiographic embolization, and her vital signs improved without deterioration in renal function. AVF can cause hemorrhagic shock, and angiographic embolization is effective for treating it.

Background Unintentional renal artery occlusion after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm remains one of the most unfavorable complications. Renal salvage options include percutaneous transluminal renal artery angioplasty (PTRA) and open hepatosplenorenal bypass. However, the usefulness of kidney autotransplantation (AutoTx) remains unclear. Case presentation A 76-year-old woman with a right solitary kidney attributable to a left renal thromboembolism had previously undergone EVAR with a stent graft for an infrarenal aortic aneurysm, which led to ostial occlusion of the right renal artery. In addition, she had undergone PTRA and stenting. Two days before admission, she developed leg edema and hypertension, leading her to visit the hospital. Her serum creatinine level was 2.4 (baseline, 1.0) mg/dL. Acute kidney injury due to renal artery in-stent restenosis was suspected; re-angioplasty was attempted on day 2 of hospitalization, but was unsuccessful. Her renal function did not improve and anuria persisted; thus, hemodialysis was initiated on the same day. The right kidney size (8.6 cm) was preserved relative to her body size, with only mild cortical atrophy. Doppler ultrasonography and mercaptoacetyltriglycine scintigraphy revealed minimal but significant perfusion of the right kidney. Therefore, we considered that kidney perfusion was sustained and renal function could be reversed. On day 25 of hospitalization, right kidney AutoTx to the right iliac fossa was performed to reestablish adequate renal perfusion and reverse the need for dialysis. Soon after the procedure, the patient started passing urine. Her renal function improved; her serum creatinine level decreased to 1.0 mg/dL on day 33 of hospitalization. Hemodialysis was discontinued after the surgery. Zero-hour kidney biopsy showed only mild tubular injury, with neither tubular necrosis nor glomerular abnormalities. Conclusions Kidney AutoTx can be performed for patients with renal artery in-stent occlusion after unsuccessful PTRA who previously underwent EVAR. Our case showed successful recovery of renal function nearly 1 month after renal artery occlusion, indicating that revascularization should be considered even if it is delayed, as the kidney might be perfused through collateral circulation.

INTRODUCTION AND OBJECTIVES:We examined whether serum N-glycan profile can be used as a diagnostic marker of graft rejection after living-donor kidney transplants (KT).METHODS:A total 197 KT recipi...

Background Bladder cancer is the most prevalent malignancy involving the urinary system and exhibits a markedly high recurrence rate. Therefore, reliable and noninvasive diagnostic and surveillance methods are desperately needed. Patients and Methods Candidate microRNAs (miRNAs) were selected from the miRNAs that were differentially expressed in bladder cancer cell lines (T24 and RT4) compared to normal ureteral epithelial tissue using miRNA-microarray analysis. The candidate miRNAs were validated by quantitative reverse transcription polymerase chain reaction assay using voided urine samples. Results We identified 3 miRNAs (miR-301b, -563, and -146a-5p) that demonstrated > 2-fold higher expression levels in cancer cell lines than in the normal ureteral epithelial tissue. Of these, only miR-146a-5p was consistently and significantly higher in urine samples from the patients with bladder cancer than in those from the normal individuals ( P = .0014). The patients with high-grade tumors exhibited significantly higher urinary miR-146a-5p levels than those with low-grade tumors, and the patients with invasive tumors tended to show higher urinary miR-146a-5p levels than those with noninvasive tumors. Elevated urinary miR-146a-5p levels in patients with bladder cancer were decreased to the normal level after transurethral resection of the tumors ( P = .0214). Conclusion Our study suggested that urinary miR-146a-5p might be useful as a new noninvasive diagnostic marker, therapeutic target, or anticancer agent for bladder cancer, as well as for increasing our understanding of cancer biology.

Page kidney refers to a clinical condition that is characterized by the acute onset of hypertension and renal dysfunction owing to external compression of the kidney by a hematoma, tumor, lymphocele, or urinoma. We report a case in which Page kidney occurred after a nonepisode protocol renal allograft biopsy. A 31-year-old man with end-stage renal disease received a living related kidney transplant from his father. One year later, a nonepisode protocol renal allograft biopsy was performed. A day later, the patient's serum creatinine level increased to 4.23 mg/dL, and a subcapsular renal hematoma was detected using ultrasonography and computed tomography. Page kidney was diagnosed, and immediate surgical removal of the hematoma was performed. Nine days after the operation, the patient's serum creatinine level had improved to 1.89 mg/dL. Page kidney is a serious but treatable complication of renal allograft biopsies, and clinicians should pay attention to such complications, even in the setting of nonepisode protocol renal allograft biopsies.

In recent years, the frequency of high-risk kidney transplantations has increased. We report a case in which a 72-year-old man with various severe comorbidities (prostate cancer, diabetes mellitus, complete atrioventricular block, coronary artery stenosis, severe stenosis of the popliteal arteries, and severe calcification of the iliac arteries) who received an orthotopic kidney transplantation. To prevent the occurrence of acute limb ischemia due to the steal phenomenon (caused by the kidney graft), we decided that a heterotopic kidney transplantation involving the iliac arteries was not an appropriate option. Therefore, as an alternative, left native nephrectomy was performed followed by an orthotopic kidney transplantation to the native renal artery and renal vein through a left subcostal incision. Postoperative ureteral stenosis occurred, and so stent exchange was required every 6 months. Despite the ureteral complication, the patient's serum creatinine level was 1.5 mg/dL at 2 years after the procedure.

Biomarker-driven cancer therapy has met with significant clinical success. Identification of a biomarker implicated in a malignant phenotype and linked to poor clinical outcome is required if we are to develop these types of therapies. A subset of prostate adenocarcinoma (PACa) cases are treatment-resistant, making them an attractive target for such an approach. To identify target molecules implicated in shorter survival of patients with PACa, we established a bioinformatics-to-clinic sequential analysis approach, beginning with 2-step in silico analysis of a TCGA dataset for localized PACa. The effect of candidate genes identified by in silico analysis on survival was then assessed using biopsy specimens taken at the time of initial diagnosis of localized and metastatic PACa. We identified PEG10 as a candidate biomarker. Data from clinical samples suggested that increased expression of PEG10 at the time of initial diagnosis was linked to shorter survival time. Interestingly, PEG10 overexpression also correlated with expression of chromogranin A and synaptophysin, markers for neuroendocrine prostate cancer, a type of treatment-resistant prostate cancer. These results indicate that PEG10 is a novel biomarker for shorter survival of patients with PACa. Also, PEG10 expression at the time of initial diagnosis may predict focal neuroendocrine differentiation of PACa. Thus, PEG10 may be an attractive target for biomarker-driven cancer therapy. Thus, bioinformatics-to-clinic sequential analysis is a valid tool for identifying targets for precision oncology.

We have reported that interferon (IFN)-α can attack cancer cells by multiple antitumor mechanisms including the induction of direct cancer cell death and the enhancement of an immune response in several pancreatic cancer models. However, an immunotolerant microenvironment in the tumors is often responsible for the failure of the cancer immunotherapy. Here we examined whether the suppression of regulatory T cells (Tregs) within tumors can enhance an antitumor immunity induced by an intratumoral IFN-α gene transfer. First we showed that an intraperitoneal administration of an agonistic anti-glucocorticoid induced TNF receptor (GITR) monoclonal antibody (mAb), which is reported to suppress the function of Tregs, significantly inhibited subcutaneous tumor growth in a murine pancreatic cancer model. The anti-GITR mAb was then combined with the intratumoral injection of the IFN-α-adenovirus vector. The treatment with the antibody synergistically augmented the antitumor effect of IFN-α gene therapy not only in the vector-injected tumors but also in the vector-uninjected tumors. Immunostaining showed that the anti-GITR mAb decreased Foxp3(+) cells infiltrating in the tumors, while the intratumoral IFN-α gene transfer increased CD4(+) and CD8(+) T cells in the tumors. Therefore, the combination therapy strongly inclined the immune balance of the tumor microenvironment in an antitumor direction, leading to a marked systemic antitumor effect. The CCR5 expression on Tregs was downregulated in the antibody-treated mice, which may explain the decrease of tumor-infiltrating Tregs. The combination of Treg-suppression by GITR mAb and the tumor immunity induction by IFN-α gene therapy could be a promising therapeutic strategy for pancreatic cancer.

We determined if the serum N-glycan profile can be used as a diagnostic marker of antibody-mediated rejection (ABMR) in living donor kidney transplant (LKTx) recipients. Glycoblotting, combined with mass spectrometry, was used to retrospectively examine N-glycan levels in the postoperative sera of 197 LKTx recipients of whom 16 recipients had ABMR with or without T-cell-mediated rejection (TCMR), 40 recipients had TCMR, and 141 recipients had no adverse events. Multivariate discriminant analysis for prediction of ABMR was performed by inputting an ABMR event as an explanatory variable and sex, age, and serum N-glycan level as objective variables. The N-glycan score was calculated by multiplying the level of candidate objective variables by objective function values. The ABMR predictive performance of the N-glycan score was assessed by receiver operator characteristic curve and Kaplan–Meier curve analyses. The N-glycan score discriminated ABMR with 81.25% sensitivity, 87.85% specificity, and an area under the curve (AUC) of 0.892 that was far superior to that of preformed donor-specific antibody status (AUC, 0.761). Recipients with N-glycan-positive scores >0.8770 had significantly shorter ABMR survival than that of recipients with N-glycan-negative scores. Although the limitations of our study includ its small sample size and retrospective nature, the serum N-glycan score may contribute to prediction of ABMR.

Solitary fibrous tumor (SFT) rarely occurs in the kidneys, and only one reported case of renal SFT has shown distant metastasis. We report the second case of renal SFT exhibiting distant metastasis. A 48-year-old man was referred to our hospital because of a right renal mass. An abdominal CT scan detected a large renal tumor, which was suspected to be a renal cell carcinoma. Right radical nephrectomy was performed, and the tumor was found to measure 28 × 18 × 10 cm. The pathological diagnosis was benign solitary fibrous tumor of the kidney. Eight years after the operation, lung and liver metastases developed. Pulmonary segmentectomy and partial hepatectomy were performed. The pathological diagnoses of these resected tissue specimens were compatible with benign SFT.

Rapid advancements have been made in alternative treatments for renal diseases. Our goal for renal regeneration is to establish a kidney graft derived from human embryonic tissues. In this study, we investigated the effects of host renal failure on the structure and activity of transplanted embryonic kidney and bladder, and found that diuretics effectively induced urine production in the transplanted kidney. Uremic conditions were reproduced using a 5/6 renal infarction rat model. An embryonic kidney plus bladder (embryonic day 15) was isolated from a pregnant Lewis rat and transplanted into the para-aortic area of a 5/6 renal-infarcted Lewis rat. Following growth, the embryonic bladder was successfully anastomosed to the host ureter. We assessed graft function in terms of survival rates and found no differences between normal (n = 5) and renal failure (n = 8) groups (median survival: 70.5 vs 74.5 h; p = 0.331) in terms of survival, indicating that the grafts prolonged rat survival, even under renal failure conditions. Furosemide (n = 9) significantly increased urine volume compared with saline-treated controls (n = 7; p

Our objectives were to compare the clinical outcomes of mizoribine (12 mg/kg/d) and mycophenolate mofetil (2000 mg/d) in combination with tacrolimus, basiliximab, and corticosteroids.We enrolled 83 recipients of living-donor renal transplant (performed between 2008 and 2013) in this study. This prospective multi-institutional randomized comparative study compared mizoribine (n = 41) and mycophenolate mofetil (n = 42) in combination with tacrolimus, basiliximab, and corticosteroids for living-donor renal transplant recipients. We compared the acute rejection and graft survival rates and adverse event rates within 1 year of renal transplant between the 2 groups using intention-to-treat analyses.During the 1-year observation period, patient and graft survival rates were 100%. The acute rejection rate was 17.1% in the mizoribine group and 19% in the mycophenolate mofetil group. The incidence rate of cytomegalovirus infection seropositivity (recipient and donor with positive cytomegalovirus antibody status) was higher in the mycophenolate mofetil group than in the mizoribine group, although the difference in these rates was not statistically significant. The incidence of leukopenia was higher in the mizoribine group than in the mycophenolate mofetil group.High-dose mizoribine at 12 mg/kg/day was a safe and efficacious immunosuppressive alternative to mycophenolate mofetil in living-donor renal transplant recipients. Leukopenia should be closely monitored in the initial period of insufficient kidney function after renal transplant.

Solitary fibrous tumor (SFT) of the kidney is a rare entity and usually displays a favorable prognosis. We herein report a second case of renal SFT developing local recurrence. A 50-year-old man was referred to our hospital because of a left renal mass. An abdominal CT detected a large renal tumor and radical nephrectomy was performed with a possible diagnosis of renal cell carcinoma. The resected tumor size was measured at 17 × 11 × 8 cm. Grossly, necrosis was observed in central lesion of the tumor but hemorrhage was not observed. Microscopically, the tumor consisted of spindle-shaped cells with scant cytoplasm accompanied by hyalinized collagenous tissue, which displayed hemangiopericytomatous patterns. The cellularity was normal and nuclear pleomorphism was not observed. Ki-67 labeling index was less than 3%. The pathological diagnosis of SFT was made without obvious malignant findings. Three years after the surgery, a follow-up CT scan detected a mass lesion in the tumor bed. Surgical resection was performed and the resected tumor was compatible with local recurrence of the SFT without obvious malignant findings. Renal SFT should be carefully monitored even in the absence of obvious malignant findings.

We report the first case in Japan of paraneoplastic dermatomyositis with pure seminoma, a tumor that extremely rarely accompanies dermatomyositis. The patient presented to the hospital with muscle weakness and erythema and was diagnosed with dermatomyositis from skin biopsy. Routine radiological screening revealed testicular tumor and massive lymph node metastases. We initially performed orchiectomy along with conventional immunotherapy. However, muscle weakness gradually worsened, and he eventually showed dysphagia and forced respiration and became bedridden. Although he seemed close to being too unstable to tolerate further treatment, we started carefully adjusted chemotherapy comprising 4 courses of etoposide plus cisplatin, which proved highly successful. Lymph node metastases completely disappeared and swallowing and respiration fully normalized after completing chemotherapy. We believe that this clinical success was due to our decision to initiate chemotherapy even in such a weak patient.

Sarcoma at advanced stages remains a clinically challenging disease. Interferons (IFNs) can target cancer cells by multiple antitumor activities, including the induction of cancer cell death and enhancement of immune response. However, the development of an effective cancer immunotherapy is often difficult, because cancer generates an immunotolerant microenvironment against the host immune system. An autologous hematopoietic stem cell transplantation (HSCT) is expected to reconstitute a fresh immune system, and expand tumor-specific T cells through the process of homeostatic proliferation. Here we examined whether a combination of autologous HSCT and IFNs could induce an effective tumor-specific immune response against sarcoma. First, we found that a type I IFN gene transfer significantly suppressed the cell growth of various sarcoma cell lines, and that IFN-β gene transfer was more effective in inducing cell death than was IFN-α in sarcoma cells. Then, to examine the antitumor effect in vivo, human sarcoma cells were inoculated in immune-deficient mice, and a lipofection of an IFN-β-expressing plasmid was found to suppress the growth of subcutaneous tumors significantly. Finally, the IFN gene transfer was combined with syngeneic HSCT in murine osteosarcoma models. Intratumoral IFN-β gene transfer markedly suppressed the growth of vector-injected tumors and inhibited formation of spontaneous lung and liver metastases in syngeneic HSCT mice, and an infiltration of many immune cells was recognized in metastatic tumors of the treated mice. The treated mice showed no significant adverse events. A combination of intratumoral IFN gene transfer with autologous HSCT could be a promising therapeutic strategy for patients with sarcoma.

Background Hepatitis B virus (HBV) infection is a risk factor of mortality in kidney transplant recipients. However, information on the risk of HBV reactivation in kidney recipients with prior resolved HBV infection is limited. This study aimed to evaluate the safety of simply monitoring viral and liver markers in living donor kidney transplantation (LDKT) recipients with prior resolved HBV infection. Methods We retrospectively examined the clinical records of LDKT recipients. Changes in the levels of alanine aminotransferase, aspartate aminotransferase, hepatitis B surface antigen (HBs Ag), surface antibody, core antibody, and HBV-DNA after transplantation were evaluated, and the occurrence of de novo HBV-related hepatitis and allograft function were monitored. Results Of 61 consecutive LDKT patients, seven had prior resolved HBV infection. Four patients underwent ABO-compatible LDKT, whereas two underwent ABO-incompatible LDKT. The median age was 64 years (range, 61–69 years), and two patients were women. The causes of end-stage kidney disease were diabetic nephropathy, hypertensive nephrosclerosis, and chronic glomerulonephritis. Five patients were referred to hepatologists. The history of HBV vaccination was not confirmed in all patients. Prophylaxis with entecavir was administered to two patients with ABO-incompatible LDKT before transplantation. All patients tested negative for HBs Ag and HBV-DNA throughout observation, and none developed de novo HBV-related hepatitis or graft loss. Conclusions Patients with HBV infection without HBV DNA positivity are eligible for kidney transplants without antiviral therapy, even those on rituximab therapy. Monitoring viral and liver markers combined with hepatologist consultations may ensure safe follow-up in LDKT recipients with prior resolved HBV infection.

Synchronous bilateral urothelial cancer is very rare. We report a 25-year-old male kidney recipient with Alport syndrome who developed bilateral synchronous urothelial cancer after transplantation. At the age of 16 this patient was referred to our clinic for a kidney transplantation. A living related donor kidney transplantation was performed with cyclosporin-based quadruple immunosuppression. He experienced no acute rejection and his graft function was excellent after transplantation. Nine years after transplantation, he complained of asymptomatic gross hematuria and was diagnosed as having a bilateral urothelial cancer in the native upper urinary tracts. A bilateral total nephroureterectomy was undertaken, and the postoperative pathological diagnosis was advanced bilateral urothelial carcinoma. The patient received adjuvant gemcitabine plus cisplatin chemotherapy at a cisplatin dosage reduced by 50%. After 4 years of follow-up, he is alive with a functioning graft and no evidence of recurrence.

Kitajima K, Koike J, Nozawa S, Yoshiike M, Takagi M, Chikaraishi T. Irreversible immunoexpression of matrix metalloproteinase-9 in proximal tubular epithelium of renal allografts with acute rejection. Clin Transplant 2011: 25: E336–E344. © 2011 John Wiley & Sons A/S. Abstract: Background: Matrix metalloproteinase-9 (MMP-9) is the most important member of the MMP family responsible for the development and progression of various renal diseases. Our study aims to investigate the localization of MMP-9 in human renal allografts and to assess whether MMP-9 immunostaining is contributory to detect pathological change in renal biopsy. Methods: We examined 150 renal allograft biopsies (48 baseline and 102 follow-up) from 49 transplants and analyzed the associations of clinical and histopathological data with the MMP-9 staining intensity using a semi-quantitative scoring. Results: MMP-9 immunostaining in proximal tubule epithelium was negative before transplantation, but positive in biopsies with episodes, particularly with acute cellular rejection (ACR) and acute calcineurin inhibitor (CNI) toxicity. Tubulitis was the most significant association factor (p

Malakoplakia is a rare chronic inflammatory condition characterized by defective macrophage function, most of which involve the genitourinary tract, and renal parenchymal involvement is uncommon. We present a case of malakoplakia affecting renal parenchyma. A 46-year-old woman with pyrexia and jaundice was referred to our department. Abdominal enhanced CT scan revealed a left pyelonephritis with ureteral stone and bilateral renal abscesses. Despite the insertion of a left ureteral stent and administration of antibiotics, the patient showed persistent high fever and elevated CRP, and no obvious improvement in clinical and imaging data. In view of the limited effectiveness of the conservative treatment in this case, we decided to perform left nephrectomy. The diagnosis of malakoplakia was made based on the histopathological findings of von Hansemann cells and Michaelis-Guttmann bodies detected in the nephrectomy specimen. She is clinically healthy up to the present (50 months after surgery) with normal clinical indicators and CT findings.

Post-transplant lymphoproliferative disorder (PTLD) is a neoplastic complication with a potentially fatal outcome that develops as a consequence of immunosuppression, and is mainly associated with Epstein-Barr virus (EBV) infection. A 70-year-old woman underwent a live unrelated, ABO-incompatible renal transplant for end-stage renal disease. One year after transplantation, protocol biopsy revealed pathological changes indicative of the histological subtype of 'early lesions of PTLD' according to the World Health Organization classification, while the patient showed no clinical signs or symptoms. The patient was finally diagnosed with EBV-positive PTLD by in situ hybridization for EBER (EBV-encoded RNA), and was successfully treated based on the reduction of immunosuppression. Protocol biopsy within the first post-transplant year is the only diagnostic measure to detect asymptomatic early PTLD, which allows for early intervention and leads to better outcomes.

Background: Lower urinary tract obstruction causes both renal failure and bladder dysfunction after birth. This study examined the early bladder wall changes after creating an obstructive uropathy focusing on bladder wall thickness and muscle integrity. Methods: We created obstructive uropathy in fetal lambs at 60 days' gestation, ligating the urethra and urachus. The fetuses (n = 28) were delivered at 48 hours and 3, 4, 5, 7, and 14 days after obstruction and at term (145 days' gestation). Sham-operated lambs were used as controls (n = 20). Histology samples were stained using α-smooth muscle actin) immunohistochemistry and also hematoxylin-eosin, Masson trichrome, and colloidal Fe stain. Results: The bladder wall initially expanded and stretched. By day 4, the bladder wall became thicker. Histologically, the bladder in obstructed lambs demonstrated a prominent submucosal fibrotic change by 7 days. The mean bladder wall thickness at 14 days after obstruction was thicker than controls, and fibrosis was prominent. Conclusion: The initial changes in the bladder wall were expansion of the muscle component followed by fibrosis. The bladder wall thickness dramatically increased 4 to 7 days after obstruction. We conclude that shunting operations to preserve bladder function may be needed earlier than expected.

Over the last decade, hemodialysis with enhanced internal filtration (IF) has been investigated as an alternative to conventional dialysis. Several factors affect IF, including the geometry and permeability of hollow-fiber dialyzers. Although various studies have been performed, the association between IF and membrane permeability has not been fully examined because of the difficulty in measuring IF. Therefore, in this study, we set up an experimental circuit and attempted to directly measure IF as well as membrane permeability in five dialyzers. In the circuit, we placed two dialyzers of the same type in series, and a special sampling port between them, thereby making it possible to determine IF by measuring the extent to which blood was concentrated between the two dialyzers. We showed that a significant amount of IF occurred in this tandem-dialyzer circuit, ranging from 23.5 to 100 ml/min, which increased linearly with increasing membrane permeability. We also showed that membrane permeability was reduced in the first dialyzer to a greater extent than in the second one after four hours of circulation, suggesting that filtration caused substantial membrane fouling. In this study we practically demonstrated that membrane permeability is highly relevant to the phenomenon of IF.

Cytomegalovirus (CMV) is a common infectious pathogen in kidney transplant patients. Here, we present a case of CMV esophagitis with antigenemia, that developed within 3 days of kidney transplantation, a timeline generally considered to be too early for development of a CMV infection. Intense immunosuppressive therapy for desensitization in ABO-incompatibility or in the presence of donor-specific antibody can increase the risk for significant opportunistic infection immediately after or even before transplantation.

It has been sporadically reported that HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) develops after living-donor kidney transplantation from HTLV-1 positive donors (D+) to negative recipients (R-). However, these details have been unknown. Thus we evaluated the incidence and clinical characteristics of HAM/TSP after living-donor kidney transplantation from D+ to R-(D+R-transplantation). Using data obtained from the Japanese Renal Transplant Registry, we analyzed 13,299 cases of living-donor kidney transplantation between 2000 and 2013 in Japan. In addition, we have collected information about 5 patients who developed HAM/TSP after D+R-transplantation. The incidence of HAM/TSP after D+R-transplantation was calculated as the ratio of “the number of recipients who developed HAM/TSP” to “the number of cases of D+R-transplantation”. The characteristics of HAM/TSP in D+R-transplant recipients such as time from transplantation to disease onset and rate of disease progression are investigated. About 70% of all 13,299 donors took a HTLV-1 antibody test and 64 cases were positive for HTLV-1 antibody. Although the remaining 4,072 donors didn't take the antibody test, we estimated the number of HTLV-1 positive donors as 36 according to the HTLV-1 prevalence in Japan. As a result, the estimated incidence of HAM/TSP after D+R-transplantation was 5%. All the 5 cases of HAM/TSP after D+R-transplantation showed an early onset after transplantation. Four out of five cases developed rapidly and had difficulty walking in one or two years. This study demonstrated that incidence rate (5%) of HAM/TSP in recipients after D+R-transplantation is extremely higher compared to the lifetime risk (0.25%) of HAM/TSP in an HTLV-1-infected person. Further, this study suggested that HAM/TSP after D+R-transplantation is characterized by rapid onset and progression. Therefore, we need to conduct nationwide survey to assess the risk of D+R-transplantation.

Background In kidney transplant recipients, the most widely used method for the reconstruction of the urinary pathway is ureteroneocystostomy, which may be difficult in cases with disused atrophic bladder. In this study, we evaluated kidney transplant recipients who underwent uretero-ureteral end-to-side anastomosis (UUA) in urinary reconstruction due to disused atrophic bladder. Methods To clarify the effectiveness of this method, we retrospectively reviewed the clinical records of kidney transplant recipients in our hospital. Results A total of 9 recipients with urinary reconstruction using UUA were evaluated. All of these patients had a history of long-term hemodialysis before transplantation, accompanied by complete anuria and small capacity of the bladder. In 4 patients, cranial native ureter was ligated, whereas it was not ligated in the remaining 5 patients. In 2 of 4 patients with cranial ligation, hydronephrosis developed in the native kidney with no further treatment being required. No patients experienced urinary tract complications including hydronephrosis in the graft, urine extravasation, or urinary tract infection in the follow-up period (757.6 ± 491.3 days). Allograft function was maintained well in all patients (serum creatinine level, 1.08 ± 0.23 mg/dL). Conclusions Although UUA is not a routine method of urinary reconstruction in kidney transplantation, it can be safely performed and should be a surgical option, especially for recipients with disused atrophic bladder. The ligation of cranial native ureter may lead to hydronephrosis of the native kidney, and it is tentatively concluded that UUA without native ureteral ligation is clinically feasible.

Peritoneal dialysis (PD) catheter-related infection is still is the most troublesome problem for continuation of PD without the need to switch to hemodialysis. We have been performing subcutaneous pathway diversion (SPD) as a surgical treatment for refractory exit-site and tunnel infection (ESTI). To clarify the efficacy and safety of SPD, we conducted a retrospective study. From August 2008 to August 2013, 30 SPDs were performed in 26 patients (16 men, 10 women; mean age: 58 +/- 13 years; 54% with diabetes; mean body mass index: 23.9 +/- 3.5 kg/ m2). The reasons for the SPDs were ESTI in 25 patients, and outer cuff extrusion in 1 patient. All patients resumed PD immediately after SPD, and the duration of hospitalization was 11.7 +/- 10.1 days. After SPD, one patient experienced a dialysate leak, and another patient experienced a mild subcutaneous hematoma. Another 4 patients developed exit-site infection (ESI) and underwent a second SPD. Of those 4 patients, 3 presented with another ESI unrelated to the first episode, and all developed an ESI after 6 months or more. The remaining 20 patients experienced no such complications. Furthermore, catheter survival after SPD was 17.4 +/- 13.4 months. To eradicate ESTTI we suggest that SPD, which does not require catheter removal or interruption of PD, is useful compared with the unroofing technique or catheter removal.

Here we report therapeutic drug monitoring of cyclosporine in a kidney transplant recipient lacking enterohepatic circulation. The patient developed steroid-resistant nephrotic syndrome at age 14 years, and was medicated with an oral cyclosporine microemulsion. However, her cyclosporine trough level was unexpectedly elevated, and subsequent investigations showed that she was deficient in drug metabolism as a result of the congenital absence of the portal vein. Her renal function gradually decreased and she became dialysis-dependent at the age of 21 years, and kidney transplantation was planned. Based on pretransplant therapeutic drug monitoring, we started cyclosporine microemulsion at half of the conventional dosage. After transplantation, the dosage was successfully adjusted to achieve a target trough level. The post-transplant course was stable with no symptoms of rejection or cyclosporine-associated nephrotoxicity.

Post-transplant lymphoproliferative disorder (PTLD) is a neoplastic complication with a potentially fatal outcome that develops as a consequence of immunosuppression, and is mainly associated with Epstein-Barr virus (EBV) infection. A 70-year-old woman underwent a live unrelated, ABO-incompatible renal transplant for end-stage renal disease. One year after transplantation, protocol biopsy revealed pathological changes indicative of the histological subtype of 'early lesions of PTLD' according to the World Health Organization classification, while the patient showed no clinical signs or symptoms. The patient was finally diagnosed with EBV-positive PTLD by in situ hybridization for EBER (EBV-encoded RNA), and was successfully treated based on the reduction of immunosuppression. Protocol biopsy within the first post-transplant year is the only diagnostic measure to detect asymptomatic early PTLD, which allows for early intervention and leads to better outcomes.

Background: Renal transplantation is a definitive therapeutic modality in end-stage renal disease (ESRD). Most ESRD patients in Japan experience dialysis prior to renal transplantation. The present study was undertaken to examine the usefulness of pre-emptive renal transplantation (PET). Methods: Between 1987 and 1998, 255 renal transplantations were carried out by the authors. Among those consecutive cases, 10 were cases of PET. In nine pediatric cases, demographics, graft and patient survival, height growth and benefits from successful transplantation were studied and compared with age-matched dialyzed transplantation controls. Results: All transplantation was living-related. There was a disparity of causes of ESRD between the two groups. In PET, acquired renal deterioration due to a congenital lower urinary tract disorder was the major cause. Graft and patient prognosis was favorable in both groups. Growth retardation in PET patients under 15 years of age was significantly less apparent at the time of transplantation and after 3 years compared to the control. The benefits from transplantation were different in the two groups. Most PET patients felt an improvement of their physical condition; however, all of the control patients felt that the major boon was the freedom from the restriction of the daily diet and time for dialysis. Conclusion: In pediatric renal transplantation, short-term preceding dialysis does not have a detrimental effect, but PET could benefit ESRD patients by maintaining their quality of life. Moreover, PET minimizes the production of renal dwarfism in prepubertal children. Thus, PET should be taken into consideration in the choice of renal replacement therapy.

A 2-year-old boy, who had the chief complaints of penile swelling and pain, was brought to the hospital by his mother. Penile contusion/trauma was suspected and he was admitted the same day to undergo emergency surgery to eliminate hematoma. The surgery revealed that the origin of the bleeding was not trauma but a tumor lesion of the penile shaft. It was histopathologically identified as a yolk sac tumor and no tumorous lesions were found except that in the penis. Therefore the patient was diagnosed as definitely having a yolk sac tumor originating in the penis. The patient received four cycles of cisplatin, etoposide and bleomycin treatment as adjuvant chemotherapy. Although it was impossible to completely resect the tumor, cisplatin, etoposide and bleomycin chemotherapy was effective and a complete response was achieved. We plan to carefully monitor the patient in the future.

We have designed a protocol for ABO-incompatible kidney transplantations based on preoperative plasmapheresis with a tacrolimus/mycophenolate mofetil/methylprednisolone/basiliximab protocol using low-dose rituximab (200 mg/body) instead of splenectomy to prevent antibody-mediated acute rejection. Eight patients successfully received transplants with this protocol. The titers of anti-A and -B antibodies as well as the number of CD20 + cells were readily maintained at a low level posttransplantation. There were no side effects. All patients have renal transplant function with a follow-up of 1–34 months.

Basiliximab is potent, relatively safe immunosuppressive induction agent used in transplantation. Prophylactic use at the time of transplantation has been advocated to improve allograft outcomes. We report two cases of kidney transplant recipients with anaphylactic reactions after initial exposure to Basiliximab.

Background: Five renal recipients with neurovesical dysfunction (NVD) were retrospectively reviewed focusing on anatomical and urodynamic abnormalities of the lower urinary tract and their management prior to kidney transplantation. Methods: The underlying anomalies in these 5 patients were a posterior urethral valve (1 with an imperforate anus; n = 2), meningomyelocele (n = 2) and a congenital short urethra with an imperforate anus (n = 1). Their urinary tracts were evaluated prior to transplantation with voiding cystourethrography, urethrocystoscopy, cystometrography and electromyography of the external urethral sphincter to identify a possible focus of urinary tract infection, urine storage and voiding function. Results: All 5 patients had NVD proven by urodynamic studies or by documentation of urinary retention in the absence of mechanical outlet obstruction. Bilateral high grade vesicoureteral reflux was noted in all patients, requiring ureteroneocystostomy. Clean intermittent catheterization (CIC) was ultimately employed for bladder emptying in all patients. Two patients with poor bladder compliance underwent augmentation cystoplasty before transplantation. The Mitrofanoff procedure was used in 2 patients with structural urethral abnormalities to access the bladder for catheterization. After eradication of possible sources of infection and establishment of a low-pressure urine storage system with bladder emptying by CIC, kidney transplantation was performed. Following kidney transplantation, all of the recipients were asymptomatic for urinary tract infections using CIC. Although 1 patient lost his graft due to chronic rejection, the other 4 other patients have good renal function. Conclusion: Kidney transplantation in patients with NVD can be performed provided that their urinary tract problems are properly resolved.

Purpose: We retrospectively evaluated the feasibility and efficacy of surgical revascularization for renal artery aneurysms.Materials and Methods: Beginning in 1984, 12 patients with renal artery aneurysm underwent renal revascularization regardless of clinical features. Postoperative results were analyzed regarding split renal function, patency of the revascularized arteries, blood pressure control and surgical complications.Results: Postoperative renal function was stable or improved in all but 1 case and patency in branched arteries was preserved in 86%. Hypertension in 8 patients was cured in 7 (88%), including 2 with renovascular hypertension, and improved in 1 (12%). Complications were minimal with only 1 ureteral stricture that required reoperation.Conclusions: The majority of renal artery aneurysm cases are amenable to surgical repair. Carefully performed renal revascularization is rewarding in that high blood pressure is better controlled, renal function is improved and the potential risk...

Lymphopenia-induced homeostatic proliferation of T cells after autologous hematopoietic stem cell transplantation (HSCT) skews the T cell repertoire by engaging tumor-associated Ags, leading to an induction of antitumor immunity. However, how HSCT alters the immunosuppressive microenvironment in the tumors is unknown. In this study, we first analyzed the kinetics of regulatory T cells (Tregs) in the tumors after syngeneic HSCT. Unexpectedly, the frequency of CD4+ cells expressing Foxp3 was increased in the spleens, whereas the frequency was clearly decreased in the tumors after HSCT. The origin of reconstituted CD4+ and Foxp3+ cells in the tumors was mainly from the expansion of transferred splenic T cells. Then, to examine the mechanism of Treg suppression after HSCT, we isolated CD11c+ cells from tumors. A large amount of Treg-inhibitory cytokine IL-6 was secreted from the CD11c+ cells in the tumors, but not in the spleens in the recipient mice. Furthermore, to understand what factor affects the activity of CD11c+ cells in the tumors after HSCT, we analyzed the expression of various cytokines/chemokines with mouse cytokine Ab arrays, and noticed that VEGF-D concentration was increased in the tumors in the early period after HSCT. The CD11c+ cells produced IL-6 in response to VEGF-D stimulation, and an administration of VEGF receptor-3 neutralizing Ab significantly suppressed the production of IL-6 from CD11c+ cells accompanied with the increase of Tregs in the tumors of HSCT recipients. Autologous HSCT creates an environment that strongly supports the enhancement of antitumor immunity in reconstituted lymphopenic recipients through the suppression of Tregs.

An arteriovenous fistula (AVF) between the radial artery and cephalic vein at the wrist is the preferred type of hemodialysis vascular access. However, in the practice of access placement, we are aware that some patients fail to form the standard forearm radial–cephalic AVF, owing to naturally small veins or acquired abnormal lesions of the veins. To identify the risk factors for failure to form the standard AVF, we examined 305 consecutive patients who underwent first-time access surgery at our hospital from January 2006 to December 2010. We compared the patients’ characteristics between those having normal vessels and successfully forming the standard AVF, and those having apparently abnormal vessels and thus forming alternative types of access instead. Histories of major and minor surgery were specifically evaluated, assuming that surgical procedures in the past could potentially damage the superficial veins. We created 207 standard and 98 alternative accesses during the period and found that significantly more patients with alternative accesses (31 %) had undergone major surgery of a variety of specialties, in comparison with those with the standard AVF (15.0 %). Multivariate logistic analysis revealed that a history of major surgery (OR = 2.39, 95 %CI 1.29–4.47, p = 0.006) and female gender (OR = 1.87, 95 %CI 1.10–3.20, p = 0.02) were independent risk factors associated with failure to construct the standard AVF. Our results indicate that previous surgery can damage the superficial veins and cause venous abnormality, which makes construction of the standard AVF difficult. We propose that care should be taken to preserve the superficial veins when patients for whom dialysis therapy is a future possibility undergo surgical procedures, especially invasive ones.

Many reports have indicated that the abnormal expression of microRNAs (miRNAs) is associated with the progression of disease and have identified miRNAs as attractive targets for therapeutic intervention. However, the bifunctional mechanisms of miRNA guide and passenger strands in RNA interference (RNAi) therapy have not yet been clarified. Here, we show that miRNA (miR)-582-5p and -3p, which are strongly decreased in high-grade bladder cancer clinical samples, regulate tumor progression in vitro and in vivo. Significantly, the overexpression of miR-582-5p or -3p reduced the proliferation and invasion of UM-UC-3 human bladder cancer cells. Furthermore, transurethral injections of synthetic miR-582 molecule suppressed tumor growth and metastasis in an animal model of bladder cancer. Most interestingly, our study revealed that both strands of miR-582-5p and -3p suppressed the expression of the same set of target genes such as protein geranylgeranyltransferase type I beta subunit (PGGT1B), leucine-rich repeat kinase 2 (LRRK2) and DIX domain containing 1 (DIXDC1). Knockdown of these genes using small interfering RNA (siRNA) resulted in the inhibition of cell growth and invasiveness of UM-UC-3. These findings uncover the unique regulatory pathway involving tumor suppression by both strands of a single miRNA that is a potential therapeutic target in the treatment of invasive bladder cancer.