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ABSTRACT: Alloantibodies contribute significantly to renal transplant rejection by activation of complement and various cytokines with a variety of effector cells, and are a major cause of allograft loss. Although there is clinical evidence of antibody- and complement-mediated injury in renal transplantation, the mechanism of antibody-mediated rejection remains largely unknown. In order to understand the sequential production of antibodies and complement components, we presensitized recipient rats by skin transplantation. Anti-donor-specific IgG levels reached a maximum 2 weeks following presensitization after which the rats underwent renal transplantation from the same donor strain. We then evaluated sequential pathological findings based on the Banff classification and several factors related to graft rejection. In this presensitized model, peritubular capillaries were already dilated and stained for C4d. Neutrophil and mononuclear cell infiltration in these capillaries was detected beginning 2 h after transplantation. Donor-specific antibody IgG levels decreased rapidly and anti-IgG antibody stained glomerular and peritubular capillaries in the grafts beginning 2 h after transplantation. Additionally, several cytokines and complement components showed marked changes in the presensitized group. Thus, in the donor-specific presensitized recipient, alloantibodies and complement were activated immediately after transplant. C4d deposition in peritubular capillaries appears to be a key factor for the diagnosis of antibody-associated rejection.Kidney International advance online publication, 24 April 2013; doi:10.1038/ki.2013.117.
Kidney International 04/2013; · 6.61 Impact Factor
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ABSTRACT: We investigated the risk factors for recurrence of IgA nephropathy after kidney transplantation. Of the 184 recipients of allografts for end-stage renal disease caused by primary IgA nephropathy at our institution and affiliated hospitals between 1990 and 2005, 70 developed recurrent IgA nephropathy (group 1), while the remaining 114 did not develop recurrent IgA nephropathy (group 2). The diagnosis of recurrent IgA nephropathy was based on case and/or protocol renal biopsies. We examined the risk factors for recurrence of IgA nephropathy by comparing the two groups. In addition, we also investigated the risk factors for graft loss in the patients with recurrent IgA nephropathy. The recipient's age at transplantation was significantly younger in group 1 than in group 2 (33.4 ± 10.4 vs. 36.7 ± 10.7, P = 0.037). No significant influence of the immunosuppressive regimens used was observed on the likelihood of recurrence of IgA nephropathy. In the analysis of the risk factors for graft loss, the mean age of the donor was significantly higher in the patient group with graft loss (59.1 ± 9.5 vs. 53.9 ± 9.0, P = 0.033), and the serum creatinine level at one year after surgery was also significantly higher in the patient group with graft loss (1.62 ± 0.52 vs. 1.34 ± 0.34, P = 0.022). Recipients with recurrent IgA nephropathy after transplantation, especially younger patients, need to be followed up carefully.
Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 04/2013; 17(2):213-20. · 1.39 Impact Factor
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ABSTRACT: BACKGROUND: Mizoribine (MZR) was approved in 1984 in Japan for the suppression of rejection in renal transplantation with an approved administration dosage of 1-3 mg/kg/day. The action of MZR resembles that of mycophenolate mofetil (MMF), but MZR dosing is markedly lower than that of MMF. To examine whether higher dosing of MZR could obtain efficacy similar to MMF in renal transplantation, we conducted a comparative study of MZR and MMF using a high daily dose of MZR. METHODS: A prospective, randomized comparative study of MZR versus MMF using tacrolimus (FK) and steroids as the base was conducted in 35 patients who had undergone living-donor renal transplantation (ABO-incompatible patients were not included) at 8 institutions in Japan between July 2005 and June 2007. Starting doses were 12 mg/kg/day for MZR and 2 g/day for MMF. Dosages of FK and steroids were set according to the protocol of each institution. RESULTS: Patient and graft survival rate at 1 year after transplantation was 100 % in each group, with no significant difference in rejection rate apparent between groups. Adverse events found in both groups were characteristic, frequently involving infection and digestive organ disorder in the MMF group and elevated uric acid levels in the MZR group. CONCLUSIONS: Based on these results, MZR and MMF are considered almost equivalent in terms of efficacy and safety.
Clinical and Experimental Nephrology 02/2013; · 1.37 Impact Factor
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ABSTRACT: OBJECTIVES: To investigate the impact of histological subtypes on the survival of patients presenting with renal cell carcinoma extending into the inferior vena cava. METHODS: From January 1985 until October 2011, 68 patients with renal cell carcinoma extending into the inferior vena cava underwent radical nephrectomy and inferior vena cava thrombectomy at Tokyo Women's Medical University, Tokyo, Japan. Their clinical and pathological parameters were reviewed from the medical charts. RESULTS: The median follow up was 19 months (range 0.1-144 months). The tumor thrombus level was I in four patients (6%), II in 38 patients (56%), III in 12 patients (18%) and IV in 14 patients (20%). Papillary histological subtype was found in seven patients (10%), and clear cell in 61 patients (90%). Patients with a papillary subtype had a significantly worse survival outcome than the patients with the clear cell subtype (median survival time 9.0 vs 36.1 months, P < 0.001). Multivariate analysis also showed that the papillary subtype was the only independent prognostic factor for unfavorable cancer-specific survival (P = 0.03). When the patients presented with metastases to lymph nodes or distant metastases, the median survival of the patients with a papillary subtype was extremely short, at just 5.2 months compared with those with a clear cell subtype (24.0 months, P = 0.001). CONCLUSIONS: Patients with renal cell carcinoma extending into the inferior vena cava with a papillary subtype show a considerably shorter survival compared with those with a clear cell subtype. The papillary renal cell carcinoma extending into the inferior vena cava patient might be an inappropriate candidate for extensive surgery when metastases to nodes or distant organs are found.
International Journal of Urology 02/2013; · 1.75 Impact Factor
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ABSTRACT: We have performed more than 200 ABO-incompatible and HLA-incompatible transplantations, using low-dose rituximab (Rit) as one of the B cell-depleting strategies. It has been revealed that a significant number of such patients who receive rituximab treatment develop late-onset neutropenia (LON). To obtain insights into the mechanism underlying the development of LON, we evaluated the kinetics of various cytokines involved in B-cell and granulocyte homeostasis. The subjects of this study could be categorized into five groups, as follows; group 1: Rit(+)LON(+), N=22 ; group 2 : Rit(+)LON(-), N=30; group 3: Rit(-)LON(+), N=15; group 4: Rit(-)LON(-), N=53; group5: CKD5 patients (N=10). Serum levels of the cytokines were examined pre-RTx, 6 mo after RTx, 12 mo after RTx and 1.5years after RTx. We investigated the association between the serum levels of the B cell-related cytokines and the incidence of acute rejection. Serum levels of BAFF were significantly elevated in groups 1, 2 and 3; in particular, group 1 patients showed marked elevation of the serum BAFF at 6 and 12months after RTx. No correlations were observed between the serum BAFF and the incidence of acute rejection. Transplant recipients treated with low-dose Rit and presenting with LON showed marked elevation of the serum BAFF levels.
Transplant Immunology 01/2013; · 1.46 Impact Factor
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ABSTRACT: We compared the survival rates in patients with metastatic renal cell carcinoma between the cytokine and molecular targeted therapy era. The study included 321 patients who were diagnosed with metastatic renal cell carcinoma between 1987 and 2011. The patients were divided into two groups according to when they started therapy for metastatic renal cell carcinoma: in the cytokine era (1987-2007) and in the targeted therapy era (after 2008). The beginning of the follow-up period was defined as the time of discovery of metastasis occurrence. Cytokine and targeted therapy eras included 235 and 86 patients, respectively. Seventy-five percent of the patients in the cytokine era actually received cytokine therapy. Eighty-one percent of the patients in the targeted therapy era received targeted therapy and 14% received both cytokine and targeted therapy. There were no significant differences in overall survival rates (cytokine 29 months, targeted 38 months, P = 0.1789).
Japanese Journal of Clinical Oncology 01/2013; · 1.78 Impact Factor
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ABSTRACT: We sought to clarify the controversial issue of whether detecting low-level anti-donor-specific HLA antibody (HLA-DSA) by single-antigen flow-bead assay (SAFB) may have a potential role in reducing acute and chronic antibody-mediated rejection (AMR). We retrospectively studied the preoperative serum of ABO-compatible living kidney transplantation recipients transplanted between 2001 and 2004 by SAFB using a Luminex platform. HLA-DSA was detected only by SAFB in 24 patients, although all of them showed negative T-cell and B-cell complement-dependent cytotoxicity (CDC) crossmatches. The HLA-DSA patients went on to have surprisingly high levels of acute and chronic AMR despite being only weakly sensitized (acute AMR, 33.3%; chronic AMR, 41.7%). After 2005, we implemented SAFB routinely and any patient having a positive HLA-DSA was considered to be a desensitization candidate. The 52 patients found to have HLA-DSA underwent kidney transplantation after prior treatment with a single dose of rituximab (RIT) and three or four sessions of double-filtration plasmapheresis (DFPP) in addition to regimens commonly used between 2001 and 2004. After 2005, there was a significant reduction in the occurrence of acute and chronic AMR (acute AMR, 4.7%, P < 0.001; chronic AMR, 4.7%, P < 0.001). The 5-year graft survival rate also improved after implementing SAFB (83.3-98.1%, P = 0.032). The RIT/DFPP-induction protocol may improve graft survival even in patients with low-level DSA.
Transplant International 07/2012; 25(9):925-34. · 2.92 Impact Factor
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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: Histopathological changes of acute vascular rejection (AVR) are characterized by intimal arteritis and transmural arteritis. According to the Banff 1997 classification, the quantitative criteria for intimal arteritis (v score) are classified: v0, v1, v2, and v3. According to Banff '09 classification, AVR may fall into one of four categories: acute T cell-mediated rejection (ATMR) Type IIA, ATMR Type IIB, ATMR Type III, and acute antibody-mediated rejection (AAMR) Type III. Both cellular and humoral immunity play roles in vascular rejection, and in some cases, AVR may be provoked by anti-donor antibodies. Anti-rejection therapies were effective in most of the v1 cases but were less effective in the v2 cases and were ineffective in the v3 cases. Some reports have indicated that the prognosis of grafts exhibiting AVR is poor, but in our series, the outcome of AVR was relatively good using recent immunosuppressive protocols. A definition for "isolated v-lesion" was originally characterized by arteritis with minimal interstitial inflammation and tubulitis. The 11th Banff conference was concluded that "isolated v1-lesions" comprised two types, T cell-mediated rejection and injury, and did not have any independent prognostic significance. However, we speculate that "isolated v-lesion" might be regarded as AAMR and ATMR.
Clinical Transplantation 07/2012; 26 Suppl 24:2-8. · 1.67 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 '09 classification.
TG was diagnosed in 58 renal allograft biopsy specimens (BS) from 37 renal transplant patients.
Among 58 BS of TG, 27 BS were mild (cg1), 16 were moderate (cg2), and 15 were severe (cg3). Peritubular capillaritis was present in 49 (84%), transplant glomerulitis was seen in 47 BS (81%), interstitial fibrosis and tubular atrophy in 47 (81%) and the thickening of the peritubular capillary (PTC) basement membrane (PTCBM) in 44 (76%), and interstitial inflammation was present in 26 BS (45%). C4d deposition in PTC was presented in 32 BS (55%). The circulating anti-HLA alloantibody was detected in 38 times (76%), of which 27/38 (54%) were donor-specific antibodies. Deterioration of renal allografts' function after biopsies was seen in 12 patients (32%) with six of them lost their graft.
We suggest that histopathological changes of TG accompanying by transplant glomerulitis, peritubular capillaritis, the thickening of the PTCBM, and circulating anti-HLA antibodies might indicate c-AMR, even if C4d deposition in PTC is negative. The prognosis of the graft exhibiting TG was relatively good under the present immunosuppression protocol in short time.
Clinical Transplantation 07/2012; 26 Suppl 24:37-42. · 1.67 Impact Factor
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ABSTRACT: Objectives: To examine the medium-term functional outcomes of partial nephrectomy for clinical T1b renal cell carcinoma, and to compare them with those of radical nephrectomy for clinical T1b and with those of partial nephrectomy for clinical T1a tumors. Methods: The participants of this study were patients operated for clinical T1a and clinical T1b tumors operated at Tokyo Women's Medical University, Tokyo, Japan, between January 1979 and June 2011. A total of 67 patients underwent partial nephrectomy for clinical T1b tumor, 195 patients underwent radical nephrectomy for clinical T1b tumors and 324 underwent partial nephrectomy for clinical T1a tumors. The outcomes of these three groups were compared. Results: Partial nephrectomy provided better preservation of residual renal function compared with radical nephrectomy for clinical T1b, and the postoperative estimated glomerular filtration rate was similar in the patients who underwent partial nephrectomy for clinical T1b and those who underwent partial nephrectomy for clinical T1a. Postoperative renal function was steadily maintained after partial nephrectomy during the medium-term follow up. The probability of freedom from new onset of chronic kidney disease after partial nephrectomy for clinical T1b tumors was significantly higher from that after radical nephrectomy for clinical T1b tumors, and similar to that after partial nephrectomy for clinical T1a tumors. Conclusions: The higher anatomical complexity of clinical T1b tumors is unlikely to provide a significant influence on postoperative renal function after partial nephrectomy, when compared with the clinical T1a tumors. These findings support the beneficial role of partial nephrectomy in the preservation of renal function of clinical T1b renal cell carcinoma patients undergoing surgery.
International Journal of Urology 06/2012; · 1.75 Impact Factor
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ABSTRACT: It has been proposed that sustained ICOS expression in chronic inflammatory immune conditions, such as autoimmunity and allergy, contributes to symptom exacerbation. Therefore modulation of ICOS gene expression could be a potential therapeutic strategy for such immune diseases. However, the precise molecular mechanisms controlling ICOS gene expression remain poorly understood. In this study, we explored transcription factors involving in ICOS gene expression and examined their roles in a physiological situation. Microarray analysis revealed that one AP-1 molecule, Fos-related antigen-2 (Fra2), was highly correlated with ICOS expression. Ectopic expression of Fra2 and other AP-1 molecules upregulated ICOS expression on T cells. We identified an AP-1-responsive site (AP1-RE) within the ICOS promoter region and demonstrated AP-1 actually binds to AP1-RE upon TCR/CD28 stimulation. Meanwhile, we found several cytokines could upregulate ICOS expression on both naïve and effector T cells in a manner independent of TCR/CD28 stimulation. These cytokine stimuli induced AP-1 binding to AP1-RE. Together, our results indicate AP-1 transcription factors are involved in ICOS gene expression downstream of both TCR/CD28 signaling and cytokine receptor signaling, and suggest AP-1 activation via cytokine receptor signaling may be one of the mechanisms maintaining high level ICOS expression in chronic inflammatory immune responses.
European Journal of Immunology 05/2012; 42(7):1850-62. · 5.10 Impact Factor
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ABSTRACT: To assess the predictors of postoperative renal insufficiency after open partial nephrectomy.
A total of 195 patients who underwent open partial nephrectomy were the participants in this study. Patients with a decrease in the estimated glomerular filtration rate of >25% from baseline were evaluated on the basis of multiple factors including patient-specific, surgical, tumor and postoperative factors. Postoperative estimated glomerular filtration rate data were recorded between 3 and 6 months after surgery.
Of the 195 patients, 18 (9%) had a decrease in estimated glomerular filtration rate of >25%. Percentage of preserved renal parenchyma (P = 0.0078), nearness of tumor to renal sinus (P = 0.0108), location of tumor to middle part of kidney (P = 0.0112), postoperative highest lactase dehydrogenase (P < 0.0001), postoperative body temperature (P = 0.0314) and postoperative acute kidney injury (P < 0.0001) were significantly different between patients with a decrease in estimated glomerular filtration rate of >25% and those with a decrease in estimated glomerular filtration rate ≤25% on univariate analysis. Multivariate analysis showed that postoperative highest lactase dehydrogenase (P = 0.0408) and acute kidney injury (P = 0.0002) were independent predictors for decrease of estimated glomerular filtration rate >25%. In contrast, patient characteristic factors (chronic kidney disease stage), surgical factors (clamping time and PPRP) and tumor factors (radius, endophytic/exophytic, nearness and location component) were not significant predictors.
Postoperative factors, lactase dehydrogenase and acute kidney injury, were strong predictors for renal insufficiency after open partial nephrectomy. Thus, a strict follow up is advisable in patients showing high postoperative levels of these two biomarkers.
International Journal of Urology 05/2012; 19(9):823-8. · 1.75 Impact Factor
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ABSTRACT: We reviewed cytoreductive nephrectomy for pT3b-T4 renal cell carcinoma with metastasis and evaluated the prognostic factors for cancer-specific survival. A total of 39 patients who underwent cytoreductive nephrectomy for renal cell carcinoma with pathological T3b-T4 (2009 Union for International Cancer Control consensus) from 1986 to 2011 in our hospital were the participants in this study. Prognostic factors for cancer-specific survival were analyzed. The median patient age was 64 years (range 31-84). Pathological T3b, T3c and T4 were found in 24 (61%), one (3%) and 14 (36%) patients, respectively. The distribution of the histological type was clear cell type in 34 (87%), papillary type in two (5%) and any type of renal cell carcinoma with a sarcomatoid component in three patients (8%). The median overall and cancer-specific survival was 7.5 and 7.6 months, respectively. Low-grade performance status, regional lymph node metastasis, higher pT stage and histological type were prognostic factors for cancer-specific survival on univariate analysis. On multivariate analysis, lymph node metastasis, higher pT stage and histological type (non-clear cell or sarcomatoid component) were significant predictors for cancer-specific survival. With cytoreductive nephrectomy for patients with pT4, lymph node metastasis and non-clear cell histology, we have to be particularly careful in terms of cancer control.
International Journal of Urology 05/2012; 19(9):875-9; author reply 879-80. · 1.75 Impact Factor
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ABSTRACT: The role of lymphadenectomy has been controversial in urological malignancies. Urothelial carcinoma of the bladder and upper urinary tract has a high potential to spread through the lymphatic network compared with other malignancies, including renal cell carcinoma or prostate cancer. In urothelial carcinoma of the bladder, lymphadenectomy of pelvic nodes had been considered as the standard procedure when radical cystectomy was carried out. Recently, many investigators have examined the influence of its extent, and the majority of the studies have supported the beneficial role of extended lymphadenectomy in accurate staging or in improving patient survival. Although randomized controlled trials are required to establish a greater level of evidence, more urological surgeons have already noticed the necessity for extended lymphadenectomy in bladder cancer. In contrast to bladder cancer, there have been far fewer studies on urothelial carcinoma of the upper urinary tract. This might be because of the smaller number of the patients with urothelial carcinoma of the upper urinary tract and the lack of understanding of regional nodes. However, studies of lymph node mapping and the retrospective analyses with respect to the benefit of lymphadenectomy have been carried out in urothelial carcinoma of the upper urinary tract by some investigators, although the results are still controversial. However, the results from multi-institutional studies by high volume centers have supported the beneficial role of lymphadenectomy in urothelial carcinoma of the upper urinary tract, as it has been proposed in bladder cancer. Thus, lymphadenectomy for urothelial carcinoma of the bladder and the upper urinary tract might have a potential role in staging and improving the oncological outcomes.
International Journal of Urology 04/2012; 19(8):710-21. · 1.75 Impact Factor
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ABSTRACT: Endothelial chimerism in transplanted organs can be defined as the presence of recipient-derived endothelial cells in the donor organ. The mechanism of endothelial chimerism is not well understood and remains controversial. The purpose of this study was twofold. First, we investigated the presence of chimerism in renal allografts of ABO-incompatible kidney transplantation recipients. Second, we analyzed the association between chimerism and the clinical course and histopathological changes.
We investigated the presence of chimerism in renal allografts of ABO-incompatible kidney transplantation recipients by immunohistochemical detection of blood type A and B antigens and assessed the association between chimerism, the clinical course, and histopathological changes. Among a total of 56 patients (29 blood group A incompatible and 27 blood group B incompatible), 49 cases (28 blood group A incompatible and 21 blood group B incompatible) were enrolled in this study. Blood group antigens were stained using immunohistochemistry.
Twelve of the 49 patients (12/49, 24.5%) exhibited endothelium chimerism in a biopsy sample. Among the 12 patients with endothelium chimerism, 7 patients (7/12, 59%) had acute and chronic active antibody-mediated rejection and 2 patients (2/12, 17%) had severe calcineurin inhibitor toxicity. The graft survival rate in the chimerism group was significantly lower than that in the no-chimerism group ([chimerism vs. no-chimerism] 3 years, 83.3% vs. 97.1%; 5 years, 74.1% vs. 97.1%; 8 years, 46.3% vs. 97.1%; P<0.0001).
Endothelial chimerism seems to be a hallmark of vigorous immune or nonimmune responses, such as antibody-mediated rejection or calcineurin inhibitor toxicity, and not of the induction of tolerance.
Transplantation 04/2012; 93(7):709-16. · 4.00 Impact Factor
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ABSTRACT: Bladder dysfunction after kidney transplantation (KTx) impairs the patients' quality of life. We examined the bladder function status perioperatively in patients undergoing KTx and performed a randomized prospective study to determine the efficacy of an antimuscarinic agent, solifenacin, in ameliorating the bladder dysfunction after KTx.
The subjects in this study were 33 patients who underwent KTx at our institution. The patients were divided into two groups: group 1 (n=18), composed of patients who were not treated with any antimuscarinic agent, and group 2 (n=15), composed of patients treated with an antimuscarinic agent. We investigated the actual bladder function status of these patients before and after KTx by the following two methods: (1) video water cystometry and (2) questionnaire study using the Overactive Bladder Symptom Score and King's Health Questionnaire.
The cystometry study revealed a significantly greater increase of the maximum cystometric capacity in group 2 than in group 1 (173.0±60.7 mL in group 1 and 260.1±51.0 mL in group 2 [P=0.005]) after KTx. In the questionnaire surveys, the decreases in the scores for all domains were observed 6 weeks after KTx. The scores in group 2 tended to be lower than those in group 1.
In all of our patients, the bladder dysfunction status improved dramatically after KTx. In addition, our results suggest that administration of the antimuscarinic agent, solifenacin, may contribute to improvement of the quality of life of patients undergoing KTx.
Transplantation 01/2012; 93(6):597-602. · 4.00 Impact Factor
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ABSTRACT: The aim of this study was to elucidate the clinical characteristics and frequency of psychiatric consultation in a routine clinical setting after kidney transplantation.
Subjects were 1,139 consecutive recipients who received kidney transplantation at our hospital between January 1997 and September 2006. The hospital patient database was searched to determine whether these recipients received psychiatric consultation after their transplantation during this period.
Among 1,139 recipients, 118 (10%) received psychiatric consultation after their transplantation. There were significantly more women among these recipients (p = 0.036). Many of the recipients had received psychiatric consultation before transplantation (p < 0.0001) and had received dialysis for a long time (p = 0.018). There were three main psychiatric diagnoses according to ICD-10 diagnostic criteria in these 118 recipients: 42 (36%) had neurotic, stress-related, and somatoform disorders (F4); 35 (30%) had organic, including symptomatic, mental disorders (F0); and 27 (23%) had mood (affective) disorders (F3). The median length of time between kidney transplantation and initial psychiatric consultation was 57 days (interquartile range: 10-650 days). The lengths were 7 days (6-17 days) for F0, 75 days (18-650 days) for F4, 243 days (35-1,004 days) for F3, and 253 days (10-1,393 days) for other diagnostic groups. Significant differences were observed among these four groups (Jonckheere-Terpstra test, p < 0.001).
Our results show that appropriate psychiatric intervention is necessary not only in early stages after kidney transplantation but also over the long term.
The International Journal of Psychiatry in Medicine 01/2012; 43(3):197-209. · 1.03 Impact Factor
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ABSTRACT: The transcription factor c-Jun is a major component of the activator protein-1 complex involved in renal physiological events, such as inflammation and fibrosis. We recently demonstrated c-Jun activation in peritubular capillary (PC) endothelial cells and infiltrating cells in acute antibody-mediated rejection after kidney transplantation. However, the clinicopathological role of PC endothelial c-Jun activation has remained undetermined.
We investigated endothelial c-Jun activation in PC using phosphorylated c-Jun (p-c-Jun) immunohistochemical staining in 21 cases of chronic active antibody-mediated rejection (CAMR), 14 cases of interstitial fibrosis and tubular atrophy (IF/TA) lacking specific etiology, and 8 normal control subjects (NC).
In CAMR cases, swollen PC endothelial cells showed strong p-c-Jun staining. More p-c-Jun-positive endothelial cells in PC were observed in CAMR than in IF/TA and NC subjects (p < 0.01). These findings were significantly correlated with reduced PC (rs = -0.78, p = 0.0005), the "ci + ct" score of the Banff classification (rs = 0.81, p = 0.0003) and serum creatinine level (rs = 0.48, p = 0.03).
Endothelial c-Jun activation in PC may contribute to PC loss, interstitial fibrosis and late allograft deterioration in CAMR. These data suggest that c-Jun is an appropriate therapeutic target of CAMR.
Clinical nephrology 01/2012; 77(1):32-9. · 1.17 Impact Factor
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International Journal of Urology 12/2011; 18(12):866-7. · 1.75 Impact Factor
