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Article ; Online: Podocyte Ercc1 is indispensable for glomerular integrity.

Hama, Eriko Yoshida / Nakamichi, Ran / Hishikawa, Akihito / Kihara, Miho / Abe, Takaya / Yoshimoto, Norifumi / Nishimura, Erina Sugita / Itoh, Hiroshi / Hayashi, Kaori

Biochemical and biophysical research communications

2024 Volume 704, Page(s) 149713

Abstract: As life expectancy continues to increase, age-related kidney diseases are becoming more prevalent. Chronic kidney disease (CKD) is not only a consequence of aging but also a potential accelerator of aging process. Here we report the pivotal role of ... ...

Abstract	As life expectancy continues to increase, age-related kidney diseases are becoming more prevalent. Chronic kidney disease (CKD) is not only a consequence of aging but also a potential accelerator of aging process. Here we report the pivotal role of podocyte ERCC1, a DNA repair factor, in maintaining glomerular integrity and a potential effect on multiple organs. Podocyte-specific ERCC1-knockout mice developed severe proteinuria, glomerulosclerosis, and renal failure, accompanied by a significant increase in glomerular DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). ERCC1 gene transfer experiment in the knockout mice attenuated proteinuria and glomerulosclerosis with reduced DNA damage. Notably, CD44
MeSH term(s)	Humans ; Mice ; Animals ; Podocytes/metabolism ; Kidney Glomerulus/metabolism ; Kidney Diseases/metabolism ; Mice, Knockout ; Proteinuria/genetics ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Endonucleases/genetics ; Endonucleases/metabolism
Chemical Substances	Ercc1 protein, mouse (EC 3.1.-) ; DNA-Binding Proteins ; Endonucleases (EC 3.1.-)
Language	English
Publishing date	2024-02-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2024.149713
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Article: A Case of New-Onset Systemic Lupus Erythematosus With Serositis in a Maintenance Hemodialysis Patient.

Kosugi, Shotaro / Yoshida, Tadashi / Yoshimoto, Norifumi / Itoh, Hiroshi / Oya, Mototsugu

Clinical medicine insights. Case reports

2021 Volume 14, Page(s) 11795476211056172

Abstract: A 61-year-old woman with a 4-year history of maintenance hemodialysis due to end-stage renal disease of unknown cause was admitted because of a recurrent fever and abdominal pain lasting for 3 months. She had rheumatoid arthritis as a complication and ... ...

Abstract	A 61-year-old woman with a 4-year history of maintenance hemodialysis due to end-stage renal disease of unknown cause was admitted because of a recurrent fever and abdominal pain lasting for 3 months. She had rheumatoid arthritis as a complication and had taken sulfasalazine for over 4 years. Laboratory data revealed thrombocytopenia, hypocomplementemia, a high C-reactive protein level, and positivity for antinuclear antibody and anti-double strand DNA antibody. Gallium scintigraphy showed pericarditis, pleuritis, and peritonitis. Nonscarring alopecia was also noted. She was diagnosed as having systemic lupus erythematosus (SLE). Drug-induced lupus elicited by sulfasalazine was ruled out because the symptoms did not improve even after the discontinuation of the drug upon admission. Oral prednisolone treatment markedly improved her symptoms and laboratory data. However, she later died of sepsis arising from proctitis on day 71 of admission. This report underscores the necessity of considering new-onset SLE in patients with unexplained fever and serositis, including pleuritis, peritonitis, or pericarditis, even if they are receiving maintenance dialysis.
Language	English
Publishing date	2021-10-27
Publishing country	United States
Document type	Case Reports
ZDB-ID	2580498-4
ISSN	1179-5476
ISSN	1179-5476
DOI	10.1177/11795476211056172
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Article ; Online: Comparison of the effects of angiotensin receptor-neprilysin inhibitors and thiazide diuretic/renin-angiotensin system inhibitor combination therapy in hypertensive patients: a retrospective cohort study.

Mitsuno, Ryunosuke / Uchiyama, Kiyotaka / Nakayama, Takashin / Takahashi, Rina / Yoshimoto, Norifumi / Yamaguchi, Shintaro / Washida, Naoki / Kanda, Takeshi / Hayashi, Kaori / Itoh, Hiroshi

Journal of human hypertension

2023 Volume 37, Issue 12, Page(s) 1049–1055

Abstract: Angiotensin receptor-neprilysin inhibitors (ARNIs) have been approved as antihypertensive agents in Japan, and thiazide diuretics (TZDs) are widely used concomitantly with renin-angiotensin system inhibitors (RASIs) for hypertension. This retrospective ... ...

Abstract	Angiotensin receptor-neprilysin inhibitors (ARNIs) have been approved as antihypertensive agents in Japan, and thiazide diuretics (TZDs) are widely used concomitantly with renin-angiotensin system inhibitors (RASIs) for hypertension. This retrospective study included patients with hypertension who switched from RASI to ARNI therapy (ARNI group) and those who were prescribed TZDs with RASIs (TZD/RASI group). Drug-related changes in the estimated glomerular filtration rate (eGFR), blood pressure (BP), body weight (BW), serum electrolytes, uric acid (UA), and triglyceride levels were compared between the two groups. Overall, 70 participants (31 and 39 in the ARNI and TZD/RASI groups, respectively) were enrolled and observed for a median of 2 months. According to linear mixed models, compared with the TZD/RASI group, the ARNI group exhibited a significant change in mean eGFR of 3.71 mL/min/1.73 m
MeSH term(s)	Humans ; Angiotensin Receptor Antagonists/adverse effects ; Antihypertensive Agents/adverse effects ; Heart Failure/drug therapy ; Hypertension/diagnosis ; Hypertension/drug therapy ; Neprilysin/pharmacology ; Neprilysin/therapeutic use ; Receptors, Angiotensin/therapeutic use ; Renin-Angiotensin System ; Retrospective Studies ; Sodium Chloride Symporter Inhibitors/therapeutic use ; Triglycerides
Chemical Substances	Angiotensin Receptor Antagonists ; Antihypertensive Agents ; Neprilysin (EC 3.4.24.11) ; Receptors, Angiotensin ; Sodium Chloride Symporter Inhibitors ; Triglycerides
Language	English
Publishing date	2023-07-24
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	639472-3
ISSN	1476-5527 ; 0950-9240
ISSN (online)	1476-5527
ISSN	0950-9240
DOI	10.1038/s41371-023-00851-9
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Zs.A 2380: Show issues

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Article ; Online: Hemodialysis treatment of vancomycin-induced drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome in a patient undergoing peritoneal dialysis.

Mitsuno, Ryunosuke / Nakayama, Takashin / Uchiyama, Kiyotaka / Yoshimoto, Norifumi / Kusahana, Ei / Morimoto, Kohkichi / Yoshino, Jun / Yoshida, Tadashi / Kanda, Takeshi / Yamaguchi, Shintaro / Hayashi, Kaori

CEN case reports

2024

Abstract: Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a severe drug-induced hypersensitivity reaction with 10% mortality. To date, there is insufficient evidence regarding the ... ...

Abstract	Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a severe drug-induced hypersensitivity reaction with 10% mortality. To date, there is insufficient evidence regarding the association between DRESS/DIHS and serum levels of vancomycin (VCM). Here, we report the case of a 46-year-old woman undergoing peritoneal dialysis who developed VCM-induced DRESS/DIHS. She was hospitalized for peritonitis with abdominal pain and treated with VCM. On day 10 of hospitalization, her abdominal symptoms improved; however, fever, skin rash, lymphadenopathy, eosinophilia, atypical lymphocytes, and liver and renal dysfunction developed. Based on the clinical course and laboratory findings, we diagnosed the patient with DRESS/DIHS due to VCM. Since her serum VCM concentration was high at 39.8 μg/mL, hemodialysis (HD) was performed to remove VCM, which caused her symptoms to improve. However, serum levels of VCM rebounded and the same symptoms recurred. Therefore, we re-performed HD; no further relapse occurred. This clinical course showed that increased serum VCM levels were associated with DRESS/DIHS onset and severity, suggesting that it is a blood level-dependent disease and that removal of VCM by HD is a potential therapeutic option.
Language	English
Publishing date	2024-02-10
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2660492-9
ISSN	2192-4449 ; 2192-4449
ISSN (online)	2192-4449
ISSN	2192-4449
DOI	10.1007/s13730-023-00847-x
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Article ; Online: Vaccination Against Receptor for Advanced Glycation End Products Attenuates the Progression of Diabetic Kidney Disease.

Azegami, Tatsuhiko / Nakayama, Takashin / Hayashi, Kaori / Hishikawa, Akihito / Yoshimoto, Norifumi / Nakamichi, Ran / Itoh, Hiroshi

Diabetes

2021 Volume 70, Issue 9, Page(s) 2147–2158

Abstract: Effective treatment of diabetic kidney disease (DKD) remains a large unmet medical need. Within the disease's complicated pathogenic mechanism, activation of the advanced glycation end products (AGEs)-receptor for AGE (RAGE) axis plays a pivotal role in ... ...

Abstract	Effective treatment of diabetic kidney disease (DKD) remains a large unmet medical need. Within the disease's complicated pathogenic mechanism, activation of the advanced glycation end products (AGEs)-receptor for AGE (RAGE) axis plays a pivotal role in the development and progression of DKD. To provide a new therapeutic strategy against DKD progression, we developed a vaccine against RAGE. Three rounds of immunization of mice with the RAGE vaccine successfully induced antigen-specific serum IgG antibody titers and elevated antibody titers were sustained for at least 38 weeks. In addition, RAGE vaccination significantly attenuated the increase in urinary albumin excretion in streptozotocin-induced diabetic mice (type 1 diabetes model) and leptin-receptor-deficient db/db mice (type 2 diabetes model). In microscopic analyses, RAGE vaccination suppressed glomerular hypertrophy and mesangial expansion in both diabetic models and significantly reduced glomerular basement membrane thickness in streptozotocin-induced diabetic mice. Results of an in vitro study indicated that the serum IgG antibody elicited by RAGE vaccination suppressed the expression of AGE-induced vascular cell adhesion molecule 1 and intracellular adhesion molecule 1 in endothelial cells. Thus, our newly developed RAGE vaccine attenuated the progression of DKD in mice and is a promising potential therapeutic strategy for patients with DKD.
MeSH term(s)	Animals ; Diabetes Mellitus, Experimental/metabolism ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/prevention & control ; Disease Progression ; Male ; Mice ; Receptor for Advanced Glycation End Products/immunology ; Receptor for Advanced Glycation End Products/metabolism ; Vaccination
Chemical Substances	Receptor for Advanced Glycation End Products
Language	English
Publishing date	2021-06-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db20-1257
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Article ; Online: Vaccination against connective tissue growth factor attenuates the development of renal fibrosis.

Nakayama, Takashin / Azegami, Tatsuhiko / Hayashi, Kaori / Hishikawa, Akihito / Yoshimoto, Norifumi / Nakamichi, Ran / Sugita, Erina / Itoh, Hiroshi

Scientific reports

2022 Volume 12, Issue 1, Page(s) 10933

Abstract: There is a critical need for efficient treatment of chronic kidney disease (CKD). Renal fibrosis is a final common pathway to end-stage renal disease independent of the underlying etiology, and connective tissue growth factor (CTGF) is a well-recognized ... ...

Abstract	There is a critical need for efficient treatment of chronic kidney disease (CKD). Renal fibrosis is a final common pathway to end-stage renal disease independent of the underlying etiology, and connective tissue growth factor (CTGF) is a well-recognized profibrotic factor in fibrosis of various organ systems. Here, we developed a novel peptide vaccine against CTGF to attenuate the development of renal fibrosis. Three inoculations with this CTGF vaccine at 2-week intervals elicited antibodies specifically binding to human full-length CTGF, and the antigen-specific serum IgG antibody titers were maintained for > 30 weeks. The efficacy of the CTGF vaccine on renal fibrosis was evaluated in adenine-induced CKD and unilateral ureteral obstruction (UUO) murine models. In adenine-induced CKD model, immunization with the CTGF vaccine attenuated renal interstitial fibrosis. Vaccinated mice showed low levels of serum creatinine and urea nitrogen and low urine albumin-creatinine ratio compared with vehicle-treated mice. In UUO model, the CTGF vaccination also suppressed the onset of renal fibrosis. In an in vitro study, CTGF vaccine-elicited IgG antibodies efficiently suppressed CTGF-induced- and transforming growth factor-β-induced α-smooth muscle actin expression in kidney fibroblasts. These results demonstrate that the CTGF vaccine is a promising strategy to attenuate the development of renal fibrosis.
MeSH term(s)	Adenine/metabolism ; Animals ; Connective Tissue Growth Factor/metabolism ; Fibrosis ; Kidney/metabolism ; Kidney Diseases/metabolism ; Mice ; Renal Insufficiency, Chronic/complications ; Ureteral Obstruction/pathology ; Vaccination/adverse effects
Chemical Substances	Connective Tissue Growth Factor (139568-91-5) ; Adenine (JAC85A2161)
Language	English
Publishing date	2022-06-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-15118-5
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Article ; Online: Combining hemodialysis with peritoneal dialysis improves cognitive function: a three-case report.

Maruki, Tomomi / Nakayama, Takashin / Morimoto, Kohkichi / Uchiyama, Kiyotaka / Washida, Naoki / Mitsuno, Ryunosuke / Tonomura, Shun / Hama, Eriko Yoshida / Kusahana, Ei / Yoshimoto, Norifumi / Hishikawa, Akihito / Hagiwara, Aika / Azegami, Tatsuhiko / Yoshino, Jun / Monkawa, Toshiaki / Yoshida, Tadashi / Yamaguchi, Shintaro / Hayashi, Kaori

CEN case reports

2024

Abstract: Chronic kidney disease (CKD) is associated with multiple complications, with recent scholarly attention underscoring cognitive impairment as a salient manifestation. Considering societal aging, preserving cognitive function has emerged as an urgent ... ...

Abstract	Chronic kidney disease (CKD) is associated with multiple complications, with recent scholarly attention underscoring cognitive impairment as a salient manifestation. Considering societal aging, preserving cognitive function has emerged as an urgent medical concern. Prolonged dialysis, encompassing hemodialysis (HD) and peritoneal dialysis (PD), has been associated with a decline in cognitive function. Here, we present the cases of three patients undergoing PD who exhibited a noticeable improvement in cognitive function upon the initiation of HD. One patient had exhibited mild cognitive decline, whereas the remaining two presented more severe impairment. Apart from a mild tendency for fluid retention, none of the three patients exhibited abnormalities in physical or imaging examinations. Evaluation using the Japanese version of the Montreal Cognitive Assessment (MoCA-J) yielded decreased scores across multiple domains, notably in executive and attention functions. However, after HD initiation, all patients demonstrated a marked enhancement in multiple MoCA-J parameters, accompanied by a significant improvement in subjective symptoms. Moreover, improvements in anemia and hypoalbuminemia were observed in all three patients, whereas consistent trends in other parameters were absent. These clinical observations suggest that the integration of HD into the therapeutic regimen of patients undergoing PD may enhance cognitive function, highlighting the contributory roles of hemoglobin and albumin in CKD-associated cognitive impairment.
Language	English
Publishing date	2024-04-26
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2660492-9
ISSN	2192-4449 ; 2192-4449
ISSN (online)	2192-4449
ISSN	2192-4449
DOI	10.1007/s13730-024-00880-4
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Article ; Online: DNA damage and expression of DNA methylation modulators in urine-derived cells of patients with hypertension and diabetes.

Hishikawa, Akihito / Hayashi, Kaori / Yoshimoto, Norifumi / Nakamichi, Ran / Homma, Koichiro / Itoh, Hiroshi

Scientific reports

2020 Volume 10, Issue 1, Page(s) 3377

Abstract: Diabetes and hypertension have become the primary causes of chronic kidney disease worldwide. However, there are no established markers for early diagnosis or predicting renal prognosis. Here, we investigated the expression profiles of DNA repair and DNA ...

Abstract	Diabetes and hypertension have become the primary causes of chronic kidney disease worldwide. However, there are no established markers for early diagnosis or predicting renal prognosis. Here, we investigated the expression profiles of DNA repair and DNA methylation factors in human urine-derived cells as a possible diagnostic or renal prognosis-predicting marker. A total of 75 subjects, aged 63.3 ± 1.9 years old, were included in this study. DNA and RNA were extracted from 50 mL of urine samples. We evaluated DNA double-strand breaks (DSBs) by the quantitative long distance-PCR method and performed real-time RT-PCR analysis to analyze the expression of renal cell-specific markers, DNA DSB repair factor KAT5, DNA methyltransferases DNMTs, and demethylation enzymes TETs. In patients with hypertension and diabetes, DNA DSBs of the nephrin gene increased with decreased urine KAT5/nephrin expression, consistent with our previous study (Cell Rep 2019). In patients with hypertension, DNA DSBs of the AQP1 gene were increased with elevated urine DNMTs/AQP1 and TETs/AQP1 expression. Moreover, urine DNMTs/AQP1 expression was significantly correlated with the annual eGFR decline rate after adjustment for age, baseline eGFR, the presence of diabetes and the amount of albuminuria, suggesting a possible role as a renal prognosis predictor.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Aquaporin 1/genetics ; Aquaporin 1/metabolism ; DNA (Cytosine-5-)-Methyltransferases/genetics ; DNA (Cytosine-5-)-Methyltransferases/metabolism ; DNA Breaks, Double-Stranded ; DNA Methylation ; Diabetes Mellitus/pathology ; Female ; Glomerular Filtration Rate ; Humans ; Hypertension/pathology ; Logistic Models ; Lysine Acetyltransferase 5/genetics ; Lysine Acetyltransferase 5/metabolism ; Male ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Middle Aged ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins/metabolism ; Urine/cytology
Chemical Substances	AQP1 protein, human ; Membrane Proteins ; Proto-Oncogene Proteins ; nephrin ; Aquaporin 1 (146410-94-8) ; DNA (Cytosine-5-)-Methyltransferases (EC 2.1.1.37) ; KAT5 protein, human (EC 2.3.1.48) ; Lysine Acetyltransferase 5 (EC 2.3.1.48)
Language	English
Publishing date	2020-02-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-60420-9
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Article ; Online: DNA-damaged podocyte-CD8 T cell crosstalk exacerbates kidney injury by altering DNA methylation.

Nakamichi, Ran / Hishikawa, Akihito / Chikuma, Shunsuke / Yoshimura, Akihiko / Sasaki, Takashi / Hashiguchi, Akinori / Abe, Takaya / Tokuhara, Tomoko / Yoshimoto, Norifumi / Nishimura, Erina Sugita / Hama, Eriko Yoshida / Azegami, Tatsuhiko / Nakayama, Takashin / Hayashi, Kaori / Itoh, Hiroshi

Cell reports

2023 Volume 42, Issue 4, Page(s) 112302

Abstract: Recent epigenome-wide studies suggest an association between blood DNA methylation and kidney function. However, the pathological importance remains unclear. Here, we show that the homing endonuclease I-PpoI-induced DNA double-strand breaks in kidney ... ...

Abstract	Recent epigenome-wide studies suggest an association between blood DNA methylation and kidney function. However, the pathological importance remains unclear. Here, we show that the homing endonuclease I-PpoI-induced DNA double-strand breaks in kidney glomerular podocytes cause proteinuria, glomerulosclerosis, and tubulointerstitial fibrosis with DNA methylation changes in blood cells as well as in podocytes. Single-cell RNA-sequencing analysis reveals an increase in cytotoxic CD8
MeSH term(s)	Humans ; Podocytes/metabolism ; DNA Methylation/genetics ; CD8-Positive T-Lymphocytes/metabolism ; NK Cell Lectin-Like Receptor Subfamily K/metabolism ; Kidney/metabolism ; Proteinuria/genetics ; Proteinuria/metabolism ; Proteinuria/pathology ; Renal Insufficiency, Chronic/pathology ; DNA Damage ; DNA/metabolism
Chemical Substances	NK Cell Lectin-Like Receptor Subfamily K ; DNA (9007-49-2)
Language	English
Publishing date	2023-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112302
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Article ; Online: DNA-damaged podocyte-CD8 T cell crosstalk exacerbates kidney injury by altering DNA methylation.

Cell reports

2023 Volume 42, Issue 5, Page(s) 112427

Language	English
Publishing date	2023-04-19
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112427
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