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ABSTRACT: Interleukin-6, a pleiotropic cytokine that functions in both innate and adaptive immune responses, has been implicated in allograft rejection. We analyzed the efficacy of anti interleukin-6 receptor monoclonal antibody in delaying allograft rejection in a murine model of a heart.
To investigate the role of interleukin-6 receptor signal transduction in acute and chronic allograft rejection, we blocked interleukin-6 receptor signaling to suppress the alloimmune response in C57BL/6 recipients of BALB/c cardiac allografts.
Administration of a high-dose α-interleukin-6 receptor monoclonal antibody prevented the intragraft infiltration of inflammatory cells and lymphocytes and prolonged allograft survival during the peritransplant period. However, all allografts were rejected by 23.5 days after transplant. In contrast, cardiac allograft recipients treated with a cytotoxic T-lymphocyte antigen 4-immunoglobulin plus continued administration of low-dose α-interleukin-6 receptor monoclonal antibody showed long-term graft survival compared with cytotoxic T-lymphocyte antigen 4-immunoglobulin monotherapy. A histologic analysis revealed that graft fibrosis was prevented in cytotoxic T-lymphocyte antigen 4-immunoglobulin plus high-dose α-interleukin-6 receptor monoclonal antibody group, but not in the cytotoxic T-lymphocyte antigen 4-immunoglobulin alone group. This suggests that deterioration of graft function associated with chronic rejection could be prevented by blocking interleukin-6 receptor signaling.
Disruption of interleukin-6 receptor signaling is an effective strategy for modulating proinflammatory immune responses and preventing chronic rejection.
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 07/2012; 10(4):375-85.
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ABSTRACT: We present a kidney transplantation patient who developed rhabdomyolysis. The patient was initially immunosuppressed with tacrolimus, mycophenolate mofetil, steroids, and chimeric CD25 monoclonal antibody. He complained of severe precordial and appendicular pain on 25th day after the operation. The patient developed rhabdomyolysis manifested as a rise in serum creatine phosphkinase (CPK) and elevation of urinary myoglobulin at approximately the same time as his symptoms. Although he was switched from tacrolimus to cyclosporine (CYA), his muscle pain and levels of serum CPK did not improve. However, dividing the daily total amount of the calcinuerin inhibitors into more frequent doses in order to reach lower serum levels resolved the rhabdomyolysis. Therefore, we conclude that his rhabdomyolysis might be a dose-related problem of calcineurin inhibitor.
Saudi journal of kidney diseases and transplantation: an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia 05/2011; 22(3):521-4.
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ABSTRACT: A new protocol for ABO-incompatible (ABO-i) kidney transplantation including rituximab was introduced in January 2005 in our institute. This study reviewed the results and evaluated the use of low-dose rituximab in ABO-i kidney transplantation.
Seventy-four de novo ABO-i kidney transplantations were performed at Tokyo Women's Medical University between January 2005 and August 2010. The immunosuppressive protocol was consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone. All the patients received induction therapy with basiliximab. The pre-conditioning protocol included double-filtration plasmapheresis and a single dose of rituximab. A dose of 500 mg/body rituximab was initially employed and yielded excellent results (Group I, n = 24). Afterward, the dose of rituximab was reduced to 200 mg/body in January 2007 (Group II, n = 50).
Seventy-four de novo ABO-i recipients were treated with this protocol, and all patients underwent kidney transplantation successfully. Effective elimination of the peripheral blood CD19 cells was observed in both groups. However, the peripheral blood CD19 levels were still low in both groups at 24 months after treatment.
The patients in Group II showed excellent results similar to Group I. These results suggest that the low dose of rituximab (200 mg/body) is the sufficient dose in ABO-i kidney transplantation.
Clinical Transplantation 12/2010; 25(6):878-84. · 1.67 Impact Factor
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ABSTRACT: Laparoscopic living donor nephrectomy (LLDN) is a standard method of donor nephrectomy. Most cases of LLDN are transperitoneal. Retroperitoneal access, however, implies a direct approach to the retroperitoneal organs without interfering with any of them. Since 2001, we have been trying to establish the technique of retroperitoneoscopic live donor nephrectomy (RPLDN). To assess the safety, feasibility, and usefulness of RPLDN, we reviewed the experience with this technique at our institution.
From July 2001 to March 2009, 425 patients underwent live donor renal transplantation at our institution with allografts procured by RPLDN. Study variables included operative time, time to retrieval of the kidney, blood loss, warm ischemia time, length of hospital stay, number and length of renal vessels, graft function, and complications.
Mean follow-up was 53 months. Donor nephrectomy was performed successfully in all patients. The complication rate was 4.9%. In one case, the procedure was changed to open donor nephrectomy because of severe adhesion in the renal hilum from previous surgery. Ureteral complications occurred in four patients, who were successfully treated with retrograde ureteral stent placement. None of the donors needed readmission. Mean warm ischemia time was 4.8 minutes. Creatinine levels returned to normal in all patients, and long-term allograft function was good. Serum creatinine levels at postoperative days 1, 7, and 14 were 3.7 mg/dL, 1.4 mg/dL, and 1.4 mg/dL on average, respectively. Slow graft function was noted in four (1.1%) cases but returned to the normal level within 2 weeks after surgery. One-year donor survival was 99%, and 1-year graft survival was 98.2%.
Excellent donor safety and allograft function were obtained with RPLDN. These results suggest that RPLDN could be an option for LLDN.
Journal of endourology / Endourological Society 10/2010; 24(11):1783-7. · 1.75 Impact Factor
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Shoichi Iida,
Hideki Ishida,
Tadahiko Tokumoto,
Kazuya Omoto,
Hiroki Shirakawa,
Tomokazu Shimizu,
Hiroyuki Amano,
Kiyoshi Setoguchi,
Taiji Nozaki,
Daisuke Toki,
Daisuke Tokita,
Kazunari Tanabe
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ABSTRACT: To evaluate the role of the oral glucose tolerance test (OGTT) before transplantation and to examine the risk factors for new-onset diabetes after transplantation (NODAT) during long-term follow-up of renal transplant recipients receiving FK-based therapy.
The study evaluated 378 patients pre-transplantation using the OGTT and assigned them to one of three groups: Group 1, normal pattern; Group 2, impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) pattern (IFG/IGT); and Group 3, DM pattern.
Although the incidence of NODAT was higher in Group 3 than in groups 1 and 2, no significant difference was found between the three groups with regard to graft survival during long-term follow-up. Multivariate analysis showed that only a family history of diabetes was a significant factor determining NODAT progression.
Impaired glucose tolerance appears to be a threshold influencing NODAT; however, it was not a significant factor in graft survival. Careful monitoring and management based on the result of the pre-transplantation OGTT appear to prevent the deterioration of impaired glucose tolerance in renal transplant recipients receiving FK-based therapy, even when a pre-operative OGTT shows impaired glycemic control.
International Urology and Nephrology 02/2010; 42(4):935-45. · 1.47 Impact Factor
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ABSTRACT: Transplant glomerulopathy (TG) is involved in the criteria of chronic active antibody-mediated rejection (c-AMR) in Banff 07 classification. In this report, we discuss the clinico-pathological analysis of TG cases after renal transplantation, and analysis of whether all TG cases are applied to c-AMR.
Transplant glomerulopathy, defined by double contours of glomerular basement membranes, was diagnosed in 13 patients from 13 renal transplant patients followed-up in our institute between January 2007 and April 2008. We retrospectively reviewed these 13 patients.
Among 13 cases of TG, three cases were mild (cg1 in Banff classification), four were moderate (cg2), and six were severe (cg3). Transplant glomerulitis and interstitial inflammation were present in all 13 biopsies, and peritubular capillaritis was present in 12 of 13 biopsies, interstitial fibrosis/tubular atrophy in 13, and the thickening of the peritubular capillary (PTC) basement membrane in 11. PTC C4d deposition was presented in six cases, three out of six cases had diffuse C4d deposits in PTC, and the remainder had focal deposits. By assaying with plastic beads coated with human leukocyte antigen (HLA) in 12 cases, the circulating anti-HLA alloantibody was detected in all 12 patients of which only 3 of 12 were donor-specific antibodies (DSA). In our cases, there was no patient who fully met criteria for c-AMR in Banff classification, which included TG, C4d deposition in PTC, and existence of DSA, but seven patients were diagnosed suspicious for c-AMR. Seven cases (54%) had proteinuria at the time of the biopsies and the severity of proteinuria was associated with the severity of TG. Deterioration of renal allografts' function after biopsies was seen in seven (54%), and two of them lost their graft.
We suggest that histopathological changes of TG accompanied by transplant glomerulitis, peritubular capillaritis, the thickening of the peritubular capillaries basement membrane, and circulating anti-HLA antibodies may indicate c-AMR, even if C4d deposition in PTC is negative. The severity of TG may be associated with proteinuria, reduced graft function, and reduced graft survival.
Clinical Transplantation 09/2009; 23 Suppl 20:39-43. · 1.67 Impact Factor
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Hayato Nishida,
Hideki Ishida,
Toshiaki Tanaka,
Hiroyuki Amano,
Kazuya Omoto,
Hiroki Shirakawa,
Tomokazu Shimizu, Shoichi Iida,
Daisuke Toki,
Yutaka Yamaguchi,
Kazunari Tanabe
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ABSTRACT: Anti-CD20 antibody (rituximab) is recently being used as a B cell-depleting agent in renal transplantation (RTx). However, the incidence of infectious complications associated with rituximab therapy remains uncertain. We evaluated the incidence of cytomegalovirus (CMV) infection associated with rituximab therapy in RTx. A total of 83 patients were enrolled. The immunosuppressive regimen consisted of tacrolimus or cyclosporin, mycophenolate mofetil, methylprednisolone and basiliximab. In 54 patients, only one dose of rituximab (200 or 500 mg/kg body weight) was given before RTx. A total of 25 of 43 (58.1%) recipients who were CMV seropositive prior to RTx and who received rituximab induction therapy developed CMV infection, compared to 18 of 24 (75%) CMV seropositive recipients who did not receive rituximab therapy (P = 0.1676). A total of 8 of 11 patients who were CMV seronegative prior to RTx and who received rituximab developed CMV infection. However, CMV seroconversion was seen in all 8 of these infected patients. Low-dose rituximab induction therapy in renal transplant recipients appears to have no influence on the incidence of CMV infection and CMV seroconversion. However, we have to consider anti-CMV prophylaxis therapy, because of high incidents of CMV infection, especially for CMV seronegative recipients who received rituximab.
Transplant International 08/2009; 22(10):961-9. · 2.92 Impact Factor
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ABSTRACT: To report on the long-term clinical outcome of high-grade (G3) non-muscle-invasive bladder cancer (NMIBC) patients treated at a single institution.
A retrospective analysis of 93 patients with NMIBC treated between January 1991 and September 2005 was performed. Patients were divided into three groups on the basis of treatment they received after transurethral resection (TUR) of the bladder. Forty-seven patients received adjuvant intravesical epirubicine after TUR of the bladder (Group 1). Twenty-four patients received intravesical bacillus Calmette-Guérin (BCG) (Group 2). A radical cystectomy (RC) was performed on twenty-two patients (Group 3).
Median follow up was 68.7 months. Overall, thirty patients (33%) experienced tumor recurrence. The survival rates of Group 3 were significantly higher than the 71 patients undergoing conservative therapy (Group 1 and 2). There was no statistically significant difference between Group 1 and 2, but treatment failure in patients treated with epirubicine was significantly higher than in those with BCG. Cases without concomitant carcinoma in situ (CIS) showed statistically significantly higher survival rates than those with concomitant CIS.
RC provides excellent survival rates in patients with high-grade NMIBC. Adjuvant therapy with BCG after a complete TUR of the bladder may be an effective treatment for high-grade NMIBC. If a conservative treatment is preferred to RC, co-existence of a concomitant CIS should be considered with caution.
International Journal of Urology 03/2009; 16(3):287-92. · 1.75 Impact Factor
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Urology 12/2008; 72(5):1088-1089. · 2.43 Impact Factor
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ABSTRACT: To assess the influence of cold ischemia on postoperative renal function and the new onset of late-stage chronic kidney disease during long-term follow-up after partial nephrectomy.
A total of 131 patients with renal tumors who underwent partial nephrectomy and were followed up for >or=12 months were included in the present study. Renal function was analyzed using the estimated glomerular filtration rate (e-GFR).
We classified the subjects into 3 groups according to the length of cold ischemia time: group 1, 1-30 minutes; group 2, 31-60 minutes; and group 3, >60 minutes. Although the postoperative e-GFR was lower in group 3 than in groups 1 and 2, no significant difference was found among the 3 groups during long-term follow-up when preoperative CKD was absent. A cold ischemia time of >or=44 minutes significantly increased the probability of freedom from the new onset of an e-GFR of <45 mL/min/1.73 m(2), but this difference was minimal. Multivariate analysis showed that the preoperative e-GFR and the relative decrease of e-GFR at 1 year after surgery were the significant factors determining postoperative renal function.
A cold ischemia time of >44 minutes appears to be a threshold influencing the new onset of late-stage CKD; however, it was not a significant factor on multivariate analysis. Thus, renal hypothermia appears to prevent the deterioration of renal function long term after surgery for patients undergoing a longer ischemia time.
Urology 10/2008; 72(5):1083-8; discussion 1088-9. · 2.43 Impact Factor
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Daisuke Toki,
Hideki Ishida,
Shigeru Horita,
Tadahiko Tokumoto,
Tomokazu Shimizu,
Jyunpei Iizuka,
Kuniko Tunoyama,
Kentaro Masumoto,
Hiroki Shirakawa,
Kiyoshi Setoguchi, Shoichi Iida,
Kazunari Tanabe,
Yutaka Yamaguchi
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ABSTRACT: Recently, B-cell infiltrates in acute rejection grafts have attracted interest as an indicator of refractory rejection. Here, we report a case of deceased donor renal transplantation in a Japanese recipient operated overseas in which the recipient suffered from persistent tubulointerstitial rejection episodes associated with B-cell infiltrates. A 59-yr-old man with end-stage renal disease caused by immunoglobulin A nephropathy underwent deceased donor renal transplantation overseas in December 2005. The initial post-operative course was uneventful. The patient was referred to our hospital one month after transplantation. He maintained stable renal function throughout the follow-up period. The maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil and methylprednisolone. His serum creatinine concentration remained around 1.0 mg/dL, with no evidence of proteinuria. However, a discrepancy was detected between the renal function and the pathological findings. The pathology showed subclinical tubulointerstitial rejection with nodular B-cell infiltrates refractory to aggressive antirejection therapy. A steroid pulse and 15-deoxyspergualin were ineffective and the patient developed interstitial fibrosis and tubular atrophy by one yr after the transplantation, with persistent tubulitis and B-cell infiltrates. We treated the refractory rejection with B-cell infiltrates with a single 200 mg/body dose of rituximab and obtained an improvement. The pathological findings after administering rituximab consisted of mild tubulitis classified as Banff borderline, and elimination of the nodular B-cell infiltrates. At present, 20 months after renal transplantation, the patient continues to maintain stable renal function, with a good serum creatinine concentration (0.87 mg/dL).
Clinical Transplantation 07/2008; 22(s19):53 - 57. · 1.67 Impact Factor
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ABSTRACT: A 54-year-old man who had been under hemodialysis therapy for 16 years presented with gross hematuria at our department in February 2005. Imaging findings revealed right renal tumor of8.2 cm in diameter. In addition, the tumor extended into inferior vena cava at the level of the hepatic vein. There were no findings of distant metastasis. Right radical nephrectomy and thrombectomy were performed on April 2006. Histopathological analysis showed that the tumor was renal cell carcinoma of clear cell type, grade 2. Postoperative course was uneventful, and the adjuvant therapy with interferon alpha was initiated. He has been free from recurrence for 22 months after surgery.
Hinyokika kiyo. Acta urologica Japonica 04/2008; 54(3):229-34.
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ABSTRACT: We report two cases of subacute inguinal swelling in uremic patients on continuous ambulatory peritoneal dialysis (CAPD). Computed tomography, scintigraphy demonstrated a mass in the right groin. Surgical repair of an inguinal hernia resulted in complete resolution of the inguinal swelling. Both patients could restart continuous ambulatory peritoneal dialysis, without complication.
Hinyokika kiyo. Acta urologica Japonica 12/2003; 49(11):683-6.
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ABSTRACT: We report a case of perineal subcutaneous abscess due to urethral fistula in a patient with spinal cord injury. A 39-year-old male visited our hospital complaining of left scrotal swelling and fever. The left scrotum and perineal skin were swollen to the size of a goose egg, and pus was discharged from the perineal swollen bump. Magnetic resonance imaging (MRI) suggested an urethral fistula with a large subcutaneous abscess. The abscess was resected with debridement of necrotic tissue, and a cystostomy was placed. Endoscopy revealed a fistula in the bulbar urethra. The characteristics of this rare entity are discussed.
Hinyokika kiyo. Acta urologica Japonica 10/2003; 49(9):567-9.
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ABSTRACT: We report a case of localized amyloidosis of the renal pelvis and upper ureter arising in a 74-year-old man who presented at our hospital with gross hematuria. The intravenous pyelogram showed right hydronephrosis and stenosis of right renal pelvis and upper ureter. The cystoscopy view was normal, but the right retrograde-ureteropyelogram showed a long irregular stricture of the renal pelvis. Ureteroscopy was performed and rubbing biopsy of edematous, bleeding lesion suggested class IIIb, transitional cell carcinoma. With the diagnosis of a right renal pelvic tumor, right nephroureterectomy was performed. The histology report stated "massive deposits of amyloids are seen in the segment of macroscopically abnormal renal pelvis". Amyloidosis of the renal pelvis is a rare entity and 12 cases were reported in the Japanese and English literature.
Hinyokika kiyo. Acta urologica Japonica 08/2003; 49(7):423-6.