[Show abstract][Hide abstract] ABSTRACT: Angiomyolipoma is a common benign renal tumor. It is typically composed of adipose tissue and hence is easily diagnosed by using imaging methods such as ultrasonography, computed tomography, and magnetic resonance imaging. However, it is difficult to differentiate an atypical angiomyolipoma such as a fat-poor angiomyolipoma from a malignant tumor by using these imaging methods. We report a case of a fat-poor angiomyolipoma with cyst-like changes in a 35-year-old man. The angiomyolipoma was initially suspected to be a cystic renal cell carcinoma according to preoperative imaging studies. A 5-cm cystic tumor with an enhanced septal wall and exophytic formation was present in the middle section of the left kidney. The patient underwent partial nephrectomy. Pathological findings showed necrosis and hematoma in almost the entire lesion, with a small amount of adipose and muscle tissue. Finally, a fat-poor angiomyolipoma was diagnosed.
World Journal of Surgical Oncology 08/2015; 13(1):251. DOI:10.1186/s12957-015-0677-4 · 1.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pathogenic role of macrophages in antibody-mediated rejection (AMR) remains unclear. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a potent chemotactic factor for monocytes and macrophages. The current studies used a murine model of AMR to investigate the role of graft-derived CCL2 in AMR and how macrophages may participate in antibody-mediated allograft injury. B6.CCR5−/−/CD8−/− recipients rejected MHC-mismatched WT A/J allografts with high donor-reactive antibody titers and diffuse C4d deposition in the large vessels and myocardial capillaries, features consistent with AMR. In contrast, A/J.CCL2−/− allografts induced low donor-reactive antibody titers and C4d deposition at Day 7 posttransplant. Decreased donor-reactive CD4 T cells producing interferon gamma were induced in response to A/J.CCL2−/− versus WT allografts. Consequently, A/J.CCL2−/− allograft survival was modestly but significantly longer than A/J allografts. Macrophages purified from WT allografts expressed high levels of IL-1β and IL-12p40 and this expression and the numbers of classically activated macrophages were markedly reduced in CCL2-deficient allografts on Day 7. The results indicate that allograft-derived CCL2 plays an important role in directing classically activated macrophages into allografts during AMR and that macrophages are important contributors to the inflammatory environment mediating graft tissue injury in this pathology, suggesting CCL2 as a therapeutic target for AMR.
American Journal of Transplantation 07/2014; 14(8). DOI:10.1111/ajt.12780 · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Differences in levels of environmentally induced memory T cells that cross-react with donor MHC molecules are postulated to account for the efficacy of allograft tolerance-inducing strategies in rodents versus their failure in nonhuman primates and human transplant patients. Strategies to study the impact of donor-reactive memory T cells on allografts in rodents have relied on the pretransplant induction of memory T cells cross-reactive with donor allogeneic MHC molecules through recipient viral infection, priming directly with donor antigen or adoptive transfer of donor antigen primed memory T cells. Each approach accelerates allograft rejection and confers resistance to tolerance induction, but also biases the T cell repertoire to strong donor reactivity. The ability of endogenous memory T cells within unprimed mice to directly reject an allograft is unknown. Here, we show a direct association between increased duration of cold ischemic allograft storage and numbers and enhanced functions of early graft infiltrating endogenous CD8 memory T cells. These T cells directly mediate rejection of allografts subjected to prolonged ischemia and this rejection is resistant to costimulatory blockade. These findings recapitulate the clinically significant impact of endogenous memory T cells with donor reactivity in a mouse transplant model in the absence of prior recipient priming.
American Journal of Transplantation 02/2014; 14(3). DOI:10.1111/ajt.12605 · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endogenous memory CD8 T cells infiltrate MHC-mismatched cardiac allografts within 12-24 h posttransplant in mice and are activated to proliferate and produce IFN-γ. To more accurately assess the graft injury directly imposed by these endogenous memory CD8 T cells, we took advantage of the ability of anti-LFA-1 mAb given to allograft recipients on days 3 and 4 posttransplant to inhibit the generation of primary effector T cells. When compared to grafts from IgG-treated recipients on day 7 posttransplant, allografts from anti-LFA-1 mAb-treated recipients had increased numbers of CD8 T cells but these grafts had marked decreases in expression levels of mRNA encoding effector mediators associated with graft injury and decreases in donor-reactive CD8 T cells producing IFN-γ. Despite this decreased activity within the allograft, CD8 T cells in allografts from recipients treated with anti-LFA-1 mAb continued to proliferate up to day 7 posttransplant and did not upregulate expression of the exhaustion marker LAG-3 but did have decreased expression of ICOS. These results indicate that endogenous memory CD8 T cells infiltrate and proliferate in cardiac allografts in mice but do not express sufficient levels of functions to mediate overt graft injury and acute rejection.
American Journal of Transplantation 08/2013; 13(9). DOI:10.1111/ajt.12372 · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lymphopenia is induced by lymphoablative therapies and chronic viral infections. We assessed the impact of lymphopenia on cardiac allograft survival in recipients conditioned with peritransplant costimulatory blockade (CB) to promote long-term graft acceptance. After vascularized MHC-mismatched heterotopic heart grafts were stably accepted through CB, lymphopenia was induced on day 60 posttransplant by 6.5 Gy irradiation or by administration of anti-CD4 plus anti-CD8 mAb. Long-term surviving allografts were gradually rejected after lymphodepletion (MST = 74 ± 5 days postirradiation). Histological analyses indicated signs of severe rejection in allografts following lymphodepletion, including mononuclear cell infiltration and obliterative vasculopathy. Lymphodepletion of CB conditioned recipients induced increases in CD44(high) effector/memory T cells in lymphatic organs and strong recovery of donor-reactive T cell responses, indicating lymphopenia-induced proliferation (LIP) and donor alloimmune responses occurring in the host. T regulatory (CD4(+) Foxp(3+) ) cell and B cell numbers as well as donor-specific antibody titers also increased during allograft rejection in CB conditioned recipients given lymphodepletion. These observations suggest that allograft rejection following partial lymphocyte depletion is mediated by LIP of donor-reactive memory T cells. As lymphopenia may cause unexpected rejection of stable allografts, adequate strategies must be developed to control T cell proliferation and differentiation during lymphopenia.
American Journal of Transplantation 07/2013; 13(9). DOI:10.1111/ajt.12342 · 6.19 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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. DOI:10.1089/end.2009.0493 · 2.10 Impact Factor
[Show abstract][Hide abstract] 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. DOI:10.1007/s11255-010-9712-0 · 1.29 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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. DOI:10.1111/j.1432-2277.2009.00903.x · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The impact of acute antibody-mediated rejection (AAMR) on the long-term outcome on ABO-incompatible (ABOI) kidney transplantation is not well understood. We retrospectively analyzed the long-term impact of AAMR and risk factors for AAMR in 57 consecutive recipients performed between 1999 and 2004. Nineteen patients (33%) who developed AAMR within 3 months posttransplantation constituted of the AMR group. The graft survival rate was significantly lower in the AMR group (AMR vs. non-AMR, respectively; 5 years: 84% vs. 95%; 8 years: 45% vs. 95%; p = 0.009). The prevalence of transplant glomerulopathy at 1 year posttransplantation was significantly higher in the AMR group (AMR 64% vs. non-AMR 3%, p < 0.001). Multivariate analysis demonstrated that anti-blood group IgG antibody titers of 1:32 at the time of transplantation (OR, 9.52; p = 0.041) and donor-specific anti-HLA antibodies (DSHA) detected by Luminex single bead method (OR, 5.68; p = 0.015) were independent risk factors for AAMR regardless of baseline anti-blood group IgG antibody titers. Our results indicate that AAMR has a heavy impact on the long-term outcome and preoperative DSHA appears to have a more significant association with poor graft outcomes than anti-blood group antibodies, even in ABOI kidney transplantation.
American Journal of Transplantation 03/2009; 9(3):567-77. DOI:10.1111/j.1600-6143.2008.02538.x · 6.19 Impact Factor
[Show abstract][Hide abstract] 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. DOI:10.1111/j.1442-2042.2008.02239.x · 1.80 Impact Factor
[Show abstract][Hide abstract] 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.