Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation.

The long-term effect of rituximab and splenectomy on de novo HLA antibody production and chronic antibody-mediated rejection after renal transplantation is uncertain. In order to gain insight on this, we studied 92 ABO-incompatible and 228 ABO-identical/compatible consecutive renal transplant patients and determined their de novo HLA antibody production and graft outcome. Patients with pretransplant donor-specific antibodies had been excluded. ABO-incompatible transplants included 30 recipients treated with rituximab, 51 by splenectomy, or 11 with neither, due to low anti-A or -B antibody titer. Graft survival in ABO-identical/compatible patients (97.7% at 5 years) was significantly higher than in ABO-incompatible (87.0% at 5 years), rituximab (96.7% at 3 years), or splenectomy (85.7% at 5 years) patients. Only four patients had clinical chronic antibody-mediated rejection (two each identical/compatible and incompatible). There was no significant difference in prevalence of de novo HLA antibody, including donor-specific and nondonor-specific antibodies among ABO-identical/compatible patients (13.9%), patients receiving rituximab (14.3%) or splenectomy (13.2%), or among those receiving cyclosporine, tacrolimus, mycophenolate mofetil, mizoribine, and everolimus. Renal function remained stable in most recipients with de novo HLA antibody. Thus, neither pretransplant splenectomy nor rituximab treatment has an inhibitory effect on de novo HLA antibody production during medium-term follow-up. Further study on long-term effects is needed.

Low skeletal muscle mass index is independently associated with low bone mineral density in kidney transplant recipients: a retrospective observational cohort study.

BACKGROUND: Osteoporosis and osteopenia are more frequent in patients who have received kidney transplants than in healthy individuals. Although osteoporosis and sarcopenia are closely related, only few studies have considered them in the post-transplantation period. We aimed to investigate the relationship between lower bone mineral density and skeletal muscle in kidney transplant recipients. METHODS: We included 371 patients in the maintenance phase of kidney transplantation (> 6 months after transplantation) followed-up at our institution from January to December 2019. The primary endpoint was the association between bone mineral density and skeletal muscle mass index. As secondary endpoints, in addition to skeletal muscle mass index, we investigated other factors associated with low bone mineral density, including kidney function and 25-hydroxy vitamin D (25(OH)D) concentration. Considering the possibility that factors affecting bone mineral density differ between men and women, we explored these factors separately for both sexes. RESULTS: Of the 371 participants, 243 (65.4%) were men. The median age and time after transplantation were 52 and 14 years, respectively. Univariate analysis showed that age, female sex, time since transplantation, cystatin C-based estimated glomerular filtration rate (eGFRcysC), 25(OH)D, and skeletal muscle mass index were associated with bone mineral density. Multivariate analysis showed associations of bone mineral density with eGFRcysC, 25(OH)D, and skeletal muscle mass index. Multivariate analysis by sex showed significant associations with eGFRcysC, hemoglobin, and skeletal muscle mass index in men and with age, eGFRcysC, albumin, and skeletal muscle mass index in women. Bone mineral density was not associated with history of dialysis prior to transplantation or time since transplantation. CONCLUSIONS: In kidney transplant recipients, an independent association between lower bone mineral density and skeletal muscle mass index was observed in both sexes.

Human RP105 monoclonal antibody enhances antigen-specific antibody production in unique culture conditions.

Detecting antibodies, particularly those targeting donor human leukocyte antigens in organ transplantation and self-antigens in autoimmune diseases, is crucial for diagnosis and therapy. Radioprotective 105 (RP105), a Toll-like receptor family protein, is expressed in immune-competent cells, such as B cells. Studies in mice have shown that the anti-mouse RP105 antibody strongly activates B cells and triggers an adjuvant effect against viral infections. However, the anti-human RP105 antibody (ɑhRP105) weakly activates human B cells. This study established new culture conditions under, which human B cells are strongly activated by the ɑhRP105. When combined with CpGDNA, specific antibody production against blood group carbohydrates, ɑGal, and SARS-CoV-2 was successfully detected in human B cell cultures. Furthermore, comprehensive analysis using liquid chromatography-electrospray ionization tandem mass spectrometry, single-cell RNA sequencing, and quantitative real-time PCR revealed that ɑhRP105 triggered a different activation stimulus compared to CpGDNA. These findings could help identify antibody-producing B cells in cases of transplant rejection and autoimmune diseases.

[A case of renal salt wasting syndrome progressing to severe hyponatremia after gemcitabine-cisplatin chemotherapy].

Renal impairment with a decreased glomerular filtration rate is a classical nephrotoxicity associated with cisplatin (CDDP). Renal salt wasting syndrome (RSWS), which is characterized by water and salt wasting, is a rare nephrotoxicity associated with CDDP. This syndrome shares many similarities with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Thus, it is important to differentiate between RSWS and SIADH because the treatment of one affects the pathogenesis of the other. Here, we report a case of RSWS after chemotherapy with CDDP. A 72-year-old man with bladder urothelial carcinoma (cT2N0M0) was admitted to our hospital for the first cycle of neoadjuvant chemotherapy with CDDP and gemcitabine. He was administered intravenous fluids on day 2 before chemotherapy. Five days later, he developed nausea, dysorexia, delirium, hyponatremia (serum sodium level 115 mEq/l), and renal dysfunction. Thus, we administered a normal saline infusion. Over the next 6 days, his serum sodium level increased to 137 mEq/l, and we stopped normal saline infusion. Three days after discontinuation of saline infusion, his serum sodium level again decreased to 128 mEq/l, and the next day, his systolic blood pressure dropped gradually between 70 and 80 mmHg. Therefore, we resumed the normal saline infusion, and after 3 days, his serum sodium level increased to 135 mEq/l and systolic blood pressure ranged between 110 and 130 mmHg. On the basis of dehydration and high urinary sodium excretion at the onset of chemotherapy, we diagnosed this clinical condition as RSWS. We abandoned neo-adjuvant chemotherapy, and performed total cystectomy and ileal conduit. Since 4 months after surgery, he has been free from recurrence and metastasis.

[A case of micropapillary bladder carcinoma].

A case of urothelial carcinoma containing micropapillary variant in the urinary bladder is reported. The micropapillary bladder carcinoma isa rare variant of urothelial carcinoma and has an aggressive clinical course. A 45-year-old man complained of hematuria in October, 2009. He visited a hospital and was diagnosed with a bladder tumor. Transurethral resection of the bladder tumor was performed at the hospital. The transurethral resection demonstrated poorly differentiated adenocarcinoma invading the bladder muscle layer. Then he consulted our hospital. Our pathologist diagnosed the case as micropapillary variant of urothelial carcinoma in the urinary bladder. Accordingly, radical cystectomy and pelvic lymph nodes dissection were performed. After the operation, he received three courses of gemcitabine and cisplatin as adjuvant chemotherapy. The patient remains free of tumor recurrence and metastasis for 28 months after the cystectomy.

[A case of interstitial pneumonia during gemcitabine and cisplatin chemotherapy for locally advanced bladder cancer].

A 76-year-old woman received chemotherapy with gemcitabine and cisplatin (GC therapy) for local advanced bladder cancer. She suffered from dyspnea on day 19 during the first course of GC therapy. Both chest X-ray and computed tomography (CT) images revealed diffuse bilateral interstitial infiltrates. She was diagnosed as having drug-induced interstitial pneumonia. We identified gemcitabine as the causative agent based on the results of examinations (CT, X-ray, KL-6 level, drug lymphocyte stimulation test (DLST)). After three months of steroid therapy, her interstitial pneumonia was completely resolved on CT scans. Although gemcitabine-induced interstitial pneumonia is a rare adverse event, it should be considered a severe complication because delayed diagnosis and treatment can lead to a fatal outcome. Thus, early detection of drug-induced interstitial pneumonia is extremely important during GC therapy.

Improved detection of donor-specific HLA-class II antibody in kidney transplant recipients by modified immunocomplex capture fluorescence analysis.

Immunocomplex capture fluorescence analysis (ICFA) which basic principle is same as Luminex crossmatch (LXM), could detect donor-specific HLA antibody (DSA). The advantages of ICFA are (i) detection of DSA and (ii) no requirement of viable cells over the flow cytometry crossmatch (FCXM). However, FCXM has been widely used because of its higher sensitivity than ICFA, in particular HLA-class II antibody detection. In this study the accuracy of DSA detection against HLA-class II was investigated by modifying the original method of ICFA. Increment of the sensitivity was found when purified peripheral blood mononuclear cells (PBMCs) were used instead of whole blood. An ICFA-PBMC in addition to FCXM-T/B was conducted for 118 patients before kidney transplantation and 13 patients with de novo DSA against HLA-class II after transplantation. Significantly positive correlation was observed between the values of ICFA-PBMC and DSA mean fluorescence intensity (MFI) targeting class II (p < 0.0001). When the cutoff level of 1.4 was determined by receiver operating characteristic curve analysis, the average DSA MFI was found to be significantly higher in the ICFA-PBMC (class II) positive group comparing to that in the negative group (12,217 vs 3885, p = 0.0027). ICFA-PBMC and optimized cutoff level could provide valid information in cases of suspected DSA.

[A case of complicated perioperative management of radical nephrectomy in a patient with a drug-eluting stent].

Drug-eluting stents (DES) are commonly used for coronary artery disease and patients with DES require antiplatelet therapy because of the risk of late stent thrombosis. Accordingly problems can occur in the perioperative period due to late thrombosis of a stent after discontinuation of antiplatelet therapy before surgery. A 64-year-old man was diagnosed as having a right renal tumor (T1aN0M0) and his performance status was 4. Three years earlier, a DES had been placed in a coronary artery and he was taking aspirin plus ticlopidine. These drugs were stopped at 7 days before surgery and we started heparin (15,000 U/day). Heparin was continued during and after radical nephrectomy. Although operative blood loss was only 178 ml, the amount of bleeding within 5 hours after surgery was 1,620 ml. The wound was re-opened, but there was no obvious bleeding source, so oozing from the muscle was controlled. His blood pressure dropped and cardiac arrest occurred at 22 hours after re-operation, but he was resuscitated with blood transfusion and the bleeding stopped after the dose of heparin was reduced. Three days after the operation, antiplatelet therapy was re-started and heparin was ceased at 10 days after surgery. The blood clot in the right retroperitoneal space formed an abscess at 28 days after radical nephrectomy. After drainage, the retroperitoneal space was washed twice a day for about 40 days. The wound healed, and he currently has no evidence of recurrence or metastasis and has no cardiac sequelae.

[A case report of transurethral resection of eroding urethral mesh after a tension-free vaginal tape procedure].

A 72-year-old woman presented with lower urinary tract symptoms (incomplete voiding, voiding pain, and gross hematuria) 2 years after a tension-free vaginal tape (TVT) procedure for stress urinary incontinence. Cystoscopy revealed erosion of the urethra associated with a urethral stone attached to a polypropylene mesh. We performed transurethral resection of the polypropylene mesh and transurethral lithotripsy. After removal of the mesh, she had stress urinary incontinence but her symptoms resolved. Urethral erosion is a rare complication of TVT, and the method of handling the intrusive mesh has not been standardized. Transurethral endoscopic resection of the eroding mesh is a minimally invasive and successful procedure that should be considered for the treatment of this complication resulting from TVT.

[Clinical importance of guideline for decontamination of endoscopes in urological field: verification of 3 processes].

UNLABELLED: Clinical guideline for decontamination of endoscopes in urological field has not been provided, although endoscopic examination should be done in aseptic circumstance. MATERIAL AND METHOD: From decontamination processes, following 3 points were selected for verification: 1) Volume of residual water in flexible scope after rinsing, estimated by weight change. 2) Concentration of eluted disinfectant from flexible scope after standard rinsing procedure for gastrointestinal endoscope. 3) Observation of possible damage of telescope, caused by repeat autoclaving. RESULTS: Wet condition of flexible scope could be suspected in 60 hours in room temperature. Eluted disinfectants were detected, but in harmless level. Repeated autoclaving merely caused minor damage, which does not interfere clinical use. CONCLUSION: We obtained a couple of evidences with cautions in decontamination processes for endoscopes. Urgent requirement of standardization in this field should be discussed widely.