Taro Iguchi

Desensitization Protocol in Highly HLA-Sensitized and ABO-Incompatible High Titer Kidney Transplantation

BACKGROUND A positive crossmatch indicates the presence of donor-specific alloantibodies and is associated with a graft loss rate of >80%; anti-ABO blood group antibodies develop in response to exposure to foreign blood groups, resulting in immediate graft loss. However, a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation has not yet been established. METHODS We treated 6 patients with high (≥1:512) anti-A/B antibody titers and 2 highly HLA-sensitized patients. Our immunosuppression protocol was initiated 1 month before surgery and included mycophenolate mofetil (1 g/d) and/or low-dose steroid (methylprednisolone 8 mg/d). Two doses of the anti-CD20 antibody rituximab (150 mg/m(2)) were administered 2 weeks before and on the day of transplantation. We performed antibody removal with 6-12 sessions of plasmapheresis (plasma exchange or double-filtration plasmapheresis) before transplantation. Splenectomy was also performed on the day of transplantation. Postoperative immunosuppression followed the same regimen as ABO-compatible cases, in which calcineurin inhibitors were initiated 3 days before transplantation, combined with 2 doses of basiliximab. RESULTS Of the 8 patients, 7 subsequently underwent successful living-donor kidney transplantation. Follow-up of our recipients showed that the patient and graft survival rates were 100%. Acute cellular rejection and antibody-mediated rejection episodes occurred in 1 of the 7 recipients. CONCLUSIONS These findings suggest that our immunosuppression regimen consisting of rituximab infusions, splenectomy, plasmapheresis, and pharmacologic immunosuppression may prove to be effective as a desensitization protocol for highly HLA-sensitized and ABO-incompatible high-titer kidney transplantation.

Edaravone inhibits acute renal injury and cyst formation in cisplatin-treated rat kidney.

Background: Although cis-diamminedichloroplatinum (II) (cisplatin) is an effective anticancer agent, its clinical use is highly limited predominantly due to its adverse effects on renal functions. The present work examined the therapeutic potential of edaravone, a free radical scavenger, for inhibiting cisplatin-induced renal injury. Methods: Edaravone, 3-methyl-1-phenyl-pyrazolin-5-one, was administrated intravenously at a dose of 30 mg/kg of body weight to male Wistar rats (200–220 g). After 30 min, cisplatin was injected intraperitoneally at a dose of 5 mg/kg of body weight. At the indicated times after the treatment, functions and histological changes of the kidney were analyzed. To test the therapeutic potential of edaravone in chemotherapy, its effect on the anticancer action of cisplatin was examined in ascites cancer-bearing rats. Results: We found that cisplatin rapidly impaired the respiratory function and DNA of mitochondria in renal proximal tubules, thereby inducing apoptosis of tubular epithelial cells within a few days and chronic renal dysfunction associated with multiple cysts one-year after the administration. Administration of edaravone inhibited the cisplatin-induced acute injury of mitochondria and their DNA and renal epithelial cell apoptosis as well as the occurrence of chronic renal dysfunction and multiple cyst formation. The anticancer effect of cisplatin remained unaffected by intravenous administrating of edaravone. Conclusions: These results indicate that edaravone may have therapeutic potential for inhibiting the acute and chronic injury of the kidney induced by cisplatin.

Clinical outcome of ABO-incompatible living unrelated donor kidney transplantation.

Background: ABO-incompatible living unrelated donor kidney transplantation is an immunologically high-risk procedure, but few reports have been made on the outcomes of these transplants. Patients and Methods: We analyzed 12 kidney transplants using ABO-incompatible living-unrelated donors performed at our institution between January 1999 and December 2007, focusing on the immunosuppressive protocols, complications and graft survivals. Results: Patient and graft survival rates were 100%. One patient experienced antibody-mediated rejection and intractable acute cellular rejection, one had antibody-mediated rejection and one had acute cellular rejection, but their grafts survived after intensive immunosuppressive treatment. There were no severe complications among the recipients. Conclusions: In ABO-incompatible living unrelated donor kidney transplantation, severe rejections may occur due to ABO incompatibility and poor histocompatibility. Therefore, appropriate desensitization, immunosuppression and recipient care are needed for a successful transplant. Recent significant improvements in outcomes indicate that it has become a viable treatment option, given the lack of available donor organs.

Association between chronic kidney disease and small residual urine volumes in patients with benign prostatic hyperplasia

Aim:  It has been well described that large residual urine volumes (≥300 mL) affect renal function in advanced benign prostatic hyperplasia (BPH). However, it is not clear whether small residual urine volumes (<100 mL) are related to renal function. The present study was performed to examine the association between chronic kidney disease (CKD) and the post‐void residual urine volume (PVR) in BPH patients.

Low-grade albuminuria reduction with angiotensin II type 1 receptor blocker in renal transplant recipients.

BACKGROUND Microalbuminuria, defined as urine albumin to urine creatinine ratio of 30 to <300 mg/g, is an established risk factor for cardiovascular morbidity and mortality in the general population. Low-grade albuminuria (<30 mg/g) is considered a marker for subclinical vascular damage that predisposes to future cardiovascular diseases and death. Lowering urinary albumin excretion reduces the risk of cardiovascular disease. Our study was designed to evaluate the influence of angiotensin II type 1 receptor blocker (ARB) in normotensive renal transplant recipients with low-grade albuminuria. PATIENTS AND METHODS Our 6-month prospective observation study used a randomized control and open-label design as we examined the effects of an ARB (valsartan) on blood pressure, urinary albumin excretion, hematocrit, serum potassium and estimated glomerular filtration rate (eGFR) in normotensive recipients with allografts of more than 1 year. A total of 35 renal transplant recipients were enrolled in this study. Patients were randomly assigned to 2 groups: ARB group (n=18), receiving 40-80 mg valsartan daily for 6 months, and the control group (n=17). RESULTS In the ARB group, urine albumin excretion was significantly reduced from 25.9 ± 19.1 mg/g to 12.0 ± 9.6 mg/g at 6 months after administration. eGFR decreased slightly at 6 months after administration. However, no patients undergoing treatment for adverse effects required discontinuation of ARB. CONCLUSIONS This study reveals that ARB is safe and reduces low-grade albuminuria in normotensive renal transplant recipients. Thus, early treatment of ARB in recipients with low-grade albuminuria may prevent cardiovascular disease after renal transplantation.

Association of MnSOD AA Genotype with the Progression of Prostate Cancer.

Purpose To investigate whether manganese superoxide dismutase (MnSOD) genetic polymorphism is associated with the clinical significance of prostate cancer. Materials and Methods Prostates were obtained from 194 deceased men 45 years or older who did not have a history of prostate cancer. Serial sections and histological examinations of the prostate were performed. The MnSOD genotypes of the specimens were determined by polymerase chain reaction restriction fragment length polymorphism analysis. Results Of the 194 men, 31 and 26 had clinically insignificant and significant prostate cancer. Clinically significant cancer comprised 29% and 58% of the cancers in men <70 and >70 years old, respectively. The age-specific proportion of significant cancer significantly increased with the advance of age (p<0.001). MnSOD AA, as compared with the other genotypes (VA and VV together), was associated with significant prostate cancer across all ages, odds ratio (OR) 2.34, 95% confidence interval (CI) 0.99-5.49, and in men older than 69 years (OR 4.89, 95% CI 1.51-15.8), but not in men younger than 70 years. The genotype was not associated with clinically insignificant cancer regardless of age. The comparison between significant and insignificant cancer, the OR (95% CI) for MnSOD AA was 5.04 (1.05-24.2) (sensitivity 0.57, specificity 0.78, positive predictive value 0.78) in men older than 69 years. Conclusions MnSOD polymorphism is strongly associated with the clinical significance of prostate cancer in men older than 69 years, but not in men younger than 70 years suggesting that oxidative stress may be involved in the progression of the disease. MnSOD may be a clinically useful marker to predict the potential of progression of prostate cancer.

Glucose intolerance in renal transplant recipients is associated with increased urinary albumin excretion

OBJECTIVE New-onset diabetes mellitus after transplantation (NODAT) is a common and serious complication of renal transplantation, and its incidence is known to be increased by immunosuppressive therapy. It has been reported that urinary albumin excretion is a potent predictor of NODAT. This study was conducted to investigate the relationship between glucose intolerance and urinary albumin excretion in renal transplant recipients. METHODS A cross-sectional study of 101 renal transplant recipients without prior evidence of diabetes was conducted. All patients underwent an oral glucose tolerance test with 75g of glucose. RESULTS The patients with glucose intolerance had a significantly greater urinary albumin excretion than those with normal glucose tolerance. Multivariate logistic regression analysis revealed that the increase of urinary albumin excretion correlated significantly with the homeostasis model assessment of insulin resistance and systolic pressure. CONCLUSION These results indicated that glucose intolerance is associated with increased albuminuria in renal transplant recipients. The rise in insulin resistance and systolic pressure may contribute to the increase of urinary albumin excretion in renal transplant recipients.

A Case of Metastatic Urachal Carcinoma Treated With FOLFIRI (irinotecan and 5-Fluorouracil/leucovorin) Plus Bevacizumab

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

Galectin 9 and PINCH, novel immunotherapy targets of renal cell carcinoma: a rationale to find potential tumour antigens and the resulting cytotoxic T lymphocytes induced by the derived peptides

To analyse and then generalize the mechanism by which partial or complete response is achieved among a limited number of patients with metastatic renal cell carcinoma (RCC) treated with interferon or interleukin‐2.

A case of scrotal neurofibroma originating from subcutaneous neural tissue

A 58-year-old man visited Osaka City University Hospital, Osaka, Japan, complaining of a left scrotal mass, which had been growing gradually for three years. The mass was 12 cm, soft, elastic, non-tender, mobile and nontransilluminable in the left scrotum (Fig. 1a). Ultrasound examination showed a heterogeneous mass in the left scrotum, which was separated from the left testis. The left testis was a normal size and consistency. Pelvic computed tomography scan and magnetic resonance imaging showed the mass to be intrascrotal and extratesticular (Fig. 1b). The overall clinical impression was a benign tumor and the tumor was surgically resected. The tumor was rich in blood vessels. When the scrotum was opened, the left testis was apparently not involved with the tumor, and it appeared that the tumor arose from the subcutaneous tissue of the scrotum. The tumor measured 12 ¥ 8 cm and weighed 460 g. The section was light-yellow, solid , elastic tissue and its capsule was unclear (Fig. 1c). In pathological findings, hematoxylin–eosin staining showed interlacing bundles of loosely arranged spindle shaped cells with oval, waving and tapering nuclei separated by collagen strands (Fig. 1d). Immunohistochemical staining showed that the tumor cells were diffusely positive in S-100 protein, which is commonly seen in supporting cells of the central or peripheral nervous tissue (Fig. 1e). The pathological diagnosis was non-plexiform neurofibroma. Neurofibroma is a benign tumor of the nerve sheath, which originates from Schwann cells. The tumor can be solitary or multiple and the multiple neurofibromas are usually classified as a neurofibromatosis. Most cases of neurofibromas are associated with neurofibromatosis type 1, known as von Recklinghausen disease. Although tumors can develop anywhere within the central or peripheral nervous system, it is rare for them to be localized in the scrotum. In the present case, the tumor originated from subcutaneous neural tissue. Thirteen cases of neurofibromas found in the scrotum have been reported and the standard treatment was surgical resection. In three cases, they might have been associated with von Recklinghausen disease because the neurofibromas were involved in pelvic structures such as the bladder, penis, urethra, perineum and abdominal wall. In these cases, additional treatments such as urethroplasty, penile and scrotum reconstruction or urinary diversion were necessary. Because von Recklinghausen disease is related to sarcomatous degeneration such as rhabdomyosarcoma, Wilms’ tumor, neurofibrosarcoma and non-lymphocytic leukemia, it is important to diagnose solitary neurofibroma