Faculty Profiles - SAITO Akihiko

Papers - SAITO Akihiko

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Effects of the Once-Weekly DPP4 Inhibitor Omarigliptin on Glycemic Control in Patients with Type 2 Diabetes Mellitus on Maintenance Hemodialysis: A 24-Week Open-Label, Multicenter Randomized Controlled Study. International journal

Yuta Yoshizawa, Michihiro Hosojima, Hideyuki Kabasawa, Naohito Tanabe, Daisuke Ugamura, Yutaka Koda, Hisaki Shimada, Tetsuya Takasawa, Takahito Ito, Tadahiro Kitamura, Masaki Kobayashi, Yoshiki Suzuki, Ichiei Narita, Akihiko Saito

Diabetes therapy : research, treatment and education of diabetes and related disorders 12 ( 3 ) 655 - 667 2021.3

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used in patients with type 2 diabetes mellitus (T2DM) on maintenance hemodialysis (HD), but the efficacy of the once-weekly DPP4 inhibitor omarigliptin is not known. METHODS: This prospective, randomized, open-label, parallel-group, non-inferiority/superiority, once-daily DPP4 inhibitor linagliptin-controlled, multicenter study examined glycemic control and safety of omarigliptin (UMIN000024284). Sample size was calculated to confirm non-inferiority in terms of changes in glycated hemoglobin (HbA1c). We enrolled 33 patients with T2DM on maintenance HD who had been treated with linagliptin for at least 3 months. The patients were randomized to receive omarigliptin (12.5 mg/week; n = 16) or linagliptin (5 mg/day; n = 17). Primary endpoints were changes in HbA1c and glycoalbumin (GA) over 24 weeks. RESULTS: Differences in the mean change in primary endpoint values between the omarigliptin and linagliptin groups were - 0.61% [- 1.14, - 0.09] for HbA1c, with a two-tailed upper 95% limit (i.e., one-tailed 97.5% upper limit) of 0.25%, below the non-inferiority limit, and - 1.67% [- 4.23, + 0.88] for GA, with a two-tailed upper 95% limit of 0.75%, above the non-inferiority limit. At 24 weeks, the omarigliptin group showed significantly greater reduction in HbA1c than the linagliptin group (- 0.2% ± 0.6% vs. 0.4% ± 0.8%, two-tailed p = 0.024) and significantly greater reduction in blood glucose after a single HD session (- 18.4 ± 31.4 mg/dL vs. 25.2 ± 59.5 mg/dL, respectively, two-tailed p = 0.019). No subjects in the omarigliptin group developed hypoglycemia. CONCLUSIONS: Our data showed that omarigliptin was non-inferior to linagliptin in glycemic control. Omarigliptin is feasible for glycemic control in patients with T2DM on maintenance HD. CLINICAL TRIALS REGISTRATION: UMIN000024284.

DOI： 10.1007/s13300-020-00991-y

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Combination therapy of cisplatin with cilastatin enables an increased dose of cisplatin, enhancing its antitumor effect by suppression of nephrotoxicity. International journal

Masashi Arita, Satoshi Watanabe, Nobumasa Aoki, Shoji Kuwahara, Ryo Suzuki, Sawako Goto, Yuko Abe, Miho Takahashi, Miyuki Sato, Satoshi Hokari, Aya Ohtsubo, Satoshi Shoji, Koichiro Nozaki, Kosuke Ichikawa, Rie Kondo, Masachika Hayashi, Yasuyoshi Ohshima, Hideyuki Kabasawa, Michihiro Hosojima, Toshiyuki Koya, Akihiko Saito, Toshiaki Kikuchi

Scientific reports 11 ( 1 ) 750 - 750 2021.1

Language：English Publishing type：Research paper (scientific journal)

Cisplatin, one of the most active anticancer agents, is widely used in standard chemotherapy for various cancers. Cisplatin is more poorly tolerated than other chemotherapeutic drugs, and the main dose-limiting toxicity of cisplatin is its nephrotoxicity, which is dose-dependent. Although less toxic methods of cisplatin administration have been established, cisplatin-induced nephrotoxicity remains an unsolved problem. Megalin is an endocytic receptor expressed at the apical membrane of proximal tubules. We previously demonstrated that nephrotoxic drugs, including cisplatin, are reabsorbed through megalin and cause proximal tubular cell injury. We further found that cilastatin blocked the binding of cisplatin to megalin in vitro. In this study, we investigated whether cilastatin could reduce cisplatin-induced nephrotoxicity without influencing the antitumor effects of cisplatin. Nephrotoxicity was decreased or absent in mice treated with cisplatin and cilastatin, as determined by kidney injury molecule-1 staining and the blood urea nitrogen content. Combined with cilastatin, a twofold dose of cisplatin was used to successfully treat the mice, which enhanced the antitumor effects of cisplatin but reduced its nephrotoxicity. These findings suggest that we can increase the dose of cisplatin when combined with cilastatin and improve the outcome of cancer patients.

DOI： 10.1038/s41598-020-80853-6

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Effects of DPP-4 Inhibitors on Blood Glucose Variability in Japanese Patients with Type 2 Diabetes on Maintenance Hemodialysis: A Prospective Observational Exploratory Study. International journal

Tomomi Ishikawa-Tanaka, Michihiro Hosojima, Hideyuki Kabasawa, Ryohei Kaseda, Ryota Yasukawa, Yusuke Yata, Shoji Kuwahara, Emiko Kono, Takuma Takata, Noriaki Iino, Takahiro Tanaka, Nobutaka Kitamura, Yoshiki Suzuki, Akihiko Saito, Ichiei Narita

Diabetes therapy : research, treatment and education of diabetes and related disorders 11 ( 12 ) 2845 - 2861 2020.12

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: The precise blood glucose (BG) profile of hemodialysis patients is unclear, as is the effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors in hemodialysis patients with type 2 diabetes. Here, we used continuous glucose monitoring (CGM) to evaluate BG variability in these patients and to assess the efficacy of DPP-4 inhibitors, particularly during hemodialysis sessions and at nighttime (UMIN000012638). METHODS: We examined BG profiles using CGM in 31 maintenance hemodialysis patients with type 2 diabetes. Differences between patients with and without DPP-4 inhibitors (n = 15 and 16, respectively) were analyzed using a linear mixed-effects model to assess changes in glucose levels in 5-min intervals. RESULTS: The model revealed that DPP-4 inhibitor use was significantly associated with suppression of a rapid drop in glucose levels, both with and without adjustment for BG levels at the start of hemodialysis. Moreover, the model revealed that the two groups differed significantly in the pattern of changes in BG levels from 0:00 to 6:55 am. DPP-4 inhibitors suppressed the tendency for subsequent nocturnal hypoglycemia. CONCLUSIONS: This prospective observational exploratory study showed that DPP-4 inhibitors could suppress BG variability during hemodialysis sessions as well as subsequent nocturnal changes in patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, UMIN000012638.

DOI： 10.1007/s13300-020-00928-5

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インスリン使用中の維持血液透析患者におけるデュラグルチド併用による血糖管理の有効性およびQOL改善に関する探索的臨床試験

宇賀村大亮, 細島康宏, 蒲澤秀門, 田邊直仁, 吉澤優太, 忰田亮平, 鈴木芳樹, 成田一衛, 斎藤亮彦

糖尿病 63 ( Suppl.1 ) S - 300 2020.8

Rice bran protein ameliorates diabetes, reduces fatty liver, and has renoprotective effects in Zucker Diabetic Fatty rats

Masatoshi Kubota, Reiko Watanabe, Michihiro Hosojima, Akihiko Saito, Ai Sasou, Takehiro Masumura, Yukikazu Harada, Hiroyuki Hashimoto, Shinobu Fujimura, Motoni Kadowaki

Journal of Functional Foods 70 103981 - 103981 2020.7

DKDと食事 Up to date CKD、DKD患者への食事療法腎臓専門医の立場から(たんぱく質制限の効果も含め)

細島康宏, 蒲澤秀門, 成田一衛, 鈴木芳樹, 斎藤亮彦

日本腎臓学会誌 62 ( 4 ) 228 - 228 2020.7

メガリンを介する腎内レニン-アンジオテンシン(Ang)系(RAS)の動的均衡化制御機構

後藤佐和子, 吉田豊, 細島康宏, 蒲澤秀門, 忰田亮平, 成田一衛, 斎藤亮彦

日本腎臓学会誌 62 ( 4 ) 370 - 370 2020.7

マウス尿中メガリン測定用サンドイッチELISAの開発とその応用

早福莉那, 後藤佐和子, 細島康宏, 蒲澤秀門, 忰田亮平, 成田一衛, 斎藤亮彦

日本腎臓学会誌 62 ( 4 ) 339 - 339 2020.7

The cellular model of albumin endocytosis uncovers link between membrane and nuclear proteins. Reviewed International journal

Seiya Urae, Yutaka Harita, Tomohiro Udagawa, Koji L Ode, Masami Nagahama, Yuko Kajiho, Shoichiro Kanda, Akihiko Saito, Hiroki R Ueda, Masaomi Nangaku, Akira Oka

Journal of cell science 133 ( 13 ) 2020.6

Language：English Publishing type：Research paper (scientific journal)

Cubilin (CUBN) and amnionless (AMN), expressed in kidney and intestine, form a multiligand receptor complex called CUBAM that plays a crucial role in albumin absorption. To date, the mechanism of albumin endocytosis mediated by CUBAM remains to be elucidated. Here, we established an assay to quantitatively evaluate the albumin uptake by CUBAM using cells expressing full-length CUBN, which elucidated the crucial role of C-terminal part of CUBN and endocytosis signal motifs of AMN in albumin endocytosis. We also demonstrated that nuclear valosin-containing protein-like 2 (NVL2), an interacting protein of AMN, is involved in this process. While NVL2 was mainly localized in the nucleolus in cells without AMN expression, it was translocated to the extranuclear compartment when co-expressed with AMN. NVL2 knockdown significantly impaired the internalization of the CUBN-albumin complex in cultured cells, demonstrating an involvement of NVL2 in endocytic regulation. These findings uncover a link between membrane and nucleolar proteins which is involved in endocytic processes.

DOI： 10.1242/jcs.242859

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Low bone mineral density due to secondary hyperparathyroidism in the GlatmTg(CAG-A4GALT) mouse model of Fabry disease. International journal

Hiroki Maruyama, Atsumi Taguchi, Mariko Mikame, Hongmei Lu, Norihiro Tada, Muneaki Ishijima, Haruka Kaneko, Mariko Kawai, Sawako Goto, Akihiko Saito, Riuko Ohashi, Yuji Nishikawa, Satoshi Ishii

FASEB bioAdvances 2 ( 6 ) 365 - 381 2020.6

Language：English Publishing type：Research paper (scientific journal)

Low bone mineral density (BMD)-diagnosed as osteoporosis or osteopenia-has been reported as a new characteristic feature of Fabry disease; however, the mechanism underlying the development of low BMD is unknown. We previously revealed that a mouse model of Fabry disease [GlatmTg(CAG-A4GALT)] exhibits impaired functioning of medullary thick ascending limb (mTAL), leading to insufficient Ca2+ reabsorption and hypercalciuria. Here, we investigated bone metabolism in GlatmTg(CAG-A4GALT) mice without marked glomerular or proximal tubular damage. Low BMD was detected by 20 weeks of age via micro-X-ray-computed tomography. Bone histomorphometry revealed that low BMD results by accelerated bone resorption and osteomalacia. Plasma parathyroid hormone levels increased in response to low blood Ca2+-not plasma fibroblast growth factor 23 (FGF-23) elevation-by 5 weeks of age and showed progressively increased phosphaturic action. Secondary hyperparathyroidism developed by 20 weeks of age and caused hyperphosphatemia, which increased plasma FGF-23 levels with phosphaturic action. The expression of 1α-hydroxylase [synthesis of 1α,25(OH)2D3] in the kidney did not decrease, but that of 24-hydroxylase [degradation of 1α,25(OH)2D3] decreased. Vitamin D deficiency was ruled out as the cause of osteomalacia, as plasma 1α,25(OH)2D3 and 25(OH)D3 levels were maintained. Results demonstrate that secondary hyperparathyroidism due to mTAL impairment causes accelerated bone resorption and osteomalacia due to hyperphosphaturia and hypercalciuria, leading to low BMD in Fabry model mice.

DOI： 10.1096/fba.2019-00080

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SGLT2阻害薬による腎保護作用機序と尿中コンパニオン診断法の検討

忰田亮平, 飯田倫理, 細島康宏, 蒲澤秀門, 後藤佐和子, 桑原頌治, 宇賀村大亮, 吉澤優太, 田中崇裕, 成田一衛, 斎藤亮彦

臨床薬理の進歩 ( 41 ) 148 - 153 2020.6

Language：Japanese Publisher：(公財)臨床薬理研究振興財団

軽度〜中等度腎機能障害を有する成人2型糖尿病患者(残存機能ネフロンに過剰代謝負荷がかかっていることが推測される)を対象に、エンパグリフロジンによる腎機能保護作用を検証するとともに尿中メガリン(およびメガリンリガンド分子)の動態を調べ、腎機能保護作用がメガリン機能に関連したものであるか検討した。さらに、尿中メガリンなどの検査がコンパニオン診断として有用であるか、探索的な検討を行った。また、SGLT2阻害薬がメガリンの発現・機能に及ぼす影響についても検討を継続した。臨床試験の被験者51名で、平均年齢は62歳であり、男性が32名であった。2名が有害反応のため脱落したが、6ヵ月後、HbA1cとBMIが減少した。現在、メガリンを含む尿中バイオマーカーの推移について解析を行っている。ダパグリフロジン、エンパグリフロジンを投与されたマウスでは尿中の糖排泄増加を認めたが血糖値に差は認められなかった。免疫組織化学染色では近位尿細管におけるメガリンの染色性が低下していることが確認された。またウエスタンブロット法において、メガリンの蛋白がvehicle群と比較して低下していることが認められた。リアルタイムRT-PCRにおいてもメガリンmRNAがvehicle群と比較して低下していることが確認された。ダパグリフロジンを添加されたIRPTCではメガリン蛋白の低下が認められ、mRNAの低下も認められた。

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Rice Endosperm Protein Administration to Juvenile Mice Regulates Gut Microbiota and Suppresses the Development of High-Fat Diet-Induced Obesity and Related Disorders in Adulthood. Reviewed International journal

Yuki Higuchi, Michihiro Hosojima, Hideyuki Kabasawa, Shoji Kuwahara, Sawako Goto, Koji Toba, Ryohei Kaseda, Takahiro Tanaka, Nobutaka Kitamura, Hayato Takihara, Shujiro Okuda, Masayuki Taniguchi, Hitoshi Arao, Ichiei Narita, Akihiko Saito

Nutrients 11 ( 12 ) 2019.12

Language：English Publishing type：Research paper (scientific journal)

Obesity and related disorders, which are increasing in adults worldwide, are closely linked to childhood diet and are associated with chronic inflammation. Rice endosperm protein (REP) intake during adulthood has been reported to improve lipid metabolism and suppress the progression of diabetic kidney disease in animal models. However, the effects of REP intake during childhood on adulthood health are unclear. Therefore, we used a mouse model to experimentally investigate the preconditioning effects of REP intake during childhood on the development of obesity and related disorders in adulthood. Male C57BL/6J mice were pair-fed a normal-fat diet containing casein or REP during the juvenile period and then a high-fat diet (HFD) containing casein or REP during adulthood. Mice fed REP during the juvenile period showed better body weight, blood pressure, serum lipid profiles, lipopolysaccharide (LPS)-binding protein levels, and glucose tolerance in adulthood than those fed casein during the juvenile period. HFD-induced renal tubulo-glomerular alterations and hepatic microvesicular steatosis were less evident in REP-fed mice than in casein-fed ones. REP intake during the juvenile period improved HFD-induced dysbiosis (i.e., Escherichia genus proliferation and reduced gut microbiota diversity), thereby suppressing endotoxin-related chronic inflammation. Indeed, REP-derived peptides showed antibacterial activity against Escherichia coli, a major producer of LPS. In conclusion, REP supplementation during the juvenile period may regulate the gut microbiota and thus suppress the development of obesity and related disorders in adulthood in mice.

DOI： 10.3390/nu11122919

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Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity: a prospective observational study. Reviewed International journal

Satoshi Shoji, Michihiro Hosojima, Hideyuki Kabasawa, Rie Kondo, Satoru Miura, Satoshi Watanabe, Nobumasa Aoki, Ryohei Kaseda, Shoji Kuwahara, Naohito Tanabe, Yoshiaki Hirayama, Ichiei Narita, Toshiaki Kikuchi, Hiroshi Kagamu, Akihiko Saito

BMC cancer 19 ( 1 ) 1170 - 1170 2019.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Cisplatin is a potent chemotherapeutic agent used to treat a variety of solid tumors. One of the major side effects of cisplatin is dose-limiting nephrotoxicity. We recently demonstrated that the renal uptake of cisplatin and resultant cisplatin-induced nephrotoxicity are mediated in part by megalin, an endocytic receptor in proximal tubule epithelial cells (PTECs). We also developed sandwich enzyme-linked immunosorbent assays to measure the megalin ectodomain (A-megalin) and full-length megalin (C-megalin) in urine using monoclonal antibodies against the amino- and carboxyl-termini of megalin, respectively. The present study examined the correlation of urinary megalin level with cisplatin-induced nephrotoxicity and its utility as a biomarker in patients with thoracic cancer. METHODS: This prospective observational study involved 45 chemotherapy-naïve patients scheduled to receive chemotherapy with ≥60 mg/m2 cisplatin for histologically diagnosed small cell lung cancer, non-small cell lung cancer, or malignant pleural mesothelioma. Before and after the first course of chemotherapy, we measured urinary A- and C-megalin and other markers of PTEC injury, such as N-acetyl-β-D-glucosaminidase, α1-microglobulin, β2-microglobulin, neutrophil gelatinase-associated lipocalin, and liver-type fatty acid-binding protein, and compared the values with the change in the estimated glomerular filtration rate (eGFR) and clinical risk factors for renal impairment. RESULTS: A negative correlation was found between baseline urinary A-megalin levels and change in eGFR (r = - 0.458, P = 0.002). According to Kaplan-Meier survival curves, eGFR decline was associated with the baseline urinary A-megalin quartile (P = 0.038). In addition, according to the hazard ratios (HRs) for eGFR decline > 10 mL/min/1.73 m2 calculated using a Cox proportional hazard model, the highest quartile had a significantly higher risk of eGFR decline compared with the lowest quartile (HR 7.243; 95% confidence interval 1.545-33.962). Other baseline urinary markers showed no correlation with eGFR decline. CONCLUSIONS: This is the first report demonstrating that prechemotherapy urinary A-megalin levels are correlated with the development of cisplatin-induced nephrotoxicity. This finding has clinical implications for the identification of patients at risk for cisplatin-induced nephrotoxicity and the development of possible prophylactic therapies.

DOI： 10.1186/s12885-019-6398-2

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Higher estimated net endogenous acid production with lower intake of fruits and vegetables based on a dietary survey is associated with the progression of chronic kidney disease. Reviewed International journal

Koji Toba, Michihiro Hosojima, Hideyuki Kabasawa, Shoji Kuwahara, Toshiko Murayama, Keiko Yamamoto-Kabasawa, Ryohei Kaseda, Eri Wada, Reiko Watanabe, Naohito Tanabe, Yoshiki Suzuki, Ichiei Narita, Akihiko Saito

BMC nephrology 20 ( 1 ) 421 - 421 2019.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Dietary acid load has been suggested to mediate the progression of chronic kidney disease (CKD). However, it is unclear what kinds of foods are actually associated with dietary acid load in patients with CKD. The self-administered diet history questionnaire (DHQ), which semi-quantitatively assesses the dietary habits of Japanese individuals through 150 question items, can estimate average daily intake of various foods and nutrients during the previous month. Using the DHQ, we investigated the association of dietary acid load with CKD progression. We also analyzed the kinds of food that significantly affect dietary acid load. METHODS: Subjects were 96 outpatients with CKD (average estimated glomerular filtration rate [eGFR], 53.0 ± 18.1 ml/min/1.73 m2) at Niigata University Hospital, who had completed the DHQ in 2011. We calculated net endogenous acid production (NEAP) from potassium and protein intake evaluated by the DHQ in order to assess dietary acid load. CKD progression was assessed by comparing eGFR between 2008 and 2014. RESULTS: NEAP was not correlated with protein intake (r = 0.088, p = 0.398), but was negatively correlated with potassium intake (r = - 0.748, p < 0.001). Reduction in eGFR from 2008 to 2014 was estimated to be significantly greater in patients with higher NEAP (NEAP > 50.1 mEq/day, n = 45) than in those with lower NEAP (NEAP ≤50.1 mEq/day, n = 50) by 5.9 (95% confidence interval [95%CI], 0.1 to 11.6) ml/min/1.73 m2. According to multiple logistic regression analysis, higher NEAP was significantly associated with lower intake of fruits (odds ratio [OR], 6.454; 95%CI, 2.19 to 19.00), green and yellow vegetables (OR, 5.18; 95%CI, 1.83 to14.66), and other vegetables (OR, 3.87; 95%CI, 1.29 to 11.62). CONCLUSIONS: Elevated NEAP could be a risk factor for CKD progression. Low intake of fruits and vegetables would increase dietary acid load and might affect the progression of renal dysfunction in Japanese CKD patients.

DOI： 10.1186/s12882-019-1591-8

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Podocyte Injury Augments Intrarenal Angiotensin II Generation and Sodium Retention in a Megalin-Dependent Manner. Reviewed International journal

Masahiro Koizumi, Kohei Ueda, Fumio Niimura, Akira Nishiyama, Motoko Yanagita, Akihiko Saito, Ira Pastan, Toshiro Fujita, Masafumi Fukagawa, Taiji Matsusaka

Hypertension (Dallas, Tex. : 1979) 74 ( 3 ) 509 - 517 2019.9

Language：English Publishing type：Research paper (scientific journal)

We have previously shown that podocyte injury increases the glomerular filtration of liver-derived Agt (angiotensinogen) and the generation of intrarenal Ang II (angiotensin II) and that the filtered Agt is reabsorbed by proximal tubules in a manner dependent on megalin. In the present study, we aimed to study the role of megalin in the generation of renal Ang II and sodium handling during nephrotic syndrome. We generated proximal tubule-specific megalin KO (knockout) mice and crossed these animals with NEP25 mice, in which podocyte-specific injury can be induced by injection of the immunotoxin LMB2. Without podocyte injury, renal Agt staining was markedly diminished and urinary Agt increased in KO mice. However, renal Ang II was similar between KO and control mice on average: 117 (95% CI, 101-134) versus 101 (95% CI, 68-133) fmol/g tissue. We next tested the effect of megalin KO on intrarenal Ang II generation with podocyte injury. Control NEP25 mice showed markedly increased renal Agt staining and renal Ang II levels: 450 (336-565) fmol/g tissue. Megalin KO/NEP25 mice showed markedly diminished Agt reabsorption and attenuated renal Ang II: 199 (156-242) fmol/g tissue (P<0.001). Compared with control NEP25 mice, megalin KO/NEP25 mice excreted 5-fold more sodium in the urine. Western blot analysis showed that megalin KO decreased NHE3 and the cleaved α and γ forms of Epithelial Na Channel. These data indicate that Agt reabsorbed by proximal tubules via megalin in nephrotic syndrome is converted to Ang II, which may contribute to sodium retention and edema formation by activating NHE3 and Epithelial Na Channel.

DOI： 10.1161/HYPERTENSIONAHA.118.12352

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シラスタチンによりシスプラチン腎症を抑制することでシスプラチン投与を増量できる(Cilastatin suppresses cisplatin-induced nephrotoxicity and enables to increase the dose of cisplatin for cancer therapy)

有田将史, 渡部聡, 青木信将, 高橋美帆, 庄子聡, 野嵜幸一郎, 市川紘将, 近藤利恵, 桑原頌治, 田中純太, 小屋俊之, 斎藤亮彦, 菊地利明

日本癌学会総会記事 78回 P - 1398 2019.9

2型糖尿病を合併した維持血液透析患者におけるオマリグリプチンの有用性の検討

吉澤優太, 細島康宏, 蒲澤秀門, 田邊直仁, 甲田豊, 島田久基, 高澤哲也, 伊藤孝仁, 鈴木芳樹, 成田一衛, 斎藤亮彦

糖尿病 62 ( 7 ) 419 - 419 2019.7

Association of estimated dietary acid load with albuminuria in Japanese adults: a cross-sectional study. Reviewed

Kabasawa K, Hosojima M, Takachi R, Nakamura K, Ito Y, Saito A, Sawada N, Tsugane S, Tanaka J, Narita I

BMC nephrology 20 ( 1 ) 194 2019.5

自記式食事歴質問票(DHQ)を用いたSGLT2阻害薬の効果と食事摂取状況の検討

村山稔子, 細島康宏, 蒲澤秀門, 桑原頌治, 田中崇裕, 鈴木芳樹, 成田一衛, 斎藤亮彦

糖尿病 62 ( Suppl.1 ) S - 263 2019.4

Significance of urinary C-megalin excretion in vitamin D metabolism in pre-dialysis CKD patients. Reviewed International journal

Toi N, Inaba M, Ishimura E, Tsugawa N, Imanishi Y, Emoto M, Hirayama Y, Nakatani S, Saito A, Yamada S

Scientific reports 9 ( 1 ) 2207 - 2207 2019.2

Language：English Publishing type：Research paper (scientific journal)

Serum 1,25(OH)2D and 24,25(OH)2D are decreased in CKD. Megalin in proximal tubular epithelial cells reabsorbs glomerular-filtered 25(OH)D-DBP complex to convert 25(OH)D to 1,25(OH)2D and 24,25(OH)2D. Urinary C-megalin excretion is increased via exocytosis from injured nephrons overloaded with megalin-mediated protein metabolism. This study investigated the significance of urinary C-megalin excretion in vitamin D metabolism in 153 pre-dialysis CKD patients. Urinary C-megalin was positively associated with urinary protein, β2MG and α1MG, and exhibited negative correlations with serum 25(OH)D, 1,25(OH)2D and 24,25(OH)2D. Multiple regression analysis showed that urinary C-megalin had a significantly negative association with 25(OH)D. Serum 1,25(OH)2D and 24,25(OH)2D, as well as 1,25(OH)2D/25(OH)D and 24,25(OH)2D/25(OH)D ratios, showed positive correlations with eGFR. Additionally, wholePTH was positively associated with 1,25(OH)2D/25(OH)D and 1,25(OH)2D/24,25(OH)2D, while FGF23 was positively associated with 24,25(OH)2D/25(OH)D and negatively with 1,25(OH)2D/24,25(OH)2D. Urinary C-megalin emerged as an independent factor positively associated with 1,25(OH)2D/25(OH)D and 1,25(OH)2D/24,25(OH)2D. Although 1,25(OH)2D and 24,25(OH)2D are decreased in CKD patient serum, our findings suggest that PTH and FGF23 retain their effects to regulate vitamin D metabolism even in the kidneys of these patients, while production of 1,25(OH)2D and 24,25(OH)2D from 25(OH)D is restricted due to either impairment of megalin-mediated reabsorption of the 25(OH)D-DBP complex or reduced renal mass.

DOI： 10.1038/s41598-019-38613-8

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