Steroid withdrawal based on lymphocyte sensitivity to endogenous steroid in renal transplant recipients.

Though steroid withdrawal is done in many renal transplant recipients, some patients must restart steroids. Little report has investigated steroid withdrawal under pharmacodynamic monitoring. We assessed lymphocyte sensitivity to endogenous cortisol as a biomarker for determining the safety of steroid withdrawal in renal transplant patients, as we hypothesized that patients hyposensitive to cortisol could not be sufficiently immunosuppressed by their intrinsic cortisol as a substitute for the reduced or withdrawn steroid. Lymphocyte sensitivity to cortisol was examined in 30 long stable renal transplant recipients. Lymphocyte sensitivity to cortisol and its relationship with the clinical outcome after steroid reduction and withdrawal was investigated. The lymphocyte sensitivities to cortisol were estimated as IC(50) of lymphocyte blastogenesis. The lymphocyte proliferation rate for concentration of serum cortisol compared between incident and non-incident groups. Serum creatinine levels (S-Cr) increased in a significantly higher number of patients hyposensitive to cortisol (IC(50)≧10000 ng/ml) than in normally sensitive patients (IC(50)<10000 ng/ml). The incidences of steroid withdrawal syndrome and necessity for increasing steroid dose or restarting steroid administration were also higher in the patients hyposensitive to cortisol. The patients in whom the lymphocyte proliferation rate was less than 60% did not show increase in S-Cr, experience steroid withdrawal symptoms, or require an increase in the steroid dose or restart of steroid administration. The patients who have the normal IC(50) values of cortisol, can withdraw steroid more safely. The lymphocyte sensitivity to cortisol may be a useful biomarker for selecting patients who can sustain steroid withdrawal.

A nonsuture anastomosis using magnetic compression for biliary stricture after living donor liver transplantation.

Magnetic compression anastomosis involves the use of two magnets that are attracted transmurally between two internal organs resulting in compression and subsequent fistula formation (1). We report on the clinical use of magnetic compression anastomosis using extracorporeal magnetic guidance for the treatment of complete obstruction of the common bile duct (CBD) following living donor liver transplantation. This novel treatment has the advantages of low invasiveness and simplicity, and it should be considered as a feasible alternative therapy for biliary obstruction.

Evidence of different pharmacokinetics including relationship among AUC, peak, and trough levels between cyclosporine and tacrolimus in renal transplant recipients using new pharmacokinetic parameter--why cyclosporine is monitored by C(2) level and tacrolimus by trough level--.

The clinical efficacy of calcineurin inhibitors administered to renal transplant patients is considered to be a strong function of the area under the concentration time curve (AUC). Interestingly, monitoring timings of blood concentrations for two similar calcineurin inhibitors, cyclosporine (CYA; Neoral) and tacrolimus (TAC; Prograf) are different. Namely, CYA blood concentration is usually monitored at 2 h after administration (C(2)) substituted for peak concentration (C(p)) and TAC at trough concentration (C(t)). In the literature, data describing such characteristics of CYA and TAC have been presented in the past. However, each of these patient groups had different backgrounds. We have attempted to examine the behavior of blood concentration curves simultaneously for both CYA and TAC by establishing controlled groups of renal transplant patients with similar clinical backgrounds. Furthermore, we have analyzed the correlation with C(p) and C(t) versus AUC implementing area under the trough level (AUTL), or area above the trough level (AATL) as new pharmacokinetic parameters, such that C(2) for CYA and C(t) for TAC have been verified using controlled clinical data. We have also found distinct differences in the pharmacokinetics between CYA and TAC with the relationships between AUC, C(p), and C(t).

Intramesocolic diverticular perforation of the sigmoid colon diagnosed by detecting air collection in anterior pararenal space on computed tomography: report of a case.

A 64-year-old woman was admitted to our hospital with lower abdominal pain. Routine laboratory values were unremarkable except for the white blood cell count (15,000/micro litter) and the C-reactive protein (CRP) value (22.5 mg/dl). A Computed tomography (CT) scan revealed air collection in the middle of the anterior pararenal space. One day later, CT revealed air collection in the anterior pararenal space spread to the right side and abscess in the sigmoid mesentery. Because an intramesocolic perforation of the sigmoid colon was suspected, an emergency operation was performed. Abscess formation was recognized in the sigmoid mesentery, and sigmoidectomy including the contaminated mesentery and Hartmann.s procedure were performed. The perforation was 3 cm in diameter, and some diverticula were present in the vicinity of the perforated site. The specimen microscopically revealed perforation at the edge of the diverticulum in association with sudden disruption of the proper muscle layer. Based on pathological findings, intramesocolic diverticular perforation of the sigmoid colon was diagnosed. The present case is a very rare condition. However, it was possible to make a diagnosis preoperatively by detecting air collection in the anterior pararenal space on CT scan. If a sigmoid perforation occurs between the leaves of the mesocolon, air extends into the root of the sigmoid mesocolon and within the anterior pararenal space.

Long-term follow-up ABO-incompatible adult living donor liver transplantation in cirrhotic patients.

ABO-incompatible liver transplantation is usually contraindicated. The presence in the recipient of preformed anti-A/B antibodies located on endothelial cells raises the risk of antibody-mediated humoral rejection of the graft. We describe four successful cases of steroid withdrawal in adult patients who had living-donor liver transplantation from ABO-incompatible donors. Antirejection therapy included multiple perioperative plasmapheresis, splenectomy, and a triple immunosuppressive regimen with tacrolimus, methylprednisolone (MPSL), and cyclophosphamide or mycophenolate mofetil (MMF). The maintenance dose of immunosuppression did not differ from that of ABO-identical cases. After transplantation, intrahepatic arterial infusion therapy with prostaglandin E1 (PG E1) was used. As a result, all four patients were able to achieve long-term graft survival without steroid use. They all have good liver function and are leading normal lifestyles. Our experience with these four patients suggests the feasibility of controlling humoral rejection and other complications in adult ABO-incompatible living donor liver transplantations with intrahepatic arterial infusion of PGE1, splenectomy, and plasmapheresis with a regular base of immunosuppression protocol to prevent antibody-mediated humoral rejection.

Application of machine perfusion preservation as a viability test for marginal kidney graft.

BACKGROUND: This study evaluated the usefulness of machine perfusion preservation parameters as indicators of kidney graft viability. METHODS: Eighty-eight cadaveric kidneys were analyzed in this study. Of these, 74 kidneys (84.1%) were procured from nonheartbeating donors. The criteria for an acceptable kidney for transplantation were a perfusion flow of more than 0.4 mL/min/g with a concurrent decreasing perfusion pressure. The average perfusion pressure was 30-50 mmHg. We divided the kidneys into three groups: group 1 (n=35), 0.45-0.65 mL/min/g machine perfusion flow (MPF); group 2 (n=30), 0.65-0.90 mL/min/g MPF; and group 3 (n=23), more than 0.9 mL/min/g MPF. RESULTS: A higher rate of primary nonfunction (PNF; 25.7%) was found in group 1, compared with 6.7% in group 2 and 0% in group 3. A higher rate of 30.4% immediate function was found in group 3, compared with 16.7% in group and 8.6% in group 1. However, a longer period of acute tubular necrosis (ATN; 12.0 days) was found in group 1 compared with 8.6 days in group 2 and 8.7 days in group 3. PNF was detected in 7 (77.8%) cases with more than 16 hr of total ischemic time (TIT) in group 1. In contrast, all of nine cases with more than 16 hr of TIT in group 3 were functional. CONCLUSIONS: MPF is a reliable indicator of graft viability based on the rate of PNF and immediate renal allograft function, especially in marginal donors.

Early graft function in kidney transplantation from non-heart-beating donors.

The shortage of kidneys for transplantation is a universal problem. The non heart beating donor (NHBD) is one such source. This study evaluates the early graft function after kidney transplantation from NHBD. We report our experience with 126 kidney transplantations retrospectively. As a result, the kidney from NHBD over 50 years of age, led to the longer ATN and high PNF (13.8+/-12.6 days and 16.9% respectively). TIT more than 720 min or less had statistically correlated with the length of ANT (13.3 v. 8.4 days). Significant higher incidence of PNF (19.3%) was shown in the group of TIT more than 720 min with WIT of 20.8+/-31.6 min. Significant low flow by machine perfusion was resulted in PNF. In conclusion, we suggest that early and delayed graft function of kidneys from NHBD should be recognized as a separate clinical entity with its own significant effects.