Takashi Kenmochi

Mesobiliverdin IXα Enhances Rat Pancreatic Islet Yield and Function

The aims of this study were to produce mesobiliverdin IXα, an analog of anti-inflammatory biliverdin IXα, and to test its ability to enhance rat pancreatic islet yield for allograft transplantation into diabetic recipients. Mesobiliverdin IXα was synthesized from phycocyanobilin derived from cyanobacteria, and its identity and purity were analyzed by chromatographic and spectroscopic methods. Mesobiliverdin IXα was a substrate for human NADPH biliverdin reductase. Excised Lewis rat pancreata infused with mesobiliverdin IXα and biliverdin IXα-HCl (1–100 μM) yielded islet equivalents as high as 86.7 and 36.5%, respectively, above those from non-treated controls, and the islets showed a high degree of viability based on dithizone staining. When transplanted into livers of streptozotocin-induced diabetic rats, islets from pancreata infused with mesobiliverdin IXα lowered non-fasting blood glucose (BG) levels in 55.6% of the recipients and in 22.2% of control recipients. In intravenous glucose tolerance tests, fasting BG levels of 56 post-operative day recipients with islets from mesobiliverdin IXα infused pancreata were lower than those for controls and showed responses that indicate recovery of insulin-dependent function. In conclusion, mesobiliverdin IXα infusion of pancreata enhanced yields of functional islets capable of reversing insulin dysfunction in diabetic recipients. Since its production is scalable, mesobiliverdin IXα has clinical potential as a protectant of pancreatic islets for allograft transplantation.

Association of DNA Amplification With Progress of BK Polyomavirus Infection and Nephropathy in Renal Transplant Recipients

PURPOSE BK polyomavirus-associated nephropathy (BKVAN) is an important cause of renal allograft loss. Immunosuppression therapy in renal transplant recipients can lead to the reactivation of latent BK polyomavirus (BKV) infection, leading to BK viruria and viremia. This single-center study aimed to clarify the association between quantitative measurement of BKV DNA and the progression of BKV infection, and secondly to identify the risk factors associated with the evolution of viruria to viremia. METHODS We retrospectively analyzed 266 patients who underwent renal transplantation in our center from October 2006 to February 2013. We examined the viral loads of BKV in urine and plasma by quantitative real-time polymerase chain reaction assay after screening all of the recipients by urinary sediment examination. BKVAN was diagnosed by histological examination with immunohistochemistry of the large T antigen in biopsy specimens. RESULTS Overall, 22 recipients showed BK viruria alone, whereas 22 progressed to BK viremia, of which 6 patients were diagnosed with BKVAN. Among BKVAN patients, 2 cases progressed to graft loss at 59 months and 31 months after diagnosis, respectively. In BKVAN group, the plasma viral loads were significantly higher than those in viremia without nephropathy (P < .001). Multivariate analysis revealed that the evolution of viruria to viremia was associated with recipient age over 55 years (odds ratio, 32.08; 95% confidence interval, 2.1-489.5) and tacrolimus exposure (odds ratio, 11.98; 95% confidence interval, 1.34-107.04). CONCLUSIONS The progression from viremia to BKVAN was strongly associated with increasing plasma viral loads for BKV DNA. The cutoff value of 1 × 10(4) copies/mL for plasma viral loads could differentiate between BKVAN and viremia alone. Further, recipient age over 55 years and tacrolimus exposure were independently associated with the evolution of viruria to viremia.

A novel screening test for detecting graft thrombosis after pancreatic transplantation using contrast-enhanced ultrasonography with sonazoid.

Pancreatic graft thrombosis is the primary cause of nonimmunologic graft loss, with an incidence ranging from 5% to 15%. Therefore, developing a screening test to detect graft thrombosis after pancreatic transplantation is important. We created a screening test to assess graft thrombosis after pancreatic transplantation using contrast-enhanced ultrasonography (CEUS) with Sonazoid in addition to Doppler ultrasonography. A total of seven patients were examined using CEUS after undergoing pancreatic transplantation. All patients were observed to have a clear blood flow from the horizontal region to the peripheral region of the splenic vein in the pancreatic graft, and only one of the seven patients exhibited a blood flow in the horizontal portion of the splenic vein on Doppler ultrasonography performed immediately after pancreatic transplantation. Results from CEUS with Sonazoid showed the blood flow in the splenic vein and parenchyma of the pancreatic graft in detail, despite the slow and lateral blood flow in the splenic vein of the pancreatic graft immediately after transplantation.

Pathologic findings of renal biopsy were a helpful diagnostic clue of stenosis of the iliac segment proximal to the transplant renal artery: a case report.

Common iliac artery stenosis after renal transplantation is a rare complication; it can occur in the course of hypertension and renal dysfunction. We report a case of suspected renal allograft rejection with iliac artery stenosis proximal to a transplanted kidney. A 52-year-old man with a history of cadaveric kidney transplantation 26 years previously underwent a second cadaveric kidney transplantation in the left iliac fossa because of graft failure 3 years before. In June 2012, the patient had progressive renal dysfunction. In July, a percutaneous needle biopsy was taken, and it showed no rejection; however, his renal function continued to get worse through September. A percutaneous allograft renal biopsy was performed under ultrasound guidance and showed hyperplasia of the juxtaglomerular apparatus and renin granules. Magnetic resonance angiography was used to evaluate the arteries in the pelvis and showed left common iliac artery stenosis, and a stent was placed. After percutaneous intervention, the patients ankle brachial pressure index was within the normal range and the allograft function had improved.

Kidney Transplantation, Cardiovascular Risk, and Long-Term Dialysis in Japan.

BACKGROUND The waiting time for deceased-donor kidney-only transplantations in Japan is long. Herein, we assessed the effect of length of dialysis on the outcomes of these patients. METHODS We divided patients into 2 groups based on length of dialysis (Group A, <15 years, and Group B, ≥15 years), and compared the background and outcomes after kidney transplantation. RESULTS Group A included 210 patients and Group B included 35 patients. In Group B, 20% of transplants were from living donors. Patient age (P = .017) and the hepatitis C infection rate (P = .018) were significantly higher in Group B, whereas hypertension (P = .011), diabetes (P = .041), and ABO-incompatibility rates (P = .015) were significantly higher in Group A. The 5- and 10-year survival rates were 97.0% and 95.4%, respectively, in Group A and 97.1% and 97.1%, respectively, in Group B. The 5- and 10-year graft survival rates were 95.4% and 84.8%, respectively, in Group A and 97.1% and 73.1%, respectively, in Group B. There were no significant differences between the groups in patient survival (P = .74) and graft survival (P = .72). The 5- and 10-year cardiovascular event-free survival rates were 95.9% and 92.4%, respectively, in Group A and 88.6% and 76.8%, respectively, in Group B. Cardiovascular event-free survival was significantly higher in Group A (P = .038). Cox stepwise multivariate analysis indicated that length of dialysis was a significant predictor of cardiovascular events (hazard risk, 1.007; range, 1.001-1.012; P = .012). CONCLUSION The prognosis after kidney transplantation is promising even after a long length of dialysis, although evaluation of the cardiovascular risk is needed in these cases.

Single institution outcomes in the first 3 years of pancreas transplantation from brain dead donors

A total of 26 pancreas transplants from brain dead donors, including 21 simultaneous pancreas and kidney (SPK) transplantation procedures, have been performed at Fujita Health University Hospital since the new pancreas transplant program was initiated in August 2012. The objective of this study is to investigate the outcomes of pancreatic transplantation in our facility in first 3 years of the program.

Combined predictive value of the expanded donor criteria for long‐term graft survival of kidneys from donors after cardiac death: A single‐center experience over three decades

Kidneys procured from the deceased hold great potential for expanding the donor pool. The aims of the present study were to investigate the post‐transplant outcomes of renal allografts recovered from donors after cardiac death, to identify risk factors affecting the renal prognosis and to compare the long‐term survival from donors after cardiac death according to the number of risk factors shown by expanded criteria donors.

LD for Pancreas Transplantation

The first extrarenal organ to be successfully transplanted using living donors was the pancreas. The first pancreas transplantation using a living donor (LDP) was performed on June 20, 1979, at the University of Minnesota [1, 2]. Furthermore, successful simultaneous pancreas and kidney transplantation from a living donor (LDSPK) was started in 1994 also at the University of Minnesota [3]. The outcome of LDPs performed at the University of Minnesota demonstrated that the segmental pancreas was able to normalize plasma glucose levels and realize an insulin independency in the severe diabetic patients. The outcome of the donors was considered to be acceptable when using the stringent donor criteria concerning the endocrine function [4].

DCD for Kidney Transplantation

The concept of brain death was introduced with the Harvard criteria in 1968 [1]. However, brain dead (DBD) donors were not used for organ transplantation in Japan until the enforcement of the Japanese Organ Transplant Law in 1997. Therefore, prior to this, all cadaveric kidney transplantations were performed using DBD donors according to the law regarding DCD for cornea and kidney transplantation. Due to a severe shortage of deceased donors, kidney transplantation is mainly performed using living donors in Japan. Changes in the number of kidney transplantation (Fig. 14.1) showed 212 patients underwent kidney transplantation from deceased donor in 2011, while 1,389 patients underwent living donor kidney transplantation [2]. Even after the enforcement of the Japanese Organ Transplant Law in 1997, the number of DBD donors remained low, such were only several donors per year. Although the number of DBD donors has been increased since the enforcement of the revised Japanese Organ Transplant Law in July 2010, deceased donor kidney transplantation is still mainly performed from DCD donors. Therefore, a history of deceased donor kidney transplantation is almost equal to the history of kidney transplantation using DCD donors.

ECD for Islet Transplantation

Pancreatic islet transplantation offers a minimally invasive option for type 1 diabetic patients. Before 2000, less than 10 % of the recipients of islet transplantation achieved insulin independency [1]. The introduction of the Edmonton Protocol, however, with a highly improved rate of insulin independency, encouraged us to promote clinical islet transplantation [2, 3]. In the Edmonton Protocol, brain-dead donors were used for islet isolation, and the donors were selected according to the factors that influence the success of islet isolation [4]. Even using the Edmonton Protocol, the results of clinical islet transplantation including a long-term graft survival were far from ideal and were significantly worse than clinical pancreas transplantation (pancreas transplant alone, PTA). The newly designed protocol from Minnesota University by Hering et al. that includes induction therapy with a T-cell-depleting antibody (anti-thymus globulin, ATG) and an inhibitor of tumor necrosis factor-α (TNF-α) achieved successful islet transplantation from a single donor. Short-term and long-term islet graft survivals were shown which were comparable to those in clinical pancreas transplantation (PTA). These results demonstrated that islet transplantation was expected to take the place of solitary pancreas transplantation for the type 1 diabetic patients without renal dysfunction.