An attempt to extend the donor criteria for successful living-related kidney transplantation from a donor with membranous nephropathy.

BACKGROUND: Marginally appropriate donors may be considered to extend the donor criteria for renal transplantation because of the donor shortage. We have reported a successful outcome after kidney transplantation from a living-related donor diagnosed with membranous nephropathy. CASE REPORT: A 38-year-old man began continuous ambulatory peritoneal dialysis (CAPD) at the age of 37. His 63-year-old father showed mild proteinuria, diagnosed as membranous nephropathy by needle biopsy. However, the father had normal renal function on preoperative examination, except for mild proteinuria. After adequate informed consent, we transplanted a kidney from the father who was diagnosed with membranous nephropathy into his son using a cyclosporine (CsA)-based immunosuppressive regimen. The postoperative course was good in both the recipient and the donor without rejection or infection. At 57 months after transplantation, the serum creatinine level was 1.7 mg/dL in the recipient and 1.2 mg/dL in the donor. An allograft needle biopsy at 39 months after transplantation showed mild spike formation with partial thickening of the glomerular basement membrane (GBM). Electron microscopy showed decreased electron-dense deposits and electron-lucent washout lesions with thickening of the GBM. This was diagnosed as stage IV membranous nephropathy, resulting from clearance of immune complexes and histological repair of the GBM. CONCLUSIONS: For the present donor, graft donation did not affect his residual renal function. Preexisting membranous nephropathy itself may show remission after transplantation into the recipient to achieve successful results, however, long-term careful observation of both the donor and recipient is required.

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.

Preemptive living donor liver transplantation in glycogen storage disease Ia: case report.

UNLABELLED: Even with substantial progress in the management of patients with glycogen storage disease type Ia (GSD-Ia), hepatic and renal complications may still develop during long-term follow-up. Herein, we report a case of preemptive living donor liver transplantation in a patient with GSD-Ia. PATIENT: The patient was a 5-year-old boy in whom GSD-Ia was diagnosed at age 10 months. Clinical symptoms included frequent hypoglycemic episodes, hyperlipidemia, hyperuricemia, and growth retardation, which were poorly controlled using conventional treatments. At age 5 years, frequent massive nasal bleeds developed, which led to severe anemia. The patient was brought to our institute for living donor liver transplantation (LDLT). Because GSD-Ia usually responds to dietary and medical treatments, we had a long discussion to determine whether preemptive LDLT was indicated. Transplantation was performed using the left lateral liver segment from the patients mother. The weight of his native liver was almost 2 kg. After reperfusion of the graft, the blood glucose concentration rapidly increased, and regular glucose was administered throughout the operation. The posttransplantation course was uneventful. The patient had no episodes of hypoglycemia with a regular diet. Total cholesterol, triglyceride, and uric acid concentrations also reverted to normal without medication. The patient had a few episodes of nasal bleeding after transplantation, which stopped spontaneously. He was discharged from our hospital with normal liver function. CONCLUSION: Patients with GSD-Ia should be considered for preemptive LDLT to improve their quality of life when clinical symptoms do not respond to appropriate treatment.

The excellent results of spousal kidney transplantation: experience in a Japanese single center.

In coping with the shortage of deceased kidney donors, living donor kidney transplantation is mainly performed in Japan. We started our living unrelated spousal kidney transplantation program in 1989. In this analysis, we compared the results of 64 spousal transplantations performed between September 1989 and May 2007 with those of living related and deceased donor grafts. Despite the older age of the recipients and the lower HLA matching, the graft survival rates of spousal transplants were as good as those from living related donors and better than those from deceased donors, (P < .01). The graft survival rate of spousal kidney transplantation is improving with advances in immunosuppression, so spouses are considered important donors in Japan, which lacks deceased donors.

Kidney transplantation for patients on long-term hemodialysis.

Patients surviving more than 10 years on hemodialysis (HD) are at risk of developing serious morbidity from unrelated conditions and from the many complications of long-term dialysis, such as cardiovascular disease, cerebrovascular disease, malignant tumors ectopic vascular calcification, diabetes mellitus, and disuse atrophy of the bladder. Long-term dialysis affects transplant patient outcomes and long-term graft survival. We analyzed 436 patients who underwent kidney transplantations between January 1987 and December 2007 to determine the impact of long-term dialysis on kidney transplant outcomes. The 39 patients who had been treated pretransplantation with dialysis for more than 10 years had an average length of dialysis treatment of 15.8 years (range, 10.0-32.5 years); they were denoted as the long-term hemodialysis group. The remaining 397 recipients showed an average of 3.7 years period of end-stage renal disease (ESRD) (range, 0-9.8, years; short-term hemodialysis group). There were significant differences in patient survival rates between the 2 groups: 93.2% vs 98.6%, at 1 year; 79.3% vs 95.4% at 5 years; and 58.4% vs 93.1% at 10 years (P = .0034). Also, graft survival was significantly different between the 2 groups: 89.2% vs 95.8% at 1 year; 60.4% vs 88.5% at 5 years; and 33.4% vs 80.4% at 10 years (P = .0026). Our results suggest that dialysis treatment for more than 10 years produces negative effects on post-transplantation patient and graft survival.

Biliary anastomosis and biliary complications following living donor liver transplantation.

Biliary complications are one of the most important problems in liver transplantation. Regardless of various improvements of surgical technique, liver transplantation is associated with significant biliary problems. In this article, we have described a biliary anastomosis method with a continuous suture (CS) technique in the posterior wall and interrupted suture (IS) technique for the anterior wall. We performed this biliary reconstruction in 28 adult patients between September 2003 and August 2007. Prior to that time our procedure was a CS anastomosis for both the anterior and posterior walls. A 5-Fr catheter is inserted into the biliary system. The current biliary complication was 3 cases (13.0%) of stenosis at the anastomosis, which is lower than that for a CS anastomosis. This anastomosis reduced biliary complications and is simple.

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.

Dexamethasone Prolongs Cardiac Allograft Survival in a Murine Model Through Myeloid-derived Suppressor Cells.

BACKGROUND: 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. MATERIAL AND METHODS: In this study, we investigated the mechanisms by which Dex modulated the immune response in mice given an allogeneic cardiac transplant. RESULTS: 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. CONCLUSION: An important role of Dex in the prevention of the rejection of cardiac grafts in mice is to expand MDSCs and Tregs.

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.

Beneficial Effects of High-Dose Mizoribine on ABO-Incompatible Living-Related Kidney Transplantation: Two-Year Results by a Japanese Multicenter Study.

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.

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.

Long-term outcome of renal transplantation in focal glomerulosclerosis.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) has a tendency to recur frequently after kidney transplantation. We evaluated 12 cases to examine the incidence and long-term outcomes of recurrent FSGS. MATERIALS AND METHODS: Twelve patients with renal failure caused by FSGS received kidney allografts from living related donors. Tacrolimus or cyclosporine was used in combination with prednisolone and azathioprine or mycophenolate mofetil. RESULTS: The mean graft survival was 87.4 +/- 46.8 months. The graft survival rates in FSGS recipients were at 1 year, 100%; 5 years, 79.6%; 10 years, 68.2%. Two out of four recipients experienced graft loss due to chronic rejection. The other two out of four recipients with graft loss displayed severe proteinuria diagnosed as recurrence of FSGS. To treat recurrent FSGS, plasma exchange was partially effective to reduce proteinuria. CONCLUSION: Our incidence of recurrent FSGS is 16.7% with graft survivals at 5 and 10 years of 79.6% and 68.2%, respectively. The recurrence of FSGS happened after scheduled reductions in immunosuppressants. Careful observation is required with maintenance of immunosuppression in these patients.

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.

Efficacy and Safety of High-Dose Mizoribine Combined With Cyclosporine, Basiliximab, and Corticosteroids in Renal Transplantation: A Japanese Multicenter Study.

Mizoribine (MZR) is an immunosuppressive agent that exhibits a less potent immunosuppressive effect at doses up to 3 mg/kg/d. We investigated whether high-dose MZR is effective and safe for renal transplant patients in conjunction with cyclosporine (CsA), basiliximab, and corticosteroids. Ninety Japanese renal transplant patients were administered MZR (6 mg/kg/d), CsA (7 mg/kg/d), prednisolone (maintenance dose, 10 mg/d), and basiliximab (20 mg/body). They were compared with a control group of 81 renal transplant patients who received mycophenolate mofetil (MMF; 1500 mg/d), CsA, prednisolone, and basiliximab. The 2-year patient and graft survival rates were 98.9% and 97.8% in the MZR group and 98.8% and 97.5% in the MMF group, respectively. The rejection rate within 2 years after transplantation was 21.1% in the MZR group and 16.0% in the MMF group; the difference was nonsignificant. None of the MZR group developed cytomegalovirus (CMV) disease, whereas 12.3% of the MMF group contracted CMV (P < .0001). CMV viremia developed in 28.9% of the MZR group vs 46.9% of the MMF group (P < .0001); their peak antigen levels were 20.4 ± 44.1 and 252.8 ± 527.0 (P < .01). Furthermore, the incidence of gastrointestinal disorder, hyperlipidemia, and blood disorder was significantly lower in the MZR group than in the MMF group. The combination of high-dose MZR with CsA, basiliximab, and corticosteroids not only provides satisfactory immunosuppression but is also associated with a low incidence of CMV infection and gastrointestinal and blood disorders.

Therapeutic drug monitoring of mycophenolic acid in renal transplant recipients.

Immunosuppressive regimens including mycophenolate mofetil (MMF, Cellcept) were used in a renal transplant transplant program since May 2000 including 67 patients in whom it was the primary drug. Acute rejection (AR) occurred in 9 cases (13%) with 1-year graft survival rate of 96.8%. Pharmacokinetic (PK) studies of mycophenolic acid (MPA) were performed in 46 recent patients (total, 127 times). There was no correlation between dose (mg/kg) and blood concentration (AUC0-9: r2= 0.27). AUC0-9 was well correlated with AUC0-4 (r2= 0.91), but not with a single timepoint concentration. MPA AUC0-9 level was significantly higher among the AR-negative group (n = 33; 34.2 +/- 16.8 ng.hr/mL) compared with AR-positive group (n = 3; 28.2 +/- 1.9 ng.hr/mL; P = .04085) over the 2 weeks after transplantation. MPA AUC0-9 level was higher among the adverse event (AE-positive) group (n = 15; 39.2 +/- 22.8 ng.hr/mL) compared with the negative group (n = 21; 30.1 +/- 8.0 ng.hr/mL; P = .08772) within 2 weeks after transplantation. These results suggest the necessity of measuring AUC for therapeutic drug monitoring (TDM) of MMF-containing immunosuppressive therapy. The possible target level of MPA AUC0-9 would be approximately 30 ng.hr/mL using the present immunosuppressive regimen.

Renovascular reconstruction of grafts with renal artery variations in living kidney transplantation.

INTRODUCTION: The shortage of grafts in living kidney transplantation has forced the use of marginal grafts with arterial disease or grafts with multiple renal arteries (MRA). We reviewed the outcomes of transplants using allografts with MRA procured by open donor nephrectomy and report two cases requiring vascular reconstruction. PATIENTS AND METHODS: We reviewed 31 cases where renovascular reconstruction of an MRA graft was performed. A ex vivo pantaloon (side-to-side) anastomosis to create a common channel was performed in 24 cases including two cases of renal artery aneurysms in the grafts, where vascular reconstruction was performed in the same fashion after resection of the aneurysm. In four cases, an accessory artery was anastomosed sequentially after revasculization of the main artery. In three cases of grafts with multiple renal arteries, multiple anastomoses were done in situ after various ex vivo renovascular reconstructions. RESULTS: Twenty one MRA grafts including grafts with a renal aneurysm are functioning well for a mean follow-up 135 months. The graft survival rate was 71.0% at 5 years after transplantation and 67.7% at 10 years. The donors whose grafts had a renal aneurysm were also well and normotensive with normal renal function at present. Ten grafts failed mainly due to chronic allograft nephropathy. CONCLUSION: MRA grafts procured by open nephrectomy, including those with renal artery aneurysms, were engrafted successfully by applying appropriate renovascular surgery. The use of those grafts was safe for both the recipient and the donor.

Twenty-five-year survival of living related kidney transplants: thirty-five years' experience.

AIM: Although better graft survival in patients treated with CsA has been obtained, chronic rejection continues to be a common complication in renal transplantation. In this study, we examined the graft survivals and complications among renal transplant patients followed for more than 25 years. METHODS: Between April 1970 and April 1979, 110 consecutive renal transplantations from living donors were performed in 110 patients. There were 83 men and 27 women of mean age of 27 +/- 7.0 years. A combination of azathioprine (AZ) and prednisolone (PSL) was used for the initial immunosuppressive therapy in all patients. RESULTS: Over 25 years postoperatively, 41 patients died with or without a functioning graft due to complications including infections and malignancies. Therefore, the 25-year patient survival was 62.5% and 34 patients returned to hemodialysis, yielding an actual 25-year graft survival of 36/110 (32.1%). The longest surviving graft is 30 years and 2 months. The main causes of death were infectious disease and malignancy; 73% of graft loss was due to chronic rejection. Mean serum creatinine of the patient with functioning grafts over 25 years is 1.2 mg/dL; 75% of patients displayed a value under 1.5 mg/dL. The mean dosage of Az was 52.3 mg/d and PSL was 5.6 mg/d.