MATSUDA Noritake, Hideki Otsuka, Ryosuke Kasai, Tamaki Otani, BOLLOS CHRISTINE ANNE LEAH LOCSIN, Shota Azane, Yamato Kunikane, Youichi Otomi, UEKI Yuya, Mana Okabe, Masafumi Amano, Masanori Tamaki, Shu Wakino, Shoichiro Takao and Masafumi Harada : Quantitative evaluation of 67Gacitrate scintigraphy in the management of nephritis, Scientific Reports, Vol.14, No.16313, 16313, 2024.
(要約)
In Ga-citrate scintigraphy (Ga-S), visual assessment is used by evaluating renal-uptake comparison with liver and spine and is simple and objective. We adopted the standardized uptake value (SUV) for Ga-citrate and proposed two quantitative indices, active nephritis volume (ANV) and total nephritis uptake (TNU). This study clarified the utility of new Ga-S-based quantitative indices in nephritis management. Before SUV measurement, the Becquerel calibration factor of Ga-citrate was obtained using a phantom experiment. Seventy patients who underwent SPECT/CT imaging were studied. SUV, ANV, and TNU were calculated using a quantitative analysis software for bone SPECT. SUV, ANV, and TNU were analyzed using the (1) threshold method (set 40%) and constant-value method for (2) vertebral SUV, and (3) vertebral SUV. ROC analysis was used to evaluate SUV, ANV, and TNU diagnostic abilities to distinguish nephritis presence and absence as well as interstitial nephritis (IN) and non-IN. The area under the curve (AUC) for nephritis presence or absence had a good value (0.80) for SUV (1), ANV (3), and TNU (3). The AUC for differentiation between IN and non-IN groups had a good value (0.80) for SUV (1). Thus, the new Ga-S-based quantitative indices were useful to evaluate nephritis and distinguish IN and non-IN.
Kazuhiro Hasegawa, Masanori Tamaki, Yusuke Sakamaki and Shu Wakino : Deficiency Causes Mitoribosome Excess in Diabetic Nephropathy Mediated by Transcriptional Repressor HIC1., International Journal of Molecular Sciences, Vol.25, No.12, 2024.
(要約)
overexpression preserved mitoribosomal function, suggesting its protective role in DN.
Kazuhiro Hasegawa, Masanori Tamaki, Eriko Shibata, Taizo Inagaki, Masanori Minato, Sumiyo Yamaguchi, Ikuko Shimizu, Shinji Miyakami, Miho Tada and Shu Wakino : Ability of NAD and Sirt1 to epigenetically suppress albuminuria., Clinical and Experimental Nephrology, Vol.28, No.7, 599-607, 2024.
(要約)
The time for diabetic nephropathy (DN) to progress from mild to severe is long. Thus, methods to continuously repress DN are required to exert long-lasting effects mediated through epigenetic regulation. In this study, we demonstrated the ability of nicotinamide adenine dinucleotide (NAD) and its metabolites to reduce albuminuria through Sirt1- or Nampt-dependent epigenetic regulation. We previously reported that proximal tubular Sirt1 was lowered before glomerular Sirt1. Repressed glomerular Sirt1 was found to epigenetically elevate Claudin-1. In addition, we reported that proximal tubular Nampt deficiency epigenetically augmented TIMP-1 levels in Sirt6-mediated pathways, leading to type-IV collagen deposition and diabetic fibrosis. Altogether, we propose that the Sirt1/Claudin-1 axis may be crucial in the onset of albuminuria at the early stages of DN and that the Nampt/Sirt6/TIMP-1 axis promotes diabetic fibrosis in the middle to late stages of DN. Finally, administration of NMN, an NAD precursor, epigenetically potentiates the regression of the onset of DN to maintain Sirt1 and repress Claudin-1 in podocytes, suggesting the potential use of NAD metabolites as epigenetic medications for DN.
Keika Adachi, Marie Yasuda, Makiko Ida, Takeshi Kanda, Akemi Morita, Shu Wakino, Shaw Watanabe and Hiroshi Itoh : Impact of dietary habits on renal function in Saku, a rural Japanese town: a cohort study., Clinical and Experimental Nephrology, Vol.28, No.8, 751-763, 2024.
(要約)
High protein intake leads to a decline in renal function in the advanced stages of chronic kidney disease (CKD). An effective diet for maintaining renal function in healthy individuals or patients in the early stages of CKD has not been established. This cohort study was conducted in Saku, Nagano Prefecture, Japan, to investigate the impact of dietary habits on renal function. In this cross-sectional cohort study, we used the Saku Control Obesity Program (UMIN000016892), including 4,446 participants who submitted a brief-type self-administered diet history questionnaire and underwent routine physical examination. The amount of food intake was divided into quartiles. After adjusting for age and sex, multivariate logistic regression analysis was used to calculate the odds ratio (OR) for the risk of developing CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m). In total, 3,899 participants were analyzed. The overall prevalence of patients with eGFR < 60 mL/min/1.73 m was 11% (n = 434, male; 7.1%, female; 4.1%). The groups with a high intake of chicken (approximately 63.4 g/day, adjusted OR: 0.632, P = 0.003), natto (fermented bean; approximately 21.7 g/day, adjusted OR: 0.679, P = 0.01), and plant protein (approximately 0.8 g/ideal body weight/day, adjusted OR: 0.695, P = 0.042) showed a low risk of developing CKD compared to the group with the lowest intake. Our cross-sectional study showed that the intake of chicken meat, natto, and plant protein was associated with high eGFR levels. This information can be of value for preventing CKD incidence in healthy Japanese individuals.
(キーワード)
Adult / Aged / Female / Humans / Male / Middle Aged / Cross-Sectional Studies / East Asian People / Glomerular Filtration Rate / Japan / Kidney / Prevalence / Renal Insufficiency, Chronic / Risk Factors / Diet
Yasushi Furukawa, Keiko Tanaka, Osamu Isozaki, Atsushi Suzuki, Tadao Iburi, Kumiko Tsuboi, Moritake Iguchi, Naotetsu Kanamoto, Kanshi Minamitani, Shu Wakino, Tetsurou Satoh, Satoshi Teramukai, Eizen Kimura, Yoshihiro Miyake and Takashi Akamizu : Prospective Multicenter Registry-Based Study on Thyroid Storm: The Guidelines for the Management from Japan are Useful., The Journal of Clinical Endocrinology and Metabolism, 2024.
(要約)
The mortality rate in thyroid storm (TS) has been reported to be higher than 10%. We aimed to evaluate the effectiveness of the 2016 guidelines for the management of TS proposed by the Japan Thyroid Association and Japan Endocrine Society. Prospective registry-based study through a secure web platform. Prospective multicenter registry. Patients with new-onset TS were registered in the Research Electronic Data Capture (REDCap). On day 30 after admission, clinical information and prognosis of each patient were added to the platform. On day 180, the prognosis was described. This study included 110 patients with TS. The median of Acute Physiology and Chronic Health Evaluation (APACHE) II score was 13, higher than the score in the previous nationwide epidemiological study, 10 (p = 0.001). Nonetheless, the mortality rate at day 30 was 5.5%, approximately half compared with 10.7% in the previous nationwide survey. Lower body mass index, shock and lower left ventricular ejection fraction were positively associated with poor prognosis at day 30, while the lack of fever ≥ 38℃ was related to the outcome. The mortality rate in patients with an APACHE II score ≥12 for whom the guidelines were not followed was significantly higher than the rate in patients for whom the guidelines were followed (50% vs. 4.7%) (p = 0.01). Prognosis seemed better than in the previous nationwide survey, even though disease severity was higher. The mortality rate was lower when the guidelines were followed. Thus, the guidelines are useful for managing TS.
Shimon Kurasawa, Sawako Kato, Takaya Ozeki, Shin'ichi Akiyama, Takuji Ishimoto, Masashi Mizuno, Naotake Tsuboi, Noritoshi Kato, Shu Wakino and Shoichi Maruyama : Rationale and design of the Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study., Clinical and Experimental Nephrology, Vol.28, No.5, 431-439, 2024.
(要約)
The Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study is a nationwide, multicenter, and prospective cohort study in Japan, enrolling adult (≥18 years) patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), C3 glomerulopathy (C3G), and lupus nephritis (LN). Baseline clinical information and plasma and urine samples will be collected at the time of immunosuppressive therapy initiation or biopsy. Follow-up data and plasma and urine samples will be collected longitudinally based on the designated protocols. Candidate biomarkers will be measured: CD80, cytotoxic T-lymphocyte antigen 4, and soluble urokinase plasminogen activator receptor for MCD and FSGS; anti-phospholipase A2 receptor and thrombospondin type-1 domain-containing protein 7A antibodies for MN; fragment Ba, C3a, factor I, and properdin for MPGN/C3G; and CD11b, CD16b, and CD163 for LN. Outcomes include complete and partial remission, relapse of proteinuria, a 30% reduction in estimated glomerular filtration rate (eGFR), eGFR decline, and initiation of renal replacement therapy. The diagnostic accuracy and predictive ability for clinical outcomes will be assessed for each biomarker.
(キーワード)
Humans / Biomarkers / Nephrotic Syndrome / Prospective Studies / Japan / Glomerulosclerosis, Focal Segmental / Receptors, Urokinase Plasminogen Activator / Glomerulonephritis, Membranous / Adult / Nephrosis, Lipoid / Research Design / Receptors, Phospholipase A2 / Thrombospondins / Glomerulonephritis, Membranoproliferative / Male / Female / Lupus Nephritis / East Asian People / B7-1 Antigen
Norito Yoshimura, Katsutoshi Yamada, Takashi Ono, Mitsuru Notoya, Hideo Yukioka, Rina Takahashi, Shu Wakino, Takeshi Kanda and Hiroshi Itoh : N-methyl-2-pyridone-5-carboxamide (N-Me-2PY) has potent anti-fibrotic and anti-inflammatory activity in a fibrotic kidney model: is it an old uremic toxin?, Clinical and Experimental Nephrology, 2023.
(要約)
NAD + metabolites, such as N-Me-2PY, are not uremic toxins but are potential therapeutic agents that have anti-fibrotic effects in CKD.
Kan Kikuchi, Masaomi Nangaku, Munekazu Ryuzaki, Tomoyuki Yamakawa, Yoshihiro Ota, Norio Hanafusa, Ken Sakai, Yoshihiko Kanno, Ryoichi Ando, Toshio Shinoda, Shu Wakino, Hidetomo Nakamoto, Yoshiaki Takemoto and Tadao Akizawa : Efficacy of molnupiravir and sotrovimab in Japanese dialysis patients with COVID-19 in clinical practice during the Omicron (BA.1 and BA.2) pandemic., Therapeutic Apheresis and Dialysis, 2023.
(要約)
A total of 1480 patients were included. The mortality of the molnupiravir, sotrovimab, and combination groups were significantly improved compared to the control group (p < 0.001). Multivariate analysis indicated that antiviral therapy improves the survival of dialysis patients with COVID-19 (hazard ratio was 0.184 for molnupiravir, 0.389 for sotrovimab, and 0.254 for combination groups, respectively).
Kazuhiro Hasegawa, Yusuke Sakamaki, Masanori Tamaki and Shu Wakino : PCK1 Protects against Mitoribosomal Defects in Diabetic Nephropathy in Mouse Models., Journal of the American Society of Nephrology, Vol.34, No.8, 1343-1365, 2023.
(要約)
PCK1 preserves mitoribosomal function and may play a novel protective role in DN.
Ayumi Yoshifuji, Masataro Toda, Munekazu Ryuzaki, Emi Oyama, Kan Kikuchi, Toru Kawai, Ken Sakai, Masayoshi Koinuma, Kazuhiko Katayama, Takashi Yokoyama, Yuki Uehara, Norio Ohmagari, Yoshihiko Kanno, Hirofumi Kon, Toshio Shinoda, Yaoko Takano, Junko Tanaka, Kazuhiko Hora, Yasushi Nakazawa, Naoki Hasegawa, Norio Hanafusa, Fumihiko Hinoshita, Keita Morikane, Shu Wakino, Hidetomo Nakamoto and Yoshiaki Takemoto : T-Cell Response and Antibody Production Induced by the COVID-19 Booster Vaccine in Japanese Chronic Kidney Disease Patients Treated with Hemodialysis., Vaccines, Vol.11, No.3, 2023.
(要約)
COVID test (T-SPOT) were measured prior to, three weeks after, and three months after the booster administration. The HD group had significantly higher SARS-CoV-2 IgG levels and neutralizing antibody titers against the original strain at three weeks and three months after the booster vaccination compared to the control group, albeit the HD group had lower SARS-CoV-2 IgG levels and neutralizing antibody titers before the booster administration. Moreover, the HD group had significantly higher T-SPOT levels at all three time points compared to the control group. The HD group also had significantly higher local and systemic adverse reaction rates than the control group. By booster vaccination, HD patients could acquire more effective SARS-CoV-2-specific humoral and cellular immunity than the control group.
Sodium benzoate (SB), a known D-amino acid oxidase (DAO) enzyme inhibitor, has an anti-inflammatory effect, although its role in renal damage has not been explored. 2,8-dihydroxyadenine crystal induced chronic kidney disease, in which TNF-α is involved in the pathogenesis, was established by oral adenine administration in C57BL/6JJcl mice (AdCKD) with or without SB to investigate its renal protective effects. SB significantly attenuated AdCKD by decreasing serum creatinine and urea nitrogen levels, and kidney interstitial fibrosis and tubular atrophy scores. The survival of AdCKD mice improved 2.6-fold by SB administration. SB significantly decreased the number of infiltrating macrophages observed in the positive F4/80 immunohistochemistry area and reduced the expression of macrophage markers and inflammatory genes, including TNF-α, in the kidneys of AdCKD. Human THP-1 cells stimulated with either lipopolysaccharide or TNF-α showed increased expression of inflammatory genes, although this was significantly reduced by SB, confirming the anti-inflammatory effects of SB. SB exhibited renal protective effects in AdCKD in DAO enzyme deficient mice, suggesting that anti-inflammatory effect of SB was independent of DAO enzyme activity. Moreover, binding to motif DNA sequence, protein level, and mRNA level of NF-κB RelB were significantly inhibited by SB in AdCKD kidneys and lipopolysaccharide treated THP-1 cells, respectively. We report that anti-inflammatory property of SB is independent of DAO enzymatic activity and is associated with down regulated NF-κB RelB as well as its downstream inflammatory genes such as TNF-α in AdCKD.
Ayumi Matsui, Ayumi Yoshifuji, Junichiro Irie, Takaya Tajima, Kiyotaka Uchiyama, Tomoaki Itoh, Shu Wakino and Hiroshi Itoh : Canagliflozin protects the cardiovascular system through effects on the gut environment in non-diabetic nephrectomized rats., Clinical and Experimental Nephrology, Vol.27, No.4, 295-308, 2023.
(要約)
The increases in colonic glucose concentration, Lactobacillus numbers and tight junction protein expression, and the decreases in serum uremic toxin concentrations and cardiac interstitial fibrosis may have been caused by the inhibition of SGLT1 by canagliflozin because similar effects were not identified in tofogliflozin-treated rats.
Kunihisa Yamaguchi, Keisuke Ozaki, Tomoya Fukawa, Yutaro Sasaki, Shu Wakino and Masayuki Takahashi : Drug-induced de novo thrombotic microangiopathy diagnosed 2 years after renal transplantation: A case report and literature review, Renal Replacement Therapy, Vol.9, 1-6, 2023.
Ayumi Yoshifuji, Masataro Toda, Munekazu Ryuzaki, Kan Kikuchi, Toru Kawai, Ken Sakai, Emi Oyama, Masayoshi Koinuma, Kazuhiko Katayama, Yuki Uehara, Norio Ohmagari, Yoshihiko Kanno, Hirofumi Kon, Toshio Shinoda, Yaoko Takano, Junko Tanaka, Kazuhiko Hora, Yasushi Nakazawa, Naoki Hasegawa, Norio Hanafusa, Fumihiko Hinoshita, Keita Morikane, Shu Wakino, Hidetomo Nakamoto and Yoshiaki Takemoto : Investigation for the efficacy of COVID-19 vaccine in Japanese CKD patients treated with hemodialysis., Renal Replacement Therapy, Vol.8, No.1, 2022.
(要約)
HD patients had significantly lower antibody titers than age- and sex-matched non-dialysis individuals over 3 months after vaccination. Dialysis time was identified as a factor affecting SARS-CoV-2 IgG titers in HD group, with longer dialysis time resulting in higher maximum SARS-CoV-2 IgG titers.
Makiko Ida-Naitoh, Hirobumi Tokuyama, Koji Futatsugi, Marie Yasuda, Keika Adachi, Takeshi Kanda, Yoshiyuki Tanabe, Shu Wakino and Hiroshi Itoh : Proximal-tubule molecular relay from early Protein diaphanous homolog 1 to late Rho-associated protein kinase 1 regulates kidney function in obesity-induced kidney damage., Kidney International, Vol.102, No.4, 798-814, 2022.
(要約)
The small GTPase protein RhoA has two effectors, ROCK (Rho-associated protein kinase 1) and mDIA1 (protein diaphanous homolog 1), which cooperate reciprocally. However, temporal regulation of RhoA and its effectors in obesity-induced kidney damage remains unclear. Here, we investigated the role of RhoA activation in the proximal tubules at the early and late stages of obesity-induced kidney damage. In mice, a three-week high-fat-diet induced proximal tubule hypertrophy and damage without increased albuminuria, and RhoA/mDIA1 activation without ROCK activation. Conversely, a 12-week high-fat diet induced proximal tubule hypertrophy, proximal tubule damage, increased albuminuria, and RhoA/ROCK activation without mDIA1 elevation. Proximal tubule hypertrophy resulting from cell cycle arrest accompanied by downregulation of the multifunctional cyclin-dependent kinase inhibitor p27Kip1 was elicited by RhoA activation. Mice overexpressing proximal tubule-specific and dominant-negative RHOA display amelioration of high-fat diet-induced kidney hypertrophy, cell cycle abnormalities, inflammation, and renal impairment. In human proximal tubule cells, mechanical stretch mimicking hypertrophy activated ROCK, which triggered inflammation. In human kidney samples from normal individuals with a body mass index of about 25, proximal tubule cell size correlated with body mass index, proximal tubule cell damages, and mDIA1 expression. Thus, RhoA activation in proximal tubules is critical for the initiation and progression of obesity-induced kidney damage. Hence, the switch in the downstream RhoA effector in proximal tubule represents a transition from normal to pathogenic kidney adaptation and to body weight gain, leading to obesity-induced kidney damage.
Kan Kikuchi, Masaomi Nangaku, Munekazu Ryuzaki, Tomoyuki Yamakawa, Ota Yoshihiro, Norio Hanafusa, Ken Sakai, Yoshihiko Kanno, Ryoichi Ando, Toshio Shinoda, Shu Wakino, Hidetomo Nakamoto, Yoshiaki Takemoto and Tadao Akizawa : Effectiveness of SARS-CoV-2 vaccines on hemodialysis patients in Japan: A nationwide cohort study., Therapeutic Apheresis and Dialysis, Vol.27, No.1, 19-23, 2022.
(要約)
Our prospective observational study showed that SRAS-CoV-2 vaccination in hemodialysis patients is vital for reducing need of oxygen supplementation and mortality risk.
Erina Sugita, Homare Sonoda, Masaki Ryuzaki, Akinori Hashiguchi, Hirobumi Tokuyama, Shu Wakino, Takeshi Kanda and Hiroshi Itoh : Diagnosis of monoclonal immunotactoid glomerulopathy with positive λ chain by immunoelectron microscopy., CEN Case Reports, Vol.12, No.1, 7-13, 2022.
(要約)
We report the case of a 73-year-old-man who developed immunotactoid glomerulopathy (ITG). ITG is a rare disease characterized by proliferative glomerulonephritis and capillary wall deposits with a 10-60 nm diameter microtubular substructure. In monoclonal ITG, immunofluorescence analysis typically exhibits IgG with light chain restriction. Recent reviews recommend distinguishing monoclonal ITG from polyclonal ITG because monoclonal ITG is associated with a higher incidence of hematological disorders and better responsiveness to clone-directed therapy and renal prognosis. In our case, IgG, IgA, and IgM were negative by routine immunofluorescence; however, immunoelectron microscopy revealed positive λ chain. At 6 months after renal biopsy, the IgG λ chain was detected in the serum and urine, reflecting possible monoclonality. Therefore, it is useful to perform immunoelectron microscopy and follow-up with serum and urine protein electrophoresis and immunofixation to diagnose monoclonal ITG, even when routine immunofluorescence shows negative or nonspecific findings.
Ayumi Yoshifuji, Munekazu Ryuzaki, Yuki Uehara, Norio Ohmagari, Toru Kawai, Yoshihiko Kanno, Kan Kikuchi, Hiroshi Kon, Ken Sakai, Toshio Shinoda, Yaoko Takano, Junko Tanaka, Kazuhiko Hora, Yasushi Nakazawa, Naoki Hasegawa, Norio Hanafusa, Fumihiko Hinoshita, Keita Morikane, Shu Wakino, Hidetomo Nakamoto and Yoshiaki Takemoto : Committee report: Questionnaire survey on the treatment of COVID-19 in patients receiving dialysis therapy., Renal Replacement Therapy, Vol.8, No.1, 2022.
(要約)
Sixty-six centers (62.9%) responded to the questionnaire. Antivirals were administered in 27.7% of facilities treating mild disease (most patients received favipiravir) and 66.7% of facilities treating moderate disease (most patients with moderate or more severe conditions received remdesivir). Whether and how remdesivir is administered varies between centers. Steroids were initiated most frequently in moderate II disease (50.8%), while 43.1% of the facilities initiated steroids in mild or moderate I disease. The type of steroid, dose, and the duration of administration were generally consistent, with most facilities administering dexamethasone 6 mg orally or 6.6 mg intravenously for 10 days. Steroid pulse therapy was administered in 48.5% of the facilities, and tocilizumab was administered in 25.8% of the facilities, mainly to patients on ventilators or equivalent medications, or to the cases of exacerbations. Furthermore, some facilities used a polymethylmethacrylate membrane during dialysis, nafamostat as an anticoagulant, and continuous hemodiafiltration in severe cases. There was limited experience of polymyxin B-immobilized fiber column-direct hemoperfusion and extracorporeal membrane oxygenation. The discharge criteria for patients receiving dialysis therapy were longer than those set by the Ministry of Health, Labor and Welfare in 22.7% of the facilities.
Kiyotaka Uchiyama, Kohkichi Morimoto, Naoki Washida, Ei Kusahana, Takashin Nakayama, Tomoaki Itoh, Takahiro Kasai, Shu Wakino and Hiroshi Itoh : Effects of a remote patient monitoring system for patients on automated peritoneal dialysis: a randomized crossover controlled trial., International Urology and Nephrology, Vol.54, No.10, 2673-2681, 2022.
(要約)
Significant improvements were observed in the TSQM-9 subscales of Effectiveness (64.4 ± 18.8 vs. 57.8 ± 18.8; P = 0.006) and Convenience (76.3 ± 15.4 vs. 63.3 ± 17.3; P < 0.001) in patients on Sharesource®. Moreover, Sharesource® reduced the total amount of healthcare resource consumption (0.80 ± 1.32 vs. 1.87 ± 2.39 times/12 weeks; P = 0.02) and consultation time during regular monthly visits (813 ± 269 vs. 1024 ± 292 s; P < 0.001). A significant increase in ultrafiltration volume was found associated with more frequent modification of APD prescription in patients with Sharesource®. Sharesource® also improved the HRQOL subscale of General Health and Vitality.
(キーワード)
Aged / Humans / Kidney Failure, Chronic / Male / Monitoring, Physiologic / Patient Satisfaction / Peritoneal Dialysis / Prospective Studies / Quality of Life
Keika Adachi, Kiyotaka Uchiyama, Kaori Muraoka, Takashin Nakayama, Marie Yasuda, Kazutoshi Miyashita, Hirobumi Tokuyama, Shu Wakino and Hiroshi Itoh : Home-Based Exercise Program Ameliorates Renal Function Decline in Patients With CKD Stage 4., Kidney International Reports, Vol.7, No.4, 899-903, 2022.
Kiyotaka Uchiyama, Keika Adachi, Kaori Muraoka, Takashin Nakayama, Takuma Oshida, Marie Yasuda, Akihito Hishikawa, Hitoshi Minakuchi, Kazutoshi Miyashita, Hirobumi Tokuyama, Shu Wakino and Hiroshi Itoh : Home-based aerobic exercise and resistance training for severe chronic kidney disease: a randomized controlled trial., Journal of Cachexia, Sarcopenia and Muscle, Vol.12, No.6, 1789-1802, 2021.
(要約)
Our 6 month home-based exercise programme improved aerobic capacity and HRQOL in patients with Stage 4 CKD, with possible beneficial effects on kidney function and CKD-related parameters.
(キーワード)
Aged / Exercise / Exercise Therapy / Humans / Male / Quality of Life / Renal Insufficiency, Chronic / Resistance Training
Keika Adachi, Hirobumi Tokuyama, Yoichi Oshima, Tomoaki Itoh, Akinori Hashiguchi, Hiroyuki Yamakawa, Tadayasu Togawa, Hitoshi Sakuraba, Shu Wakino and Hiroshi Itoh : Fabry disease associated with multiple myeloma: a case report., CEN Case Reports, Vol.11, No.1, 146-153, 2021.
(要約)
Fabry disease (FD) is an X-linked genetic lysosomal disorder caused by alpha-galactosidase A (GLA) deficiency. Multiple myeloma (MM) predominately affects older adults, which ranks as the second commonest hematological malignancy. Their overlap has rarely been reported. We present a case of the coexistence of FD and MM in a patient. We report the case of a 68-year-old woman who was referred to our hospital for the evaluation of thoracic spine tumor with bone destruction. On admission, her serum creatinine (Cr) level was elevated to 12.70 mg/dL from the baseline value of 0.91 mg/dL. Bone marrow aspiration revealed MM. Renal biopsy showed myeloma cast nephropathy, which was the primary cause of acute kidney injury. Renal pathology also showed podocyte swelling and tubule myeloid bodies in a mosaic pattern compatible with female FD. Consequently, the patient was diagnosed as FD based on the germ line mutation in GLA. The patient was treated with bortezomib and dexamethasone therapy, which significantly improved the renal function. This is the second case demonstrating a potential pathogenic relationship between FD and MM. Since FD is one of the few genetic diseases for which there are therapeutic agents with fewer side effects, diagnostic value of FD is high. If an MM patient has multiple organ abnormalities or any familial history, the physician should suspect FD.
Takashin Nakayama, Kiyotaka Uchiyama, Kohkichi Morimoto, Naoki Washida, Takahiro Kasai, Ran Nakamichi, Ei Kusahana, Shu Wakino and Hiroshi Itoh : Efficacy of dexmedetomidine on peritoneal dialysis catheter insertion., International Urology and Nephrology, Vol.54, No.1, 209-215, 2021.
(要約)
Of a total of 44 patients, 9 patients received DEX, and 35 did not. After propensity score matching, each group consisted of 8 patients. Peak NRS was significantly lower (P = 0.003) in the DEX group compared with the non-DEX group. Maximum mean BP during the operation was also significantly lower in the DEX group compared with the non-DEX group (P = 0.020), with no significant differences in minimum mean BP between the two groups (P = 0.831). The DEX group showed a trend of shortened operative time (P = 0.068). There were no significant differences in the occurrence of nausea (P = 1.000). Moreover, there was no clinically important adverse event associated with use of DEX.
Itaru Yasuda, Kazuhiro Hasegawa, Yusuke Sakamaki, Hirokazu Muraoka, Takahisa Kawaguchi, Ei Kusahana, Takashi Ono, Takeshi Kanda, Hirobumi Tokuyama, Shu Wakino and Hiroshi Itoh : Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic Nephropathy., Journal of the American Society of Nephrology, Vol.32, No.6, 1355-1370, 2021.
(要約)
salvage pathway, both of which indicate NMN legacy effects on DN.
Kaori Hayashi, Akinori Hashiguchi, Masako Ikemiyagi, Hirobumi Tokuyama, Shu Wakino and Hiroshi Itoh : Development of nephropathy in an adult patient after Fontan palliation for cyanotic congenital heart disease., CEN Case Reports, Vol.10, No.3, 354-358, 2021.
(要約)
Cyanotic congenital heart disease is occasionally associated with kidney dysfunction, which is known as cyanotic nephropathy or cyanotic glomerulopathy. The clinical presentation of cyanotic nephropathy includes proteinuria, decreased estimated glomerular filtration rate, hyperuricemia, thrombocytopenia, or polycythemia. Although advances in surgical procedures have improved the prognosis of cyanotic congenital heart diseases, adult cases of cyanotic nephropathy are still rare, and there are few reports of kidney biopsy in adults with cyanotic nephropathy. Here, we present the case of a 41-year-old patient with Fontan palliation who developed nephrotic range proteinuria and had a kidney biopsy, which showed glomerular hypertrophy with segmental glomerulosclerosis around vascular poles, suggesting adaptive focal segmental glomerulosclerosis. This case provides further understanding of kidney dysfunction due to cyanotic congenital heart disease and shows the need for attention in the management for prevention of progression to end-stage renal disease and in the selection of renal replacement therapy.
Takahisa Kawaguchi, Kazuhiro Hasegawa, Itaru Yasuda, Hirokazu Muraoka, Hiroyuki Umino, Hirobumi Tokuyama, Akinori Hashiguchi, Shu Wakino and Hiroshi Itoh : Diabetic condition induces hypertrophy and vacuolization in glomerular parietal epithelial cells., Scientific Reports, Vol.11, No.1, 2021.
(要約)
Diabetic nephropathy (DN) is accompanied by characteristic changes in the glomerulus, but little is known about the effect of diabetes on parietal epithelial cells (PECs). In this study, a descriptive analysis of PECs was undertaken in diabetic db/db mice and in diabetic patients. PEC hypertrophy was significantly more prominent in diabetic mice than in nondiabetic mice, and this was evident even at the early stage. Additionally, the number of vacuoles in PECs was markedly increased in diabetic mice, suggesting the presence of cellular injury in PECs in DN. Although rare, binuclear cells were observed in mice with early diabetes. In cultured PECs, a high glucose condition, compared with normal glucose condition, induced cellular hypertrophy and apoptosis. Flow cytometry showed that some PECs in the G0 phase reentered the cell cycle but got arrested in the S phase. Finally, in human diabetic subjects, hypertrophy and vacuolization were observed in the PECs. Our data showed that PECs undergo substantial changes in DN and may participate in rearrangement for differentiation into podocytes.
Itaru Yasuda, Hirobumi Tokuyama, Akinori Hashiguchi, Kazuhiro Hasegawa, Kiyotaka Uchiyama, Masaki Ryuzaki, Marie Yasuda, Ryuichi Mizuno, Shigeto Ishidoya, Shu Wakino and Hiroshi Itoh : Malignancy-associated membranous nephropathy with PLA2R double-positive for glomeruli and carcinoma., CEN Case Reports, Vol.10, No.2, 281-286, 2021.
(要約)
Phospholipase A2 receptor (PLA2R) is the most common primary target antigen of idiopathic membranous nephropathy (MN) although PLA2R antibodies are also reported to be present in malignancy-associated MN. However, a case of PLA2R-positive MN secondary to PLA2R-positive carcinoma has not been reported. A 26-year-old Japanese woman presented with general fatigue, fever, and nonproductive cough. Computed tomography demonstrated a left kidney mass with pathologic diagnosis of Xp11.2 translocation renal cell carcinoma (RCC). After the second time of administration with Sunitinib, the patients exhibited significant proteinuria and hypoalbuminemia. Renal biopsy revealed a diagnosis of diffuse MN secondary to RCC. Immunofluorescence staining showed granular patterns positive for immunoglobulin (Ig) G, IgA, and C3c. PLA2R and IgG1-3 were positive, while IgG4 was negative. For the treatment of severe nephrotic syndrome, we attempted steroid therapy without any clinical improvement. Open nephrectomy was performed and surprisingly, RCC was stained for PLA2R with polarity for the basal side. At outpatient follow-up, 4 months after the operation, urinary protein had still persisted, although serum albumin was slightly increased. We report a case of PLA2R-positive MN secondary to PLA2R-positive RCC.
Takashin Nakayama, Kiyotaka Uchiyama, Naoki Washida, Kohkichi Morimoto, Kaori Muraoka, Keika Adachi, Takahiro Kasai, Kazutoshi Miyashita, Shu Wakino and Hiroshi Itoh : Exercise Parameters Predict Technique Survival in Patients on Peritoneal Dialysis., Blood Purification, Vol.50, No.3, 380-389, 2020.
(要約)
The ISWT is an important predictor of technique survival for patients on PD. Monitoring and enhancing ISWT as a marker of aerobic capacity might improve PD-related outcomes.
(キーワード)
Aged / Aged, 80 and over / Exercise / Exercise Tolerance / Female / Follow-Up Studies / Hand Strength / Humans / Male / Middle Aged / Peritoneal Dialysis / Peritonitis / Prognosis / Survival Analysis / Survival Rate
Hitoshi Minakuchi, Shu Wakino, Hidenori Urai, Arata Kurokochi, Kazuhiro Hasegawa, Takeshi Kanda, Hirobumi Tokuyama and Hiroshi Itoh : The effect of aldosterone and aldosterone blockade on the progression of chronic kidney disease: a randomized placebo-controlled clinical trial., Scientific Reports, Vol.10, No.1, 2020.
(要約)
/year, p = 0.0047). In the final intervention study, in the eplerenone group, eGFR dropped at 6 months after the initiation of the study, and thereafter eGFR was maintained until the end of the study. At 24 months and 36 months, eGFR was significantly higher in the eplerenone group than in the placebo group. In conclusion, MRA can be an effective strategy in preventing CKD progression, especially in patients with high plasma aldosterone.
Shaw Watanabe, Kyoka Adachi, Shu Wakino, Takahisa Hisada and Jun Mochizuki : Dietary therapy with low protein genmai (brown rice) to improve the gut-kidney axis and reduce CKD progression., Asia Pacific Journal of Clinical Nutrition, Vol.31, No.3, 341-347, 2022.
(要約)
Low protein rice can be part of a nutritionally adequate dietary pattern in the prevention of chronic kidney disease. We developed a low protein fermented genmai (brown rice) LPFG) to improve chronic kidney disease (CKD) management. The principal functional features of brown rice are retained in LPFG, lessening the negative spiral of gut-kidney associative spiral attributable to uremic dysbiosis and a leaky gut. LPFG is characterized by (1) an energy value the same as white rice, (2) a protein content less than 0.2 g/ 100 g, (3) a potassium content almost zero, (4) phosphorus less than a quarter that of conventional rice, (5) the presence of dietary fiber, (6) having γ-oryzanol, and (7) antioxidant activity. Dietary therapy for CKD patients is challenged by the joint needs to provide enough energy and to restrict protein. Patients replaced staple foods with LPFG without side dish restriction. Preliminary study of intervention with 3 months of LPFG reduced constipation probably by increased Blautia wexlerae, Bifidobacteria, acetic acid, and a decrease in potentially harmful bacteria. Protein intake decreased from 60 to 50 g per day. Urinary protein excretion decreased from 510 to 300 mg per day, and β2-microglobulin from 926 to 250 μg/L. Adherence to the LPFG diet enabled improvement in glomerular and tubular function.
Hamamoto Riko, Hirokazu Ohminami, Shu Wakino and Yutaka Taketani : Effectiveness of protein restriction diet on chronic kidney disease: a systematic review, The International Workshop on Gut-kidney Axis and Chronic Kidney Disease, Tokyo, Mar. 2023.