Abstract 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 31of 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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Recently, myeloid-derived suppressor cells (MDSCs) have attracted considerable attention because of their cancer-promoting and immunosuppressive effects. The glucocorticoid dexamethasone (Dex) is an ...important immunosuppressive agent used to treat autoimmune diseases and organ transplant rejection. However, the mechanism by which it modulates the immune system is not completely understood.
In this study, we investigated the mechanisms by which Dex modulated the immune response in mice given an allogeneic cardiac transplant.
Dex injection significantly prolonged heart graft survival compared with phosphate-buffered saline–injected controls. Dex treatment increased the number of splenic MDSCs. Moreover, Gr-1high/CD11b+ MDSCs and CD3+/CD4+/Foxp3+ regulatory T cells (Tregs) were significantly increased in the Dex group compared with controls. Administration of anti–Gr-1 antibody (Ab) to the Dex group significantly shortened mouse heart graft survival. In addition, anti–Gr-1 Ab treatment significantly reduced Tregs in the Dex + anti–Gr-1 co-treatment group compared with the Dex group. These observations suggest that Dex treatment increased both MDSCs and Tregs, and that MDSCs regulated the incidence of Tregs in this immunosuppressive pathway.
An important role of Dex in the prevention of the rejection of cardiac grafts in mice is to expand MDSCs and Tregs.
•Anti–Gr-1 antibody shortens graft survival in cardiac transplanted mice.•Gr-1high/CD11b+ MDSCs expand regulatory T cells.•Dexamethasone treatment prolongs heart graft survival by increasing myeloid-derived suppressor cells and regulatory T cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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.
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.
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.
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.
•Immunocomplex capture fluorescence analysis (ICFA) is a useful technique to identify intragraft donor-specific anti-MHC antibodies.•Graft ICFA can be also applied in mice cardiac transplantation.•Graft ICFA would shed light on antibody-mediated rejection management.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Isolated superior mesenteric artery (SMA) dissection (SMAD) is considered a relatively rare disease. Especially, isolated SMAD following liver transplant has been rarely reported.
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.
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.
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.
•Isolated superior mesenteric artery (SMA) dissection (SMAD) following liver transplantation is a relatively rare vascular disease, but potentially life-threating.•Mechanical shear stress for SMA during surgery may contribute to the onset of SMAD.•It is necessary to quickly determine whether emergency revascularization should be performed for SMAD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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.
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.
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.
We found that donor age ≥65, with or without antihypertensive treatment, had no effect on graft or patient survival.
•More recipients from younger donors underwent preemptive transplantation.•Incidence of arteriosclerosis was higher in recipients from older donors.•Donor age had no effect on graft or patient survival.•Use of antihypertensive treatment had no effect on graft or patient survival.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract 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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Mizoribine (MZ) has been developed as an immunosuppressive agent in Japan, but it has a less-potent immunosuppressive effect up to 3 mg/kg/d. In the previous study, a Japanese ...multicenter study, we reported that high-dose MZ, at 6 mg/kg/d, with a calcineurin inhibitor was effective and safe in reducing the frequency of cytomegalovirus (CMV)-related events in ABO-incompatible (ABO-i) living-related kidney transplantation (LKT). In the present study, therefore, we investigated the effects of high-dose MZ with a CNI in ABO-i LKT recipients in a Japanese multicenter study. Methods A total of 37 patients were treated with high-dose MZ (6 mg/kg), a CNI (cyclosporine CsA or tacrolimus Tac), basiliximab (Bas), rituximab (Rit), and corticosteroids. CsA was started at a dose of 7 mg/kg to maintain blood levels 200 ng/mL (C0), 6000 ng-h/mL (AUC 0–9). Tac was started at a dose of 0.2 mg/kg to maintain blood levels 8–10 ng/mL (C0), 100 ng-h/mL (AUC 0–9). Bas (20 mg/body) was administrated on day 0 and day 4 after transplantation. Rit (100–200 mg/body) was administrated on day −14 and day −7 before transplantation. MZ was adjusted to maintain target C0 levels of 1.5 to 2.0 μg/mL. Results Patient and graft survival rates for 2 years were 100% in the CsA group (n = 22) and 93.3% in the Tac group (n = 15) (not significant, NS). Overall incidence of acute rejection for 2 years was 22.7% in the CsA group and 26.7% in the Tac group. Mean serum creatinine levels at 2 years were 1.29 ± 0.2 mg/dL in the CsA group and 1.21 ± 0.34 mg/dL in the Tac group (NS). The incidence of CMV disease was 0% in both groups, and positive rates of CMV antigenemia were 50.0% and 26.7% in the CsA and Tac groups, respectively (NS). Mean serum uric acid levels were 5.5 ± 1.3 mg/dL and 6.4 ± 1.2 mg/dL at 2 years (NS) in the CsA and Tac groups, respectively. Conclusions A high-dose MZ regimen including calcineurin inhibitor (CsA or Tac), Bas, Rit, and steroids was effective and safe in reducing the frequency of CMV-related events in ABO-i LKT.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract 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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract 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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract 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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
