Kazumasa Oka

Publications (17)40.16 Total impact

• Article: Japan Renal Biopsy Registry and Japan Kidney Disease Registry: Committee Report for 2009 and 2010.

  Hitoshi Sugiyama, Hitoshi Yokoyama, Hiroshi Sato, Takao Saito, Yukimasa Kohda, Shinichi Nishi, Kazuhiko Tsuruya, Hideyasu Kiyomoto, Hiroyuki Iida, Tamaki Sasaki, [......], Norishige Yoshikawa, Akira Shimizu, Hiroshi Kitamura, Yukio Yuzawa, Seiichi Matsuo, Yutaka Kiyohara, Kensuke Joh, Michio Nagata, Takashi Taguchi, Hirofumi Makino
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  ABSTRACT: The Japan Renal Biopsy Registry (J-RBR) was started in 2007 and the Japan Kidney Disease Registry (J-KDR) was then started in 2009 by the Committee for Standardization of Renal Pathological Diagnosis and the Committee for the Kidney Disease Registry of the Japanese Society of Nephrology. The purpose of this report is to describe and summarize the registered data from 2009 and 2010. For the J-KDR, data were collected from 4,016 cases, including 3,336 (83.1 %) by the J-RBR and 680 (16.9 %) other cases from 59 centers in 2009, and from 4,681 cases including 4,106 J-RBR cases (87.7 %) and 575 other cases (12.3 %) from 94 centers in 2010, including the affiliate hospitals. In the J-RBR, 3,165 native kidneys (94.9 %) and 171 renal grafts (5.1 %) and 3,869 native kidneys (94.2 %) and 237 renal grafts (5.8 %) were registered in 2009 and 2010, respectively. Patients younger than 20 years of age comprised 12.1 % of the registered cases, and those 65 years and over comprised 24.5 % of the cases with native kidneys in 2009 and 2010. The most common clinical diagnosis was chronic nephritic syndrome (55.4 % and 50.0 % in 2009 and 2010, respectively), followed by nephrotic syndrome (22.4 % and 27.0 %); the most frequent pathological diagnosis as classified by the pathogenesis was IgA nephropathy (31.6 % and 30.4 %), followed by primary glomerular diseases (except IgA nephropathy) (27.2 % and 28.1 %). Among the primary glomerular diseases (except IgA nephropathy) in the patients with nephrotic syndrome, membranous nephropathy was the most common histopathology in 2009 (40.3 %) and minor glomerular abnormalities (50.0 %) were the most common in 2010 in native kidneys in the J-RBR. Five new secondary and longitudinal research studies by the J-KDR were started in 2009 and one was started in 2010.
  Clinical and Experimental Nephrology 02/2013; · 1.37 Impact Factor
• Article: Renal disease in the elderly and the very elderly Japanese: analysis of the Japan Renal Biopsy Registry (J-RBR).

  Hitoshi Yokoyama, Hitoshi Sugiyama, Hiroshi Sato, Takashi Taguchi, Michio Nagata, Seiichi Matsuo, Hirofumi Makino, Tsuyoshi Watanabe, Takao Saito, Yutaka Kiyohara, [......], Masafumi Fukagawa, Makoto Hiramatsu, Yoshio Terada, Osamu Uemura, Tetsuya Kawata, Akira Matsunaga, Aki Kuroki, Yasukiyo Mori, Koji Mitsuiki, Haruyoshi Yoshida
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  ABSTRACT: BACKGROUND AND OBJECTIVES: Data regarding renal disease in the elderly (age ≥65 years old) and very elderly (age ≥80 years old) Japanese are extremely limited. The aim of this study was to examine the causes of renal disease and their clinical presentations in elderly patients who underwent renal biopsy. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: From July 2007 to November 2011, all of the elderly native renal biopsy patients who had been registered in the Japan Renal Biopsy Registry (J-RBR; 2802 including 1596 males and 1206 females) were identified. Their data were compared with a control group of 7416 patients who ranged in age from 20 to 64 years old and were registered on the J-RBR over the same period. In addition, the clinical and pathological classifications of 276 very elderly patients were also analyzed. RESULTS: The indications for biopsy were nephrotic syndrome (NS) in 36.2 and 50.7 % of the elderly and the very elderly patients, chronic nephritic syndrome in 31.8 and 17.4 %, and acute kidney injury including rapidly progressive glomerulonephritis in 18.6 and 22.5 %, respectively. Primary glomerular disease was the most frequent diagnosis, followed by MPO-ANCA-positive nephritis, IgA nephropathy (IgAN), and diabetic nephropathy. In primary GN including IgAN, membranous nephropathy (MN) was the most frequent histological type, followed by IgAN and minor glomerular abnormalities. A comparison with the control group showed that MN, MPO-ANCA-positive nephritis, and amyloid nephropathy were more common in the elderly (P < 0.001), and IgAN was less common (P < 0.001). As for nephrotic syndrome in the elderly, MN was the most common histological type, followed by minimal change NS, diabetic nephropathy, amyloid nephropathy, and focal segmental glomerulosclerosis. There was a significant discrepancy between the urinary protein/creatinine ratio and daily proteinuria after the 7th decade of life. CONCLUSIONS: Renal biopsy is a valuable diagnostic tool, even in elderly and very elderly Japanese patients. In the future, modified clinical guidelines for elderly renal disease should be developed.
  Clinical and Experimental Nephrology 10/2012; · 1.37 Impact Factor
• Article: Japan Renal Biopsy Registry: the first nationwide, web-based, and prospective registry system of renal biopsies in Japan.

  Hitoshi Sugiyama, Hitoshi Yokoyama, Hiroshi Sato, Takao Saito, Yukimasa Kohda, Shinichi Nishi, Kazuhiko Tsuruya, Hideyasu Kiyomoto, Hiroyuki Iida, Tamaki Sasaki, [......], Yuichiro Fukasawa, Atsushi Fukatsu, Kunio Morozumi, Norishige Yoshikawa, Yukio Yuzawa, Seiichi Matsuo, Yutaka Kiyohara, Kensuke Joh, Takashi Taguchi, Hirofumi Makino
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  ABSTRACT: The Committee for the Standardization of Renal Pathological Diagnosis and the Working Group for Renal Biopsy Database of the Japanese Society of Nephrology started the first nationwide, web-based, and prospective registry system, the Japan Renal Biopsy Registry (J-RBR), to record the pathological, clinical, and laboratory data of renal biopsies in 2007. The patient data including age, gender, laboratory data, and clinical and pathological diagnoses were recorded on the web page of the J-RBR, which utilizes the system of the Internet Data and Information Center for Medical Research in the University Hospital Medical Information Network. We analyzed the clinical and pathological diagnoses registered on the J-RBR in 2007 and 2008. Data were collected from 818 patients from 18 centers in 2007 and 1582 patients from 23 centers in 2008, including the affiliated hospitals. Renal biopsies were obtained from 726 native kidneys (88.8%) and 92 renal grafts (11.2%) in 2007, and 1400 native kidneys (88.5%) and 182 renal grafts (11.5%) in 2008. The most common clinical diagnosis was chronic nephritic syndrome (47.4%), followed by nephrotic syndrome (16.8%) and renal transplantation (11.2%) in 2007. A similar frequency of the clinical diagnoses was recognized in 2008. Of the native kidneys, the most frequent pathological diagnosis as classified by pathogenesis was immunoglobulin (Ig) A nephropathy (IgAN) both in 2007 (32.9%) and 2008 (30.2%). Among the primary glomerular diseases (except IgAN), membranous nephropathy (MN) was the most common disease both in 2007 (31.4%) and 2008 (25.7%). In a cross-sectional study, the J-RBR has shown IgAN to be the most common disease in renal biopsies in 2007 and 2008, consistent with previous Japanese studies. MN predominated in the primary glomerular diseases (except for IgAN). The frequency of the disease and the clinical and demographic correlations should be investigated in further analyses by the J-RBR.
  Clinical and Experimental Nephrology 03/2011; 15(4):493-503. · 1.37 Impact Factor
• Article: Early diagnosis and treatment may prevent the development of complications in an adult patient with glycogen storage disease type Ia.

  Toshikazu Araoka, Hiroya Takeoka, Hideharu Abe, Seiji Kishi, Makoto Araki, Keisuke Nishioka, Masaki Ikeda, Tetsuro Mazaki, Shiori Ikemura, Makiko Kondo, Azusa Hoshina, Kojiro Nagai, Akira Mima, Taichi Murakami, Rokuro Mimura, Kazumasa Oka, Takao Saito, Toshio Doi
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  ABSTRACT: Type Iota(a) glycogen storage disease (GSD Iota(a)) is caused by the deficiency of glucose-6-phosphatase activity, which results in metabolic disorder and organ failure, including renal failure. GSD Iota(a) patients are generally diagnosed at a median age of 6 months. However, we report a 20-year-old Japanese female with newly diagnosed GSD Iota(a) . The renal disorder of GSD Iota(a) is considered to be produced by glomerular hyperfiltration, TGF-beta expression which is induced by renin-angiotensin-aldosterone system (RAS) and uric acid, and the increase in both small dense LDL and modified LDL which is characteristic of GSD Iota(a) as well as hypertriglyceridemia. With the administration of intensive therapies, including angiotensin type 1-receptor blocker and some lipid lowering drugs, along with traditional dietary therapy, daily proteinuria of the patient improved from 2.1 g to 0.78 g. Although the patients of GSD Iota(a) should receive an early and accurate diagnosis and effective therapies before the age of 1 year, the combination of traditional dietary therapies and intensive therapies may have therapeutic potential for the complications of adult patients. In this report, we describe the management of renal disease and the characteristic features of this metabolic disorder.
  Internal Medicine 01/2010; 49(16):1787-92. · 0.94 Impact Factor
• Article: Valvular injury in a patient with PR3-ANCA-associated glomerulonephritis.

  Hirotsugu Iwatani, Yasuyuki Nagasawa, Kazumasa Oka, Yoshitaka Isaka, Enyu Imai
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  ABSTRACT: Background An 11-year-old boy who had hematuria at a routine health check-up was later diagnosed with proteinase 3 (PR3) antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. Despite treatment with corticosteroids and immunosuppressants, he went on to develop end-stage renal disease. The patient received a renal transplant at the age of 16 years, but relapse of PR3-ANCA-related nephritis to the graft occurred three times. Each relapse was successfully treated with corticosteroids and immunosuppressants. An echocardiogram at the age of 19 years revealed moderate-to-severe aortic regurgitation. The patient died of pneumonia when he was 24 years old. Autopsy revealed a perforation in the noncoronary cusp of the aortic valve and recurrence of crescentic glomerulonephritis in the transplanted kidney.Investigations Physical examinations, urine and blood analyses, renal biopsies, echocardiograms and autopsy.Diagnosis PR3-ANCA-associated glomerulonephritis, recurrence of crescentic glomerulonephritis to the graft, aortic regurgitation and perforation in the noncoronary cusp of the aortic valve.Management Immunosuppressants and corticosteroids.
  Nature Clinical Practice Nephrology 10/2008; 4(10):576-82. · 6.08 Impact Factor
• Article: Histological reaction of sintered nanohydroxyapatite-coated cuff and its fibroblast-like cell hybrid for an indwelling catheter.

  Tsutomu Furuzono, Mitsuki Ueki, Harumi Kitamura, Kazumasa Oka, Enyu Imai
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  ABSTRACT: Rapid tissue-ingrowth of a sintered hydroxyapatite(HAp)-coated and cell-hybrid subcutaneous cuff equipped with an indwelling catheter was developed. The rod-like HAp nanoparticles were coated by covalent bonding on the surface of the silk fibroin (SF) fibers for about 100 microm of the length. The fibers were transplanted three-dimensionally on a cuff substrate made of silicone elastomer with an adhesive. The fibroblast-like cells, explanted and proliferated from skin tissue containing the epidermis, dermis, and subcutaneous tissue of Japanese white rabbits, were incubated on the three-dimensional cuff for three days. Three types of cuff--polyester, HAp-coated, and cell-hybrid cuffs--were percutaneously implanted into the backs of the same animals for 3 and 7 days. The subcutaneous tissues around the cuffs were stained with hematoxylin-eosin. Immunohistochemical staining to identify macrophages and alpha-smooth muscle actin (alpha-SMA) was also done and examined by light microscopy. The alpha-SMA-positive area was very limited in the polyester cuff group even after 7 days, although many macrophages infiltrated into the fibers. In the cell-hybrid cuff group, on the other hand, an alpha-SMA-positive area was formed extensively after 3 and 7 days, causing severe inflammation. In the HAp-coated cuff group, an alpha-SMA-positive area was formed among the fibers with little inflammation. The extent order of the alpha-SMA-positive area was cell-hybrid cuff > HAp-coated cuff > polyester cuff, while the degree of inflammatory cells order was cell-hybrid cuff > polyester cuff > HAp-coated cuff.
  Journal of Biomedical Materials Research Part B Applied Biomaterials 09/2008; 89(1):77-85. · 2.15 Impact Factor
• Article: Adiponectin binds to chemokines via the globular head and modulates interactions between chemokines and heparan sulfates.

  Hiroaki Masaie, Kenji Oritani, Takafumi Yokota, Isao Takahashi, Takahiro Shirogane, Hidetoshi Ujiie, Michiko Ichii, Norimitsu Saitoh, Tetsuo Maeda, Rie Tanigawa, Kazumasa Oka, Yoshihiko Hoshida, Yoshiaki Tomiyama, Yuzuru Kanakura
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  ABSTRACT: Adiponectin, a fat cell-derived protein, has been attracting considerable attention because of its antidiabetic and antiatherogenic activities. The aim of the present study is to identify molecules physiologically associating with adiponectin and to understand how the protein displays diverse biological activities. We used an expression cloning method combined with enzyme-linked immunosorbent assay to clone adiponectin-binding proteins from the MS-5 complementary DNA library. We successfully isolated two chemokines, stromal cell-derived factor-1 (SDF-1) and CCF18, and verified that adiponectin bound to them via its globular head. Adiponectin bound with various chemokines in vitro, such as macrophage-inflammatory protein-1alpha (MIP-1alpha), RANTES, and monocyte chemoattractant protein-1 (MCP-1), suggesting that the protein had a feature commonly to bind to the chemokine family. The middle part of chemokines, dispensable for interacting with their receptors, was found to be important for the adiponectin binding. Although the interaction of adiponectin to SDF-1 affected neither the SDF-1-CXCR4 binding nor the SDF-1 signaling in Jurkat cells, adiponectin and heparin mutually interfered in their association to SDF-1 and MCP-1 in vitro, implying that their association might influence the distribution of adiponectin and SDF-1 in inflammatory sites. Indeed, both adiponectin and SDF-1 was positively immunostained in vascular walls in guts from acute graft-vs-host disease patients. In addition, peripheral blood of adiponectin-deficient mice contained more hematopoietic progenitors than that of wild-type mice. Adiponectin may be involved in regulation of inflammation via binding to specific chemokines. Additionally, the interaction possibly enables adiponectin to gather and play its role in inflammatory sites.
  Experimental Hematology 07/2007; 35(6):947-56. · 2.90 Impact Factor
• Article: Association of treatment with 15-deoxyspergualin and BK virus nephropathy in kidney allograft recipients.

  Yi Shi, Toshiki Moriyama, Yukiomi Namba, Masaki Yamanaka, Takanori Hanafuse, Ryoichi Imamura, Naotsugu Ichimaru, Kazumasa Oka, Masahiro Kyo, Ye Tian, Shiro Takahara, Seiji Ichikawa, Akihiko Okuyama
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  ABSTRACT: 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. A total of 114 biopsy specimens from 88 living-related kidney transplantation recipients (performed between January 1999 to April 2003) were retrospectively analyzed. Patients received immunosuppression therapy based on calcineurin inhibitors and corticosteroid [tacrolimus (TAC) 33 and cyclosporin (CyA) 55]. Additionally, mycophenolate mofeteil (MMF) was used in 21 patients; DSG was used in seven patients; and anti-CD3 monoclonal antibody was used in 16 patients. We analyzed the degree of donor/recipient human leucocyte antigen (HLA) compatibility assessed by the number of HLA-A, -B, and -DR-mismatched antigens in 88 patients. The diagnosis of BKVN was made by the light microscopic examination and a positive immunohistochemical staining of anti-40 antibody in biopsy specimens. Patients were divided into two groups of group A (mild histological change) and group B (moderate or severe histological change) to determine the risk factors in different histological staging. The clinical course of two typical patients in different histological stage is described briefly to outline the risk factors of BKVN. We identified seven cases of BKVN (8.0%) from 88 transplanted patients. Significantly higher incidence of combination regimen consisting of TAC and MMF in BKVN group was noticed compared with non-BKVN group (57.1% vs. 9.9%; p = 0.003). BKVN was associated with a significantly higher incidence of DSG administration compared with non-BKVN group (57.1% vs. 3.7%; p </= 0.001). No difference was found in HLA mismatch between BKVN and non-BKVN group. Additionally, a significantly higher incidence of acute rejection episode prior to BKVN diagnosis was found in group B compared with group A (100% vs. 0%; p = 0.002), and the same statistical difference was shown in the number of anti-rejection therapy between group B and group A (100% vs. 0%; p = 0.002). We recognized a significant difference between group B and group A in terms of the combine regimen therapy of TAC with MMF (p = 0.002) and no difference in graft loss rate (p = 0.092), even though it was 50% in group B and was 0% in group A. In this study, our data indicated excessive intense immunosuppression with TAC-MMF is related to the development of BKVN. In addition, we found that anti-rejection therapy, especially with DSG, may accelerate the development of BKVN.
  Clinical Transplantation 05/2007; 21(4):502-9. · 1.67 Impact Factor
• Article: Incidence of positive C4d deposition in long-term survival cases over 10 yr after renal transplantation.

  Yukiomi Namba, Kazumasa Oka, Toshiki Moriyama, Masahiro Kyo, Ryoichi Imamura, Yi Shi, Naotsugu Ichimaru, Yoshitaka Isaka, Shiro Takahara, Akihiko Okuyama
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  ABSTRACT: 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. We examined 14 protocol biopsy cases performed at Osaka University Hospital between March 2004 and March 2005. The average interval between the operation and the day of biopsy was 15.4 yr. Histological diagnosis was made in accordance with the Banff 97 classification. Paraffin-embedded tissue was stained with polyclonal anti-C4d antibody. Detection of donor-specific antibody (DSA) was determined by flow cytometric assay. The cases were divided according to C4d positivity. Three of 14 cases (21.4%) were C4d positive and belonged to the C4d+/DSA+ group, while 11 cases were of the C4d-/DSA- group. There were no significant differences between the two groups in serum creatinine (sCr) or proteinuria at the time of biopsy. A trend towards decreasing rate of the inverse of sCr (1/sCr) in the C4d+/DSA+ group was noted. In the C4d+/DSA+ group, three transplant glomerulopathy (TGP) were identified. On the other hand, TGP were identified in six of 11 cases of the C4d-/DSA- group. We investigated the relevance of typical chronic rejection (CR) features and the positivity of C4d. No significant differences were observed between the CR features and C4d depositions in PTC (p = 0.26). In long-term survival cases with positive C4d, a trend towards decreasing rate of 1/sCr was revealed, but their histological characteristic features was not recognized.
  Clinical Transplantation 02/2006; 20 Suppl 15:20-5. · 1.67 Impact Factor
• Article: Correlation between the Banff 97 classification of renal allograft biopsies and clinical outcome

  Toshiyuki Tanaka, Masahiro Kyo, Yukito Kokado, Shiro Takahara, Motoaki Hatori, Kazuhiro Suzuki, Masaru Hasumi, Kiyohide Toki, Naotsugu Ichimaru, Koji Yazawa, Toru Hanafusa, Yukiomi Namba, Kazumasa Oka, Toshiki Moriyama, Enyu Imai, Akihiko Okuyama, Hidetoshi Yamanaka
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  ABSTRACT: Abstract The 1997 fourth Banff meeting revised the consensus for describing transplant biopsies. We have conducted a retrospective analysis of biopsies correlated between the Banff 97 classification and clinical outcome. The patients (n=149), who had a total of 404 biopsy-proven rejections, were assessed and the biopsies taken from these patients were re-examined and classified according to the Banff 97 classification. Morphological changes in the glomeruli (g), interstitium (i), tubules(t), and arterial vessels (v) were scored. Severity of acute rejection was statistically associated with unresponsiveness to anti-rejection treatment (P< 0.0001) and predicted an increased risk of graft failure (p<0.05). Each quantitative criterion (g, i, t, and v) was also statistically associated with unresponsiveness to anti-rejection treatment. Mean serum creatinine levels were significantly higher in the groups graded Banff 97 type I–III after 1 and 2 years of follow-up. The Banff 97 classification correlated with reversibility of rejection episodes and long-term graft survival.
  Transplant International 03/2005; 17(2):59 - 64. · 2.92 Impact Factor
• Article: Prevalence, characteristics, and outcome of BK virus nephropathy in Japanese renal transplant patients: analysis in protocol and episode biopsies.

  Yukiomi Namba, Toshiki Moriyama, Masahiro Kyo, Ryoichi Imamura, Yi Shi, Naotsugu Ichimaru, Kazumasa Oka, Shiro Takahara, Akihiko Okuyama
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  ABSTRACT: 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. We retrospectively analyzed 112 biopsy specimens from 87 renal transplant patients. All transplantations were from living donors. Of the 112 biopsy specimens, 71 were from protocol biopsies and 41 were from episode biopsies. Calcineurin inhibitors and corticosteroid were used in all patients (tacrolimus 32 and cyclosporin 55). In addition, azathioprine was used in 43 patients, mizoribine was used in 24 patients, and mycophenolate mofetil was used in 20 patients. BKN was diagnosed by light microscopic examination and a positive immunohistochemical staining of anti-SV40 antibody in a biopsy specimen. In order to investigate the outcome and potential risk factors of patients with different histological staging, we divided the patients into groups A (mild histological change) and B (moderate or severe histological change). Of the 87 patients, six were diagnosed with BKN. There were no significant differences between BKN patients and non-BKN patients, except for the number of patients with graft loss (p < 0.001). Of the six BKN patients, three were in group A, and three were in group B. We recognized a significant difference between group A and group B in terms of anti-rejection treatment including glucocorticoid, tacrolimus trough levels of over 8 ng/mL, episode of acute rejection within 1-month post-transplantation, and the time period between transplantation and BKN diagnosis. This is the first report of BKN in Japanese renal allograft recipients. In our hospital, the prevalence, risk factors, and outcome were similar to those previously for non-Japanese recipients.
  Clinical Transplantation 03/2005; 19(1):97-101. · 1.67 Impact Factor
• Article: Nilvadipine attenuates mesangial expansion and glomerular hypertrophy in diabetic db/db mice, a model for type 2 diabetes.

  Toshiki Moriyama, Kazumasa Oka, Hirotsugu Ueda, Enyu Imai
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  ABSTRACT: The renoprotection achieved by angiotensin II blockade in the treatment of diabetic nephropathy is well established in both the clinical and the experimental settings. In contrast, the therapeutic efficacy of calcium channel blockers (CCBs) in the treatment of diabetic nephropathy still remains controversial. In the present study, we compared the effects of an angiotensin-converting enzyme inhibitor, enalapril, and a dihydropyridine CCB, nilvadipine, on nephropathy in the db/db mouse, a rodent model of type 2 diabetes. Male db/db mice were divided into the following three groups at the age of 11 weeks, when treatment was started: vehicle, enalapril (10 mg/kg per day), and nilvadipine (10 mg/kg per day). Blood pressure, urine, and blood chemistry were monitored at the age of 17 and 27 weeks, and kidney samples were obtained at 29 weeks. Morphological changes were analyzed on periodic acid-Schiff-stained sections. Lipid peroxidation in kidney homogenates was measured. Blood pressure remained normal and was similar in the three groups until 27 weeks. Blood glucose exceeded 300 mg/dl throughout the study in all groups. Reduction of microalbuminuria at 27 weeks, compared to the vehicle group, was 37% and 52% in the enalapril- and nilvadipine-treated groups, respectively. Increased lipid peroxidation was suppressed by 15% and 83% in the enalapril- and nilvadipine-treated groups, respectively. Glomerular hypertrophy, assessed by cross-sectional glomerular area, was significantly suppressed in the nilvadipine group, but not in the enalapril group, compared to the vehicle group. Nilvadipine shows a stronger renoprotective effect than enalapril in the db/db mouse, independent of the blood-pressure-lowering effect. An antioxidative effect, indicated by the reduction in lipid peroxidation, may partly contribute to the renoprotection conferred by nilvadipine.
  Clinical and Experimental Nephrology 10/2004; 8(3):230-6. · 1.37 Impact Factor
• Article: NK-cell related neoplasms in Osaka, Japan.

  Hajime Miyazato, Shin-ichi Nakatsuka, Zhiming Dong, Tetsuya Takakuwa, Kazumasa Oka, Hitoshi Hanamoto, Yoichi Tatsumi, Akihisa Kanamaru, Katsuyuki Aozasa
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  ABSTRACT: The frequency of NK-cell related neoplasms was estimated among lymphoproliferative diseases diagnosed and treated in Osaka, Japan, from 1999 to 2003. The total number of registered cases was 1,400, among which 1,092 patients were diagnosed as having malignant lymphomas. There were 987 cases of non-Hodgkin's lymphoma (NHL) and 105 (9.6%) of Hodgkin's lymphoma. Immunophenotypic analysis revealed that 743 patients had B-cell lymphomas and 209 T/NK-cell lymphomas. Among the T/NK-cell lymphomas, 40 showed positive immunoreactivity for CD56, and thus they were judged to be NK/T-cell lymphomas. They included one blastic NK-cell lymphoma and 39 NK/T-cell lymphomas. NK/T-cell lymphomas were further divided into three categories based on the main site of lesions: nasal type (23 cases), non-nasal extranodal type (11 cases), and nodal type (5 cases). The positive rate of infection with the Epstein-Barr virus determined by in situ hybridization was 83%, 36%, and 25% in the nasal, non-nasal, and nodal type, respectively. A mosquito allergy was found in one patient with EBV-positive non-nasal NK/T-cell lymphoma. The present study showed that the frequency of NK-cell related neoplasms among all NHLs was 4% in an ATL-non-endemic area of Japan.
  American Journal of Hematology 08/2004; 76(3):230-5. · 4.67 Impact Factor
• Article: Correlation between the Banff 97 classification of renal allograft biopsies and clinical outcome.

  Toshiyuki Tanaka, Masahiro Kyo, Yukito Kokado, Shiro Takahara, Motoaki Hatori, Kazuhiro Suzuki, Masaru Hasumi, Kiyohide Toki, Naotsugu Ichimaru, Koji Yazawa, Toru Hanafusa, Yukiomi Namba, Kazumasa Oka, Toshiki Moriyama, Enyu Imai, Akihiko Okuyama, Hidetoshi Yamanaka
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  ABSTRACT: The 1997 fourth Banff meeting revised the consensus for describing transplant biopsies. We have conducted a retrospective analysis of biopsies correlated between the Banff 97 classification and clinical outcome. The patients ( n=149), who had a total of 404 biopsy-proven rejections, were assessed and the biopsies taken from these patients were re-examined and classified according to the Banff 97 classification. Morphological changes in the glomeruli (g), interstitium (i), tubules(t), and arterial vessels (v) were scored. Severity of acute rejection was statistically associated with unresponsiveness to anti-rejection treatment ( P<0.0001) and predicted an increased risk of graft failure ( P<0.05). Each quantitative criterion (g, i, t, and v) was also statistically associated with unresponsiveness to anti-rejection treatment. Mean serum creatinine levels were significantly higher in the groups graded Banff 97 type I-III after 1 and 2 years of follow-up. The Banff 97 classification correlated with reversibility of rejection episodes and long-term graft survival.
  Transplant International 02/2004; 17(2):59-64. · 2.92 Impact Factor
• Article: Effects of the oral adsorbent AST-120 on tryptophan metabolism in uremic patients.

  Yoshiharu Tsubakihara, Yoshitsugu Takabatake, Kazumasa Oka, Tatsuya Shoji, Masaki Togawa, Noriyuki Okada, Ito Takahito, Enyu Imai
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  ABSTRACT: Tryptophan (TRP), an essential amino acid, is bound mostly to albumin in plasma. However, it is reported that binding is inhibited by indoles that accumulate in uremic plasma. This may be responsible for the malnutrition observed in uremic patients. AST-120, an oral adsorbent of uremic toxins, can reduce concentrations of indoxyl sulfate (IS), the most abundant indolic metabolite in uremic plasma. We therefore investigated whether AST-120 recovers TRP binding to plasma proteins and improves the nutritional state of uremic patients. The in vitro binding ratio of TRP to bovine serum albumin (BSA) was measured in the presence of IS by the equilibrium dialysis technique. In addition, five predialysis patients with chronic renal failure (CRF) were administered AST-120 for 2 months. Plasma concentrations of total TRP, IS, and free TRP were measured in five healthy volunteers (normal [N] group) and five patients with CRF before and after 2 weeks of AST-120 therapy (6 g/d). Their nutritional statuses also were compared before and after 2 months of AST-120 administration. IS inhibited in vitro binding of TRP to BSA in a dose-dependent manner. Total TRP concentrations and protein-binding ratios in patients with CRF (0.90 +/- 0.08 mg/dL and 68.7% +/- 6.8%, respectively) were significantly lower than those in the N group (2.45 +/- 0.45 mg/dL and 92.0% +/- 1.4%, respectively). However, a 2-week administration of AST-120 significantly reduced IS levels from 1.79 +/- 1.01 to 1.15 +/- 0.85 mg/dL (N group, 0.06 +/- 0.01 mg/dL), increased total TRP levels (1.16 +/- 0.18 mg/dL), and improved the TRP plasma protein-binding ratio to 83.1% +/- 3.8%, whereas total protein and albumin levels remained unchanged. After 2 months of AST-120 administration, serum albumin and transferrin levels increased significantly. AST-120 improves nutritional state, at least partly through correcting impaired TRP metabolism, in patients with CRF.
  American Journal of Kidney Diseases 04/2003; 41(3 Suppl 1):S38-41. · 5.43 Impact Factor
• Article: The differences between late graft loss group and long‐term graft survival group in renal transplantation

  Toshiyuki Tanaka, Shiro Takahara, Motoaki Hatori, Kiyohide Toki, Jing-Ding Wang, Sompol Permpongkosol, Koji Yazawa, Yukito Kokado, Kazumasa Oka, Masahiro Kyo, Akihiko Okuyama, Hidetoshi Yamanaka
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  ABSTRACT: Tanaka T, Takahara S, Hatori M, Toki K, Wang J-D, Permpongkosol S, Yazawa K, Kokado Y, Oka K, Kyo M, Okuyama A, Yamanaka H. The differences between late graft loss group and long-term graft survival group in renal transplantation. Clin Transplantation 2001: 15 (Supplement 5): 16–21. ©Munksgaard, 2001In renal transplantation, the long-term graft survival rate has not been improved. Until now, the differences between late graft loss and long-term graft survival have still not been estimated thoroughly. We have attempted to define clinical risk factors and parameters for late graft loss by comparing the differences in these two groups. Data from the Osaka University Database were assessed on 156 renal allografts during a 7-yr period. Thirty-six patients comprised the late graft loss group (patients in this group had graft function without need for dialysis for more than 3 yr post-transplantation, afterwards lost the allograft: ‘loss group’). One hundred and twenty patients comprised the long-term graft survival group (patients in this group had graft function without need for dialysis until 31 December 1999: ‘survival group’). Various immunological and non-immunological parameters were included in an univariate regression analysis. This analysis showed that donor age (P < 0.01), HLA mismatch number (P < 0.01) and a repeat of acute rejection (P < 0.01) were significant factors. Serum creatinine levels at 3 months (P=0.01), proteinuria at 1 yr (P < 0.01) and antihypertensive treatment at 2 yr (P=0.03) after transplantation were predictive of the risk of late graft loss. CsA trough concentration at 3–6 months (P < 0.05) and body mass index increase at 1 yr (P=0.046) were elevated in the loss group. These results from a single centre suggest that immunological as well as non-immunological factors are associated with the pathogenesis of late graft loss.
  Clinical Transplantation 02/2002; 15(s5):16 - 21. · 1.67 Impact Factor
• Article: A clinicopathological study of IgA nephropathy in renal transplant recipients: beneficial effect of angiotensin-converting enzyme inhibitor

  Kazumasa Oka, Enyu Imai, Toshiki Moriyama, Yoshitaka Akagi, Akio Ando, Masatsugu Hori, Akihiko Okuyama, Kiyohide Toki, Masahiro Kyo, Yukito Kokado, Shiro Takahara
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  ABSTRACT: Background.  Prolonging the survival of transplant kidneys is a major task of modern nephrology. It has recently been shown that deteriorating renal function and substantial graft loss were observed in 55&percnt; of renal allograft recipients with recurrent IgA nephropathy &lpar;IgAN&rpar; at long&hyphen;term follow&hyphen;up. To gain a useful insight into the therapeutic approach towards protecting allograft kidneys from deteriorating graft function, we compared the histological characteristics of post&hyphen;transplant IgAN to primary IgAN and investigated the effects of an ACE inhibitor. Methods.  Twenty&hyphen;one patients with post&hyphen;transplant IgAN and 63 patients with primary IgAN were included in the histopathological study. The effectiveness of angiotensin&hyphen;converting enzyme &lpar;ACE&rpar; inhibitor treatment in post&hyphen;transplant IgAN was also studied in 10 patients. Results.  The prevalence of glomeruli with adhesions and&sol;or cellular crescents in primary IgAN was significantly greater than in post&hyphen;transplant IgAN &lpar; P <0.05&rpar;, but the proportion of glomeruli with segmental sclerosis was similar in both groups. The rate of global obsolescence, and the degree of interstitial fibrosis in post&hyphen;transplant IgAN were significantly greater than in primary IgAN &lpar; P <0.05&rpar;. The degree of glomerular obsolescence and the severity of interstitial fibrosis correlated with the severity of glomerular lesion in primary IgAN, but not in post&hyphen;transplant IgAN. In primary IgAN, glomerular diameter significantly correlated with the proportions of glomerular obsolescence, but not in post&hyphen;transplant IgAN, suggesting that allograft kidneys may be in a hyperfiltration state. Both the blood pressure and the urinary protein excretion significantly improved after ACE&hyphen;inhibitor treatment &lpar; P <0.001&rpar;. Conclusion.  In post&hyphen;transplant IgAN, histopathological lesions indicative of acute inflammatory insults were suppressed, and glomerular hypertrophy, which may relate to haemodynamic burden such as hyperfiltration, was prominent. Preliminary study of ACE&hyphen;inhibitor treatment in 10 patients showed favourable effects. A future long&hyphen;term follow&hyphen;up study is required to establish the effectiveness of ACE inhibitors in treatment of post&hyphen;transplant IgAN.