Long-Term Outcomes in Kidney Transplantation From Expanded-Criteria Donors After Circulatory Death.

The number of recipients waiting for a transplant is increasing. In Japan, there is more frequent use of organs from expanded-criteria donors (ECDs) after circulatory death. We retrospectively analyzed long-term outcomes of kidney transplantation (KT) from expanded-criteria donation after circulatory death (DCD). From 1995 to 2013, 97 cases of KT from DCD donors were performed in our department. Death-censored graft survival rates of ECD kidneys (n = 50) versus standard-criteria deceased-donor (SCD) kidneys (n = 47) for 1, 5, and 10 years after transplantation were 84.0% vs 97.9%, 74.8% vs 95.6%, and 70.2% vs 81.8%, respectively. No significant difference was found between the 2 groups (P = .102). Kidneys from donors with a history of hypertension (HTN) and cerebrovascular events (CVE) and contribution from older donors had significantly lower 10-year graft survival rates (P values of .010, .036, and .050, respectively). Cox proportional hazard regression analyses showed donor age to be significantly associated with long-term graft survival independently from other factors. These results suggest that ECD kidneys remain an acceptable alternative to dialysis under certain conditions. Increased donor age was a significant risk factor determining long-term graft function. Moreover, comorbidities of HTN and CVE could become significant risk factors, especially in older donors.

Efficacy and safety of febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase for the treatment of hyperuricemia in kidney transplant recipients.

BACKGROUND: Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia. In this study, we evaluated the efficacy and safety of febuxostat for the management of hyperuricemia in renal transplant recipients. PATIENTS AND METHODS: Between June 2012 and January 2013, a total of 22 renal transplant recipients (56 ± 10 years old) with hyperuricemia were enrolled in this study. All patients underwent de novo kidney transplantation, except for 1 patient, who received a second kidney transplant. Ten patients receiving allopurinol and 3 patients receiving benzbromarone were converted to febuxostat at doses of 10-20 mg/d. In the remaining 9 patients, who did not have a history of other urate-lowering medications, febuxostat was initiated at a dose of 10 mg/d. RESULTS: Uric acid levels after initiation of febuxostat were significantly lower than before treatment (5.7 ± 0.7 mg/mL vs 8.0 ± 0.8 mg/mL; P < .001). At last follow-up visit, 16 of the 22 patients (73%) achieved uric acid levels of ≤ 6.0 mg/dL, despite the low dosage of febuxostat. All patients were maintained on febuxostat without serious adverse events, except for 1 patient, who discontinued febuxostat because of numbness in the arms. CONCLUSIONS: Low-dose febuxostat is a promising alternative to allopurinol or benzbromarone for the treatment of hyperuricemia in kidney transplant recipients. The long-term urate-lowering efficacy and safety of febuxostat with regard to renal function in kidney transplant recipients with hyperuricemia requires further investigation.

How can we increase living related donor renal transplantations?

BACKGROUND: In Japan, living donor renal transplantation has gained momentum due to an increased number of patients with end-stage renal disease. Living donation not only provides better outcomes, but also the recipients usually need less medications, thereby increasing the quality of life and reducing the potential side effects of immunosuppression. MATERIALS AND METHODS: For the past 25 years, our center had performed 140 open donor nephrectomy (OPNx) renal transplantations. Since July 2003, we changed our procurement operation to living hand-assisted laparoscopic donor nephrectomy (HALNx) in 49 cases. Our operative technique consisted of two 12-mm ports placed in the midaxillary line at the superior and inferior levels of the umbilicus. Next, a 5-cm incision was made in the midline periumbilicus and the hand port system fitted through a midline abdominal incision. RESULTS: In 49 cases, HALNx was completed successfully; no patient required conversion to laparotomy. The estimated blood loss was 33.0 +/- 43.4 g and no patient required blood transfusion. In comparison, in OPNx the blood loss was 426.5 +/- 247.6 g (P < .001). The mean operative times were 167.4 +/- 39.7 minutes for HALNx and 228.4 +/- 35.7 minutes for OPNx (P < .001). The postoperative hospital stays were 9.1 +/- 3.8 days for HALNx and 13.0 +/- 1.9 days for OPNx (P < .001). For 3 years prior to introduction of HALNx, we had performed only 10 living donor renal transplantations. Since the introduction of HALNx in 2003, the number of living donors has tripled during the following 3 years. CONCLUSIONS: Herein we have reported that HALNx was superior in terms of less operative time and blood loss, postoperative pain and recovery, and shorter hospital stay. Overall donor patient satisfaction was also better in the HALNx group. HALNx is a safe procedure that makes kidney donation more appealing to potential live donors and has increased the living donor pool at our center.

Hand-assisted laparoscopic splenectomy in ABO-incompatible kidney transplant recipients.

OBJECTIVE: We perform living-related ABO-incompatible kidney transplantations to alleviate the organ shortage in our country. Splenectomy has been performed routinely in these recipients, although its clinical significance remains controversial. In this study, we have reported our experience with a hand-assisted laparoscopic splenectomy (HALS) technique. METHODS: Between April 2000 and December 2006, 50 patients (23 males) underwent ABO-incompatible kidney transplantation with HALS. The mean age and weight of the recipients were 44 +/- 13 years and 56 +/- 12 kg, respectively. All patients underwent preoperative plasmapheresis to reduce isoagglutinin (A and/or B antibody). In 6/50 patients, a hand-assisted device was placed through a peritoneal window in the right lower abdominal skin incision for kidney engraftment. In the remaining 44 patients, a 6-cm upper midline or periumbilical midline incision was made for the hand-assisted device in the lateral position. RESULTS: An ABO-incompatible procedure was completed successfully in all cases. The average HALS time was 118 +/- 42 minutes, with an average pneumoperitoneum time of 79 +/- 40 minutes and average blood loss of 48 +/- 81 g. There were two conversions to open splenectomy because of intraoperative bleeding and suspected pneumothorax. Two other cases required relaparotomy because of hematoma and perforation of the ileum. Successfully operations were achieved through the previous periumbilical incision. CONCLUSIONS: Although meticulous, rigorous surgical technique is essential, HALS is safe and feasible for recipients of ABO-incompatible grafts with tissue weakness and a bleeding tendency because of renal failure and preoperative plasmapheresis.

Effects of immunosuppressants on the progression of hepatitis C in hepatitis C virus-positive renal transplantation and the usefulness of interferon therapy.

OBJECTIVE: The purpose of this study was to analyze the effects of immunosuppressants on hepatitis C virus (HCV) replication to establish optimal immunosuppressive therapy in HCV-positive renal transplantation. MATERIALS AND METHODS: Cyclosporine (CsA), tacrolimus (Tac), mycophenolate acid (MPA), the active metabolite of mycophenolate mofetil (MMF), and methylprednisolone (MP) were administered to HCV replicon cells alone or in combination with interferon (IFN). HCV RNA was quantitatively determined. Of our 2064 recipients of renal transplantations between 1980 and 2005, 153 were HCV-positive. We analyzed changes in hepatic function and the efficacy of IFN therapy in these patients. RESULTS: Only CsA strongly inhibited the growth of HCV RNA (13.1% at 1.0 microg/mL). MPA enhanced the inhibition of the growth of HCV RNA in the presence of IFN. Tac and MP reduced, rather than enhanced, the efficacy of IFN. Progression to chronic hepatitis occurred in a significantly smaller number of patients in the CsA than the Tac group (6 vs 19; P = .04). Serum alanine aminotransferase (ALT) levels were comparable pretransplantation and posttransplantation in the CsA group (24.8 +/- 20.5 vs 28.9 +/- 28.3 IU/L, respectively, while a significant elevation was noted in the Tac group (22.2 +/- 21.5 vs 32.6 +/- 30.8 IU/L, respectively; P = .024). Two of 4 patients who underwent combination therapy with IFN and ribavirin during treatment with CsA and MMF obtained an HCV-negative status for over 24 weeks. CONCLUSIONS: CsA effectively prevents the progression of chronic hepatitis in HCV-positive renal transplant patients. A greater response rate can be expected by concurrent administration of CsA and MMF under IFN therapy.

Successful third kidney transplantation with intensive immunosuppression in a highly sensitized recipient.

HLA sensitization associated with previous kidney transplantation is a major drawback to retransplantation. Recently we successfully performed a third graft using intensive immunosuppression for a highly sensitized recipient. The patient was a 31-year-old man who had previously undergone a living donor graft from his father at our institute in 1999. His kidney graft function had deteriorated due to chronic allograft nephropathy, returning to hemodialysis therapy in 2005. He received a second graft from a deceased donor in another country on August 14, 2006. It rejected on postoperative day 3 possibly due to acute accelerated rejection. He was offered a third kidney from his brother. Panel-reactive antibody (PRA) tested before the third procedure revealed positive class I (88%) and class II (96%) PRAs. Mycophenolate mofetil (MMF) was started 3 weeks before the third transplantation, and preoperative plasmapheresis performed thrice. He underwent the living donor graft on March 9, 2007. Immunosuppression consisted of tacrolimus, MMF, methylprednisolone, and basiliximab. Immediately afterward there was a sudden decrease in allograft blood flow and urine output, implying hyperacute rejection. Following treatment with plasmapheresis and a single dose of rituximab (200 mg), the kidney allograft function recovered, although the PRA at 3 weeks was still positive. Six months posttransplantation, he is well with a creatinine of 0.9 mg/dL. Our protocol may reduce the risk for graft loss in a highly sensitized transplant recipient.

Improved outcomes of renal transplantation from cardiac death donors: a 30-year single center experience.

Outcomes of renal transplantation from donation after cardiac death (DCD) donors over 30 years were analyzed. Between 1975 and 2004, 256 renal transplantations from DCD donors were performed. The recipients were divided into four groups according to a time period as follows: 1975-1979 (Group 1; n = 18), 1980-1989 (Group 2; n = 81), 1990-1999 (Group 3; n = 84) and 2000-2004 (Group 4; n = 73). Of the 256 transplanted kidneys from DCD donors, 38 (15%) functioned immediately after transplantation. The incidence of delayed graft function (DGF) was 72%. Warm ischemic time and total ischemic time were 7.4 +/- 9.4 min and 11.9 +/- 5.6 h, respectively. The overall graft survival rates at 1, 5 and 10 years were 80%, 72% and 53%, respectively. Graft survival rates in each group have continually improved over time (5-year graft survival; 23% vs. 64% vs. 74% vs. 91%, respectively). However, there was no significant difference in graft survival rates between the groups of patients who survived with a functioning graft for more than 1 year. A multivariate Cox regression analysis showed acute rejection and donor age to be independently associated with graft outcome. DCD donors are a valuable source of kidneys for transplantation with promising long-term outcomes.

Cyclosporine-sparing effect of basiliximab in renal transplant recipients with mycophenolate mofetil.

UNLABELLED: Basiliximab added to a maintenance regimen consisting of cyclosporine microemulsion and mycophenolate mofetil was studied for its effectiveness in allowing early steroid withdrawal in renal transplantation. Furthermore, the cyclosporine-sparing effects between groups with and without basiliximab induction therapy were compared. PATIENTS: Between September 2001 and June 2003, 90 patients underwent renal transplants with cyclosporine-based immunosuppression, namely, cyclosporine, mycophenolate mofetil, and methylprednisolone, (group 1; n = 25). During the latter half of the study basiliximab was administered during the induction phase (group 2; n = 65). In group 2, steroids were completely withdrawn on postoperative day 14 in 57 patients. RESULTS: The incidence of acute rejection was significantly higher among group 1 patients (P = .005). The incidence of steroid-resistant rejection in group 1 patients was significantly higher (P = .025). At each time point cyclosporine levels in group 1 patients were significantly higher (P < .01). The incidence of infection was comparable between the groups. Patient and graft survival rates in group 1 were 100% and 100%; in group 2, they were 99% and 99%, respectively. In group 2, steroids were discontinued in 57 patients with permanent withdrawal achieved in 32 patients (56%). CONCLUSION: The use of basiliximab, together with mycophenolate mofetil allowed for a significant reduction in the cyclosporine dose without increasing the risk of acute rejection. Although further follow-up is necessary to confirm the effect, this regimen may attenuate cyclosporine nephrotoxicity thereby affecting the long-term outcomes of renal transplantation.

Hand-assisted laparoscopic live donor nephrectomy: report of 100 cases.

INTRODUCTION: Laparoscopic live donor nephrectomy is not yet widespread in Japan. After our first hand-assisted laparoscopic live donor nephrectomy (HALapNx) in 2001, we report our 100 cases and examine the possibility of making this technique widely available in Japan. METHODS: HALapNx was performed in 100 cases (44 males and 56 females) from February 2001 through July 2003. The operative procedure for HALapNx was briefly described here. First, 2 12-mm ports were placed in the midaxillary line at the superior and inferior level of the umbilicus. Next, a 5-cm incision was made in the midline periumbilicus and the hand port system was fitted through the abdominal incision. After 10 mm Hg pneumoperitoneum, HALapNx begins with mobilization of the left colon. RESULTS: HALapNx was completed successfully in all cases and no patients required conversion to laparotomy. The estimated blood loss was 33.5 +/- 40.3 g and no patient required blood transfusion. The mean operative time was 168.8 +/- 47.6 minutes, and there was no major complication in a donor. CONCLUSIONS: HALapNx is technically feasible and may offer several advantages over open donor nephrectomy in terms of less blood loss, less postoperative pain, and minimal cosmetic disfigurement. In Japan, laparoscopic donor nephrectomy is not yet widespread, possibly due to the need for surgical laparoscopic skills. We believe that the best way to make laparoscopic donor naphrectomy widely available is through hand-assisted laparoscopic surgery.

Results of kidney transplantation in patients receiving MMF- or MMF and basiliximab-containing immunosuppression.

UNLABELLED: Mycophenolate mofetil (MMF) is a more potent immunosuppressive drug than azathioprine or mizoribine in combination with cyclosporine (CsA) and steroids. Recently, basiliximab (BA), an interleukin-2 receptor antagonist, has become available in Japan. The purpose of this study was to evaluate the efficacy of an extremely low CsA dose immunosuppressive protocol with MMF versus MMF plus BA after renal transplantation (RTx). PATIENTS: Between September 2001 and March 2003, we performed 79 RTx with CsA-based immunosuppression, including nine from cadavers and 70 from living donors with 15 ABO-incompatible RTx. Immunosuppression consisted of methylprednisolone (MP), CsA and MMF (group 1; n = 24) versus added BA during the induction phase (group 2; n = 55). In group 2, MP was withdrawn on postoperative day 14. Supplementary MP, muromonab-CD3, or gusperimus was administered if rejection was suspected clinically or diagnosed by biopsy. RESULTS: The incidence of biopsy-proven acute rejection (AR) was significantly higher among group 1 than group 2 patients (P < .05). CsA C2 levels in group 1 were significantly higher than group 2 at each time (P < .01). The incidence of infection was comparable. Patient and graft survival rates in group 1 were 100% and 100%; in group 2, they were 98% and 98%, respectively. CONCLUSION: The short-term results of RTx were favorable in both the MMF, and the MMF plus BA immunosuppression. In addition, BA significantly reduced the number of AR episodes. Early steroid withdrawal in recipients receiving BA induction was not associated with an increased risk of AR.

Efficacy of basiliximab induction therapy in ABO-incompatible kidney transplantation: a rapid steroid withdrawal protocol.

INTRODUCTION: We have performed ABO-incompatible (ABO-i) kidney transplantation (KT) to alleviate the severe organ shortage in our country. Induction therapy with basiliximab, a monoclonal anti-interleukin-2 receptor antibody, is known to be effective in reducing the incidence of acute rejection (AR) after ABO-compatible KT. However, the efficacy of basiliximab in ABO-i KT is still unknown. In this study, we evaluated the effect of basiliximab to decrease overall maintenance immunosuppression (a steroid withdrawal protocol) and to improve the outcome of ABO-i KT. PATIENTS AND METHODS: Between April 2002 and May 2003, 14 adult patients underwent ABO-i KT from living donors with cyclosporine (CsA)-based immunosuppression. There were seven men and seven women of mean age 48 +/- 10 years. Three of the 12 cases were second KT. Three sessions of plasmapheresis were performed to remove anti-AB antibodies before KT. Splenectomy was performed in all patients. Immunosuppression consisted of methylprednisolone (MP), CsA, and mycophenolate mofetil, in addition to antibody induction with basiliximab. MP was completely withdrawn on postoperative day 14. RESULTS: In 3 of 14 recipients, MP was restarted because of AR or a suspicion of AR. Both patient and graft survivals were 100%. The incidence of biopsy-proven AR was 14% (2/14). There was no adverse effect related to the antibody therapy. CONCLUSION: The use of basiliximab induction therapy may eliminate the need for steroid maintenance therapy without increasing AR risk, even among ABO-i KT recipients. We conclude that basiliximab provides safe and effective induction immunosuppression in ABO-i KT recipients.

An intraoperative fluorescent imaging system in organ transplantation.

UNLABELLED: An intraoperative fluorescent imaging system (SPY system; Novadaq Technologies, Inc, Concord, Ontario, Canada) that enables vascular surgeons to confirm the location and states of the reconstructed vessels during surgery, has been developed in the field of open heart surgery. In this paper, we evaluated the usefulness of the SPY system in kidney and liver transplantation. PATIENTS AND METHODS: SPY system visualizes arteries and grafts intraoperatively, using indocyanine green (ICG) with a portable imaging device. The modality was evaluated in 15 patients undergoing kidney (n = 13) or liver (n = 2) transplantation with respect to safety, feasibility of use, and image quality. Images were generated and acquired with a portable laser diode/infrared camera device after injection of 10 mL of ICG (2.5 mg/mL) intravenously. RESULT: There was no complication associated with ICG injection or the imaging device. The SPY system was easily used during transplant surgery and adequately demonstrated reconstructed arteries and patency in all patients. CONCLUSION: The intraoperative imaging system enables the surgeon to view, record, and replay real-time images of the reconstructed arteries during surgery. The system may provide useful information during surgery such as solid organ transplantation that requires vascular reconstruction.

Living related liver transplantation for biliary atresia with portopulmonary hypertension: case report.

Portopulmonary hypertension is a complication of end-stage liver disease that adversely affects the outcome of liver transplantation (LT). We report a case of living related LT who developed severe pulmonary hypertension during and after LT. This 16-year-old girl suffered from biliary atresia, having undergone a portoenterostomy at 60 days of age, at the time of discovery of liver cirrhosis. She had been admitted to a local hospital several times for episodes of esophageal variceal bleeding. Neither dyspnea nor cyanosis was discerned until LT. Although pulmonary hypertension (PH) was disclosed by echocardiogram upon preoperative evaluation, we did not consider this a contraindication for LT, because the PH was mild. She underwent living LT from her father (graft volume/recipient body weight ratio: 0.99%). After induction of anesthesia for LT, a pulmonary flotation catheterization showed severe PH (>40 mm Hg). The pulmonary artery pressure continued to be elevated during surgery, although it was possible that her severe scoliosis affected the data. Hyperbilirubinemia was observed after LT, despite good liver function tests. On postoperative day 12, a portal vein thrombosis was detected requiring emergency thrombectomy and splenectomy. Her general condition worsened after the second surgery. She died due to cardiopulmonary failure. Autopsy showed marked hypertrophy of the right ventricle with intimal thickening in the pulmonary artery. In this case, the underestimated PH might have resulted in the unfortunate outcome. Before LT, PH should be carefully evaluated by measures including invasive assessment.

Alteration of collagen IV in acutely deteriorated renal allografts.

BACKGROUND: The changes in the basement membrane occurring in acutely deteriorated renal allografts (ADR) have not been extensively investigated. Our purpose is to elucidate the alteration of collagen IV, a main constituent of the basement membrane in ADR. METHODS: Fifty biopsy specimens of ADR and 10 of chronic transplant nephropathy (CTN) were examined with two monoclonal antibodies specific for collagen IV. JK199 and JK132 are monoclonal antibodies that recognize triple helical collagen IV containing the alpha1 chain. JK199 recognizes all the basement membrane containing [alpha1 (IV)]2alpha2(IV), although JK132 reacts only with a limited portion of it. In the normal kidney, JK199 reacts with the mesangial matrix, the basement membrane of Bowman's capsule (BBM), and the tubular basement membrane, as well as with the glomelular basement membrane (GBM). JK132 reacts with the mesangial matrix, BBM, and the tubular basement membrane. RESULTS: In ADR, increased intensity of JK199 was observed in GBM, the mesangial matrix, BBM, the tubular basement membrane, and the interstitium. Increased intensity of JK132 was observed in the mesangial matrix, BBM, and the tubular basement membrane, but was not remarkable in GBM or the interstitium. In contrast, biopsy specimens of CTN showed increased intensity of JK132 in GBM, the mesangial matrix, BBM, the tubular basement membrane and the interstitium. CONCLUSION: These results suggest that collagen IV is up-regulated in ADR. Differential staining of collagen IV with JK199 and JK132 in GBM and the interstitium may contribute to diagnose CTN.

An experimental sclerosing encapsulating peritonitis model in mice.

BACKGROUND: Sclerosing encapsulating peritonitis (SEP) is a life-threatening complication of continuous ambulatory peritoneal dialysis. To elucidate the mechanism and develop treatments for this condition, an experimental SEP model in mice was constructed. METHODS: C57BL/6 mice were administered 0.3 ml of 0.1% chlorhexidine gluconate and 15% ethanol dissolved in saline, intraperitoneally, on a daily basis for 56 days (group 1, n=15). A control group of C57BL/6 mice were administered 0.3 ml of phosphate-buffered saline only in the same manner (group 2, n=15). The mice were sacrificed on days 3, 7, 21, 56 and were prepared for histological analysis. RESULTS: In group 1, all mice had developed macroscopic evidence of SEP 56 days after the injection. Microscopically we observed peritoneal fibrosis and an increase in infiltrates of mononuclear cells over time. The peritoneal fibrosis reached the chronic inflammatory stage by 56 days after the injection. CONCLUSION: We have developed a convenient experimental model of SEP in mice, which may be useful in elucidating the pathogenesis of SEP and in establishing possible treatments.