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Kazuhide Saito

Publications and source records attributed to Kazuhide Saito.

At least 19 recordsLinked to original sources
PubMed2006

Immunohistochemical evidence of activated lectin pathway in kidney allografts with peritubular capillary C4d deposition.

BACKGROUND: Complement 4d (C4d) deposition in the peritubular capillary (PTC) in the kidney allograft is a useful diagnostic marker for humoral rejection. C4d is produced not only by the classical pathway but also by the lectin pathway of the complement activation cascade. We have recently reported the in situ role of the later phase of the complement cascade in renal allografts with C4d deposition; however, the initial process prior to C4d deposition is yet to be resolved. METHODS: To clarify the early phases of the complement activation cascade, we evaluated the deposition of initial proteins of the above two pathways; IgG, IgM, mannose-binding lectin (MBL), H-ficolin, L-ficolin, MBL-associated serine protease (MASP)-1 and MASP-2 in kidney allografts with PTC C4d deposition. RESULTS: Sixty kidney allograft specimens were divided into two groups on the basis of the presence of C4d deposition in PTC. The C4d-positive group (n = 18) included nine ABO-identical and nine ABO-incompatible cases, and the C4d-negative group (n = 42) had 34 ABO-identical and eight ABO-compatible (but not identical) cases. In the C4d-positive group, 16 of 18 cases showed diffuse H-ficolin and IgM deposition in PTC. In contrast, H-ficolin and IgM were not detected in PTC in the C4d-negative group. Other initial proteins were not detected in all cases. CONCLUSIONS: Our study suggested for the first time that the lectin pathway activated by H-ficolin may be involved in C4d deposition on PTC in the kidney allograft.

Adult↗
PubMed2006

Correlation between pharmacological efficacy of cyclosporine A and tacrolimus, evaluated by lymphocyte immunosuppressant-sensitivity test (LIST) with MTT assay procedure in renal transplant recipients.

The dose of calcineurin inhibitors in renal transplantation has been adjusted, based on the therapeutic drug monitoring data. However, the data do not always correlate with clinical drug efficacy. In vitro response of peripheral-blood mononuclear cells to immunosuppressive drugs is reported to correlate with the recipient-response to therapeutic efficacy of the drug. We report, here, usefulness of a lymphocyte immunosuppressant sensitivity test for the estimation of individual drug sensitivity in renal transplant recipients. The LIST we have developed includes MTT assay procedures without the use of radioisotope-labeled compounds, which is convenient for general hospital use. Utilizing this procedure, we compared the pharmacological efficacy between cyclosporine A and tacrolimus in 41 renal transplant recipients.

Adult↗
PubMed2006

Pinpoint targeted immunosuppression: anti-CD20/MMF desensitization with anti-CD25 in successful ABO-incompatible kidney transplantation without splenectomy.

BACKGROUND: In Japan, ABO-incompatible (ABO-I) kidney transplantation began in 1989; these transplantations have flourished because of the lack of cadaveric donors, and more than 600 cases were performed up to 2004. Splenectomy has been considered to be necessary for successful ABO-I kidney transplantation, and the majority of pre-conditioning protocols include splenectomy in Japan. However, we have lost some grafts due to antibody-mediated rejection (AMR) accompanying explosive elevation of anti-A/B antibody (Ab) titer even though the patients had a low pre-operative Ab titer. PATIENTS AND METHODS: We utilized two doses of anti-CD20, rituximab, simply combined with mycophenolate mofetil (MMF)/low-dose steroid desensitization started 1 month before surgery in ABO-I kidney transplantation. Two sessions of pre-operative Ab removal by double filtration plasmapheresis or plasma exchange were carried out. We performed six ABO-I kidney transplantations without splenectomy. Anti-A/B Ab titers were more than 16 to 32 times before treatment. We did not plan any post-operative repeated Ab removal or intravenous immunoglobulin G (IVIG). RESULTS: Pre-operative anti-A/B Ab titers were successfully reduced to less than eight times in all cases. Except for one case in which we had to remove the graft due to aspiration pneumonia and methicillin-resistant staphylococcus epidermidis (MRSE) sepsis, the other five cases did not experience antibody-mediated rejection (AMR). An additional session of post-operative Ab removal and/or IVIG was not necessary. In all patients, B cells (CD19+, CD20+, CD21+) and activated T cells (CD25+) were selectively suppressed, although CD3+, CD4+ and CD8+ cell populations remained stable, thus we call our protocol "pinpoint targeted immunosuppression." Plasma immunoglobulin level was also successfully suppressed, especially after 6 weeks of surgery. CONCLUSION: Anti-CD20/MMF desensitization is safe and allows successful ABO-I kidney transplantation without splenectomy.

ABO Blood-Group System↗
PubMed2006

Present status of ABO-incompatible kidney transplantation in Japan.

BACKGROUND: We have been making continuous efforts in ABO-incompatible kidney transplantation since 1989 to expand the opportunities for kidney transplantation from living donors in Japan. PATIENTS AND METHOD: From the Japanese registry, we reviewed the long-term patient and graft survival of ABO-incompatible kidney transplantation. This survey focused on 564 patients who received ABO-incompatible kidney grafts from January 1989 to December 2003 in whom monitoring follow-up could be achieved in 60 institutions all over Japan. The mean age of 367 (65%) male and 197 (35%) female patients at surgery was 34.5 yr. Pre-operative anti-A/B antibody (Ab) removal and splenectomy (n = 553, 98%) were routinely performed combined with triple or quadruple immunosuppression using calcinurine inhibitor (CNI), anti-metabolites and steroids with or without deoxyspurgualin (DSG) or anti-lymphocyte Abs. RESULTS: The overall patient survival rate at 1, 3, 5 and 10 yr after transplantation was 94, 91, 88 and 81%, with overall graft survival rates of 86, 82, 74 and 53%, respectively. The graft survival rate was significantly higher in patients aged 29 and younger compared with those aged 30 and older. Children aged 15 or younger in particular have shown excellent graft survival rates at 1, 3, 5 and 10 yr of 90, 90, 86 and 76%, respectively. Patients with anticoagulation therapy (n = 285) showed a significantly higher graft survival rate than those without anticoagulation (n = 213), with 10-yr graft survival rates of 59 vs. 48%. There were no significant differences between A and B incompatibility with respect to clinical outcomes. There were also no significant difference in numbers of human leukocyte antigen mismatches, induction and maintenance CNI (cyclosporin A (CYA) vs. tacrolimus) and donor/recipient relationships with respect to the outcomes. We divided the patients into five groups according to the transplanted year periods. The outcome of the most recent 124 cases since 2001 had dramatically improved, with 2-yr graft survival of 94%, and there is a significant difference between the groups in 2001 onwards and the other four groups. CONCLUSION: This study confirms that the long-term outcome of ABO-incompatible living kidney transplantation is excellent and is similar to that of ABO-compatible cases. Recent data show that short-term graft survival has also improved. ABO-incompatible kidney transplantation is a radical, but safe and effective, treatment choice for end-stage renal disease.

ABO Blood-Group System↗
PubMed2006

A series of surveys on assay for anti-A/B antibody by Japanese ABO-incompatible Transplantation Committee.

BACKGROUND: The measurement of anti-blood groups A and B antibody (Ab) titers is considered to be important in ABO-incompatible transplantation. However, no standard method for quantitative determination has yet been established in Japan. Inter-examiner variability was likely because Ab titer was determined mainly by visual observation. In order to assess inter-institutional variation in the measurement of anti-A/B Ab titer, a series of surveys was conducted by the Japanese ABO-incompatible Transplantation Committee. METHODS AND RESULTS: In 2003, the first national survey was conducted. Serum samples from six healthy volunteers with blood groups A (n = 2), B (n = 2) and O (n = 2) were sent to 29 institutions and anti-A/B Ab titer was measured by their customary methods. Isohemagglutinin assay in serial-doubling dilutions of serum using a test tube was widely used in all institutions. Inter-institutional difference between maximum and minimum value reached as much as 32-fold in immunoglobulin M (IgM) and 256-fold in IgG. As detailed protocol for assay seemed to be different between institutions, we attempted to standardize the protocol based on the result of a questionnaire survey. In 2004, a second survey was conducted in the same manner as the previous one, except participation involved 38 institutions and the measurement was performed in a uniform way using a provisional standard protocol. Analysis of the survey revealed that intra-institutional variation was reduced to below eightfold, except that several institutions showed a large difference from the mean titer and required some guidance. CONCLUSIONS: A periodical quality control survey is considered necessary to improve the accuracy of measurement. Anti-A/B Ab titer would provide useful information towards the prediction of rejection and the indication of treatments such as (double filtration) plasmapheresis, splenectomy, anti-CD20 monoclonal antibody and intravenous immunoglobulin. Standardization of the assay for anti-A/B Ab titer is essential for the fulfillment of a precise multicenter study, which will elucidate the significance of the measurement of anti-A/B Ab titer.

ABO Blood-Group System↗
PubMed2006

Interleukin-2 receptor antagonist induction in modern immunosuppression regimens for renal transplant recipients.

Addition of interleukin-2 receptor antagonist (IL-2RA) induction to calcineurin inhibitor (CNI)-based regimens reduces biopsy-proven acute rejection by 30-40%. IL-2RA induction facilitates early withdrawal of steroids, and supports the safe use of reduced-exposure CNI or delayed CNI introduction. IL-2RAs and rabbit antithymocyte globulin (Thymoglobulin) show comparable efficacy in patients at standard or low immunologic risk, but the adverse event profiles of lymphocyte-depleting agents are less favorable. IL-2RAs, uniquely, provide effective immunosuppression with similar tolerability to placebo.

Animals↗
PubMed2005

The morphological compensatory change of peritubular capillary network in chronic allograft rejection.

To clarify the compensatory hemodynamic alterations in the interstitium of renal allograft biopsies with chronic rejection, we evaluated the morphological changes in the peritubular capillary (PTC) network. Seven renal biopsy specimens from recipients with chronic rejection presenting with elevation of serum creatinine of 1.9 +/- 0.5 mg/dL were examined. Renal biopsy specimens from their counterpart donors were used as normal controls. In each specimen, non-pathological interstitial areas without fibrosis, tubular atrophy or cell infiltration were compared with pathological areas (PA) showing fibrosis and/or tubular atrophy using a computer image analysis. Morphological measurements revealed that the mean cut surface area of the PTC in the non-pathological and pathological interstitial areas in the recipient biopsies were significantly larger than that of the normal controls (p < 0.001 and 0.001, respectively). In the recipient biopsies, both of the mean cut surface areas of the tubules and PTC in the non-pathological areas were significantly higher than those in the PA (p < 0.001). The mean glomerular diameter in the recipient biopsies was also significantly higher than that of the donors (p < 0.01). In this study, we provided pathological evidence for the compensatory interstitial and glomerular hemodynamic alterations in kidney graft with chronic rejection and the condition as single kidney.

Adult↗
PubMed2005

A prospective trial of steroid withdrawal after renal transplantation treated with cyclosporine and mizoribine in children: results obtained between 1990 and 2003.

A prospective trial of adrenocorticostertoid (steroid) withdrawal after pediatric renal transplantation was begun in 1990. Ninety-four pediatric renal transplant recipients were enrolled in our multicenter study. Immunosuppressive therapy with cyclosporine (CyA), methylprednisolone (MPL), and mizoribine (MZ) was started after transplantation. MPL was reduced to administration on alternate days in 69 patients (73.4%) and was withdrawn in 27 patients (28.7%). Rejection episodes occurred in nine patients (33.3%) after withdrawal of MPL. It occurred within 3 months after withdrawal of MPL in two patients and more than 6 months in the others. Among them, two patients lost the grafts. Thirteen-year patient survival rate and graft survival rate were 94.6 and 83.1%, respectively. Forty-four of the 94 patients reached their final height. Mean final height was 155.0 cm in males and 146.3 cm in females and their height standard deviation score was -2.6 s.d., the same as that at the time of transplantation. Management of growth retardation before transplantation and further reduction in the steroid dose after transplantation will increase the final height of children with chronic renal failure.

Adolescent↗
PubMed2005

Immunosuppressive efficacy of mycophenolate mofetil when compared with azathioprine and mizoribine against peripheral lymphocytes from renal transplant recipients.

Mycophenolate mofetil is currently used instead of azathioprine in clinical transplantation. However, comparative studies for the immunosuppressive potency of anti-metabolites used for organ transplantation have not been well documented. We compared the pharmacological efficacy of mycophenolic acid (MPA), 6-meraputopurine (6-MP), and mizoribine (MZ) for inhibiting purine synthesis of peripheral blood mononuclear cells (PBMCs) in vitro by a mitogen assay procedure. PBMCs were obtained from 18 renal transplant recipients before operation and 18 healthy subjects. The inhibitory efficacy of 6-MP against concanavalin A-induced PBMC blastogenesis exhibited large variations between subjects in both recipients and healthy subjects. In contrast, the pharmacological efficacy of MPA on PBMC blastogenesis showed the smallest inter-individual variation of all the purine synthesis inhibitors examined. Furthermore, the effects of MPA were almost similar in the recipients and healthy subjects. The pharmacological efficacy of MZ against PBMC blastogenesis was weaker than that of the other two agents and the inter-individual variation of MZ IC50 against PBMCs of the patients was larger than that of MZ IC50 against PBMCs of healthy subjects. Reproducible immunosuppressive efficacy of MPA compared with other purinesynthesis inhibitors could be expected from the viewpoint of MPA pharmacodynamics against PBMCs in renal transplantation.

Adult↗
PubMed2004

Excellent long-term outcome of ABO-incompatible living donor kidney transplantation in Japan.

Owing to the severe shortage of cadaveric grafts in Japan, we have performed ABO-incompatible living donor kidney transplantation since 1989. This study assessed short- and long-term outcomes in 441 patients who received ABO-incompatible living donor kidney transplants between January 1989 and December 2001. We compared our results with historical data from 1055 recipients of living kidney transplantation. Overall patient survival rates 1, 3, 5, 7, and 9 years after ABO-incompatible transplantation were 93%, 89%, 87%, 85%, and 84%, respectively. Corresponding overall graft survival rates were 84%, 80%, 71%, 65%, and 59%. After ABO-incompatible transplantation, graft survival rates were significantly higher in patients 29 years or younger than in those 30 years or older and in patients who received anticoagulation therapy than in those who did not receive such therapy. There were no significant differences between A-incompatible and B-incompatible recipients with respect to clinical outcomes. The graft survival rate at 1 year in the historical controls was slightly but not significantly higher than that in our recipients of ABO-incompatible transplants. We conclude that long-term outcome in recipients of ABO-incompatible living kidneys is excellent. Transplantation of ABO-incompatible kidneys from living donors is a radical, but effective treatment for end-stage renal disease.

ABO Blood-Group System↗
PubMed2004

[Favorable course of collagenofibrotic glomerulopathy after kidney transplantation and questionnaire survey about the prognosis of collagenofibrotic glomerulopathy].

Collagenofibrotic glomerulopathy is a recently recognized entity that is characterized by massive accumulation of collagen fibrils in the mesangial and subendothelial areas, and an elevated serum level of procollagen III peptide (PIIIP). We report the first case of a collagenofibrotic glomerulopathy patient who received a kidney transplantation. She received the kidney transplantation at the age of 18 years and the post-operative course was uneventful with good renal function on immunosuppression, which consisted of methylprednisolone, tacrolimus and basiliximab. Although urinary protein was negative, the serum level of PIIIP gradually elevated which suggests new collagen production in the graft. These findings indicate that the recipient had a systemic factor that stimulated collagen production. To investigate the prognosis of collagenofibrotic glomerulopathy, we carried out a questionnaire survey on 14 patients at 9 hospitals. None of these patients had received a kidney transplantation. However, 7 already had end-stage renal failure. Ten years after diagnosis, the renal survival rate was 49%. This rate is lower than cited in previous reports.

Adult↗
PubMed2003

[Intermittent oral hormonal chemotherapy using estramustine phosphate and etoposide for the treatment of hormone-refractory prostate cancer].

Seventeen patients were given lower dose and intermittent oral administration of estramustine phosphate (6 mg/kg/day) and etoposide (30 mg/m2/day) for 7 days. Then administration was discontinued for 7 days. This administration cycle was repeated. Therapy was continued until evidence of disease progression or unacceptable toxicity occurred. Fifteen of the 17 patients were finally evaluated for PSA response. Overall, the pretreatment PSA levels were lowered at least 50% from baseline in 7 (47%) of the 15 patients. The median survival was 65 weeks. Five of the 17 patients complained of anorexia or nausea during the treatment, but none of them showed over grade 2 anorexia, none requiring transfusion or hospitalization. None of the patients showed edema, deep venous thrombosis, thrombocytopenia, anemia or myocardial infarction. Because of its rare and mild adverse effects, this intermittent administration of oral estramustine and oral etoposide may be a useful and secure regimen for hormone refractory prostate cancer.

Administration, Oral↗