Kazuki Kitajima

Therapeutic Effects of MicroRNA-582-5p and -3p on the Inhibition of Bladder Cancer Progression

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.

ABO Blood Type Incompatible Kidney Transplantation Without Splenectomy Prepared With Plasma Exchange and Rituximab

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.

Irreversible immunoexpression of matrix metalloproteinase-9 in proximal tubular epithelium of renal allografts with acute rejection.

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.

Urinary Tract Reconstruction Using Uretero-Ureteral End-To-Side Anastomosis in Kidney Transplant Recipients

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.

Autologous blood transfusion for kidney transplant recipients.

Autologous blood transfusion (ABT) is rarely employed in patients with end-stage renal disease (ESRD); these patients are usually anemic. Since 1998, we have attempted ABT for ESRD patients undergoing living-related kidney transplantation. Among 20 patients enrolled in this study the preoperative hemoglobin and hematocrit levels were 10.0 +/- 1.2 mg/dL (range, 8.1-11.7) and 30.0 +/- 3.7% (range, 24.7-34.3), respectively. Blood volume collected on each occasion was 235.7 +/- 57.7 mL (range, 200-400), and the number of blood collections was 2.45 +/- 0.9 (range, 1-4). Total collected volume was 567.5 +/- 157.5 mL (range, 400-800). Symptomatic hypotension was seen in two patients, but vital signs recovered spontaneously. No other problems related to blood collection were observed. Allogeneic transfusion was need in only one patient (5%). ABT was safe and efficacious in ESRD patients scheduled for living-related kidney transplantation.

Solitary Fibrous Tumor of the Kidney Developing Local Recurrence.

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.

Asymptomatic post-transplant lymphoproliferative disorder diagnosed at one year protocol renal allograft biopsy.

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.

Follow-up rates of living kidney donor in Japan: A single center study.

Long-term follow-up of kidney donors is needed not only for the individual donors benefit but also to establish analyzable databases to improve the selection criteria for future donors. We collected data including the date of transplantation, the date of the last follow-up, donors age, sex, their relationship to the recipient, renal function, proteinuria, and the prevalence of hypertension. Of 124 donors, 52 donors were not being followed up. The mean duration of follow-up was 4.3 ± 3.6 years. Follow-up rates were 83.9%, 74.6%, and 59.2% at 1 year, 2 years, and 5 years postdonation, respectively. Of those not being followed up, 75% dropped out. Follow-up rates did not differ between parent and spouse donors 5 years (57.1% vs. 71.4%; P = 0.4) postdonation. Similarly, follow-up rates at 5 years did not differ between donors aged 60 years or older and those younger than 60 (57.5% vs. 61.3%; P = 0.6). Of 72 donors being followed up, 75.0% had estimated glomerular filtration rate of <60 mL/min/1.73 m2, 8.3% had proteinuria, and 41.7% had hypertension requiring medication. There is a limitation to the endeavor of each transplant center to follow-up all their donors. Long-term donor follow-up in Japan requires a national registration system and mandates transplant center participation.