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.

Hyperuricemia and Acute Renal Failure in Renal Transplant Recipients Treated With High-Dose Mizoribine.

BACKGROUND: Hyperuricemia is a common adverse event frequently found in renal transplant recipients with mizoribine (MZ). Hyperuricemia itself will be a cause of renal dysfunction, and renal dysfunction also will be a cause of hyperuricemia simultaneously. This study investigates frequency of hyperuricemia and renal failure in renal transplant recipients treated with high-dose MZ. PATIENTS AND METHODS: From December 2007 to October 2015, there was a total of 32 living related renal transplant recipients treated with high-dose MZ. Of the 32 patients, 28 were treated with urate-lowering medications. RESULTS: One patient received allopurinol (AP) and 13 patients received benzbromarone (BB). For 6 of them, their urate-lowering medications were converted to febuxostat (FX) form AP or BB. In the remaining 14 patients, FX was administered from the beginning. In 2 cases of ABO-incompatible living related renal transplant recipients who were maintained with high-dose MZ and BB, severe hyperuricemia and acute renal failure occurred. One patient was a 48-year-old man, and his creatinine (Cr) level increased to 8.14 mg/dL and his serum uric acid (UA) was 24.6 mg/dL. Another patient was a 57-year-old man, and his Cr level increased to 3.59 mg/dL and his UA was 13.2 mg/dL. In both cases Cr and UA were improved, and no finding of acute rejection and drug toxicity was observed in graft biopsy specimens. BB was switched to FX and discontinuance or reduction of MZ was done. CONCLUSION: Combination of MZ and BB has the risk of acute renal dysfunction after renal transplantation. Latent renal dysfunction should be watched for in renal transplant recipients receiving high-dose MZ.

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.

How long should we follow the post-transplantation patient after graft loss? A case report of renal cancer in the grafted kidney that occurred 16 years after graft loss.

BACKGROUND: Renal cancers commonly occur in the native kidneys of renal transplant recipients, whereas renal cancer in the grafted kidney has been reported occasionally. Renal cancer in the grafted kidney occurred 16 years after graft loss in this case, which would be a more rare case. CASE REPORT: A 60-year-old man who had a kidney transplant from his mother at the age of 31 years and had hemodialysis again because of chronic rejection from the age of 44 years had right lower abdominal pain. Computerized tomography (CT) showed tumor involvement in the grafted kidney. Positron-emission tomography-CT also showed hot spots in the liver, cervical vertebra, and costal bone. Needle biopsy for grafted kidney and liver tumors were done, and pathologic findings revealed renal cancer of grafted kidney and metastatic liver tumor. Graftectomy was done, and renal cancer was diagnosed as spindle cell carcinoma. Irradiation for cervical bone metastasis was done after the surgery. He complained of abdominal pain and eating disturbance 2 months after the surgery. CT showed a huge recurrence tumor and multiple tumor dissemination. Small intestine was involved and obstructed by the main tumor. He died of recurrence of renal cancer 3 months after the surgery. CONCLUSIONS: It is reported that the rate of renal cell carcinoma in the grafted kidney was 0.19%-0.5% and it occurred at a mean of 12.6 years after renal transplantation. Herein, we report a rare case of renal cancer that occurred 29 years after renal transplantation. Long-term observation should be required for recipients who had rehemodialysis.

Acute renal failure caused by hyperuremic acidemia in ABO-incompatible kidney transplant maintained with cyclosporine and high-dose mizoribine: a case report.

INTRODUCTION: The shortage of cadaver organs has led to expansion of living donor kidney transplantations with, 30% increase among ABO-incompatible cases in Japan and the use of marginal extended donors. Herein we have reported the outcome after an ABO-incompatible kidney transplantation from an aged living-related donor who suffered from mild diabetes mellitus and hypertension. CASE REPORT: A 48-year-old man underwent ABO-incompatible kidney transplantation from his 76-year-old father, using anti-CD20 antibody induction, followed by cyclosporine (CsA), mycophenolate mofetil (MMF), and prednisolone. After the operation, MMF was switched to high-dose mizoribine (MZ). He was discharged from the hospital on postoperative day (POD) 28 with a serum creatinine (sCr) of 1.47 mg/dL. On POD 34 when the sCr was 8.14 mg/dL, his urine examination showed uric acid crystals with serum uric acid of 24.6 mg/dL. Biopsy findings showed no evidence of acute rejection but mild tubulointerstitial injury. Hemodialysis performed twice to reduce uric acid was accompanied by hydration. CsA/MZ was switched to tacrolims/MMF; benzbromarone, to febuxostat to treat hyperuric acidemia. On POD 58, sCr reduced to 1.75 mg/dL he was discharged. On POD 416, graft function was stable with sCr of 1.70 mg/dL. CONCLUSION: Common side effect of MZ is hyperuricemia which presumably caused acute renal failure of this aged marginal donor kidney.

Excellent results with high-dose mizoribine combined with cyclosporine, corticosteroid, and basiliximab in renal transplant recipients: multicenter study in Japan.

We performed a multicenter study in Japan to assess the efficacy and safety of immunosuppressive therapy with high-dose mizoribine (MZR; 6 mg/kg) combined with basiliximab (Bas), cyclosporine (CyA), and a corticosteroid in 90 patients. MZR was adjusted to maintain a target trough level of 1 to 2 µg/mL. CyA was started at 7 mg/kg to maintain blood levels in the target therapeutic range of 200 ng/mL (trough [C0]), 1200 ng/mL (2-hour post-dose [C2]), and 6000 ng·h/mL (area under the curve(0-9)). Bas (20 mg/body weight) was administered on the day of transplantation and on postoperative day 4. Rejection was diagnosed by episode and protocol biopsies. Cytomegalovirus (CMV) antigenemia (direct immunological staining of leukocytes using peroxidase-labeled monoclonal antibody [C7-HRP]) levels were measured every 2 weeks for 6 months. At 12 months, all patients and grafts were surviving except for one death from infection: the 1-year patient and graft survival rate was 98.9%. The acute rejection rate was 21.1%. The mean serum creatinine level at 1 year was 1.51 ± 0.61 mg/dL. The incidence of CMV disease was 0% with 28.9%, CMV antigenemia and 5.6%, ganoyclovir treatment. The incidence of BK virus disease was 2.2%. The mean serum uric acid level was 7.15 ± 1.79 mg/dL at 1 month and 7.06 ± 1.78 mg/dL at 3 months. We observed that a high-dose MZR regimen in combination with CyA, Bas, and corticosteroid was safe and effective to reduce the frequency of CMV and BK virus-related events in renal transplant recipients.

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.

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.

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.

Microbubble destruction with ultrasound augments neovascularisation by bone marrow cell transplantation in rat hind limb ischaemia.

OBJECTIVE: To examine the effects of microbubble destruction with ultrasound (MB) combined with bone marrow derived mononuclear cell transplantation (BMT) into ischaemic tissues in rat hind limb ischaemia. METHODS AND RESULTS: Unilateral hind limb ischaemia was surgically induced in Lewis rats. At postoperative day 7, rats were randomly divided into three groups: a vehicle treated group, an ultrasound treated group, and an MB treated group. MB treatment increased vascular endothelial growth factor mRNA as assessed by real time polymerase chain reaction (3.0-fold, p < 0.05). At four weeks, the MB group had increases in laser Doppler blood flow index (LDBFI; 1.2-fold, p < 0.05), angiographically detectable collateral vessels (angiographic score: 1.4-fold, p < 0.01), and capillary to muscle fibre ratio (1.4-fold, p < 0.01) in ischaemic limbs compared with the vehicle treated group. No differences were seen between the vehicle and ultrasound treated groups. Secondly, rats were allocated to vehicle treatment, BMT (5 x 10(6) cells/rat), or a combination of MB and BMT (MB+BMT) at seven days after hind limb ischaemia. BMT treatment significantly increased LDBFI, angiographic score, and capillary to muscle fibre ratio compared with vehicle treatment. Interestingly, MB+BMT treatment produced significantly greater LDBFI (1.2-fold, p < 0.01), angiographic score (1.5-fold, p < 0.01), and capillary to muscle fibre ratio (1.5-fold, p < 0.05) than BMT treatment alone. CONCLUSIONS: MB may be a useful technique to enhance BMT induced neovascularisation.

Improved graft survival in ABO-incompatible living donor kidney transplantation.

INTRODUCTION: We reviewed ABO-incompatible living donor kidney transplantations (LDKT) performed in our institute. PATIENTS: Fourteen ABO-incompatible LDKT were carried out in the first era (September 1990-August 1996) and 13 were in the second era (October 2001-July 2004). All patients were treated with sessions of plasmapheresis before transplantation to reduce antibody titers <1:8. In the second era, those with rebound increase of antibody titers >1:64 after repeated plasmapheresis were not subjected to transplantation. Posttransplantation immunosuppression consisted of cyclosporin, predonisone, azathioprine, gusperimus hydrochloride (DSG), and antilymphocyte globulin (ALG) in the first era, and tacrolimus, mycophenolate mofetil, predonisone, and DSG in the second era. Splenectomy was performed during the transplantation. Anticoagulant therapy was introduced in the second era. RESULTS: One-, 2-, and 5-year graft survival in the first era was 57%, 57%, and 50%, respectively, values that were significantly lower than those of ABO-compatible cases in the same period (n = 101), namely, 1-, 3-, and 5-year graft survival rates 93%, 83%, and 76%, respectively. The main reason for graft and patient losses was infectious complications. In the second era, no recipient suffered a severe infectious complication and 1- and 2-year graft survival rates were both 100%. Four patients in the first era and 1 in the second era experienced a graft rejection episode between 10 days and 14 months after transplantation, but they were successfully treated with steroid pulse therapy. CONCLUSION: Although patients with high blood group antibody titers remain problematic, ABO-incompatible LDKT is an increasingly viable option for patients whose only donor is blood group-incompatible.

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.

Effects of eplerenone on transcriptional factors and mRNA expression related to cardiac remodelling after myocardial infarction.

OBJECTIVE: To examine the effects of eplerenone, a selective aldosterone blocker, on cardiac function after myocardial infarction (MI) and myocardial remodelling related transcriptional factors and mRNA expression in non-infarcted myocardium. METHODS: MI was induced by ligation of the coronary artery in Wistar rats. Rats were randomly assigned to a vehicle treated group or an eplerenone treated group (100 mg/kg/day). RESULTS: At four weeks after MI, left ventricular (LV) end diastolic pressure, LV weight, and LV end diastolic dimension were increased in MI rats. Eplerenone significantly reduced the increase in LV end diastolic pressure, LV weight, and LV end diastolic dimension. In the MI rats the decreased ejection fraction indicated systolic dysfunction and the increased E wave to A wave ratio and E deceleration rate indicated diastolic dysfunction. Eplerenone significantly attenuated this systolic and diastolic dysfunction. Myocardial interstitial fibrosis, transcriptional activities of activator protein 1 and nuclear factor kappaB, and mRNA expression of monocyte chemoattractant protein 1, plasminogen activator inhibitor 1, atrial natriuretic peptide, brain natriuretic peptide, and collagen types I and III were significantly increased at four weeks after MI. Eplerenone significantly attenuated interstitial fibrosis and suppressed transcriptional activity and mRNA expression of these genes. CONCLUSIONS: When administered after MI, eplerenone prevents cardiac remodelling accompanied by systolic and diastolic dysfunction and inhibits abnormal myocardial transcriptional activities and gene expression.

Recurrence of focal glomerulosclerosis in post-renal transplant recipients: report of two cases.

INTRODUCTION: Focal segmental glomerulosclerosis (FGS) has a tendency to recur frequently after kidney transplantation. To evaluate the incidence and outcome of recurrence of FGS, we report 2 cases of recurrence. PATIENTS: Among 12 patients with renal failure caused by biopsy-proved FGS who received kidney allografts from living related donors, 2 experienced recurrent FGS. CASE REPORTS: Case 1 was a 28-year-old man who received a renal transplant from his mother. The recurrence of FGS happened just after the scheduled reduction in immunosuppressants at 36 months after the transplantation. He developed subsequently end-stage renal failure (ESRD) 50 months after transplantation. Case 2 was a 22-year-old man who received a renal transplant from this ABO disparate mother. A few days after renal transplantation, he displayed a severe nephrotic syndrome due to recurrent FGS, reaching ESRD at 23 months. To treat recurrent FGS, plasma exchange was partially effective, reducing the proteinuria but not stopping the progression of disease. DISCUSSION: Two recipients with severe proteinuria were diagnosed as having recurrent FGS. The incidence of recurrent FGS was 16.7% with 5-year and 10-year graft survival rates among recipients with ESRD caused by FGS of 79.6% and 68.2%, respectively. The incidence and graft survival rates were better than those expected based upon previous reports. Once the recurrence occurred, it was difficult to halt the progression of disease. Effective prevention of FGS and careful observations with maintained of immunosuppression are necessary in these patients.

An autopsy case of bacterial septic shock 12 years following ABO-incompatible renal transplantation.

We report the case of an ABO-incompatible kidney transplant recipient who died suddenly following a good transplant course of 12 years. For 10 years after transplantation, the graft function had been stable (s-Cr: 1.0-1.5 mg/dL), although chronic hepatitis C had developed, with elevation of transaminase. In the 11th year, he was admitted into the hospital with low-grade fever and general fatigue. Jaundice and anaemia progressed, and he died 2 months after admission. The autopsy diagnosis was: (1) post-renal transplantation state, (2) phlegmonous enterocolitis with septic infarction, (3) cellulitis and necrotic myositis, and (4) sepsis. The transplanted kidney graft showed well-preserved glomeruli and tubules, corresponding to chronic allograft nephropathy (CAN) grade Iota (ci1, ct1, cv1), according to the Banff classification. The pathological changes observed in this long-surviving ABO-incompatible kidney graft were similar to those of an ABO-compatible graft, although its degree was milder.

Optimization of the use of cyclosporine in renal transplantation.

The immunological barrier remains the major obstacle to the widespread use of transplantation as a replacement therapy for terminal organ failure. Since the first successful renal transplant performed by Hume et al in 1952, there has been an elusive search for agents rendering the immune mechanism unresponsive to the specific alloantigen stimulus of the engrafted organ while sparing nonspecific host resistance. Immunosuppressive therapies in organ transplantation can be divided into the following four main classes; chemical (pharmaceutical), biological (immunological), physical (radiological), and surgical. Of these, chemical agents (drugs) have continued to play a principal role. The discovery of new immunosuppressive drugs such as corticosteroids, azathioprine, cyclosporine (CsA), tacrolimus, mycophenolate mofetils and so on made an epoch at each stage in history of clinical organ transplantation. The recent immunosuppressants were designed to focus their action selectively on T and /or B cells by inhibiting cytokine synthesis (CsA, FK506), cytokine action (Rapamycin), or cell differentiation (15-deoxyspergualin) pathways rather than to act on immune systems in a nonselective fashion. CsA has improved the success of kidney transplantation, reducing the incidence and severity of acute rejection and improving the patient and graft survival. Sandimmun Neoral offers promise due to its better bioavailability and limited dependence on bile flow for absorption. Long-term studies are under way to determine its effectiveness and safety. Therapeutic drug monitoring and combination therapy with CsA are investigated also.