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Rie Jo, Hirotaka Shibata, Isao Kurihara, Kenichi Yokota, Sakiko Kobayashi, Ayano Murai-Takeda, Yuko Mitsuishi, Takeshi Hayashi, Toshifumi Nakamura, Hiroshi Itoh

Hypertension research : official journal of the Japanese Society of Hypertension 46 ( 1 ) 19 - 31 2023.01

ISSN 09169636

This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. Coimmunoprecipitation assays in HEK293T cells showed that MR is a target of O-GlcNAc modification (O-GlcNAcylation). The expression levels and transcriptional activities of the receptor increased in parallel with its O-GlcNAcylation under high-glucose conditions. Liquid chromatography-tandem mass spectrometry revealed O-GlcNAcylation of the MR at amino acids 295-307. Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. The administration of 6-diazo-5-oxo-L-norleucin, an inhibitor of O-GlcNAcylation, reduced tissue O-GlcNAc levels and MR protein levels in db/db mice. Thus, our study showed that O-GlcNAcylation of the MR directly increases protein levels and transcriptional activities of the receptor under high-glucose conditions in vitro and in vivo. These findings provide a novel mechanism of MR as a target for prevention of complications associated with diabetes mellitus.

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MECHANISMS OF MINERALOCORTICOID RECEPTOR-ASSOCIATED HYPERTENSION IN DIABETES MELLITUS: ROLE OF O-GLCNAC MODIFICATION

Jo, R; Shibata, H; Kurihara, I; Yokota, K; Kobayashi, S; Murai-Takeda, A; Mitsuishi, Y; Hayashi, T; Nakamura, T; Itoh, H

JOURNAL OF HYPERTENSION 41 E285 - E286 2023.01

ISSN 0263-6352

ISH2022KYOTO Hypertension Zero Declaration

Tomaszewski, M; Itoh, H

HYPERTENSION RESEARCH 46 ( 1 ) 1 - 2 2023.01

ISSN 0916-9636

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RENIN-ANGIOTENSIN SYSTEM INHIBITORS IN PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE ASSOCIATED WITH A LOWER RISK OF UNPLANNED DIALYSIS INITIATION

Nakayama, T; Morimoto, K; Uchiyama, K; Kusahana, E; Washida, N; Azegami, T; Kanda, T; Yoshida, T; Itoh, H

JOURNAL OF HYPERTENSION 41 E385 - E385 2023.01

ISSN 0263-6352

RENOVASCULAR HYPERTENSION FROM FIBROMUSCULAR DYSPLASIA WITHOUT ABNORMALITIES IN RENAL DOPPLER ULTRASOUND: A CASE REPORT.

Kato, K; Mizutani, Y; Nakamura, T; Kinouchi, K; Kobayashi, S; Miyashita, K; Itoh, H

JOURNAL OF HYPERTENSION 41 E350 - E350 2023.01

ISSN 0263-6352

INTERMITTENTLY SCANNED CONTINUOUS GLUCOSE MONITORING IN A DIFFICULT PATIENT WITH GESTATIONAL DIABETES MELLITUS AND SUBCLINICAL CUSHING'S SYNDROME: A CASE REPORT.

Iwahara, A; Sugiyama, K; Tsuchiya, T; Itoh, A; Nakajima, Y; Saisho, Y; Kinouchi, K; Kobayashi, S; Miyashita, K; Irie, J; Meguro, S; Ikenoue, S; Tanaka, M; Itoh, H

JOURNAL OF HYPERTENSION 41 E437 - E437 2023.01

ISSN 0263-6352

HYPOBILIRUBINEMIA AND HYPERTENSION AS RISK FACTORS FOR DIABETIC RETINOPATHY OF TYPE 1 AND TYPE 2 DIABETES MELLITUS

Tanaka, M; Nishimura, T; Itoh, H

JOURNAL OF HYPERTENSION 41 E382 - E382 2023.01

ISSN 0263-6352

HIGH BODY MASS INDEX IS A RISK FACTOR FOR TRANSITION TO HEMODIALYSIS OR HYBRID THERAPY AND PERITONEAL DIALYSIS-RELATED INFECTION

Hama, EY; Uchiyama, K; Nagasaka, T; Kusahana, E; Nakayama, T; Yasuda, I; Morimoto, K; Washida, N; Hayashi, K; Itoh, H

JOURNAL OF HYPERTENSION 41 E385 - E386 2023.01

ISSN 0263-6352

THE IMPACT OF ANTIHYPERTENSIVE DRUG USE ON INTRADIALYTIC BLOOD PRESSURE DECLINE CONSIDERING SEASONAL VARIATION: A RETROSPECTIVE COHORT STUDY

Uchiyama, K; Washida, N; Shibagaki, K; Yanai, A; Nakayama, T; Morimoto, K; Itoh, H

JOURNAL OF HYPERTENSION 41 E386 - E386 2023.01

ISSN 0263-6352

STUDY OF THE ANTIHYPERTENSIVE EFFECTS OF ORAL SEMAGLUTIDE, GLP 1 RECEPTOR AGONIST

Meguro, S; Itoh, H

JOURNAL OF HYPERTENSION 41 E381 - E381 2023.01

ISSN 0263-6352

THE ASSOCIATION BETWEEN INSULIN RESISTANCE AND DECLINE IN ORGAN FUNCTION IN NON-OBESE JAPANESE INDIVIDUALS

Kaneko, K; Hirota, RS; Makino, K; Nagasaka, T; Kojima, D; Takaishi, H; Yoshino, J; Itoh, H

JOURNAL OF HYPERTENSION 41 E465 - E465 2023.01

ISSN 0263-6352

WISDOM FOR CONQUERING HYPERTENSION---FOOD, MOVE, AI: TOWARDS SUSTAINABLE WELL-BEING

Itoh, H

JOURNAL OF HYPERTENSION 41 E6 - E6 2023.01

ISSN 0263-6352

TRANSARTERIAL EMBOLIZATION, THORACIC SPINE DECOMPRESSION AND FUSION OF METASTATIC PHEOCHROMOCYTOMA: A CASE REPORT.

Kinouchi, K; Mizutani, Y; Nakamura, T; Yamaguchi, S; Homma, K; Kobayashi, S; Miyashita, K; Kurihara, I; Shibata, H; Itoh, H

JOURNAL OF HYPERTENSION 41 E437 - E438 2023.01

ISSN 0263-6352

Compared effectiveness of sodium zirconium cyclosilicate and calcium polystyrene sulfonate on hyperkalemia in patients with chronic kidney disease.

Takashin Nakayama, Shintaro Yamaguchi, Kaori Hayashi, Kiyotaka Uchiyama, Takaya Tajima, Tatsuhiko Azegami, Kohkichi Morimoto, Tadashi Yoshida, Jun Yoshino, Toshiaki Monkawa, Takeshi Kanda, Hiroshi Itoh

Frontiers in medicine 10 1137981 - 1137981 2023

ISSN 2296-858X

Hyperkalemia is a well-recognized electrolyte abnormality in patients with chronic kidney disease (CKD). Potassium binders are often used to prevent and treat hyperkalemia. However, few studies have evaluated the difference in serum potassium (K+) level-lowering effect during the post-acute phase between the novel potassium binder, sodium zirconium cyclosilicate (ZSC), and conventional agents. This retrospective study included patients who received potassium binders (either ZSC or calcium polystyrene sulfonate [CPS]) in our hospital between May 2020 and July 2022. The patients were divided into the ZSC and CPS groups. After propensity score matching, we compared changes from baseline to the first follow-up point, at least 4 weeks after initiating potassium binders, in electrolytes including K+ level between the two groups. Of the 132 patients, ZSC and CPS were administered in 48 and 84 patients, respectively. After matching, 38 patients were allocated to each group. The ZSC group showed greater reduction in K+ levels than did the CPS group (P < 0.05). Moreover, a significant increase in serum sodium minus chloride levels, a surrogate marker for metabolic acidosis, was observed in the ZSC group (P < 0.05). Our results demonstrated that ZSC could potentially improve hyperkalemia and metabolic acidosis in patients with CKD.

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Correlation between acylcarnitine/free carnitine ratio and cardiopulmonary exercise test parameters in patients with incident dialysis.

Wataru Ito, Kiyotaka Uchiyama, Ryunosuke Mitsuno, Erina Sugita, Takashin Nakayama, Toshinobu Ryuzaki, Rina Takahashi, Yoshinori Katsumata, Kaori Hayashi, Takeshi Kanda, Naoki Washida, Kazuki Sato, Hiroshi Itoh

Frontiers in physiology 14 1155281 - 1155281 2023

ISSN 1664-042X

Objective: Diminished physical capacity is common and progressive in patients undergoing dialysis, who are also prone to deficiency in carnitine, which plays a pivotal role in maintaining skeletal muscle and cardiac function. The present study aimed to evaluate the association of carnitine profile with exercise parameters in patients with incident dialysis. Design and Methods: This was a single-center cross-sectional study including 87 consecutive patients aged 20-90 years who were initiated on dialysis in Keio University Hospital between December 2019 and December 2022 and fulfilled the eligibility criteria. Exercise parameters were evaluated via cardiopulmonary testing (CPX) using the electronically braked STRENGTH ERGO 8 ergometer, whereas the carnitine profile was assessed by determining serum free carnitine (FC), acylcarnitine (AC) levels and AC/FC ratio. Results: The mean cohort age was 62.1 ± 15.2 years, with male and hemodialysis predominance (70% and 73%, respectively). AC/FC was 0.46 ± 0.15, and CPX revealed peak oxygen consumption (VO2) of 13.9 ± 3.7 (mL/kg/min) with percent-predicted peak VO2 of 53.6% ± 14.7% and minute ventilation (VE)/carbon dioxide output (VCO2) slope of 35.1 ± 8.0. Fully-adjusted multivariate linear regression analysis showed that AC/FC was significantly associated with decreased peak VO2 (β, -5.43 [95% confidence interval (CI), -10.15 to -0.70]) and percent-predicted peak VO2 (β, -19.98 [95% CI, -38.43 to -1.52]) and with increased VE/VCO2 slope (β, 13.76 [95% CI, 3.78-23.75]); FC and AC did not exhibit similar associations with these parameters. Moreover, only AC/FC was associated with a decreased peak work rate (WR), percent-predicted WR, anaerobic threshold, delta VO2/delta WR, and chronotropic index. Conclusion: In patients on incident dialysis, exercise parameters, including those related to both skeletal muscle and cardiac function, were strongly associated with AC/FC, a marker of carnitine deficiency indicating altered fatty acid metabolism. Further studies are warranted to determine whether carnitine supplementation can improve exercise capacity in patients on incident dialysis.

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