Renal Tubular Acidosis Secondary to FK506 in Living Donor Liver Transplantation: A Case Report

FK506 is an immunosuppressant that is thought to be less nephrotoxic than cyclosporine A. However, complications due to renal tubular acidosis (RTA) have recently been reported. We report a case of RTA secondary to FK506 administration in liver transplantation. A 6-month-old girl was treated with FK506 after undergoing living donor liver transplantation for fulminant hepatitis. On postoperative day 17, she demonstrated hyperkalaemia and metabolic acidosis; she was diagnosed to have hyperkalaemic distal RTA with aldosterone deficiency (type IV). Intravenous sodium bicarbonate and furosemide, and intrarectal calcium polystyrenesulfonate were administered to correct the acidosis and promote potassium secretion. Thereafter, the FK506 concentration in whole blood gradually decreased, and the hyperkalaemia and metabolic acidosis following RTA improved. RTA is one type of nephrotoxicity induced by FK506, and it is reversible in mild cases when appropriately treated. The mechanism of RTA induced by FK506 has not yet been clearly elucidated. Surgeons and physicians should therefore be aware of the potential for RTA to occur with FK506 after any organ transplantation. The treatment for acidosis and hyperkalaemia should be started as soon as RTA is diagnosed, and the dosage of FK506 should also be reduced if possible

Effectiveness of Sirolimus in Combination with Cyclosporine against Chronic Rejection in a Pediatric Liver Transplant Patient

The patient is a 3-year-old boy who received living-donor liver transplantation (LDLT) for hepatoblastoma, with his mother as the donor. Oral tacrolimus was started at a dose of 0.3 mg every 12 h from day 1, with the dosage adjusted on the basis of trough concentrations. The levels of aspartate aminotransferase (AST), alanine transferase (ALT), and total bilirubin (T-bil) were 110 U/L, 182 U/L, and 12.6 mg/dL, respectively, when chronic rejection (CR) was pathologically diagnosed. Then, sirolimus at a dose of 1.0 mg/d was added to the tacrolimus-based regimen. The T-bil level rapidly decreased to 5.4 mg/dL, without changes in AST and ALT. Because the intracellular receptor of sirolimus and tacrolimus is FK506-binding protein 12, we switched tacrolimus to cyclosporine at a dose of 60 mg/d to avoid competitive inhibition between these 2 drugs. The target trough concentration of sirolimus and cyclosporine was set to around 15 ng/mL and 180 ng/mL, respectively. The concentration/dose ratio of sirolimus was significantly correlated with the blood cyclosporine level (r=0.5293, p<0.05), suggesting the pharmacokinetic interaction between these 2 drugs. Thereafter, the levels of AST and ALT as well as the T-bil were successfully decreased to 73 U/L, 83 U/L, and 3.0 mg/dL, respectively. These results suggest that sirolimus therapy in combination with cyclosporine may be an effective treatment against CR after liver transplantation

Effectiveness of Sirolimus in Combination with Cyclosporine against Chronic Rejection in a Pediatric Liver Transplant Patient

The patient is a 3-year-old boy who received living-donor liver transplantation (LDLT) for hepatoblastoma, with his mother as the donor. Oral tacrolimus was started at a dose of 0.3 mg every 12 h from day 1, with the dosage adjusted on the basis of trough concentrations. The levels of aspartate aminotransferase (AST), alanine transferase (ALT), and total bilirubin (T-bil) were 110 U/L, 182 U/L, and 12.6 mg/dL, respectively, when chronic rejection (CR) was pathologically diagnosed. Then, sirolimus at a dose of 1.0 mg/d was added to the tacrolimus-based regimen. The T-bil level rapidly decreased to 5.4 mg/dL, without changes in AST and ALT. Because the intracellular receptor of sirolimus and tacrolimus is FK506-binding protein 12, we switched tacrolimus to cyclosporine at a dose of 60 mg/d to avoid competitive inhibition between these 2 drugs. The target trough concentration of sirolimus and cyclosporine was set to around 15 ng/mL and 180 ng/mL, respectively. The concentration/dose ratio of sirolimus was significantly correlated with the blood cyclosporine level (r=0.5293, p<0.05), suggesting the pharmacokinetic interaction between these 2 drugs. Thereafter, the levels of AST and ALT as well as the T-bil were successfully decreased to 73 U/L, 83 U/L, and 3.0 mg/dL, respectively. These results suggest that sirolimus therapy in combination with cyclosporine may be an effective treatment against CR after liver transplantation

A Study of the Difference in Intestinal Adaptation between the Residual Jejunum and the Ileum in Rats with Short Bowel Syndrome

Objectives : Controversy remains regarding which residual segment, namely the jejunum or ileum, is more beneficial for intestinal adaptation in patients with short bowel syndrome (SBS). The aim of our study is to evaluate the residual intestinal adaptation after a massive small intestinal resection and thereby determine which of the two residual segments demonstrates a better intestinal adaptation. Methods : The SBS rats underwent about a 70 % resection of either the jejunum or ileum, respectively. Sham rats underwent an ileal transection with a subsequent reanastomosis of the same portion. The body weight was measured every day after the operation. Two weeks after the operation, all rats were sacrificed. The intestinal length, the hematological and serum chemical data, and the histological findings of the residual intestine were investigated in all rats to evaluate the intestinal adaptation. Results : The body weight gain in the rats with the residual ileum (ileum group) was similar to that of the Sham group and better than that of the rats with residual jejunum (jejunum group). The length of the residual intestines in the jejunum group was longer than that in both the sham and ileum groups. Regarding hematological and serum chemical studies, the jejunum group tended to demonstrate more anemia and malnutrition than both the sham and ileum groups. In a histological study, the villous height in both the jejunum and ileum groups was significantly larger than in the preoperative condition. In both groups, the degree of crypt depth only significantly increased in the ileum group in comparison to the preoperative condition. Regarding the thickness of the muscular layers, a no difference was observed among all groups. Conclusion : Based on our data, in patients with SBS, the use of the residual ileum was thereforefound to be preferable to that of the residual jejunum regarding intestinal adaptation

短腸症候群ラットモデルにおける残存小腸のadaptationの部位別の違いに関する研究

Objectives : Controversy remains regarding which residual segment, namely the jejunum or ileum, is more beneficial for intestinal adaptation in patients with short bowel syndrome (SBS). The aim of our study is to evaluate the residual intestinal adaptation after a massive small intestinal resection and thereby determine which of the two residual segments demonstrates a better intestinal adaptation. Methods : The SBS rats underwent about a 70 % resection of either the jejunum or ileum, respectively. Sham rats underwent an ileal transection with a subsequent reanastomosis of the same portion. The body weight was measured every day after the operation. Two weeks after the operation, all rats were sacrificed. The intestinal length, the hematological and serum chemical data, and the histological findings of the residual intestine were investigated in all rats to evaluate the intestinal adaptation. Results : The body weight gain in the rats with the residual ileum (ileum group) was similar to that of the Sham group and better than that of the rats with residual jejunum (jejunum group). The length of the residual intestines in the jejunum group was longer than that in both the sham and ileum groups. Regarding hematological and serum chemical studies, the jejunum group tended to demonstrate more anemia and malnutrition than both the sham and ileum groups. In a histological study, the villous height in both the jejunum and ileum groups was significantly larger than in the preoperative condition. In both groups, the degree of crypt depth only significantly increased in the ileum group in comparison to the preoperative condition. Regarding the thickness of the muscular layers, a no difference was observed among all groups. Conclusion : Based on our data, in patients with SBS, the use of the residual ileum was thereforefound to be preferable to that of the residual jejunum regarding intestinal adaptation