Isolated Superior Mesenteric Artery Dissection Following Liver Transplant: Report of 3 Cases.

BACKGROUND: Isolated superior mesenteric artery (SMA) dissection (SMAD) is considered a relatively rare disease. Especially, isolated SMAD following liver transplant has been rarely reported. REPORT OF CASES: Among 96 consecutive adult recipients who underwent liver transplant at our institution, 3 recipients (3.1%) demonstrated isolated noncommunicating SMAD, type IV according to Sakamoto's classification. Patient characteristics are the following: mean age, 53 years (range, 49-60 years); male to female ratio, 2:1, right lobe graft to left lobe graft ratio, 2:1; operating time, 760 minutes (range, 614-880 minutes); and blood loss, 6570 mL (range, 2435-13,329 mL). New onset of abdominal pain was noted in 33.3% (1/3). The diagnosis was made by the first follow-up computed tomography scan after liver transplant. The mean distance between the proximal end of SMAD and the root of SMA was 21.3 mm (range, 9-40 mm). There were no signs of ischemic changes in the small intestine in any of the 3 patients. Thus, conservative managements such as anticoagulation therapy were performed without other aggressive interventions. One patient died because of subarachnoid hemorrhage. In the other 2 patients, SMAD disappeared at 6 months following the diagnosis. DISCUSSION: The morbidity of isolated SMAD is around less than 0.1% at the autopsy. Compared with this result, we found significantly higher morbidity rate in liver transplant recipients. It is true that mechanical stress from retraction of the stomach to the caudal end including the root of SMA may play an important role in the onset of SMA dissection. CONCLUSION: Isolated SMA dissection following living donor liver transplant is a rare but potentially life-threatening condition. It is required to ascertain whether emergency revascularization should be considered.

Graft Immunocomplex Capture Fluorescence Analysis Can Detect Intragraft Anti-Major Histocompatibility Complex Antibodies in Mice Cardiac Transplant.

BACKGROUND: Immunocomplex capture fluorescence analysis has recently been applied as a method for detection of intragraft donor-specific anti-major histocompatibility complex (MHC) antibodies (DSA) in humans. Although intragraft DSA in humans is an intense topic of investigation, there is no report to assess intragraft DSA in murine organ transplantation. METHODS: A model of presensitized mouse cardiac transplantation by donor splenocytes was used. To capture mouse MHC, anti-MHC class I/II antibodies were immobilized on Luminex beads. The MHC/DSA complexes were captured by the Luminex beads followed by detection of phycoerythrin-conjugated antimouse IgG antibodies where DSA had already reacted with the allograft in vivo. RESULTS: Luminex beads were capable of detecting class I DSA in the cardiac allograft, though results for class II DSA were negative. Immunohistochemical investigation revealed that cardiac allografts had abundant MHC class I expression but only minor expression of MHC class II. Furthermore, MHC/class II DSA complexes were successfully detected in splenocytes and serum from a presensitized recipient. CONCLUSIONS: These data suggested that graft immunocomplex capture fluorescence analysis can be also applied in murine cardiac transplantation. This novel application in mice would accelerate our comprehension of DSA through mechanistic studies.

Short- and Long-Term Outcomes of Live Donor Renal Allografts From Older and Younger Donors.

BACKGROUND: The rising demand for living renal donors has led to the recruitment of older donors. Findings vary, but these grafts appear to survive as long as grafts from standard criteria deceased and expanded criteria deceased donors. We investigated the effects of donor age ≥65 years and the presence or absence of donor antihypertensive therapy on patient condition 1 year after transplantation, and retrospectively examined 1-year (273 patients), 3-year (217 patients), and 5-year (140 patients) patient and graft survival. METHODS: We divided 273 donor-recipient pairs into Group Y (donor age <65 years, n = 224) and Group O (donor age ≥65 years, n = 49). Group O was subdivided into donors receiving treatment for hypertension (subgroup O-1, n = 16) and those not receiving treatment for hypertension (subgroup O-2, n = 33). We compared results of 1 hour post-transplant biopsies and looked at a small number of 1 year post-transplant biopsies. RESULTS: Although a significantly larger percentage of recipients from younger donors were undergoing preemptive transplantation, and the incidence of arteriosclerosis was significantly higher in the Group O kidneys, there were no significant differences between the 2 groups in terms of patient or graft survival at 1, 3, or 5 years; serum creatinine levels; or number of episodes of acute rejection. The presence or absence of donor antihypertensive treatment had no effect. CONCLUSIONS: We found that donor age ≥65, with or without antihypertensive treatment, had no effect on graft or patient survival.

Effective Treatment With Daclatasvir and Asunaprevir in Kidney Transplant Patients Infected With Hepatitis C Virus: A Report of Two Cases.

BACKGROUND: Hepatitis C virus (HCV) infection is known to affect long-term patient and graft survivals after kidney transplantation (KT). Recently, combination therapy with the use of 2 oral direct-acting antivirals, daclatasvir (DCV) and asunaprevir (ASV) reportedly showed a high rate of HCV eradication. We report the safety and efficacy of DCV and ASV therapy in 2 KT patients. METHODS: The safety and viral responses were investigated in a prospective study of KT patients infected with HCV genotype 1. Two patients received 60 mg DCV once daily plus 100 mg ASV twice daily for 24 weeks. RESULTS: A 69-year-old woman and a 57-year-old man underwent DCV and ASV therapy for 24 weeks. In both cases, the HCV genotype was 1b. Case 1 had undergone KT twice and had received treatment with pegylated interferon and ribavirin. She received DCV and ASV therapy 12 years after the 2nd KT, and had undetectable virus after only 6 weeks of treatment and at 24 weeks after the end of treatment (SVR24). The post-transplantation immunosuppressive therapy at that time comprised tacrolimus, mycophenolate mofetil, and prednisolone. The other case, after failure of interferon treatment, received DCV and ASV therapy 27 years after his KT and achieved SVR24. His immunosuppressive regimen at that time was mizoribine and prednisolone. DCV and ASV therapy did not affect renal graft function or tacrolimus blood concentrations. CONCLUSIONS: DCV and ASV therapy had high antiviral effect and a low rate of adverse events in KT patients.

Living Donor Kidney Transplantation After Brachytherapy for Prostate Cancer: Case Report.

INTRODUCTION: There is no obvious criterion about kidney transplantation for patients with pretransplant malignancy. Minimum tumor-free waiting periods differ according to type of cancer, staging, site of occurrence, response to therapy, and risk of cancer recurrence. We report a case of living donor kidney transplantation (LDKT) in a patient after brachytherapy for prostate cancer. CASE REPORT: The patient was a 65-year-old man with chronic kidney disease due to chronic glomerular nephritis. He received hemodialysis 3 times a week. His prostate-specific antigen level (PSA) was high (6.57 ng/mL), and he was diagnosed with prostate cancer (T1cN0M0, Gleason Score 3 + 4 = 7, 3/10) by needle biopsy in urology. He was treated with maximum androgen blockade (MAB) therapy and brachytherapy in May 2014. He underwent LDKT from a spousal donor at our department in December 2015, because urologists concluded that the prostate cancer was completely cured. Immunosuppression consisted of induction with basiliximab and maintenance with tacrolimus, mizoribine, and steroids. The postoperative course was uneventful. He discharged at postoperative day 29 with a serum creatinine level of 1.30 mg/dL. Three months after LDKT, his PSA level was 0.477 ng/mL, and there was no evidence of prostate cancer recurrence. CONCLUSION: This is the first case of LDKT for patients with prostate cancer after brachytherapy in combination with MAB. There is no recurrence of prostate cancer so far; however, careful follow-up including PSA is necessary and important.

Influences of Pre-formed Donor-Specific Anti-Human Leukocyte Antigen Antibodies in Living-Donor Renal Transplantation: Results With Graft Immunocomplex Capture Fluorescence Analysis.

BACKGROUND: Advances in immunosuppressants enable organ transplantation for sensitized patients. However, influences of pre-formed donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have not been fully understood in renal transplantation (RT). On the other hand, immunocomplex capture fluorescence analysis (ICFA) is a reliable method to detect donor-specific anti-HLA antibodies and HLA antigen complexes. Graft ICFA can detect DSA in an allograft (g-DSA). METHODS: To elucidate the consequences of pre-formed DSA, 198 patients who underwent living-donor RT were enrolled for this study (observation period: 57.8 ± 34.9 months); 187 patients in the DSA- group (excluding ABO-incompatible cases) and 11 patients in the DSA+ group. Before RT, all DSA+ patients had undergone rituximab administration and plasmapheresis. For a graft ICFA, the biopsy specimen (1 × 105 cells) was dissolved, and HLA antigens were captured by anti-HLA beads. Finally, DSA-HLA complexes were detected by means of PE-conjugated anti-human IgG antibodies and analyzed by use of a Luminex system. A ratio (sample/blank beads, mean of fluorescence intensity) was calculated: ≥1.0 was determined as positive g-DSA. RESULTS: There were no significant differences in 5-year graft survival (87.9%/100% in the DSA-/DSA+ groups, respectively). In terms of antibody-mediated rejection (AMR), within 1 month after RT, pathologically determined AMR occurred 3.2% and 63.4% in the DSA- and DSA+ groups, respectively (P < .0001). However, interestingly, more than half of them (57.1%) indicated only subclinical AMR, that is, no fluctuation of S-Cr. As representative of 2 cases of subclinical AMR, g-DSA deposition could be confirmed (1.15 ± 0.04) at 1 hour after reperfusion by graft ICFA. Furthermore, g-DSA shifted to 2.20 ± 0.98 at 3 weeks after transplantation, along with a decline in s-DSA mean of fluorescence intensity (1718-506.5). CONCLUSIONS: Although pathologically determined AMR occurred more frequently in pre-formed DSA+ recipients, it can be argued that a successful de-sensitization protocol inhibits further production of DSA and graft destruction.

Elderly Living Donor Liver Transplant Recipients Over 60 Years Old at a Japanese Single Center.

BACKGROUND: Among living donor liver transplant (LDLT) recipients, the number of elderly individuals has been increasing because of longer survival due to the improvement of treatment for hepatic diseases such as hepatitis C (HCV). Here we report the outcomes of living donor recipients over the age of 60 years. MATERIALS AND METHODS: In 76 adult LDLT patients at our institution before September 2015, there were 21 recipients over 60 years old. We divided all of the recipients into 2 groups ("elderly" recipient group >60 years of age [n = 21], and a "nonelderly" recipient group <60 years [n = 55]), and we investigated outcomes in each group. RESULTS: The graft survival rates in the elderly group were 89.9% at 1 year, 89.9% at 3 years, 83.0% at 5 years, and 83.0% at 10 years. The graft survival rates in the nonelderly group was 91.1% at 1 year, 85.2% at 3 years, 82.8% at 5 years, and 82.9% at 10 year. There was no significant difference between the 2 age groups. In the elderly group, 3 patients died (2 patients had HCV recurrence and 1 patient had fungal infection in the brain, leading to a fatal subarachnoid hemorrhage). In the nonelderly group, 4 of 10 patients died of graft failure due to the graft size being too small. CONCLUSION: Elderly patients, at the end stage of liver failure, are likely very frail and may have latent infections. Careful examination for latent infections before LDLT should be carefully performed in regard to indications for LDLT, which might reach satisfactory outcomes as in nonelderly LDLT recipients. Even if elderly patients are approved for transplantation, very careful management is needed.

Effectiveness of the Combination of Everolimus and Tacrolimus With High Dosage of Mizoribine for Living Donor-Related Kidney Transplantation.

BACKGROUND: Everolimus (EVR) has been used widely for the purpose of reducing the dosage of calcineurin inhibitor (CNI), leading to decreasing CNI nephrotoxicity. In Japan, high-dose mizoribine (MZR) (6 mg/kg/day) has been increasingly used because of incidences of virus infection and gastrointestinal disorder in kidney transplant recipients. However, the efficacy and safety of EVR and MZR combination therapy is still uncertain. METHODS: A total of 29 living kidney transplant recipients from October 2012 to June 2014 were analyzed. Tacrolimus (TAC), MZR, basiliximab, and prednisolone were administered to all recipients. EVR was added to the regimen for 10 recipients from postoperative day 10 to 14; TAC trough levels were minimized simultaneously (EVR group). The remaining 19 recipients were defined as the control group. We evaluated the outcomes between the 2 groups. RESULTS: The mean TAC trough level was 5.17 ng/mL at 1 month after transplantation in the EVR group, and 7.89 ng/mL in the control group (P = .007), respectively. The mean TAC trough level was 4.0 ng/mL at 18 months after transplantation in the EVR group, and 6.97 ng/mL in the control group (P = .003) respectively. There were no differences in the rate of acute rejection and serum creatinine level. There was no significant difference in the incidence of histological nephrotoxicity between the 2 groups in the 1-year biopsy results. CONCLUSIONS: We succeeded in reducing TAC trough level immediately after transplantation by adding EVR. Our study results suggest that this combination therapy is effective for kidney transplantation recipients.

Living-donor kidney transplantation with existing anti-donor specific antibodies at a Japanese single center.

Improving the short-term outcome of kidney transplantation, the rejection induced by anti-donor specific antibody (DSA) has been the large complication. We analyzed 324 living-donor kidney transplant recipients (procedures performed between April 2003 and August 2014) to investigate the outcome of kidney transplant recipients with DSA. We divided them into four groups (anti-blood type antibody alone, group A [n = 73]; anti-human lymphocyte antigen [HLA] antibody alone, group B [n = 11]; both antibodies, group C [n = 8]; and no DSA, group D [n = 232]) and investigated the incidence of rejection and those histologic findings. Each case with DSA underwent some desensitization therapy before transplantation. There was no significant difference in graft survival (all cases: 100% at 1 year, group A: 97.6%, B: 95.9%, C: 100%, and at 5 years, group D: 96.1%). There were some significant differences in incidence of acute antibody-mediated rejection (AAMR) and chronic active antibody-mediated rejection (CAAMR) among four groups (group A: 4.1% and 2.7%, B: 18.2% and 9.1%, C: 12.5% and 12.5%, D: 0% and 0.9%, respectively). Each AAMR case was improved by ordinary desensitization therapy, but half of the CAAMR cases, diagnosed early after transplantation, had no effect of any therapy to result in graft failure. Our results suggested that even the case with DSA could be transplanted safely by some desensitization therapy. However, we should be cautious regarding recipients with DSA for the long term even if there is no histologic change early after transplantation because graft loss may occur due to CAAMR.

Advantages and disadvantages of pre-emptive kidney transplantation: results from a single transplantation center.

BACKGROUND: There is a growing tendency to perform pre-emptive kidney transplantation (PKT). However, less research has been performed on outcomes of PKT and kidney transplantation (KT) after long-term dialysis (LD). METHODS: To elucidate advantages of PKT to KTLD, 96 patients who underwent living-donor KT at our university from 2000 to 2011 were enrolled for this study: 64 patients in the PKT0 (0 months dialysis) group; 14 patients in the PKT-3 group (less than 3 months dialysis); 18 patients in the LD (dialysis > 120 months) group. All recipients were assessed for patients' survival, graft survival, urinary tract infection, laboratory data, episodes of acute rejection, cytomegalovirus-related diseases, and other significant infectious diseases which required hospitalization. RESULTS: Although there were no significant differences in 5-year graft survival (93.8% in PKT0, 85.7% in PKT-3, and 83.7% in control), 5-year patient survival is better in the PKT0 group (96.9%) and the PKT-3 group (92.9%) compared to 88.9% in the control group. Urinary tract infection is clearly correlated with the LD group (44.4% in the LD group vs 19.2% in the PKT group) primarily due to atrophic bladder and subsequent vesicoureteral reflux. Slightly higher rates of acute rejection were found in the PKT groups (30.8% vs 26.3%). CONCLUSION: This study revealed that there are both advantages and disadvantages of PKT. It is clear, therefore, that PKT can be recommended for end-stage renal disease patients provided enough attention is paid to the onset of acute rejection.

Histopathologic impacts of everolimus introduction on kidney transplant recipients.

BACKGROUND: Introduction of everolimus (RAD) has been established as a new immunosuppressive medication for kidney transplant (KT) recipients. Administration of RAD is capable of reducing the dosage of coadministrated calcineurin inhibitors (CNI). However, histological investigations have rarely been performed. METHODS: To clarify histopathologic effects of RAD, a total of 9 adult KT recipients were enrolled (RAD group, n = 5; Mycophenolate mofetil (MMF) group, n = 4). Renal graft biopsies had been performed at 3 weeks and 1 year following KT. RESULTS: There were no differences in 1-, 3-, and 5-year graft survival rates (RAD group: 100%, 100%, and 80%, respectively; MMF group: 100%, 100%, and 75%, respectively), and patient survival between the 2 groups (no deaths during the 5 years post-transplantation). Interestingly, although 2 patients in the RAD group had developed CNI nephrotoxicity clinically, renal biopsies had proven no CNI-related lesions 1 year later, which might be due to the reduction in CNI. On the other hand, 1 patient, in the MMF group, had been diagnosed histologically with new-onset CNI nephrotoxicity 1 year following KT. Importantly, the frequency and mean arteriolar hyalinosis (ah) scores, which reflect CNI nephrotoxicity, were significantly higher in the MMF group at 1-year biopsy (P < .05, P < .0001). Two patients in the RAD group improved their ah scores between 3 weeks and 1 year. CONCLUSIONS: Pathological findings revealed that reversible CNI nephrotoxicity can be improved by RAD with reduced CNI maintenance therapy. It is reasonable to believe, therefore, that introduction of RAD is useful for patients who have been diagnosed with CNI nephrotoxicity.

Evaluation of renal allograft fibrosis by transient elastography (Fibro Scan).

BACKGROUND: Chronic allograft injury (CAI) is one of the most important factors for graft failure after renal transplantation. Protocol biopsy is the most valuable tool for revealing subclinical renal allograft failure. Transient elastography (TE) is a noninvasive technique that has shown utility for the assessment of hepatic and renal fibrosis. This study sought to evaluate whether TE was a viable and effective method for the assessment of renal allograft failure. PATIENTS AND METHODS: Thirty-five patients underwent TE by Fibro Scan (Echosense, Paris, France). Biopsies were performed in 27 patients, allowing classification according to Banff chronic changes in the interstitium grade 0, grade 1 or grade 2. RESULTS: Measurement of parenchymal stiffness was successful in 31 of 35 patients (91%). Stiffness was significantly correlated with interstitial fibrosis (P < .05) and inversely related with estimated glomerular filtration rate (eGFR; P < .05). Stiffness values of patients with eGFR > 50 mL/min were lower than those of patients with eGFR < 50 mL/min (P < .05). Patients classed as CAI Banff grade 0 had significantly less parenchymal stiffness than patients with Banff grade 1 or grade 2 CAI (P < .05). Parenchymal stiffness measured by TE reflected interstitial fibrosis in renal allograft. CONCLUSION: Assessment of parenchymal renal allograft stiffness by TE was effective for identifying patients with CAI who may subsequently benefit from biopsy and modification of the immunosuppressive regimen. Assessment of parenchymal renal allograft stiffness can be effective for identifying patients with CAI. TE has the potential to reduce the number of renal allograft biopsies required for accurate assessment of CAI.

Evaluation of rituximab dosage for ABO-incompatible living-donor kidney transplantation.

BACKGROUND: The introduction of rituximab has led to a growing tendency to perform ABO-incompatible living-donor kidney transplantation (LDKT) without splenectomy. However, the optimal dosage of rituximab is undefined. METHOD: Fifty-five LDKT recipients who had neither a history of hepatitis B infection nor positive crossmatch were enrolled between October 2005 and June 2014. Recipients were divided into three groups by year of transplantation: 2005 to 2008; 2009 to 2011; and 2012 to 2014. Percentages of CD20-positive B lymphocytes and blood-group antibody titers were monitored before renal transplantation. An initial rituximab dosage of 100 mg/body (for titers below 64) or 200 mg/body (for titers above 128) was administered 2 weeks before transplantation. If the percentage of peripheral B lymphocytes remained greater than 0.5%, additional rituximab (100 mg or 200 mg) was administered. Patient demographics, patient survival, graft survival, and complication rates were compared. RESULTS: Nine patients received rituximab 100 mg/body (low-dose rituximab [LDR] group). Overall survival and graft survival rates did not differ significantly between the LDR group and other cases. The incidences of myelosuppression and viral infection were lower in the LDR group than the other cases. CONCLUSION: A low dose of rituximab (100 mg/body) is adequate in ABO-incompatible LDKT, especially in cases with low blood-type antibody titer against ABO-antigens. Rituximab dosage reduction has been successful in our hospital without serious complications. Moreover, as over-dosage of rituximab may cause myelosuppression, it is reasonable to believe that LDR is a suitable option to safely perform ABO-incompatible LDKT without splenectomy.

Usefulness of follow-up biopsies at one year after ABO-incompatible kidney transplantation.

BACKGROUND: Due to the shortage of deceased donor kidneys, we have expanded the indications for living-donor kidney transplantation (LKT) including ABO-incompatible (ABO-i) donors in Japan. In this study, the utility of protocol biopsies was discussed in ABO-i LKT. METHODS: Protocol biopsies have been performed on kidney graft 1 hour, 3 weeks, and 1 year after LKT in our institution. The relationship between biopsies and clinical courses was considered retrospectively in 38 cases of ABO-i LKT. The immunosuppressive regimen consisted of anti-CD20 antibody, mycophenolate mofetil, prednisolone, calcineurin inhibitor (cyclosporine or tacrolimus), and anti-CD25 antibody. Anti-ABO blood type antibody removal by plasmapheresis was performed before LKT up to 32 times. The post-transplantation regimen consisted of mycophenolate mofetil or mizoribine as an antimetabolite. RESULTS: Episode biopsies have been performed in 6 cases within 3 weeks post-transplantation. Each pathological diagnosis was as follows: antibody-mediated rejection (AMR; 5 cases) and calcineurin inhibitor (CNI) nephrotoxicity (1 case). Subclinical chronic active AMR was found at 1 year post-transplantation follow-up biopsies in 4 of the 6 cases. Episode biopsies have been done in the other 6 cases from 1 month to 1 year post-transplantation. Each pathological diagnosis was as follows: acute T-cell-mediated rejection (TMR; 1 case), vesicoureteral reflux (VUR; 3 cases), CNI nephrotoxicity (2 cases), and VUR + CNI nephrotoxicity (1 case). AMR was also not found at 1 year post-transplantation follow-up biopsies in them. In all cases episode biopsies were performed based on pathological diagnosis and had no graft dysfunction after that. CONCLUSIONS: Pathological study revealed that acute AMR was found early (ie, within 3 weeks) following transplantation. Although appropriate treatment made AMR go into remission once, chronic active AMR was often found at 1-year follow-up biopsies.

Usefulness and safety of high-dose mizoribine on ABO-incompatible living related kidney transplantation using anti-CD20 and anti-CD25 antibodies without splenectomy: 3-year results.

BACKGROUND: Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but has a less potent immunosuppressive effect up to 3 mg/kg/d. We previously reported that high-dose MZR, at 6 mg/kg/d, would be effective and safe for ABO-incompatible(ABO-i) living donor kidney transplantation (LDKT) patients when combined with cyclosporine (CsA) or tacrolimus(FK), anti-CD20 and anti-CD25 monoclonal antibodies, and corticosteroid without splenectomy in a 1-year study. Therefore, we observed these patients for 3 years. METHODS: From 2007 to 2010, we encountered 24 cases of ABO-i LDKT using anti-CD20 and anti-CD25 monoclonal antibodies without splenectomy. The pretransplantation immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF, 25 mg/kg/d), prednisolone, calcineurin inhibitor (CNI; CsA 7 mg/kg or (FK 0.2 mg/kg) and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LDKT up to several times according to the antibody titer. The post-transplantation regimen consisted of high-dose MZR (6 mg/kg/d) instead of MMF (MZR group, N = 12) . RESULTS: The 3-year graft survival rates for the MZR and MMF groups were 91.7% and 100%, respectively. Serum creatinine levels for the MZR and MMF groups were 1.44 mg/dL and 1.31 mg/dL at 1 year, 1.55 mg/dL and 1.41 mg/dL at 2 years, and 1.51 mg/dL and 1.48 mg/dL at 3 years, respectively (not significant [NS]). The MZR group did not show a higher rate of elevated serum uric acid values. The percentage of patients who were administered anti-uric medication was 42.5% (5/12) in the MZR group and 50% (6/12) in the MMF group (P = NS) at the third year. Severe infection, such as cytomegalovirus, herpes zoster, was not observed at the second and third years in both groups. CONCLUSION: A high-dose MZR regimen including CNI (CsA or FK), steroid, and anti-CD20 and anti-CD25 antibodies without splenectomy was effective and safe in ABO-i renal transplantation.

Results of kidney transplantation for diabetic nephropathy: a single-center experience.

In Japan, diabetic nephropathy accounted for 16,225 (43.7%) of the 38,473 patients who began hemodialysis in 2010 and the number increases year by year. In 1991, we started a kidney transplantation program for patients with diabetic nephropathy in our institution, and the ratio of patients who underwent kidney transplantation for diabetic nephropathy traces the course of increase. Among the 516 patients who underwent primary kidney transplantation in our institution from January 1991 to February 2013, we divided them into 2 groups. One group was the diabetes mellitus (DM) group, which included patients with primary disease of diabetic nephropathy, and the other group was the non-DM group. The DM group included 50 patients, and in our institution the ratio traces the course to increase. There was no significant difference for the 1-year and 5-year patient survival rates and graft survival rates between the DM group and the non-DM group. Moreover, the rate of acute rejection in the 2 groups was not significantly different. Furthermore, when we investigated the causes of death in the 2 groups, there was no significant difference with the mortality of cases due to heart vascular disease in the DM group and the non-DM group. Also, no case in which the graft lost function due to recurrence of diabetic nephropathy was observed. Although the early outcome of kidney transplantation for diabetic nephropathy in our institution did not have inferiority in comparison with kidney transplantation for the other primary disease, we think that careful diabetic control after kidney transplantation is required for long-term outcome.

Excellent results of high-dose mizoribine combined with cyclosporine, basiliximab, and corticosteroids in renal transplant recipients--4-year results.

BACKGROUND: Mizoribine (MZR) at 3 mg/kg/d shows less potent immunosuppressive effects, but high-dose MZR (6 mg/kg/d) was effective and safe in a 2-year study in conjunction with a regimen of cyclosporine (CsA), basiliximab, and corticosteroids. METHODS: We compared 40 living-related kidney recipients administered MZR (6 mg/kg/d), CsA (7 mg/kg/d), prednisolone (maintenance dose 10 mg/d), and basiliximab (20 mg/body) with control group (n = 38) treated with CsA, mycophenolate mofetil (MMF; 25 mg/kg/d), basiliximab, and corticosteroids. RESULTS: The 4-year graft survival rates for the MZR vs MMF groups were 92.5% vs 94.7%, respectively, with serum creatinine levels of 1.66 ± 1.0 mg/dL vs 1.41 ± 0.42 mg/dL at 3 years, and 1.72 ± 1.16 mg/dL vs 1.56 ± 1.26 mg/dL at 4 years. There was no significant difference in serum creatinine levels between the 2 groups. The MZR group demonstrated a significantly higher rate of elevated serum uric acid values (29.7%). The numbers of patients treated with allopurinol at 4 years were 11/37 (29.7%) for MZR vs 2/36 (5.6%) for the MMF subjects (P < .05). Mean serum uric acid levels of the MZR vs MMF group at 4 years were 7.1 ± 1.9 mg/dL vs 7.0 ± 1.6 mg/dL, respectively (NS). There was no significant difference between the 2 groups regarding bone marrow suppression or liver dysfunction. Severe cytomegalovirus infection was not observed at 3 and 4 years in either group. There were no severe gastrointestinal symptoms among the MZR or the MMF group at 3 or 4 years. CONCLUSIONS: The combination of high-dose MZR with CsA, basiliximab, and corticosteroids displayed excellent results over a 4-year follow-up.

Investigation of histological vascular invasion from preoperative evaluation in patients with hepatocellular carcinoma who underwent living donor liver transplantation.

Tumor vascular invasion is one of the worst factors of metastasis and/or recurrence in hepatocellular carcinoma (HCC) patients after living donor liver transplantation (LDLT), leading to poor outcomes. We investigated the relevance between preoperative parameters and histological vascular invasion among HCC patients who underwent LDLT. We enrolled 27 HCC patients who underwent LDLT from September 2003 to February 2011 in our hospital. Their primary diseases were hepatitis C (n=16) hepatitis B (n=9), primary biliary cirrhosis (n=1), and cryptogenic liver cirrhosis (n=1). The 2 groups were positive (N=7) versus negative (N=20) histological vascular invasion. We compared the greatest size and numbers of tumors from preoperative enhanced computerized axial tomography (CAT) scans, preoperative serum levels of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), as well as preoperative anticancer therapy. The preoperative greatest average diameter and numbers of tumor were 2.99 cm and 2.43, respectively, among positive patients, and 1.93 cm and 1.3, respectively, among patients with negative vascular invasion. The mean values of AFP and PIVKA-II were 3568.7 ng/mL and 2511.7 mAU/mL, respectively, among positive patients, and 812.8 ng/mL and 134.8 mAU/mL, respectively, among patients with negative vascular invasion. Five positive and 11 negative patients received preoperative anticancer therapy. Even if the tumor was within Milan criteria, namely, maximum size 3 cm and number of tumors 3, preoperative treatment may be a preoperative predictive factor for positive histological vascular invasion.

The efficacy and safety of high-dose mizoribine in ABO-incompatible kidney transplantation using anti-CD20 and anti-CD25 antibody without splenectomy treatment.

BACKGROUND: Mizoribine (MZR) has been developed as an immunosuppressive agent in Japan, but it shows less potent immunosuppressive effects at doses up to 3 mg/kg/d. In this study, we investigated whether high-dose MZR (6 mg/kg/d) was effective for ABO-incompatible (ABO-i) living donor kidney transplantation (LKT) using treatment with anti-CD25 and anti-CD20 monoclonal antibodies without splenectomy. METHODS: Since 2007, we encountered 24 cases of ABO-i LKT using anti-CD20 and anti-CD25 monoclonal antibody without splenectomy. The pretransplant immunosuppressive regimen consisted of two doses of anti-CD20 antibody, mycophenolate mofetil (MMF), prednisolone, a calcineurin inhibitor (cyclosporine [7 mg/kg] or tacrolimus [0.2 mg/kg] and two doses of anti-CD25 antibody. Antibody removal by plasmapheresis was performed before LKT up to several times according to the antibody titer. The posttransplant regimen consisted of high-dose mizoribine (6 mg/kg/d) instead of MMF (MZR group, n = 12). RESULTS: The 1-year graft survival rates for the MZR and MMF groups were both 100%. The rejection rate in the MZR group (eight %) was not significantly higher than that in the MMF group (seventeen %) Serum creatinine level was not significantly different between the two groups. In the MZR group 6 (50%) patients developed CMV antigenemia-positivity versus 11 (92%) in the MMF group (P < .05). The number of patients who developed CMV disease was 0 in the MZR group and 1 (8%) in the MMF group. The number of patients treated with ganciclovir was 0% and 8%, respectively (not significant). CONCLUSIONS: We obtain good clinical results with high-dose MZR in ABO-i LKT using anti-CD20 and anti-CD25 antibody treatment without splenectomy.

A case of living-donor renal transplantation for chronic renal failure caused by secondary amyloidosis.

In Japan, amyloidosis is a rare cause of renal failure and of renal transplantation. We treated a patient who underwent a renal transplantation because of chronic renal failure caused by secondary amyloidosis with a good result. The patient was a 50-year-old woman who was diagnosed with secondary amyloidosis and an amyloid kidney. She underwent living donor renal transplantation after about 7 years of hemodialysis. During the 3-year posttransplantation period, she maintained good allograft function with a serum creatinine level about 1.2 mg/dL. Because of amyloidosis is a systemic disease, amyloid kidney patients often experience fatal complications, so the indications for renal transplantation in amyloid patients are still controversial. But if the patient's general condition is good, renal transplantation can be an effective therapy for patients with kidney failure caused by amyloidosis.