Common Drug Pipelines for the Treatment of Diabetic Nephropathy and Hepatopathy: Can We Kill Two Birds with One Stone?

Sumida, Yoshio; Yoneda, Masashi; Toyoda, Hidenori; Yasuda, Satoshi; Tada, Toshifumi; Hayashi, Hideki; Nishigaki, Yoichi; Suzuki, Yusuke; Naiki, Taku; Morishita, Asahiro; Tobita, Hiroshi; Sato, Shuichi; Kawabe, Naoto; Fukunishi, Shinya; Ikegami, Tadashi; Kessoku, Takaomi; Ogawa, Yasuhiro; Honda, Yoshihiro; Nakahara, Takashi; Munekage, Kensuke; Ochi, Tsunehiro; Sawada, Koji; Takahashi, Atsushi; Arai, Taeang; Kogiso, Tomomi; Kimoto, Satoshi; Tomita, Kengo; Notsumata, Kazuo; Nonaka, Michihiro; Kawata, Kazuhito; Takami, Taro; Kumada, Takashi; Tomita, Eiichi; Okanoue, Takeshi; Nakajima, Atsushi

doi:10.3390/ijms21144939

Cited by 13 publications

(16 citation statements)

References 145 publications

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“…Among 96,373 participants over 6.9 years, 3844 incident congestive heart failure (CHF) events occurred. [82]. These results suggest that hepatic fibrosis (mild to severe) is associated with incident HF in the general population.…”

Section: Fib-4 Index and Risk Of Cardiovascular Diseasementioning

confidence: 67%

“…Among 96,373 participants over 6.9 years, 3844 incident congestive heart failure (CHF) events occurred. FIB-4 between 1.45 and 3.25 and FIB-4 > 3.25 were associated with incident CHF (HR [95% CI], 1.17 [1.07–1.27], and 1.65 [1.43–1.92], respectively) [ 82 ]. These results suggest that hepatic fibrosis (mild to severe) is associated with incident HF in the general population.…”

Section: Fib-4 Index and Risk Of Cardiovascular Diseasementioning

confidence: 99%

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FIB-4 First in the Diagnostic Algorithm of Metabolic-Dysfunction-Associated Fatty Liver Disease in the Era of the Global Metabodemic

Sumida

Yoneda

Tokushige

et al. 2021

Life

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The prevalence of obesity or metabolic syndrome is increasing worldwide (globally metabodemic). Approximately 25% of the adult general population is suffering from nonalcoholic fatty liver disease (NAFLD), which has become a serious health problem. In 2020, global experts suggested that the nomenclature of NAFLD should be updated to metabolic-dysfunction-associated fatty liver disease (MAFLD). Hepatic fibrosis is the most significant determinant of all cause- and liver -related mortality in MAFLD. The non-invasive test (NIT) is urgently required to evaluate hepatic fibrosis in MAFLD. The fibrosis-4 (FIB-4) index is the first triaging tool for excluding advanced fibrosis because of its accuracy, simplicity, and cheapness, especially for general physicians or endocrinologists, although the FIB-4 index has several drawbacks. Accumulating evidence has suggested that vibration-controlled transient elastography (VCTE) and the enhanced liver fibrosis (ELF) test may become useful as the second step after triaging by the FIB-4 index. The leading cause of mortality in MAFLD is cardiovascular disease (CVD), extrahepatic malignancy, and liver-related diseases. MAFLD often complicates chronic kidney disease (CKD), resulting in increased simultaneous liver kidney transplantation. The FIB-4 index could be a predictor of not only liver-related mortality and incident hepatocellular carcinoma, but also prevalent and incident CKD, CVD, and extrahepatic malignancy. Although NITs as milestones for evaluating treatment efficacy have never been established, the FIB-4 index is expected to reflect histological hepatic fibrosis after treatment in several longitudinal studies. We here review the role of the FIB-4 index in the management of MAFLD.

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Section: Fib-4 Index and Risk Of Cardiovascular Diseasementioning

confidence: 67%

Section: Fib-4 Index and Risk Of Cardiovascular Diseasementioning

confidence: 99%

FIB-4 First in the Diagnostic Algorithm of Metabolic-Dysfunction-Associated Fatty Liver Disease in the Era of the Global Metabodemic

Sumida

Yoneda

Tokushige

et al. 2021

Life

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“…As of 2015, about 415 million people in the world were suffering from diabetes, and by 2040 this number is expected to increase to 642 million [19]. Diabetic nephropathy is one of the most common complications of diabetes at present [20]. The end-stage renal disease caused by diabetic nephropathy has a very high morbidity and mortality rate worldwide.…”

Section: Discussionmentioning

confidence: 99%

Maslinic Acid Activates Renal Ampk/sirt1 Signaling Pathway to Protect Against Diabetic Nephropathy in Mice

Gao

Wu²

2021

Preprint

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BackgroundDiabetic nephropathy has been a devastating complication. Clinically, there is an urgent need for nephroprotective agents to delay the onset of diabetic nephropathy and ameliorate its symptoms. Maslinic acid is a pentacyclic triterpene acid with protective effect on multiple organs from oxidative stress and inflammation. However, the therapeutic effect of maslinic acid on diabetic nephropathy remains unclear.MethodsC57BL/6J male mice administrated with 50 mg/kg of Streptozocin (STZ) daily were used to establish diabetic mouse model (blood glucose levels > 300 mg/dL). Urinary levels of albumin, total proteins, and creatinine were analyzed by an automatic analyzer. H&E staining was used to evaluate renal damage. qRT-PCR and ELISA assay were performed to investigate the inflammation and oxidative stress of renal tissues. Western-blotting assay was used to demonstrate the activation of AMPK signaling.ResultsMaslinic acid treatment alleviated the loss of body weight and blood glucose in diabetic mice. The renal structure and function were protected by maslinic acid in diabetic mice. 20 mg/kg maslinic acid treatment for 8 weeks alleviated the oxidative stress and inflammation in the kidney of diabetic rats dramatically. Maslinic acid treatment activated renal AMPK/SIRT1 signaling.ConclusionMaslinic acid ameliorated diabetic nephropathy via activating AMPK/SIRT1 signaling pathway.

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“…Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis [68]. A variety of common drug pipelines exists for NASH and CKD [69,70]. In a cross sectional study based on 755 patients with US-based diagnosed NAFLD, high FIB-4 index (> 1.10) is associated with an increased risk of prevalent CKD.…”

Section: Fib-4 Index and Risk Of Chronic Kidney Diseasementioning

confidence: 99%

FIB-4 First in Diagnostic Algorithm of MAFLD at the Era of “Global Metabodemic “

Sumida¹,

Yoneda²,

Tokushige³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

The prevalence of obesity or metabolic syndrome is increasing worldwide (“Globally metabodemic”). Approximately 25% of adult general population is suffering from nonalcoholic fatty liver disease (NAFLD) which has become serious health problem. Hepatic fibrosis is the most significant determinant of all cause and liver -related mortality in NAFLD. Noninvasive test (NIT) should be urgently required to evaluate hepatic fibrosis in NAFLD. Fibrosis-4 (FIB-4) index is the 1st triaging tool for excluding advanced fibrosis because of its accuracy, simplicity, and cheapness especially for general physicians or endocrinologists, although FIB-4 index has several drawbacks. Accumulating evidence has suggested that vibration controlled transient elastography (VCTE) and the enhanced liver fibrosis (ELF) test may become useful as the 2nd step after triaging by FIB-4 index. The leading cause of mortality in NAFLD is cardiovascular disease (CVD), extrahepatic malignancy, and liver-related diseases. NAFLD often complicates chronic kidney disease (CKD), resulting in increased simultaneous liver kidney transplantation (SLKT). FIB-4 index could be a predictor of not only liver-related mortality and incident hepatocullar carcinoma (HCC) but also prevalent and incident CKD, CVD, and extrahepatic malignancy. Although NITs as milestones for evaluating treatment efficacy have never been established, FIB- 4 index is expected to reflect histological hepatic fibrosis after treatment in several longitudinal studies. We here review the role of FIB-4 index as 1st step NIT in management of NAFLD.

show abstract

Common Drug Pipelines for the Treatment of Diabetic Nephropathy and Hepatopathy: Can We Kill Two Birds with One Stone?

Cited by 13 publications

References 145 publications

FIB-4 First in the Diagnostic Algorithm of Metabolic-Dysfunction-Associated Fatty Liver Disease in the Era of the Global Metabodemic

FIB-4 First in the Diagnostic Algorithm of Metabolic-Dysfunction-Associated Fatty Liver Disease in the Era of the Global Metabodemic

Maslinic Acid Activates Renal Ampk/sirt1 Signaling Pathway to Protect Against Diabetic Nephropathy in Mice

FIB-4 First in Diagnostic Algorithm of MAFLD at the Era of “Global Metabodemic “

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