記述言語：英語   掲載種別：研究論文（学術雑誌）  

MicroRNAs (miRNAs) are sequence-specific inhibitors of post-transcriptional gene expression. However, the physiological functions of these non-coding RNAs in renal interstitial mesenchymal cells remain unclear. To conclusively evaluate the role of miRNAs, we generated conditional knockout (cKO) mice with platelet-derived growth factor receptor-β (PDGFR-β)-specific inactivation of the key miRNA pathway gene Dicer. The cKO mice were subjected to unilateral ureteral ligation, and renal interstitial fibrosis was quantitatively evaluated using real-time polymerase chain reaction and immunofluorescence staining. Compared with control mice, cKO mice had exacerbated interstitial fibrosis exhibited by immunofluorescence staining and mRNA expression of PDGFR-β. A microarray analysis showed decreased expressions of miR-9-5p, miR-344g-3p, and miR-7074-3p in cKO mice compared with those in control mice, suggesting an association with the increased expression of PDGFR-β. An analysis of the signaling pathways showed that the major transcriptional changes in cKO mice were related to smooth muscle cell differentiation, regulation of DNA metabolic processes and the actin cytoskeleton, positive regulation of fibroblast proliferation and Ras protein signal transduction, and focal adhesion-PI3K/Akt/mTOR signaling pathways. Depletion of Dicer in mesenchymal cells may downregulate the signaling pathway related to miR-9-5p, miR-344g-3p, and miR-7074-3p, which can lead to the progression of chronic kidney disease. These findings highlight the possibility for future diagnostic or therapeutic developments for renal fibrosis using miR-9-5p, miR-344g-3p, and miR-7074-3p.

DOI： 10.1038/s41598-024-61560-y

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Membranous nephropathy (MN) is a common cause of nephrotic syndrome in middle-aged and older adults. MN etiology is mainly primary or idiopathic; however, it may also be secondary to infections, drugs, neoplasms, and autoimmune diseases. We present the case of a 52-year-old Japanese man with coexisting nephrotic MN and immune thrombocytopenic purpura (ITP). Renal biopsy revealed glomerular basement membrane thickening with immunoglobulin (Ig) G and complement component 3 deposition. Glomerular IgG subclass analysis revealed predominant IgG4 deposition with weak IgG1 and IgG2 deposition. IgG3 and phospholipase A2 receptor deposits were negative. Upper endoscopy revealed no ulcers, but histological examination demonstrated Helicobacter pylori infection in the gastric mucosa with elevated IgG antibodies. After gastric Helicobacter pylori eradication, the nephrotic-range proteinuria and thrombocytopenia of the patient were markedly improved without initiation of immunosuppressive treatment. Therefore, clinicians should consider the possibility of Helicobacter pylori infection in patients with coexisting MN and ITP. Further studies are required to demonstrate the associated pathophysiological aspects.

DOI： 10.1007/s13730-023-00805-7

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Adequate blood pressure (BP) management poses a significant challenge in improving the prognosis of patients undergoing dialysis. We aimed to investigate the relationship between pre-dialysis systolic blood pressure (SBP) and underlying disease in Japanese patients undergoing dialysis, based on prefectural location, and assess the association between pre-dialysis SBP and cardiovascular disease (CVD) mortality rate. We extracted the basic information of 336,182 patients who were undergoing dialysis in 2021 from the Web-based Analysis of Dialysis Data Archives database. Data on average pre-dialysis SBP were analyzed according to sex, prefectural location, and diabetic status, and the CVD mortality rate for each prefecture was calculated. The mean pre-dialysis SBP of the patients (males, 66.3%; mean age, 69.7 ± 12.5 years) was 151.9 ± 24.7 mmHg. Overall, 133,037 patients had underlying diabetic kidney disease (DKD). The patients with DKD were younger, had a shorter dialysis duration, and a higher pre-dialysis SBP than those with non-DKD comorbidities. The prefecture-based mean pre-dialysis SBP values were all higher than 140 mmHg. At the prefectural level, CVD mortality rate was positively correlated with pre-dialysis SBP (r = 0.3127, p = 0.0324) and diastolic blood pressure (r = 0.3378, p = 0.0202) among female patients. At the prefectural level, pre-dialysis SBP is >140 mmHg in Japanese patients undergoing dialysis, especially in those with DKD. The positive association between pre-dialysis SBP and CVD mortality rate suggests that optimal BP management at the prefectural level may reduce CVD mortality rates. At the prefectural level, pre-dialysis SBP is higher than 140 mmHg in Japanese patients undergoing dialysis, especially higher in those with DKD.

DOI： 10.1038/s41440-023-01415-7

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The prevalence of hypertension is high among patients undergoing dialysis. We extracted data of patients undergoing dialysis between 2012 and 2020 with recorded pre-dialysis systolic blood pressure (SBP) using a web-based national database in Japan. Following the 2019 Japanese Society of Hypertension guidelines, we classified SBP and assessed its trends over time based on sex, age, diabetes status, and the anti-hypertensive medication use. Using the 2020 database, we examined 336,759 Japanese patients undergoing dialysis (114,249 female; 222,510 male). The mean age was 69.4 ± 12.5 years, and the mean SBP was 152.3 ± 24.7 mm Hg. The prevalence rate of pre-dialysis hypertension was 70.2%, with 32.5%, 24.5%, and 13.2% of patients having grade I, grade II, and grade III hypertension, respectively. From 2014 to 2020, prevalence rate of pre-dialysis hypertension and absolute values of pre-dialysis SBP were higher in dialysis patients with diabetes than in those without diabetes across all age groups and sexes. Younger patients with diabetes or those on anti-hypertensive medication exhibited an SBP of approximately 160 mm Hg. Cerebrovascular death in patients with diabetes was associated with a higher rate of pre-dialysis hypertension than that in those without diabetes, and there was a significant difference in the prevalence of grade III hypertension between the two groups. In conclusion, the mean pre-dialysis SBP among patients undergoing dialysis remained high, and younger patients with diabetes or those receiving anti-hypertensive medications had poor blood pressure control. Optimal blood pressure management may be necessary to reduce the risk of cardiovascular mortality.

DOI： 10.1111/jch.14736

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

We describe the cases of 47- and 45-year-old sisters who were diagnosed with Fabry disease by genomic analysis. Although the only abnormal finding was the presence of mulberry cells in their urinary sediment, the renal pathological scores, which were evaluated by light and electron microscopy, were unexpectedly very high due to severe accumulation of globotriaosylceramide in the glomerular podocytes and tubular epithelial cells. Nephrologists and laboratory technicians should recognize the importance of screening for mulberry cells during urinalysis as this is a simple, inexpensive, and non-invasive method for early diagnosis, leading to early treatment of Fabry disease.

DOI： 10.1016/j.ymgmr.2022.100874

PubMed

researchmap