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Original Article
- Basic research
- Reducing Oxidative Stress and Inflammation by Pyruvate Dehydrogenase Kinase 4 Inhibition Is Important in Prevention of Renal Ischemia-Reperfusion Injury in Diabetic Mice
- Ah Reum Khang, Dong Hun Kim, Min-Ji Kim, Chang Joo Oh, Jae-Han Jeon, Sung Hee Choi, In-Kyu Lee
- Diabetes Metab J. 2024;48(3):405-417. Published online February 1, 2024
- DOI: https://doi.org/10.4093/dmj.2023.0196
- 4,176 View
- 332 Download
- 2 Web of Science
- 2 Crossref
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Abstract
PDF
Supplementary Material
PubReader 
ePub - Background
Reactive oxygen species (ROS) and inflammation are reported to have a fundamental role in the pathogenesis of ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury. The present study investigated the role of pyruvate dehydrogenase kinase 4 (PDK4) in ROS production and inflammation following IR injury.
Methods
We used a streptozotocin-induced diabetic C57BL6/J mouse model, which was subjected to IR by clamping both renal pedicles. Cellular apoptosis and inflammatory markers were evaluated in NRK-52E cells and mouse primary tubular cells after hypoxia and reoxygenation using a hypoxia work station.
Results
Following IR injury in diabetic mice, the expression of PDK4, rather than the other PDK isoforms, was induced with a marked increase in pyruvate dehydrogenase E1α (PDHE1α) phosphorylation. This was accompanied by a pronounced ROS activation, as well as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) production. Notably, sodium dichloroacetate (DCA) attenuated renal IR injury-induced apoptosis which can be attributed to reducing PDK4 expression and PDHE1α phosphorylation levels. DCA or shPdk4 treatment reduced oxidative stress and decreased TNF-α, IL-6, IL-1β, and MCP-1 production after IR or hypoxia-reoxygenation injury.
Conclusion
PDK4 inhibition alleviated renal injury with decreased ROS production and inflammation, supporting a critical role for PDK4 in IR mediated damage. This result indicates another potential target for reno-protection during IR injury; accordingly, the role of PDK4 inhibition needs to be comprehensively elucidated in terms of mitochondrial function during renal IR injury. -
Citations
Citations to this article as recorded by
Review
- Others
- Risk Prediction and Management of Chronic Kidney Disease in People Living with Type 2 Diabetes Mellitus
- Ying-Guat Ooi, Tharsini Sarvanandan, Nicholas Ken Yoong Hee, Quan-Hziung Lim, Sharmila S. Paramasivam, Jeyakantha Ratnasingam, Shireene R. Vethakkan, Soo-Kun Lim, Lee-Ling Lim
- Diabetes Metab J. 2024;48(2):196-207. Published online January 26, 2024
- DOI: https://doi.org/10.4093/dmj.2023.0244
- 4,338 View
- 530 Download
-
Abstract
PDFSupplementary MaterialPubReader ePub
- People with type 2 diabetes mellitus have increased risk of chronic kidney disease and atherosclerotic cardiovascular disease. Improved care delivery and implementation of guideline-directed medical therapy have contributed to the declining incidence of atherosclerotic cardiovascular disease in high-income countries. By contrast, the global incidence of chronic kidney disease and associated mortality is either plateaued or increased, leading to escalating direct and indirect medical costs. Given limited resources, better risk stratification approaches to identify people at risk of rapid progression to end-stage kidney disease can reduce therapeutic inertia, facilitate timely interventions and identify the need for early nephrologist referral. Among people with chronic kidney disease G3a and beyond, the kidney failure risk equations (KFRE) have been externally validated and outperformed other risk prediction models. The KFRE can also guide the timing of preparation for kidney replacement therapy with improved healthcare resources planning and may prevent multiple complications and premature mortality among people with chronic kidney disease with and without type 2 diabetes mellitus. The present review summarizes the evidence of KFRE to date and call for future research to validate and evaluate its impact on cardiovascular and mortality outcomes, as well as healthcare resource utilization in multiethnic populations and different healthcare settings.
Original Article
- Drug/Regimen
- Abrupt Decline in Estimated Glomerular Filtration Rate after Initiating Sodium-Glucose Cotransporter 2 Inhibitors Predicts Clinical Outcomes: A Systematic Review and Meta-Analysis
- Min-Hsiang Chuang, Yu-Shuo Tang, Jui-Yi Chen, Heng-Chih Pan, Hung-Wei Liao, Wen-Kai Chu, Chung-Yi Cheng, Vin-Cent Wu, Michael Heung
- Diabetes Metab J. 2024;48(2):242-252. Published online January 26, 2024
- DOI: https://doi.org/10.4093/dmj.2023.0201
- 3,564 View
- 366 Download
-
Abstract
PDFSupplementary MaterialPubReader ePub
- Background
The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined.
Methods
We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis.
Results
We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group.
Conclusion
Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.
Review
- Complications
- Dyslipidemia in Patients with Chronic Kidney Disease: An Updated Overview
- Sang Heon Suh, Soo Wan Kim
- Diabetes Metab J. 2023;47(5):612-629. Published online July 24, 2023
- DOI: https://doi.org/10.4093/dmj.2023.0067
- 8,097 View
- 775 Download
- 12 Web of Science
- 12 Crossref
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Abstract
PDFPubReader ePub
- Dyslipidemia is a potentially modifiable cardiovascular risk factor. Whereas the recommendations for the treatment target of dyslipidemia in the general population are being more and more rigorous, the 2013 Kidney Disease: Improving Global Outcomes clinical practice guideline for lipid management in chronic kidney disease (CKD) presented a relatively conservative approach with respect to the indication of lipid lowering therapy and therapeutic monitoring among the patients with CKD. This may be largely attributed to the lack of high-quality evidence derived from CKD population, among whom the overall feature of dyslipidemia is considerably distinctive to that of general population. In this review article, we cover the characteristic features of dyslipidemia and impact of dyslipidemia on cardiovascular outcomes in patients with CKD. We also review the current evidence on lipid lowering therapy to modify the risk of cardiovascular events in this population. We finally discuss the association between dyslipidemia and CKD progression and the potential strategy to delay the progression of CKD in relation to lipid lowering therapy.
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Citations
Citations to this article as recorded by- Statin Therapy and Lipid Indices in Chronic Kidney Disease: A Systematic
Review and Meta-analysis of Randomized Control Trials
Jafar Karami, Bahman Razi, Danyal Imani, Saeed Aslani, Mahdi Pakjoo, Mahdieh Fasihi, Keyhan Mohammadi, Amirhossein Sahebkar
Current Pharmaceutical Design.2024; 30(5): 362. CrossRef - Lipoprotein glomerulopathy with markedly increased arterial stiffness successfully treated with a combination of fenofibrate and losartan: a case report
Junichiro Kato, Hideo Okonogi, Go Kanzaki, Haruki Katsumata, Yasuyuki Nakada, Makoto Sagasaki, Kazumasa Komine, Kenji Ito, Takao Saito, Akira Matsunaga, Koh Tokutou, Kazuho Honda, Nobuo Tsuboi, Takashi Yokoo
BMC Nephrology.2024;[Epub] CrossRef - Atherogenic index of plasma: a new indicator for assessing the short-term mortality of patients with acute decompensated heart failure
Meng Yu, Hongyi Yang, Maobin Kuang, Jiajun Qiu, Changhui Yu, Guobo Xie, Guotai Sheng, Yang Zou
Frontiers in Endocrinology.2024;[Epub] CrossRef - Association between lipid accumulation product index and chronic kidney disease: A systematic review and meta-analysis
Feixiang Wu, Chenmin Cui, Junping Wu, Yunqing Wang
Experimental and Therapeutic Medicine.2024;[Epub] CrossRef - Potential impact of sodium glucose co-transporter (SGLT2) inhibitors on cholesterol fractions in stage 3 chronic kidney disease
Rabab Mahmoud Ahmed, Nehal Kamal Rakha, Ahmed Yousry, Amin Roshdy Soliman
The Egyptian Journal of Internal Medicine.2024;[Epub] CrossRef - Pulmonary Hypertension in Hemodialysis Patients and Its Determinants: A Hospital Based Cross-Sectional Study
Qingfei Yu, Qin Zhang
International Journal of General Medicine.2024; Volume 17: 3919. CrossRef - Relationship Between Serum Uromodulin as a Marker of Kidney Damage and Metabolic Status in Patients with Chronic Kidney Disease of Non-Diabetic Etiology
Radmila Žeravica, Branislava Ilinčić, Dragan Burić, Ana Jakovljević, Veljko Crnobrnja, Dalibor Ilić, Marija Vukmirović Papuga
International Journal of Molecular Sciences.2024; 25(20): 11159. CrossRef - Dyslipidemia in Peritoneal Dialysis: Implications for Peritoneal Membrane Function and Patient Outcomes
Natalia Stepanova
Biomedicines.2024; 12(10): 2377. CrossRef - Causal associations between kidney function and aortic valve stenosis: a bidirectional Mendelian randomization analysis
Wanqian Pan, Le Zhou, Rui Han, Xiaojiao Du, Weixiang Chen, Tingbo Jiang
Renal Failure.2024;[Epub] CrossRef - U-shaped association between dietary niacin intake and chronic kidney disease among US elderly: a nationwide cross-sectional study
Zhouzhou Xie, Shansen Peng, Gejun Ou, Xiaoqi Zhou, Guihao Zhang, Huiming Jiang, Tianhui Zhang, Nanhui Chen
Frontiers in Endocrinology.2024;[Epub] CrossRef - Association between dried fruit intake and kidney function: research from univariate and multivariate Mendelian randomized studies
Yuhang Gao, Xinghai Yue, Wanchao Zhao, Fang Yuan
Frontiers in Nutrition.2024;[Epub] CrossRef - The Dual Burden: Exploring Cardiovascular Complications in Chronic Kidney Disease
Alfredo Caturano, Raffaele Galiero, Maria Rocco, Giuseppina Tagliaferri, Alessia Piacevole, Davide Nilo, Giovanni Di Lorenzo, Celestino Sardu, Vincenzo Russo, Erica Vetrano, Marcellino Monda, Raffaele Marfella, Luca Rinaldi, Ferdinando Carlo Sasso
Biomolecules.2024; 14(11): 1393. CrossRef
- Statin Therapy and Lipid Indices in Chronic Kidney Disease: A Systematic
Review and Meta-analysis of Randomized Control Trials
Brief Reports
- Complications
- Trends in the Incidence, Prevalence, and Mortality of End-Stage Kidney Disease in South Korea
- Min-Jeong Lee, Kyoung Hwa Ha, Dae Jung Kim, Inwhee Park
- Diabetes Metab J. 2020;44(6):933-937. Published online December 23, 2020
- DOI: https://doi.org/10.4093/dmj.2020.0156
- 7,043 View
- 263 Download
- 17 Web of Science
- 18 Crossref
-
Abstract
PDFSupplementary MaterialPubReader ePub
- Knowledge of the epidemiologic characteristics of end-stage kidney disease (ESKD) patients is essential. The trends in the prevalence, incidence, and mortality rates of ESKD were analyzed retrospectively using the Korean National Health Insurance ServiceNational Sample Cohort database between 2006 and 2015. From 2006 to 2015, the incidence of ESKD decreased from 28.6 to 24.0 per 100,000 people and showed a decreasing pattern with or without diabetes mellitus. However, the incidence of those aged ≥75 years increased, as did the mean age at the onset of ESKD. From 2007 to 2015, the prevalence of ESKD increased in all age groups, but particularly in those aged ≥75 years. The prevalence of ESKD differed by sex and diabetes mellitus status and this gap widened over time. Mortality rates in ESKD patients remained relatively constant throughout the study period. However, mortality rates in ESKD without diabetes decreased over the same period.
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Citations
Citations to this article as recorded by- Kidney Health Plan 2033 in Korea: bridging the gap between the present and the future
Do Hyoung Kim, Young Youl Hyun, Jin Joo Cha, Sua Lee, Hyun Kyung Lee, Jong Wook Choi, Su-Hyun Kim, Sang Youb Han, Cheol Whee Park, Eun Young Lee, Dae Ryong Cha, Sung Gyun Kim, Chun Soo Lim, Sun-Hee Park
Kidney Research and Clinical Practice.2024; 43(1): 8. CrossRef - Remnant cholesterol is an independent risk factor for the incidence of chronic kidney disease in newly-diagnosed type 2 diabetes: A nationwide population-based study
Soo Yeon Jang, Minwoong Kang, Eyun Song, Ahreum Jang, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo
Diabetes Research and Clinical Practice.2024; 210: 111639. CrossRef - Effects of Kt/Vurea on outcomes according to age in patients on maintenance hemodialysis
Junseok Jeon, Gui Ok Kim, Bo Yeon Kim, Eun Jung Son, Jun Young Do, Jung Eun Lee, Seok Hui Kang
Clinical Kidney Journal.2024;[Epub] CrossRef - 2023 Diabetic Kidney Disease Fact Sheet in Korea
Nam Hoon Kim, Mi-Hae Seo, Jin Hyung Jung, Kyung Do Han, Mi Kyung Kim, Nan Hee Kim
Diabetes & Metabolism Journal.2024; 48(3): 463. CrossRef - Clinical Validation of a Mobile-Based ACR (Urine Albumin-to-Creatinine Ratio) Test Kit: Comparative Analysis with Benchtop Devices
Jiwon RYU, Eung-Kyu PARK, JunHyuck JANG, Dong-Hoon LEE
Korean Journal of Health Promotion.2024; 24(3): 118. CrossRef - Kidney replacement therapy trends in end-stage kidney disease patients in South Korea during the COVID-19 pandemic
Ah-Young Kim, Min-Jeong Lee, Heejung Choi, Hankil Lee, Inwhee Park
The Korean Journal of Internal Medicine.2024; 39(6): 967. CrossRef - Waist circumference and end‐stage renal disease based on glycaemic status: National Health Insurance Service data 2009–2018
Yun Kyung Cho, Ji Hye Huh, Shinje Moon, Yoon Jung Kim, Yang‐Hyun Kim, Kyung‐do Han, Jun Goo Kang, Seong Jin Lee, Sung‐Hee Ihm
Journal of Cachexia, Sarcopenia and Muscle.2023; 14(1): 585. CrossRef - Usefulness of continuous glucose monitoring of blood glucose control in patients with diabetes undergoing hemodialysis: A pilot study
Sua Lee, Soyoung Lee, Kyeong Min Kim, Jong Ho Shin
Frontiers in Medicine.2023;[Epub] CrossRef - Association between N-Terminal Prohormone Brain Natriuretic Peptide and Decreased Skeletal Muscle Mass in a Healthy Adult Population: A Cross-Sectional Study
Tae Kyung Yoo, Marie Yung-Chen Wu, Moon Soo Kim, Mi-Yeon Lee, Yong-Taek Lee, Kyung Jae Yoon, Chul-Hyun Park
Endocrinology and Metabolism.2023; 38(2): 269. CrossRef - Age at Mortality in Patients with Type 2 Diabetes Who Underwent Kidney Transplantation: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018
Sun Ok Song, Eugene Han, Kang Ju Son, Bong-Soo Cha, Byung-Wan Lee
Journal of Clinical Medicine.2023; 12(9): 3160. CrossRef - Epigenome-wide association study of diabetic chronic kidney disease progression in the Korean population: the KNOW-CKD study
Hye Youn Sung, Sangjun Lee, Miyeun Han, Woo Ju An, Hyunjin Ryu, Eunjeong Kang, Yong Seek Park, Seung Eun Lee, Curie Ahn, Kook-Hwan Oh, Sue K. Park, Jung-Hyuck Ahn
Scientific Reports.2023;[Epub] CrossRef - Effects of Dapagliflozin in Asian Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF
Kieran F. Docherty, Inder S. Anand, Chern-En Chiang, Vijay K. Chopra, Akshay S. Desai, Masafumi Kitakaze, Subodh Verma, Pham N. Vinh, Silvio E. Inzucchi, Lars Køber, Mikhail N. Kosiborod, Felipe A. Martinez, Olof Bengtsson, Piotr Ponikowski, Marc S. Sabat
JACC: Asia.2022; 2(2): 139. CrossRef - Glomerular filtration rate as a kidney outcome of diabetic kidney disease: a focus on new antidiabetic drugs
Hyo Jin Kim, Sang Soo Kim, Sang Heon Song
The Korean Journal of Internal Medicine.2022; 37(3): 502. CrossRef - The risk of Parkinson's disease according to diabetic kidney disease status in a Korean population
Seung Eun Lee, Juhwan Yoo, Han Seok Choi, Kyungdo Han, Kyoung-Ah Kim
Parkinsonism & Related Disorders.2022; 100: 13. CrossRef - Renoprotective Mechanism of Sodium-Glucose Cotransporter 2 Inhibitors: Focusing on Renal Hemodynamics
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Diabetes & Metabolism Journal.2022; 46(4): 543. CrossRef - The Incidence and Risk Factors of Renal Insufficiency among Korean HIV infected Patients: The Korea HIV/AIDS Cohort Study
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Infection & Chemotherapy.2022; 54(3): 534. CrossRef - Sex difference in the association among nutrition, muscle mass, and strength in peritoneal dialysis patients
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Scientific Reports.2022;[Epub] CrossRef - Additive interaction of diabetes mellitus and chronic kidney disease in cancer patient mortality risk
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Scientific Reports.2022;[Epub] CrossRef
- Kidney Health Plan 2033 in Korea: bridging the gap between the present and the future
- Drug/Regimen
- Evogliptin, a Dipeptidyl Peptidase-4 Inhibitor, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice
- Mi-Jin Kim, Na-young Kim, Yun-A Jung, Seunghyeong Lee, Gwon-Soo Jung, Jung-Guk Kim, In-Kyu Lee, Sungwoo Lee, Yeon-Kyung Choi, Keun-Gyu Park
- Diabetes Metab J. 2020;44(1):186-192. Published online October 31, 2019
- DOI: https://doi.org/10.4093/dmj.2018.0271
- 6,575 View
- 116 Download
- 10 Web of Science
- 10 Crossref
-
Abstract
PDFSupplementary MaterialPubReader
Renal fibrosis is considered to be the final common outcome of chronic kidney disease. Dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated protective effects against diabetic kidney disease. However, the anti-fibrotic effect of evogliptin, a DPP-4 inhibitor, has not been studied. Here, we report the beneficial effects of evogliptin on unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Evogliptin attenuated UUO-induced renal atrophy and tubulointerstitial fibrosis. Immunohistochemistry and Western blotting demonstrated that evogliptin treatment inhibits pro-fibrotic gene expressions and extracellular matrix production.
In vitro findings showed that the beneficial effects of evogliptin on renal fibrosis are mediated by inhibition of the transforming growth factor-β/Smad3 signaling pathway. The present study demonstrates that evogliptin is protective against UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of kidney disease of non-diabetic origin.-
Citations
Citations to this article as recorded by- Targeting cluster of differentiation 26 / dipeptidyl peptidase 4 (CD26/DPP4) in organ fibrosis
Birte Ohm, Isabelle Moneke, Wolfgang Jungraithmayr
British Journal of Pharmacology.2023; 180(22): 2846. CrossRef - Linagliptin ameliorates pulmonary fibrosis in systemic sclerosis mouse model via inhibition of endothelial-to-mesenchymal transition
Biwei Pei, Na Zhang, Tingting Pang, Gengyun Sun
Molecular and Cellular Biochemistry.2022; 477(4): 995. CrossRef - Association Between DPP4 Inhibitor Use and the Incidence of Cirrhosis, ESRD, and Some Cancers in Patients With Diabetes
Yewon Na, Soo Wan Kim, Ie Byung Park, Soo Jung Choi, Seungyoon Nam, Jaehun Jung, Dae Ho Lee
The Journal of Clinical Endocrinology & Metabolism.2022; 107(11): 3022. CrossRef - Evogliptin Directly Inhibits Inflammatory and Fibrotic Signaling in Isolated Liver Cells
Hye-Young Seo, So-Hee Lee, Eugene Han, Jae Seok Hwang, Sol Han, Mi Kyung Kim, Byoung Kuk Jang
International Journal of Molecular Sciences.2022; 23(19): 11636. CrossRef - Optimization and validation of a fluorogenic dipeptidyl peptidase 4 enzymatic assay in human plasma
Hyunyee Yoon, Su Hee Cho, Yu Rim Seo, Kyung-Sang Yu, Sung Sup Park, Moon Jung Song
Analytical Biochemistry.2021; 612: 113952. CrossRef - Use of Anti-Diabetic Agents in Non-Diabetic Kidney Disease: From Bench to Bedside
Sungjin Chung, Gheun-Ho Kim
Life.2021; 11(5): 389. CrossRef - Targeting Dermal Fibroblast Subtypes in Antifibrotic Therapy: Surface Marker as a Cellular Identity or a Functional Entity?
Xin Huang, Yimin Khoong, Chengyao Han, Dai Su, Hao Ma, Shuchen Gu, Qingfeng Li, Tao Zan
Frontiers in Physiology.2021;[Epub] CrossRef - Efficacy and safety of evogliptin treatment in patients with type 2 diabetes: A multicentre, active‐controlled, randomized, double‐blind study with open‐label extension (the EVERGREEN study)
Gyuri Kim, Soo Lim, Hyuk‐Sang Kwon, Ie B. Park, Kyu J. Ahn, Cheol‐Young Park, Su K. Kwon, Hye S. Kim, Seok W. Park, Sin G. Kim, Min K. Moon, Eun S. Kim, Choon H. Chung, Kang S. Park, Mikyung Kim, Dong J. Chung, Chang B. Lee, Tae H. Kim, Moon‐Kyu Lee
Diabetes, Obesity and Metabolism.2020; 22(9): 1527. CrossRef Effect of Switching from Linagliptin to Teneligliptin Dipeptidyl Peptidase-4 Inhibitors in Older Patients with Type 2 Diabetes Mellitus
Eugene Han, Minyoung Lee, Yong-ho Lee, Hye Soon Kim, Byung-wan Lee, Bong-Soo Cha, Eun Seok Kang
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 4113. CrossRef- Efficacy and safety of novel dipeptidyl-peptidase-4 inhibitor evogliptin in the management of type 2 diabetes mellitus: A meta-analysis
Deep Dutta, Saptarshi Bhattacharya, Aishwarya Krishnamurthy, LokeshKumar Sharma, Meha Sharma
Indian Journal of Endocrinology and Metabolism.2020; 24(5): 434. CrossRef
- Targeting cluster of differentiation 26 / dipeptidyl peptidase 4 (CD26/DPP4) in organ fibrosis
Original Articles
- Basic Research
- Fibroblast Growth Factor 21 Attenuates Diabetes-Induced Renal Fibrosis by Negatively Regulating TGF-β-p53-Smad2/3-Mediated Epithelial-to-Mesenchymal Transition via Activation of AKT
- Sundong Lin, Lechu Yu, Yongqing Ni, Lulu He, Xiaolu Weng, Xuemian Lu, Chi Zhang
- Diabetes Metab J. 2020;44(1):158-172. Published online October 28, 2019
- DOI: https://doi.org/10.4093/dmj.2018.0235
- 6,792 View
- 122 Download
- 40 Web of Science
- 38 Crossref
-
Abstract
PDFSupplementary MaterialPubReader
Background Epithelial-to-mesenchymal transition (EMT) is required for renal fibrosis, which is a characteristic of diabetic nephropathy (DN). Our previous study demonstrated that fibroblast growth factor 21 (FGF21) prevented DN associated with the suppressing renal connective tissue growth factor expression, a key marker of renal fibrosis. Therefore, the effects of FGF21 on renal fibrosis in a DN mouse model and the underlying mechanisms were investigated in this study.
Methods Type 1 diabetes mellitus was induced in C57BL/6J mice by intraperitoneal injections of multiple low doses of streptozotocin. Then, diabetic and non-diabetic mice were treated with or without FGF21 in the presence of pifithrin-α (p53 inhibitor) or 10-[4′-(N,N-Diethylamino)butyl]-2-chlorophenoxazine hydrochloride (10-DEBC) hydrochloride (Akt inhibitor) for 4 months.
Results DN was diagnosed by renal dysfunction, hypertrophy, tubulointerstitial lesions, and glomerulosclerosis associated with severe fibrosis, all of which were prevented by FGF21. FGF21 also suppressed the diabetes-induced renal EMT in DN mice by negatively regulating transforming growth factor beta (TGF-β)-induced nuclear translocation of Smad2/3, which is required for the transcription of multiple fibrotic genes. The mechanistic studies showed that FGF21 attenuated nuclear translocation of Smad2/3 by inhibiting renal activity of its conjugated protein p53, which carries Smad2/3 into the nucleus. Moreover pifithrin-α inhibited the FGF21-induced preventive effects on the renal EMT and subsequent renal fibrosis in DN mice. In addition, 10-DEBC also blocked FGF21-induced inhibition of renal p53 activity by phosphorylation of mouse double minute-2 homolog (MDM2).
Conclusion FGF21 prevents renal fibrosis via negative regulation of the TGF-β/Smad2/3-mediated EMT process by activation of the Akt/MDM2/p53 signaling pathway.
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Citations
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Biomedicines.2024; 12(3): 487. CrossRef - FGF21 Inhibits Hypoxia/Reoxygenation-induced Renal Tubular Epithelial Cell Injury by Regulating the PPARγ/NF-κB Signaling Pathway
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Cell Biochemistry and Biophysics.2024; 82(2): 909. CrossRef - Advances in the Treatment of Kidney Disorders using Mesenchymal Stem Cells
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Mada Ghanem, Gabrielle Archer, Bruno Crestani, Arnaud A. Mailleux
Pharmacology & Therapeutics.2024; 259: 108669. CrossRef - Elevation of p53 sensitizes obese kidney to adriamycin-induced aberrant lipid homeostasis via repressing HNF4α-mediated FGF21 sensitivity
Jiahao Li, Yufeng Tang, Guangping Lu, Qingbo Liu, Yuanfang Guo, Jie Wang, Mengjie Xiao, Ting Gao, Xiaohui Zhang, Junlian Gu
Journal of Advanced Research.2024;[Epub] CrossRef - Gemigliptin mitigates TGF-β-induced renal fibrosis through FGF21-mediated inhibition of the TGF-β/Smad3 signaling pathway
Jun-Kyu Byun, Gwon-Soo Jung
Biochemical and Biophysical Research Communications.2024; 733: 150425. CrossRef - Myostatin regulates energy homeostasis through autocrine- and paracrine-mediated microenvironment communication
Hui Wang, Shanshan Guo, Huanqing Gao, Jiyang Ding, Hongyun Li, Xingyu Kong, Shuang Zhang, Muyang He, Yonghao Feng, Wei Wu, Kexin Xu, Yuxuan Chen, Hanyin Zhang, Tiemin Liu, Xingxing Kong
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- Gemigliptin Attenuates Renal Fibrosis Through Down-Regulation of the NLRP3 Inflammasome
- Jung Beom Seo, Yeon-Kyung Choi, Hye-In Woo, Yun-A Jung, Sungwoo Lee, Seunghyeong Lee, Mihyang Park, In-Kyu Lee, Gwon-Soo Jung, Keun-Gyu Park
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- DOI: https://doi.org/10.4093/dmj.2018.0181
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Abstract
PDFPubReader
Background The hypoglycemic drugs dipeptidyl peptidase-4 (DPP-4) inhibitors have proven protective effects on diabetic kidney disease, including renal fibrosis. Although NOD-like receptor protein 3 (NLRP3) inflammasome activation is known to play an important role in the progression of renal fibrosis, the impact of DPP-4 inhibition on NLRP3-mediated inflammation while ameliorating renal fibrosis has not been fully elucidated. Here, we report that the renoprotective effect of gemigliptin is associated with a reduction in NLRP3-mediated inflammation in a murine model of renal fibrosis.
Methods We examined the effects of gemigliptin on renal tubulointerstitial fibrosis induced in mice by unilateral ureteral obstruction (UUO). Using immunohistochemical and Western blot analysis, we quantitated components of the NLRP3 inflammasome in kidneys with and without gemigliptin treatment, and
in vitro in human kidney tubular epithelial human renal proximal tubule cells (HK-2) cells, we further analyzed the effect of gemigliptin on transforming growth factor-β (TGF-β)-stimulated production of profibrotic proteins.Results Immunohistological examination revealed that gemigliptin ameliorated UUO-induced tubular atrophy and renal fibrosis. Gemigliptin-treated kidneys showed a reduction in levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin-1β, which had all been markedly increased by UUO. In line with the
in vivo Conclusion The present study shows that activation of the NLRP3 inflammasome contributes to UUO-induced renal fibrosis and the renoprotective effect of gemigliptin is associated with attenuation of NLRP3 inflammasome activation.
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- Soluble Dipeptidyl Peptidase-4 Levels Are Associated with Decreased Renal Function in Patients with Type 2 Diabetes Mellitus
- Eun-Hee Cho, Sang-Wook Kim
- Diabetes Metab J. 2019;43(1):97-104. Published online October 8, 2018
- DOI: https://doi.org/10.4093/dmj.2018.0030
- 5,157 View
- 60 Download
- 14 Web of Science
- 15 Crossref
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Abstract
PDFPubReader
Background Dipeptidyl peptidase-4 (DPP-4) is strongly expressed in the kidney, and soluble levels of this protein are used as a marker in various chronic inflammatory diseases, including diabetes, coronary artery disease, and cancer. This study examined the association between the serum soluble DPP-4 levels and renal function or cardiovascular risk in patients with type 2 diabetes mellitus.
Methods In this retrospective analysis, soluble DPP-4 levels were measured in preserved sera from 140 patients with type 2 diabetes mellitus who had participated in our previous coronary artery calcium (CAC) score study.
Results The mean±standard deviation soluble DPP-4 levels in our study sample were 645±152 ng/mL. Univariate analyses revealed significant correlations of soluble DPP-4 levels with the total cholesterol (
r =0.214,P =0.019) and serum creatinine levels (r =−0.315,P <0.001) and the estimated glomerular filtration rate (eGFR; estimated using the modification of diet in renal disease equation) (r =0.303,P =0.001). The associations of soluble DPP-4 levels with serum creatinine and GFR remained significant after adjusting for age, body mass index, and duration of diabetes. However, no associations were observed between soluble DPP-4 levels and the body mass index, waist circumference, or CAC score.Conclusion These data suggest the potential use of serum soluble DPP-4 levels as a future biomarker of deteriorated renal function in patients with type 2 diabetes mellitus.
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International Journal of Molecular Sciences.2023; 24(7): 6532. CrossRef - Evaluation of the efficacy of dipeptidyl peptidase-4 enzyme and selenium element in people with kidney failure in Kirkuk governorate
Ibrahim Abdullah Ali Al-Jubouri, Nadia Ahmed Saleh Al-Jubouri
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Harshit Sajal, Shashank M. Patil, Ranjith Raj, Abdullah M. Shbeer, Mohammed Ageel, Ramith Ramu
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- Obesity and Metabolic Syndrome
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- DOI: https://doi.org/10.4093/dmj.2017.0052
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Abstract
PDFPubReader
Background Chronic kidney disease (CKD) has emerged as a public health burden globally. Obesity and long-term hyperglycaemia can initiate the renal vascular complications in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the association of body mass index (BMI) with the CKD in patients with T2DM.
Methods This study has used retrospective medical records, biochemical reports, and anthropometric measurements of 3,580 T2DM patients which were collected between January to December 2015 from a district hospital in Thailand. CKD was defined according to the measurement of estimated glomerular filtration rate (<60 mL/min/1.73 m2). Multiple logistic regression analysis was used to explore the association between BMI and CKD in patients with T2DM.
Results The mean age of the participants was 60.86±9.67 years, 53.68% had poor glycaemic control, and 45.21% were overweight. About one-in-four (23.26%) T2DM patients had CKD. The mean BMI of non-CKD group was slightly higher (25.30 kg/m2 vs. 24.30 kg/m2) when compared with CKD patients. Multivariable analysis showed that older age, female sex, hypertension, and microalbuminuria were associated with the presence of CKD. No association was observed between CKD and poorly controlled glycosylated hemoglobin or hypercholesterolemia. Adjusted analysis further showed overweight and obesity were negatively associated with CKD (adjusted odds ratio [AOR], 0.73; 95% confidence interval [CI], 0.58 to 0.93) and (AOR, 0.53; 95% CI, 0.35 to 0.81), respectively.
Conclusion The negative association of BMI with CKD could reflect the reverse causality. Lower BMI might not lead a diabetic patient to develop CKD, but there are possibilities that CKD leads the patient to experience reduced BMI.
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Abozaid Mohammed Elemam
Sudan Journal of Medical Sciences.2019;[Epub] CrossRef
- Increased Body Mass Index is Independently Associated with Chronic Kidney Disease among People with Type 2 Diabetes
- Complications
- Glycated Albumin Is a More Useful Glycation Index than HbA1c for Reflecting Renal Tubulopathy in Subjects with Early Diabetic Kidney Disease
- Ji Hye Huh, Minyoung Lee, So Young Park, Jae Hyeon Kim, Byung-Wan Lee
- Diabetes Metab J. 2018;42(3):215-223. Published online May 2, 2018
- DOI: https://doi.org/10.4093/dmj.2017.0091
- 5,078 View
- 58 Download
- 10 Web of Science
- 10 Crossref
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Abstract
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Background The aim of this study was to investigate which glycemic parameters better reflect urinary N-acetyl-β-D-glucosaminidase (uNAG) abnormality, a marker for renal tubulopathy, in subjects with type 2 diabetes mellitus (T2DM) subjects with normoalbuminuria and a normal estimated glomerular filtration rate (eGFR).
Methods We classified 1,061 participants with T2DM into two groups according to uNAG level—normal vs. high (>5.8 U/g creatinine)—and measured their biochemical parameters.
Results Subjects with high uNAG level had significantly higher levels of fasting and stimulated glucose, glycated albumin (GA), and glycosylated hemoglobin (HbA1c) and lower levels of homeostasis model assessment of β-cell compared with subjects with normal uNAG level. Multiple linear regression analyses showed that uNAG was significantly associated with GA (standardized β coefficient [β]=0.213,
P =0.016), but not with HbA1c (β=−0.137,P =0.096) or stimulated glucose (β=0.095,P =0.140) after adjusting confounding factors. In receiver operating characteristic analysis, the value of the area under the curve (AUC) for renal tubular injury of GA was significantly higher (AUC=0.634; 95% confidence interval [CI], 0.646 to 0.899) than those for HbA1c (AUC=0.598; 95% CI, 0.553 to 0.640), stimulated glucose (AUC=0.594; 95% CI, 0.552 to 0.636), or fasting glucose (AUC=0.558; 95% CI, 0.515 to 0.600). The optimal GA cutoff point for renal tubular damage was 17.55% (sensitivity 59%, specificity 62%).Conclusion GA is a more useful glycation index than HbA1c for reflecting renal tubulopathy in subjects with T2DM with normoalbuminuria and normal eGFR.
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Ran Li, Dunmin She, Zhengqin Ye, Ping Fang, Guannan Zong, Yong Zhao, Kerong Hu, Liya Zhang, Sha Lei, Keqin Zhang, Ying Xue
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 1331. CrossRef - Use of glycated albumin for the identification of diabetes in subjects from northeast China
Guo-Yan Li, Hao-Yu Li, Qiang Li
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Dongjun Dai, Yifei Mo, Jian Zhou
Obesity Medicine.2020; 19: 100256. CrossRef - Hepatic fibrosis is associated with total proteinuria in Korean patients with type 2 diabetes
Eugene Han, Yongin Cho, Kyung-won Kim, Yong-ho Lee, Eun Seok Kang, Bong-Soo Cha, Byung-wan Lee
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- Glucagon-Like Peptide 1 Receptor Agonist Improves Renal Tubular Damage in Mice with Diabetic Kidney Disease
- Others
- The Effect of Glycemic Status on Kidney Stone Disease in Patients with Prediabetes
- Tzu-Hsien Lien, Jin-Shang Wu, Yi-Ching Yang, Zih-Jie Sun, Chih-Jen Chang
- Diabetes Metab J. 2016;40(2):161-166. Published online April 25, 2016
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Abstract
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Background While the evidence supporting a positive association between diabetes mellitus and kidney stone disease (KSD) is solid, studies examining the association between impaired fasting glucose (IFG) and KSD show inconsistent results. Currently, there are no studies examining the relationship between impaired glucose tolerance (IGT) and KSD. The objective of this study is to investigate the effects of different glycemic statuses on KSD. The results may help to motivate patients with diabetes to conform to treatment regimens.
Methods We conducted a cross sectional study of a population that underwent health check-ups between January 2000 and August 2009 at the Health Evaluation Center of National Cheng Kung University Hospital. A total of 14,186 subjects were enrolled. The following categories of glycemic status were used according to the criteria of the 2009 American Diabetes Association: normal glucose tolerance, isolated IGT, isolated IFG, combined IFG/IGT, and diabetes. The existence of KSD was evaluated using renal ultrasonography, and the presence of any hyperechoic structures causing acoustic shadowing was considered to be indicative of KSD.
Results The prevalence of KSD was 7.4% (712/9,621), 9.3% (163/1,755), 10.8% (78/719), 12.0% (66/548), and 11.3% (174/1,543) in subjects with NGT, isolated IGT, isolated IFG, combined IFG/IGT, and diabetes, respectively. Isolated IFG, combined IFG/IGT, and diabetes were associated with KSD after adjusting for other clinical variables, but isolated IGT was not. Age (41 to 64 years vs. ≤40 years, ≥65 years vs. ≤40 years), male gender, hypertension, and hyperuricemia were also independently associated with KSD.
Conclusion Isolated IFG, combined IFG/IGT, and diabetes, but not isolated IGT, were associated with a higher risk of KSD.
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Citations
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泽伟 于
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Ilham Akbar Rahman, Ilham Fauzan Nusaly, Syakri Syahrir, Harry Nusaly, Makbul Aman Mansyur
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В. А. Слободянюк
Health of Man.2020; (1): 75. CrossRef - Re: Evidence of Disordered Calcium Metabolism in Adolescent Girls with Type 1 Diabetes: An Observational Study Using a Dual-Stable Calcium Isotope Technique
Dean G. Assimos
Journal of Urology.2018; 199(2): 335. CrossRef - Metabolic syndrome and uric acid nephrolithiasis: insulin resistance in focus
Leonardo Spatola, Pietro Manuel Ferraro, Giovanni Gambaro, Salvatore Badalamenti, Marco Dauriz
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- Related Risk Factor Analysis for Upper Urinary Tract Stones in Patients with Abnormal Glucose Metabolism
- Chronic Kidney Disease and Associated Cardiovascular Risk Factors in Chinese with Type 2 Diabetes
- Qing-Lin Lou, Xiao-Jun Ouyang, Liu-Bao Gu, Yong-Zhen Mo, Ronald Ma, Jennifer Nan, Alice Kong, Wing-Yee So, Gary Ko, Juliana Chan, Chun-Chung Chow, Rong-Wen Bian
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- 29 Crossref
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Abstract
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Background To determine the frequency of chronic kidney disease (CKD) and its associated risk factors in Chinese type 2 diabetic patients, we conducted a cross-sectional study in Nanjing, China, in the period between January 2008 and December 2009.
Methods Patients with type 2 diabetes under the care by Jiangsu Province Official Hospital, Nanjing, China were invited for assessment. CKD was defined as the presence of albuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m2. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥30 mg/g.
Results We recruited 1,521 urban Chinese patients with type 2 diabetes (mean age, 63.9±12.0 years). The frequency of CKD and albuminuria was 31.0% and 28.9%, respectively. After adjusted by age and sex, hypertension, anemia and duration of diabetes were significantly associated with CKD with odds ratio (95% confidence interval) being 1.93 (1.28 to 2.93), 1.70 (1.09 to 2.64), and 1.03 (1.00 to 1.06), respectively.
Conclusion In conclusion, CKD was common in the urban Nanjing Chinese with type 2 diabetes. Strategies to prevent or delay progression of kidney disease in diabetes should be carried out at the early disease course of type 2 diabetes.
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Abstract
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Background Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of acute kidney injury. There is a growing body of evidence suggesting that NGAL is also a marker of kidney disease and severity in chronic kidney disease (CKD). We studied the utility of urinary NGAL in more accurately predicting renal function in patients with diabetic CKD.
Methods We studied possible relationships between urinary NGAL, estimated glomerular filtration rate (eGFR), and proteinuria in diabetic CKD patients and in healthy populations.
Results Urinary NGAL levels were significantly higher in CKD patients than in healthy controls (96.0 [2.7 to 975.2] ng/mL vs. 18.8 [1.3 to 81.9] ng/mL,
P =0.02), and the GFR was lower among CKD patients (49.3 [13.1 to 78.3] mL/min/1.73 m2 vs. 85.6 [72 to 106.7] mL/min/1.73 m2,P <0.0001). The urinary NGAL level showed a significant inverse correlation with GFR (r =-0.5634,P <0.0001). The correlation analyses between urinary protein level and urinary NGAL levels and GFR were as follows: urine protein and urinary NGAL (r =0.3009,P =0.0256), urine protein and GFR (r =-0.6245,P <0.0001), urine microalbumin and urinary NGAL (r =0.1794,P =0.2275), and urine microalbumin and GFR (r =-0.5190,P =0.0002).Conclusion From these results, we concluded that urinary NGAL is a reliable marker of renal function in diabetic CKD patients. However, urinary NGAL did not provide more accurate information regarding renal function than GFR.
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Review
- Role of Peroxisome Proliferator-Activated Receptor α in Diabetic Nephropathy
- Sungjin Chung, Cheol Whee Park
- Diabetes Metab J. 2011;35(4):327-336. Published online August 31, 2011
- DOI: https://doi.org/10.4093/dmj.2011.35.4.327
- 65,535 View
- 50 Download
- 18 Crossref
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Abstract
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With a developing worldwide epidemic of diabetes mellitus, the renal complications associated with diabetes have become a serious health concern. Primary therapy for treating diabetic nephropathy is a multifactorial process. Peroxisome proliferator-activated receptor alpha (PPARα) agonists have been used primarily in clinical practice for the treatment of dyslipidemia and insulin resistance. Given that PPARα expression and regulation of metabolic pathways are involved in oxidative stress, inflammation, blood pressure regulation, and the renin-angiotensin aldosterone system, PPARα likely influences the development and pathogenesis of diabetic nephropathy via indirect effects on glucose and lipid homeostasis and also by direct action on the kidneys. These findings suggest that PPARα may become an important therapeutic target for treating diabetic renal complications.
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