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ABSTRACT: BACKGROUND: Mizoribine (MZR) has been developed as an immunosuppressive agent, but has a less potent immunosuppressive effect up to 3 mg/kg/day MZR. Therefore, we investigated whether high-dose MZR, at 6 mg/kg/day, would be effective and safe for kidney transplant patients in conjunction with cyclosporine (CsA), basiliximab, and corticosteroids. METHODS: A total of 40 living related patients were administered MZR (6 mg/kg/day), CsA (7 mg/kg/day), prednisolone (maintenance dose 10 mg/day), and basiliximab (20 mg/body). A control group (n = 38) treated with CsA, mycophenolate mofetil (MMF, 25 mg/kg/day), basiliximab, and corticosteroids was also employed in this study. RESULTS: The 2-year graft survival rates for the MZR and MMF groups were 100 and 94.7 %, respectively. The rejection rate in the MZR group (25 %) was not significantly higher than that in the MMF group (16 %). Serum creatinine level was not significant between the two groups. The number of patients who developed cytomegalovirus (CMV) disease was 0 (0 %) in the MZR group and 7 (18.4 %) in the MMF group (P < 0.05). The number of patients treated with ganciclovir was 3 (7.5 %) and 11 (28.9 %) (P < 0.05), respectively. CONCLUSIONS: The combination of high-dose MZR with CsA, basiliximab, and corticosteroids can establish not only satisfactory immunosuppression but also a low rate of CMV infection in vivo.
Clinical and Experimental Nephrology 08/2012; · 1.37 Impact Factor
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ABSTRACT: We describe a renal transplant recipient with systemic lupus erythematosus (SLE) who showed continuous proteinuria and low complement levels without clinical evidence of active SLE. Her first renal allograft biopsy, performed nine yr and eight months after transplantation, revealed unusual histological change of glomeruli, and it initially led us to make a contradictory diagnosis based on light and electron microscopic examinations. Diffuse global double- or multi-contour glomerular basement membrane was caused by chronic endothelial injury owing to chronic rejection, and mesangial proliferation associated with mesangial electron-dense deposit was a histological change characteristic of recurrent lupus nephritis (RLN). Immunofluorescence study displayed weak mesangial staining of IgM and C1q. We concluded that this case presented overlapped chronic rejection and RLN. Because both transplant nephropathy and lupus nephritis present constellations of various histologies, it is difficult to diagnose their overlap. Complete morphologic studies with both immunofluorescence and electron microscopic evaluations in addition to microscopic examination should be performed to elucidate complex histological findings.
Clinical Transplantation 07/2011; 25 Suppl 23:49-52. · 1.67 Impact Factor
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ABSTRACT: A 15-yr-old girl with end-stage kidney disease caused by primary focal segmental glomerulosclerosis (FSGS) underwent a living-related donor kidney transplantation. The allograft functioned well immediately after reperfusion, but massive proteinuria exceeding 50 g/d appeared on day 3. Treatment with rituximab and plasma exchange (PE) successfully decreased the proteinuria to 10 g/d. A biopsy specimen on day 30 showed no segmental glomerulosclerosis but partial interstitial infiltration of inflammatory cells. An increased number of podocytes showed intracytoplasmic vacuolization, and an electron micrograph showed diffuse mild subendothelial edema and foot process effacement. The podocytes were hypertrophied but were not detached from the basement membrane. As the therapies used to reduce the patient's proteinuria were having a limited effect, intravenous steroid pulse therapy followed by low-density lipoprotein apheresis was performed. A biopsy specimen taken on day 120 showed no segmental glomerulosclerosis. Thrombus formation in one glomerulus and packed lymphocytes in the capillary loop of another glomerulus were detected. The patient's clinical course was compatible with FSGS recurrence. Although the early pathological changes were not typical of FSGS, they might be indicative of the primary lesion that subsequently progresses to typical FSGS.
Clinical Transplantation 07/2011; 25 Suppl 23:53-8. · 1.67 Impact Factor
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Nippon rinsho. Japanese journal of clinical medicine 11/2010; 68 Suppl 9:197-201.
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ABSTRACT: Because the safety of living organ donors is essential, we have been performing donor kidney biopsy before donation in cases where decision-making regarding suitability is marginal. To clarify the degree to which pathological change in the kidney can be predicted on the basis of clinical data obtained non-invasively, we analyzed preexisting lesions found by one-h biopsy in 76 living kidney donors, and compared the findings with clinical parameters at the time of donation. Pathological change in living kidney donors was correlated to some extent with predonation clinical parameters including age, serum creatinine, estimated glomerular filtration rate and presence of hypertension, while the lesions influenced by glucose intolerance were not completely correlated with the results of oral glucose tolerance test. A follow-up study will be required to determine whether these mild histological findings at the time of donation influence long-term outcome in the donor.
Clinical Transplantation 07/2010; 24 Suppl 22:27-30. · 1.67 Impact Factor
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ABSTRACT: As immunosuppressive therapy has advanced, we have markedly improved the outcome of ABO blood group incompatible living donor kidney transplantation. Consequently, graft survival at early phase after ABO-incompatible transplantation has been favorable than ABO-compatible transplantation in Japan. But in these days, it has been assumed that transplant glomerulopathy within one yr after ABO-incompatible kidney transplantation might be significantly precipitated. That may be because of chronic, active antibody-mediated rejection (AMR). We performed kidney graft biopsies at the early phase within 90 d after living donor kidney transplantation that involved the episode and protocol biopsies and studied findings of graft biopsy specimens when compared with ABO incompatible and compatible involving non-identical and identical transplantations. In ABO-incompatible transplant cases, the ratio occurring glomerulitis, especially severe injury of g 2-3, was significantly higher than that of identical and non-identical transplant cases (p < 0.01). There was no significant difference in t score, i score, ptc score and v score between three transplant groups. The cases occurring AMR were concordant with the cases recognized with severe glomerulitis. AMR was difficult to be diagnosed by C4d analysis in ABO-incompatible transplant cases. Glomerular injury score, g score, may be considered as more significant and the injury should be cured thoroughly.
Clinical Transplantation 07/2010; 24 Suppl 22:16-21. · 1.67 Impact Factor
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ABSTRACT: Because of lack of deceased donors in Japan, there has been a need to expand the eligibility criteria for live kidney donation. To assess the indications for live kidney donation in glucose intolerance (GI), we analyzed perioperative complications associated with donor nephrectomies performed at our institution and followed up the long-term consequences.
The 444 live kidney donors were divided into two groups based on the results of the 75-g oral glucose tolerance test: a GI group (n=71) who showed a diabetic (n=27) or impaired glucose tolerance (n=44) pattern, and a non-GI group (n=373) who showed a normal oral glucose tolerance test pattern. Perioperative complications, longterm survival rate, and frequencies of hypertension, diabetes, hyperlipidemia, and renal dysfunction in long term were compared in each group.
The incidence of perioperative complications was not higher in the GI group than in the non-GI group (4.3% vs. 5.4%, respectively; NS). Survival rates in the GI group at 5, 10, and 20 years were 98.3%, 95.1%, and 89.2%, respectively, whereas those in the non-GI group were 98.0%, 96.1%, and 91.5%, thus showing equivalent mortality. None of the patients in the diabetes mellitus group had developed severe diabetic complications or end-stage renal disease at a mean follow-up point of 88+/-71 (range, 14-225) months.
Our results suggest that individuals who have GI without diabetic complication may be able to donate their kidney safely with little surgical complication and little major morbidity if strict evaluation is performed before transplant.
Transplantation 06/2010; 89(11):1391-5. · 4.00 Impact Factor
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ABSTRACT: Recent advances in immunosuppressant therapy have dramatically reduced the frequency of acute rejection of organ transplants. Subsequently, the short-term graft survival rate has been improved, and ABO blood type-incompatible and existing anti-HLA antibody-positive kidney transplantation has been enabled, which has increased the availability of living kidney donors. Japan has a unique history and strategies of liver transplantation (LT) for various liver diseases. The outcomes of living donor liver transplantation (LDLT) in Japan is comparable to that of deceased donor liver transplantation (DDLT) in Western countries despite the relatively short history of LT. The main disadvantage of LT in Japan is donor shortage mainly due to the small number of available deceased donors. There are some disadvantages with LDLT in autoimmune liver diseases because of the dependence on blood relative donors. The first brain-dead pancreas transplantation (PTx) was performed in 2000. Since that time, 42 brain-dead PTx, 2 non-heart beating PTx, and 14 living donor PTx had been performed by the end of 2007. One of the 44 recipients of deceased donor PTx died of unknown causes 11 months after transplantation. Although most of the deceased donors in Japan were marginal and their condition was not favorable, the results of these cases were comparable to those of Western countries. Fourteen intestinal transplantations (ITx) had been performed by the end of 2007 in four transplant centers. There were 3 deceased donor and 11 live donor transplants. The original diseases included short bowel syndrome (n = 6), intestinal function disorder (n = 6), and retransplantation (n = 2). The graft and patient survival rate are 60% and 69%, respectively. Eight recipients survived and stopped parenteral nutrition with full-functioning grafts. Amendment of the Japanese law for the utilization of deceased donors should increase the number available donors in the future.
Surgery Today 06/2010; 40(6):514-25. · 1.22 Impact Factor
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Kiyokazu Akioka,
Masahiko Okamoto, Hidetaka Ushigome,
Shuji Nobori,
Tomoyuki Suzuki,
Kazuki Sakai,
Seisuke Sakamoto,
Koji Urasaki,
Akio Yanagisawa,
Atsushi Fukatsu,
Norio Yoshimura
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ABSTRACT: When a patient who had renal replacement therapy becomes older, an elder donor candidate may be considered as a potential donor for living-related transplantation. Elder donor candidate might have pre-existing disease including mild renal dysfunction, such as proteinuria. Marginally appropriate donors might be considered for renal graft because of the shortage of donors. A successful outcome after kidney transplantation from a living-related donor diagnosed as membranous nephropathy is reported.
A 38-yr-old male had been on continuous ambulatory peritoneal dialysis (CAPD) since the age of 37. His 63-yr-old father had mild proteinuria, and had been diagnosed with membranous nephropathy by needle biopsy at the age of 60. However, renal function of the father was found to be stable for three yr in a preoperative examination for donor; the father had normal renal function except for mild proteinuria. After adequate informed consent, we transplanted a kidney from the father, diagnosed with membranous nephropathy, to his son with a cyclosporine A-based immunosuppression regimen. In both the recipient and the donor, postoperative course was stable without complication such as rejection or infection. At 57 months after transplantation, the serum creatine level was 1.7 mg/dL in the recipient and 1.2 mg/dL in the donor. At 39 months after transplantation, allograft needle biopsy showed mild spike formation with partial thickening of the glomerular basement membrane (GBM). Decreases in electron-dense deposits and electron-lucent washout lesions with thickening of the GBM were observed using electron microscopy. This was diagnosed as Stage IV membranous nephropathy, showing clearance of the immune complexes and histological repair of the GBM.
Donation of the kidney did not affect the residual renal function of the father with membranous nephropathy. Pre-existing membranous nephropathy itself might show remission after transplantation in the recipient. However, long-term careful observation for both the donor and recipient is required.
Clinical Transplantation 09/2009; 23 Suppl 20:62-6. · 1.67 Impact Factor
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ABSTRACT: From January 2007, we started to perform the tonsillectomy for every patient with recurrent IgA nephropathy (IgAN) after kidney transplantation. Up to September 2008, four recipients with primary IgAN had biopsy-proven recurrent IgAN. They had also progressive hematuria or proteinuria from on the average 14.3 months after transplantation. Then their specimens diagnosed as recurrent IgAN were collected and they underwent tonsillectomies on the average 52.3 months after transplantation. Abnormal urinary findings of all patients favorably improved after tonsillectomy. All cases but one had mild renal injury, where the severity of glomerular lesions, glomerular hypercellularity, segmental lesions, and sclerosis was mild, and no deteriorated serum creatinine (SCr) before their tonsillectomies. Even the case with exacerbated SCr and severe renal injury, where the severity of glomerular lesions was severe, had her urinary findings ameliorated promptly after tonsillectomy likely as others. At present, they have almost no symptoms after tonsillectomy and no remarkable change of SCr level compared with before and after tonsillectomy and maintain ameliorated urinary findings continuously. Tonsillectomy had possibility to be a favorable treatment of hematuria or proteinuria in recurrent IgAN recipients.
Clinical Transplantation 09/2009; 23 Suppl 20:17-22. · 1.67 Impact Factor
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Masahiko Okamoto,
Kazuki Sakai,
Tomoyuki Suzuki,
Shuji Nobori, Hidetaka Ushigome,
Seisuke Sakamoto,
Koji Urasaki,
Yasukiyo Mori,
Kiyokazu Akioka,
Shoichiro Daimon,
Norio Yoshimura
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ABSTRACT: A lack of deceased kidney donors in Japan has led to dependence on living donors in as many as 80% of cases. At the same time, indications for living-donor kidney donation have been expanding in terms of donor medical status as well as HLA matching and ABO compatibility, thus emphasizing the donor shortage. To facilitate final medical decision-making for living kidney donation, we attempted kidney biopsy in six donor candidates who had problems such as mild diabetes and slight proteinuria. The biopsy specimens showed various degrees of tissue injury ranging from partial glomerular sclerosis to arteriole hyalinization. On the basis of the biopsy findings, kidney donation was subsequently performed in three of the six cases with full informed consent, and not done in the remaining three cases. Longer-term studies will be needed to clarify the outcome in both the donors and recipients in these cases.
Clinical Transplantation 09/2009; 23 Suppl 20:58-61. · 1.67 Impact Factor
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Pancreas 08/2009; 38(5):597-9. · 2.39 Impact Factor
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Transplant International 03/2009; 22(7):763-5. · 2.92 Impact Factor
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ABSTRACT: The lack of deceased donors in Japan means that living-donor kidney transplantation is necessary in as many as 80% of cases. However, there are few data on perioperative complications and long-term outcome for live kidney donors.
To determine associated perioperative morbidity and long-term mortality among live kidney donors, we reviewed 601 donor nephrectomies performed at our institution between 1970 and 2006 and attempted to contact all of the donors (or their families) to ascertain their present physical status. The survival rate and causes of death were compared with an age- and gender-matched cohort from the general population.
Although three donors (0.5%) experienced major perioperative complications, that is, femoral nerve compression, pulmonary thrombosis, and acute renal failure, all of the donors recovered and left hospital without complications. Among 481 donors (80%) for whom details were available at the time of inspection, 426 (88.5%) were still surviving. Donor survival rates at 5, 10, 20, and 30 years were 98.3%, 94.7%, 86.4%, and 66.2%, respectively. The mean interval between kidney donation and death was 183+/-102 (7-375) months, and the mean age at death was 70+/-11 years. The survival rate of kidney donors was better than the age- and gender-matched cohort from the general population, and the patterns and causes of death were similar.
Our data suggest that continuation of living-donor kidney transplantation programs is justified in short- and long-term donor safety.
Transplantation 03/2009; 87(3):419-23. · 4.00 Impact Factor
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ABSTRACT: We report a case of thrombotic microangiopathy developing after minor ABO-mismatched living donor kidney transplantation. The patient was a 57-yr-old woman whose blood group was B-positive. She received a kidney transplant from her husband whose blood group was O-positive. The recipient human leukocyte antigen haplotype was entirely different from that of the donor and the direct lymphocyte cross-match test was negative. The patient’s hemoglobin and platelet (Plt) count fell rapidly from 11.0 g/dL and 34 × 104/μL to 6.0 g/dL and 0.4 × 104/μL between days 10 and 15 after kidney transplantation, with no evidence of bleeding. On day 8, anti-group B IgG and IgM antibodies were found in her serum. This anti-B antibody was thought to be produced from passenger B lymphocytes in the donor’s kidney. Although in the case of hemolytic anemia after minor mismatched transplantation, the kidney function usually remains stable, the serum creatinine (s-Cr) rose from 0.8 to 5.2 mg/dL. On day 16, the helmet cells appeared in the serum and a total of 20 units of group O packed red blood cells and 30 units of group O Plts were transfused. Biopsy of the transplanted kidney was performed, which revealed thrombotic microangio-pathy, and appropriate therapy for DIC was administered, including anticoagulants, and cyclosporine A and mizoribine were replaced with tacrolimus and mycophenolate mofetil. Frequent plasma exchanges (PEX) with fresh frozen plasma were carried out. Furthermore, the anti-CD20 antibody rituximab was administered, because PEX had no effect. Following the adoption of these measures, the anti-donor antibodies disappeared to reduce the reaction on flow cytometric cross-match test; an anti-groupB antibody did not completely disappear but decreased in titer, and all the symptoms resolved immediately. The graft function recovered to a s-Cr level of 1.6 mg/dL by 34 d after the transplantation and she was discharged by 36 d after the transplantation. At present, she is entirely healthy and the graft function remains good with a s-Cr level of 1.1 mg/dL.
Clinical Transplantation 07/2008; 22(s19):25 - 30. · 1.67 Impact Factor
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ABSTRACT: We performed protocol kidney biopsies for the early diagnosis of asymptomatic histopathological acute rejection (AR), commonly defined as subclinical rejection and drug nephrotoxicity. Forty-seven kidney recipients that had asymptomatic and stable kidney function underwent protocol biopsies both one month and one yr after kidney transplantation. The protocol biopsies one month after transplantation revealed borderline change in 13 of 47 cases (27.6%). AR 1a was observed in eight cases (17.2%) and AR 1b was observed in three cases (6.4%). The AR 1a and AR 1b groups were treated with methyl prednisolone pulse and deoxyspergualin. Toxic tubulopathy was found in four cases (8.5%). In the cases of nephrotoxicity, cyclosporine or tacrolimus was reduced. The borderline change group was observed without any additional treatment. Every case diagnosed with acute rejection one month after transplantation improved histopathologically one yr after transplantation, and the borderline change group partially remained borderline change and partially improved histopathologically one yr after transplantation. The nephrotoxicity group improved histopathologically one yr after transplantation. In our institution, protocol biopsies one month and one yr after kidney transplantation proved useful in screening for subclinical rejection and toxic tubulopathy and subsequently effective in improving long-term graft survival.
Clinical Transplantation 07/2008; 22(s19):8 - 12. · 1.67 Impact Factor
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ABSTRACT: A 51-year-old female received a kidney transplant, donated by her husband. The patient was induced with tacrolimus, mycophenolate mofetil and prednisolone. After methyl prednisolone pulse therapy without biopsy, allograft biopsy on POD 160 showed severe tubulo-interstitial nephritis with intranuclear inclusions. Urine cytology also showed decoy cells. Blood PCR detected an increase of BK virus DNA. She was diagnosed as having BK virus-associated nephropathy . Reduction of tacrolimus and switching of mycophenolate mofetil to mizoribine were done. Serum Creatinin (sCr) still rose to 3.0 mg/dl with persistent viremia and viruria. From on POD 268, 0.25 mg/kg of cidofovir was administered intravenously every two weeks over about four months. Biopsy on POD 387 revealed the disappearance of tubulitis with intranuclear inclusions, and decoy cells also disappeared from urine cytology. BK virus DNA in the blood decreased under the threshold level. sCr was stable and remained about 2.2 mg/dl for three months after the final treatment of cidofovir.
International Journal of Urology 05/2008; 15(4):369-71. · 1.75 Impact Factor
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ABSTRACT: In the post-cyclosporine A era, it has been reported that acute rejection after kidney transplantation is commonly revealed as an asymptomatic increase in the serum creatinine level. Nephrotic range proteinuria is observed in patients with recurrent or de novo glomerulonephritis, or with chronic transplant nephropathy and glomerulopathy in the late phase. Acute rejection occurring with nephrotic range proteinuria without a rise of serum creatinine has been rarely reported. Here, we report a rare case of vascular rejection in a renal transplant recipient with nephrotic range proteinuria. A 34-yr-old male renal transplant recipient presented with acute vascular rejection and early-onset nephrotic syndrome. Severe nephrotic range proteinuria was detected with a minimally elevated level of serum creatinine. Biopsy showed severe glomerulitis and vasculitis, which was relieved by conversion of the immunosupressant regimen. Severe proteinuria was a sign of acute vascular rejection with severe glomerulitis and vasculitis. Careful observation to ensure maintenance of immunosuppression is necessary in such cases.
Clinical Transplantation 06/2007; 21(s18):18 - 22. · 1.67 Impact Factor
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Transplantation 06/2007; 83(10):1408-9. · 4.00 Impact Factor
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Nippon rinsho. Japanese journal of clinical medicine 04/2007; 65 Suppl 3:542-9.
