Yukiomi Namba

Erythropoietin protects the kidneys against ischemia reperfusion injury by activating hypoxia inducible factor-1alpha.

Background. Ischemia/reperfusion (I/R) injury is closely associated with tissue damage in various organs, as well as in kidney transplants. Erythropoietin (EPO) has been shown to have a cytoprotective effect against hypoxia. We examined the effect of EPO against renal I/R injury and the underlying mechanism. Methods. Human umbilical vein endothelial cells and human renal proximal tubular epithelial cells were cultured under hypoxic conditions with various EPO concentrations at 37°C and examined the mechanism of cell proliferation by EPO. Moreover, to demonstrate the renoprotective effect in vivo, we treated Sprague-Dawley rats with 100 IU/kg EPO every 2 days for 2 weeks (a total of 6 doses). One day after the last injection, the operations to produce renal I/R injury (bilateral renal occlusion for 60 min) were done, and rats were killed at the end of the reperfusion period (24 hr and 72 hr after reperfusion began). Results. First, we demonstrated in vitro that EPO increased hypoxia inducible factor-1α (HIF-1α) expression and stimulated proliferation of both cells under hypoxic conditions. Next, we demonstrated in vivo that EPO treatment increased the number of HIF-1α-positive cells, and markedly induced the expression of vascular endothelial growth factor messenger RNA. Using pimonidazole, a molecular probe that detects hypoxia, we found that EPO markedly attenuated tubular hypoxia, and reduced the number of terminal transferase dUTP nick end labeling–positive apoptotic cells and α-smooth muscle actin–positive interstitial cells. Conclusions. We suggested a novel HIF-1α induction pathway by EPO under hypoxic conditions. Thus, EPO may protect the kidneys against ischemia reperfusion injury by activating HIF-1α.

Risk factors for malignancy in Japanese renal transplant recipients

Among recipients of renal transplants, the incidences of renal cancer and gastrointestinal cancer are higher and that of skin cancer is much lower in Japan than in Europe and North America.

Prevalence, characteristics, and outcome of BK virus nephropathy in Japanese renal transplant patients: analysis in protocol and episode biopsies

Abstract:  Background:  BK virus nephropathy (BKN) is recognized as a cause of graft loss in renal transplant patients. This may be related to the introduction of new and potent immunosuppressive regimens. In Japan, our experience regarding its prevalence, clinical significance, and outcome is still limited. In this study, our primary purpose is to outline the prevalence, outcome, and clinical characteristics of BKN as observed at Osaka University Hospital.

Association of treatment with 15-deoxyspergualin and BK virus nephropathy in kidney allograft recipients

Abstract:  Objective:  BK virus nephropathy (BKVN) has been proposed as an important cause of allograft dysfunction and loss in kidney allograft recipient over the last decade. Intense immunosuppression and tubular injury have been shown to promote the replication of polyomavirus. 15‐deoxyspergualin (DSG), an effective immunosuppressive agent, is used as a rescue drug for acute rejection in clinical renal transplantation in Japan. To determine whether DSG is a risk factor for BKVN and outline the relationship among BKVN, DSG, and other risk factors, we analyzed 88 patients who received living‐related renal transplantation between January 1999 and April 2003.

Long term efficacy of simvastatin in renal transplant recipients treated with cyclosporine or tacrolimus

Abstract:  Background:  Hyperlipidemia is frequently developed following renal transplantation and results in worsening of the patients prognosis.

Incidence of positive C4d deposition in long-term survival cases over 10 yr after renal transplantation

Abstract:  Background:  The incidence of positive C4d deposition in peritubular capillaries (PTC) in long‐term survival cases remains controversial. Some incidences of positive C4d deposition in PTC in cases of long‐term survival less than 10 yr have been reported. We retrospectively examined the incidence of positive C4d deposition in long‐term survival cases over 10 yr after renal transplantation and the histological and clinical characteristics of the positive C4d staining cases.

ABO-incompatible kidney transplantation with anti-CD20 monoclonal antibodies, intravenous immunoglobulin and plasmapheresis without splenectomy: a case report

Abstract: A 24‐yr‐old man was admitted to our hospital for ABO‐incompatible kidney transplantation. His blood type was O, and the donors (his fathers) blood type was B. The recipient had pancytopenia, splenomegaly, splenorenal shunts and esophageal varices due to congenital hepatic fibrosis. Therefore, if splenorectomy was performed, the blood pressure of the portal vein and the growth of esophageal varices were predicted. Eventually, in return for splenectomy, anti‐CD20 monoclonal antibodies (rituximab), intravenous immunoglobulin and plasmapheresis was performed for additional immunosuppression. Because of progression of pancytopenia, we had to decrease the dose of mycophenolate mofetil and gave up on using deoxyspagalin. Nevertheless the serum creatinine level decreased and remained in the 1.6 to 1.8 mg/dl range.

Differential diagnosis of kidney transplant rejection and cyclosporin/tacrolimus nephropathy using urine cytology

Abstract: A total of 9000 urine samples from 69 kidney transplant recipients were studied for differential diagnoses of transplant rejection and cyclosporin/tacrolimus toxicity. New–Sternheimer and Papanicolaou staining were used to differentiate cells in urine. We also employed an immunocytochemical technique for further identification of exfoliated cells. With New–Sternheimer and Papanicolaou staining, the predominance of proximal tubular cells was useful to differentiate cyclosporin/tacrolimus toxicity from acute rejection in cases of increased serum creatinine level. During rejection episodes, an increased number of mononuclear cells and renal epithelial cells were found. Immunocytochemical analysis showed a significant increase of CD2‐, CD4‐ CD8‐, CD25‐ and HLA‐DR‐positive cells with rejection. However, there was no relationship between Banff criteria rejection grade and the increase of mononuclear cells.

Clinicopathological Study of Expression of Lymphatic Vessels in Renal Allograft Biopsy After Treatment for Acute Rejection

BACKGROUND Lymph vessel expression is related to inflammatory cell infiltration, around renal tubules in acute rejection episodes (ARE) of transplanted kidneys. However, there is little information on the lymph vessels after treatment of an ARE, particularly in relation to renal function and histological findings. PATIENTS AND METHODS We investigated 13 cases of ARE diagnosed by kidney transplant biopsy performed from 1997 to 2005 within 3 years of transplantation. Treatment of the ARE lead to an improved serum creatinine level in all cases. There was neither an ABO-incompatible nor an acute humoral rejection case. Lymphatic vessels in re-biopsies were examined using immunohistochemical staining with D2-40 antibody that detected lymphatic endothelium. Re-biopsy cases in which the baseline creatinine had increased by more than 20% despite treatment were considered the severe group; the others, as the stable group. The relation between lymphatic vessel density (LVD) and renal function was examined using Banff scores. RESULTS LVD was significantly higher in the severe than the stable group. The expression of lymph vessels versus the Banff score showed a direct relation: greater Banff scores showed higher expressions of lymph vessels. CONCLUSIONS The expression of lymph vessels in renal allograft specimens after treatment of an ARE was related to deterioration of renal function and inflammatory cell invasion. We plan a further examination of the relationship between the expression of lymph vessels and long-term prognosis.

Comparison of histopathological characteristics of allograft biopsy between responder and non‐responder to antiproteinuric effect of angiotensin‐converting enzyme inhibitor (ACEI)

Abstract:  Angiotensin‐converting enzyme inhibitor (ACEI) has become recognized as agents that have renoprotective effects in the treatment of progressive renal diseases including post‐transplant kidneys. Previously we demonstrated the safety and effectiveness of ACEI treatment on the hypertensive proteinuric post‐transplant patients (N = 10) who had been followed up for 12 months. However, not all patients show good response in urinary protein reduction. We aimed to analyse the histopathological factor(s) affecting the responsiveness of proteinuria to ACEI treatment. Fourteen post‐transplant patients with proteinuria who were treated with ACEI and underwent allograft biopsy were analysed. Eight patients showed 50% or more reduction in proteinuria (responder). The other 6 patients showed less (< 50%) reduction in proteinuria (non‐responder). There was no difference in clinical characteristics (BP, renal function, donor age, recipient body mass index), dietary sodium or protein intake, and diuretic use between the two groups. As a histopathological characteristic, glomerular size in responder group was significantly larger than that in non‐responder group. This suggests that the large glomerular size at least partly contributes to the responsiveness in urinary protein reduction to ACEI treatment in kidney allograft recipients with proteinuria.