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T Fukunishi

Publications and source records attributed to T Fukunishi.

At least 19 recordsLinked to original sources
PubMed1998

Retrospective study on the impact of hepatitis C virus infection on kidney transplant patients over 20 years.

BACKGROUND: The majority of chronic hepatitis is ascribable to hepatitis C virus (HCV) infection, whereas the clinical impact has not been understood in kidney transplant recipients. Our current study was carried out to assess the impact of HCV infection on kidney recipients over the long-term, and to investigate the effect and risk of interferon-alpha (IFN-alpha) therapy for chronic active hepatitis C. METHODS: Hepatitis B surface antigen (HBsAg) and antibody to HCV (HCVAb) were examined prospectively and retrospectively in 280 patients, who underwent kidney transplants in the period from 1973 to 1996. The patient survival rate, the graft survival rate, the incidence of liver dysfunction and the cause of mortality among the HCV infected and noninfected groups were analyzed. IFN-alpha therapy was performed on 10 patients with chronic active hepatitis C. RESULTS: Prevalence of the hepatitis virus was quite high at 34.3% (96/280): the frequency of the HBsAg carrier was 3.2% (9/280), that of the HCVAb carrier was 28.6% (80/280) and that of the both carriers was 2.5% (7/280). The other 184 cases (65.7%) were negative for both HBsAg and HCVAb. Liver dysfunction developed at the significantly higher incidence of 55% in HCVAb carriers compared to the 9.2% of the noninfected group (P<0.01). HCVAb carriers had a poor survival rate in the second decade compared to the noninfected group: 83.7% vs. 88.91% for 10-year survival (P=0.44) and 63.9% vs. 87.9% for 20-year survival (P<0.05). The poor survival rate was a result of the mortality from liver disorder. Five patients died of such disease in the infected groups whereas no noninfected patient died in the same period (p<0.01). As the result of IFN-alpha therapy, biochemical activity normalized or improved in eight cases, whereas the HCV-RNA titer was reduced only in three patients. Only one patient maintained normal biochemical markers and undetectable levels of HCV-RNA for 2 years after treatment. The therapy was discontinued for five patients with the adverse effects of acute rejection, deterioration of diabetes, and depression. CONCLUSIONS: HCV infection has a significant impact on kidney transplant recipients over the long term and in particular affects them in the second decade. Our pilot study revealed only partial efficacy of IFN-alpha therapy for HCV-infected recipients, but with the high risk of acute rejection.

Adult↗
PubMed1998

A 20-year case study of a kidney transplant recipient with chronic active hepatitis C: clinical course and successful treatment for late acute rejection induced by interferon therapy.

BACKGROUND: The influence of hepatitis C virus (HCV) infection has been discussed in kidney transplantation. Our case study focused on four points: the clinical course of an HCV-infected recipient; the pathogenesis of hepatic disorders in such a patient; interferon (IFN)-alpha therapy; and the risk of IFN-alpha therapy. METHOD: A patient was suspected of acquiring HCV via transfusion at kidney transplant. He was examined several times serologically, virologically, endoscopically, and pathologically during a 20-year follow-up. RESULTS: Abnormal biochemical markers were found within a month after transplantation but recovery occurred without any treatment. Within 3 years postoperatively, hepatic disorder developed including peliosis hepatis, nodular regenerative hyperplasia, and cholestasis. These pathological conditions were ascribed to immunosuppressants: cyclophosphamide and azathioprine. Abnormal chemical markers decreased to normal values for 4 consecutive years with the substitution of cyclophosphamide and azathioprine for mizoribine. During the subsequent 13 years, the patient developed chronic hepatitis with clinical and morphological features of hepatitis C infection. Anti-HCV antibody was positive from the second post-transplant year and HCV genome was detected in the 17th year. IFN-alpha therapy was initiated in the 17th year and resulted in normal transaminase activities with no effect on viremia. However, acute cellular rejection developed. The rejection was steroid resistant but responsive to OKT3. CONCLUSION: HCV might remain latent for approximately 7 years even in kidney recipients unless toxic hepatitis occurs. Hepatotoxic drugs may cause a wide spectrum of liver diseases in HCV carriers as a result of the overload of immunosuppressants on hepatocytes. IFN-alpha could induce acute cellular rejection even in the 17th year. Such acute rejection can be reversible with OKT3.

Adult↗
PubMed1998

Malignant neoplasm in kidney transplantation.

BACKGROUND: The kidney recipient is at a higher risk for cancer than is the general population, although the incidence of neoplasms in general is considered lower in Japan than in Western countries. The cause of this increased risk associated with either transplantation or geography has not yet been established. METHOD: The incidences and sites of malignant neoplasms were analyzed in 285 kidney recipients, who had been followed up for 3007 patient-years. The relationship between immunosuppressive states, the numbers of CD4-positive T lymphocytes, and the presence of malignant neoplasms was studied retrospectively. RESULTS: Eighteen malignant neoplasms were found in 17 of the 285 patients (6%). The malignancies developed in these patients an average of++ 1 26.5 months after transplantation. The incidence was only 3.9% at 10 years, increasing to 13.9% at 20 years. No difference in the time-course incidence was found between azathioprine-based and cyclosporin-based immunosuppressive regimens. The malignancies developed in the digestive organs in more than half of the patients, and were mainly in the liver, colon and rectum, and stomach, with a relatively low incidence of skin cancer and lymphoma. There was only one case of Epstein-Barr virus genome found in 5 specimens that were tested. Concerning the immunosuppressive state, CD4-positive T lymphocyte counts were not related directly with malignancies in our series. CONCLUSION: The cumulative incidence of malignancy increased markedly in the second posttransplant decade. The site of cancers in kidney recipients mirrors that of general Japanese malignancies. Our results revealed neither the cause nor predictor for malignancies in kidney transplant patients.

Adolescent↗
PubMed1997

Haplotypic diversity of DQA1*03 and *05 subtypes differing at amino acid residue 160 encoded in the third exon in 2215 Japanese individuals.

We analyzed the frequencies and haplotypes of DQA1*03 and *05 subtypes, DQA1*03011 or DQA1*0302 and DQA1*0501 or DQA1*0503, respectively, differing only at codon 160 in the non-polymorphic third exon of the DQA1 gene. Of these, 1,862 and 337 individuals selected as DQA1*03- and DQA1*05-positive samples, respectively among 2,215 unrelated Japanese were typed for their nucleotide variation at residue 160 using PCR-SSP. As observed in other populations, all the samples carrying DQA1*03011 (Gene Frequency, GF: 7.8%) were found to share DQB1*0302, whereas those carrying DQA1*0302 (GF: 44.3%) were associated with a variety of DQB1 alleles including DQB1*0302. Both of the DQA1-DQB1 haplotypes with DQA1*03011 and DQA1*0302 carrying DRB1*0406, DQA1*03011-DQB1*0302 and DQA1*0302-DQB1*0302, showed a strong linkage disequilibrium with B62 (p < 0.001, p < 0.05). These results suggested that DQA1*03011 was generated from a single amino acid change at residue 160 in the DQA1*0302-DQB1*0302 haplotype. However, none of the haplotypes with two different DQA1*03 subtypes carrying DRB1*0403,*0405,*0802 and *0901 showed a linkage disequilibrium with any common B-locus antigens, revealing extensive haplotypic diversity of the DQA1*03 group. For example, DRB1*0802 haplotypes showed linkage disequilibria with two different B-locus antigens, B35 and B61 depending on the presence of DQA1*03011 and DQA1*0302, respectively. The GFs of DQA1*0501 and *0503 were 5.1% and 2.7%, respectively. The DQA1*05 associated haplotypes in the DR52-antigen group with DQB1*0301 were divided into two groups, depending on the bimorphism at residue 160. Such a high degree of haplotypic diversity in association with DRB1 and B alleles observed in the DQA1*03 and *05 groups related to amino acid variation at residue 160, which may affect biological function such as the interaction between CD4 and HLA-DQ molecules, seems to reflect selective pressure in the evolutionary process of HLA antigens.

Alleles↗
PubMed1996

Three-times-daily monotherapy with tacrolimus (FK 506) in kidney transplantation.

BACKGROUND: Tacrolimus (FK 506) was introduced into organ transplantation as a powerful immunosuppressive but with several adverse effects. In fact, an appropriate protocol for using this agent has not yet been established. On the basis of pharmacokinetic studies and the reports of its administration as a continuous intravenous infusion, we designed the regimen of every eight hours in order to reduce the daily dosage. METHODS: Tacrolimus was given to nine patients in the Japanese FK506 study. Although it was discontinued in two patients within two months because of adverse effects and acute rejection, seven other patients tolerated the agent for a long period and received the drug three times a day. Concomitant prednisolone was gradually tapered and finally withdrawn in these patients. RESULTS: The smaller dosage of tacrolimus led to a higher trough concentration of 14.1 +/- 1.6 ng/mL in the three-times-a-day regimen compared with 12.7 +/- 1.9 ng/ml in twice-a-day therapy (P < 0.01). The daily dosage of tacrolimus proved to be reducible even further. Our target trough concentration was decreased finally to < 5 ng/mL. Concomitant prednisolone was withdrawn in all of the seven patients. The course of these patients has been uneventful for a year after withdrawal of prednisolone. CONCLUSION: Our regimen of three-times-a-day oral administration of tacrolimus is a likely protocol for reduction of its daily dosage, which lowers its adverse effects while maintaining its immunosuppressive action at a lower trough concentration without concomitant prednisolone.

Administration, Oral↗
PubMed1996

[Experience of 28 deliveries in 21 kidney transplant recipients].

BACKGROUND: Risk factors to induce graft dysfunction during pregnancy in kidney transplant recipients were studied. METHODS: A total of 28 deliveries from 21 female kidney transplant recipients were analyzed. RESULTS: All recipients were maintained on either azathioprine-based (n = 17) or cyclosporine-based (n = 11) immunosuppressive regimens. Graft dysfunction (creatinine clearance < 40 ml/min) occurred in 8 cases (8 patients) during pregnancy. No acute rejection, however, could be observed. In a case-controlled study comparing a group with graft dysfunction vs. a group with good graft function, there were significantly differences in the incidence of the cases with pre-existing hypertension (62.5% vs. 10.0%), the age of the grafted kidney (58.1 vs 47.6 year), the maternal anemia (Hb: 10.3 vs. 11.8 g/dl) and the creatinine level (1.4 vs. 1.0 mg/dl) at the first trimester. These findings suggested that poorer graft function had been underlying before pregnancy and that additional loading of the pregnancy reduced further graft function, while the deterioration would be recovered after delivery in all cases except one case. CONCLUSION: Risk factors to induce graft dysfunction during pregnancy are as follows. 1) high age of the grafted kidney (> 50 year), 2) pre-existing hypertension, 3) maternal anemia (Hb: < 11 g/dl) and 4) high creatinine level (> 1.3 mg/dl) at the first trimester.

Adult↗
PubMed1994

Laparoscopic study of peliosis hepatis and nodular transformation of the liver before and after renal transplantation: natural history and aetiology in follow-up cases.

Although peliosis hepatis and nodular transformation of the liver can occur after renal transplantation, their prevalence has not been well defined. To investigate the incidence of these complications, 137 laparoscopies were studied, 52 in 50 cases before and 85 in 66 cases after renal transplantation. To elucidate the aetiology and natural history of these diseases, cases were followed up by repeated laparoscopies. Peliosis was observed after transplantation (before: n = 1, after: n = 15 [22%], p < 0.005). Nodular transformation was seen only after transplantation (n = 5 [7%]), and was accompanied by peliosis (n = 4, p < 0.01). On observation before and after transplantation in the same cases, these diseases appeared after transplantation (peliosis: n = 9, p < 0.005; nodular transformation: n = 2). In follow-up cases, these diseases were confirmed after the discontinuation of or the controlled administration of immunosuppressants. The aetiology of the micronodular transformation which appeared following peliosis in a case treated without cyclosporin was shown to be azathioprine. However, the macronodular transformation observed in two cases treated with both azathioprine and cyclosporin seemed to be due to cyclosporin. This suggests that cases of peliosis hepatis and nodular transformation which appear after renal transplantation are associated with immunosuppressants, and that cyclosporin treatment may also affect the morphogenesis of nodular transformation.

Adult↗