Excellent Long-term Outcome of ABO-Incompatible Living Donor Kidney Transplantation in Japan

Owing to the severe shortage of cadaveric grafts in Japan, we have performed ABO-incompatible living donor kidney transplantation since 1989. This study assessed short- and long-term outcomes in 441 patients who received ABO-incompatible living donor kidney transplants between January 1989 and December 2001. We compared our results with historical data from 1055 recipients of living kidney transplantation. Overall patient survival rates 1, 3, 5, 7, and 9 years after ABO-incompatible transplantation were 93%, 89%, 87%, 85%, and 84%, respectively. Corresponding overall graft survival rates were 84%, 80%, 71%, 65%, and 59%. After ABO-incompatible transplantation, graft survival rates were significantly higher in patients 29 years or younger than in those 30 years or older and in patients who received anticoagulation therapy than in those who did not receive such therapy. There were no significant differences between A-incompatible and B-incompatible recipients with respect to clinical outcomes. The graft survival rate at 1 year in the historical controls was slightly but not significantly higher than that in our recipients of ABO-incompatible transplants. We conclude that long-term outcome in recipients of ABO-incompatible living kidneys is excellent. Transplantation of ABO-incompatible kidneys from living donors is a radical, but effective treatment for end-stage renal disease.     

Secondary erythrocytosis associated with distal renal tubular acidosis

AIMS: Diagnosis and classification of renal tubular acidosis (RTA) have traditionally been made on the basis of functional studies. Despite recent expanding knowledge about the molecular abnormalities involved in renal bicarbonate (HCO3-) and H+ transport, the pathophysiology of secondary erythrocytosis in association with distal RTA remains obscure. CASE HISTORY: A 2-month-old boy with severe hyperchloremic metabolic acidosis with positive urine anion gap was diagnosed with distal RTA. Replacement therapy with sodium bicarbonate and potassium citrate succeeded in improving his metabolic acidosis and growth. His renal function remained normal. He had persistent erythrocytosis. CONCLUSION: Secondary erythrocytosis is a rarely reported association of distal RTA. It may increase the risk of thromboembolism.     

Diabetic osteopenia and circulating levels of vitamin D metabolites in type 2 (noninsulin-dependent) diabetes

The degree of diabetic osteopenia and serum vitamin D metabolite levels were measured in 168 type 2 (noninsulin-dependent) diabetic patients. Based on six indices obtained by microdensitometry, we found the bone mass in 26.2% of diabetic patients to be clearly decreased and in 11.9% to be severely decreased. Our direct method of analysis of bone mass shows that diabetic osteopenia differs from typical osteoporosis in character. In addition, serum 24,25-dihydroxyvitamin D was significantly decreased (P less than 0.01), but 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were similar to those of controls.     

A nonerythropoietic derivative of erythropoietin inhibits tubulointerstitial fibrosis in remnant kidney

Background

The tissue-protective effects of erythropoietin (EPO) have been extensively investigated, and EPO administration can raise the hemoglobin (Hb) concentration. Recently, we reported that carbamylated erythropoietin (CEPO) protected kidneys from ischemia-reperfusion injury as well as EPO.

Methods

To investigate the clinical applications of CEPO, we next evaluated the long-term therapeutic effect of CEPO using a tubulointerstitial model rat. We randomized remnant kidney model rats to receive saline, EPO, or CEPO for 8?weeks.

Results

CEPO- and EPO-treated rats had improved serum creatinine levels compared with saline-treated remnant kidney model rats, although the Hb level was significantly increased in EPO-treated rats. Two-photon microscopy revealed that EPO/CEPO significantly ameliorated tubular epithelial cell damage assessed by endocytosis. In addition, CEPO or EPO protected endothelial cells with a sustained blood flow rate. EPO or CEPO suppressed the number of TUNEL-positive apoptotic cells with weak ??SMA staining. Furthermore, PCR analysis demonstrated that TGF-?? and type I collagen expression was attenuated in EPO- or CEPO-treated rats, accompanied by a significant decrease in interstitial fibrosis.

Conclusion

We established a long-term therapeutic approach to protect tubulointerstitial injury with CEPO, and thus, the therapeutic value of this approach warrants further attention and preclinical studies.     

A screening model for low bone mass in elderly Japanese men using quantitative ultrasound measurements: Fujiwara-Kyo Study

Screening for low bone mass is important to prevent fragility fractures in men as well as women, although men show a much lower prevalence of osteoporosis than women. The purpose of this study was to establish a screening model for low bone mineral density (BMD) using a quantitative ultrasound parameter and easily obtained objective indices for elderly Japanese men. We examined 1633 men (65-84 yr old) who were subjects of the Fujiwara-Kyo Study. Speed of sound (SOS) at the calcaneus was determined, and BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine (LS), total hip (TH), and femoral neck (FN). Low BMD was defined as >1 standard deviation below the young adult mean, in accordance with World Health Organization criteria. We performed receiver operating characteristic (ROC) analysis to identify a better screening model incorporating SOS and determined the optimal cutoff value using Youden index. Prevalences of low BMD at the 3 skeletal sites were 27.8% (LS), 33.5% (TH), 48.6% (FN), and 43.3% at either LS or TH. The greatest area under the ROC curve (0.806, 95% confidence interval: 0.785-0.828) and smallest Akaike's information criterion were obtained in the multivariate model incorporating SOS, age, height, and weight for predicting low BMD at all skeletal sites. This model predicted low BMD at TH with the sensitivity of 0.726 and specificity of 0.739, whereas a similar model predicted low BMD at LS with much lower validity. We conclude that the multivariate model for TH could be used to screen for low BMD in elderly Japanese men.     

Tissue factor antisense oligonucleotides prevent renal ischemia-reperfusion injury

BACKGROUND: Tissue factor (TF) expression is induced on macrophages and endothelial cells during the immune response. We designed an antisense (AS) phosphorothioate oligodeoxynucleotide (ODN) to specifically inhibit the expression of rat TF to study the effects of the AS ODN on renal ischemia-reperfusion injury in the rat. METHOD: AS-1 ODN for TF was delivered intravenously to inhibit the expression of TF in endothelial cells. After 8 hr, the right kidney was harvested and the left renal artery and vein were clamped. The kidney was reperfused after 90 min of ischemia, and rats were killed at 0, 1.5, 5, 12, and 24 hr after reperfusion. TF expression was analyzed by immunohistochemical staining using monoclonal antibody. RESULTS: In the untreated ischemic group, 0 of 20 rats survived beyond day 3. However, treatment with AS-1/TF led to 12 of 20 rats surviving beyond day 4. TF was detected on distal tubular epithelial cells, endothelial cells, and blood vessels but not on necrotic and proximal tubular epithelial cells. The necrotic area extended and encompassed nearly all of the ischemic kidney within 12 hr after reperfusion. The necrotic area and the grade of TF staining were more significantly reduced in the AS-1/TF-treated group than in the control group. Furthermore, fluorescein isothiocyanate-labeled AS-1/TF was significantly intense in tubular epithelial cells 8 hr after intravenous administration. CONCLUSIONS: The results indicate that AS-1/TF inhibited the ischemia-reperfusion injury of the kidney. Microcirculatory incompetence resulting from microthrombus may cause the formation and development of necrosis.     

Laparoscopy-assisted Billroth-I gastrectomy (LADG) for cancer: our 10 years' experience

To evaluate laparoscopy-assisted Billroth-I gastrectomy (LADG), we examined the outcome of its use over the last 10 years. From December 1991 to December 2001, 116 patients with early gastric cancer underwent LADG in the surgical department of Oita Medical University and Koga hospital by the same surgical staffs. An operation record and clinical sheets were reviewed to obtain the operative findings, clinical course, and pathologic findings of resected specimens to evaluate the usefulness of LADG in the management of early gastric cancer. In all LADG procedures, regional lymph nodes dissection (D1+alpha) was successfully performed using laparoscopy. The mean operative duration and blood loss were 234 minutes and 139 mL, respectively. There were only four major complications, including pneumonia, leakage of anastomosis, pancreatic injury, and anastomotic stenosis, but all these cases were successfully treated conservatively. The mean length of postoperative stay was 16.3 +/- 2.5 days. All patients except one, who died not of cancer but of cerebral bleeding, were alive without recurrence or port-site metastasis during mean follow-up period of 45 months. We successfully performed 116 LADG procedures over 10 years. This procedure is recommended for the treatment of patients with early gastric cancer because of the associated good prognosis and several benefits, including less invasiveness and early recovery.     

Development of intrahepatic biliary stones after excision of choledochal cysts

Background: The incidence of intrahepatic cholelithiasis and cholangitis has not yet been well studied postoperatively in patients with choledochal cysts. Methods: One hundred three patients with choledochal cysts had operative cholangiography, underwent standard excision of a choledochal cyst with Roux-en-Y hepatico-jejunal anastomosis, and were at a mean follow-up of 12[frac12] years. The incidence of intrahepatic bile duct stones was analyzed according to the 3 morphologic types of intrahepatic bile duct observed at initial operative cholangiography: type 1, no dilatation of the intrahepatic bile ducts; type 2, dilatation of the intrahepatic bile ducts but without any downstream stenosis; and type 3, dilatation of the intrahepatic bile ducts associated with downstream stenosis. Initially, there was no evidence of intrahepatic bile duct stones in any of the 103 patients. Results: Among 50 type 1 patients, intrahepatic cholelithiasis developed in only 1 patient (2%). Among 43 type 2 patients, 1 patient (2%) had intrahepatic cholelithiasis, and 2 (5%) had postoperative cholangitis. Among 10 type 3 patients, 4 (40%) had intrahepatic cholelithiasis (P [lt ] .01), and 3 (30%) had postoperative cholangitis. Time intervals between the initial surgery and the first identification of intrahepatic stones ranged from 3 to 22 years. Conclusions: One of the major causes of formation of intrahepatic cholelithiasis has been clarified; patients with intrahepatic biliary dilatation with downstream stenosis can get intrahepatic bile duct stones long after excision of a choledochal cyst.     

Results of a multicenter prospective clinical study in Japan for evaluating efficacy and safety of desensitization protocol based on rituximab in ABO-incompatible kidney transplantation

Background

Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy.

Methods

Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m² at day ?14 and day ?1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant.

Results

Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year.

Conclusion

Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

     

Retroperitoneal lymph node recurrence of seminoma 6 years after high orchiectomy

Late recurrence of stage I testicular seminoma is rare. We herein report a case of retroperitoneal lymph node recurrence of testicular seminoma 6 years after high orchiectomy. A 39-year-old man had a left high orchiectomy for stage I testicular tumor in November 1997. Histopathological findings revealed seminoma (pT3). In 2003, follow up computed tomography showed retroperitoneal lymph nodes swelling. Serum tumor markers had been normal since 1997. Retroperitoneal lymph nodes were dissected in April 2004. Histopathological findings were recurrence of seminoma.