Intrinsic and extrinsic factors causing hyperplasia of the prostate.

Prostatic hyperplasia is very common in elderly men and is a typical disease that reduces quality of life. Histologically, hyperplasia of the prostate gland causes obstruction at the bladder outlet, resulting in symptoms such as a weak urine stream. Various factors have been considered to cause histological enlargement of the prostate, but the underlying cause is still unknown. The factors that cause prostate hyperplasia can be broadly classified into intrinsic and extrinsic ones. Extrinsic factors include things that we directly come into contact with such as bacteria and food. On the other hand, intrinsic factors are those that cause changes in functions originally provided in the body due to some cause, including extrinsic factors, such as chronic inflammation and an imbalance of sex hormones. A large number of reports have been made to date regarding the etiology of prostatic hyperplasia, although they have not yet clarified the fundamental cause(s). The various factors currently known should be outlined for future research. Should it be possible to prevent this highly prevalent prostatic hyperplasia which is mainly cause of dcreasing quality of life, there is no doubt that it would be a huge contribution to humanity.

[Two Cases of Retroperitoneal Synovial Sarcoma].

We experienced two cases of renal primary synovial sarcoma. Case 1: A 29-year-old man underwent laparoscopic radical nephrectomy and was originally diagnosed with renal cell carcinoma. Case 2: A 25-year-old man was treated by open radical nephrectomy since radiographical findings indicated tumor invasion to the ureter causing hydronephrosis. Both cases were pathologically diagnosed as renal synovial sarcomas, and were followed using computed tomography. Recurrence was observed within a year in both cases.

Development and preliminary evaluation of a novel procedure for creation of an ileal conduit stoma aimed at preventing parastomal hernia.

OBJECTIVES: Our previous study suggested that the operative procedure is critical for the development of parastomal hernia. We developed a novel procedure for the creation of an ileal conduit stoma to prevent parastomal hernia. Herein we evaluate the efficacy and safety of the procedure. METHODS: A total of 113 Japanese patients underwent radical cystectomy and ileal conduit diversion for bladder cancer from January 2017 through December 2021 at our institution. After excluding those with incomplete data, 103 patients consisting of 46 (44.7%) with the conventional procedure and 57 (55.3%) with the novel procedure were consecutively enrolled. The main points of the novel procedure are as follows: (1) the passage of the ileal conduit is ≤2.4 cm in diameter in principle; (2) the posterior rectus sheath and peritoneum are vertically incised 2 cm laterally from the middle of the stoma site to make an oblique passage for the ileal conduit; and (3) the anterior rectus sheath and posterior rectus sheath with peritoneum are fixed to the ileal conduit separately. RESULTS: Radiography-based parastomal hernia was observed in 11 patients (10.7%) with a median follow-up of 22.0 months. The incidences of parastomal hernia were 3.5% and 19.6% in the novel and the conventional procedure groups, respectively (p = 0.011). The former had a significantly lower cumulative incidence of parastomal hernia (p = 0.008, log-rank test). No specific complications associated with the procedure were observed. CONCLUSIONS: The results of the preliminary cohort study suggest that the novel procedure is safe and effective for the prevention of parastomal hernia.

Efficacy of cognitive behavioral therapy using self-check sheet for patients with nocturia in real-world clinical practice.

OBJECTIVES: We previously demonstrated the efficacy of cognitive behavioral therapy (CBT) using a self-check sheet for patients with nocturia in a randomized controlled study. Additionally, we investigated the efficacy of the intervention in real-world clinical practice. METHODS: Two hundred forty-three outpatients with complaint of nocturia who practiced CBT for 4 weeks using a self-check sheet were included in this trial, which took place from April 2021 to March 2022 in 20 institutions. RESULTS: Of the 243 patients, 215 who achieved 50% or more of the behavioral therapy tasks were included in the analysis. Their mean age ± SD was 77.1 ± 7.7. A significant decrease was observed in nighttime frequency at 4 weeks after CBT using self-check sheets (pre 3.3 and post 2.8, p < .001). Nighttime frequency was decreased one or more times and was defined as treatment success in 102 patients (47.4%). Pretreatment nighttime frequency in the treatment-success group was significantly higher than that of the failure group (3.5 ± 1.0 vs. 3.2 ± 1.0, p = .013). In multivariate logistic regression analysis, predictive factors of treatment success were pretreatment nocturnal frequency of four or more (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.01-3.30; p = .046) and the absence of diabetes mellitus (OR 3.08, 95% CI 1.34-7.06; p = .008). CONCLUSIONS: CBT using a self-check sheet requiring less time, less labor, less cost, and less medication is very beneficial for both patients and medical staff in real-world clinical practice.

Successful therapeutic strategy for a patient with obese end-stage kidney disease by simultaneous laparoscopic sleeve gastrectomy and implantation of a buried peritoneal dialysis catheter: A case report.

For morbidly obese patients with end-stage kidney disease (ESKD), there are often difficulties in accessing, implementing, and maintaining kidney replacement therapy (KRT). Although recent weight-loss surgery has the potential to solve these problems, its therapeutic strategy and appropriate perioperative management for morbidly obese patients with ESKD have not been established. Here, we describe the case history of a 47-year-old man diagnosed with ESKD due to obesity-related glomerulopathy with an uncorrected estimated glomerular filtration rate (eGFR) of 16.1 ml/min. He hoped for kidney transplantation but was not eligible due to his high body mass index (BMI) (36.9 kg/m2). Therefore, a combination strategy for both attaining weight loss and preparing for KRT was needed. We performed modified laparoscopic sleeve gastrectomy (LSG) combined with a buried catheter for peritoneal dialysis (PD), which resulted in reduction of multiple surgical invasions while simultaneously preparing for PD. After these operations, his body mass dropped to below 30.0 kg/m2, making him a candidate for kidney transplantation, while maintaining PD. Finally, he was able to have kidney transplantation with success. Collectively, in this case, our novel therapeutic approach was able to avoid multiple surgeries, to assist catheter insertion by laparoscopy, and to provide optimal KRT for an obese patient with ESKD. Simultaneous LSG and implantation of a buried PD catheter may be a promising strategy for morbidly obese patients with ESKD.

Are there differences in the characteristics of patients who respond to gemcitabine plus cisplatin chemotherapy and those who respond to pembrolizumab therapy for metastatic urothelial carcinoma? Multicenter retrospective study.

OBJECTIVES: To evaluate factors to predict overall survival of metastatic urothelial carcinoma patients treated with gemcitabine plus cisplatin chemotherapy or pembrolizumab therapy. METHODS: We retrospectively evaluated two metastatic urothelial carcinoma cohorts treated with (i) gemcitabine plus cisplatin or (ii) pembrolizumab. The gemcitabine plus cisplatin cohort was treated from December 2005 through December 2014 while the pembrolizumab cohort was treated from January 2018 through December 2020. Using multivariate analyses, we evaluated the risk factors for overall survival in each cohort and compared them. None of the gemcitabine plus cisplatin cohort patients were treated with pembrolizumab. All patients in the pembrolizumab cohort were treated with prior platinum-based chemotherapy. RESULTS: There were 184 patients in the gemcitabine plus cisplatin cohort and 91 in the pembrolizumab cohort. The mean follow-up periods were 714 and 284 days, respectively. In multivariate analysis, the risk factors for overall survival in the gemcitabine plus cisplatin cohort were liver metastasis, worse Eastern Cooperative Oncology Group performance status (1 or more), no primary site resection, and a high prognostic index (1 or more). In the pembrolizumab cohort, liver metastasis, bone metastasis, and worse Eastern Cooperative Oncology Group-performance status (1 or more), and high prognostic index (1 or more) were the risk factors for overall survival. In the pembrolizumab cohort, patients with a complete response or partial response during prior platinum-based chemotherapy had better overall survival with the following pembrolizumab treatment than those with stable or progressive disease (P = 0.004). CONCLUSIONS: Considering the similarity of these risk factors in two sequential treatments, it may be possible to predict the response to pembrolizumab according to the response to prior chemotherapy.

Heat shock protein 90 is a new potential target of anti-rejection therapy in allotransplantation.

The critical roles of heat shock protein 90 (HSP90) in immune reactions associated with viral infection and autoimmune disease are well known. To date, however, its roles in the alloimmune response and the immunosuppressive effect of HSP90 inhibitors in allotransplantation have remained unknown. The purpose of this study was to examine the therapeutic efficacy of the HSP90 inhibitor 17-DMAG in allotransplantation models. C57BL/6 (H-2b) and BALB/c (H-2d) mice were used as donors for and recipients of skin and heart transplantation, respectively. Treatment with 17-DMAG (daily i.p.) or a vehicle was initiated 3 days before transplantation. Immunological outcomes were assessed by histopathological examinations, flow cytometric analysis, quantitative RT-PCR, ELISA, ELISPOT assay, and MLR. 17-DMAG treatment significantly prolonged the survival of both skin and heart allografts. In 17-DMAG-treated mice, donor-reactive splenocytes producing IFN-γ were significantly reduced along with the intragraft mRNA expression level and serum concentration of IFN-γ. Intragraft mRNA expression of cytokines and chemokines associated with both innate and adaptive immunity was suppressed in 17-DMAG-treated group. MLR showed suppression of the donor-specific proliferation of CD4 + T and CD19 + B cells in the spleens of 17-DMAG-treated mice. 17-DMAG treatment also reduced the number of activated NK cells. Furthermore, the treatment lowered the titers of donor-specific antibodies in the serum and prolonged a second skin allograft in mice sensitized by previous skin transplantation. HSP90 inhibition by 17-DMAG can affect various immune responses, including innate immunity, adaptive immunity, and humoral immunity, suggesting its therapeutic potential against acute rejection in allotransplantation.

Significance of urinary liver-type fatty acid-binding protein in patients with normal renal function after undergoing intestinal urinary diversion: a preliminary study.

BACKGROUND: Liver-type fatty acid-binding protein (L-FABP) in urine is one of the early diagnostic biomarkers for acute and chronic kidney injuries. Although this protein is also identified in the intestine, there is no verified reference value for patients with intestinal urinary diversion (UD). The aim of the present study was to measure L-FABP values in such patients and compare them with the results for patients without UD. METHODS: Spot urine specimens were collected from 41 patients with UD and 50 subjects without UD with estimated glomerular filtration rates of over 60 ml/min/1.73 m2, and the L-FABP values were measured. The normal upper cutoff value in healthy subjects without UD is considered to be 7.24 µg/g Cr. First, the median values of the two groups were compared. Next, the subjects with negative proteinuria and without comorbidities associated with renal function were further selected and the median values of the groups were compared. RESULTS: The mean age was significantly higher in the UD group. The types of UD were ileal conduit (38 patients) and ileal neobladder (three patients). The median L-FABP value in the UD group was significantly higher than that in the non-diversion group (89.1 µg/g Cr vs. 2.0 µg/g Cr, p < 0.0001). After adjustment for their backgrounds, the median value remained higher in the UD group. CONCLUSIONS: L-FABP values in subjects with UD are higher than in those without UD. By this result, to develop a reference value in patients with intestinal UD population, further studies are required.

[Fever after Gemcitabine Administration is a Poor Prognostic Factor in Patients with Metastatic Urothelial Carcinoma : Multicenter Retrospective Study].

Gemcitabine (GEM) is currently a standard chemotherapeutic agent for metastatic urothelial carcinoma (mUC). Fever isknown to be an adverse effect of GEM ; however, itsincidence, etiology and clinical significance have not been evaluated. The objective of this study was to elucidate the characteristics and clinical significance of fever associated with GEM in patients with mUC receiving GEM plus cisplatin (GC) chemotherapy. Between 2005 and 2014, 184 patientswith mUC who received first-line GC therapy at 10 institutions were enrolled. GEM-associated fever (GEMAF) was defined as a body temperature ≥37.5ºC within 96 hours after administration of GEM with no evidence of specific conditions causing fever including infection. Clinical parametersbefore GC therapy were evaluated to determine predictorsof GEMAF. Furthermore, the impact of GEMAF on clinical outcomeswasals o evaluated. The median age was70 years and median follow-up was14.2 months. GEMAF wasobs erved in 44 patients (23.9%). In multivariate analysis, elevated C-reactive protein (CRP) before chemotherapy was an independent predictive factor for GEMAF (oddsratio 2.450, p＝0.041). There was a significant difference in progression-free survival (median 6.7 vs 8.0 months, p＝0.031) and cancer-specific survival (median 12.0 vs 15.8 months, p＝0.045) between patients with and without GEMAF. Results of this study suggest that GEMAF is a common adverse event of GC therapy for mUC and can be a poor prognostic factor. GEMAF may be associated with systemic inflammatory response induced by the tumor in patients with mUC.

[Necrotizing Fasciitis of the Right Thigh Caused by Emphysematous Pyelonephritis Due to a Staghorn Stone : A Case Report].

We report a rare case of necrotizing fasciitis in the thigh induced by emphysematous pyelonephritis due to a staghorn stone. A 60-year-old female was diagnosed with a staghorn stone in the right kidney at another clinic. We referred her to another hospital for indication of percutaneous nephrolithotripsy. However, she chose not to visit the hospital. One year and three months later, she was transported to the emergencyward of our hospital because of a high fever and right hip joint pain. The diagnosis of right emphysematous pyelonephritis with a perinephric abscess was diagnosed by computed tomography. Transurethral ureteral stenting and percutaneous abscess drainage were performed and her condition improved. However, two weeks after the initial treatment, she developed swelling and pain in the right thigh. Computed tomographyrevealed multiple areas of gas in the right thigh and urgent debridement was performed. Escherichia coli was isolated from the cultures of urine and debrided tissues. The patient received several treatments, including two additional debridements, negative pressure wound therapy, and antimicrobial chemotherapy. Three months after the first debridement, the open wound of the right thigh was completely closed. Necrotizing fasciitis in the thigh due to emphysematous pyelonephritis is very rare. A favorable outcome was obtained byprompt debridement and negative pressure wound therapyin this case.

Dynamic changes of bone metastasis predict bone-predominant status to benefit from radium-223 dichloride for patients with castration-resistant prostate cancer.

BACKGROUND: To best employ radium-223 dichloride (Ra-223) for patients with castration-resistant prostate cancer (CRPC) and bone metastasis, we investigated the bone-predominant status in patients treated with Ra-223. METHODS: We retrospectively evaluated 127 CRPC patients who underwent treatment with Ra-223. The patients were divided into three groups based on the types of dynamic changes of bone metastasis between diagnosis and just before Ra-223: (a) only known lesions; (b) de novo lesions; (c) new progressive lesions. We developed the risk assessment using predictive factors based on progression-free survival (PFS). RESULTS: During the median follow-up period of 10.4 months, the median PFS in the only known lesions group was 11.3 months compared to 8.1 months in the de novo lesions group and 5.1 months in the new progressive lesions group (P < .001). In multivariate analysis, the type of the new progressive lesions in bone metastasis (HR 1.45, 95% CI 1.13-1.66, P = .003), performance status of >1 (HR 1.74, 95% CI 1.04-2.89, P = .034), PSA value of >100 ng/mL (HR 1.59, 95% CI 1.02-2.50, P = .043), and PSA doubling time (PSADT) of <3 months (HR 1.53, 95% CI 1.11-2.03, P = .007) were independent unfavorable predictive factors for PFS. The risk assessment for PFS was highlighted when the type of dynamic changes of bone metastasis was combined with PSADT just before Ra-223 treatment. This was associated with non-bone metastasis progression, especially visceral metastasis, and overall survival. CONCLUSIONS: Risk assessment in combination with dynamic changes of bone metastasis and PSADT determines the bone-predominant metastasis type to benefit from Ra-223.

Modified Nephrometry Score With Body Mass Index More Accurately Predicts Ischemic Time in Transabdominal Laparoscopic Partial Nephrectomy for Small Renal Masses.

OBJECTIVE: To accurately predict the ischemic time (IT) and select candidates for transabdominal laparoscopic partial nephrectomy (LPN). METHODS: Transabdominal LPN was performed for 135 Japanese patients with renal masses <7 cm in diameter between 2009 and 2016 by a single surgeon in a single institute. The renal parenchymal sutures were done with a combination of felt, Hem-o-lok and Lapra-Ty. The original R.E.N.A.L. nephreometry score (NS) was modified as follows. In terms of the tumor size (R), 1, 2, and 3 points were given for ≤2.5, 2.5-4, and >4 cm, respectively. For tumor location (A), 1, 2, and 3 points were given for anterior, on the coronal plane, and posterior, respectively. RESULTS: The median IT was 24.6 minutes. Using the original NS, 64, 65, and 6 patients were categorized into low (4-6), moderate (7-9), and high (10-12) complexity, respectively. With the modified NS, 42, 75, and 18 patients were categorized into low (5-7), moderate (8-11), and high (12-15) complexity, respectively. Pearson's correlation coefficient (R) between the original NS and IT was 0.297, whereas the R was improved to 0.388 when the modified NS was employed. If the modified NS was low complexity, 95.2% achieved IT <30 minutes. Of them, none showed IT ≥30 minutes if the body mass index was <25 kg/m2. CONCLUSION: The modified NS had a better correlation to the IT than the original NS for patients with tumor sizes <7 cm who underwent transabdominal LPN. The modified NS with body mass index is a practical tool to select candidates for transabdominal LPN.

Neoadjuvant chemotherapy with gemcitabine and cisplatin for muscle-invasive bladder cancer: multicenter retrospective study.

OBJECTIVES: The aim of this study was to evaluate the efficacy of neoadjuvant gemcitabine and cisplatin (GC) therapy for muscle-invasive bladder cancer (MIBC). METHODS: We retrospectively evaluated patients who underwent neoadjuvant GC therapy followed by radical cystectomy from April 2009 through December 2015 in the Sapporo Medical University Urologic Consortium. The efficacy of neoadjuvant chemotherapy (NAC) was assessed based on the pathological T0 (pT0) rate in radical cystectomy specimens, and the recurrence-free survival, cause-specific survival and overall survival (OS) rates. To compare the oncological benefit of NC with GC to that of the methotrexate, vinblastine, adriamycin and cisplatin (MVAC) regimen, we also utilized historical clinical data of patients who were treated with MVAC as NAC followed by radical cystectomy in our institute from 1986 through 2010. RESULTS: Fifty-eight patients receiving neoadjuvant GC therapy and 74 receiving neoadjuvant MVAC were included. The pT0 achieving rates were comparable between the two groups (20.7% vs. 18.9%, P = 0.83). Neoadjuvant GC was associated with a better 2-year OS rate than neoadjuvant MVAC for clinical T2 disease (95.2% vs. 70.8%, P = 0.036). In contrast, in patients with clinical T3 or more advanced disease, neoadjuvant MVAC provided more pT0 (20.0% vs. 5.6%, P = 0.07) and better 2-year OS than neoadjuvant GC (71.1% vs. 55.0%, P = 0.142), although the difference did not reach statistical significance. CONCLUSIONS: Neoadjuvant GC had no inferiority in oncological outcomes to MVAC for MIBC.

Laparoscopic Surgery for Seminal Vesicle Cysts and Ureterocele with Urination Disorder: A Case Report of Zinner Syndrome.

Background: Zinner syndrome is defined as seminal vesicle cysts with ipsilateral renal agenesis and an ectopic ureter. Symptomatic cases are very rare. In this article, we present a laparoscopic approach for a case of Zinner syndrome. Case Presentation: The patient was a 21-year-old male with difficult urination. A right seminal vesicle cyst and right kidney agenesis associated with ureterocele were found on examination and he was diagnosed with Zinner syndrome. First, we performed transperineal puncture of the ureterocele because it closed the bladder neck during voiding. Although voiding symptoms temporarily improved, the ureterocele recurred soon and the urination disorder was reexacerbated. Next, we selected laparoscopic removal of the ureterocele and the seminal vesicle cyst. The procedure was performed with transperitoneal access using four trocars. Perioperative and postoperative complications were not observed, and micturition was satisfactory after surgery. Conclusion: Treatment for difficult urination because of Zinner syndrome is mostly selected puncture of the ureterocele or seminal vesicle cyst. However, some patients experience recurrence. The laparoscopic approach is minimally invasive and provides a satisfactory surgical field. Therefore, it should be considered the method of treatment for symptomatic Zinner syndrome.

[Clinical Evaluation of Diagnostic and Treatment Protocol of Idiopathic Retroperitoneal Fibrosis Incorporating Consideration of Possible IgG4-Related Disease].

About half of idiopathic retroperitoneal fibrosis might be classified as a IgG4-related disease, a newly characterized disease that is especially known to be sensitive to steroid therapy. We developed a new protocol for diagnosis and treatment of retroperitoneal fibrosis, which included aggressive diagnosis of IgG4- related disease. We retrospectively reviewed 22 cases with idiopathic retroperitoneal fibrosis that were diagnosed and treated according to our protocol. Of them, 10 patients (45.5%) had no evidence of IgG4- related disease (non-IgG4RD group), whereas 12 patients (54.5%) were diagnosed with IgG4-related disease (IgG4RD group). All patients received steroid therapy, and 13 patients (59.1%) underwent ureteral stenting or received prednisolone (PNS). There was no severe adverse event and planned steroid therapy was completed in all patients. In principle, maintenance steroid therapy was continued after induction therapy in the IgG4RD group, whereas steroid therapy was discontinued in the non-IgG4RD group. Regression of retroperitoneal plaque was achieved in all 22 patients. Four (57.1%) out of 7 patients and 3 (50.0%) out of 6 patients achieved freedom from ureteral stent or PNS in the non-IgG4RD group and IgG4RD group, respectively. All 3 patients with PNS became catheter-free after treatment, whereas only 4 (40.0%) of the 10 patients withureteral stent could become stent-free. Steroid therapy could be discontinued in 7 patients (70.0%) in the non-IgG4RD group. The results of this study suggest that similar efficacy of steroid therapy can be expected in the non-IgG4RD group and IgG4RD group.

[A Case of Renal Cell Carcinoma in a Crossed Fused Ectopic Kidney Treated with Partial Nephrectomy].

A 76-year-old man came to the department of gastrointestinal medicine with lower left abdominal discomfort and constipation. A crossed fused ectopic kidney with a renal tumor in the left upper pole of the kidney was detected by computed tomography. We performed left partial nephrectomy safely in spite of the complicated shape and complexity of the blood vessels. The pathological diagnosis was clear cell renal cell carcinoma, pT3a, with a negative surgical margin. After surgery, renal function was well preserved.

The discrepancy between serum creatinine and cystatin C can predict renal function after treatment for postrenal acute kidney injury: multicenter study and pooled data analysis.

BACKGROUND: Although serum cystatin C and creatinine are used as practical markers of renal function, the discrepancy between them in postrenal acute kidney injury (AKI) cases was reported. The aim of this study was to determine whether the preoperative serum cystatin C (pre-CysC) level could predict clinical outcomes after treatment in patients with postrenal AKI. METHODS: Patients who underwent urological interventions with postrenal AKI were enrolled in this prospective observational study. Associations among preoperative serum creatinine (pre-sCr), pre-CysC, and nadir postoperative serum creatinine (post-sCr) were evaluated. In addition, based on our results in combination with detailed data from the literature, a predictive equation for postoperative serum creatinine (post-sCr) was developed by simple regression analysis and validated using Bland-Altman plots. RESULTS: Finally, 19 patients were eligible for analysis in this study. The value calculated by subtracting pre-CysC (mg/L) from pre-sCr (mg/dl) had a strong correlation to the decrement of serum creatinine (r = 0.9508, p < 0.0001). We added the data of 16 patients obtained from the literature to our series, which were totally randomized into 2 groups, training set and validation set in a 2:1 ratio (n = 23 and 12, respectively) to develop and validate a predictive equation for post-sCr. The mean difference between the predictive and actual post-sCr, -0.68 mg/dl (95% CI -1.62 to 0.26) in the validation set was within the limits of agreement. CONCLUSION: We showed that the discrepancy between pre-sCr and pre-CysC could predict improvement of renal function after intervention in patients with postrenal AKI.

[INITIAL EXPERIENCE OF DENOSUMAB TREATMENT FOR OSTEOPOROSIS AFTER KIDNEY TRANSPLANTATION].

(Purpose) Denosumab is a fully human monoclonal antibody against RANKL, which was developed for treatment of osteoporosis and prevention of fractures. However, its efficacy in patients after kidney transplantation remains unclear. Treatment cases of denosumab for osteoporosis after kidney transplantation in our department were examined. (Methods) We retrospectively reviewed four patients with osteoporosis after kidney transplantation who were treated with denosmab in our hospital. Osteoporosis was diagnosed using the dual energy X-ray absorptiometry. (Results) After 12 months, bone mineral density of total lumbar spine and femoral neck increased by 5.5% and 3.0%, respectively. Biomarkers of bone turnover (Tartrate-resistant acid phosphatase-5b and Intact-procollagen type 1 N-terminal propeptide) markedly decreased in the first one month and remained at the low level thereafter. Obvious adverse event was not recognized and graft function was stable in all cases. (Conclusion) Denosumab was considered to be safe and effective in patients who underwent kidney transplantation.

Heat Shock Protein 90α Is a Potential Serological Biomarker of Acute Rejection after Renal Transplantation.

BACKGROUND: Heat shock protein 90 (HSP90), a molecular chaperone associated with the activation of client proteins, was recently reported to play an important role in immunologic reactions. To date, the role of HSP90 in solid organ transplantations has remained unknown. The aim of this study was to evaluate the relationship between serum HSP90α levels and acute allograft rejection after organ and tissue transplantation using serum samples from kidney allograft recipients, an in vitro antibody-mediated rejection model, and a murine skin transplantation. RESULTS: Serum HSP90α levels were significantly higher in kidney recipients at the time of acute rejection (AR) than in those with no evidence of rejection. In most cases with AR, serum HSP90 decreased to baseline after the treatment. On the other hand, serum HSP90α was not elevated as much in patients with chronic rejection, calcineurin inhibitor nephrotoxicity, or BK virus nephropathy as in AR patients. In vitro study showed that HSP90α concentration in the supernatant was significantly higher in the supernatant of human aortic endothelial cells cocultured with specific anti-HLA IgG under complement attack than in that of cells cocultured with nonspecific IgG. In mice receiving skin transplantation, serum HSP90α was elevated when the first graft was rejected and the level further increased during more severe rejection of the second graft. CONCLUSIONS: The results suggest that HSP90α is released into the serum by cell damage due to AR in organ and tissue transplantation, and it is potentially a new biomarker to help detect AR in kidney recipients.

Serum cystatin C can be used as a marker of renal function even in patients with intestinal urinary diversion.

OBJECTIVE: Recently, serum cystatin C (CysC) has been used as a novel marker of renal function. However, there is a lack of data on CysC levels in patients with intestinal urinary diversion (UD). Here we report CysC levels in such patients. METHODS: We prospectively observed 38 patients who were diagnosed with bladder cancer and subsequently treated with radical cystectomy and UD at our institution in 2012 and 2013. Serum creatinine (sCr) and CysC were obtained optionally at the same time at least 1 month after radical cystectomy and UD. RESULTS: The median CysC and sCr concentrations were 1.12 mg/L (range 0.75-2.47 mg/L) and 0.99 mg/dL (range 0.61-2.22 mg/dL), respectively. The median estimated concentrations of glomerular filtration rate (GFR) based on CysC (eGFRcys) and GFR based on creatinine (eGFRcreat) were 61.08 mL/min/1.73 m2 (range 22.64-99.89 mL/min/1.73 m2) and 58.01 mL/min/1.73 m2 (range 23.48-91.82 mL/min/1.73 m2), respectively. CysC had a significant correlation with sCr (r = 0.8607, p < 0.0001) and eGFRcreat (r = -0.8993, p < 0.0001). eGFRcys also had a significant correlation with eGFRcreat (r = 0.8104, p < 0.0001). CONCLUSION: The correlation between CysC and sCr was strong and the correlation coefficient was equivalent to that in patients without UD. The results suggest that CysC is not affected by UD and can be used as a marker of renal function similarly to sCr in patients with UD.